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Sample records for exerts neuroprotective effects

  1. Post-stroke treatment with 17β-estradiol exerts neuroprotective effects in both normotensive and hypertensive rats.

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    Stoop, Wendy; De Geyter, Deborah; Verachtert, Sofie; Brouwers, Sofie; Verdood, Peggy; De Keyser, Jacques; Kooijman, Ron

    2017-04-21

    Although ischemic stroke is a major cause of death worldwide and the predominant cause of acquired disability, the only effective drug therapy that has been developed thus far is reperfusion by tissue plasminogen activator. Since most patients do not qualify for this treatment, new methods have to be developed. It is well known that estradiol (E 2 ) exerts neuroprotective effects in different models of cerebral ischemia, but post-stroke treatment after an acute stroke has hardly been investigated. As many patients with an acute ischemic stroke have arterial hypertension, it is also of interest to evaluate the influence of this co-morbidity on the treatment efficacy of E 2 . The effects of E 2 administered 30min after a transient middle cerebral artery occlusion (tMCAO) induced by an intracerebral injection of endothelin-1 were assessed in male normotensive Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). Treatment with E 2 reduced infarct size in both WKY and SHRs and decreased the number of degenerating neurons, indicating that acute treatment with E 2 is indeed neuroprotective. To address the role of glia in neuroprotection, the effects of E 2 on the activation of microglia and astrocytes was determined. It appeared that E 2 had no effect on microglial activation, but reduced the activation of astrocytes in SHRs but not in the normotensive controls. We conclude that post-stroke E 2 treatment in both normotensive and hypertensive rats is neuroprotective. Although the presence of hypertension changed the astrocytic response to E 2 , it did not affect treatment efficacy. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Phytochemical allylguaiacol exerts a neuroprotective effect on hippocampal cells and ameliorates scopolamine-induced memory impairment in mice.

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    Lim, Hye-Sun; Kim, Bu-Yeo; Kim, Yu Jin; Jeong, Soo-Jin

    2018-02-26

    Allylguaiacol is a phytochemical occurring in various plants such as cloves, cinnamon, basil, and nutmeg. Pharmacological effects of allylguaiacol include antimicrobial, anti-inflammatory, anticancer, antioxidant, and neuroprotective activity. Although allylguaiacol is considered to have neuroprotective effects, there is no report on its regulatory mechanisms at the molecular level. In the present study, we investigated the mechanisms of allylguaiacol as an antioxidant and neuroprotective agent using hydrogen peroxide (H 2 O 2 )-treated HT22 hippocampal cells. Allylguaiacol increased the scavenging activities of free radicals 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH), and enhanced the expression of antioxidant enzymes manganese superoxide dismutase (MnSOD) and catalase. In addition, allylguaiacol inhibited H 2 O 2 -induced damage of HT22 with increasing production of brain-derived neurotrophic factor (BDNF), phosphorylation of phosphoinositide 3-kinase (PI3K), and cyclic AMP response element-binding protein (CREB). Furthermore, antibody microarray data revealed that phospho-regulation of nuclear factor kappa B (NF-κB) p65 and death domain-associated protein (DAXX) is involved in protection against neuronal cell damage. In a mouse model of short-term memory impairment, allylguaiacol (2.5 or 5mg/kg) significantly ameliorated scopolamine-mediated cognitive impairment in a passive avoidance task. In addition, allylguaiacol significantly increased the expression of TrkA and B in the hippocampus from scopolamine-treated mice. Taken together, our findings suggest that allylguaiacol exerts a neuroprotective effect through the antioxidant activation and protein regulation of NF-κB p65 and DAXX-related signaling. The ameliorating effect of allylguaiacol may be useful for treatment of memory impairment in Alzheimer's and its related diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. A c-Src Inhibitor Peptide Based on Connexin43 Exerts Neuroprotective Effects through the Inhibition of Glial Hemichannel Activity.

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    Gangoso, Ester; Talaverón, Rocío; Jaraíz-Rodríguez, Myriam; Domínguez-Prieto, Marta; Ezan, Pascal; Koulakoff, Annette; Medina, José M; Giaume, Christian; Tabernero, Arantxa

    2017-01-01

    . In fact, TAT-Cx43 266-283 and dasatinib, a potent c-Src inhibitor, strongly reduced the activation of astrocyte hemichannels. In conclusion, our results suggest that TAT-Cx43 266-283 exerts a neuroprotective effect through the reduction of hemichannel activity likely mediated by c-Src in astrocytes. These data unveil a new role of c-Src in the regulation of Cx43-hemichannel activity that could be part of the mechanism by which astroglial c-Src participates in neuroinflammation.

  4. A c-Src Inhibitor Peptide Based on Connexin43 Exerts Neuroprotective Effects through the Inhibition of Glial Hemichannel Activity

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    Ester Gangoso

    2017-12-01

    bromide (EtBr uptake assay. In fact, TAT-Cx43266–283 and dasatinib, a potent c-Src inhibitor, strongly reduced the activation of astrocyte hemichannels. In conclusion, our results suggest that TAT-Cx43266–283 exerts a neuroprotective effect through the reduction of hemichannel activity likely mediated by c-Src in astrocytes. These data unveil a new role of c-Src in the regulation of Cx43-hemichannel activity that could be part of the mechanism by which astroglial c-Src participates in neuroinflammation.

  5. Ginger and Propolis Exert Neuroprotective Effects against Monosodium Glutamate-Induced Neurotoxicity in Rats

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    Usama K. Hussein

    2017-11-01

    Full Text Available Central nervous system cytotoxicity is linked to neurodegenerative disorders. The objective of the study was to investigate whether monosodium glutamate (MSG neurotoxicity can be reversed by natural products, such as ginger or propolis, in male rats. Four different groups of Wistar rats were utilized in the study. Group A served as a normal control, whereas group B was orally administered with MSG (100 mg/kg body weight, via oral gavage. Two additional groups, C and D, were given MSG as group B along with oral dose (500 mg/kg body weight of either ginger or propolis (600 mg/kg body weight once a day for two months. At the end, the rats were sacrificed, and the brain tissue was excised and levels of neurotransmitters, ß-amyloid, and DNA oxidative marker 8-OHdG were estimated in the brain homogenates. Further, formalin-fixed and paraffin-embedded brain sections were used for histopathological evaluation. The results showed that MSG increased lipid peroxidation, nitric oxide, neurotransmitters, and 8-OHdG as well as registered an accumulation of ß-amyloid peptides compared to normal control rats. Moreover, significant depletions of glutathione, superoxide dismutase, and catalase as well as histopathological alterations in the brain tissue of MSG-treated rats were noticed in comparison with the normal control. In contrast, treatment with ginger greatly attenuated the neurotoxic effects of MSG through suppression of 8-OHdG and β-amyloid accumulation as well as alteration of neurotransmitter levels. Further improvements were also noticed based on histological alterations and reduction of neurodegeneration in the brain tissue. A modest inhibition of the neurodegenerative markers was observed by propolis. The study clearly indicates a neuroprotective effect of ginger and propolis against MSG-induced neurodegenerative disorders and these beneficial effects could be attributed to the polyphenolic compounds present in these natural products.

  6. Palmitoylethanolamide exerts neuroprotective effects in mixed neuroglial cultures and organotypic hippocampal slices via peroxisome proliferator-activated receptor-α

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    Scuderi Caterina

    2012-03-01

    Full Text Available Abstract Background In addition to cytotoxic mechanisms directly impacting neurons, β-amyloid (Aβ-induced glial activation also promotes release of proinflammatory molecules that may self-perpetuate reactive gliosis and damage neighbouring neurons, thus amplifying neuropathological lesions occurring in Alzheimer's disease (AD. Palmitoylethanolamide (PEA has been studied extensively for its anti-inflammatory, analgesic, antiepileptic and neuroprotective effects. PEA is a lipid messenger isolated from mammalian and vegetable tissues that mimics several endocannabinoid-driven actions, even though it does not bind to cannabinoid receptors. Some of its pharmacological properties are considered to be dependent on the expression of peroxisome proliferator-activated receptors-α (PPARα. Findings In the present study, we evaluated the effect of PEA on astrocyte activation and neuronal loss in models of Aβ neurotoxicity. To this purpose, primary rat mixed neuroglial co-cultures and organotypic hippocampal slices were challenged with Aβ1-42 and treated with PEA in the presence or absence of MK886 or GW9662, which are selective PPARα and PPARγ antagonists, respectively. The results indicate that PEA is able to blunt Aβ-induced astrocyte activation and, subsequently, to improve neuronal survival through selective PPARα activation. The data from organotypic cultures confirm that PEA anti-inflammatory properties implicate PPARα mediation and reveal that the reduction of reactive gliosis subsequently induces a marked rebound neuroprotective effect on neurons. Conclusions In line with our previous observations, the results of this study show that PEA treatment results in decreased numbers of infiltrating astrocytes during Aβ challenge, resulting in significant neuroprotection. PEA could thus represent a promising pharmacological tool because it is able to reduce Aβ-evoked neuroinflammation and attenuate its neurodegenerative consequences.

  7. Clostridium butyricum exerts a neuroprotective effect in a mouse model of traumatic brain injury via the gut-brain axis.

    Science.gov (United States)

    Li, H; Sun, J; Du, J; Wang, F; Fang, R; Yu, C; Xiong, J; Chen, W; Lu, Z; Liu, J

    2017-11-27

    Traumatic brain injury (TBI) is a common occurrence following gastrointestinal dysfunction. Recently, more and more attentions are being focused on gut microbiota in brain and behavior. Glucagon-like peptide-1 (GLP-1) is considered as a mediator that links the gut-brain axis. The aim of this study was to explore the neuroprotective effects of Clostridium butyricum (Cb) on brain damage in a mouse model of TBI. Male C57BL/6 mice were subjected to a model of TBI-induced by weight-drop impact head injury and were treated intragastrically with Cb. The cognitive deficits, brain water content, neuronal death, and blood-brain barrier (BBB) permeability were evaluated. The expression of tight junction (TJ) proteins, Bcl-2, Bax, GLP-1 receptor (GLP-1R), and phosphorylation of Akt (p-Akt) in the brain were also measured. Moreover, the intestinal barrier permeability, the expression of TJ protein and GLP-1, and IL-6 level in the intestine were detected. Cb treatment significantly improved neurological dysfunction, brain edema, neurodegeneration, and BBB impairment. Meanwhile, Cb treatment also significantly increased the expression of TJ proteins (occludin and zonula occluden-1), p-Akt and Bcl-2, but decreased expression of Bax. Moreover, Cb treatment exhibited more prominent effects on decreasing the levels of plasma d-lactate and colonic IL-6, upregulating expression of Occludin, and protecting intestinal barrier integrity. Furthermore, Cb-treated mice showed increased the secretion of intestinal GLP-1 and upregulated expression of cerebral GLP-1R. Our findings demonstrated the neuroprotective effect of Cb in TBI mice and the involved mechanisms were partially attributed to the elevating GLP-1 secretion through the gut-brain axis. © 2017 John Wiley & Sons Ltd.

  8. Electro-acupuncture at LI11 and ST36 acupoints exerts neuroprotective effects via reactive astrocyte proliferation after ischemia and reperfusion injury in rats.

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    Tao, Jing; Zheng, Yi; Liu, Weilin; Yang, Shanli; Huang, Jia; Xue, Xiehua; Shang, Guanhao; Wang, Xian; Lin, Ruhui; Chen, Lidian

    2016-01-01

    Reactive astrogliosis is a common phenomenon in central nervous system (CNS) injuries such as ischemic stroke. The present study aimed to deeply investigate the relationships between the neuroprotective effect of electro-acupuncture (EA) and reactive astrocytes following cerebral ischemia. EA treatment at the Quchi (LI11) and Zusanli (ST36) acupoints at Day 3 attenuated neurological deficits and cerebral infarct volume in ischemia and reperfusion (I/R) injured rats. Animal behavior assessments found that the speed of Catwalk gait, equilibrium and coordination of Rotarod test were improved. Furthermore, EA treatment exerted neuroprotective effects via activation of glial fibrillary acidic protein (GFAP), vimentin and nestin positive cells. Simultaneously, an obvious increase in GFAP/vimentin, GFAP/nestin and GFAP/BrdU co-labeling appeared in the peri-infract cortex and striatum, suggesting EA can promote the proliferation of GFAP/vimentin/nestin-positive reactive astrocytes. The expression of cell cycle-associated proteins Cyclin Dl, CDK4 and phospho-Rb were increased in the peri-infract cortex and striatum, indicating proliferated reactive astrocytes-mediated CyclinDl/CDK4 regulation of the transition of the G1-to-S cell cycle phases. In addition, EA enhanced the localized expression of brain-derived neurotrophic factor (BDNF) in the peri-infract cortex and striatum. These results demonstrated that EA treatment at the LI11 and ST36 acupoints on Day 3 exerted neuroprotection via proliferation of GFAP/vimentin/nestin-positive reactive astrocytes and, potentially, secretion of reactive astrocytes-derived BDNF in I/R injured rats. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Apigetrin from Scutellaria baicalensis Georgi Inhibits Neuroinflammation in BV-2 Microglia and Exerts Neuroprotective Effect in HT22 Hippocampal Cells.

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    Lim, Hye-Sun; Kim, Ohn-Soon; Kim, Bu-Yeo; Jeong, Soo-Jin

    2016-11-01

    Apigetrin is a flavonoid isolated from various herbal medicines such as Scutellaria baicalensis Georgi, Matricaria chamomilla, Stachys tibetica Vatke, and Teucrium gnaphalodes. In the present study, we investigated the inhibitory effects of apigetrin on neuroinflammation using the BV-2 microglia cell line. Our data revealed that apigetrin significantly reduced secretion and mRNA expression of inflammatory cytokines, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), in lipopolysaccharide (LPS)-stimulated BV-2 mouse microglia. Apigetrin also significantly decreased LPS-mediated production of prostaglandin E 2 (PGE 2 ) level and nitric oxide (NO) production as well as expression of cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) in BV-2 cells. In addition, apigetrin suppressed nuclear expression of nuclear factor kappa B (NF-κB) in LPS-stimulated BV-2 cells. Furthermore, apigetrin significantly impaired reactive oxygen species (ROS) generation and enhanced expression of antioxidant enzymes, hempxygenase 1 (HO-1) and nuclear factor-like 2 (Nrf2), in BV-2 cells. Apigetrin also increased 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activity, indicating antioxidative activity of apigetrin. Moreover, we found that apigetrin inhibited hydrogen peroxide (H 2 O 2 )-induced cell death in HT22 hippocampal cells. Overall, our findings indicate that apigetrin has inhibitory effects on neuroinflammation as well as antioxidation and neuroprotection, suggesting the potential prophylactic activity for neurodegenerative diseases through the inter-regulation of neuroinflammation, oxidative stress, and neuronal injury.

  10. Intravenous administration of mesenchymal stem cells exerts therapeutic effects on parkinsonian model of rats: Focusing on neuroprotective effects of stromal cell-derived factor-1α

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    Tayra Judith

    2010-04-01

    Full Text Available Abstract Background Mesenchymal stem cells (MSCs are pluripotent stem cells derived from bone marrow with secretory functions of various neurotrophic factors. Stromal cell-derived factor-1α (SDF-1α is also reported as one of chemokines released from MSCs. In this research, the therapeutic effects of MSCs through SDF-1α were explored. 6-hydroxydopamine (6-OHDA, 20 μg was injected into the right striatum of female SD rats with subsequent administration of GFP-labeled MSCs, fibroblasts, (i.v., 1 × 107 cells, respectively or PBS at 2 hours after 6-OHDA injection. All rats were evaluated behaviorally with cylinder test and amphetamine-induced rotation test for 1 month with consequent euthanasia for immunohistochemical evaluations. Additionally, to explore the underlying mechanisms, neuroprotective effects of SDF-1α were explored using 6-OHDA-exposed PC12 cells by using dopamine (DA assay and TdT-mediated dUTP-biotin nick-end labeling (TUNEL staining. Results Rats receiving MSC transplantation significantly ameliorated behaviorally both in cylinder test and amphetamine-induced rotation test compared with the control groups. Correspondingly, rats with MSCs displayed significant preservation in the density of tyrosine hydroxylase (TH-positive fibers in the striatum and the number of TH-positive neurons in the substantia nigra pars compacta (SNc compared to that of control rats. In the in vitro study, SDF-1α treatment increased DA release and suppressed cell death induced by 6-OHDA administration compared with the control groups. Conclusions Consequently, MSC transplantation might exert neuroprotection on 6-OHDA-exposed dopaminergic neurons at least partly through anti-apoptotic effects of SDF-1α. The results demonstrate the potentials of intravenous MSC administration for clinical applications, although further explorations are required.

  11. Resveratrol exerts anti-inflammatory and neuroprotective effects to prevent memory deficits in rats exposed to chronic unpredictable mild stress.

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    Yazir, Yusufhan; Utkan, Tijen; Gacar, Nejat; Aricioglu, Feyza

    2015-01-01

    A number of studies have recently focused on the neuroprotective and anti-inflammatory effects of resveratrol. In prior studies, we described its beneficial effects on scopolamine-induced learning deficits in rats. The aim of this study was to investigate the effects of resveratrol on emotional and spatial cognitive functions, neurotropic factor expression, and plasma levels of proinflammatory cytokines in rats exposed to chronic unpredictable mild stress (CUMS), which is known to induce cognitive deficits. Resveratrol (5 or 20mg/kg) was administered intraperitoneally for 35 days. Rats in the CUMS group and in the 5mg/kg resveratrol+CUMS group performed poorly in tasks designed to assess emotional and spatial learning and memory. The 20mg/kg resveratrol+CUMS group showed improved performance compared to the CUMS group. In addition, the CUMS procedure induced lower expression of brain-derived neurotrophic factor and c-Fos in hippocampal CA1 and CA3 and in the amygdala of stressed rats. These effects were reversed by chronic administration of resveratrol (20mg/kg). In addition, plasma levels of tumor necrosis factor-alpha and interleukin-1 beta were increased by CUMS, but were restored to normal by resveratrol. These results indicate that resveratrol significantly attenuates the deficits in emotional learning and spatial memory seen in chronically stressed rats. These effects may be related to resveratrol-mediated changes in neurotrophin factor expression in hippocampus and in levels of proinflammatory cytokines in circulation. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Early applied electric field stimulation attenuates secondary apoptotic responses and exerts neuroprotective effects in acute spinal cord injury of rats.

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    Zhang, C; Zhang, G; Rong, W; Wang, A; Wu, C; Huo, X

    2015-04-16

    Injury potential, which refers to a direct current voltage between intact and injured nerve ends, is mainly caused by injury-induced Ca2+ influx. Our previous studies revealed that injury potential increased with the onset and severity of spinal cord injury (SCI), and an application of applied electric field stimulation (EFS) with the cathode distal to the lesion could delay and attenuate injury potential formation. As Ca2+ influx is also considered as a major trigger for secondary injury after SCI, we hypothesize that EFS would protect an injured spinal cord from secondary injury and consequently improve functional and pathological outcomes. In this study, rats were divided into three groups: (1) sham group, laminectomy only; (2) control group, subjected to SCI only; and (3) EFS group, received EFS immediately post-injury with the injury potential modulated to 0±0.5 mV by EFS. Functional recovery of the hind limbs was assessed using the Basso, Beattie, and Bresnahan (BBB) locomotor scale. Results revealed that EFS-treated rats exhibited significantly better locomotor function recovery. Luxol fast blue staining was performed to assess the spared myelin area. Immunofluorescence was used to observe the number of myelinated nerve fibers. Ultrastructural analysis was performed to evaluate the size of myelinated nerve fibers. Findings showed that the EFS group rats exhibited significantly less myelin loss and had larger and more myelinated nerve fibers than the control group rats in dorsal corticospinal tract (dCST) 8 weeks after SCI. Furthermore, we found that EFS inhibited the activation of calpain and caspase-3, as well as the expression of Bax, as detected by Western blot analysis. Moreover, EFS decreased cellular apoptosis, as measured by TUNEL, within 4 weeks post-injury. Results suggest that early EFS could significantly reduce spinal cord degeneration and improve functional and historical recovery. Furthermore, these neuroprotective effects may be related to

  13. Humanin Exerts Neuroprotection During Cardiac Ischemia-Reperfusion Injury.

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    Kumfu, Sirinart; Charununtakorn, Savitree T; Jaiwongkam, Thidarat; Chattipakorn, Nipon; Chattipakorn, Siriporn C

    2018-01-01

     Cardiac ischemia-reperfusion (I/R) injury has been shown to impair brain function. Humanin analogue (HNG) given prior to cardiac ischemia has been shown to attenuate both heart and brain mitochondrial dysfunction caused by cardiac I/R injury. In a clinical setting, patients received medical treatment for acute myocardial infarction either during or after the onset of myocardial ischemia; thus, in this study, we tested the hypothesis that the administration of HNG during cardiac I/R injury has therapeutic potential for brain protection. Thirty-six male Wistar rats were divided into two groups: a cardiac I/R group (n = 30), and a sham group (n = 6). The I/R rats were then divided into five subgroups to receive: 1) vehicle; 2) HNG (84 μg/kg); 3) HNG (168 μg/kg); 4) HNG (252 μg/kg) intravenously administered during the cardiac-ischemia; and 5) HNG at 252 μg/kg given at the onset of reperfusion. At the end of treatment, brains were removed for determination of blood-brain barrier (BBB) breakdown, oxidative stress, brain mitochondrial function, brain mitochondrial dynamics, p-tau, amyloid-β (Aβ) and apoptosis. HNG at a dose of 168 and 252 μg/kg administered during ischemia, and 252 μg/kg given at the onset of reperfusion effectively attenuated the brain mitochondrial dysfunction, tau hyperphosphorylation and Aβ accumulation, and apoptosis, without reducing BBB breakdown, brain oxidative stress, or mitochondrial dynamic, caused by cardiac I/R injury. In conclusion, humanin exerted neuroprotection during induced cardiac I/R injury via improvement in brain mitochondrial function, and the reduction of Alzheimer's disease pathology and apoptosis.

  14. [Neuroprotective effects of curcumin].

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    Li, Yong; Wang, Pengwen

    2009-12-01

    Traditionally, turmeric has been put to use as a food additive and herbal medicine in Asia. Curcumin is an active principle of the perennial herb curcuma longa (commonly known as turmeric). Recent evidence suggests that curcumin has activities with potential for neuroprotective efficacy, including anti-inflammatory, antioxidant, and antiprotein-aggregate activities. In the current review, we provide the newly evidence for the potential role of curcumin in the neuroprotective effects of neurodegenerative diseases like Alzheimer's disease (AD).

  15. Tenoxicam exerts a neuroprotective action after cerebral ischemia in rats.

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    Galvão, Rita I M; Diógenes, João P L; Maia, Graziela C L; Filho, Emídio A S; Vasconcelos, Silvânia M M; de Menezes, Dalgimar B; Cunha, Geanne M A; Viana, Glauce S B

    2005-01-01

    In this study we investigated the effects of Tenoxicam, a type 2 cyclooxygenase (COX-2) inhibitor, on brain damage induced by ischemia-reperfusion. Male Wistar rats (18-month old average) were anesthetized and submitted to ischemia occlusion of both common carotid arteries (BCAO) for 45 min. After 24 h of reperfusion, rats were decapitated and hippocampi removed for further assays. Animals were divided into sham-operated, ischemia, ischemia + Tenoxicam 2.5 mg/kg, and ischemia + Tenoxicam 10 mg/kg groups. Tenoxicam was administered intraperitoneally immediately after BCAO. Histological analyses show that ischemia produced significant striatal as well as hippocampal lesions which were reversed by the Tenoxicam treatment. Tenoxicam also significantly reduced, to control levels, the increased myeloperoxidase activity in hippocampus homogenates observed after ischemia. However, nitrite concentrations showed only a tendency to decrease in the ischemia + Tenoxicam groups, as compared to that of ischemia alone. On the other hand, hippocampal glutamate and aspartate levels were not altered by Tenoxicam. In conclusion, we showed that ischemia is certainly related to inflammation and to increased free radical production, and selective COX-2 inhibitors might be neuroprotective agents of potential benefit in the treatment of cerebral brain ischemia.

  16. Activation of Neuropeptide Y Receptors Modulates Retinal Ganglion Cell Physiology and Exerts Neuroprotective Actions In Vitro

    DEFF Research Database (Denmark)

    Martins, João; Elvas, Filipe; Brudzewsky, Dan

    2015-01-01

    -reperfusion injury, pretreatment with NPY or (Leu31, Pro34)-NPY was not able to prevent apoptosis or rescue RGCs. In conclusion, we found modulatory effects of NPY application that for the first time were detected at the level of RGCs. However, further studies are needed to evaluate whether NPY neuroprotective...

  17. Neuroprotective effects of Ellagic acid on Neonatal Hypoxic Brain ...

    African Journals Online (AJOL)

    Purpose: To investigate if ellagic acid exerts neuroprotective effects in hypoxic ischemic (HI) brain injury by inhibiting apoptosis and inflammatory responses. Methods: Separate groups of rat pups from post-natal day 4 (D4) were administered with ellagic acid (10, 20 or 40 mg/kg body weight) orally till post- natal day 10 ...

  18. Topiramate via NMDA, AMPA/kainate, GABAAand Alpha2 receptors and by modulation of CREB/BDNF and Akt/GSK3 signaling pathway exerts neuroprotective effects against methylphenidate-induced neurotoxicity in rats.

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    Motaghinejad, Majid; Motevalian, Manijeh; Fatima, Sulail; Beiranvand, Tabassom; Mozaffari, Shiva

    2017-11-01

    Chronic abuse of methylphenidate (MPH) often causes neuronal cell death. Topiramate (TPM) carries neuroprotective effects, but its exact mechanism of action remains unclear. In the present study, the role of various doses of TPM and its possible mechanisms, receptors and signaling pathways involved against MPH-induced hippocampal neurodegeneration were evaluated in vivo. Thus, domoic acid (DOM) was used as AMPA/kainate receptor agonist, bicuculline (BIC) as GABA A receptor antagonist, ketamine (KET) as NMDA receptor antagonist, yohimbine (YOH) as α 2 adrenergic receptor antagonist and haloperidol (HAL) was used as dopamine D 2 receptor antagonist. Open field test (OFT) was used to investigate the disturbances in motor activity. Hippocampal neurodegenerative parameters were evaluated. Protein expressions of CREB/BDNF and Akt/GSK3 signaling pathways were also evaluated. Cresyl violet staining was performed to show and confirm the changes in the shape of the cells. TPM (70 and 100 mg/kg) reduced MPH-induced rise in lipid peroxidation, oxidized form of glutathione (GSSG), IL-1β and TNF-α levels, Bax expression and motor activity disturbances. In addition, TPM treatment increased Bcl-2 expression, the level of reduced form of glutathione (GSH) and the levels and activities of superoxide dismutase, glutathione peroxidase and glutathione reductase enzymes. TPM also inhibited MPH-induced hippocampal degeneration. Pretreatment of animals with DOM, BIC, KET and YOH inhibited TPM-induced neuroprotection and increased oxidative stress, neuroinflammation, neuroapoptosis and neurodegeneration while reducing CREB, BDNF and Akt protein expressions. Also pretreatment with DOM, BIC, KET and YOH inhibited TPM-induced decreases in GSK3. It can be concluded that the mentioned receptors by modulation of CREB/BDNF and Akt/GSK3 pathways, are involved in neuroprotection of TPM against MPH-induced neurodegeneration.

  19. Electroacupuncture Exerts Neuroprotection through Caveolin-1 Mediated Molecular Pathway in Intracerebral Hemorrhage of Rats

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    Hui-Qin Li

    2016-01-01

    Full Text Available Spontaneous intracerebral hemorrhage (ICH is one of the most devastating types of stroke. Here, we aim to demonstrate that electroacupuncture on Baihui (GV20 exerts neuroprotection for acute ICH possibly via the caveolin-1/matrix metalloproteinase/blood-brain barrier permeability pathway. The model of ICH was established by using collagenase VII. Rats were randomly divided into three groups: Sham-operation group, Sham electroacupuncture group, and electroacupuncture group. Each group was further divided into 4 subgroups according to the time points of 6 h, 1 d, 3 d, and 7 d after ICH. The methods were used including examination of neurological deficit scores according to Longa’s scale, measurement of blood-brain barrier permeability through Evans Blue content, in situ immunofluorescent detection of caveolin-1 in brains, western blot analysis of caveolin-1 in brains, and in situ zymography for measuring matrix metalloproteinase-2/9 activity in brains. Compared with Sham electroacupuncture group, electroacupuncture group has resulted in a significant improvement in neurological deficit scores and in a reduction in Evans Blue content, expression of caveolin-1, and activity of matrix metalloproteinase-2/9 at 6 h, 1 d, 3 d, and 7 d after ICH (P<0.05. In conclusion, the present results suggested that electroacupuncture on GV20 can improve neurological deficit scores and reduce blood-brain barrier permeability after ICH, and the mechanism possibly targets caveolin-1/matrix metalloproteinase/blood-brain barrier permeability pathway.

  20. Neuroprotective effects of Lepidium meyenii (Maca).

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    Pino-Figueroa, Alejandro; Nguyen, Diane; Maher, Timothy J

    2010-06-01

    The neuroprotective activity of the plant Lepidium meyenii (Maca) was studied in two experimental models: in vitro and in vivo. Crayfish neurons were pretreated with vehicle or the pentane extract from Maca, subjected to H(2)O(2), and their viability determined microscopically and chemically. A significant concentration-neuroprotective effect relationship was demonstrated. The pentane extract was then administered intravenously to rats prior to and following middle cerebral artery occlusion. While infarct volumes were decreased for the lower dose, higher doses increased infarct volumes compared to controls. These results suggest a potential application of Maca as a neuroprotectant.

  1. Proliferative Activity and Neuroprotective Effect of Ligustrazene ...

    African Journals Online (AJOL)

    Proliferative Activity and Neuroprotective Effect of. Ligustrazene Derivative by Irritation of Vascular. Endothelial Growth Factor Expression in Middle Cerebral. Artery Occlusion Rats. Zhang Huazheng1, Wang Penglong2, Ren Liwei1, Wang Xiaobo2, Li Guoliang2,. Wang Mina1, Chu Fuhao2, Gong Yan2, Xu Bing2, Bi Siling1, ...

  2. Extract of Antrodia camphorata Exerts Neuroprotection against Embolic Stroke in Rats without Causing the Risk of Hemorrhagic Incidence

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    Ye-Ming Lee

    2014-01-01

    Full Text Available In this study, the neuroprotective effect of an extract of Antrodia camphorata (A. camphorata, a fungus commonly used in Chinese folk medicine for treatment of viral hepatitis and cancer, alone or in combination with aspirin was investigated in a rat embolic stroke model. An ischemic stroke was induced in rats by a selective occlusion of the middle cerebral artery (MCA with whole blood clots and then orally treated with A. camphorata (0.25 and 0.75 g/kg/day alone and combined with aspirin (5 mg/kg/day. Sixty days later, the brains were removed, sectioned, and stained with triphenyltetrazolium chloride and analysed by a commercial image processing software program. Brain infarct volume, neurobehavioral score, cerebral blood perfusion, and subarachnoid and intracerebral hemorrhage incidence were perceived. In addition, potential bleeding side effect of the combinative therapy was assessed by measuring hemoglobin (Hb content during intracerebral hemorrhage and gastric bleeding, prothrombin time (PT, and occlusion time (OT after oral administration. Posttreatment with high dose A. camphorata significantly reduced infarct volume and improved neurobehavioral score (P < 0.05. Since A. camphorata alone or with aspirin did not alter the Hb level, this treatment is safe and does not cause hemorrhagic incident. Remarkably, the combination of A. camphorata and aspirin did not show a significant effect on the bleeding time, PT and OT increase suggesting that A. camphorata may have the neuroprotective effect without the prolongation of bleeding time or coagulation time. From these observations, we suggest that combinative therapy of A. camphorata and aspirin might offer enhanced neuroprotective efficacies without increasing side effects.

  3. Pulmonary antioxidants exert differential protective effects against ...

    Indian Academy of Sciences (India)

    Unknown

    fractions than on the PM2⋅5–0⋅1 fractions, supporting the previous findings that respirable PM and urban samples contain fewer free radical sources than inhalable PM and industrial samples. [Greenwell L L, Moreno T and Richards R J 2003 Pulmonary antioxidants exert differential protective effects against urban and ...

  4. Pulmonary antioxidants exert differential protective effects against ...

    Indian Academy of Sciences (India)

    When repeated in the presence of a low molecular weight fraction of fresh pulmonary lavage fluid, as well as in artificial lung lining fluid (200 M urate, glutathione and ascorbate), the DNA damage was significantly reduced in all cases ( < 0.05). The antioxidants exerted a greater effect on the industrial samples than on ...

  5. Neuroprotective Effects of Lutein in the Retina

    Science.gov (United States)

    Ozawa, Yoko; Sasaki, Mariko; Takahashi, Noriko; Kamoshita, Mamoru; Miyake, Seiji; Tsubota, Kazuo

    2012-01-01

    Although a large variety of pharmaceutical therapies for treating disease have been developed in recent years, there has been little progress in disease prevention. In particular, the protection of neural tissue is essential, because it is hardly regenerated. The use of nutraceuticals for maintaining the health has been supported by several clinical studies, including cross-sectional and interventional studies for age-related macular disease. However, mechanistic evidence for their effects at the molecular level has been very limited. In this review, we focus on lutein, which is a xanthophyll type of carotenoid. Lutein is not synthesized in mammals, and must be obtained from the diet. It is delivered to the retina, and in humans, it is concentrated in the macula. Here, we describe the neuroprotective effects of lutein and their underlying molecular mechanisms in animal models of vision-threatening diseases, such as innate retinal inflammation, diabetic retinopathy, and light-induced retinal degeneration. In lutein-treated mouse ocular disease models, oxidative stress in the retina is reduced, and its downstream pathological signals are inhibited. Furthermore, degradation of the functional proteins, rhodopsin (a visual substance) and synaptophysin (a synaptic vesicle protein also influenced in other neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease), the depletion of brain-derived neurotrophic factor (BDNF), and DNA damage are prevented by lutein, which preserves visual function. We discuss the possibility of using lutein, an antioxidant, as a neuroprotective treatment for humans. PMID:22211688

  6. Angiotensin II Type 2 Receptor Agonist Experts Sustained Neuroprotective Effects In Aged Rats

    DEFF Research Database (Denmark)

    Sumners, Colin; Isenberg, Jacob; Harmel, Allison

    2016-01-01

    OBJECTIVE: The renin angiotensin system is a promising target for stroke neuroprotection and therapy through activation of angiotensin type II receptors (AT2R). The selective non-peptide AT2R agonist, Compound 21 (C21), has been shown to exhibit neuroprotection and improve stroke outcomes...... in preclinical studies, effects that likely involve neurotropic actions. However, these beneficial actions of C21 have not been demonstrated to occur beyond 1 week post stroke. The objective of this study was to determine if systemic administration of C21 would exert sustained neuroprotective effects in aged...... min), 24 h, and 48 h after stroke. Infarct size was assessed by magnetic resonance imaging at 21 days post MCAO. Animals received blinded neurological exams at 4 h, 24 h, 72 h, 7d, 14d, and 21d post-MCAO. RESULTS: Systemic treatment with C21 after stroke significantly improved neurological function...

  7. Neuroprotective-Neurotrophic Effect of Endogenous Dehydroepiandrosterone Sulfate During Intense Stress Exposure

    Science.gov (United States)

    2014-06-02

    Combination treatment with progesterone and vitamin D hormone may be more effective than monotherapy for traumatic brain injury. Front Neuroendocrinol...Taylor).Marcus K. Taylor a,b,c,⇑, Michael Stone a,c, Heidemarie K. Laurent b, d , Mitchell J. Rauh a,c, Douglas A. Granger b,e aBiobehavioral Sciences...and neurogenesis [20]. Regarding neuroprotection, DHEA(S) is thought to exert pro-survival effects by modulating gamma-ami- nobutyric acid [18

  8. Antihypertensive and neuroprotective effects of astaxanthin in experimental animals.

    Science.gov (United States)

    Hussein, Ghazi; Nakamura, Masami; Zhao, Qi; Iguchi, Tomomi; Goto, Hirozo; Sankawa, Ushio; Watanabe, Hiroshi

    2005-01-01

    Astaxanthin is a natural antioxidant carotenoid that occurs in a wide variety of living organisms. We investigated, for the first time, antihypertensive effects of astaxanthin (ASX-O) in spontaneously hypertensive rats (SHR). Oral administration of ASX-O for 14 d induced a significant reduction in the arterial blood pressure (BP) in SHR but not in normotensive Wistar Kyoto (WKY) strain. The long-term administration of ASX-O (50 mg/kg) for 5 weeks in stroke prone SHR (SHR-SP) induced a significant reduction in the BP. It also delayed the incidence of stroke in the SHR-SP. To investigate the action mechanism of ASX-O, the effects on PGF(2alpha)-induced contractions of rat aorta treated with NG-nitro-L-arginine methyl ester (L-NAME) were studied in vitro. ASX-O (1 to 10 microM) induced vasorelaxation mediated by nitric oxide (NO). The results suggest that the antihypertensive effect of ASX-O may be due to a NO-related mechanism. ASX-O also showed significant neuroprotective effects in ischemic mice, presumably due to its antioxidant potential. Pretreatment of the mice with ASX-O significantly shortened the latency of escaping onto the platform in the Morris water maze learning performance test. In conclusion, these results indicate that astaxanthin can exert beneficial effects in protection against hypertension and stroke and in improving memory in vascular dementia.

  9. Neuroprotective effect of paeonol against isoflurane- induced ...

    African Journals Online (AJOL)

    Purpose: To investigate whether paeonol affords neuroprotection against isoflurane-induced neurotoxicity. Methods: Separate ... significant improvement in the general behaviour and working memory of the rats. Conclusion: Paeonol significantly .... any visual impairments and/or swimming difficulties. The pool was covered ...

  10. Neuroprotective effect of paeonol against isofluraneinduced ...

    African Journals Online (AJOL)

    Purpose: To investigate whether paeonol affords neuroprotection against isoflurane-induced neurotoxicity. Methods: Separate groups of neonatal rat pups were administered paeonol (20, 40 or 80 mg/kg) from post-natal day 3 (P3) to post-natal day 15. On post-natal day 7, the pups were exposed to 6 h of isoflurane (0.75 ...

  11. Cortical spreading depression produces a neuroprotective effect activating mitochondrial uncoupling protein-5

    Directory of Open Access Journals (Sweden)

    Viggiano E

    2016-07-01

    Full Text Available Emanuela Viggiano,1,2 Vincenzo Monda,1 Antonietta Messina,1 Fiorenzo Moscatelli,3 Anna Valenzano,3 Domenico Tafuri,4 Giuseppe Cibelli,3 Bruno De Luca,1 Giovanni Messina,1,3 Marcellino Monda1 1Department of Experimental Medicine, Section of Human Physiology and Unit of Dietetics and Sports Medicine, Second University of Naples, Naples, 2Department of Medicine, University of Padua, Padua, 3Department of Clinical and Experimental Medicine, University of Foggia, Foggia, 4Department of Motor Sciences and Wellness, University of Naples “Parthenope”, Naples, Italy Abstract: Depression of electrocorticogram propagating over the cortex surface results in cortical spreading depression (CSD, which is probably related to the pathophysiology of stroke, epilepsy, and migraine. However, preconditioning with CSD produces neuroprotection to subsequent ischemic episodes. Such effects require the expression or activation of several genes, including neuroprotective ones. Recently, it has been demonstrated that the expression of the uncoupling proteins (UCPs 2 and 5 is amplified during brain ischemia and their expression exerts a long-term effect upon neuron protection. To evaluate the neuroprotective consequence of CSD, the expression of UCP-5 in the brain cortex was measured following CSD induction. CSD was evoked in four samples of rats, which were sacrificed after 2 hours, 4 hours, 6 hours, and 24 hours. Western blot analyses were carried out to measure UCP-5 concentrations in the prefrontal cortices of both hemispheres, and immunohistochemistry was performed to determine the localization of UCP-5 in the brain cortex. The results showed a significant elevation in UCP-5 expression at 24 hours in all cortical strata. Moreover, UCP-5 was triggered by CSD, indicating that UCP-5 production can have a neuroprotective effect. Keywords: cortical spreading depression, neuroprotective effect, uncoupling protein-5

  12. Rubia cordifolia, Fagonia cretica linn and Tinospora cordifolia exert neuroprotection by modulating the antioxidant system in rat hippocampal slices subjected to oxygen glucose deprivation

    Directory of Open Access Journals (Sweden)

    Biswas Saibal K

    2004-08-01

    Full Text Available Abstract Background The major damaging factor during and after the ischemic/hypoxic insult is the generation of free radicals, which leads to apoptosis, necrosis and ultimately cell death. Rubia cordifolia (RC, Fagonia cretica linn (FC and Tinospora cordifolia (TC have been reported to contain a wide variety of antioxidants and have been in use in the eastern system of medicine for various disorders. However, their mechanism of action was largely unknown. We therefore selected these herbs for the present study to test their neuroprotective ability and the associated mechanism in rat hippocampal slices subjected to oxygen-glucose deprivation (OGD. Methods Hippocampal Slices were subjected to OGD (oxygen glucose deprivation and divided into 3 groups: control, OGD and OGD + drug treated. Cytosolic Cu-Zn superoxide dismutase (Cu-Zn SOD, reduced glutathione (GSH, glutathione peroxidase (GPx, nitric oxide (NO was measured as nitrite (NO2 in the supernatant and protein assays were performed in the respective groups at various time intervals. EPR was used to establish the antioxidant effect of RC, FC and TC with respect to superoxide anion (O2.-, hydroxyl radicals (. OH, nitric oxide (NO radical and peroxynitrite anion (ONOO generated from pyrogallol, menadione, DETA-NO and Sin-1 respectively. RT-PCR was performed for the three groups for GCLC, iNOS, Cu-Zn SOD and GAPDH gene expression. Results All the three herbs were effective in elevating the GSH levels, expression of the gamma-glutamylcysteine ligase and Cu-Zn SOD genes. The herbs also exhibited strong free radical scavenging properties against reactive oxygen and nitrogen species as studied by electron paramagnetic resonance spectroscopy. In addition all the three herbs significantly diminished the expression of iNOS gene after 48 hours which plays a major role in neuronal injury during hypoxia/ischemia. Conclusions RC, FC and TC therefore attenuate oxidative stress mediated cell injury during OGD

  13. The Neuroprotective Effect Of Electro-Acupuncture Against Ischemic ...

    African Journals Online (AJOL)

    The Neuroprotective Effect Of Electro-Acupuncture Against Ischemic Stroke In Animal Model: A Review. ... Conclusion: An awareness of the benefits of acupuncture might lead more patients into accepting acupuncture therapy for the management of patients with ischemic stroke and patients with high risk of ischemic stroke.

  14. Neuroprotective effect of Terminalia chebula extracts and ellagic ...

    African Journals Online (AJOL)

    Background: Alzheimer's disease (AD) is one of the common neurodegenerative disorders among elderly. The purpose of this study was to determine the neuroprotective effect and mechanisms of action underlying the Terminalia chebula extracts and ellagic acid by using beta-amyloid25-35 (Aβ25-35)-induced cell toxicity ...

  15. Neuroprotective effect corilagin in spinal cord injury rat model by ...

    African Journals Online (AJOL)

    Background: Neurological functions get altered in a patient suffering from spinal cord injury (SCI). Present study evaluates the neuroprotective effect of corilagin in spinal cord injury rats by inhibiting nuclear factor-kappa B (NF-κB), inflammatory mediators and apoptosis. Materials and method: Spinal cord injury was ...

  16. TRPV1 may increase the effectiveness of estrogen therapy on neuroprotection and neuroregeneration

    Directory of Open Access Journals (Sweden)

    Ricardo Ramírez-Barrantes

    2016-01-01

    Full Text Available Aging induces physical deterioration, loss of the blood brain barrier, neuronal loss-induced mental and neurodegenerative diseases. Hypotalamus-hypophysis-gonad axis aging precedes symptoms of menopause or andropause and is a major determinant of sensory and cognitive integrated function. Sexual steroids support important functions, exert pleiotropic effects in different sensory cells, promote regeneration, plasticity and health of the nervous system. Their diminution is associated with impaired cognitive and mental health and increased risk of neurodegenerative diseases. Then, restoring neuroendocrine axes during aging can be key to enhance brain health through neuroprotection and neuroregeneration, depending on the modulation of plasticity mechanisms. Estrogen-dependent transient receptor potential cation channel, subfamily V, member 1 (TRPV1 expression induces neuroprotection, neurogenesis and regeneration on damaged tissues. Agonists of TRPV1 can modulate neuroprotection and repair of sensitive neurons, while modulators as other cognitive enhancers may improve the survival rate, differentiation and integration of neural stem cell progenitors in functional neural network. Menopause constitutes a relevant clinical model of steroidal production decline associated with progressive cognitive and mental impairment, which allows exploring the effects of hormone therapy in health outcomes such as dysfunction of CNS. Simulating the administration of hormone therapy to virtual menopausal individuals allows assessing its hypothetical impact and sensitivity to conditions that modify the effectiveness and efficiency.

  17. Neuroprotective effects of anticonvulsants in rat hippocampal slice cultures exposed to oxygen/glucose deprivation

    DEFF Research Database (Denmark)

    Rekling, Jens C

    2003-01-01

    cell death induced by OGD. The newer anticonvulsants carbamazepine, felbamate, lamotrigine, tiagabine, and oxcarbazepine also had significant neuroprotective effects, but gabapentin, valproic acid (10 mM), levetiracetam and retigabine were not neuroprotective at a concentration up to 300 micro...

  18. The Long Run: Neuroprotective Effects of Physical Exercise on Adult Neurogenesis from Youth to Old Age

    Science.gov (United States)

    Saraulli, Daniele; Costanzi, Marco; Mastrorilli, Valentina; Farioli-Vecchioli, Stefano

    2017-01-01

    Background The rapid lengthening of life expectancy has raised the problem of providing social programs to counteract the age-related cognitive decline in a growing number of older people. Physical activity stands among the most promising interventions aimed at brain wellbeing, because of its effective neuroprotective action and low social cost. The purpose of this review is to describe the neuroprotective role exerted by physical activity in different life stages. In particular, we focus on adult neurogenesis, a process which has proved being highly responsive to physical exercise and may represent a major factor of brain health over the lifespan. Methods The most recent literature related to the subject has been reviewed. The text has been divided into three main sections, addressing the effects of physical exercise during childhood/adolescence, adulthood and aging, respectively. For each one, the most relevant studies, carried out on both human participants and rodent models, have been described. Results The data reviewed converge in indicating that physical activity exerts a positive effect on brain functioning throughout the lifespan. However, uncertainty remains about the magnitude of the effect and its biological underpinnings. Cellular and synaptic plasticity provided by adult neurogenesis are highly probable mediators, but the mechanism for their action has yet to be conclusively established. Conclusion Despite alternative mechanisms of action are currently debated, age-appropriate physical activity programs may constitute a large-scale, relatively inexpensive and powerful approach to dampen the individual and social impact of age-related cognitive decline. PMID:27000776

  19. The neuroprotective effect of nicotine in Parkinson’s disease models is associated with inhibiting PARP-1 and caspase-3 cleavage

    Directory of Open Access Journals (Sweden)

    Justin Y.D. Lu

    2017-10-01

    Full Text Available Clinical evidence points to neuroprotective effects of smoking in Parkinson’s disease (PD, but the molecular mechanisms remain unclear. We investigated the pharmacological pathways involved in these neuroprotective effects, which could provide novel ideas for developing targeted neuroprotective treatments for PD. We used the ETC complex I inhibitor methylpyridinium ion (MPP+ to induce cell death in SH-SY5Y cells as a cellular model for PD and found that nicotine inhibits cell death. Using choline as a nicotinic acetylcholine receptor (nAChR agonist, we found that nAChR stimulation was sufficient to protect SH-SY5Y cells against cell death from MPP+. Blocking α7 nAChR with methyllycaconitine (MLA prevented the protective effects of nicotine, demonstrating that these receptors are necessary for the neuroprotective effects of nicotine. The neuroprotective effect of nicotine involves other pathways relevant to PD. Cleaved Poly (ADP-ribose polymerase-1 (PARP-1 and cleaved caspase-3 were decreased by nicotine in 6-hydroxydopamine (6-OHDA lesioned mice and in MPP+-treated SH-SY5Y cells. In conclusion, our data indicate that nicotine likely exerts neuroprotective effects in PD through the α7 nAChR and downstream pathways including PARP-1 and caspase-3. This knowledge could be pursued in future research to develop neuroprotective treatments for PD.

  20. Jieyuanshen decoction exerts antidepressant effects on depressive ...

    African Journals Online (AJOL)

    Conclusion: JYAS-D had a significant antidepressant-like effect on rat model through regulating serum concentration of CORT, ACTH and CRH, increasing the content of hippocampus GR and regulating the equilibrium of amino acids neurotransmitter. Keywords: Hypothalamic-pituitary-adrenal (HPA) axis; Glucocorticoid/ ...

  1. Neuroprotective effects of Resveratrol in Alzheimer Disease Pathology

    Directory of Open Access Journals (Sweden)

    Shraddha D Rege

    2014-09-01

    Full Text Available Alzheimer’s disease (AD is a chronic neurodegenerative disorder characterized by a progressive loss of cognitive and behavioral abilities. Extracellular senile plaques and intracellular neurofibrillary tangles are hallmarks of AD. Researchers aim to analyze the molecular mechanisms underlying AD pathogenesis; however, the therapeutic options available to treat this disease are inadequate. In the past few years, several studies have reported interesting insights about the neuroprotective properties of the polyphenolic compound resveratrol (3, 5, 4’-trihydroxy-trans-stilbene when used with in vitro and in vivo models of AD. The aim of this review is to focus on the neuroprotective and antioxidant effects of resveratrol on AD and its multiple potential mechanisms of action. In addition, because the naturally occurring forms of resveratrol have a very limited half-life in plasma, a description of potential analogues aimed at increasing bioavailability in plasma is also discussed.

  2. Molecular Basis for Certain Neuroprotective Effects of Thyroid Hormone

    Directory of Open Access Journals (Sweden)

    Paul eDavis

    2011-10-01

    Full Text Available The pathophysiology of brain damage that is common to ischemia-reperfusion inury and brain trauma includes disordered neuronal and glial cell energetics, intracellular acidosis, calcium toxicity, extracellular excitotoxic glutamate accumulation and dysfunction of the cytoskeleton and endoplasmic reticulum. Thyroid hormone isoforms, 3, 5, 3'-triiodo-L-thyronine (T3 and L-thyroxine (T4, have nongenomic and genomic actions that are relevant to repair of certain features of the pathophysiology of brain damage. Thyroid hormone can nongenomically repair intracullar H+ accumulation by stimulation of the Na+/H+ exchanger and can support desirably low [Ca2+]i.c. by activation of plasma membrane Ca2+-ATPase. Thyroid hormone nongenomically stimulates astrocyte glutamate uptake, an action that protects both glial cells and neurons. The hormone supports the integrity of the cytoskeleton by its effect on actin. Several proteins linked to thyroid hormone action are also neuroprotective. For example, the hormone stimulates expression of the seladin-1 gene whose gene product is anti-apoptotic and is potentially protection in the setting of neurodegeneration. Transthyretin (TTR is a serum transport protein for T4 that is important to blood-brain barrier transfer of the hormone and TTR has also been found to be neuroprotective in the setting of ischemia. Finally, the interesting thyronamine derivatives of T4 have been shown to protect against ischemic brain damage through their ability to induce hypothermia in the intact organism. Thus, thyroid hromone or hormone derivatives have experimental promise as neuroprotective agents.

  3. Neuroprotective effects of daphnetin against NMDA receptor-mediated excitotoxicity.

    Science.gov (United States)

    Yang, Le; Yang, Qi; Zhang, Kun; Li, Yu-Jiao; Wu, Yu-Mei; Liu, Shui-Bing; Zheng, Lian-He; Zhao, Ming-Gao

    2014-09-15

    The accumulation of glutamate can excessively activate the N-methyl-d-aspartate (NMDA) receptors and cause excitotoxicity. Daphnetin (Dap), a coumarin derivative, is a protein kinase inhibitor that exhibits antioxidant and neuroprotective properties. However, little is known about the neuroprotective effects of Dap on glutamate-induced excitotoxicity. We evaluated the neuroprotective activities in the primary cultured cortical neurons against NMDA-induced excitotoxicity. Pretreatment with Dap significantly prevented NMDA-induced neuronal cell loss. Dap significantly inhibited the neuronal apoptosis by regulating balance of Bcl-2 and Bax expression. Furthermore, pretreatment of Dap reversed the up-regulation of NR2B-containing NMDA receptors and inhibited the intracellular Ca2+ overload induced by NMDA exposure. In addition, Dap prevented cerebral ischemic injury in mice induced via a 2 h middle cerebral artery occlusion and a 24 h reperfusion in vivo. The findings suggest that Dap prevents the excitotoxicity through inhibiting the NR2B-containing NMDA receptors and the subsequent calcium overload in cultured cortical neurons.

  4. Neuroprotective effects of 17β-estradiol rely on estrogen receptor membrane initiated signals

    Directory of Open Access Journals (Sweden)

    Marco eFiocchetti

    2012-04-01

    Full Text Available 17β-estradiol (E2 exerts protective effects in the central nervous system besides its crucial role in many physiological and pathological events. E2 effects are not restricted to the brain areas related with the control of the reproductive function, but rather are widespread throughout the developing and the adult brain. E2 actions are mediated by estrogen receptors (i.e., ERα and ERβ belonging to the nuclear receptor super family. As members of the ligand-regulated transcription factor family, the actions of ERs in the brain were thought to mediate only the E2 long-term transcriptional effects. However, a growing body of evidence has emerged indicating the presence of rapid, membrane initiated E2 effects in the brain which result independent from ER transcriptional activities and involved in E2-induced neuroprotection. Aim of this review is to focus on the rapid effects of E2 in the brain taking into account the specific contribution of the signaling pathway of ERβ subtype in neuroprotective actions of E2.

  5. Novel insights into lithium's mechanism of action: neurotrophic and neuroprotective effects.

    Science.gov (United States)

    Quiroz, Jorge A; Machado-Vieira, Rodrigo; Zarate, Carlos A; Manji, Husseini K

    2010-01-01

    The monovalent cation lithium partially exerts its effects by activating neurotrophic and neuroprotective cellular cascades. Here, we discuss the effects of lithium on oxidative stress, programmed cell death (apoptosis), inflammation, glial dysfunction, neurotrophic factor functioning, excitotoxicity, and mitochondrial stability. In particular, we review evidence demonstrating the action of lithium on cyclic adenosine monophosphate (cAMP)-mediated signal transduction, cAMP response element binding activation, increased expression of brain-derived neurotrophic factor, the phosphatidylinositide cascade, protein kinase C inhibition, glycogen synthase kinase 3 inhibition, and B-cell lymphoma 2 expression. Notably, we also review data from clinical studies demonstrating neurotrophic effects of lithium. We expect that a better understanding of the clinically relevant pathophysiological targets of lithium will lead to improved treatments for those who suffer from mood as well as neurodegenerative disorders. Copyright 2010 S. Karger AG, Basel.

  6. Neuroprotective effect of 3-morpholinosydnonimine against Zn²⁺-induced PC12 cell death.

    Science.gov (United States)

    An, Jeong Mi; Moon, Seong Ah; Hong, Soo Young; Kang, Jeong Wan; Seo, Jeong Taeg

    2015-02-05

    Excessive intracellular accumulation of zinc (Zn(2+)) is neurotoxic and contributes to a number of neuropathological conditions. Here, we investigated the protective effect of 3-morpholinosydnonimine (SIN-1) against Zn(2+)-induced neuronal cell death in differentiated PC12 cells. We found that Zn(2+)-induced PC12 cell death was reduced in a concentration-dependent manner by pretreatment with SIN-1. The intracellular accumulation of Zn(2+) was not affected by pretreatment with SIN-1, indicating that SIN-1-induced neuroprotection was not attributable to reduced influx of Zn(2+) into cells. SIN-1C, the stable decomposition product of SIN-1, failed to prevent Zn(2+)-induced cell death. Furthermore, the protective effect of SIN-1 against Zn(2+)-induced PC12 cell death was almost completely abolished by uric acid, a free radical scavenger, suggesting that reactive oxygen and nitrogen species generated by SIN-1 may contribute to the protective effect. SIN-1 prevented the inactivation of glutathione reductase (GR) and the increase in the ratio of oxidized glutathione/total glutathione (GSSG/total GSH) induced by Zn(2+). Addition of membrane permeable GSH ethyl ester (GSH-EE) to PC12 cells prior to Zn(2+) treatment significantly increased cell viability. We therefore conclude that SIN-1 may exert neuroprotective effect against Zn(2+)-induced cell death in differentiated PC12 cells by preventing inhibition of GR and increase in GSSG/total GSH ratio. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Ketogenic Diet Provides Neuroprotective Effects against Ischemic Stroke Neuronal Damages

    Directory of Open Access Journals (Sweden)

    Sheida Shaafi

    2014-12-01

    Full Text Available Ischemic stroke is a leading cause of death and disability in the world. Many mechanisms contribute in cell death in ischemic stroke. Ketogenic diet which has been successfully used in the drug-resistant epilepsy has been shown to be effective in many other neurologic disorders. The mechanisms underlying of its effects are not well studied, but it seems that its neuroprotective ability is mediated at least through alleviation of excitotoxicity, oxidative stress and apoptosis events. On the basis of these mechanisms, it is postulated that ketogenic diet could provide benefits to treatment of cerebral ischemic injuries.

  8. Neuroprotective effects of polygalacic acid on scopolamine-induced memory deficits in mice.

    Science.gov (United States)

    Guo, Changrun; Shen, Jinyang; Meng, Zhaoqing; Yang, Xiaolin; Li, Fei

    2016-02-15

    Polygala tenuifolia Willd is a Traditional Chinese Medicine used for the treatment of learning and memory deficits. Triterpenoid saponins, the main bioactive compounds of Polygala tenuifolia Willd, are easily hydrolyzed to polygalacic acid (PA). The present study was undertaken to investigate the neuroprotective effects of PA on scopolamine-induced cognitive dysfunction and to elucidate its underlying mechanisms of action. PA (3, 6, and 12 mg/kg) was administered orally to mice for fourteen days, and scopolamine (1 mg/kg) was injected intraperitoneally for fourteen days to induce memory impairment. Memory-related behaviors were evaluated using the Morris water maze. Cholinergic and neuroinflammatory activities were measured in brain tissue. Superoxide dismutase activities, malondialdehyde and reduced glutathione contents were also measured in the brains. Treatment with scopolamine significantly increased the escape latency time, decreased the number of crossings, and shortened the time spent in the target quadrant, while PA reversed these scopolamine-induced effects. PA significantly improved cholinergic system reactivity, as indicated by decreased acetylcholinesterase (AChE) activity, increased choline acetyltransferase (ChAT) activity, and elevated levels of acetylcholine (ACh) in the hippocampus and frontal cortex. PA also significantly ameliorated neuroinflammation and oxidative stress in mice. These results suggest that PA might exert a significant neuroprotective effect on cognitive impairment, driven in part by the modulation of cholinergic activity and neuroinflammation. Copyright © 2015 Elsevier GmbH. All rights reserved.

  9. The Neuroprotective Effects of SIRT1 on NMDA-Induced Excitotoxicity

    Directory of Open Access Journals (Sweden)

    Xiaorong Yang

    2017-01-01

    Full Text Available Silent information regulator 1 (SIRT1, an NAD+-dependent deacetylase, is involved in the regulation of gene transcription, energy metabolism, and cellular aging and has become an important therapeutic target across a range of diseases. Recent research has demonstrated that SIRT1 possesses neuroprotective effects; however, it is unknown whether it protects neurons from NMDA-mediated neurotoxicity. In the present study, by activation of SIRT1 using resveratrol (RSV in cultured cortical neurons or by overexpression of SIRT1 in SH-SY5Y cell, we aimed to evaluate the roles of SIRT1 in NMDA-induced excitotoxicity. Our results showed that RSV or overexpression of SIRT1 elicited inhibitory effects on NMDA-induced excitotoxicity including a decrease in cell viability, an increase in lactate dehydrogenase (LDH release, and a decrease in the number of living cells as measured by CCK-8 assay, LDH test, and Calcein-AM and PI double staining. RSV or overexpression of SIRT1 significantly improved SIRT1 deacetylase activity in the excitotoxicity model. Further study suggests that overexpression of SIRT1 partly suppressed an NMDA-induced increase in p53 acetylation. These results indicate that SIRT1 activation by either RSV or overexpression of SIRT1 can exert neuroprotective effects partly by inhibiting p53 acetylation in NMDA-induced neurotoxicity.

  10. Neuroprotective effects of probenecid in a transgenic animal model of Huntington's disease.

    Science.gov (United States)

    Vamos, Eniko; Voros, Krisztina; Zadori, Denes; Vecsei, Laszlo; Klivenyi, Peter

    2009-09-01

    Huntington's disease (HD) is an autosomal dominantly inherited disorder, caused by an expanded polyglutamine region of a protein called huntingtin. The excitotoxicity, oxidative damage and altered membrane transport may have an important role in the pathogenesis of HD. Probenecid is a non-selective inhibitor of multidrug resistance-associated proteins, but it also inhibits organic anion transporters. In this study, we examined the effects of probenecid on the survival, behaviour and immunohistochemical changes in the N171-82Q transgenic mouse model of HD. After probenecid administration, the duration of survival improved by 35%. The motor activity was significantly ameliorated as compared with the control transgenic group. Probenecid treatment significantly reduced the neuronal loss and the number of neuronal intranuclear aggregates. These results suggest that probenecid may exert a neuroprotective effect by increasing the membrane transport of protective compounds, and/or inhibiting the toxic compounds.

  11. Neuroprotective Effects of Palm vitamin E Tocotrienols

    Directory of Open Access Journals (Sweden)

    Yuen Kah Hay

    2014-11-01

    Full Text Available Cell and animal studies have convincingly shown the tocotrienols to be neuro protective. However, many compounds have been proven neuro protective in pre-clinical studies but none succeeded in human trials. Such failures can be attributed to the use of a wrong study model, example acute ischemic stroke. Stroke has a short treatment time window of about 4.5 hours and hence the difficulty of giving the compound within this time period. Furthermore, disruption of blood flow to the affected areas will limit the administered agent from reaching the target tissues. Therefore, the compound should best be given before the stroke event, like in the animal studies. Considering the above, the present study was conducted to investigate the neuro protective effects of palm vitamin E tocotrienols using human volunteers with white matter lesions (WMLs. WMLs are associated with ischemic small blood vessel disease of the brain leading to bundles of nerve fibers degenerating. The lesions are self-progressive and can be quantified using magnetic resonance imaging (MRI. In the present study, 121 volunteers with WMLs were randomized 200mg palm tocotrienols twice daily or placebo and imaged at baseline, after 1 year and 2 years of supplementation. Changes in the volume of WMLs from baseline were then determined. Results obtained showed that the mean WML volume of the treated group remained essentially unchanged after 2 years, whereas the placebo group showed a mark progression. The change in the mean WML volume of the 2 groups was significantly different (p<0.05 after 2 years. Hence, the present study provided clinical evidence that palm vitamin E tocotrienols are neuro protective and may help to minimize tissue injury of the brain during a stroke event, thus making a difference in the stroke outcome when taken as a supplement.

  12. The Long Run: Neuroprotective Effects of Physical Exercise on Adult Neurogenesis from Youth to Old Age.

    Science.gov (United States)

    Saraulli, Daniele; Costanzi, Marco; Mastrorilli, Valentina; Farioli-Vecchioli, Stefano

    2017-01-01

    The rapid lengthening of life expectancy has raised the problem of providing social programs to counteract the age-related cognitive decline in a growing number of older people. Physical activity stands among the most promising interventions aimed at brain wellbeing, because of its effective neuroprotective action and low social cost. The purpose of this review is to describe the neuroprotective role exerted by physical activity in different life stages. In particular, we focus on adult neurogenesis, a process which has proved being highly responsive to physical exercise and may represent a major factor of brain health over the lifespan. The most recent literature related to the subject has been reviewed. The text has been divided into three main sections, addressing the effects of physical exercise during childhood/ adolescence, adulthood and aging, respectively. For each one, the most relevant studies, carried out on both human participants and rodent models, have been described. The data reviewed converge in indicating that physical activity exerts a positive effect on brain functioning throughout the lifespan. However, uncertainty remains about the magnitude of the effect and its biological underpinnings. Cellular and synaptic plasticity provided by adult neurogenesis are highly probable mediators, but the mechanism for their action has yet to be conclusively established. Despite alternative mechanisms of action are currently debated, age-appropriate physical activity programs may constitute a large-scale, relatively inexpensive and powerful approach to dampen the individual and social impact of age-related cognitive decline. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Ethanol and Cognition: Indirect Effects, Neurotoxicity and Neuroprotection: A Review

    Directory of Open Access Journals (Sweden)

    John C.M. Brust

    2010-04-01

    Full Text Available Ethanol affects cognition in a number of ways. Indirect effects include intoxication, withdrawal, brain trauma, central nervous system infection, hypoglycemia, hepatic failure, and Marchiafava-Bignami disease. Nutritional deficiency can cause pellagra and Wernicke-Korsakoff disorder. Additionally, ethanol is a direct neurotoxin and in sufficient dosage can cause lasting dementia. However, ethanol also has neuroprotectant properties and in low-to-moderate dosage reduces the risk of dementia, including Alzheimer type. In fetuses ethanol is teratogenic, and whether there exists a safe dose during pregnancy is uncertain and controversial.

  14. A New Triterpene from Buddleja lindleyana with Neuroprotective Effect

    Directory of Open Access Journals (Sweden)

    Ya-Shuo Ren

    2017-07-01

    Full Text Available In the phytochemical investigation of Buddleja lindleyana , a new 3-acetyl substituted triterpene, 13, 28-epoxy-23-hydroxy-3β-acetoxy-olean-11-ene (1, together with four same skeleton type known compounds (2-5 were isolated. The structure of 1 was elucidated by means of extensive spectroscopic analysis. Their neuroprotective effect against 1-methyl-4 -phenylpyridinium ion-induced (MPP +-induced neurotoxicity in SH-SY5Y cells were evaluated. The structure activity relationship of compounds 1-5 has been discussed preliminarily.

  15. Neuroprotective effect of melatonin in experimentally induced hypobaric hypoxia.

    Science.gov (United States)

    Vornicescu, Corina; Boşca, Bianca; Crişan, Doiniţa; Yacoob, Sumaya; Stan, Nora; Filip, Adriana; Şovrea, Alina

    2013-01-01

    Melatonin (MEL) is an endogenous neurohormone with many biological functions, including a powerful antioxidant effect. The aim of the present study was to determine whether MEL protects the brain tissue from the oxidative stress induced by hypobaric hypoxia (HH) in vivo. This study was performed on Wistar rats randomly assigned in four groups, according to the pressure conditions and treatment: Group 1: normoxia and placebo; Group 2: HH and placebo; Group 3: normoxia and MEL; and Group 4: HH and MEL. The following aspects were evaluated: cognitive function (space reference and memory), oxidative stress parameters - serum and brain malondialdehyde (MDA) and reduced glutathione (GSH) levels -, and brain tissue macroscopic and microscopic morphological changes. Exposure to oxidative stress results in cognitive dysfunctions and biochemical alterations: significant increase of MDA and reduction of GSH in both serum and brain tissue. The most important morphological changes were observed in Group 2: increased cellularity, loss of pericellular haloes, shrunken neurons with scanty cytoplasm and hyperchromatic, pyknotic or absent nuclei; reactive gliosis, edema and blood-brain barrier alterations could also be observed in some areas. MEL treatment significantly diminished all these effects. Our results suggest that melatonin is a neuroprotective antioxidant both in normoxia and hypobaric hypoxia that can prevent and counteract the deleterious effects of oxidative stress (neuronal death, reactive astrogliosis, memory impairment and cognitive dysfunctions). Dietary supplements containing melatonin might be useful neuroprotective agents for the therapy of hypoxia-induced consequences.

  16. Antivasoconstrictor effect of the neuroprotective agent dexrazoxane in rat aorta.

    Science.gov (United States)

    Vidrio, Horacio; Carrasco, Omar F; Rodríguez, Rodolfo

    2006-12-14

    Dexrazoxane is used clinically to reduce the cardiotoxicity of anthracycline cancer chemotherapeutic agents, acting by an iron-chelating antioxidant mechanism. In a study designed to explore the possible mechanism of the recently described neuroprotective effect of the drug in cerebral ischemia, its influence on vascular reactivity was determined in rat aortic rings. Dexrazoxane was found to be devoid of direct contractile or relaxant activity and to have no influence on responses to acetylcholine or histamine (relaxation), or to angiotensin or serotonin (contraction). In contrast, it decreased contractions to norepinephrine, as evidenced by rightward displacement of the concentration-response curves. The effect was prevented by the removal of the endothelium and by the alpha(2)-adrenoceptor antagonist yohimbine; it was partially antagonized by the endothelium-derived depolarizing factor inhibitor clotrimazole, but was not affected by L-NAME or indomethacin, inhibitors of endothelial nitric oxide and prostacyclin production. The anti-contractile effect did not occur in rings stimulated with the alpha(1)-adrenoceptor agonist phenylephrine. It was concluded that dexrazoxane opposes norepinephrine vascular contraction by enhancing endothelial alpha(2)-adrenoceptor-mediated release of relaxing factor(s). The drug could thus offset the deleterious vasoconstriction elicited by the increased circulating catecholamines present during cerebral ischemia, and by this mechanism produce neuroprotection.

  17. Neuroprotective effects of anticonvulsants in rat hippocampal slice cultures exposed to oxygen/glucose deprivation

    DEFF Research Database (Denmark)

    Rekling, Jens C

    2003-01-01

    Some anticonvulsants show neuroprotective effects, and may be of use in reducing neuronal death resulting from stroke or traumatic brain injury. Here I report that a broad range of anticonvulsants protect cells in hippocampal slice cultures from death induced by oxygen/glucose deprivation (OGD...... cell death induced by OGD. The newer anticonvulsants carbamazepine, felbamate, lamotrigine, tiagabine, and oxcarbazepine also had significant neuroprotective effects, but gabapentin, valproic acid (10 mM), levetiracetam and retigabine were not neuroprotective at a concentration up to 300 micro......M. In conclusion, several classical and newer anticonvulsants have neuroprotective properties in an in vitro model that simulates cerebral ischemia....

  18. The neuroprotective role of endocannabinoids against chemical-induced injury and other adverse effects.

    Science.gov (United States)

    Zogopoulos, Panagiotis; Vasileiou, Ioanna; Patsouris, Efstratios; Theocharis, Stamatios

    2013-04-01

    Considerable progress has been made, recently, in understanding the role of the endocannabinoid system in regard to neuroprotection. Endogenous cannabinoids have received increasing attention as potential protective agents in several cases of neuronal injury. The endocannabinoid system is comprised of cannabinoid receptors (CB1 and CB2), their endogenous ligands (endocannabinoids) and proteins responsible for their metabolism. Endocannabinoids serve as retrograde signalling messengers in GABAergic and glutamatergic synapses, as well as modulators of post-synaptic transmission, interacting with other neurotransmitters, including norepinephrine and dopamine. Furthermore, endocannabinoids modulate neuronal, glial and endothelial cell function and exert neuromodulatory, anti-excitotoxic, anti-inflammatory and vasodilatory effects. Physiological stimuli and pathological conditions lead to differential increases in brain endocannabinoids that regulate distinct biological functions. The purpose of this review is to present the available in vivo and in vitro experimental data, up to date, regarding the endocannabinoid system and its role in neuroprotection, as well as its possible therapeutic perspectives. Copyright © 2013 John Wiley & Sons, Ltd.

  19. Ghrelin-AMPK Signaling Mediates the Neuroprotective Effects of Calorie Restriction in Parkinson's Disease

    Science.gov (United States)

    Bayliss, Jacqueline A.; Lemus, Moyra B.; Stark, Romana; Santos, Vanessa V.; Thompson, Aiysha; Rees, Daniel J.; Galic, Sandra; Elsworth, John D.; Kemp, Bruce E.; Davies, Jeffrey S.

    2016-01-01

    Calorie restriction (CR) is neuroprotective in Parkinson's disease (PD) although the mechanisms are unknown. In this study we hypothesized that elevated ghrelin, a gut hormone with neuroprotective properties, during CR prevents neurodegeneration in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD. CR attenuated the MPTP-induced loss of substantia nigra (SN) dopamine neurons and striatal dopamine turnover in ghrelin WT but not KO mice, demonstrating that ghrelin mediates CR's neuroprotective effect. CR elevated phosphorylated AMPK and ACC levels in the striatum of WT but not KO mice suggesting that AMPK is a target for ghrelin-induced neuroprotection. Indeed, exogenous ghrelin significantly increased pAMPK in the SN. Genetic deletion of AMPKβ1 and 2 subunits only in dopamine neurons prevented ghrelin-induced AMPK phosphorylation and neuroprotection. Hence, ghrelin signaling through AMPK in SN dopamine neurons mediates CR's neuroprotective effects. We consider targeting AMPK in dopamine neurons may recapitulate neuroprotective effects of CR without requiring dietary intervention. SIGNIFICANCE STATEMENT The neuroprotective mechanisms of calorie restriction (CR) in Parkinson's disease are unknown. Indeed, the difficulty to adhere to CR necessitates an alternative method to recapitulate the neuroprotective benefits of CR while bypassing dietary constraints. Here we show that CR increases plasma ghrelin, which targets substantia nigra dopamine to maintain neuronal survival. Selective deletion on AMPK beta1 and beta2 subunits only in DAT cre-expressing neurons shows that the ghrelin-induced neuroprotection requires activation of AMPK in substantia nigra dopamine neurons. We have discovered ghrelin as a key metabolic signal, and AMPK in dopamine neurons as its target, which links calorie restriction with neuroprotection in Parkinson's disease. Thus, targeting AMPK in dopamine neurons may provide novel neuroprotective benefits in Parkinson's disease. PMID

  20. Neuroprotective Effects of Butanol Fraction of Cordyceps cicadae on Glutamate-Induced Damage in PC12 Cells Involving Oxidative Toxicity.

    Science.gov (United States)

    Wang, Dan; Wang, Jibiao; Wang, Dujun; Yu, Xiaofeng; Olatunji, Opeyemi Joshua; Ouyang, Zhen; Wei, Yuan

    2018-01-01

    The current study was aimed at investigating the neuroprotective effects of the butanol fraction from Cordyceps cicadae (C BU ), which was responsible for the anti-aging effect of this medicine. Glutamate-induced PC12 cells were used as a model to determine the neuroprotective effect against oxidative cell death. Cell viability, cytotoxicity, flow cytometry, mitochondrial transmembrane potential (MMP), reactive oxygen species (ROS), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) levels were analyzed to assess neuronal cell survival or death. The results obtained from the above evaluations showed that C BU was the most effective fraction and even better than pure compounds present in C. cicadae in terms of suppressing glutamate-induced damage in PC12 cells, increasing cell viability, decreasing lactase dehydrogenase (LDH) release, and reduction of apoptosis induced by exposure to glutamate. Furthermore, C BU protected cells against mitochondrial dysfunction and oxidative stress as indicated by the suppression of ROS accumulation and up regulation of the levels of GSH-Px and SOD. In summary, the above results showed that C BU exerted neuroprotective effect against oxidative damage, and this activity could be partly due to the action of nucleosides present in the C BU . © 2018 Wiley-VHCA AG, Zurich, Switzerland.

  1. Novel Neuroprotective Effects of Melanin-Concentrating Hormone in Parkinson's Disease.

    Science.gov (United States)

    Park, Ji-Yeun; Kim, Seung-Nam; Yoo, Junsang; Jang, Jaehwan; Lee, Ahreum; Oh, Ju-Young; Kim, Hongwon; Oh, Seung Tack; Park, Seong-Uk; Kim, Jongpil; Park, Hi-Joon; Jeon, Songhee

    2017-12-01

    Acupuncture has shown the therapeutic effect on various neurodegenerative disorders including Parkinson's disease (PD). While investigating the neuroprotective mechanism of acupuncture, we firstly found the novel function of melanin-concentrating hormone (MCH) as a potent neuroprotective candidate. Here, we explored whether hypothalamic MCH mediates the neuroprotective action of acupuncture. In addition, we aimed at evaluating the neuroprotective effects of MCH and elucidating underlying mechanism in vitro and in vivo PD models. First, we tested whether hypothalamic MCH mediates the neuroprotective effects of acupuncture by challenging MCH-R1 antagonist (i.p.) in mice PD model. We also investigated whether MCH has a beneficial role in dopaminergic neuronal protection in vitro primary midbrain and human neuronal cultures and in vivo MPTP-induced, Pitx3 -/- , and A53T mutant mice PD models. Transcriptomics followed by quantitative PCR and western blot analyses were performed to reveal the neuroprotective mechanism of MCH. We first found that hypothalamic MCH biosynthesis was directly activated by acupuncture treatment and that administration of an MCH-R1 antagonist reverses the neuroprotective effects of acupuncture. A novel finding is that MCH showed a beneficial role in dopaminergic neuron protection via downstream pathways related to neuronal survival. This is the first study to suggest the novel neuroprotective action of MCH as well as the involvement of hypothalamic MCH in the acupuncture effects in PD, which holds great promise for the application of MCH in the therapy of neurodegenerative diseases.

  2. Neuroprotective effect of apocynin nitrone in oxygen glucose ...

    African Journals Online (AJOL)

    Purpose: To investigate the neuroprotective potential of apocynin nitrone (AN-1), a nitrone analogue of apocynin, in rat brain tissue as a novel candidate for ischemic stroke treatment. Methods: In vitro neuroprotection of AN-1 was studied in SH-SY5Y cells treated with oxygen glucose deprivation (OGD). Cell viability was ...

  3. Neuroprotective effect of melatonin on soluble Aβ1-42-induced cortical neurodegeneration via Reelin-Dab1 signaling pathway.

    Science.gov (United States)

    Hu, Chunli; Wang, Pan; Zhang, Shuman; Ren, Lili; Lv, Yiheng; Yin, Rui; Bi, Jing

    2017-07-01

    Soluble Aβ 1-42 oligomers play a vital role in the development and pathogenesis of Alzheimer's disease (AD). Melatonin could delay the progress of AD through multiple mechanisms. Reelin-Dab1 signaling plays an important role in AD, including neuronal function and synaptic plasticity. However, whether melatonin could exert its neuroprotective function against soluble Aβ 1-42 -induced neurotoxicity during AD development through regulating Reelin-Dab1 signaling remains poorly understood. AD rat model was established by soluble Aβ 1-42 repeated intracerebroventricular injection. Using immunohistochemistry and Western blot analyses, the effect of melatonin on synaptic plasticity, neuritic degeneration, and astrocyte activation was investigated in cerebral cortex. Meanwhile, the expression of Reelin and Dab1 was also examined in cerebral cortex. In our in vitro study, Reelin-Dab1 signaling was inhibited by Reelin antibody, and neuroprotective effect of melatonin against Aβ 1-42 was further determined. Melatonin ameliorated the neurotoxiciy and astrocyte activation induced by Aβ 1-42 in the cerebral cortex. Melatonin also blocked the reduction in Reelin and Dab1 expression induced by Aβ 1-42 . Using in vitro study, Reelin inactivation completely abolished the protective effect of melatonin against Aβ 1-42 -induced neurotoxicity. Melatonin might play its neuroprotective role against Aβ 1-42 through mediating Reelin-Dab1 signaling pathway. Melatonin could be a safe and remarkable therapeutic candidate for AD and other aged-associated neurodegenerative diseases.

  4. Neuroprotective effects of DHA in Alzheimer’s disease models

    Directory of Open Access Journals (Sweden)

    Florent-Béchard Sabrina

    2007-05-01

    Full Text Available Alzheimer’s disease (AD is a major public health concern in all developped countries. Although the precise cause of AD is still unknown, a growing body of evidence supports the notion that soluble oligomers of amyloid b-peptide (Aβ may be the proximate effectors of synaptic injuries and neuronal death in the early stages of AD. AD patients display lower levels of docosahexaenoic acid (DHA, C22:6; n-3 in plasma and brain tissues as compared to control subjects of same age. Furthermore, epidemiological studies suggest that high DHA intake might have protective properties against neurodegenerative diseases. These observations are supported by in vivo studies showing that DHA-rich diets limit the synaptic loss and cognitive defects induced by Aβ peptide. Although the molecular basis underlying these neuroprotective effects remains unknown, several mechanisms have been proposed such as (i regulation of the expression of potentially protective genes, (ii activation of antiinflammatory pathways, (iii modulation of functional properties of the synaptic membranes along with changes in their physicochemical and structural features. We recently demonstrated that DHA protects neurons from soluble Aβ oligomer-induced apoptosis. Indeed, DHA pretreatment was observed to significantly increase neuronal survival upon Aβ treatment by preventing cytoskeleton perturbations, caspase activation and apoptosis, as well as by promoting ERK-related survival pathways. These data suggest that DHA enrichment most likely induces changes in neuronal membrane properties with functional outcomes, thereby increasing protection from soluble Aβ oligomers. Such neuroprotective effects could be of major interest in the prevention of AD and other neurodegenerative diseases.

  5. Pridopidine, a dopamine stabilizer, improves motor performance and shows neuroprotective effects in Huntington disease R6/2 mouse model.

    Science.gov (United States)

    Squitieri, Ferdinando; Di Pardo, Alba; Favellato, Mariagrazia; Amico, Enrico; Maglione, Vittorio; Frati, Luigi

    2015-11-01

    Huntington disease (HD) is a neurodegenerative disorder for which new treatments are urgently needed. Pridopidine is a new dopaminergic stabilizer, recently developed for the treatment of motor symptoms associated with HD. The therapeutic effect of pridopidine in patients with HD has been determined in two double-blind randomized clinical trials, however, whether pridopidine exerts neuroprotection remains to be addressed. The main goal of this study was to define the potential neuroprotective effect of pridopidine, in HD in vivo and in vitro models, thus providing evidence that might support a potential disease-modifying action of the drug and possibly clarifying other aspects of pridopidine mode-of-action. Our data corroborated the hypothesis of neuroprotective action of pridopidine in HD experimental models. Administration of pridopidine protected cells from apoptosis, and resulted in highly improved motor performance in R6/2 mice. The anti-apoptotic effect observed in the in vitro system highlighted neuroprotective properties of the drug, and advanced the idea of sigma-1-receptor as an additional molecular target implicated in the mechanism of action of pridopidine. Coherent with protective effects, pridopidine-mediated beneficial effects in R6/2 mice were associated with an increased expression of pro-survival and neurostimulatory molecules, such as brain derived neurotrophic factor and DARPP32, and with a reduction in the size of mHtt aggregates in striatal tissues. Taken together, these findings support the theory of pridopidine as molecule with disease-modifying properties in HD and advance the idea of a valuable therapeutic strategy for effectively treating the disease. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  6. Neuroprotective effects of tempol acyl esters against retinal ganglion cell death in a rat partial optic nerve crush model.

    Science.gov (United States)

    Thaler, Sebastian; Fiedorowicz, Michal; Grieb, Pawel; Wypych, Zbigniew; Knap, Narcyz; Borowik, Tomasz; Zawada, Katarzyna; Kaminski, Jaroslaw; Wozniak, Michal; Rejdak, Robert; Zrenner, Eberhart; Schuettauf, Frank

    2011-11-01

    The aim of this study is to search for more effective derivatives of the superoxide dismutase mimetic tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl). Although tempol is neuroprotective in a rat partial optic nerve crush (PONC) model, relatively high doses are required to exert this effect. Tempol acyl esters with different-length fatty acids (tempol-C4, tempol-C8, tempol-C12 and tempol-C16) were synthesized and the following properties were evaluated: water-octanol partition coefficient, liposome-liposome energy transfer, and electron paramagnetic resonance (EPR). Brown Norway rats underwent PONC and received tempol or acyl esters intraperitoneally once daily for 7 consecutive days. We then compared the effects of tempol and its four esters on retinal ganglion cell (RGC) damage using a retrograde labelling method. The water-octanol partition coefficient increased with increasing length of attached acyl chain. However, the energy of the liposome-liposome transfer seemed to be optimal for tempol-C8 and tempol-C12. The EPR signal was very similar for all tested compounds, suggesting similar efficiency of superoxide scavenging. Partial optic nerve crush in vehicle-treated animals reduced RGC numbers by approx. 59% when compared with sham-operated eyes. Tempol did not affect RGC loss at a dose of 1 mg/kg. In contrast, at molar doses equivalent to 1 mg/kg of tempol, tempol-C8 showed a significant neuroprotective effect, whereas tempol-C4, tempol-C12 and tempol-C16 did not act neuroprotectively. Manipulating the hydrophobicity of tempol seems to be a promising tool for developing more potent neuroprotectants in the PONC degeneration model. However, the resulting compounds need further pharmacological evaluation. © 2011 The Authors. Acta Ophthalmologica © 2011 Acta Ophthalmologica Scandinavica Foundation.

  7. GlyT1 Inhibitor NFPS Exerts Neuroprotection via GlyR Alpha1 Subunit in the Rat Model of Transient Focal Cerebral Ischaemia and Reperfusion

    Directory of Open Access Journals (Sweden)

    Baosheng Huang

    2016-05-01

    Full Text Available Background/Aims: Glycine is a strychnine-sensitive inhibitory neurotransmitter in the central nervous system (CNS, especially in the spinal cord, brainstem, and retina. The objective of the present study was to investigate the potential neuroprotective effects of GlyT1 inhibitor N [3-(4'-fluorophenyl-3-(4'-phenylphenoxy propyl] sarcosine (NFPS in the rat model of experimental stroke. Methods: In vivo ischaemia was induced by transient middle cerebral artery occlusion (tMCAO. The methods of Western Blotting, Nissl Staining and Morris water maze methods were applied to analyze the anti-ischaemia mechanism. Results: The results showed that high dose of NFPS (H-NFPS significantly reduced infarct volume, neuronal injury and the expression of cleaved caspase-3, enhanced Bcl-2/Bax, and improved spatial learning deficits which were administered three hours after transient middle cerebral artery occlusion (tMCAO induction in rats, while, low dose of NFPS (L-NFPS exacerbated the injury of ischaemia. These findings suggested that low and high dose of NFPS produced opposite effects. Importantly, it was demonstrated that H-NFPS-dependent neuronal protection was inverted by salicylate (Sal, a specific GlyR ɑ1 antagonist. Such effects could probably be attributed to the enhanced glycine level in both synaptic and extrasynaptic clefts and the subsequently altered extrasynaptic GlyRs and their subtypes. Conclusions: These data imply that GlyT1 inhibitor NFPS may be a novel target for clinical treatment of transient focal cerebral ischaemia and reperfusion which are associated with altered GlyR alpha 1 subunits.

  8. Neuroprotective effects of statins against amyloid β-induced neurotoxicity

    Directory of Open Access Journals (Sweden)

    Hsin-Hua Li

    2018-01-01

    Full Text Available A growing body of evidence suggests that disruption of the homeostasis of lipid metabolism affects the pathogenesis of Alzheimer's disease (AD. In particular, dysregulation of cholesterol homeostasis in the brain has been reported to considerably increase the risk of developing AD. Thus, dysregulation of lipid homeostasis may increase the amyloid β (Aβ levels by affecting amyloid precursor protein (APP cleavage, which is the most important risk factor involved in the pathogenesis of AD. Previous research demonstrated that Aβ can trigger neuronal insulin resistance, which plays an important role in response to Aβ-induced neurotoxicity in AD. Epidemiological studies also suggested that statin use is associated with a decreased incidence of AD. Therefore, statins are believed to be a good candidate for conferring neuroprotective effects against AD. Statins may play a beneficial role in reducing Aβ-induced neurotoxicity. Their effect involves a putative mechanism beyond its cholesterol-lowering effects in preventing Aβ-induced neurotoxicity. However, the underlying molecular mechanisms of the protective effect of statins have not been clearly determined in Aβ-induced neurotoxicity. Given that statins may provide benefits beyond the inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA reductase, these drugs may also improve the brain. Thus, statins may have beneficial effects on impaired insulin signaling by activating AMP-activated protein kinase (AMPK in neuronal cells. They play a potential therapeutic role in targeting Aβ-mediated neurotoxicity.

  9. Epobis is a Nonerythropoietic and Neuroprotective Agonist of the Erythropoietin Receptor with Anti-Inflammatory and Memory Enhancing Effects

    DEFF Research Database (Denmark)

    Dmytriyeva, Oksana; Pankratova, Stanislava; Korshunova, Irina

    2016-01-01

    The cytokine erythropoietin (EPO) stimulates proliferation and differentiation of erythroid progenitor cells. Moreover, EPO has neuroprotective, anti-inflammatory, and antioxidative effects, but the use of EPO as a neuroprotective agent is hampered by its erythropoietic activity. We have recently....... These data reveal Epobis to be a nonerythropoietic and neuroprotective EPO receptor agonist with anti-inflammatory and memory enhancing properties....

  10. Anticonvulsant and neuroprotective effects of Pimpinella anisum in rat brain

    Directory of Open Access Journals (Sweden)

    Karimzadeh Fariba

    2012-06-01

    Full Text Available Abstract Background Essential oil of Pimpinella anisum L. Apiaceae (anise oil has been widely used in traditional Persian medicine to treat a variety of diseases, including some neurological disorders. This study was aimed to test the possible anti-seizure and anti-hypoxia effects of anise oil. Methods The effects of different concentrations of anise oil were tested on seizure attacks induced by pentylenetetrazol (PTZ injection and neuronal hypoxia induced by oxygen withdrawal as well as on production of dark neurons and induction of long-term potentiation (LTP in in vivo and in vitro experimental models of rat brain. Results Anise oil significantly prolonged the latency of seizure attacks and reduced the amplitude and duration of epileptiform burst discharges induced by injection of intraperitoneal PTZ. In addition, anise oil significantly inhibited production of dark neurons in different regions of the brain in epileptic rats. Anise oil also significantly enhanced the duration of the appearance of anoxic terminal negativity induced by oxygen withdrawal and inhibited induction of LTP in hippocampal slices. Conclusions Our data indicate the anticonvulsant and neuroprotective effects of anise oil, likely via inhibition of synaptic plasticity. Further evaluation of anise oil to use in the treatment of neurological disorders is suggested.

  11. Anticonvulsant and neuroprotective effects of Pimpinella anisum in rat brain.

    Science.gov (United States)

    Karimzadeh, Fariba; Hosseini, Mahmoud; Mangeng, Diana; Alavi, Hassan; Hassanzadeh, Gholam Reza; Bayat, Mohamad; Jafarian, Maryam; Kazemi, Hadi; Gorji, Ali

    2012-06-18

    Essential oil of Pimpinella anisum L. Apiaceae (anise oil) has been widely used in traditional Persian medicine to treat a variety of diseases, including some neurological disorders. This study was aimed to test the possible anti-seizure and anti-hypoxia effects of anise oil. The effects of different concentrations of anise oil were tested on seizure attacks induced by pentylenetetrazol (PTZ) injection and neuronal hypoxia induced by oxygen withdrawal as well as on production of dark neurons and induction of long-term potentiation (LTP) in in vivo and in vitro experimental models of rat brain. Anise oil significantly prolonged the latency of seizure attacks and reduced the amplitude and duration of epileptiform burst discharges induced by injection of intraperitoneal PTZ. In addition, anise oil significantly inhibited production of dark neurons in different regions of the brain in epileptic rats. Anise oil also significantly enhanced the duration of the appearance of anoxic terminal negativity induced by oxygen withdrawal and inhibited induction of LTP in hippocampal slices. Our data indicate the anticonvulsant and neuroprotective effects of anise oil, likely via inhibition of synaptic plasticity. Further evaluation of anise oil to use in the treatment of neurological disorders is suggested.

  12. Additive Neuroprotective Effect of Borneol with Mesenchymal Stem Cells on Ischemic Stroke in Mice

    Directory of Open Access Journals (Sweden)

    Xiao-Guang Zhang

    2018-01-01

    Full Text Available Intravenous stem cell transplantation initiates neuroprotection related to the secretion of trophic factor. Borneol, a potential herbal neuroprotective agent, is a penetration enhancer. Here, we aimed to investigate whether they have additive neuroprotective effect on cerebral ischemia. Borneol was given to mice by gavage 3 days before middle cerebral artery occlusion (MCAO induction until the day when the mice were sacrificed. Mesenchymal stem cells (MSCs were intravenously injected at 24 h after MCAO induction. Neurological deficits, infarct volume, cell death, and neurogenesis were evaluated. Combined use of MSCs and borneol could more effectively reduce infarction volume and cell apoptosis, enhance neurogenesis, and improve the functional recovery than that of MSCs alone. The findings showed that combined use of borneol and stem cells provided additive neuroprotective effect on cerebral ischemia. However, the supposed effect of borneol on the improved MSC penetration still needs further direct evidence.

  13. In Vitro Neuroprotective Effect of Shikimic Acid Against Hydrogen Peroxide-Induced Oxidative Stress.

    Science.gov (United States)

    Rabelo, Thallita Kelly; Zeidán-Chuliá, Fares; Caregnato, Fernanda Freitas; Schnorr, Carlos Eduardo; Gasparotto, Juciano; Serafini, Mairim Russo; de Souza Araújo, Adriano Antunes; Quintans-Junior, Lucindo José; Moreira, José Cláudio Fonseca; Gelain, Daniel Pens

    2015-08-01

    Shikimic acid (SA), originally extracted from Illicium verum Hook. fil., is an indispensable starting material for the synthesis of the antiviral drug Oseltamivir (Tamiflu(®)) with very limited number of studies regarding its biological effects in vitro. Therefore, we here evaluated the thermoanalytical profile, redox properties, and in vitro effects of SA on human neuronal-like cells (SH-SY5Y). The thermoanalytical profile of SA was studied by using differential scanning calorimetry (DSC) and thermogravimetry/derivative thermogravimetry (TG/DTG) characterization. Both antioxidant potential and in vitro lipoperoxidation levels were analyzed. Cell viability and intracellular reactive species (RS) production was determined by DCF and SRB assays, respectively. Our results show in vitro antioxidant activity of SA without exerting cytotoxic effects on SH-SY5Y cells at tested concentrations of 10 nM, 10 μM, and 10 mM. In addition, SA protected the cells against H2O2-induced toxicity; effect that could be related, at least in part, with decreased intracellular RS production and its antioxidant potential. The present study shows evidence for neuroprotective actions of SA against oxidative stress-induced toxicity on SH-SY5Y cells, inviting for further investigation about its potential use in the context of oxidative stress-associated neurodegenerative diseases.

  14. Neuroprotective effect of resveratrol against scopolamine-induced cognitive impairment and oxidative stress in rats

    Directory of Open Access Journals (Sweden)

    Pushpalatha Bunadri

    2013-01-01

    Full Text Available The objective of this study was to examine the neuroprotective effect of resveratrol on cognitive impairment induced by scopolamine, a muscarinic antagonist, in rats. Memory impairment was induced by administration of scopolamine (1 mg/kg intraperitoneally. Cognitive functions were assessed using radial arm maze, an active avoidance paradigm. Oxidative stress parameters like malondialdehyde, catalase and superoxide dismutase were assessed and acetylcholinesterase activity was estimated. More working and reference memory errors in the radial arm maze test and fewer avoidances in the active avoidance test were observed with scopolamine in the 1 mg/kg i.p.-treated animals. This phenomenon is a clear indication of memory impairment. Oral administration of resveratrol (20 mg/kg inhibited the occurrence of higher working, reference memory errors and prevented the incidence of less avoidances. Resveratrol appeared to have exerted memory-enhancing effects by inhibiting acetylcholinesterase activity and prevented the rise in malondialdehyde levels and loss of antioxidant enzymes catalase and superoxide dismutase, showing antioxidant potential. Based on the above results of behavioral and biochemical studies, it can be concluded that resveratrol protected against scopolamine-induced loss of cognition. The results also indicate that resveratrol is an antioxidant and an acetylcholinesterase inhibitor, and it is likely that resveratrol’s protective effect is related to its antioxidant and cholinesterase inhibitory effects.

  15. Neuroprotective effects of phytochemicals on dopaminergic neuron cultures.

    Science.gov (United States)

    Sandoval-Avila, S; Diaz, N F; Gómez-Pinedo, U; Canales-Aguirre, A A; Gutiérrez-Mercado, Y K; Padilla-Camberos, E; Marquez-Aguirre, A L; Díaz-Martínez, N E

    2016-06-21

    Parkinson's disease is a progressive neurodegenerative disorder characterised by a loss of dopaminergic neurons in the substantia nigra pars compacta, which results in a significant decrease in dopamine levels and consequent functional motor impairment. Although its aetiology is not fully understood, several pathogenic mechanisms, including oxidative stress, have been proposed. Current therapeutic approaches are based on dopamine replacement drugs; these agents, however, are not able to stop or even slow disease progression. Novel therapeutic approaches aimed at acting on the pathways leading to neuronal dysfunction and death are under investigation. In recent years, such natural molecules as polyphenols, alkaloids, and saponins have been shown to have a neuroprotective effect due to their antioxidant and anti-inflammatory properties. The aim of our review is to analyse the most relevant studies worldwide addressing the benefits of some phytochemicals used in in vitro models of Parkinson's disease. Copyright © 2016 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  16. Comparative Neuroprotective Effects of Dexamethasone and Minocycline during Hepatic Encephalopathy

    Science.gov (United States)

    Gamal, Maha; Abdel Wahab, Zainab; Eshra, Mohamed; Rashed, Laila; Sharawy, Nivin

    2014-01-01

    Objective. Encephalopathy and brain edema are serious complications of acute liver injury and may lead to rapid death of patients. The present study was designed to investigate the role of the inflammatory mediators and oxidative stress in the cytotoxic brain oedema and the neuroprotective effects of both minocycline and dexamethasone. Methods. 48 male albino rats were divided into 4 groups: control group, acute liver injury (ALI) group, minocycline pretreated ALI group, and dexamethasone pretreated ALI group. 24 hours after acute liver injury serum ammonia, liver enzymes, brain levels of heme oxygenase-1 gene, iNOS gene expression, nitrite/nitrate, and cytokines were measured. In addition, the grades of encephalopathy and brain water content were assessed. Results. ALI was associated with significant increases in all measured inflammatory mediators, oxidative stress, iNOS gene expression, and nitrite/nitrate. Both minocycline and dexamethasone significantly modulated the inflammatory changes and the oxidative/nitrosative stress associated with ALI. However, only minocycline but not dexamethasone significantly reduced the cytotoxic brain oedema. Conclusion. Both minocycline and dexamethasone could modulate inflammatory and oxidative changes observed in brain after ALI and could be novel preventative therapy for hepatic encephalopathy episodes. PMID:24693424

  17. The Neuroprotection Effect of Oxygen Therapy: A Systematic Review ...

    African Journals Online (AJOL)

    2018-04-04

    Apr 4, 2018 ... OR “acute ischemic stroke (AIS)” OR “TBI” AND. “Clinical trial”. We also reviewed the .... Table 1: Characteristics of studies that compared normobaric oxygen treatment and controls in stroke patients. Study Year Study design ...... Young AR, Ali C, Duretête A, Vivien D. Neuroprotection and stroke: Time for a ...

  18. Neuroprotective effect of creatine against propionic acid toxicity in ...

    African Journals Online (AJOL)

    edoja

    2013-07-31

    Jul 31, 2013 ... management of autism as a neurodevelopmental disorder recently related to PA neurotoxicity. Key words: Propionic acid, creatine, SH-SY5Y, comet assay, DNA fragmentation assay, apoptosis, neuroprotection. INTRODUCTION. Propionic acid (PA) is a short chain fatty acid that is dietary obtained (Zarate ...

  19. Neuroprotective effect of creatine against propionic acid toxicity in ...

    African Journals Online (AJOL)

    With sufficient research and clinical trials in future, this could prove to be successful in treatment or management of autism as a neurodevelopmental disorder recently related to PA neurotoxicity. Keywords: Propionic acid, creatine, SH-SY5Y, comet assay, DNA fragmentation assay, apoptosis, neuroprotection. African Journal ...

  20. Neuroprotective effects of α-lipoic acid against hypoxic– ischemic ...

    African Journals Online (AJOL)

    Purpose: To explore the neuroprotective efficacy of α-lipoic acid (ALA) against hypoxic-ischemic encephalopathy (HIE) in neonatal rats. Methods: Forty-eight rats (P7-pups) were randomly assigned to one of four groups: group I received saline; group II (HI) underwent unilateral carotid artery ligation and hypoxia (92 % N2 ...

  1. Petiveria alliacea exerts mnemonic and learning effects on rats.

    Science.gov (United States)

    Silva, Mallone Lopes; Luz, Diandra Araújo; Paixão, Thiago Portal da; Silva, João Paulo Bastos; Belém-Filho, Ivaldo Jesus Almeida; Fernandes, Luanna Melo Pereira; Gonçalves, Ana Cristina Baetas; Fontes-Júnior, Enéas Andrade; de Andrade, Marciene Ataíde; Maia, Cristiane Socorro Ferraz

    2015-07-01

    Petiveria alliacea L. (Phytolaccaceae) is a perennial shrub native to the Amazon region and other tropical areas such as Central America and the Caribbean. Popularly known as mucuracaá, P. alliacea is used in the folk medicine for a broad variety of therapeutic purpose and also in religious ceremonies by slaves as a sedative, which highlights its properties on the Central Nervous System (CNS). The present study evaluated the effects of the P. alliacea leaves hydroalcoholic extract (PaLHE) on the cognition, including learning and memory. Three-month-old male and female Wistar rats (n=8-10/group) were administered with 900mg/kg of PaLHE. The behavioral assays included Step-down Inhibitory avoidance (IA) and Morris Water Maze (MWM) tests. Consistent with our previous reports, P. alliacea improved long-term memory. It also exerted previously unreported effects on short-term and spatial memory improvement, and increased learning in the tasks. The P. alliacea extract elicited mnemonic effects and improved the learning process in both IA and MWM tests. Our results highlight the importance of further studies in order to identify the active substances of the PaLHE and investigate the pharmacological mechanisms that underlies the reported effects. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. Assessment of C-phycocyanin effect on astrocytes-mediated neuroprotection against oxidative brain injury using 2D and 3D astrocyte tissue model.

    Science.gov (United States)

    Min, Seul Ki; Park, Jun Sang; Luo, Lidan; Kwon, Yeo Seon; Lee, Hoo Cheol; Shim, Hyun Jung; Kim, Il-Doo; Lee, Ja-Kyeong; Shin, Hwa Sung

    2015-09-24

    Drugs are currently being developed to attenuate oxidative stress as a treatment for brain injuries. C-phycocyanin (C-Pc) is an antioxidant protein of green microalgae known to exert neuroprotective effects against oxidative brain injury. Astrocytes, which compose many portions of the brain, exert various functions to overcome oxidative stress; however, little is known about how C-Pc mediates the antioxidative effects of astrocytes. In this study, we revealed that C-Pc intranasal administration to the middle cerebral artery occlusion (MCAO) rats ensures neuroprotection of ischemic brain by reducing infarct size and improving behavioral deficits. C-Pc also enhanced viability and proliferation but attenuated apoptosis and reactive oxygen species (ROS) of oxidized astrocytes, without cytotoxicity to normal astrocytes and neurons. To elucidate how C-Pc leads astrocytes to enhance neuroprotection and repair of ischemia brain, we firstly developed 3D oxidized astrocyte model. C-Pc had astrocytes upregulate antioxidant enzymes such as SOD and catalase and neurotrophic factors BDNF and NGF, while alleviating inflammatory factors IL-6 and IL-1β and glial scar. Additionally, C-Pc improved viability of 3D oxidized neurons. In summary, C-Pc was concluded to activate oxidized astrocytes to protect and repair the ischemic brain with the combinatorial effects of improved antioxidative, neurotrophic, and anti-inflammatory mechanisms.

  3. Neuroprotective and Memory-Enhancing Effect of the Combined Extract of Purple Waxy Corn Cob and Pandan in Ovariectomized Rats.

    Science.gov (United States)

    Kirisattayakul, Woranan; Wattanathorn, Jintanaporn; Iamsaard, Sittichai; Jittiwat, Jinatta; Suriharn, Bhalang; Lertrat, Kamol

    2017-01-01

    The neuroprotectant and memory enhancer supplement for menopause is required due to the side effects of hormone replacement therapy. Since purple waxy corn cob and pandan leaves exert antioxidant and acetylcholinesterase inhibition (AChEI) effects, we hypothesized that the combined extract of both plants (PCP) might provide synergistic effect leading to the improved brain damage and memory impairment in experimental menopause. To test this hypothesis, female Wistar rats were ovariectomized bilaterally and orally given various doses of the functional drink at doses of 20, 40, and 80 mg/kg for 28 days. The animals were assessed nonspatial memory using object recognition test every 7 days throughout the study period. At the end of study, they were assessed with oxidative stress status, AChEI, neuron density, and ERK1/2 signal in the prefrontal cortex (PFC). Interestingly, all doses of PCP increased object recognition memory and neuron density but decreased oxidative stress status in PFC. Low dose of PCP also decreased AChE activity while medium dose of PCP increased phosphorylation of ERK1/2 in PFC. Therefore, the improved oxidative stress status and cholinergic function together with signal transduction via ERK in PFC might be responsible for the neuroprotective and memory-enhancing effects of PCP.

  4. Neuroprotective and Memory-Enhancing Effect of the Combined Extract of Purple Waxy Corn Cob and Pandan in Ovariectomized Rats

    Directory of Open Access Journals (Sweden)

    Woranan Kirisattayakul

    2017-01-01

    Full Text Available The neuroprotectant and memory enhancer supplement for menopause is required due to the side effects of hormone replacement therapy. Since purple waxy corn cob and pandan leaves exert antioxidant and acetylcholinesterase inhibition (AChEI effects, we hypothesized that the combined extract of both plants (PCP might provide synergistic effect leading to the improved brain damage and memory impairment in experimental menopause. To test this hypothesis, female Wistar rats were ovariectomized bilaterally and orally given various doses of the functional drink at doses of 20, 40, and 80 mg/kg for 28 days. The animals were assessed nonspatial memory using object recognition test every 7 days throughout the study period. At the end of study, they were assessed with oxidative stress status, AChEI, neuron density, and ERK1/2 signal in the prefrontal cortex (PFC. Interestingly, all doses of PCP increased object recognition memory and neuron density but decreased oxidative stress status in PFC. Low dose of PCP also decreased AChE activity while medium dose of PCP increased phosphorylation of ERK1/2 in PFC. Therefore, the improved oxidative stress status and cholinergic function together with signal transduction via ERK in PFC might be responsible for the neuroprotective and memory-enhancing effects of PCP.

  5. The neuroprotective effects of an ethanolic turmeric (Curcuma longa L.) extract against trimethyltin-induced oxidative stress in rats.

    Science.gov (United States)

    Yuliani, Sapto; Mustofa; Partadiredja, Ginus

    2018-03-07

    Oxidative stress is known to contribute to the pathogenesis of neurodegenerative disorders. An ethanolic turmeric (Curcuma longa L.) extract containing curcumin has been reported to produce antioxidant effects. The present study aims to investigate the possible neuroprotective effects of the ethanolic turmeric extract against trimethyltin (TMT)-induced oxidative stress in Sprague Dawley rats. The ethanolic turmeric extract and citicoline were administered to the TMT exposed rats from day 1 to day 28 of the experiment. The TMT injection was administered on day 8 of the experiment. The plasma and brain malondialdehyde (MDA) and reduced glutathione (GSH) levels, and the activities of the superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) enzymes in the brain were examined at the end of the experiment. The administration of 200 mg/kg bw of the ethanolic turmeric extract prevented oxidative stress by decreasing the plasma and brain MDA levels and increasing the SOD, CAT, and GPx enzyme activities and GSH levels in the brain. These effects seem to be comparable to those of citicoline. The ethanolic turmeric extract at a dose of 200 mg/kg bw may exert neuroprotective effects on TMT-exposed Sprague Dawley rats by preventing them from oxidative stress.

  6. Enhancing hippocampal blood flow after cerebral ischemia and vasodilating basilar arteries: in vivo and in vitro neuroprotective effect of antihypertensive DDPH

    Directory of Open Access Journals (Sweden)

    Li Sun

    2015-01-01

    Full Text Available 1-(2,6-Dimethylphenoxy-2-(3,4-dimethoxyphenylethylamino-propane hydrochloride (DDPH is a novel antihypertensive agent based on structural characteristics of mexiletine and verapamine. We investigated the effect of DDPH on vasodilatation and neuroprotection in a rat model of cerebral ischemia in vivo, and a rabbit model of isolated basilar arteries in vitro. Our results show that DDPH (10 mg/kg significantly increased hippocampal blood flow in vivo in cerebral ischemic rats, and exerted dose-dependent relaxation of isolated basilar arteries contracted by histamine or KCl in the in vitro rabbit model. DDPH (3 × 10 -5 M also inhibited histamine-stimulated extracellular calcium influx and intracellular calcium release. Our findings suggest that DDPH has a vasodilative effect both in vivo and in vitro, which mediates a neuroprotective effect on ischemic nerve tissue.

  7. Cannabidiol exerts antiepileptic effects by restoring hippocampal interneuron functions in a temporal lobe epilepsy model.

    Science.gov (United States)

    Khan, Archie A; Shekh-Ahmad, Tawfeeq; Khalil, Ayatakin; Walker, Matthew C; Ali, Afia B

    2018-03-25

    A non-psychoactive phytocannabinoid, cannabidiol (CBD), shows promising results as an effective potential antiepileptic drug in some forms of refractory epilepsy. In an attempt to understand the mechanisms by which CBD exerts its anti-seizure effects, we investigated the effects of CBD at synaptic connections, and the intrinsic membrane properties of hippocampal CA1 pyramidal cells and two major inhibitory interneurons: fast spiking, parvalbumin -expressing (PV) and adapting, cholecystokinin-expressing (CCK) interneurons. We also investigated whether in vivo treatment with CBD altered the fate of CCK and PV interneurons using immunohistochemistry. Electrophysiological intracellular whole-cell recordings combined with neuroanatomy were performed in acute brain slices of rat temporal lobe epilepsy (in vivo kainic acid-induced) and in vitro (Mg 2+ -free-induced) epileptic seizure models. For immunohistochemistry experiments, CBD was administered in vivo (100 mg kg -1 ) at zero time and 90 minutes post status epilepticus (SE) induced with kainic acid. Bath-application of CBD (10 μM), dampened excitability at unitary synapses between pyramidal cells, but enhanced inhibitory synaptic potentials elicited by fast spiking and adapting interneurons at postsynaptic pyramidal cells. Furthermore, CBD restored impaired membrane excitability of PV, CCK, and pyramidal cells in a cell type-specific manner. These neuroprotective effects of CBD were corroborated by immunohistochemistry experiments that revealed a significant reduction of atrophy and death of PV- and CCK-expressing interneurons after CBD treatment. In conclusion, our data suggest CBD restores excitability and morphological impairment in epileptic models to pre-epilepsy control levels through multiple mechanisms to restore normal network function. This article is protected by copyright. All rights reserved.

  8. Neuroprotective Effects of β-Caryophyllene against Dopaminergic Neuron Injury in a Murine Model of Parkinson’s Disease Induced by MPTP

    Directory of Open Access Journals (Sweden)

    Juan M. Viveros-Paredes

    2017-07-01

    Full Text Available Parkinson’s disease (PD is one of the most common neurodegenerative disorders and is characterized by the loss of dopaminergic neurons in the substantia nigra (SN. Although the causes of PD are not understood, evidence suggests that its pathogenesis is associated with oxidative stress and inflammation. Recent studies have suggested a protective role of the cannabinoid signalling system in PD. β-caryophyllene (BCP is a natural bicyclic sesquiterpene that is an agonist of the cannabinoid type 2 receptor (CB2R. Previous studies have suggested that BCP exerts prophylactic and/or curative effects against inflammatory bowel disease through its antioxidative and/or anti-inflammatory action. The present study describes the neuroprotective effects of BCP in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP-induced murine model of PD, and we report the results of our investigation of its neuroprotective mechanism in neurons and glial cells. In the murine model, BCP pretreatment ameliorated motor dysfunction, protected against dopaminergic neuronal losses in the SN and striatum, and alleviated MPTP-induced glia activation. Additionally, BCP inhibited the levels of inflammatory cytokines in the nigrostriatal system. The observed neuroprotection and inhibited glia activation were reversed upon treatment with the CB2R selective antagonist AM630, confirming the involvement of the CB2R. These results indicate that BCP acts via multiple neuroprotective mechanisms in our murine model and suggest that BCP may be viewed as a potential treatment and/or preventative agent for PD.

  9. Therapeutic effects of cannabinoids in animal models of seizures, epilepsy, epileptogenesis, and epilepsy-related neuroprotection.

    Science.gov (United States)

    Rosenberg, Evan C; Patra, Pabitra H; Whalley, Benjamin J

    2017-05-01

    The isolation and identification of the discrete plant cannabinoids in marijuana revived interest in analyzing historical therapeutic claims made for cannabis in clinical case studies and anecdotes. In particular, sources as old as the 11th and 15th centuries claimed efficacy for crude marijuana extracts in the treatment of convulsive disorders, prompting a particularly active area of preclinical research into the therapeutic potential of plant cannabinoids in epilepsy. Since that time, a large body of literature has accumulated describing the effects of several of the >100 individual plant cannabinoids in preclinical models of seizures, epilepsy, epileptogenesis, and epilepsy-related neuroprotection. We surveyed the literature for relevant reports of such plant cannabinoid effects and critically reviewed their findings. We found that acute CB 1 R agonism in simple models of acute seizures in rodents typically produces anti-convulsant effects whereas CB 1 R antagonists exert converse effects in the same models. However, when the effects of such ligands are examined in more complex models of epilepsy, epileptogenesis and neuroprotection, a less simplistic narrative emerges. Here, the complex interactions between (i) brain regions involved in a given model, (ii) relative contributions of endocannabinoid signaling to modulation of synaptic transmission in such areas, (iii) multi-target effects, (iv) cannabinoid type 1 and type 2 receptor signaling interactions and, (v) timing, (vi) duration and (vii) localization of ligand administration suggest that there is both anti-epileptic therapeutic potential and a pro-epileptic risk in up- and down-regulation of endocannabinoid signaling in the central nervous system. Factors such receptor desensitization and specific pharmacology of ligands used (e.g. full vs partial agonists and neutral antagonists vs inverse agonists) also appear to play an important role in the effects reported. Furthermore, the effects of several plant

  10. Neuroprotective effect of a new variant of Epo nonhematopoietic against oxidative stress

    Directory of Open Access Journals (Sweden)

    C. Castillo

    2018-04-01

    Full Text Available Human erythropoietin is mainly recognized for its hematopoietic function; however, by binding to its receptor (EpoR, it can activate different signaling pathways as STAT, PI3K, MAPK and RAS to increase cellular differentiation or provide neuroprotective effects, among others. A recombinant human erythropoietin variant with low glycosylation and without hematopoietic effect (EpoL was purified from skimmed goat milk. Recombinant human erythropoietin (Epo was obtained from CHO cell line and used as control to compare EpoL effects. Neuroprotection studies were performed in PC12 cells and rat hippocampal slices. Cells were pretreated during 1 h with EpoL or Epo and exposed to oxidative agents (H2O2 or FCCP; cell viability was assayed at the end of the experiment by the MTT method. Hippocampal slices were exposed to 15 min of oxygen and glucose deprivation (OGD and the neuroprotective drugs EpoL or Epo were incubated for 2 h post-OGD in re-oxygenated medium. Cell cultures stressed with oxidative agents, and pretreated with EpoL, showed neuroprotective effects of 30% at a concentration 10 times lower than that of Epo. Moreover, similar differences were observed in OGD ex vivo assays. Neuroprotection elicited by EpoL was lost when an antibody against EpoR was present, indicating that its effect is EpoR-dependent. In conclusion, our results suggest that EpoL has a more potent neuroprotective profile than Epo against oxidative stress, mediated by activation of EpoR, thus EpoL represents an important target to develop a potential biopharmaceutical to treat different central nervous system pathologies related to oxidative stress such as stroke or neurodegenerative diseases. Keywords: Erythropoietin, Erythropoietin receptor, Neuroprotection, Oxidative stress

  11. Multiple Mechanisms of Anti-Cancer Effects Exerted by Astaxanthin

    Directory of Open Access Journals (Sweden)

    Li Zhang

    2015-07-01

    Full Text Available Astaxanthin (ATX is a xanthophyll carotenoid which has been approved by the United States Food and Drug Administration (USFDA as food colorant in animal and fish feed. It is widely found in algae and aquatic animals and has powerful anti-oxidative activity. Previous studies have revealed that ATX, with its anti-oxidative property, is beneficial as a therapeutic agent for various diseases without any side effects or toxicity. In addition, ATX also shows preclinical anti-tumor efficacy both in vivo and in vitro in various cancer models. Several researches have deciphered that ATX exerts its anti-proliferative, anti-apoptosis and anti-invasion influence via different molecules and pathways including signal transducer and activator of transcription 3 (STAT3, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB and peroxisome proliferator-activated receptor gamma (PPARγ. Hence, ATX shows great promise as chemotherapeutic agents in cancer. Here, we review the rapidly advancing field of ATX in cancer therapy as well as some molecular targets of ATX.

  12. Effect of radiation exerted to creep rate of resin

    Energy Technology Data Exchange (ETDEWEB)

    Hirade, Tetsuya; Hama, Yoshimasa (Waseda Univ., Tokyo (Japan)); Udagawa, Akira; Takeda, Nobuo; Seguchi, Tadao

    1990-12-01

    One of the high performance composite materials which became to be manufactured by the progress of working techniques and the improvement of material performance is fiber-reinforced plastics (FRP). Carbon fiber-reinforced plastics (CFRP) are used as space and aircraft material, and glass fiber-reinforced plastics (GFRP) are expected as the structural material for superconducting magnets in nuclear fusion. In these materials, the use for long term must be considered, and the creep characteristics, of resin should be taken as one of the design factors. Therefore, the effect that radiation exerted to the stress relaxation of epoxy resin was measured, and its mechanism was investigated. The sample was bisphenol F system epoxy. The measurements of DSC, dynamic viscoelasticity and stress relaxation were carried out. The stress relaxation in bisphenol F system epoxy resin occurred down to 10 % of the initial stress only at 3 MGy. This is the dose far lower than the life in the radiation resistance of this resin. It is considered that the stress relaxation of the resin was caused by the change in molecular structure instead of the cut of molecular chain, as energy was given to the microscopic region by the interaction with radiation. (K.I.).

  13. [Similarity of cycloprolylglycine to piracetam in antihypoxic and neuroprotective effects].

    Science.gov (United States)

    Kolisnikova, K N; Gudasheva, T A; Nazarova, G A; Antipov, T A; Voronina, T A; Seredenin, S B

    2012-01-01

    The antihypoxic activity of the endogenous cyclic dipeptide cycloprolylglycine (CPG) has been studied on a model of normobaric hypoxia with hypercapnia and its neuroprotective activity has been studied on a model of human neuroblastoma SH-SY5Y cell damage by 6-hydroxydopamine. It is established that CPG exhibits the antihypoxic activity at doses of 0.5 and 1.0 mg/kg (i.p.) on outbred and BALB/c mice, but not on C57B1/6 mice. The neuroprotective activity of CPG was detected in 10(-5) - 10(-8) M concentration range only when the treatment was carried out 24h before toxin introduction. The obtained data confirm the hypothesis that piracetam is a mimetic of the endogenous CPG neuropeptide.

  14. Neuroprotective Drug for Nerve Trauma Revealed Using Artificial Intelligence.

    Science.gov (United States)

    Romeo-Guitart, David; Forés, Joaquim; Herrando-Grabulosa, Mireia; Valls, Raquel; Leiva-Rodríguez, Tatiana; Galea, Elena; González-Pérez, Francisco; Navarro, Xavier; Petegnief, Valerie; Bosch, Assumpció; Coma, Mireia; Mas, José Manuel; Casas, Caty

    2018-01-30

    Here we used a systems biology approach and artificial intelligence to identify a neuroprotective agent for the treatment of peripheral nerve root avulsion. Based on accumulated knowledge of the neurodegenerative and neuroprotective processes that occur in motoneurons after root avulsion, we built up protein networks and converted them into mathematical models. Unbiased proteomic data from our preclinical models were used for machine learning algorithms and for restrictions to be imposed on mathematical solutions. Solutions allowed us to identify combinations of repurposed drugs as potential neuroprotective agents and we validated them in our preclinical models. The best one, NeuroHeal, neuroprotected motoneurons, exerted anti-inflammatory properties and promoted functional locomotor recovery. NeuroHeal endorsed the activation of Sirtuin 1, which was essential for its neuroprotective effect. These results support the value of network-centric approaches for drug discovery and demonstrate the efficacy of NeuroHeal as adjuvant treatment with surgical repair for nervous system trauma.

  15. Multiple effects of adenosine in the arterially perfused mammalian eye. Possible mechanisms for the neuroprotective function of adenosine in the retina.

    Science.gov (United States)

    Macaluso, Claudio; Frishman, Laura J; Frueh, Beatrice; Kaelin-Lang, Alain; Onoe, Shoken; Niemeyer, Günter

    2003-01-01

    It has been postulated that the major physiological role of adenosine is protection of the central nervous system in conditions such as ischemia, hypoxia, or prolonged neuronal excitation. Under these conditions adenosine is released, and exerts multiple effects, including vasodilation, inhibition of neuronal activity, and enhancement of glycogenolysis, resulting in neuroprotection. In this article, published as well as unpublished data on the multiple effects of exogenous adenosine and application of adenosine-related agents, performed using the arterially perfused cat eye, will be reviewed and discussed within the framework of the neuroprotective role of adenosine. The isolated, arterially perfused eye preparation has the advantage of combining integrity of the eye structure, exact control of arterial concentration and timing of applied pharmacological agents, and access to electrophysiological parameters of both retina and optic nerve, as well as the ability to control and monitor perfusate flow. The absence of red blood cells in the perfusate prevents adenosine from being metabolized prior to reaching the eye.

  16. Neuroprotective effect of geniposide on Parkinson's disease model mice

    Directory of Open Access Journals (Sweden)

    Yi-mei CHEN

    2015-07-01

    Full Text Available Objective  To investigate the neuroprotective effect of geniposide on 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP induced Parkinson's disease (PD model mice and possible mechanism.  Methods  A total of 48 male C57BL/6 mice were randomly divided into control, model, geniposide and MPTP + geniposide groups. The behaviors of C57BL/6 mice were assessed by using open field test, the tyrosine hydroxylase (TH and Bcl-2 positive neurons in the midbrain substantia nigra of mice were detected by immunohistochemistry and the number of apoptosis neurons were observed with TdT-mediated dUTP-biotin nick end labeling (TUNEL.  Results  The number of mobile grid [(76.33 ± 8.59 times/5 min], standing [(19.58 ± 3.97 times/5 min], TH-positive neurons [(12.83 ± 2.32/HPF] and Bcl-2-positive neurons [(10.83 ± 2.23/HPF] in model group were significantly lower than those in the control group [(142.50 ± 11.65 times/5 min, (39.17 ± 4.75 times/5 min, (35.67 ± 1.75/HPF, (20.67 ± 1.75/HPF; P = 0.000, for all]. The apoptosis neurons in model group [(20.33 ± 2.58/HPF] were significantly higher than that in control group [(3.83 ± 1.67 /HPF, P = 0.000. The number of mobile grid [(97.67 ± 13.15 times/5 min, P = 0.000], standing [(29.33 ± 2.90 times/5 min, P = 0.000], TH-positive neurons [(17.50 ± 2.07/HPF, P = 0.002] and Bcl-2-positive neurons [(15.17 ± 2.79 /HPF, P = 0.003] in MPTP + geniposide group were significantly higher than those in model group. The number of apoptosis neurons [(14.67 ± 3.08 /HPF] in MPTP + geniposide group was significantly lower than that in model group (P = 0.001. Conclusions Geniposide can protect dopaminergic neurons in MPTP-induced neurodegeneration and the mechanism may be associated with the inhibition of neuronal apoptosis. DOI: 10.3969/j.issn.1672-6731.2015.06.012

  17. Nrf2 signaling contributes to the neuroprotective effects of urate against 6-OHDA toxicity.

    Directory of Open Access Journals (Sweden)

    Ning Zhang

    Full Text Available BACKGROUND: Mounting evidence shows that urate may become a biomarker of Parkinson's disease (PD diagnosis and prognosis and a neuroprotectant candidate for PD therapy. However, the cellular and molecular mechanisms underlying its neuroprotective actions remain poorly understood. RESULTS: In this study, we showed that urate pretreatment protected dopaminergic cell line (SH-SY5Y and MES23.5 against 6-hydroxydopamine (6-OHDA- and hydrogen peroxide- induced cell damage. Urate was found to be accumulated into SH-SY5Y cells after 30 min treatment. Moreover, urate induced NF-E2-related factor 2 (Nrf2 accumulation by inhibiting its ubiquitinationa and degradation, and also promoted its nuclear translocation; however, it did not modulate Nrf2 mRNA level or Kelch-like ECH-associated protein 1 (Keap1 expression. In addition, urate markedly up-regulated the transcription and protein expression of γ-glutamate-cysteine ligase catalytic subunit (γ-GCLC and heme oxygenase-1 (HO-1, both of which are controlled by Nrf2 activity. Furthermore, Nrf2 knockdown by siRNA abolished the intracellular glutathione augmentation and the protection exerted by urate pretreatment. CONCLUSION: Our findings demonstrated that urate treatment may result in Nrf2-targeted anti-oxidant genes transcription and expression by reducing Nrf2 ubiquitination and degradation and promoting its nuclear translocation, and thus offer neuroprotection on dopaminergic cells against oxidative stresses.

  18. Neuroprotective Effect of Sodium Butyrate against Cerebral Ischemia/Reperfusion Injury in Mice

    Directory of Open Access Journals (Sweden)

    Jing Sun

    2015-01-01

    Full Text Available Sodium butyrate (NaB is a dietary microbial fermentation product of fiber and serves as an important neuromodulator in the central nervous system. In this study, we further investigated that NaB attenuated cerebral ischemia/reperfusion (I/R injury in vivo and its possible mechanisms. NaB (5, 10 mg/kg was administered intragastrically 3 h after the onset of reperfusion in bilateral common carotid artery occlusion (BCCAO mice. After 24 h of reperfusion, neurological deficits scores were estimated. Morphological examination was performed by electron microscopy and hematoxylin-eosin (H&E staining. The levels of oxidative stress and inflammatory cytokines were assessed. Apoptotic neurons were measured by TUNEL; apoptosis-related protein caspase-3, Bcl-2, Bax, the phosphorylation Akt (p-Akt, and BDNF were assayed by western blot and immunohistochemistry. The results showed that 10 mg/kg NaB treatment significantly ameliorated neurological deficit and histopathology changes in cerebral I/R injury. Moreover, 10 mg/kg NaB treatment markedly restored the levels of MDA, SOD, IL-1β, TNF-α, and IL-8. 10 mg/kg NaB treatment also remarkably inhibited the apoptosis, decreasing the levels of caspase-3 and Bax and increasing the levels of Bcl-2, p-Akt, and BDNF. This study suggested that NaB exerts neuroprotective effects on cerebral I/R injury by antioxidant, anti-inflammatory, and antiapoptotic properties and BDNF-PI3K/Akt pathway is involved in antiapoptotic effect.

  19. Cognitive Enhancing and Neuroprotective Effect of the Embryo of the Nelumbo nucifera Seed

    Directory of Open Access Journals (Sweden)

    Eun Sil Kim

    2014-01-01

    Full Text Available The aim of the present study was to evaluate the effect of ENS on cognitive impairment induced by scopolamine and its potential neuroprotective effect against glutamate-induced cytotoxicity in HT22 cell and to investigate the underlying mechanisms. ENS (3, 10, 30, and 100 mg/kg, scopolamine (1 mg/kg, and donepezil (1 mg/kg were administered to mice during a test period. Scopolamine impaired memory and learning in a water maze test and a passive avoidance test. The neuroprotective effect of ENS (10 and 100 μg/mL was investigated on glutamate-induced cell death in HT22 cells by MTT assay. We investigated acetylcholinesterase inhibition in hippocampus and antioxidant activity, ROS levels, and Ca2+ influx in HT22 cells to elucidate the potential mechanisms of ENS. We found that ENS significantly ameliorated scopolamine-induced memory impairment and inhibited AChE activity in hippocampus. In vitro, ENS showed potent neuroprotective effects against glutamate-induced neurotoxicity in the HT22 cell. In addition, ENS induced a decrease in ROS production and intercellular Ca2+ accumulation and showed DPPH radical and H2O2 scavenging activity. In conclusion, ENS showed both a memory improving effect and a neuroprotective effect. Our results indicate that ENS may be of use in the treatment and prevention of neurodegenerative disorders.

  20. Cognitive Enhancing and Neuroprotective Effect of the Embryo of the Nelumbo nucifera Seed

    Science.gov (United States)

    Kim, Eun Sil; Weon, Jin Bae; Yun, Bo-Ra; Lee, Jiwoo; Eom, Min Rye; Oh, Kyoung-Hee; Ma, Choong Je

    2014-01-01

    The aim of the present study was to evaluate the effect of ENS on cognitive impairment induced by scopolamine and its potential neuroprotective effect against glutamate-induced cytotoxicity in HT22 cell and to investigate the underlying mechanisms. ENS (3, 10, 30, and 100 mg/kg), scopolamine (1 mg/kg), and donepezil (1 mg/kg) were administered to mice during a test period. Scopolamine impaired memory and learning in a water maze test and a passive avoidance test. The neuroprotective effect of ENS (10 and 100 μg/mL) was investigated on glutamate-induced cell death in HT22 cells by MTT assay. We investigated acetylcholinesterase inhibition in hippocampus and antioxidant activity, ROS levels, and Ca2+ influx in HT22 cells to elucidate the potential mechanisms of ENS. We found that ENS significantly ameliorated scopolamine-induced memory impairment and inhibited AChE activity in hippocampus. In vitro, ENS showed potent neuroprotective effects against glutamate-induced neurotoxicity in the HT22 cell. In addition, ENS induced a decrease in ROS production and intercellular Ca2+ accumulation and showed DPPH radical and H2O2 scavenging activity. In conclusion, ENS showed both a memory improving effect and a neuroprotective effect. Our results indicate that ENS may be of use in the treatment and prevention of neurodegenerative disorders. PMID:25610484

  1. Neuroprotective effect of apocynin nitrone in oxygen glucose ...

    African Journals Online (AJOL)

    Results: In OGD-treated SH-SY5Y cells, AN-1 reduced cell death and ROS level. In I/R rats, AN-1 exerted potential protection against neurological deficit by reducing infarction area, decreasing neurological deficit score and relieving oxidative stress. AN-1 exhibited stronger action than its parent compound apocynin in vitro, ...

  2. Paracrine effect of carbon monoxide - astrocytes promote neuroprotection through purinergic signaling in mice.

    Science.gov (United States)

    Queiroga, Cláudia S F; Alves, Raquel M A; Conde, Sílvia V; Alves, Paula M; Vieira, Helena L A

    2016-08-15

    The neuroprotective role of carbon monoxide (CO) has been studied in a cell-autonomous mode. Herein, a new concept is disclosed - CO affects astrocyte-neuron communication in a paracrine manner to promote neuroprotection. Neuronal survival was assessed when co-cultured with astrocytes that had been pre-treated or not with CO. The CO-pre-treated astrocytes reduced neuronal cell death, and the cellular mechanisms were investigated, focusing on purinergic signaling. CO modulates astrocytic metabolism and extracellular ATP content in the co-culture medium. Moreover, several antagonists of P1 adenosine and P2 ATP receptors partially reverted CO-induced neuroprotection through astrocytes. Likewise, knocking down expression of the neuronal P1 adenosine receptor A2A-R (encoded by Adora2a) reverted the neuroprotective effects of CO-exposed astrocytes. The neuroprotection of CO-treated astrocytes also decreased following prevention of ATP or adenosine release from astrocytic cells and inhibition of extracellular ATP metabolism into adenosine. Finally, the neuronal downstream event involves TrkB (also known as NTRK2) receptors and BDNF. Pharmacological and genetic inhibition of TrkB receptors reverts neuroprotection triggered by CO-treated astrocytes. Furthermore, the neuronal ratio of BDNF to pro-BDNF increased in the presence of CO-treated astrocytes and decreased whenever A2A-R expression was silenced. In summary, CO prevents neuronal cell death in a paracrine manner by targeting astrocytic metabolism through purinergic signaling. © 2016. Published by The Company of Biologists Ltd.

  3. Neuroprotective Effect of Arctigenin via Upregulation of P-CREB in Mouse Primary Neurons and Human SH-SY5Y Neuroblastoma Cells

    Directory of Open Access Journals (Sweden)

    Tingguo Kang

    2013-09-01

    Full Text Available Arctigenin (Arc has been shown to act on scopolamine-induced memory deficit mice and to provide a neuroprotective effect on cultured cortical neurons from glutamate-induced neurodegeneration through mechanisms not completely defined. Here, we investigated the neuroprotective effect of Arc on H89-induced cell damage and its potential mechanisms in mouse cortical neurons and human SH-SY5Y neuroblastoma cells. We found that Arc prevented cell viability loss induced by H89 in human SH-SY5Y cells. Moreover, Arc reduced intracellular beta amyloid (Aβ production induced by H89 in neurons and human SH-SY5Y cells, and Arc also inhibited the presenilin 1(PS1 protein level in neurons. In addition, neural apoptosis in both types of cells, inhibition of neurite outgrowth in human SH-SY5Y cells and reduction of synaptic marker synaptophysin (SYN expression in neurons were also observed after H89 exposure. All these effects induced by H89 were markedly reversed by Arc treatment. Arc also significantly attenuated downregulation of the phosphorylation of CREB (p-CREB induced by H89, which may contribute to the neuroprotective effects of Arc. These results demonstrated that Arc exerted the ability to protect neurons and SH-SY5Y cells against H89-induced cell injury via upregulation of p-CREB.

  4. Neuroprotective Effect of Arctigenin via Upregulation of P-CREB in Mouse Primary Neurons and Human SH-SY5Y Neuroblastoma Cells

    Science.gov (United States)

    Zhang, Nan; Wen, Qingping; Ren, Lu; Liang, Wenbo; Xia, Yang; Zhang, Xiaodan; Zhao, Dan; Sun, Dong; Hu, Yv; Hao, Haiguang; Yan, Yaping; Zhang, Guangxian; Yang, Jingxian; Kang, Tingguo

    2013-01-01

    Arctigenin (Arc) has been shown to act on scopolamine-induced memory deficit mice and to provide a neuroprotective effect on cultured cortical neurons from glutamate-induced neurodegeneration through mechanisms not completely defined. Here, we investigated the neuroprotective effect of Arc on H89-induced cell damage and its potential mechanisms in mouse cortical neurons and human SH-SY5Y neuroblastoma cells. We found that Arc prevented cell viability loss induced by H89 in human SH-SY5Y cells. Moreover, Arc reduced intracellular beta amyloid (Aβ) production induced by H89 in neurons and human SH-SY5Y cells, and Arc also inhibited the presenilin 1(PS1) protein level in neurons. In addition, neural apoptosis in both types of cells, inhibition of neurite outgrowth in human SH-SY5Y cells and reduction of synaptic marker synaptophysin (SYN) expression in neurons were also observed after H89 exposure. All these effects induced by H89 were markedly reversed by Arc treatment. Arc also significantly attenuated downregulation of the phosphorylation of CREB (p-CREB) induced by H89, which may contribute to the neuroprotective effects of Arc. These results demonstrated that Arc exerted the ability to protect neurons and SH-SY5Y cells against H89-induced cell injury via upregulation of p-CREB. PMID:24025424

  5. Neuroprotective effects of daidzein on focal cerebral ischemia injury in rats

    OpenAIRE

    Adem Bozkurt Aras; Mustafa Guven; Tarık Akman; Adile Ozkan; Halil Murat Sen; Ugur Duz; Yıldıray Kalkan; Coskun Silan; Murat Cosar

    2015-01-01

    Daidzein, a plant extract, has antioxidant activity. It is hypothesized, in this study, that daidzein exhibits neuroprotective effects on cerebral ischemia. Rat models of middle cerebral artery occlusion were intraperitoneally administered daidzein. Biochemical and immunohistochemical tests showed that superoxide dismutase and nuclear respiratory factor 1 expression levels in the brain tissue decreased after ischemia and they increased obviously after daidzein administration; malondialdehyde ...

  6. Neuroprotective Effect of Insulin-like Growth Factor-II on 1- Methyl-4 ...

    African Journals Online (AJOL)

    Purpose: To evaluate the receptor-mediated neuroprotective effect of insulin-like growth factor-II (IGF-. II) on 1-methyl-4-phenyl pyridinium (MPP)-induced oxidative damage in adult cortical neuronal cultures. Methods: Adult rats were randomly divided into 5 groups. Cortical neurons were prepared from rats. The cells were ...

  7. Neuroprotective Effect of Insulin-like Growth Factor-II on 1- Methyl-4 ...

    African Journals Online (AJOL)

    Purpose: To evaluate the receptor-mediated neuroprotective effect of insulin-like growth factor-II (IGFII) on 1-methyl-4-phenyl pyridinium (MPP) induced oxidative damage in adult cortical neuronal cultures. Methods: Adult rats were randomly divided into 5 groups. Cortical neurons were prepared from rats. The cells were ...

  8. Neuroprotective effect of whole-plant extract of Torilis leptophylla in ...

    African Journals Online (AJOL)

    Purpose: To investigate the neuroprotective effect of Torilis leptophylla (TL) extract on animals exposed to isoflurane-induced anesthesia. Methods: General anesthesia was induced in diabetic rats by administration of 2 % sevoflurane (v/v) in 100 % oxygen. The animals from the treatment group were orally administered TL ...

  9. Neuroprotective effect of progesterone on acute phase changes induced by partial global cerebral ischaemia in mice.

    Science.gov (United States)

    Aggarwal, Raman; Medhi, Bikash; Pathak, Ashis; Dhawan, Veena; Chakrabarti, Amitava

    2008-06-01

    The possible neuroprotective effect of progesterone, a steroid hormone, on acute phase changes in a mouse model of cerebral ischaemia induced by bilateral common carotid artery occlusion (BCAO) was studied. A total of 72 male mice were included in the study. The BCAO model was used to induce partial global cerebral ischaemia. Morphological assessment included measurement of infarct size and brain oedema. Post-ischaemic seizure susceptibility was assessed using a subconvulsive dose of pentylenetetrazole (30 mgkg(-1) i.p.). Biochemical estimations included tumour necrosis factor alpha (TNF-alpha) levels and enzyme parameters such as lipid peroxidation, superoxide dismutase, catalase and glutathione peroxidase, and protein estimation. BCAO induced a significant infarct size and oedema in the saline-treated control group, along with an increase in oxidative stress, indicated by increased lipid peroxidation and decreased levels of antioxidants such as superoxide dismutase, catalase and glutathione peroxidase. Progesterone (15 mgkg(-1) i.p.) administration showed a neuro-protective effect by significantly reducing the cerebral infarct size as compared with the control group. Post-ischaemic seizure susceptibility was also reduced as the number of positive responders decreased. Brain oedema subsided, but not significantly. Progesterone significantly reduced TNF-alpha levels compared with the ischaemia group. Progesterone improved levels of all the antioxidants, indicating activity against oxidative stress induced by BCAO. The results demonstrate the neuroprotective effect of progesterone against ischaemic insult, suggesting a role for the steroid as a neuroprotective agent.

  10. Neuroprotective effect of ketamine/xylazine on two rat models of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    M.M. Ferro

    2007-01-01

    Full Text Available There is a great concern in the literature for the development of neuroprotectant drugs to treat Parkinson's disease. Since anesthetic drugs have hyperpolarizing properties, they can possibly act as neuroprotectants. In the present study, we have investigated the neuroprotective effect of a mixture of ketamine (85 mg/kg and xylazine (3 mg/kg (K/X on the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP or 6-hydroxydopamine (6-OHDA rat models of Parkinson's disease. The bilateral infusion of MPTP (100 µg/side or 6-OHDA (10 µg/side into the substantia nigra pars compacta of adult male Wistar rats under thiopental anesthesia caused a modest (~67% or severe (~91% loss of tyrosine hydroxylase-immunostained cells, respectively. On the other hand, an apparent neuroprotective effect was observed when the rats were anesthetized with K/X, infused 5 min before surgery. This treatment caused loss of only 33% of the nigral tyrosine hydroxylase-immunostained cells due to the MPTP infusion and 51% due to the 6-OHDA infusion. This neuroprotective effect of K/X was also suggested by a less severe reduction of striatal dopamine levels in animals treated with these neurotoxins. In the working memory version of the Morris water maze task, both MPTP- and 6-OHDA-lesioned animals spent nearly 10 s longer to find the hidden platform in the groups where the neurotoxins were infused under thiopental anesthesia, compared to control animals. This amnestic effect was not observed in rats infused with the neurotoxins under K/X anesthesia. These results suggest that drugs with a pharmacological profile similar to that of K/X may be useful to delay the progression of Parkinson's disease.

  11. The ameliorating effects of 2,3-dihydroxy-4-methoxyacetophenone on scopolamine-induced memory impairment in mice and its neuroprotective activity.

    Science.gov (United States)

    Weon, Jin Bae; Ko, Hyun-Jeong; Ma, Choong Je

    2013-12-15

    We isolated 2,3-dihydroxy-4-methoxyacetophenone, a neuroprotective compound from Cynenchum paniculatum in our previous study. The present study was conducted to investigate the possible neuroprotective effect of 2,3-dihydroxy-4-methoxyacetophenone that has been previously isolated from Cynenchum paniculatum on hippocampal neuronal cell line, HT22 cells and its possible cognitive-enhancing effect on scopolamine-induced amnesia in mice. Neuroprotective effect against glutamate-induced neurotoxicity in HT22 cells was evaluated by MTT assay. Also, cognitive enhancing effect against scopolamine (1mg/kg, ip) induced learning and memory deficit was measured by Morris water maze test. Oral administered of 2,3-dihydroxy-4-methoxyacetophenone (1, 10, 20, 40 and 50mg/kg) to amnesic mice induced by scopolamine. In Morris water maze test, 2,3-dihydroxy-4-methoxyacetophenone (50mg/kg) improved the impairment of spatial memory induced by scopolamine. 2,3-Dihydroxy-4-methoxyacetophenone protect HT22 cells on glutamate induced cell-death in a dose-dependent manner (EC50 value: 10.94μM). Furthermore, 2,3-dihydroxy-4-methoxyacetophenone was found to inhibit [Ca(2+)] accumulation in HT22 cells and had antioxidantive activity. The results showed that 2,3-dihydroxy-4-methoxyacetophenone exert neuroprotective and cognitive-enhancing activities through its antioxidant activity. We suggest that 2,3-dihydroxy-4-methoxyacetophenone improves cognitive function and may be helpful for the treatment of Alzheimer's disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Two new compounds from the fruits of Buddleja lindleyana with neuroprotective effect.

    Science.gov (United States)

    Wu, De-Ling; Wang, Yang-Kui; Liu, Jing-Song; Wang, Xun-Cui; Zhang, Wei

    2012-01-01

    Two new triterpenoid glycosides, mimengosides H (1) and I (2), were isolated from the fruits of Buddleja lindleyana Fort. Their structures were determined by extensive spectroscopic methods. Neuroprotective effects of these isolates against 1-methyl-4-phenylpyridinium ion-induced neurotoxicity in PC12 cells were evaluated. Pretreatment with compound 1 had potential protective effect in a concentration range from 0.1 to 1 μmol l⁻¹.

  13. Neuroprotective Effects of Psalmotoxin-1, an Acid-Sensing Ion Channel (ASIC) Inhibitor, in Ischemia Reperfusion in Mouse Eyes.

    Science.gov (United States)

    Dibas, Adnan; Millar, Cameron; Al-Farra, Abraham; Yorio, Thomas

    2018-03-29

    The purpose of the current study is to assess changes in the expression of Acid-Sensing Ion Channel (ASIC)1a and ASIC2 in retinal ganglion cells (RGCs) after retinal ischemia and reperfusion (I/R) injury and to test if inhibition of ASIC1a provides RGC neuroprotection. Transient ischemia was induced in one eye of C57BL/6 mice by raising intraocular pressure to 120 mmHg for 60 min followed by retinal reperfusion by restoring normal pressure. RGC function was measured by Pattern electroretinography (PERG). In addition, retinal ASIC1a and ASIC2 were observed by immunohistochemistry and western blot. Changes in calpain, fodrin, heat shock protein 70 (HSP70), Brn3a, super oxide dismutase-1 (SOD1), catalase, and glutathione perioxidase-4 (GPX4) protein levels were assessed by western blot. RGC numbers were measured by immunohistochemistry on whole retinal flat mounts using anti-RNA binding protein with multiple splicing (RBPMS) antibodies. Intravitreal injection of psalmotoxin-1, a selective ASIC1a blocker, was used to assess the neuroprotective effect of ASIC1a inhibition. Levels of ASIC1a and ASIC2 after I/R increased in RGCs. Upregulation of ASIC1a but not ASIC2 was attenuated by intravitreal injection of psalmotoxin-1. I/R induced activation of calpain and degradation of fodrin, HSP70, and reduction in Brn3a. In contrast, while psalmotoxin-1 attenuated calpain activation and increased Brn3a levels, it failed to block HSP70 degradation. Unlike SOD1 protein which was reduced, catalase protein levels increased after I/R. Psalmotoxin-1, although not affecting SOD1 and GPX4, increased catalase levels significantly. Psalmotoxin-1 also increased RBPMS-labeled RGCs following I/R as judged by immunohistochemistry of retinal flat mounts. Finally, psalmotoxin-1 enhanced the amplitude of PERG following I/R, suggesting partial rescue of RGC function. Psalmotoxin-1 appears to exert a neuroprotective effect under ischemic insults and targeting inhibition of ASICs may represent a

  14. Neuroprotective effects of daidzein on focal cerebral ischemia injury in rats

    Directory of Open Access Journals (Sweden)

    Adem Bozkurt Aras

    2015-01-01

    Full Text Available Daidzein, a plant extract, has antioxidant activity. It is hypothesized, in this study, that daidzein exhibits neuroprotective effects on cerebral ischemia. Rat models of middle cerebral artery occlusion were intraperitoneally administered daidzein. Biochemical and immunohistochemical tests showed that superoxide dismutase and nuclear respiratory factor 1 expression levels in the brain tissue decreased after ischemia and they increased obviously after daidzein administration; malondialdehyde level and apoptosis-related cysteine peptidase caspase-3 and caspase-9 immunoreactivity in the brain tissue increased after ischemia and they decreased obviously after daidzein administration. Hematoxylin-eosin staining and luxol fast blue staining results showed that intraperitoneal administration of daidzein markedly alleviated neuronal damage in the ischemic brain tissue. These findings suggest that daidzein exhibits neuroprotective effects on ischemic brain tissue by decreasing oxygen free radical production, which validates the aforementioned hypothesis

  15. Neuroprotective effects of daidzein on focal cerebral ischemia injury in rats

    Science.gov (United States)

    Aras, Adem Bozkurt; Guven, Mustafa; Akman, Tarık; Ozkan, Adile; Sen, Halil Murat; Duz, Ugur; Kalkan, Yıldıray; Silan, Coskun; Cosar, Murat

    2015-01-01

    Daidzein, a plant extract, has antioxidant activity. It is hypothesized, in this study, that daidzein exhibits neuroprotective effects on cerebral ischemia. Rat models of middle cerebral artery occlusion were intraperitoneally administered daidzein. Biochemical and immunohistochemical tests showed that superoxide dismutase and nuclear respiratory factor 1 expression levels in the brain tissue decreased after ischemia and they increased obviously after daidzein administration; malondialdehyde level and apoptosis-related cysteine peptidase caspase-3 and caspase-9 immunoreactivity in the brain tissue increased after ischemia and they decreased obviously after daidzein administration. Hematoxylin-eosin staining and luxol fast blue staining results showed that intraperitoneal administration of daidzein markedly alleviated neuronal damage in the ischemic brain tissue. These findings suggest that daidzein exhibits neuroprotective effects on ischemic brain tissue by decreasing oxygen free radical production, which validates the aforementioned hypothesis. PMID:25788936

  16. Neuroprotective effects of Withania somnifera Dunn. in hippocampal sub-regions of female albino rat.

    Science.gov (United States)

    Jain, S; Shukla, S D; Sharma, K; Bhatnagar, M

    2001-09-01

    The neuroprotective effects of W. somnifera were studied on stressed adult female Swiss albino rats. Experimental rats were subjected to immobilization stress for 14 h and were treated with a root powder extract of W. somnifera available as Stresscom capsules (Dabur India Ltd). Control rats were maintained in completely, non stressed conditions. Thionin stained serial coronal sections (7 microm) of brain passing through the hippocampal region of stressed rats (E(1) group) demonstrated 85% degenerating cells (dark cells and pyknotic cells) in the CA(2) and CA(3) sub-areas. Treatment with W. somnifera root powder extract significantly reduced (80%) the number of degenerating cells in both the areas. The study thus demonstrates the antistress neuroprotective effects of W. somnifera. Copyright 2001 John Wiley & Sons, Ltd.

  17. Differential effects of synthetic progestagens on neuron survival and estrogen neuroprotection in cultured neurons.

    Science.gov (United States)

    Jayaraman, Anusha; Pike, Christian J

    2014-03-25

    Progesterone and other progestagens are used in combination with estrogens for clinical purposes, including contraception and postmenopausal hormone therapy. Progesterone and estrogens have interactive effects in brain, however interactions between synthetic progestagens and 17β-estradiol (E2) in neurons are not well understood. In this study, we investigated the effects of seven clinically relevant progestagens on estrogen receptor (ER) mRNA expression, E2-induced neuroprotection, and E2-induced BDNF mRNA expression. We found that medroxyprogesterone acetate decreased both ERα and ERβ expression and blocked E2-mediated neuroprotection and BDNF expression. Conversely, levonorgestrel and nesterone increased ERα and or ERβ expression, were neuroprotective, and failed to attenuate E2-mediated increases in neuron survival and BDNF expression. Other progestagens tested, including norethindrone, norethindrone acetate, norethynodrel, and norgestimate, had variable effects on the measured endpoints. Our results demonstrate a range of qualitatively different actions of progestagens in cultured neurons, suggesting significant variability in the neural effects of clinically utilized progestagens. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Methamphetamine-induced dopaminergic toxicity prevented owing to the neuroprotective effects of salicylic acid.

    Science.gov (United States)

    Thrash-Williams, Bessy; Karuppagounder, Senthilkumar S; Bhattacharya, Dwipayan; Ahuja, Manuj; Suppiramaniam, Vishnu; Dhanasekaran, Muralikrishnan

    2016-06-01

    Methamphetamine (Schedule-II drug, U.S. Drug Enforcement Administration) is one of the most abused illicit drug following cocaine, marijuana, and heroin in the USA. There are numerous health impairments and substantial economic burden caused by methamphetamine abuse. Salicylic acid, potent anti-inflammatory drug and a known neuroprotectant has shown to protect against toxicity-induced by other dopaminergic neurotoxins. Hence, in this study we investigated the neuroprotective effects of salicylic acid against methamphetamine-induced toxicity in mice. The current study investigated the effects of sodium salicylate and/or methamphetamine on oxidative stress, monoamine oxidase, mitochondrial complex I & IV activities using spectrophotometric and fluorimetric methods. Behavioral analysis evaluated the effect on movement disorders-induced by methamphetamine. Monoaminergic neurotransmitter levels were evaluated using high pressure liquid chromatography-electrochemical detection. Methamphetamine caused significant generation of reactive oxygen species and decreased complex-I activity leading to dopamine depletion. Striatal dopamine depletion led to significant behavioral changes associated with movement disorders. Sodium salicylate (50 & 100mg/kg) significantly scavenged reactive oxygen species, blocked mitochondrial dysfunction and exhibited neuroprotection against methamphetamine-induced neurotoxicity. In addition, sodium salicylate significantly blocked methamphetamine-induced behavioral changes related to movement abnormalities. One of the leading causative theories in nigral degeneration associated with movement disorders such as Parkinson's disease is exposure to stimulants, drugs of abuse, insecticide and pesticides. These neurotoxic substances can induce dopaminergic neuronal insult by oxidative stress, apoptosis, mitochondrial dysfunction and inflammation. Salicylic acid due to its antioxidant and anti-inflammatory effects could provide neuroprotection against the

  19. Analyzing Exertion of Hardy's Tragic Effect in "Tess"

    Science.gov (United States)

    Yang, Wei

    2009-01-01

    This paper begins with a brief introduction to [Thomas] Hardy's whole life and his works, especially this novel "Tess [of the D'Urbervilles]" and points out the tragic effect's importance and Hardy's tragic idea. Linked to this tragic effect, this paper analyzes the nice application in "Tess." At last, we can understand more…

  20. Neuroprotective effects of SMADs in a rat model of cerebral ischemia/reperfusion

    Directory of Open Access Journals (Sweden)

    Fang-fang Liu

    2015-01-01

    Full Text Available Previous studies have shown that up-regulation of transforming growth factor β1 results in neuroprotective effects. However, the role of the transforming growth factor β1 downstream molecule, SMAD2/3, following ischemia/reperfusion remains unclear. Here, we investigated the neuroprotective effects of SMAD2/3 by analyzing the relationships between SMAD2/3 expression and cell apoptosis and inflammation in the brain of a rat model of cerebral ischemia/reperfusion. Levels of SMAD2/3 mRNA were up-regulated in the ischemic penumbra 6 hours after cerebral ischemia/reperfusion, reached a peak after 72 hours and were then decreased at 7 days. Phosphorylated SMAD2/3 protein levels at the aforementioned time points were consistent with the mRNA levels. Over-expression of SMAD3 in the brains of the ischemia/reperfusion model rats via delivery of an adeno-associated virus containing the SMAD3 gene could reduce tumor necrosis factor-α and interleukin-1β mRNA levels, down-regulate expression of the pro-apoptotic gene, capase-3, and up-regulate expression of the anti-apoptotic protein, Bcl-2. The SMAD3 protein level was negatively correlated with cell apoptosis. These findings indicate that SMAD3 exhibits neuroprotective effects on the brain after ischemia/reperfusion through anti-inflammatory and anti-apoptotic pathways.

  1. A new look at an old drug: neuroprotective effects and therapeutic potentials of lithium salts

    Directory of Open Access Journals (Sweden)

    Dell’Osso L

    2016-07-01

    Full Text Available Liliana Dell’Osso, Claudia Del Grande, Camilla Gesi, Claudia Carmassi, Laura Musetti Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy Abstract: Increasing evidence highlights bipolar disorder as being associated with impaired neurogenesis, cellular plasticity, and resiliency, as well as with cell atrophy or loss in specific brain regions. This has led most recent research to focus on the possible neuroprotective effects of medications, and particularly interesting findings have emerged for lithium. A growing body of evidence from preclinical in vitro and in vivo studies has in fact documented its neuroprotective effects from different insults acting on cellular signaling pathways, both preventing apoptosis and increasing neurotrophins and cell-survival molecules. Furthermore, positive effects of lithium on neurogenesis, brain remodeling, angiogenesis, mesenchymal stem cells functioning, and inflammation have been revealed, with a key role played through the inhibition of the glycogen synthase kinase-3, a serine/threonine kinase implicated in the pathogenesis of many neuropsychiatric disorders. These recent evidences suggest the potential utility of lithium in the treatment of neurodegenerative diseases, neurodevelopmental disorders, and hypoxic–ischemic/traumatic brain injury, with positive results at even lower lithium doses than those traditionally considered to be antimanic. The aim of this review is to briefly summarize the potential benefits of lithium salts on neuroprotection and neuroregeneration, emphasizing preclinical and clinical evidence suggesting new therapeutic potentials of this drug beyond its mood stabilizing properties. Keywords: bipolar disorder, GSK-3, neurodegeneration, neurogenesis, neurodevelopmental disorders

  2. Treadmill Exercise Exerts Neuroprotection and Regulates Microglial Polarization and Oxidative Stress in a Streptozotocin-Induced Rat Model of Sporadic Alzheimer’s Disease

    Science.gov (United States)

    Lu, Yujiao; Dong, Yan; Tucker, Donovan; Wang, Ruimin; Ahmed, Mohammad Ejaz; Brann, Darrell; Zhang, Quanguang

    2017-01-01

    Recent work has suggested that exercise may be beneficial in preventing or ameliorating symptoms of several neurological disorders, although the mechanism is not entirely understood. The current study was designed to examine the potential beneficial effect of treadmill exercise upon cognitive function in a streptozotocin (STZ)-induced rat model of Alzheimer’s disease (AD). Animals underwent treadmill exercise (30 min/day, 5 days/week) for 4 weeks after bilateral STZ intracerebroventricular injection (2.4 mg/kg). We demonstrated that treadmill exercise significantly attenuated STZ-induced neurodegeneration in the rat hippocampal CA1 region and strongly preserved hippocampal-dependent cognitive functioning. Further mechanistic investigation displayed a marked suppression of STZ-induced amyloid-β accumulation and tau phosphorylation. Intriguingly, treadmill exercise remarkably inhibited reactive gliosis following STZ insult and effectively shifted activated microglia from a pro-inflammatory M1 to an anti-inflammatory M2 phenotype, which was correlated with a significantly reduced expression of pro-inflammatory mediators and a corresponding enhancement of anti-inflammatory cytokine expression in the hippocampus. Furthermore, treadmill exercise caused a robust suppression of oxidative damage as evidenced by significantly reduced peroxynitrite production, lipid peroxidation, and oxidized DNA damage. Finally, treadmill exercise strongly attenuated STZ-induced mitochondrial dysfunction manifested by a dramatically elevated intra-mitochondrial cytochrome c oxidase activity and ATP synthesis, and markedly inhibited neuronal apoptosis in the hippocampus. These findings demonstrate that treadmill exercise has a multifactorial effect to attenuate many of the pathological processes that play a key role in AD, and provide further support for the beneficial role of exercise as a potential therapeutic option in AD treatment. PMID:28157094

  3. Treadmill Exercise Exerts Neuroprotection and Regulates Microglial Polarization and Oxidative Stress in a Streptozotocin-Induced Rat Model of Sporadic Alzheimer's Disease.

    Science.gov (United States)

    Lu, Yujiao; Dong, Yan; Tucker, Donovan; Wang, Ruimin; Ahmed, Mohammad Ejaz; Brann, Darrell; Zhang, Quanguang

    2017-01-01

    Recent work has suggested that exercise may be beneficial in preventing or ameliorating symptoms of several neurological disorders, although the mechanism is not entirely understood. The current study was designed to examine the potential beneficial effect of treadmill exercise upon cognitive function in a streptozotocin (STZ)-induced rat model of Alzheimer's disease (AD). Animals underwent treadmill exercise (30 min/day, 5 days/week) for 4 weeks after bilateral STZ intracerebroventricular injection (2.4 mg/kg). We demonstrated that treadmill exercise significantly attenuated STZ-induced neurodegeneration in the rat hippocampal CA1 region and strongly preserved hippocampal-dependent cognitive functioning. Further mechanistic investigation displayed a marked suppression of STZ-induced amyloid-β accumulation and tau phosphorylation. Intriguingly, treadmill exercise remarkably inhibited reactive gliosis following STZ insult and effectively shifted activated microglia from a pro-inflammatory M1 to an anti-inflammatory M2 phenotype, which was correlated with a significantly reduced expression of pro-inflammatory mediators and a corresponding enhancement of anti-inflammatory cytokine expression in the hippocampus. Furthermore, treadmill exercise caused a robust suppression of oxidative damage as evidenced by significantly reduced peroxynitrite production, lipid peroxidation, and oxidized DNA damage. Finally, treadmill exercise strongly attenuated STZ-induced mitochondrial dysfunction manifested by a dramatically elevated intra-mitochondrial cytochrome c oxidase activity and ATP synthesis, and markedly inhibited neuronal apoptosis in the hippocampus. These findings demonstrate that treadmill exercise has a multifactorial effect to attenuate many of the pathological processes that play a key role in AD, and provide further support for the beneficial role of exercise as a potential therapeutic option in AD treatment.

  4. Acute neuroprotective effects of extremely low-frequency electromagnetic fields after traumatic brain injury in rats.

    Science.gov (United States)

    Yang, Yang; Li, Ling; Wang, Yan-Gang; Fei, Zhou; Zhong, Jun; Wei, Li-Zhou; Long, Qian-Fa; Liu, Wei-Ping

    2012-05-10

    Traumatic brain injury commonly has a result of a short window of opportunity between the period of initial brain injury and secondary brain injury, which provides protective strategies and can reduce damages of brain due to secondary brain injury. Previous studies have reported neuroprotective effects of extremely low-frequency electromagnetic fields. However, the effects of extremely low-frequency electromagnetic fields on neural damage after traumatic brain injury have not been reported yet. The present study aims to investigate effects of extremely low-frequency electromagnetic fields on neuroprotection after traumatic brain injury. Male Sprague-Dawley rats were used for the model of lateral fluid percussion injury, which were placed in non-electromagnetic fields and 15 Hz (Hertz) electromagnetic fields with intensities of 1 G (Gauss), 3 G and 5 G. At various time points (ranging from 0.5 to 30 h) after lateral fluid percussion injury, rats were treated with kainic acid (administered by intraperitoneal injection) to induce apoptosis in hippocampal cells. The results were as follows: (1) the expression of hypoxia-inducible factor-1α was dramatically decreased during the neuroprotective time window. (2) The kainic acid-induced apoptosis in the hippocampus was significantly decreased in rats exposed to electromagnetic fields. (3) Electromagnetic fields exposure shortened the escape time in water maze test. (4) Electromagnetic fields exposure accelerated the recovery of the blood-brain barrier after brain injury. These findings revealed that extremely low-frequency electromagnetic fields significantly prolong the window of opportunity for brain protection and enhance the intensity of neuroprotection after traumatic brain injury. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  5. Uric acid demonstrates neuroprotective effect on Parkinson's disease mice through Nrf2-ARE signaling pathway.

    Science.gov (United States)

    Huang, Ting-Ting; Hao, Dong-Lin; Wu, Bo-Na; Mao, Lun-Lin; Zhang, Jin

    2017-12-02

    Uric acid has neuroprotective effect on Parkinson's disease (PD) by inhibiting oxidative damage and neuronal cell death. Our previous study has shown that uric acid protected dopaminergic cell line damage through inhibiting accumulation of NF-E2-related factor 2 (Nrf2). This study aimed to investigate its in vivo neuroprotective effect. PD was induced by MPTP intraperitoneally injection for 7 d in male C57BL/6 mice. Mice were treated with either uric acid (intraperitoneally injection 250 mg/kg) or saline for a total of 13 d. We showed that uric acid improved behavioral performances and cognition of PD mice, increased TH-positive dopaminergic neurons and decreased GFAP-positive astrocytes in substantia nigra (SN). Uric acid increased mRNA and protein expressions of Nrf2 and three Nrf2-responsive genes, including γ-glutamate-cysteine ligase catalytic subunit (γ-GCLC), heme oxygenase-1 (HO-1) and NQO1. Uric acid significantly increased superoxide dismutase (SOD), CAT, glutathione (GSH) levels and decreased malondialdehyde (MDA) level in SN regions of MPTP-treated mice. Uric acid inhibited the hippocampal expression of IL-1β and decreased serum and hippocampus levels of interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α). In conclusion, uric acid demonstrates neuroprotective properties for dopaminergic neurons in PD mice through modulation of neuroinflammation and oxidative stress. Copyright © 2017. Published by Elsevier Inc.

  6. Neuroprotective effect of adenoviral catalase gene transfer in cortical neuronal cultures.

    Science.gov (United States)

    Gáspár, Tamás; Domoki, Ferenc; Lenti, Laura; Institoris, Adám; Snipes, James A; Bari, Ferenc; Busija, David W

    2009-05-13

    Reduced availability of reactive oxygen species is a key component of neuroprotection against various toxic stimuli. Recently we showed that the hydrogen peroxide scavenger catalase plays a central role in delayed preconditioning induced by the mitochondrial ATP-sensitive potassium channel opener BMS-191095. The purpose of the experiments discussed here was to investigate the neuroprotective effect of catalase in vitro using a recombinant adenoviral catalase gene transfer protocol. To induce catalase overexpression, cultured rat cortical neurons were infected with the adenoviral vector Ad5CMVcatalase and control cells were incubated with Ad5CMVntLacZ for 24 h. Gene transfer effectively increased catalase protein levels and activity, but did not influence other antioxidants tested. Ad5CMVcatalase, with up to 10 plaque forming units (pfu) per neuron, did not affect cell viability under control conditions and did not protect against glutamate excitotoxicity or oxygen-glucose deprivation. In contrast, catalase overexpression conferred a dose-dependent protection against exposure to hydrogen peroxide (viability: control, 33.02+/-1.09%; LacZ 10 pfu/cell, 32.85+/-1.51%; catalase 1 pfu/cell, 62.09+/-4.17%*; catalase 2 pfu/cell, 98.71+/-3.35%*; catalase 10 pfu/cell, 99.68+/-1.99%*; *pcatalase inhibitor 3-aminotriazole. Our results support the view that enhancing cellular antioxidant capacity may play a crucial role in neuroprotective strategies.

  7. Neuroprotective effect of the endogenous neural peptide apelin in cultured mouse cortical neurons

    International Nuclear Information System (INIS)

    Zeng, Xiang Jun; Yu, Shan Ping; Zhang, Like; Wei, Ling

    2010-01-01

    The adipocytokine apelin and its G protein-coupled APJ receptor were initially isolated from a bovine stomach and have been detected in the brain and cardiovascular system. Recent studies suggest that apelin can protect cardiomyocytes from ischemic injury. Here, we investigated the effect of apelin on apoptosis in mouse primary cultures of cortical neurons. Exposure of the cortical cultures to a serum-free medium for 24 h induced nuclear fragmentation and apoptotic death; apelin-13 (1.0-5.0 nM) markedly prevented the neuronal apoptosis. Apelin neuroprotective effects were mediated by multiple mechanisms. Apelin-13 reduced serum deprivation (SD)-induced ROS generation, mitochondria depolarization, cytochrome c release and activation of caspase-3. Apelin-13 prevented SD-induced changes in phosphorylation status of Akt and ERK1/2. In addition, apelin-13 attenuated NMDA-induced intracellular Ca 2+ accumulation. These results indicate that apelin is an endogenous neuroprotective adipocytokine that may block apoptosis and excitotoxic death via cellular and molecular mechanisms. It is suggested that apelins may be further explored as a potential neuroprotective reagent for ischemia-induced brain damage.

  8. Neuroprotective Effects of Cannabidiol in Hypoxic Ischemic Insult. The Therapeutic Window in Newborn Mice.

    Science.gov (United States)

    Mohammed, Nagat; Ceprian, Maria; Jimenez, Laura; Pazos, M Ruth; Martínez-Orgado, Jose

    2017-01-01

    A relevant therapeutic time window (TTW) is an important criterion for considering the clinical relevance of a substance preventing newborn hypoxic-ischemic (HI) brain damage. To test the TTW of the neuroprotective effects of cannabidol (CBD), a non-psychoactive cannabinoid in a model of newborn HI brain damage. 9-10 day-old C57BL6 mice underwent a HI insult (10% oxygen for 90 min after left carotid artery electrocoagulation). Then, CBD 1 mg/kg or vehicle were administered s.c. 15 min, or 1, 3, 6, 12, 18 or 24 h after the end of the HI insult. Seven days later brain damage was assessed using T2W Magnetic Resonance Imaging scan (ipsilateral hemisphere volume loss, IVHL) and histological studies: Nissl staining (neuropathological score), TUNEL staining (apoptotic damage) and immunohistochemistry with glial fibrillary acidic protein (astrocyte viability) or ionized calcium binding adaptor molecule (microglial activation). CBD administered up to 18 h after HI reduced IHVL and neuropathological score by 60%, TUNEL+ count by 90% and astrocyte damage by 50%. In addition, CBD blunted the HI-induced increase in microglial population. When CBD administration was delayed 24 h, however, the neuroprotective effect was lost in terms of IHVL, apoptosis or astrogliosis reduction. CBD shows a TTW of 18 h when administered to HI newborn mice, which represents a broader TTW than reported for other neuroprotective treatments including hypothermia. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. The neuroprotective effect of hyperbaric oxygen treatment on laser-induced retinal damage in rats

    Science.gov (United States)

    Vishnevskia-Dai, Victoria; Belokopytov, Mark; Dubinsky, Galina; Nachum, Gal; Avni, Isaac; Belkin, Michael; Rosner, Mordechai

    2005-04-01

    Retinal damage induced by mechanical trauma, ischemia or laser photocoagulation increases considerably by secondary degeneration processes. The spread of damage may be ameliorated by neuroprotection that is aimed at reducing the extent of the secondary degeneration and promote healing processes. Hyperbaric oxygen (HBO) treatment consists of inspiration of oxygen at higher than one absolute atmospheric pressure. Improved neural function was observed in patients with acute brain trauma or ischemia treated with HBO. This study was designed to evaluate the neuroprotective effect of hyperbaric oxygen (HBO) on laser induced retinal damage in a rat model. Standard argon laser lesions were created in 25 pigmented rats divided into three groups: Ten rats were treated immediately after the irradiation with HBO three times during the first 24 hr followed by 12 consecutive daily treatments. Five rats received a shorter treatment regimen of 10 consecutive HBO treatments. The control group (10 rats) underwent the laser damage with no additional treatment. The retinal lesions were evaluated 20 days after the injury. All outcome measures were improved by the longer HBO treatment (Ptreatment was less effective, showing an increase only in nuclei density at the central area of lesion (Pretinal damage in a rat model. In the range of HBO exposures studied, longer exposure provides more neuroprotection. These results encourage further evaluation of the potential therapeutic use of hyperbaric oxygen in diseases and injuries of the retina.

  10. Neuroprotective effect of the endogenous neural peptide apelin in cultured mouse cortical neurons

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Xiang Jun [Department of Pathophysiology, Capital Medical University, Beijing 100069 (China); Department of Anesthesiology, 101 Woodruff Circle, Suite 617, Emory University School of Medicine, Atlanta, GA 30322 (United States); Yu, Shan Ping [Department of Anesthesiology, 101 Woodruff Circle, Suite 617, Emory University School of Medicine, Atlanta, GA 30322 (United States); Zhang, Like [Department of Pathophysiology, Capital Medical University, Beijing 100069 (China); Wei, Ling, E-mail: lwei7@emory.edu [Department of Anesthesiology, 101 Woodruff Circle, Suite 617, Emory University School of Medicine, Atlanta, GA 30322 (United States)

    2010-07-01

    The adipocytokine apelin and its G protein-coupled APJ receptor were initially isolated from a bovine stomach and have been detected in the brain and cardiovascular system. Recent studies suggest that apelin can protect cardiomyocytes from ischemic injury. Here, we investigated the effect of apelin on apoptosis in mouse primary cultures of cortical neurons. Exposure of the cortical cultures to a serum-free medium for 24 h induced nuclear fragmentation and apoptotic death; apelin-13 (1.0-5.0 nM) markedly prevented the neuronal apoptosis. Apelin neuroprotective effects were mediated by multiple mechanisms. Apelin-13 reduced serum deprivation (SD)-induced ROS generation, mitochondria depolarization, cytochrome c release and activation of caspase-3. Apelin-13 prevented SD-induced changes in phosphorylation status of Akt and ERK1/2. In addition, apelin-13 attenuated NMDA-induced intracellular Ca{sup 2+} accumulation. These results indicate that apelin is an endogenous neuroprotective adipocytokine that may block apoptosis and excitotoxic death via cellular and molecular mechanisms. It is suggested that apelins may be further explored as a potential neuroprotective reagent for ischemia-induced brain damage.

  11. Neuroprotective Effects of Galantamine on Nerve Agent-Induced Neuroglial and Biochemical Changes.

    Science.gov (United States)

    Golime, RamaRao; Palit, Meehir; Acharya, J; Dubey, D K

    2017-09-19

    Neuroprotection from nerve agent such as soman-induced neural damage is a major challenge for existing drugs. Nerve agent exposure can cause many neural effects in survivors arising mainly due to acetylcholinesterase (AChE) inhibition or death within minutes. Unraveling the mechanisms underlying the nerve agent-induced multiple neurological effects is useful to develop better and safe drugs. The present study aimed to understand the molecular response during soman exposure and to evaluate the neuroprotective efficacy of galantamine on nerve agent-induced neurotoxic changes. mRNA expression studies using quantitative real-time PCR revealed significant changes in S-100β, Gfap, c-fos, and Bdnf in the hippocampus and piriform cortex after soman (90 μg/kg, s.c) exposure. Immunoblot analysis showed acute soman exposure significantly increased the protein levels of neuroglial markers (S100-β and GFAP); c-Fos and protein oxidation in discrete rat brain areas indicate their role in nerve agent-induced neurotoxicity. Induction of BDNF levels during soman exposure may indicate the recovery mechanisms activation. AChE was inhibited in the blood and brain up to 82% after soman exposure. Antidotal treatment with galantamine alone (3 mg/kg) and galantamine plus atropine (10 mg/kg) has protected animals from nerve agent-induced intoxication, death, and soman-inhibited AChE up to 45% in the blood and brain. Animal received galantamine displayed increased levels of neuroprotective genes (nAChRα-7, Bcl-2, and Bdnf) in the brain suggest the neuroprotective value of galantamine. Neuroglial changes, c-Fos, and protein oxidation levels significantly reduced after galantamine and galantamine plus atropine treatment indicate their potential antidotal value in nerve agent treatment.

  12. Galectin-1 exerts inhibitory effects during DENV-1 infection.

    Directory of Open Access Journals (Sweden)

    Karina Alves Toledo

    Full Text Available Dengue virus (DENV is an enveloped RNA virus that is mosquito-transmitted and can infect a variety of immune and non-immune cells. Response to infection ranges from asymptomatic disease to a severe disorder known as dengue hemorrhagic fever. Despite efforts to control the disease, there are no effective treatments or vaccines. In our search for new antiviral compounds to combat infection by dengue virus type 1 (DENV-1, we investigated the role of galectin-1, a widely-expressed mammalian lectin with functions in cell-pathogen interactions and immunoregulatory properties. We found that DENV-1 infection of cells in vitro exhibited caused decreased expression of Gal-1 in several different human cell lines, suggesting that loss of Gal-1 is associated with virus production. In test of this hypothesis we found that exogenous addition of human recombinant Gal-1 (hrGal-1 inhibits the virus production in the three different cell types. This inhibitory effect was dependent on hrGal-1 dimerization and required its carbohydrate recognition domain. Importantly, the inhibition was specific for hrGal-1, since no effect was observed using recombinant human galectin-3. Interestingly, we found that hrGal-1 directly binds to dengue virus and acts, at least in part, during the early stages of DENV-1 infection, by inhibiting viral adsorption and its internalization to target cells. To test the in vivo role of Gal-1 in DENV infection, Gal-1-deficient-mice were used to demonstrate that the expression of endogenous Galectin-1 contributes to resistance of macrophages to in vitro-infection with DENV-1 and it is also important to physiological susceptibility of mice to in vivo infection with DENV-1. These results provide novel insights into the functions of Gal-1 in resistance to DENV infection and suggest that Gal-1 should be explored as a potential antiviral compound.

  13. Panax ginseng exerts antiproliferative effects on rat hepatocarcinogenesis.

    Science.gov (United States)

    Kim, Hyemee; Lee, Hae-Jeung; Kim, Dae Joong; Kim, Tae Myoung; Moon, Hyun-Seuk; Choi, Haymie

    2013-09-01

    It has been proposed that ginseng has chemopreventive effects against several types of cancer in animals and humans. However, the mechanisms underlying the chemopreventive activities of fresh ginseng against hepatocarcinogenesis have not yet been elucidated. Therefore, we hypothesized that these ginseng species may prevent hepatocarcinogenesis but that the chemopreventive mechanisms may differ by species. To determine the chemopreventive and therapeutic potential of 3 different types of fresh ginseng on hepatocarcinogenesis, Sprague-Dawley rats were injected with diethylnitrosamine and fed diets containing 2% Panax japonicus CA Meyer (JN), P. quinquefolius L (QQ), or P. ginseng CA Meyer (GS) for 10 weeks. Glutathione S-transferase P form (GST-P)-positive foci, a stable marker for rat hepatocarcinogenesis, were shown in all carcinogen-injected rats; but only the GS diet significantly reduced the area and number (62% and 68%, respectively; P < .05) of GST-P-positive foci compared with the diethylnitrosamine control group. In addition, the number of proliferating cell nuclear antigen-positive hepatocytes in the GST-P-positive area was significantly decreased in the GS group but not in the JN or QQ groups. Using cDNA microarray analyses to investigate the underlying molecular mechanisms, we observed that the p53 signaling pathway was altered by the GS diet and that the expression of Cyclin D1, Cyclin G1, Cdc2a, and Igf-1, which are involved in the p53 signaling pathway, was downregulated by the GS diet. Our data demonstrate, for the first time, that GS, but not JN or QQ, induces cell cycle arrest in hepatocarcinogenesis. This study suggests that fresh GS has potential chemopreventive effects and may prove to be a therapeutic agent against hepatocarcinogenesis. © 2013.

  14. Neuroprotective effect of Cucumis melo Var. flexuosus leaf extract on the brains of rats with streptozotocin-induced diabetes.

    Science.gov (United States)

    Ibrahim, Doaa S

    2017-02-01

    The central nervous system is one of the most vulnerable organs affected by the oxidative stress associated with diabetes mellitus. Healthy food provides an important source for antioxidants. Therefore, the protective effect of Cucumis melo var. flexuosus (C. melo var. flexuosus) leaf extract on the brains of diabetic rats was investigated. Adult male albino rats divided into 5 groups of 6 rats each were assigned into a normal control group and four diabetic groups. Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin (STZ; 60 mg/kg bw). One of the four diabetic groups was left untreated and was considered as a diabetic control group while the three other groups were treated with C. melo var. flexuosus leaf extract at the doses of 30, 60 and 120 mg/kg bw for a period of 30 days. After completion of experimental duration plasma and brains were used for evaluating biochemical changes. The obtained data showed that C. melo var. flexuosus leaf extract treatment lowered blood glucose, glycated hemoglobin, brain tumor necrosis factor-alpha, interleukin levels, brain malondialdehyde content and caspase-3 activity. Furthermore, the treatment resulted in a marked increase in plasma dopamine, melatonin, brain vascular endothelial growth factor-A levels, brain catalase and superoxide dismutase activities. From the present study, it can be concluded that the C. melo var. flexuosus leaf extract exerts a neuroprotective effect against oxidative damage associated with diabetes.

  15. Role of histidine/histamine in carnosine-induced neuroprotection during ischemic brain damage.

    Science.gov (United States)

    Bae, Ok-Nam; Majid, Arshad

    2013-08-21

    Urgent need exists for new therapeutic options in ischemic stroke. We recently demonstrated that carnosine, an endogenous dipeptide consisting of alanine and histidine, is robustly neuroprotective in ischemic brain injury and has a wide clinically relevant therapeutic time window. The precise mechanistic pathways that mediate this neuroprotective effect are not known. Following in vivo administration, carnosine is hydrolyzed into histidine, a precursor of histamine. It has been hypothesized that carnosine may exert its neuroprotective activities through the histidine/histamine pathway. Herein, we investigated whether the neuroprotective effect of carnosine is mediated by the histidine/histamine pathway using in vitro primary astrocytes and cortical neurons, and an in vivo rat model of ischemic stroke. In primary astrocytes, carnosine significantly reduced ischemic cell death after oxygen-glucose deprivation, and this effect was abolished by histamine receptor type I antagonist. However, histidine or histamine did not exhibit a protective effect on ischemic astrocytic cell death. In primary neuronal cultures, carnosine was found to be neuroprotective but histamine receptor antagonists had no effect on the extent of neuroprotection. The in vivo effect of histidine and carnosine was compared using a rat model of ischemic stroke; only carnosine exhibited neuroprotection. Taken together, our data demonstrate that although the protective effects of carnosine may be partially mediated by activity at the histamine type 1 receptor on astrocytes, the histidine/histamine pathway does not appear to play a critical role in carnosine induced neuroprotection. Copyright © 2013. Published by Elsevier B.V.

  16. Emotional stimuli exert parallel effects on attention and memory.

    Science.gov (United States)

    Talmi, Deborah; Ziegler, Marilyne; Hawksworth, Jade; Lalani, Safina; Herman, C Peter; Moscovitch, Morris

    2013-01-01

    Because emotional and neutral stimuli typically differ on non-emotional dimensions, it has been difficult to determine conclusively which factors underlie the ability of emotional stimuli to enhance immediate long-term memory. Here we induced arousal by varying participants' goals, a method that removes many potential confounds between emotional and non-emotional items. Hungry and sated participants encoded food and clothing images under divided attention conditions. Sated participants attended to and recalled food and clothing images equivalently. Hungry participants performed worse on the concurrent tone-discrimination task when they viewed food relative to clothing images, suggesting enhanced attention to food images, and they recalled more food than clothing images. A follow-up regression analysis of the factors predicting memory for individual pictures revealed that food images had parallel effects on attention and memory in hungry participants, so that enhanced attention to food images did not predict their enhanced memory. We suggest that immediate long-term memory for food is enhanced in the hungry state because hunger leads to more distinctive processing of food images rendering them more accessible during retrieval.

  17. Ramadan Fasting Exerts Immunomodulatory Effects: Insights from a Systematic Review

    Directory of Open Access Journals (Sweden)

    Mohammad Adawi

    2017-11-01

    Full Text Available Ramadan is the ninth month of the Islamic lunar calendar and is observed by Muslims as a month of fasting. All Muslim adults are expected to fast; nevertheless certain subgroups, including sick, frail subjects, and pregnant women, among others, are exempted. Ramadan fasting has been shown to impact on body systems in different manners. The influence of Ramadan fasting on immune system regulation remains elusive; however, immune system changes, such as the modulation of body response to various infectious, stressful, and other harmful events, are of great interest during fasting. In this paper, we performed an extensive systematic literature review of different scholarly databases (ISI/Web of Science, Scopus, PubMed,/MEDLINE, Google Scholar, Directory of Open Access Journals, EbscoHOST, Scirus, Science Direct, the Cochrane Library, and ProQuest, using the following key words: “fasting,” “Ramadan,” “Islam,” and “immunity.” Conclusions drawn from these findings included: (1 Ramadan fasting has been shown to only mildly influence the immune system and the alterations induced are transient, returning to basal pre-Ramadan status shortly afterward. (2 Ramadan fasting during the second trimester of pregnancy was shown to be safe and did not result in negative fetal outcomes, or maternal oxidative status alterations. (3 In cardiac patients, Ramadan fasting can have beneficial effects including lipid profile improvement and alleviation of oxidative stress. (4 In asthmatic patients as well as in patients with human immunodeficiency virus/acquired immunodeficiency syndrome and autoimmune disorders, fasting was safe. (5 In psychiatric patients, such as those suffering from schizophrenia, fasting could increase immunologic markers. (6 Fasting Muslim athletes who maintain intensive training schedule during Ramadan showed fluctuations of immunologic markers.

  18. Ramadan Fasting Exerts Immunomodulatory Effects: Insights from a Systematic Review.

    Science.gov (United States)

    Adawi, Mohammad; Watad, Abdulla; Brown, Stav; Aazza, Khadija; Aazza, Hicham; Zouhir, Mohamed; Sharif, Kassem; Ghanayem, Khaled; Farah, Raymond; Mahagna, Hussein; Fiordoro, Stefano; Sukkar, Samir Giuseppe; Bragazzi, Nicola Luigi; Mahroum, Naim

    2017-01-01

    Ramadan is the ninth month of the Islamic lunar calendar and is observed by Muslims as a month of fasting. All Muslim adults are expected to fast; nevertheless certain subgroups, including sick, frail subjects, and pregnant women, among others, are exempted. Ramadan fasting has been shown to impact on body systems in different manners. The influence of Ramadan fasting on immune system regulation remains elusive; however, immune system changes, such as the modulation of body response to various infectious, stressful, and other harmful events, are of great interest during fasting. In this paper, we performed an extensive systematic literature review of different scholarly databases (ISI/Web of Science, Scopus, PubMed,/MEDLINE, Google Scholar, Directory of Open Access Journals, EbscoHOST, Scirus, Science Direct, the Cochrane Library, and ProQuest), using the following key words: "fasting," "Ramadan," "Islam," and "immunity." Conclusions drawn from these findings included: (1) Ramadan fasting has been shown to only mildly influence the immune system and the alterations induced are transient, returning to basal pre-Ramadan status shortly afterward. (2) Ramadan fasting during the second trimester of pregnancy was shown to be safe and did not result in negative fetal outcomes, or maternal oxidative status alterations. (3) In cardiac patients, Ramadan fasting can have beneficial effects including lipid profile improvement and alleviation of oxidative stress. (4) In asthmatic patients as well as in patients with human immunodeficiency virus/acquired immunodeficiency syndrome and autoimmune disorders, fasting was safe. (5) In psychiatric patients, such as those suffering from schizophrenia, fasting could increase immunologic markers. (6) Fasting Muslim athletes who maintain intensive training schedule during Ramadan showed fluctuations of immunologic markers.

  19. Ramadan Fasting Exerts Immunomodulatory Effects: Insights from a Systematic Review

    Science.gov (United States)

    Adawi, Mohammad; Watad, Abdulla; Brown, Stav; Aazza, Khadija; Aazza, Hicham; Zouhir, Mohamed; Sharif, Kassem; Ghanayem, Khaled; Farah, Raymond; Mahagna, Hussein; Fiordoro, Stefano; Sukkar, Samir Giuseppe; Bragazzi, Nicola Luigi; Mahroum, Naim

    2017-01-01

    Ramadan is the ninth month of the Islamic lunar calendar and is observed by Muslims as a month of fasting. All Muslim adults are expected to fast; nevertheless certain subgroups, including sick, frail subjects, and pregnant women, among others, are exempted. Ramadan fasting has been shown to impact on body systems in different manners. The influence of Ramadan fasting on immune system regulation remains elusive; however, immune system changes, such as the modulation of body response to various infectious, stressful, and other harmful events, are of great interest during fasting. In this paper, we performed an extensive systematic literature review of different scholarly databases (ISI/Web of Science, Scopus, PubMed,/MEDLINE, Google Scholar, Directory of Open Access Journals, EbscoHOST, Scirus, Science Direct, the Cochrane Library, and ProQuest), using the following key words: “fasting,” “Ramadan,” “Islam,” and “immunity.” Conclusions drawn from these findings included: (1) Ramadan fasting has been shown to only mildly influence the immune system and the alterations induced are transient, returning to basal pre-Ramadan status shortly afterward. (2) Ramadan fasting during the second trimester of pregnancy was shown to be safe and did not result in negative fetal outcomes, or maternal oxidative status alterations. (3) In cardiac patients, Ramadan fasting can have beneficial effects including lipid profile improvement and alleviation of oxidative stress. (4) In asthmatic patients as well as in patients with human immunodeficiency virus/acquired immunodeficiency syndrome and autoimmune disorders, fasting was safe. (5) In psychiatric patients, such as those suffering from schizophrenia, fasting could increase immunologic markers. (6) Fasting Muslim athletes who maintain intensive training schedule during Ramadan showed fluctuations of immunologic markers. PMID:29230208

  20. Novel fermented chickpea milk with enhanced level of γ-aminobutyric acid and neuroprotective effect on PC12 cells.

    Science.gov (United States)

    Li, Wen; Wei, Mingming; Wu, Junjun; Rui, Xin; Dong, Mingsheng

    2016-01-01

    In this study, novel fermented chickpea milk with high γ -aminobutyric acid (GABA) content and potential neuroprotective activity was developed. Fermentation starter that can produce GABA was selected from 377 strains of lactic acid bacteria isolated from traditional Chinese fermented foods. Among the screened strains, strain M-6 showed the highest GABA-producing capacity in De Man-Rogosa and Sharp (MRS) broth and chickpea milk. M-6 was identified as Lactobacillus plantarum based on Gram staining, API carbohydrate fermentation pattern testing, and 16s rDNA sequencing. The complete gene encoding glutamate decarboxylase was cloned to confirm the presence of the gene in L. plantarum M-6. The fermentation condition was optimized by response surface methodology. Results demonstrated that L. plantarum M-6 produced the highest GABA content of 537.23 mg/L. The optimal condition included an inoculum concentration of 7%, presence of 0.2% (m/v) monosodium glutamate and 55 µ M pyridoxal-5-phosphate, incubation temperature of 39 °C and fermentation time of 48 h . GABA-enriched chickpea milk exerted protective effects on PC12 cells against MnCl2 -induced injury. GABA-enriched chickpea milk improved cell viability and markedly attenuated the release of lactate dehydrogenase compared with the impaired cells.

  1. Novel fermented chickpea milk with enhanced level of γ-aminobutyric acid and neuroprotective effect on PC12 cells

    Directory of Open Access Journals (Sweden)

    Wen Li

    2016-08-01

    Full Text Available In this study, novel fermented chickpea milk with high γ -aminobutyric acid (GABA content and potential neuroprotective activity was developed. Fermentation starter that can produce GABA was selected from 377 strains of lactic acid bacteria isolated from traditional Chinese fermented foods. Among the screened strains, strain M-6 showed the highest GABA-producing capacity in De Man–Rogosa and Sharp (MRS broth and chickpea milk. M-6 was identified as Lactobacillus plantarum based on Gram staining, API carbohydrate fermentation pattern testing, and 16s rDNA sequencing. The complete gene encoding glutamate decarboxylase was cloned to confirm the presence of the gene in L. plantarum M-6. The fermentation condition was optimized by response surface methodology. Results demonstrated that L. plantarum M-6 produced the highest GABA content of 537.23 mg/L. The optimal condition included an inoculum concentration of 7%, presence of 0.2% (m/v monosodium glutamate and 55 µ M pyridoxal-5-phosphate, incubation temperature of 39 °C and fermentation time of 48 h . GABA-enriched chickpea milk exerted protective effects on PC12 cells against MnCl2 -induced injury. GABA-enriched chickpea milk improved cell viability and markedly attenuated the release of lactate dehydrogenase compared with the impaired cells.

  2. Specific neuroprotective effects of manual stimulation of real ...

    African Journals Online (AJOL)

    The objective of this study was to investigate the effectiveness and specific effects of acupuncture on ischemic-induced damage in rats after permanent middle cerebral artery occlusion. Cerebral ischemia was induced by middle cerebral artery occlusion in male Wistar rats. The rats were divided into the following 4 groups: ...

  3. Potential Neuroprotective Effects of Adiponectin in Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Roy Chun-Laam Ng

    2017-03-01

    Full Text Available The adipocyte-secreted protein adiponectin (APN has several protective functions in the peripheral tissues including insulin sensitizing, anti-inflammatory and anti-oxidative effects that may benefit neurodegenerative diseases such as Alzheimer’s disease (AD. In addition, dysregulation of cerebral insulin sensitivities and signaling activities have been implicated in AD. Emerging insights into the mechanistic roles of adiponectin and AD highlight the potential therapeutic effects for AD through insulin signaling.

  4. The neuroprotective effects of caffeine in neurodegenerative diseases.

    Science.gov (United States)

    Kolahdouzan, Mahshad; Hamadeh, Mazen J

    2017-04-01

    Caffeine is the most widely used psychostimulant in Western countries, with antioxidant, anti-inflammatory and anti-apoptotic properties. In Alzheimer's disease (AD), caffeine is beneficial in both men and women, in humans and animals. Similar effects of caffeine were observed in men with Parkinson's disease (PD); however, the effect of caffeine in female PD patients is controversial due to caffeine's competition with estrogen for the estrogen-metabolizing enzyme, CYP1A2. Studies conducted in animal models of amyotrophic lateral sclerosis (ALS) showed protective effects of A 2 A R antagonism. A study found caffeine to be associated with earlier age of onset of Huntington's disease (HD) at intakes >190 mg/d, but studies in animal models have found equivocal results. Caffeine is protective in AD and PD at dosages equivalent to 3-5 mg/kg. However, further research is needed to investigate the effects of caffeine on PD in women. As well, the effects of caffeine in ALS, HD and Machado-Joseph disease need to be further investigated. Caffeine's most salient mechanisms of action relevant to neurodegenerative diseases need to be further explored. © 2017 John Wiley & Sons Ltd.

  5. Dose-related neuroprotective effects of chronic nicotine in 6-hydroxydopamine treated rats, and loss of neuroprotection in α4 nicotinic receptor subunit knockout mice

    Science.gov (United States)

    Ryan, R E; Ross, S A; Drago, J; Loiacono, R E

    2001-01-01

    The present study examined the effect of a range of doses of chronic nicotine (0.75, 1.5, 3.0 and 30.0 mg kg−1 day−1, s.c., 14 days) upon striatal dopaminergic nerve terminal survival following 6-hydroxydopamine (6-OHDA; 10 μg intrastriatal unilaterally) in rats; and the effects of acute nicotine (1 mg kg−1, s.c.) pretreatment upon striatal neurodegeneration induced by methamphetamine (5 mg kg−1, i.p., three doses at 2 h intervals) in wild-type and α4 nicotinic receptor (nAChR) subunit knockout mice.In both models of Parkinsonian-like damage, loss of striatal dopaminergic nerve terminals was assessed by [3H]-mazindol autoradiography.In rats, chronic nicotine infusion delivered by osmotic minipump implanted subcutaneously 7 days prior to intrastriatal 6-OHDA injection produced significant and dose-related protection against 6-OHDA-induced neurodegeneration. Low (0.75 and 1.5 mg kg−1 day−1) but not high (3.0 and 30.0 mg kg−1 day−1) nicotine doses significantly inhibited 6-OHDA-induced degeneration.In wild-type mice, acute nicotine treatment produced significant inhibition of methamphetamine-induced neurodegeneration. In α4 nAChR subunit knockout mice, acute nicotine treatment failed to inhibit methamphetamine-induced neurodegeneration.Nicotine is capable of protecting dopaminergic neurons against Parkinsonian-like neurodegeneration in vivo. In rats, this neuroprotective effect is critically dependent upon nicotine dose and is consistent with the activation of nAChRs, as high, desensitizing doses of nicotine fail to be neuroprotective. Further, neuroprotection is absent in α4 nAChR subunit knockout mice. The current results therefore suggest that activation of α4 subunit containing nAChRs constitutes a major component of the neuroprotective effect of nicotine upon Parkinsonian-like damage in vivo. PMID:11309235

  6. 17β-Estradiol augments antidepressant efficacy of escitalopram in ovariectomized rats: Neuroprotective and serotonin reuptake transporter modulatory effects.

    Science.gov (United States)

    Ibrahim, Weam W; Safar, Marwa M; Khattab, Mahmoud M; Agha, Azza M

    2016-12-01

    The prevalence or recurrence of depression is seriously increased in women during the transition to and after menopause. The chronic hypo-estrogenic state of menopause may reduce the response to antidepressants; however the influence of estrogen therapy on their efficacy is still controversial. This study aimed at investigating the effects of combining escitalopram with 17β-estradiol on depression and cognitive impairment induced by ovariectomy, an experimental model of human menopause. Young adult female Wistar rats were subjected to either sham operation or ovariectomy. Ovariectomized animals were treated chronically with escitalopram (10mg/kg/day, i.p) alone or with four doses of 17β-estradiol (40μg/kg, s.c) given prior to the behavioral tests. Co-administration of 17β-estradiol improved escitalopram-induced antidepressant effect in forced swimming test verified as more prominent decrease in the immobility time without opposing its memory enhancing effect in Morris water maze. 17β-estradiol augmented the modulatory effects of escitalopram on the hippocampal levels of brain-derived neurotrophic factor and serotonin reuptake transporter as well as tumor necrosis factor-alpha without altering its effects on the gene expressions of serotonin receptor 1A, estrogen receptors alpha and beta, or acetylcholinestearase content. This combined therapy afforded synergistic protective effects on the brain histopathological architecture, particularly, the hippocampus. The antidepressant effect of 17β-estradiol was abolished by pretreatment with estrogen receptor antagonist, tamoxifen (10mg/kg, p.o). In conclusion, 17β-estradiol-induced antidepressant effect was confined to intracellular estrogen receptors activation. Moreover, 17β-estradiol enhanced escitalopram's efficiency in ameliorating menopausal-like depression, via exerting synergistic neuroprotective and serotonin reuptake transporter modulatory effects, without impeding escitalopram-mediated cognitive

  7. A review on the possible neuroprotective effects of Moringa oleifera ...

    African Journals Online (AJOL)

    Moringa oleifera is an edible plant that has been reputed to be a miracle plant by numerous authors, with effects on practically every body system. Phytochemical analyses have demonstrated that the leaves are rich in various minerals, vitamins and antioxidants. Its use in some continents dates back to Antiquity.

  8. Neuroprotective Effects of Garlic: A review | Mathew | Libyan Journal ...

    African Journals Online (AJOL)

    Garlic has been investigated extensively for health benefits, resulting in more than one thousand publications over the last decade alone. It is considered one of the best disease preventive foods, based on its potent and varied effects. Midlife risk factors for cardiovascular diseases, such as high serum total cholesterol, ...

  9. Neuroprotective Effect of Sargassum thunbergii (Mertens ex Roth ...

    African Journals Online (AJOL)

    Purpose: To evaluate the anti-oxidant and anti-neuroinflammatory effects of the Sargassum thunbergii extract (Mertens ex Roth) Kuntze (STE) in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells in vitro. Methods: STE antioxidative activity was evaluated with an Electron Spin Resonance (ESR) spectrometer, which ...

  10. The Neuroprotection Effect of Oxygen Therapy: A Systematic Review ...

    African Journals Online (AJOL)

    2018-04-04

    Apr 4, 2018 ... NBO on oxidative cerebral metabolism and oxygen treatment for severe TBI was not an all or nothing phenomenon but represented a graduated effect.[27] In the following clinical trial, they evaluated the combination of HBO and NBO as a single treatment. Compared with standard care (control treatment), ...

  11. Neuroprotective effects of phytosterol esters against high cholesterol-induced cognitive deficits in aged rat.

    Science.gov (United States)

    Rui, Xu; Wenfang, Li; Jing, Cheng; Meng, Chen; Chengcheng, Ding; Jiqu, Xu; Shuang, Rong

    2017-03-22

    Accumulating epidemiological and experimental studies have confirmed that a high-cholesterol diet is detrimental to cognitive performance in animal models. Phytosterols, a class of naturally occurring structural components in plant foods, have been demonstrated to possess cholesterol-lowering and antioxidant effects. Phytosterol esters (PSE) are esters of phytosterol. The aim of this study was to evaluate the neuroprotective effects of PSE on cognitive deficit induced by a cholesterol-enriched diet in aged rats, and to explore their underlying mechanisms for these effects. Based on their Morris water maze performance, the latencies differed by <1.5 standard deviations (SDs) on days 3-5 of testing, 60 rats were chosen from 12-month-old female Sprague Dawley aged rats and were randomized into three groups, which were fed either a control diet, a high cholesterol diet (HCD) or a high-cholesterol diet supplemented with 2% PSE (HCD + PSE) for 6 months. In our study, we found that PSE treatment maintained the body weight balance, reduced the serum lipid levels, and improved the cognitive performance of aged rats in the Morris water maze test, as evaluated by shortened escape latencies. Importantly, histological and immunohistochemical results in the brain showed that PSE supplementation may have a neuroprotective effect that alleviates neuroinflammation in aged rats. This neuroprotective effect significantly inhibited degeneration, resulting in a significant increase in the number of pyramidal cells and an apparent decrease in the number of astrocytes compared to rats that were fed only a HCD. Furthermore, PSE improved cholinergic activities by restoring the acetylcholine (ACh) content and decreasing acetylcholinesterase (AChE) activity in the cerebral cortex, as well as by elevating choline acetyl transferase (ChAT) activity in the hippocampus and the cerebral cortex. These results suggest that PSE can play a useful role in alleviating cognitive deficit induced by a

  12. A Neuroprotective Sericin Hydrogel As an Effective Neuronal Cell Carrier for the Repair of Ischemic Stroke.

    Science.gov (United States)

    Wang, Zheng; Wang, Jian; Jin, Yang; Luo, Zhen; Yang, Wen; Xie, Hongjian; Huang, Kai; Wang, Lin

    2015-11-11

    Ischemic stroke causes extensive cellular loss that impairs brain functions, resulting in severe disabilities. No effective treatments are currently available for brain tissue regeneration. The need to develop effective therapeutic approaches for treating stroke is compelling. A tissue engineering approach employing a hydrogel carrying both cells and neurotrophic cytokines to damaged regions is an encouraging alternative for neuronal repair. However, this approach is often challenged by low in vivo cell survival rate, and low encapsulation efficiency and loss of cytokines. To address these limitations, we propose to develop a biomaterial that can form a matrix capable of improving in vivo survival of transplanted cells and reducing in vivo loss of cytokines. Here, we report that using sericin, a natural protein from silk, we have fabricated a genipin-cross-linked sericin hydrogel (GSH) with porous structure and mild swelling ratio. The GSH supports the effective attachment and growth of neurons in vitro. Strikingly, our data reveal that sericin protein is intrinsically neurotrophic and neuroprotective, promoting axon extension and branching as well as preventing primary neurons from hypoxia-induced cell death. Notably, these functions are inherited by the GSH's degradation products, which might spare a need of incorporating costly cytokines. We further demonstrate that this neurotrophic effect is dependent on the Lkb1-Nuak1 pathway, while the neuroprotective effect is realized through regulating the Bcl-2/Bax protein ratio. Importantly, when transplanted in vivo, the GSH gives a high cell survival rate and allows the cells to continuously proliferate. Together, this work unmasks the neurotrophic and neuroprotective functions for sericin and provides strong evidence justifying the GSH's suitability as a potential neuronal cell delivery vehicle for ischemic stroke repair.

  13. Neuroprotective Effect of Gui Zhi (Ramulus Cinnamomi on Ma Huang- (Herb Ephedra- Induced Toxicity in Rats Treated with a Ma Huang-Gui Zhi Herb Pair

    Directory of Open Access Journals (Sweden)

    Fang-hao Zheng

    2015-01-01

    Full Text Available Herb Ephedra (Ma Huang in Chinese and Ramulus Cinnamomi (Gui Zhi in Chinese are traditional Chinese herbs, often used together to treat asthma, nose and lung congestion, and fever with anhidrosis. Due to the adverse effects of ephedrine, clinical use of Ma Huang is restricted. However, Gui Zhi extract has been reported to decrease spontaneous activity in rats and exert anti-inflammatory and neuroprotective effects. The present study explored the possible inhibitory effect of Gui Zhi on Ma Huang-induced neurotoxicity in rats when the two herbs were used in combination. All Ma Huang and Ma Huang-Gui Zhi herb pair extracts were prepared using methods of traditional Chinese medicine and were normalized based on the ephedrine content. Two-month-old male Sprague-Dawley rats (n=6 rats/group were administered Ma Huang or the Ma Huang-Gui Zhi herb pair extracts for 7 days (ephedrine = 48 mg/kg, and locomotor activity was measured. After 7 days, oxidative damage in the prefrontal cortex was measured. Gui Zhi decreased hyperactivity and sensitization produced by repeated Ma Huang administration and attenuated oxidative stress induced by Ma Huang. The results of this study demonstrate the neuroprotective potential of Gui Zhi in Ma Huang-induced hyperactivity and oxidative damage in the prefrontal cortex of rats when used in combination.

  14. Neuroprotective effects of compounds with antioxidant and anti-inflammatory properties in a Drosophila model of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Yang Yufeng

    2009-09-01

    Full Text Available Abstract Background Parkinson's disease (PD is the most common movement disorder. Extrapyramidal motor symptoms stem from the degeneration of the dopaminergic pathways in patient brain. Current treatments for PD are symptomatic, alleviating disease symptoms without reversing or retarding disease progression. Although the cause of PD remains unknown, several pathogenic factors have been identified, which cause dopaminergic neuron (DN death in the substantia nigra (SN. These include oxidative stress, mitochondrial dysfunction, inflammation and excitotoxicity. Manipulation of these factors may allow the development of disease-modifying treatment strategies to slow neuronal death. Inhibition of DJ-1A, the Drosophila homologue of the familial PD gene DJ-1, leads to oxidative stress, mitochondrial dysfunction, and DN loss, making fly DJ-1A model an excellent in vivo system to test for compounds with therapeutic potential. Results In the present study, a Drosophila DJ-1A model of PD was used to test potential neuroprotective drugs. The drugs applied are the Chinese herb celastrol, the antibiotic minocycline, the bioenergetic amine coenzyme Q10 (coQ10, and the glutamate antagonist 2,3-dihydroxy-6-nitro-7-sulphamoylbenzo[f]-quinoxaline (NBQX. All of these drugs target pathogenic processes implicated in PD, thus constitute mechanism-based treatment strategies. We show that celastrol and minocycline, both having antioxidant and anti-inflammatory properties, confer potent dopaminergic neuroprotection in Drosophila DJ-1A model, while coQ10 shows no protective effect. NBQX exerts differential effects on cell survival and brain dopamine content: it protects against DN loss but fails to restore brain dopamine level. Conclusion The present study further validates Drosophila as a valuable model for preclinical testing of drugs with therapeutic potential for neurodegenerative diseases. The lower cost and amenability to high throughput testing make Drosophila PD

  15. Hydrocortisone Infusion Exerts Dose- and Sex-Dependent Effects on Attention to Emotional Stimuli

    Science.gov (United States)

    Breitberg, Alaina; Drevets, Wayne C.; Wood, Suzanne E.; Mah, Linda; Schulkin, Jay; Sahakian, Barbara J.; Erickson, Kristine

    2013-01-01

    Glucocorticoid administration has been shown to exert complex effects on cognitive and emotional processing. In the current study we investigated the effects of glucocorticoid administration on attention towards emotional words, using an Affective Go/No-go task on which healthy humans have shown an attentional bias towards positive as compared to…

  16. Neuroprotective Effects of Hesperidin, a Plant Flavanone, on Rotenone-Induced Oxidative Stress and Apoptosis in a Cellular Model for Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Kuppusamy Tamilselvam

    2013-01-01

    Full Text Available Rotenone a widely used pesticide that inhibits mitochondrial complex I has been used to investigate the pathobiology of PD both in vitro and in vivo. Studies have shown that the neurotoxicity of rotenone may be related to its ability to generate reactive oxygen species (ROS, leading to neuronal apoptosis. The current study was carried out to investigate the neuroprotective effects of hesperidin, a citrus fruit flavanol, against rotenone-induced apoptosis in human neuroblastoma SK-N-SH cells. We assessed cell death, mitochondrial membrane potential, ROS generation, ATP levels, thiobarbituric acid reactive substances, reduced glutathione (GSH levels, and the activity of catalase, superoxide dismutase (SOD and glutathione peroxidase (GPx using well established assays. Apoptosis was determined in normal, rotenone, and hesperidin treated cells, by measuring the protein expression of cytochrome c (cyt c, caspases 3 and 9, Bax, and Bcl-2 using the standard western blotting technique. The apoptosis in rotenone-induced SK-N-SH cells was accompanied by the loss of mitochondrial membrane potential, increased ROS generation, the depletion of GSH, enhanced activities of enzymatic antioxidants, upregulation of Bax, cyt c, and caspases 3 and 9, and downregulation of Bcl-2, which were attenuated in the presence of hesperidin. Our data suggests that hesperidin exerts its neuroprotective effect against rotenone due to its antioxidant, maintenance of mitochondrial function, and antiapoptotic properties in a neuroblastoma cell line.

  17. Neuroprotective effects of bis(7-tacrine against glutamate-induced retinal ganglion cells damage

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    Xu Zhi

    2010-03-01

    Full Text Available Abstract Background Glutamate-mediated excitotoxicity, primarily through N-methyl-D-aspartate (NMDA receptors, may be an important cause of retinal ganglion cells (RGCs death in glaucoma and several other retinal diseases. Bis(7-tacrine is a noncompetitive NMDA receptors antagonist that can prevent glutamate-induced hippocampal neurons damage. We tested the effects of bis(7-tacrine against glutamate-induced rat RGCs damage in vitro and in vivo. Results In cultured neonatal rats RGCs, the MTT assay showed that glutamate induced a concentration- and time-dependent toxicity. Bis(7-tacrine and memantine prevented glutamate-induced cell death in a concentration-dependent manner with IC50 values of 0.028 μM and 0.834 μM, respectively. The anti-apoptosis effects of bis(7-tacrine were confirmed by annexin V-FITC/PI staining. In vivo, TUNEL analysis and retrograde labeling analysis found that pretreatment with bis(7-tacrine(0.2 mg/kg induced a significant neuroprotective effect against glutamate-induced RGCs damage. Conclusions Our results showed that bis(7-tacrine had neuroprotective effects against glutamate-induced RGCs damage in vitro and in vivo, possibly through the drug's anti-NMDA receptor effects. These findings make bis(7-tacrine potentially useful for treating a variety of ischemic or traumatic retinopathies inclusive of glaucoma.

  18. trans-Resveratrol as A Neuroprotectant

    Directory of Open Access Journals (Sweden)

    Ellen L. Robb

    2010-03-01

    Full Text Available Epidemiological evidence indicates that nutritionally-derived polyphenols such as resveratrol (RES have neuroprotective properties. Administration of RES to culture media protects a wide variety of neuronal cell types from stress-induced death. Dietary supplementation of RES can ameliorate neuronal damage and death resulting from both acute and chronic stresses in rodents. The specific molecular mechanisms by which RES acts at the cellular level remain incompletely understood. However, many experimental data indicate that RES reduces or prevents the occurrence of oxidative damage. Here we discuss possible mechanisms by which RES might exert protection against oxidative damage and cell death. Evidence suggesting that RES’s chemical antioxidant potential is not sufficient explanation for its effects is discussed. Putative biological activities, including interactions with estrogen receptors and sirtuins are critically discussed. We provide a synthesis of how RES’s phytoestrogenic properties might mediate the neuronal stress resistance underlying its observed neuroprotective properties.

  19. Neuroprotective Effect of Lutein on NMDA-Induced Retinal Ganglion Cell Injury in Rat Retina.

    Science.gov (United States)

    Zhang, Chanjuan; Wang, Zhen; Zhao, Jiayi; Li, Qin; Huang, Cuiqin; Zhu, Lihong; Lu, Daxiang

    2016-05-01

    Lutein injection is a possible therapeutic approach for retinal diseases, but the molecular mechanism of its neuroprotective effect remains to be elucidated. The aim of this study was to investigate its protective effects in retinal ganglion cells (RGCs) against N-methyl-D-aspartate (NMDA)-induced retinal damage in vivo. Retinal damage was induced by intravitreal NMDA injection in rats. Each animal was given five daily intraperitoneal injections of Lutein or vehicle along with intravitreal NMDA injections. Electroretinograms were recorded. The number of viable RGCs was quantified using the retinal whole-mount method by immunofluorescence. Proteins were measured by Western blot assays. Lutein reduced the retinal damage and improved the response to light, as shown by an animal behavior assay (the black-and-white box method) in rats. Furthermore, Lutein treatment prevented the NMDA-induced reduction in phNR wave amplitude. Lutein increased RGC number after NMDA-induced retina damage. Most importantly, Bax, cytochrome c, p-p38 MAPK, and p-c-Jun were all upregulated in rats injected with NMDA, but these expression patterns were reversed by continuous Lutein uptake. Bcl-2, p-GSK-3β, and p-Akt in the Lutein-treated eyes were increased compared with the NMDA group. Lutein has neuroprotective effects against retinal damage, its protective effects may be partly mediated by its anti-excitability neurotoxicity, through MAPKs and PI3K/Akt signaling, suggesting a potential approach for suppressing retinal neural damage.

  20. Oil palm phenolics confer neuroprotective effects involving cognitive and motor functions in mice.

    Science.gov (United States)

    Leow, Soon-Sen; Sekaran, Shamala Devi; Tan, YewAi; Sundram, Kalyana; Sambanthamurthi, Ravigadevi

    2013-09-01

    Phenolics are important phytochemicals which have positive effects on chronic diseases, including neurodegenerative ailments. The oil palm (Elaeis guineensis) is a rich source of water-soluble phenolics. This study was carried out to discover the effects of administering oil palm phenolics (OPP) to mice, with the aim of identifying whether these compounds possess significant neuroprotective properties. OPP was given to BALB/c mice on a normal diet as fluids for 6 weeks while the controls were given distilled water. These animals were tested in a water maze and on a rotarod weekly to assess the effects of OPP on cognitive and motor functions, respectively. Using Illumina microarrays, we further explored the brain gene expression changes caused by OPP in order to determine the molecular mechanisms involved. Real-time quantitative reverse transcription-polymerase chain reaction experiments were then carried out to validate the microarray data. We found that mice given OPP showed better cognitive function and spatial learning when tested in a water maze, and their performance also improved when tested on a rotarod, possibly due to better motor function and balance. Microarray gene expression analysis showed that these compounds up-regulated genes involved in brain development and activity, such as those under the regulation of the brain-derived neurotrophic factor. OPP also down-regulated genes involved in inflammation. These results suggest that the improvement of mouse cognitive and motor functions by OPP is caused by the neuroprotective and anti-inflammatory effects of the extract.

  1. Neuroprotective effects of ultrasound-guided nerve growth factor injections after sciatic nerve injury

    Science.gov (United States)

    Li, Hong-fei; Wang, Yi-ru; Huo, Hui-ping; Wang, Yue-xiang; Tang, Jie

    2015-01-01

    Nerve growth factor (NGF) plays an important role in promoting neuroregeneration after peripheral nerve injury. However, its effects are limited by its short half-life; it is therefore important to identify an effective mode of administration. High-frequency ultrasound (HFU) is increasingly used in the clinic for high-resolution visualization of tissues, and has been proposed as a method for identifying and evaluating peripheral nerve damage after injury. In addition, HFU is widely used for guiding needle placement when administering drugs to a specific site. We hypothesized that HFU guiding would optimize the neuroprotective effects of NGF on sciatic nerve injury in the rabbit. We performed behavioral, ultrasound, electrophysiological, histological, and immunohistochemical evaluation of HFU-guided NGF injections administered immediately after injury, or 14 days later, and compared this mode of administration with intramuscular NGF injections. Across all assessments, HFU-guided NGF injections gave consistently better outcomes than intramuscular NGF injections administered immediately or 14 days after injury, with immediate treatment also yielding better structural and functional results than when the treatment was delayed by 14 days. Our findings indicate that NGF should be administered as early as possible after peripheral nerve injury, and highlight the striking neuroprotective effects of HFU-guided NGF injections on peripheral nerve injury compared with intramuscular administration. PMID:26807123

  2. Neuroprotective effects of ultrasound-guided nerve growth factor injections after sciatic nerve injury.

    Science.gov (United States)

    Li, Hong-Fei; Wang, Yi-Ru; Huo, Hui-Ping; Wang, Yue-Xiang; Tang, Jie

    2015-11-01

    Nerve growth factor (NGF) plays an important role in promoting neuroregeneration after peripheral nerve injury. However, its effects are limited by its short half-life; it is therefore important to identify an effective mode of administration. High-frequency ultrasound (HFU) is increasingly used in the clinic for high-resolution visualization of tissues, and has been proposed as a method for identifying and evaluating peripheral nerve damage after injury. In addition, HFU is widely used for guiding needle placement when administering drugs to a specific site. We hypothesized that HFU guiding would optimize the neuroprotective effects of NGF on sciatic nerve injury in the rabbit. We performed behavioral, ultrasound, electrophysiological, histological, and immunohistochemical evaluation of HFU-guided NGF injections administered immediately after injury, or 14 days later, and compared this mode of administration with intramuscular NGF injections. Across all assessments, HFU-guided NGF injections gave consistently better outcomes than intramuscular NGF injections administered immediately or 14 days after injury, with immediate treatment also yielding better structural and functional results than when the treatment was delayed by 14 days. Our findings indicate that NGF should be administered as early as possible after peripheral nerve injury, and highlight the striking neuroprotective effects of HFU-guided NGF injections on peripheral nerve injury compared with intramuscular administration.

  3. Neuroprotective effects of (-)-linalool against oxygen-glucose deprivation-induced neuronal injury.

    Science.gov (United States)

    Park, Hyeon; Seol, Geun Hee; Ryu, Sangwoo; Choi, In-Young

    2016-04-01

    (-)-Linalool, a major component of many essential oils, is widely used in cosmetics and flavoring ingredients as well as in traditional medicines. Although various in vitro and in vivo studies have shown that (-)-linalool has anti-convulsant, anti-nociceptive, anti-inflammatory and anti-oxidative properties, its anti-ischemic/hypoxic effects have yet to be determined. This study assessed the neuroprotective effects of (-)-linalool against oxygen-glucose deprivation/reoxygenation (OGD/R)-induced cortical neuronal injury, an in vitro model of ischemic stroke. (-)-Linalool significantly attenuated OGD/R-evoked cortical neuronal injury/death, although it did not inhibit N-methyl-D-aspartate (NMDA)-induced excitotoxicity. (-)-Linalool significantly reduced intracellular oxidative stress during OGD/R-induced injury, as well as scavenging peroxyl radicals (Trolox equivalents or TE = 3.8). This anti-oxidant effect was found to correlate with the restoration of OGD/R-induced decreases in the activities of SOD and catalase. In addition, (-)-linalool inhibited microglial migration induced by monocyte-chemoattractant protein-1 (MCP-1), a chemokine released by OGD/R. These findings show that (-)-linalool has neuroprotective effects against OGD/R-induced neuronal injury, which may be due to its anti-oxidant and anti-inflammatory activities. Detailed examination of the anti-ischemic mechanisms of (-)-linalool may indicate strategies for the development of drugs to treat cerebral ischemic injury.

  4. Neuroprotective effect of Portulaca oleracea extracts against 6-hydroxydopamine-induced lesion of dopaminergic neurons

    Directory of Open Access Journals (Sweden)

    WALESKA B. MARTINS

    2016-01-01

    Full Text Available ABSTRACT The Portulaca oleracea L. (Portulacaceae is a cosmopolitan species with a wide range of biological activities, including antioxidant and neuroprotective actions. We investigated the effects of P. oleracea extracts in a 6-hydroxydopamine rat model of Parkinson's disease, a debilitating disorder without effective treatments. Chemical profiles of aqueous and ethanolic extracts of whole plant were analyzed by thin layer chromatography and the antioxidant activity was assessed by 2,2-diphenyl-1-picrilhidrazila method. Male Wistar rats received intrastriatal 6-hydroxydopamine and were treated with vehicle or extracts (oral, 200 and 400 mg/kg daily for two weeks. The behavioral open field test was conducted at days 1 and 15. Immunohistochemical analysis was performed 4 weeks after surgery to quantify tyrosine-hydroxylase cell counts in the substantia nigra pars compacta. Extracts presented antioxidant activity in concentrations above 300 µg/kg. The chromatographic analysis revealed the presence of Levodopa, alkaloids, flavonoids, saponins, tannins, terpenoids and polysaccharides. Both extracts improved motor recovery 15 days after lesion and protected from tyrosine-hydroxylase cell loss after 4 weeks, but these effects were more evident for the aqueous extract. Because the dopamine precursor is present, in addition to antioxidant compounds and neuroprotective effects, P. oleracea can be considered as potential strategy for treating Parkinson's disease.

  5. Neuroprotective effect of Portulaca oleracea extracts against 6-hydroxydopamine-induced lesion of dopaminergic neurons.

    Science.gov (United States)

    Martins, Waleska B; Rodrigues, Sheyla A; Silva, Hatamy K; Dantas, Camila G; Júnior, Waldecy DE Lucca; Filho, Lauro Xavier; Cardoso, Juliana C; Gomes, Margarete Z

    2016-09-01

    The Portulaca oleracea L. (Portulacaceae) is a cosmopolitan species with a wide range of biological activities, including antioxidant and neuroprotective actions. We investigated the effects of P. oleracea extracts in a 6-hydroxydopamine rat model of Parkinson's disease, a debilitating disorder without effective treatments. Chemical profiles of aqueous and ethanolic extracts of whole plant were analyzed by thin layer chromatography and the antioxidant activity was assessed by 2,2-diphenyl-1-picrilhidrazila method. Male Wistar rats received intrastriatal 6-hydroxydopamine and were treated with vehicle or extracts (oral, 200 and 400 mg/kg) daily for two weeks. The behavioral open field test was conducted at days 1 and 15. Immunohistochemical analysis was performed 4 weeks after surgery to quantify tyrosine-hydroxylase cell counts in the substantia nigra pars compacta. Extracts presented antioxidant activity in concentrations above 300 µg/kg. The chromatographic analysis revealed the presence of Levodopa, alkaloids, flavonoids, saponins, tannins, terpenoids and polysaccharides. Both extracts improved motor recovery 15 days after lesion and protected from tyrosine-hydroxylase cell loss after 4 weeks, but these effects were more evident for the aqueous extract. Because the dopamine precursor is present, in addition to antioxidant compounds and neuroprotective effects, P. oleracea can be considered as potential strategy for treating Parkinson's disease.

  6. Neuroprotective effects of ultrasound-guided nerve growth factor injections after sciatic nerve injury

    Directory of Open Access Journals (Sweden)

    Hong-fei Li

    2015-01-01

    Full Text Available Nerve growth factor (NGF plays an important role in promoting neuroregeneration after peripheral nerve injury. However, its effects are limited by its short half-life; it is therefore important to identify an effective mode of administration. High-frequency ultrasound (HFU is increasingly used in the clinic for high-resolution visualization of tissues, and has been proposed as a method for identifying and evaluating peripheral nerve damage after injury. In addition, HFU is widely used for guiding needle placement when administering drugs to a specific site. We hypothesized that HFU guiding would optimize the neuroprotective effects of NGF on sciatic nerve injury in the rabbit. We performed behavioral, ultrasound, electrophysiological, histological, and immunohistochemical evaluation of HFU-guided NGF injections administered immediately after injury, or 14 days later, and compared this mode of administration with intramuscular NGF injections. Across all assessments, HFU-guided NGF injections gave consistently better outcomes than intramuscular NGF injections administered immediately or 14 days after injury, with immediate treatment also yielding better structural and functional results than when the treatment was delayed by 14 days. Our findings indicate that NGF should be administered as early as possible after peripheral nerve injury, and highlight the striking neuroprotective effects of HFU-guided NGF injections on peripheral nerve injury compared with intramuscular administration.

  7. Comparative Neuroprotective Effects of Rasagiline and Aminoindan with Selegiline on Dexamethasone-Induced Brain Cell Apoptosis

    Science.gov (United States)

    Tazik, Shawna; Johnson, Shakevia; Lu, Deyin; Johnson, Chandra; Youdim, Moussa B. H.; Stockmeier, Craig A.

    2009-01-01

    Stress can affect the brain and lead to depression; however, the molecular pathogenesis is unclear. An association between stress and stress-induced hypersecretion of glucocorticoids occurs during stress. Dexamethasone (a synthetic glucocorticoid steroid) has been reported to induce apoptosis and increase the activity of monoamine oxidase (MAO) (Youdim et al. 1989). MAO is an enzyme for the degradation of aminergic neurotransmitters; dopamine, noradrenaline and serotonin and dietary amines and MAO inhibitors are classical antidepressant drugs. In this study, we have compared the ability of rasagiline (Azilect) and its main metabolite, R-aminoindan with selegiline (Deprenyl) in prevention of dexamethasone-induced brain cell death employing human neuroblastoma SH-SY5Y cells and glioblastoma 1242-MG cells. Dexamethasone reduced cell viability as measured by MTT test, but rasagiline, selegiline, and 1-R-aminoindan could significantly prevent dexamethasone-induced brain cell death. Among three drugs, rasagiline had the highest neuroprotective effect. Furthermore, the inhibitory effects of these drugs on MAOB catalytic activity and on apoptotic DNA damage (TUNEL staining) were examined. Rasagiline exhibited highest inhibition on MAO B enzymatic activity and prevention on DNA damage as compared to selegiline and 1-R-aminoindan. In summary, the greater neuroprotective effect of rasagiline may be associated with the combination of the parent drug and its metabolite 1-R-aminoindan. PMID:19384601

  8. Anticonvulsant and neuroprotective effects of Rosa damascena hydro-alcoholic extract on rat hippocampus

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    Mansour Homayoun

    2015-04-01

    Full Text Available Objective: Previously, analgesic, hypnotic, and anticonvulsant effects have been suggested for Rosa damascena (R. damascena. In the present study, possible anti-seizure and neuro-protective effects of hydro-alcoholic extract of R. damascena has been investigated after inducing seizures in rats by pentylenetetrazole (PTZ. Materials and Methods: The rats were divided to five groups: (1 Control: received saline, (2 PTZ: 100 mg/kg, i.p., (3 PTZ-Extract 50 mg/kg(PTZ-Ext 50, (4 PTZ- Extract 100 mg/kg(PTZ-Ext 100, and (5 PTZ- Extract 200 mg/kg(PTZ-Ext 200 groups which were treated with 50, 100, and 200 mg/kg respectively of hydro-alcoholic extract of R. damascena for one week before PTZ injection. The animals were examined for electrocorticography (ECoG recording and finally, the brains were removed for histological study. Results: The hydro-alcoholic extract of R. damascena significantly prolonged the latency of seizure attacks and reduced the frequency and amplitude of epileptiform burst discharges induced by PTZ injection. Moreover, all three doses of the extract significantly inhibited production of dark neurons in different regions of the hippocampus in the mentioned animal model. Conclusion: The present study showed that the hydro-alcoholic extract of R. damascena has anticonvulsant and neuroprotective effects. More investigations are needed to be done in order to better understand the responsible compound(s as well as the possible mechanism(s.

  9. Neuroprotective effect of Buddleja officinalis extract on transient middle cerebral artery occlusion in rats.

    Science.gov (United States)

    Lee, Dae-Hee; Ha, Nina; Bu, Yung-Min; Choi, Hyoung Il; Park, Yoo Guen; Kim, Yoon Bum; Kim, Mi-Yeon; Kim, Hocheol

    2006-08-01

    The flower buds of Buddleja officinalis MAXIM (Loganiaceae) are used to treat headache and inflammatory diseases in traditional Korean medicine. In the present study, the neuroprotective effects of the methanolic extract of B. officinalis (BOME) and of its hexane fraction (BOHF) were investigated in a middle cerebral artery occlusion (MCAo, 120 min occlusion, 24 h reperfusion) Sprague-Dawley rat model. BOME or BOHF (100 mg/kg, p.o.) was twice administered 30 min before the onset of MCAo and 2 h after reperfusion. BOME and BOHF treated groups showed infarct volumes reduced by 33.9% and 68.2%, respectively, at 2 h occlusion. In BOHF treated animals, cyclooxygenase-2 and iNOS inductions were inhibited in ischemic hemispheres at both the mRNA and protein levels. Furthermore, in vitro studies showed that BOME and BOHF both inhibited LPS-induced nitric oxide production in BV-2 mouse microglial cells. These results suggest that the anti-inflammatory and the microglial activation inhibitory effects of B. officinalis extract may contribute to its neuroprotective effects in brain ischemia.

  10. A Systematic, Integrated Study on the Neuroprotective Effects of Hydroxysafflor Yellow A Revealed by H1 NMR-Based Metabonomics and the NF-κB Pathway

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    Yuanyan Liu

    2013-01-01

    Full Text Available Hydroxysafflor yellow A (HSYA is the main active component of the Chinese herb Carthamus tinctorius L.. Purified HSYA is used as a neuroprotective agent to prevent cerebral ischemia. Injectable safflor yellow (50 mg, containing 35 mg HSYA is widely used to treat patients with ischemic cardiocerebrovascular disease. However, it is unknown how HSYA exerts a protective effect on cerebral ischemia at the molecular level. A systematical integrated study, including histopathological examination, neurological evaluation, blood-brain barrier (BBB, metabonomics, and the nuclear factor-κB (NF-κB pathway, was applied to elucidate the pathophysiological mechanisms of HSYA neuroprotection at the molecular level. HSYA could travel across the BBB, significantly reducing the infarct volume and improving the neurological functions of rats with ischemia. Treatment with HSYA could lead to relative corrections of the impaired metabolic pathways through energy metabolism disruption, excitatory amino acid toxicity, oxidative stress, and membrane disruption revealed by 1H NMR-based metabonomics. Meanwhile, HSYA treatment inhibits the NF-κB pathway via suppressing proinflammatory cytokine expression and p65 translocation and binding activity while upregulating an anti-inflammatory cytokine.

  11. Citrus-derived flavonoid naringenin exerts uterotrophic effects in female mice at human relevant doses

    DEFF Research Database (Denmark)

    Breinholt, Vibeke Miller; Svendsen, Gitte Winkel; Dragsted, Lars Ove

    2004-01-01

    ingestion of 400-760 ml of orange juice (Erlund et al. 2001). This could be taken to suggests that ingestion of orange juice and other citrus fruits and juices may give rise to sufficiently high tissue levels of naringenin in man to exert a biological effect....

  12. Neuroprotective effects of oligodendrocyte progenitor cell transplantation in premature rat brain following hypoxic-ischemic injury.

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    Long-Xia Chen

    Full Text Available Periventricular leukomalacia (PVL is a common ischemic brain injury in premature infants for which there is no effective treatment. The objective of this study was to determine whether transplanted mouse oligodendrocyte progenitor cells (OPCs have neuroprotective effects in a rat model of PVL. Hypoxia-ischemia (HI was induced in 3-day-old rat pups by left carotid artery ligation, followed by exposure to 6% oxygen for 2.5 h. Animals were assigned to OPC transplantation or sham control groups and injected with OPCs or PBS, respectively, and sacrificed up to 6 weeks later for immunohistochemical analysis to investigate the survival and differentiation of transplanted OPCs. Apoptosis was evaluated by double immunolabeling of brain sections for caspase-3 and neuronal nuclei (NeuN, while proliferation was assessed using a combination of anti-Nestin and -bromodeoxyuridine antibodies. The expression of brain-derived neurotrophic factor (BDNF and Bcl-2 was examined 7 days after OPC transplantation. The Morris water maze was used to test spatial learning and memory. The results showed that transplanted OPCs survived and formed a myelin sheath, and stimulated BDNF and Bcl-2 expression and the proliferation of neural stem cells (NSC, while inhibiting HI-induced neuronal apoptosis relative to control animals. Moreover, deficits in spatial learning and memory resulting from HI were improved by OPC transplantation. These results demonstrate an important neuroprotective role for OPCs that can potentially be exploited in cell-based therapeutic approaches to minimize HI-induced brain injury.

  13. Neuroprotective effects of the triterpenoid, CDDO methyl amide, a potent inducer of Nrf2-mediated transcription.

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    Lichuan Yang

    Full Text Available The NF-E2-related factor-2 (Nrf2/antioxidant response element (ARE signaling pathway regulates phase 2 detoxification genes, including a variety of antioxidative enzymes. We tested neuroprotective effects of the synthetic triterpenoid CDDO-MA, a potent activator of the Nrf2/ARE signaling. CDDO-MA treatment of neuroblastoma SH-SY5Y cells resulted in Nrf2 upregulation and translocation from cytosol to nucleus and subsequent activation of ARE pathway genes. CDDO-MA blocked t-butylhydroperoxide-induced production of reactive oxygen species (ROS by activation of ARE genes only in wild type, but not Nrf2 knockout mouse embryonic fibroblasts. Oral administration of CDDO-MA resulted in significant protection against MPTP-induced nigrostriatal dopaminergic neurodegeneration, pathological alpha-synuclein accumulation and oxidative damage in mice. Additionally, CDDO-MA treatment in rats produced significant rescue against striatal lesions caused by the neurotoxin 3-NP, and associated increases in the oxidative damage markers malondialdehyde, F(2-Isoprostanes, 8-hydroxy-2-deoxyguanosine, 3-nitrotyrosine, and impaired glutathione homeostasis. Our results indicate that the CDDO-MA renders its neuroprotective effects through its potent activation of the Nrf2/ARE pathway, and suggest that triterpenoids may be beneficial for the treatment of neurodegenerative diseases like Parkinson's disease and Huntington's disease.

  14. In vitro evaluation of antioxidant and neuroprotective effects of curcumin loaded in Pluronic micelles

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    Cvetelina Gorinova

    2016-09-01

    Full Text Available Curcumin is a polyphenolic substance with attractive pharmacological activities (e.g. antioxidant, anti-inflammatory, anticancer. Incorporation of curcumin in polymeric micelles could overcome the problems associated with its instability and low aqueous solubility. The aim of this study was to load curcumin in polymeric micelles based on Pluronic® P 123 or Pluronic® F 127 triblock copolymers and evaluate the antioxidant and neuroprotective effects after micellization. The micelles were prepared and loaded with curcumin by applying the dissolution method. Higher encapsulation efficiency was observed in the micelles formulated with Pluronic® P 123. These micelles were characterized with small size and narrow size distribution. The effects of micellar curcumin were investigated in two in vitro models. First, the capacity of micellar curcumin to inhibit iron/ascorbic acid-induced lipid peroxidation in rat liver microsomes was evaluated. Micellar curcumin and free drug showed similar inhibition of lipid peroxidation. Second, micellar curcumin and free curcumin showed protective potential in a model of 6-hydroxydopamine induced neurotoxicity in rat brain synaptosomes. The results from both methods indicated preservation of antioxidant and neuroprotective activity of curcumin in micelles. The small micellar size, high loading capacity and preservation of antioxidant activity of curcumin into Pluronic micelles, suggested their further evaluation as a curcumin delivery system.

  15. Neuroprotective effects of cactus polysaccharide on oxygen and glucose deprivation induced damage in rat brain slices.

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    Huang, Xianju; Li, Qin; Zhang, Yingpei; Lü, Qing; Guo, Lianjun; Huang, Lin; He, Zhi

    2008-06-01

    1. The neuroprotective effect of cactus polysaccharide (CP) on oxygen and glucose deprivation (OGD) and reoxygenation (REO)-induced damage in the cortical and hippocampal slices of rat brain was investigated. 2. Cell viability was evaluated by using the 2, 3, 5-triphenyl tetrazolium chloride (TTC) method. The fluorescence of propidium iodide (PI) staining was used for quantification of cellular survival, and lactate dehydrogenase (LDH) activity in incubation medium was assessed by LDH assay to evaluate the degree of injury. 3. The OGD ischemic condition significantly decreased cellular viability and increased LDH release in the incubation medium. CP (0.2 mg/l approximately 2 mg/l) protected brain slices from OGD injury in a dosage dependent manner as demonstrated by increased A 490 value of TTC, decreased PI intensity and LDH release. At the above concentration, CP also prevented the increase of nitric oxide (NO) content and inducible nitric oxide synthase (iNOS) activity induced by OGD. 4. CP can protect the brain slices (cortical and hippocampus) against injury induced by OGD. Its neuroprotective effect may be partly mediated by the NO/iNOS system induced by OGD insult.

  16. Histidine Neuroprotective Effect on CA1 Region of Rat Hippocampus Following Transient Brain Ischemia

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    H Vaghefi Eftekhar

    2012-02-01

    Full Text Available Background & Aim: There are multiple processes that lead to cell death after brain ischemia, such as glutamate release and inflammatory reactions. Histamine is able to suppress inflammatory reactions and glutamate release. Since histidine is precursor of histamine, this study was conducted to evaluate its neuroprotective effects on CA1 region of rat hippocampus following brain ischemia. Methods: In the present experimental study, thirty-six male Wistar rats were randomly divided into six groups as the following: control, surgical control, ischemia, and three groups which different doses (200, 500, and 1000 mg/kg of histidine. Focal cerebral ischemia, for 60 min, was provoked by transient occlusion of the right middle cerebral artery in all groups except the two control groups, and histidine neuro-protective effects on neuronal death was evaluated in CA1 of hippocampus neurons after 7 days. The gathered data was analyzed using one-way ANOVA. Results: The results showed that the mean number of neuronal degeneration and pancellular necrosis in groups which received doses of 500 and 1000 mg/kg of histidine have significantly decreased in comparison with the ischemia group (p=0.001. This reduction in dose of 200 mg/kg of histidine was not statistically significant (p=0.05. Conclusion: Our present findings show that intraperitoneal administration of histidine before reperfusion alleviated CA1 damage.

  17. Neuroprotective effects of sildenafil against oxidative stress and memory dysfunction in mice exposed to noise stress.

    Science.gov (United States)

    Sikandaner, Hu Erxidan; Park, So Young; Kim, Min Jung; Park, Shi Nae; Yang, Dong Won

    2017-02-15

    Noise exposure has been well characterized as an environmental stressor, and is known to have auditory and non-auditory effects. Phosphodiesterase 5 (PDE5) inhibitors affect memory and hippocampus plasticity through various signaling cascades which are regulated by cGMP. In this study, we investigated the effects of sildenafil on memory deficiency, neuroprotection and oxidative stress in mice caused by chronic noise exposure. Mice were exposed to noise for 4h every day up to 14days at 110dB SPL of noise level. Sildenafil (15mg/kg) was orally administered 30min before noise exposure for 14days. Behavioral assessments were performed using novel object recognition (NOR) test and radial arm maze (RAM) test. Higher levels of memory dysfunction and oxidative stress were observed in noise alone-induced mice compared to control group. Interestingly, sildenafil administration increased memory performance, decreased oxidative stress, and increased neuroprotection in the hippocampus region of noise alone-induced mice likely through affecting memory related pathways such as cGMP/PKG/CREB and p25/CDK5, and induction of free radical scavengers such as SOD1, SOD2, SOD3, Prdx5, and catalase in the brain of stressed mice. Copyright © 2016. Published by Elsevier B.V.

  18. Neuroprotective Effect of Salvianolic Acids against Cerebral Ischemia/Reperfusion Injury

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    Shuai Hou

    2016-07-01

    Full Text Available This study investigated the neuroprotective effect of salvianolic acids (SA against ischemia/reperfusion (I/R injury, and explored whether the neuroprotection was dependent on mitochondrial connexin43 (mtCx43 via the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT pathway. In vitro, we measured astrocyte apoptosis, mitochondrial membrane potential, and also evaluated the morphology of astrocyte mitochondria with transmission electron microscopy. In vivo, we determined the cerebral infarction volume and measured superoxide dismutase (SOD activity and malondialdehyde (MDA content. Additionally, mtCx43, p-mtCx43, AKT, and p-AKT levels were determined. In vitro, we found that I/R injury induced apoptosis, decreased cell mitochondrial membrane potential (MMP, and damaged mitochondrial morphology in astrocytes. In vivo, we found that I/R injury resulted in a large cerebral infarction, decreased SOD activity, and increased MDA expression. Additionally, I/R injury reduced both the p-mtCx43/mtCx43 and p-AKT/AKT ratios. We reported that both in vivo and in vitro, SA ameliorated the detrimental outcomes of the I/R. Interestingly, co-administering an inhibitor of the PI3K/AKT pathway blunted the effects of SA. SA represents a potential treatment option for cerebral infarction by up-regulating mtCx43 through the PI3K/AKT pathway.

  19. Biochemical Properties and Neuroprotective Effects of Compounds in Various Species of Berries

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    Erin Kelly

    2017-12-01

    Full Text Available Several species of berries, such as blueberries (Vaccinium angustifolium and lingonberries (Vaccinium vitis-idaea L., have attracted much scientific attention in recent years, especially due to their reported antioxidant and anti-inflammatory properties. Berries, as with other types of plants, have developed metabolic mechanisms to survive various environmental stresses, some of which involve reactive oxygen species. In addition, the fruits and leaves of berries have high amounts of polyphenols, such as flavonoids, which act as potent antioxidants. These compounds could potentially be beneficial for brain aging and neurodegenerative disorders. There are now several studies documenting the beneficial effects of various berries in cell models of neurotoxicity as well as in vivo models of neurodegenerative disease. In the current review, we discuss the metabolic strategies that plants and animals have developed in order to combat reactive oxygen species. We then discuss issues of bioavailability of various compounds in mammals and provide a synopsis of studies demonstrating the neuroprotective ability of berries and polyphenols. We also summarize findings from our own research group. For example, we have detected various polyphenols in samples of blueberries and lingonberries and have found that the leaves have a much higher antioxidant capacity than the fruits. Extracts from these species have also demonstrated neuroprotective effects in cellular models of toxicity and inflammation, which are being further pursued in animal models.

  20. Neuroprotective effects of leptin in the context of obesity and metabolic disorders.

    Science.gov (United States)

    Davis, Cecilia; Mudd, Jeremy; Hawkins, Meredith

    2014-12-01

    As the population of the world ages, the prevalence of neurodegenerative disease continues to rise, accompanied by increases in disease burden related to obesity and metabolic disorders. Thus, it will be essential to develop tools for preventing and slowing the progression of these major disease entities. Epidemiologic studies have shown strong associations between obesity, metabolic dysfunction, and neurodegeneration, while animal models have provided insights into the complex relationships between these conditions. Experimentally, the fat-derived hormone leptin has been shown to act as a neuroprotective agent in various animal models of dementia, toxic insults, ischemia/reperfusion, and other neurodegenerative processes. Specifically, leptin minimizes neuronal damage induced by neurotoxins and pro-apoptotic conditions. Leptin has also demonstrated considerable promise in animal models of obesity and metabolic disorders via modulation of glucose homeostasis and energy intake. However, since obesity is known to induce leptin resistance, we hypothesize that resistance to the neuroprotective effects of leptin contributes to the pathogenesis of obesity-associated neurodegenerative diseases. This review aims to explore the literature pertinent to the role of leptin in the protection of neurons from the toxic effects of aging, obesity and metabolic disorders, to investigate the physiological state of leptin resistance and its causes, and to consider how leptin might be employed therapeutically in the prevention and treatment of neurodegenerative disease. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Neuroprotective and antioxidative effect of cactus polysaccharides in vivo and in vitro.

    Science.gov (United States)

    Huang, Xianju; Li, Qin; Li, Huige; Guo, Lianjun

    2009-12-01

    Cactus polysaccharides (CP), some of the active components in Opuntia dillenii Haw have been reported to display neuroprotective effects in rat brain slices. In the present study, we investigated the neuroprotective properties of CP and their potential mechanisms on brain ischemia-reperfusion injury in rats, and on oxidative stress-induced damage in PC12 cells. Male Sprague-Dawley rats with ischemia following middle cerebral artery occlusion and reperfusion were investigated. CP (200 mg/kg) significantly decreased the neurological deficit score, reduced infarct volume, decreased neuronal loss in cerebral cortex, and remarkably reduced the protein synthesis of inducible nitric oxide synthase which were induced by ischemia and reperfusion. Otherwise, the protective effect of CP was confirmed in in vitro study. CP protected PC12 cells against hydrogen peroxide (H(2)O(2)) insult. Pretreatment with CP prior to H(2)O(2) exposure significantly elevated cell viability, reduced H(2)O(2)-induced apoptosis, and decreased both intracellular and total accumulation of reactive oxygen species (ROS) production. Furthermore, CP also reversed the upregulation of Bax/Bcl-2 mRNA ratio, the downstream cascade following ROS. These results suggest that CP may be a candidate compound for the treatment of ischemia and oxidative stress-induced neurodegenerative disease.

  2. [Studying the neuroprotective effect of the novel glutamic acid derivative neiroglutam on focal cerebral ischemia in rats].

    Science.gov (United States)

    Tiurenkov, I N; Kurkin, D V; Bakulin, D A; Volotova, E V

    2014-01-01

    We have studied the neuroprotective effect of the novel glutamic acid derivative neiroglutam on reversible focal cerebral ischemia in rats. The neuroprotective drug action was assessed by the ability to reduce the severity of neurological deficit (1, 2, 3, 5 and 7 days), forelimb fine-motor disorders (in the ladder test), hind limb motor activity (beam-walking test), and volume of the infarct zone upon 7-day pathologic exposure. It was found that the therapeutic administration of neiroglutam (26 mg/kg, i.p., for 7 days) reduces the volume of necrosis of cerebral tissues in case of focal brain ischemia in animals (on the average by 38%, (p < 0.05) and decreases the severity of motor disorders, which indicates the presence of neuroprotective effect of this compound.

  3. The Neuroprotective Effect of Kefir on Spinal Cord Ischemia/Reperfusion Injury in Rats.

    Science.gov (United States)

    Guven, Mustafa; Akman, Tarik; Yener, Ali Umit; Sehitoglu, Muserref Hilal; Yuksel, Yasemin; Cosar, Murat

    2015-05-01

    The main causes of spinal cord ischemia are a variety of vascular pathologies causing acute arterial occlusions. We investigated neuroprotective effects of kefir on spinal cord ischemia injury in rats. Rats were divided into three groups : 1) sham operated control rats; 2) spinal cord ischemia group fed on a standard diet without kefir pretreatment; and 3) spinal cord ischemia group fed on a standard diet plus kefir. Spinal cord ischemia was performed by the infrarenal aorta cross-clamping model. The spinal cord was removed after the procedure. The biochemical and histopathological changes were observed within the samples. Functional assessment was performed for neurological deficit scores. The kefir group was compared with the ischemia group, a significant decrease in malondialdehyde levels was observed (pkefir group were significantly higher than ischemia group (pkefir group is compared with ischemia group, there was a significant decrease in numbers of dead and degenerated neurons (pkefir group compared with ischemia group (pkefir group were significantly higher than ischemia group at 24 h (pkefir pretreatment in spinal cord ischemia/reperfusion reduced oxidative stress and neuronal degeneration as a neuroprotective agent. Ultrastructural studies are required in order for kefir to be developed as a promising therapeutic agent to be utilized for human spinal cord ischemia in the future.

  4. Effects of acclimation on water and electrolitic disbalance in soldiers during exertional heat stress

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    Radaković Sonja S.

    2007-01-01

    Full Text Available Background/Aim. Exertional heat stress is a common problem in military services. The aim of this study was to examine changes in body water and serum concentrations of some electrolites in soldiers during exertional heat stress (EHST, as well as effects of 10-day passive or active acclimation in a climatic chamber. Methods. Forty male soldiers with high aerobic capacity, performed EHST either in cool (20 ºC, 16 ºC WBGT-wet bulb globe temperature, or hot (40 ºC, 25 ºC WBGT environment, unacclimatized, or after 10 days of passive or active acclimation. The subjects were allowed to drink tap water ad libitum during EHST. Mean skin (Tsk and tympanic (Tty temperatures and heart rates (HR measured physiological strain, while sweat rate (SwR, and serum concentrations of sodium, potassium and osmolality measured changes in water and electrolyte status. Blood samples were collected before and immediately after the EHST. Results. Exertional heat stress in hot conditions induced physiological heat stress (increase in Tty, HR, and SwR, with significant decrease in serum sodium concentration (140.6±1.52 before vs 138.5±1.0 mmol/l after EHST, p < 0.01 and osmolality (280.7±3.8 vs 277.5±2.6 mOsm/kg, p < 0.05 in the unacclimatized group. The acclimated soldiers suffered no such effects of exertional heat stress, despite almost the same degree of heat strain, measured by Tty, HR and SwR. Conclusion. In the trained soldiers, 10-day passive or active acclimation in a climatic chamber can prevent disturbances in water and electrolytic balance, i.e. decrease in serum sodium concentrations and osmolality induced by exertional heat stress.

  5. Neuroprotective effects of ganoderma lucidum polysaccharides against oxidative stress-induced neuronal apoptosis.

    Science.gov (United States)

    Sun, Xin-Zhi; Liao, Ying; Li, Wei; Guo, Li-Mei

    2017-06-01

    Ganoderma lucidum polysaccharides have protective effects against apoptosis in neurons exposed to ischemia/reperfusion injury, but the mechanisms are unclear. The goal of this study was to investigate the underlying mechanisms of the effects of ganoderma lucidum polysaccharides against oxidative stress-induced neuronal apoptosis. Hydrogen peroxide (H 2 O 2 ) was used to induce apoptosis in cultured cerebellar granule cells. In these cells, ganoderma lucidum polysaccharides remarkably suppressed H 2 O 2 -induced apoptosis, decreased expression of caspase-3, Bax and Bim and increased that of Bcl-2. These findings suggested that ganoderma lucidum polysaccharides regulate expression of apoptosis-associated proteins, inhibit oxidative stress-induced neuronal apoptosis and, therefore, have significant neuroprotective effects.

  6. Neuroprotective effects of ganoderma lucidum polysaccharides against oxidative stress-induced neuronal apoptosis

    Science.gov (United States)

    Sun, Xin-zhi; Liao, Ying; Li, Wei; Guo, Li-mei

    2017-01-01

    Ganoderma lucidum polysaccharides have protective effects against apoptosis in neurons exposed to ischemia/reperfusion injury, but the mechanisms are unclear. The goal of this study was to investigate the underlying mechanisms of the effects of ganoderma lucidum polysaccharides against oxidative stress-induced neuronal apoptosis. Hydrogen peroxide (H2O2) was used to induce apoptosis in cultured cerebellar granule cells. In these cells, ganoderma lucidum polysaccharides remarkably suppressed H2O2-induced apoptosis, decreased expression of caspase-3, Bax and Bim and increased that of Bcl-2. These findings suggested that ganoderma lucidum polysaccharides regulate expression of apoptosis-associated proteins, inhibit oxidative stress-induced neuronal apoptosis and, therefore, have significant neuroprotective effects. PMID:28761429

  7. Retinal Neuroprotective Effects of Flibanserin, an FDA-Approved Dual Serotonin Receptor Agonist-Antagonist.

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    Aaron S Coyner

    Full Text Available To assess the neuroprotective effects of flibanserin (formerly BIMT-17, a dual 5-HT1A agonist and 5-HT2A antagonist, in a light-induced retinopathy model.Albino BALB/c mice were injected intraperitoneally with either vehicle or increasing doses of flibanserin ranging from 0.75 to 15 mg/kg flibanserin. To assess 5-HT1A-mediated effects, BALB/c mice were injected with 10 mg/kg WAY 100635, a 5-HT1A antagonist, prior to 6 mg/kg flibanserin and 5-HT1A knockout mice were injected with 6 mg/kg flibanserin. Injections were administered once immediately prior to light exposure or over the course of five days. Light exposure lasted for one hour at an intensity of 10,000 lux. Retinal structure was assessed using spectral domain optical coherence tomography and retinal function was assessed using electroretinography. To investigate the mechanisms of flibanserin-mediated neuroprotection, gene expression, measured by RT-qPCR, was assessed following five days of daily 15 mg/kg flibanserin injections.A five-day treatment regimen of 3 to 15 mg/kg of flibanserin significantly preserved outer retinal structure and function in a dose-dependent manner. Additionally, a single-day treatment regimen of 6 to 15 mg/kg of flibanserin still provided significant protection. The action of flibanserin was hindered by the 5-HT1A antagonist, WAY 100635, and was not effective in 5-HT1A knockout mice. Creb, c-Jun, c-Fos, Bcl-2, Cast1, Nqo1, Sod1, and Cat were significantly increased in flibanserin-injected mice versus vehicle-injected mice.Intraperitoneal delivery of flibanserin in a light-induced retinopathy mouse model provides retinal neuroprotection. Mechanistic data suggests that this effect is mediated through 5-HT1A receptors and that flibanserin augments the expression of genes capable of reducing mitochondrial dysfunction and oxidative stress. Since flibanserin is already FDA-approved for other indications, the potential to repurpose this drug for treating retinal

  8. Dose-dependent neuroprotective effect of enoxaparin on cold-induced traumatic brain injury.

    Science.gov (United States)

    Keskin, Ilknur; Gunal, M Yalcin; Ayturk, Nilufer; Kilic, Ulkan; Ozansoy, Mehmet; Kilic, Ertugrul

    2017-05-01

    Recent evidence exists that enoxaparin can reduce brain injury because of its anticoagulant activity. To investigate the potential therapeutic effect of enoxaparin on cold-induced traumatic brain injury, at 20 minutes after modeling, male BALB/c mouse models of cold-induced traumatic brain injury were intraperitoneally administered 3 and 10 mg/kg enoxaparin or isotonic saline solution. Twenty-four hours later, enoxaparin at 10 mg/kg greatly reduced infarct volume, decreased cell apoptosis in the cortex and obviously increased serum level of total antioxidant status. By contrast, administration of enoxaparin at 3 mg/kg did not lead to these changes. These findings suggest that enoxaparin exhibits neuroprotective effect on cold-induced traumatic brain injury in a dose-dependent manner.

  9. Comparative study of neuroprotective effect of tricyclics vs. trazodone on animal model of depressive disorder.

    Science.gov (United States)

    Marinescu, Ileana P; Predescu, Anca; Udriştoiu, T; Marinescu, D

    2012-01-01

    The neurobiological model of depressive disorder may be correlated with the animal model on rat, hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, the increase of cortisol level being specific to the model of depression in women. The neurobiological model of depression in women presents vulnerabilities for some cerebral structures (hippocampus, frontal cortex, cerebral amygdala). A decrease of frontal cortex and hippocampus volumes are recognized in depressive disorder in women, depending on duration of disease and antidepressant therapy. Neurobiological vulnerability may be pronounced through cholinergic blockade. The purpose of the study was to highlight the cytoarchitectural changes in the frontal cortex and hippocampus by comparing two antidepressant substances: amitriptyline with a strong anticholinergic effect and trazodone, without anticholinergic effect. The superior neuroprotective qualities of trazodone for the frontal cortex, hippocampus and dentate gyrus are revealed. The particular neurobiological vulnerability of depression in women requires a differentiated therapeutic approach, avoiding the use of antidepressants with anticholinergic action.

  10. Polyphenolic compounds with antioxidant potential and neuro-protective effect from Cimicifuga dahurica (Turcz.) Maxim.

    Science.gov (United States)

    Qin, Rulan; Zhao, Ying; Zhao, Yudan; Zhou, Wanrong; Lv, Chongning; Lu, Jincai

    2016-12-01

    Three new phenolic compounds (1-3), along with five known compounds (4-8) were isolated from the rhizome of Cimicifuga dahurica (Turcz.) Maxim. Their structures were elucidated by spectroscopic methods including 1D-NMR, 2D-NMR and HR-MS techniques. DPPH method and protective effect on PC12 cells against H 2 O 2 -induced oxidative damage model were carried to evaluate the antioxidant capability of these compounds. Compound 5 showed significant antioxidant activity with IC 50 values 9.33μM in DPPH assay and compound 2 displayed marked neuro-protective effect with 87.65% cell viability at the concentration of 10μM. Additionally, the possible structure-activity relationships of these phenolic compounds were tentatively discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Caffeine and theanine exert opposite effects on attention under emotional arousal.

    Science.gov (United States)

    Giles, Grace E; Mahoney, Caroline R; Brunyé, Tad T; Taylor, Holly A; Kanarek, Robin B

    2017-01-01

    Tea is perceived as more relaxing than coffee, even though both contain caffeine. L-theanine in tea may account for the difference. Consumed together, caffeine and theanine exert similar cognitive effects to that of caffeine alone, but exert opposite effects on arousal, in that caffeine accentuates and theanine mitigates physiological and felt stress responses. We evaluated whether caffeine and theanine influenced cognition under emotional arousal. Using a double-blind, repeated-measures design, 36 participants received 4 treatments (200 mg caffeine + 0 mg theanine, 0 mg caffeine + 200 mg theanine, 200 mg caffeine + 200 mg theanine, 0 mg caffeine + 0 mg theanine) on separate days. Emotional arousal was induced by highly arousing negative film clips and pictures. Mood, salivary cortisol, and visual attention were evaluated. Caffeine accentuated global processing of visual attention on the hierarchical shape task (p Caffeine reduced flanker conflict difference scores on the Attention Network Test (p caffeine and theanine exert opposite effects on certain attentional processes, but when consumed together, they counteract the effects of each other.

  12. Neuroprotection in glaucoma

    Directory of Open Access Journals (Sweden)

    Azadeh Doozandeh

    2016-01-01

    Full Text Available Glaucoma is a degenerative optic neuropathy characterized by retinal ganglion cell (RGC loss and visual field defects. It is known that in some glaucoma patients, death of RGCs continues despite intraocular pressure (IOP reduction. Neuroprotection in the field of glaucoma is defined as any treatment, independent of IOP reduction, which prevents RGC death. Glutamate antagonists, ginkgo biloba extract, neurotrophic factors, antioxidants, calcium channel blockers, brimonidine, glaucoma medications with blood regulatory effect and nitric oxide synthase inhibitors are among compounds with possible neuroprotective activity in preclinical studies. A few agents (such as brimonidine or memantine with neuroprotective effects in experimental studies have advanced to clinical trials; however the results of clinical trials for these agents have not been conclusive. Nevertheless, lack of compelling clinical evidence has not prevented the off-label use of some of these compounds in glaucoma practice. Stem cell transplantation has been reported to halt experimental neurodegenerative disease processes in the absence of cell replacement. It has been hypothesized that transplantation of some types of stem cells activates multiple neuroprotective pathways via secretion of various factors. The advantage of this approach is a prolonged and targeted effect. Important concerns in this field include the secretion of unwanted harmful mediators, graft survival issues and tumorigenesis. Neuroprotection in glaucoma, pharmacologically or by stem cell transplantation, is an interesting subject waiting for broad and multidisciplinary collaborative studies to better clarify its role in clinical practice.

  13. Evidence of neuroprotective effects of saffron and crocin in a Drosophila model of parkinsonism.

    Science.gov (United States)

    Rao, Sriranjini Venkat; Muralidhara; Yenisetti, Sarat Chandra; Rajini, Padmanabhan S

    2016-01-01

    Evidence suggests that saffron and its major bioactives exhibit significant neuromodulatory effects in various animal models. However, specific data related to their efficacy to attenuate oxidative stress and neurotoxicity in animal models of Parkinson's disease (PD) are limited. Hence, we investigated the neuroprotective efficacy of saffron methanolic extract (SME) and its active constituent, crocin (CR) employing a Drosophila model of parkinsonism. We focussed on attenuation of Rotenone (ROT)-induced locomotor phenotype, oxidative stress, mitochondrial dysfunction and neurotoxicity in this model. SME and CR-enrichment significantly reduced ROT (500μM) induced mortality, rescued the locomotor phenotype and diminished the enhanced levels of oxidative stress markers in head/body regions of flies. The reduced levels of reduced glutathione (GSH) and total thiols (TSH) resulting from ROT exposure were significantly restored with concomitant enhancement of the antioxidant enzymes activities. Further, ROT-induced mitochondrial dysfunctions (MTT reduction, activities of SDH and NADH-Cyt C reductase (complexes I-III) enzymes) were markedly attenuated by SME/CR enrichment. While ROT elevated the activity of acetylcholinesterase (AChE) in head/body regions, both the treatments caused marked diminution of AChE activity and restored the dopamine levels suggesting their effectiveness to mitigate cholinergic function. Interestingly, SME/CR enrichment significantly delayed the onset of locomotor deficits and extended life span of flies among ROT (50μM)-stressed flies. In a satellite study, flies provided with SME/CR prophylaxis exhibited marked resistance to an acute Paraquat (PQ) challenge as evidenced by the lower incidence of lethality and improved locomotor phenotype. Taken together, the neuroprotective effects of saffron and crocin in the fly model may be largely attributable to its antioxidant action. Based on our findings, we propose that saffron may be exploited as a

  14. Synthesis, binding affinity at glutamic acid receptors, neuroprotective effects, and molecular modeling investigation of novel dihydroisoxazole amino acids

    DEFF Research Database (Denmark)

    Conti, Paola; De Amici, Marco; Grazioso, Giovanni

    2005-01-01

    neuroprotective effect when tested in an oxygen glucose deprivation (OGD) cell culture test. The same compounds were preliminarily assayed using Xenopus oocytes expressing cloned rat NMDA receptors containing the NR1 subunit in combination with either NR2A, NR2B, NR2C, or NR2D subunit. In this assay, all three...

  15. Comparison of neuroprotective effects of erythropoietin (EPO) and carbamylerythropoietin (CEPO) against ischemia-like oxygen-glucose deprivation (OGD) and NMDA excitotoxicity in mouse hippocampal slice cultures

    DEFF Research Database (Denmark)

    Montero, Maria; Rom Poulsen, Frantz; Noraberg, Jens

    2007-01-01

    In addition to its well-known hematopoietic effects, erythropoietin (EPO) also has neuroprotective properties. However, hematopoietic side effects are unwanted for neuroprotection, underlining the need for EPO-like compounds with selective neuroprotective actions. One such compound, devoid...... of hematopoietic bioactivity, is the chemically modified, EPO-derivative carbamylerythropoietin (CEPO). For comparison of the neuroprotective effects of CEPO and EPO, we subjected organotypic hippocampal slice cultures to oxygen-glucose deprivation (OGD) or N-methyl-d-aspartate (NMDA) excitotoxicity. Hippocampal...... cultures. To elucidate a possible mechanism involved in EPO and CEPO neuroprotection against OGD, the integrity of alpha-II-spectrin cytoskeletal protein was studied. Both EPO and CEPO significantly reduced formation of spectrin cleavage products in the OGD model. We conclude that CEPO is at least...

  16. The neuroprotective effects of tocotrienol rich fraction and alpha tocopherol against glutamate injury in astrocytes

    Directory of Open Access Journals (Sweden)

    Thilaga Rati Selvaraju

    2014-11-01

    Full Text Available Tocotrienol rich fraction (TRF is an extract of palm oil, which consists of 25% alpha tocopherol (α-TCP and 75% tocotrienols. TRF has been shown to possess potent antioxidant, anti-inflammatory, anticancer, neuroprotection, and cholesterol lowering activities. Glutamate is the main excitatory amino acid neurotransmitter in the central nervous system of mammalian, which can be excitotoxic, and it has been suggested to play a key role in neurodegenerative disorders like Parkinson’s and Alzheimer’s diseases. In this present study, the effects of vitamin E (TRF and α-TCP in protecting astrocytes against glutamate injury were elucidated. Astrocytes induced with 180 mM of glutamate lead to significant cell death. However, glutamate mediated cytotoxicity was diminished via pre and post supplementation of TRF and α-TCP. Hence, vitamin E acted as a potent antioxidant agent in recovering mitochondrial injury due to elevated oxidative stress, and enhanced better survivability upon glutamate toxicity.  

  17. Neuroprotective effects of xanthohumol, a prenylated flavonoid from hops (Humulus lupulus), in ischemic stroke of rats.

    Science.gov (United States)

    Yen, Ting-Lin; Hsu, Chung-King; Lu, Wan-Jung; Hsieh, Cheng-Ying; Hsiao, George; Chou, Duen-Suey; Wu, Gong-Jhe; Sheu, Joen-Rong

    2012-02-29

    Xanthohumol is the principal prenylated flavonoid in hops (Humulus lupulus L.), an ingredient of beer. Xanthohumol was found to be a potent chemopreventive agent; however, no data are available concerning its neuroprotective effects. In the present study, the neuroprotective activity and mechanisms of xanthohumol in rats with middle cerebral artery occlusion (MCAO)-induced cerebral ischemia were examined. Treatment with xanthohumol (0.2 and 0.4 mg/kg; intraperitoneally) 10 min before MCAO dose-dependently attenuated focal cerebral ischemia and improved neurobehavioral deficits in cerebral ischemic rats. Xanthohumol treatment produced a marked reduction in infarct size compared to that in control rats. MCAO-induced focal cerebral ischemia was associated with increases in hypoxia-inducible factor (HIF)-1α, tumor necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS), and active caspase-3 protein expressions in ischemic regions. These expressions were obviously inhibited by treatment with xanthohumol. In addition, xanthohumol (3-70 μM) concentration-dependently inhibited platelet aggregation stimulated by collagen (1 μg/mL) in human platelet-rich plasma. An electron spin resonance (ESR) method was used to examine the scavenging activity of xanthohumol on free radicals which had formed. Xanthohumol (1.5 and 3 μM) markedly reduced the ESR signal intensity of hydroxyl radical (OH•) formation in the H₂O₂/NaOH/DMSO system. In conclusion, this study demonstrates for the first time that in addition to its originally being considered an agent preventing tumor growth, xanthohumol possesses potent neuroprotective activity. This activity is mediated, at least in part, by inhibition of inflammatory responses (i.e., HIF-1α, iNOS expression, and free radical formation), apoptosis (i.e., TNF-α, active caspase-3), and platelet activation, resulting in a reduction of infarct volume and improvement in neurobehavior in rats with cerebral ischemia. Therefore, this

  18. The Neuroprotective Functions of Transforming Growth Factor Beta Proteins

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    Gábor Lovas

    2012-07-01

    Full Text Available Transforming growth factor beta (TGF-β proteins are multifunctional cytokines whose neural functions are increasingly recognized. The machinery of TGF-β signaling, including the serine kinase type transmembrane receptors, is present in the central nervous system. However, the 3 mammalian TGF-β subtypes have distinct distributions in the brain suggesting different neural functions. Evidence of their involvement in the development and plasticity of the nervous system as well as their functions in peripheral organs suggested that they also exhibit neuroprotective functions. Indeed, TGF-β expression is induced following a variety of types of brain tissue injury. The neuroprotective function of TGF-βs is most established following brain ischemia. Damage in experimental animal models of global and focal ischemia was shown to be attenuated by TGF-βs. In addition, support for their neuroprotective actions following trauma, sclerosis multiplex, neurodegenerative diseases, infections, and brain tumors is also accumulating. The review will also describe the potential mechanisms of neuroprotection exerted by TGF-βs including anti-inflammatory, -apoptotic, -excitotoxic actions as well as the promotion of scar formation, angiogenesis, and neuroregeneration. The participation of these mechanisms in the neuroprotective effects of TGF-βs during different brain lesions will also be discussed.

  19. The Neuroprotective Functions of Transforming Growth Factor Beta Proteins

    Science.gov (United States)

    Dobolyi, Arpád; Vincze, Csilla; Pál, Gabriella; Lovas, Gábor

    2012-01-01

    Transforming growth factor beta (TGF-β) proteins are multifunctional cytokines whose neural functions are increasingly recognized. The machinery of TGF-β signaling, including the serine kinase type transmembrane receptors, is present in the central nervous system. However, the 3 mammalian TGF-β subtypes have distinct distributions in the brain suggesting different neural functions. Evidence of their involvement in the development and plasticity of the nervous system as well as their functions in peripheral organs suggested that they also exhibit neuroprotective functions. Indeed, TGF-β expression is induced following a variety of types of brain tissue injury. The neuroprotective function of TGF-βs is most established following brain ischemia. Damage in experimental animal models of global and focal ischemia was shown to be attenuated by TGF-βs. In addition, support for their neuroprotective actions following trauma, sclerosis multiplex, neurodegenerative diseases, infections, and brain tumors is also accumulating. The review will also describe the potential mechanisms of neuroprotection exerted by TGF-βs including anti-inflammatory, -apoptotic, -excitotoxic actions as well as the promotion of scar formation, angiogenesis, and neuroregeneration. The participation of these mechanisms in the neuroprotective effects of TGF-βs during different brain lesions will also be discussed. PMID:22942700

  20. Neuroprotective effects of triterpene glycosides from glycine max against glutamate induced toxicity in primary cultured rat cortical cells.

    Science.gov (United States)

    Moon, Hyung-In; Lee, Jai-Heon

    2012-01-01

    To examine the neuroprotective effects of Glycine max, we tested its protection against the glutamate-induced toxicity in primary cortical cultured neurons. In order to clarify the neuroprotective mechanism(s) of this observed effect, isolation was performed to seek and identify active fractions and components. From such fractionation, two triterpene glycosides, 3-O-[α-l-rhamnopyranosyl(1-2)-β-d-glucopyranosyl(1-2)-β-d-glucuronopyranosyl]olean-12-en-3β,22β,24-triol (1) and 3-O-[β-d-glucopyranosyl(1-2)-β-d-galactopyranosyl(1-2)-β-d-glucuronopyranosyl]olean-12-en-3β,22β,24-triol (2) were isolated with the methanol extracts with of air-dried Glycine max. Among these compounds, compound 2 exhibited significant neuroprotective activities against glutamate-induced toxicity, exhibiting cell viability of about 50% at concentrations ranging from 0.1 μM to 10 μM. Therefore, the neuroprotective effect of Glycine max might be due to the inhibition of glutamate-induced toxicity by triterpene glycosides.

  1. Antiepileptogenic and Neuroprotective Effects of Pergularia daemia on Pilocarpine Model of Epilepsy

    Directory of Open Access Journals (Sweden)

    Antoine K. Kandeda

    2017-06-01

    Full Text Available In this study, we investigated antiepileptogenic and neuroprotective effects of the aqueous extract of Pergularia daemia roots (PDR using in vivo and in vitro experimental models. In in vivo studies, status epilepticus caused by pilocarpine injection triggers epileptogenesis which evolves during about 1–2 weeks. After 2 h of status epilepticus, mice were treated during the epileptogenesis period for 7 days with sodium valproate and vitamin C (standards which demonstrated to alter epileptogenesis, or Pergularia daemia. The animals were then, 1 week after status epilepticus, challenged with acute pentylenetetrazole (PTZ administration to test behaviorally the susceptibility to a convulsant agent of animals treated or not with the plan extract. Memory was assessed after PTZ administration in the elevated plus maze and T-maze paradigms at 24 and 48 h. Antioxidant and acetylcholinesterase activities were determined in the hippocampus after sacrifice, in vitro studies were conducted using embryonic rat primary cortical cultures exposed to L-glutamate. Cell survival rate was measured and apoptotic and necrotic cell death determined. The results showed that chronic oral administration of PDR significantly and dose-dependently increased the latency to myoclonic jerks, clonic seizures and generalized tonic–clonic seizures, and the seizure score. In addition, PDR at all doses (from 4.9 to 49 mg/kg significantly decreased the initial and retention transfer latencies in the elevated plus maze. Interestingly PDR at the same doses significantly increased the time spent and the number of entries in T-maze novel arm. PDR significantly increased the activities of acetylcholinesterase and antioxidant enzymes superoxide dismutase, catalase, and total glutathione and proteins, and decreased malondialdehyde level. Furthermore, PDR increased viability rate of primary cortical neurons after L-glutamate-induced excitotoxicity, in a dose dependent manner. Altogether

  2. [Neuroprotective effect of curcumin to Aβ of double transgenic mice with Alzheimer's disease].

    Science.gov (United States)

    Feng, Hui-Li; Fan, Hui; Dang, Hui-Zi; Chen, Xiao-Pei; Ren, Ying; Yang, Jin-Duo; Wang, Peng-Wen

    2014-10-01

    To observe the changes in Aβ40, Aβ42 and ADDLs in brains of 3 month-old APPswe/PS1dE9 double transgenic mice after six-month intervention with curcumin, in order to discuss the neuroprotective effect of curcumin. APPswe/PS1dE9dtg mice were randomly divided into the model group, the Rosiglitazone group (10 mg x kg(-1) x d(-1)) and curcumin high (400 mg x kg9-1) x d(-1)), medium (200 mg x kg(-1) x d(-1)) and low (100 mg x kg(-1) x d(-1)) dosage groups, with C57/BL6J mice of the same age and the same background in the normal control group. After 6 months, the immunohistochemical staining (IHC) and the Western blot method were used to observe the changes in positive cell of Aβ40, Aβ42 and ADDLs in hippocampal CA1 area, their distribution and protein expressions. Both of the immunohistochemical staining and the Western blot method showed more positive cell of Aβ40, Aβ42 and ADDLs in hippocampal CA1 area and higher protein expressions in the model group than the normal group (P curcumin high group, the medium group showed a significant decrease (P curcumin can significantly reduce the expressions of hippocampal Aβ40, Aβ42 and ADDLs in brains of APPswe/PS1dE9 double transgenic mice. Whether curcumin can impact Aβ cascade reaction by down-regulating expressions of Aβ40, Aβ42 and ADDLs and show the neuroprotective effect needs further studies.

  3. Neuroprotective effects of Thalassia testudinum leaf extract BM-21 on focal ischemia in rats

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    Teidy E. García

    2017-05-01

    Full Text Available Context: The extract from the marine plant Thalassia testudinum BM-21, standardized to thalassiolin B content (5.8 ± 0.3%, possesses antioxidant, anti-inflammatory and neuroprotective effects on acrylamide-induced neurotoxicity in mice and global ischemia in Mongolian gerbils. Aims: To determine whether or not BM-21 possesses neuroprotective effects against cerebral ischemia induced by permanent middle cerebral artery occlusion (pMCAo, a clinically relevant model of stroke. Methods: BM-21 was administered orally (400 mg/kg, once-a–day/10 days prior to ischemia. Twenty-four hours after occlusion, we studied neurological signs, infarct volume, cerebral edema, histological damage and oxidative stress in cortex and striatum. In addition, brain susceptibility to in vitro lipid peroxidation induced by kainic acid and 2,2′-azobis(2-amidinopropane dihydrochloride was studied after the BM-21 administration. Results: BM-21 prevented behavioral deficit; reduced infarct volume and cerebral edema; markedly decreased neuronal damage in striatum and cortex region. After occlusion, there was a significant increase of oxidative stress in cortex and striatum. Treatment of ischemic rats with BM-21 (400 mg/kg prevented lipid peroxidation and protein damage and increased the antioxidant enzymatic activities and glutathione. BM-21 also inhibited the in vitro lipid peroxidation in total brain homogenates. Conclusions: Oral pre-treatment of BM-21 protects rats against pMCAo ischemia-induced damage in the striatum and cortex. Results suggest that the protection of BM-21 involve at least partially, the increase resistance to oxidative stress.

  4. Defining the Focus of Attention: Effects of Attention on Perceived Exertion and Fatigue.

    Directory of Open Access Journals (Sweden)

    Keith eLohse

    2011-11-01

    Full Text Available This manuscript presents two experiments designed to explore the effects of attention on perceived exertion and time to failure in a fatiguing athletic task. There were two major motivating factors for these experiments. First, there are few studies evaluating attentional focus effects in endurance tasks and, second, there is a lack of integration between studies of attentional focus as external/internal (e.g., Wulf, 2007 compared to associative/dissociative (e.g., Stevenson & Biddle, 1998. In Experiment 1, we used a fatiguing wall-sit posture (essentially a complex, isometric task to compare two different types of external attention with an internal focus on the position of the legs. An external focus (regardless of type increased the time taken to failure and reduced perceived exertion. In Experiment 2, we manipulated subjects’ expectancy of fatigue to test the interaction of attention and expectancy (both top-down factors in this highly fatiguing task. Previous theories of attention during endurance tasks have suggested that as fatigue/pain increase, bottom-up factors begin to dominate subjects’ attention. While this may be true, Experiment 2 showed that even in a highly fatiguing task, attentional strategies and expectancies affected the time to failure and perceived exertion.

  5. The neuroprotective effects of purslane (Portulaca oleracea) on rotenone-induced biochemical changes and apoptosis in brain of rat.

    Science.gov (United States)

    Abdel Moneim, Ahmed E

    2013-09-01

    Purslane (Portulaca oleraceae L.), a member of the Portulacaceae family, is widespread as a weed and has been ranked as the eighth most common plant in the world. In order to evaluate purslane herbal aqueous juice as a neuroprotective agent, the antioxidant activity of purslane juice was assessed in vitro and the neuroprotective effects of purslane (1.5 mL/Kg bwt) on rotenone (12 mg/Kg bwt for 12 days) induced biochemical changes and apoptosis in striatum of rats were also examined. The repeated administration of rotenone produced dramatic increases in intercellular content of calcium, dopamine metabolites and apoptosis in the striatum. In addition, rotenone administration caused significant decrease in complex I activity. These biochemical changes and apoptosis inductions were effectively counteracted by administration of purslane. Overall, the present study demonstrated the neuroprotective role of purslane in the striatum and proposes its prophylactic potential against developing brain damage and Parkinson's disease induction followed by rotenone administration, and that purslane may be considered as a potential neuroprotective agent against environmental factors affecting the function of the dopaminergic system.

  6. Neuroprotective effects of bee venom acupuncture therapy against rotenone-induced oxidative stress and apoptosis.

    Science.gov (United States)

    Khalil, Wagdy K B; Assaf, Naglaa; ElShebiney, Shaimaa A; Salem, Neveen A

    2015-01-01

    Parkinson's disease (PD), the most common neurodegenerative movement disorder, is characterized by dopaminergic neurodegeneration, mitochondrial impairment, and oxidative stress. Exposure of animals to rotenone induces a range of responses characteristic of PD, including reactive oxygen species production and dopaminergic cell death. Although l-dopa is the drug of choice for improving core symptoms of PD, it is associated with involuntary movements. The current study was directed to evaluate the neuroprotective effect of bee venom acupuncture therapy (BVA) against rotenone-induced oxidative stress, neuroinflammation, and apoptosis in PD mouse model. Forty male Swiss mice were divided into four groups: (1) received saline solution orally and served as normal control, (2) received rotenone (1.5 mg/kg, s.c. every other day for 6 doses), (3) received rotenone concomitantly with l-dopa (25 mg/kg, daily, p.o. for 6 days), and finally (4) received rotenone concomitantly with BVA (0.02 ml once every 3 days for two weeks). Rotenone-treated mice showed impairment in locomotor behavior and a significant reduction in brain dopamine, serotonin, norepinephrine, GSH levels, and paraoxonase activity, whereas a significant increase was observed in brain malondialdehyde, tumor necrosis factor-α, interleukin-β levels besides DNA damage, and over-expression of caspase-3, Bax, and Bcl-2 genes. Significant improvement of the aforementioned parameters was demonstrated after BVA compared to l-dopa therapy. In conclusion, bee venom normalized all the neuroinflammatory and apoptotic markers and restored brain neurochemistry after rotenone injury. Therefore, BVA is a promising neuroprotective therapy for PD. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Neuroprotective effect of Arthrospira (Spirulina) platensis against kainic acid-neuronal death.

    Science.gov (United States)

    Pérez-Juárez, Angélica; Chamorro, Germán; Alva-Sánchez, Claudia; Paniagua-Castro, Norma; Pacheco-Rosado, Jorge

    2016-08-01

    Context Arthrospira (Spirulina) platensis (SP) is a cyanobacterium which has attracted attention because of its nutritional value and pharmacological properties. It was previously reported that SP reduces oxidative stress in the hippocampus and protects against damaging neurobehavioural effects of systemic kainic acid (KA). It is widely known that the systemic administration of KA induces neuronal damage, specifically in the CA3 hippocampal region. Objective The present study determines if the SP sub-chronic treatment has neuroprotective properties against KA. Materials and methods Male SW mice were treated with SP during 24 d, at doses of 0, 200, and 800 mg/kg, once daily, and with KA (35 mg/kg, ip) as a single dose on day 14. After the treatment, a histological analysis was performed and the number of atrophic neuronal cells in CA3 hippocampal region was quantified. Results Pretreatment with SP does not protect against seizures induced by KA. However, mortality in the SP 200 and the SP 800 groups was of 20%, while for the KA group, it was of 60%. A single KA ip administration produced a considerable neuronal damage, whereas both doses of SP sub-chronic treatment reduced the number of atrophic neurons in CA3 hippocampal region with respect to the KA group. Discussion The SP neurobehaviour improvement after KA systemic administration correlates with the capacity of SP to reduce KA-neuronal death in CA3 hippocampal cells. This neuroprotection may be related to the antioxidant properties of SP. Conclusion SP reduces KA-neuronal death in CA3 hippocampal cells.

  8. Team Size and Stretching-Exercise Effects on Simulated Chest Compression Performance and Exertion

    Directory of Open Access Journals (Sweden)

    Jessica C. Schoen

    2017-09-01

    Full Text Available Introduction: Investigators conducted a prospective experimental study to evaluate the effect of team size and recovery exercises on individual providers’ compression quality and exertion. Investigators hypothesized that 1 larger teams would perform higher quality compressions with less exertion per provider when compared to smaller teams; and 2 brief stretching and breathing exercises during rest periods would sustain compressor performance and mitigate fatigue. Methods: In Phase I, a volunteer cohort of pre-clinical medical students performed four minutes of continuous compressions on a Resusci-Anne manikin to gauge the spectrum of compressor performance in the subject population. Compression rate, depth, and chest recoil were measured. In Phase II, the highest-performing Phase I subjects were placed into 2-, 3-, and/or 4-compressor teams; 2-compressor teams were assigned either to control group (no recovery exercises or intervention group (recovery exercises during rest. All Phase II teams participated in 20-minute simulations with compressor rotation every two minutes. Investigators recorded compression quality and real-time heart rate data, and calculated caloric expenditure from contact heart rate monitor measurements using validated physiologic formulas. Results: Phase I subjects delivered compressions that were 24.9% (IQR1–3: [0.5%–74.1%] correct with a median rate of 112.0 (IQR1–3: [103.5–124.9] compressions per minute and depth of 47.2 (IQR1–3: [35.7–55.2] mm. In their first rotations, all Phase II subjects delivered compressions of similar quality and correctness (p=0.09. Bivariate analyses of 2-, 3-, and 4-compressor teams’ subject compression characteristics by subsequent rotation did not identify significant differences within or across teams. On multivariate analyses, only subjects in 2-compressor teams exhibited significantly lower compression rates (control subjects; p<0.01, diminished chest release (intervention

  9. Neuroprotective effect of G14-humanin on global cerebral ischemia/reperfusion by activation of SOCS3 - STAT3 - MCL-1 signal transduction pathway in rats.

    Science.gov (United States)

    Gao, Guangsheng; Fan, Huaihai; Zhang, Xiaoying; Zhang, Fusen; Wu, Haiyan; Qi, Feng; Zhao, Lei; Li, Yun

    2017-10-01

    Humanin (HN) has been identified to suppress neuron death. Gly 14 -HN (HNG), as a variant of HN, can decrease infarct volume after ischemia/reperfusion (I/R) injury. This study aimed to investigate the neuroprotective mechanism of HNG on global cerebral I/R (GI) in rats. Rats were randomly divided into 13 groups: Sham group, GI groups and HNG groups. Both GI group and HNG groups included six time points (1, 3, 6, 12, 24, and 72 h). At 24 h after reperfusion, Nissl staining was used to observe positive neurons, and p-STAT3, MCL-1, SOCS3, Bax and Caspase-3 in different groups were detected by immunohistochemistry. qRT-PCR and western blot were used to evaluate the expression of STAT3, p-STAT3, MCL-1, and SOCS3. The immunohistochemistry also showed a significant increase in Bax (0.29 ± 0.007 vs. 0.22 ± 0.007, P < 0.01) and Caspase-3 (0.24 ± 0.02 vs. 0.18 ± 0.006, P < 0.01) in GI group compared with Sham group, while Bax (0.26 ± 0.01 vs. 0.29 ± 0.008, P < 0.01) and Caspase-3 (0.20 ± 0.008 vs. 0.24 ± 0.02, P < 0.01) were significantly decreased by HNG-treatment compared with GI group. Along with immunohistochemistry, western blot and qRT-PCR indicated that the protein and mRNA levels of STAT3, MCL-1, and SOCS3 were up-regulated after administration of HNG at six time points after global cerebral I/R in rat. HNG might exert neuroprotective effects through alleviating apoptosis and activating of SOCS3 - STAT3 - MCL-1 signal transduction pathway. Highlights (1) Cerebral ischemia led to neuronal loss in hippocampal CA1 region of rats. (2) HNG had neuroprotective effects on ischemia/reperfusion rats. (3) The protective effect of HNG might be related to the SOCS3 - STAT3 - MCL-1 pathway.

  10. Neuroprotective and Cognition-Enhancing Effects of Compound K Isolated from Red Ginseng.

    Science.gov (United States)

    Seo, Ji Yeon; Ju, Sung Hee; Oh, Jisun; Lee, Seung Kwon; Kim, Jong-Sang

    2016-04-13

    The present study was aimed at elucidating the effect of compound K derived from red ginseng on memory function in mouse model and glutamate-induced cytotoxicity in mouse hippocampal HT22 cells. Compound K induced antioxidant enzymes in nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-mediated manner, and effectively attenuated cytotoxicity and mitochondrial damage induced by glutamate in HT22 cells. However, the cytoprotective effect by compound K was abolished by heme oxygenase-1 inhibitor, tin protophorphyrin IX, suggesting that neuroprotective effect of compound K was caused by its Nrf2-mediated induction of antioxidant enzymes. Further, memory deficit induced by scopolamine was restored by compound K, which did not inhibit acetylcholine esterase, in C57BL/6 mice but not in Nrf2 knockout mice as assessed by passive avoidance test, Y-maze and water maze tests, suggesting that scopolamine-induced memory impairment was overcome by the induction of Nrf2-mediated antioxidant enzymes by the compound K. Overall, our data indicate that compound K could be useful in prevention and treatment of reactive oxygen species-induced neurological disorders such as Alzheimer's disease.

  11. Neuroprotective effects of yoga practice: age-, experience-, and frequency-dependent plasticity

    Directory of Open Access Journals (Sweden)

    Chantal eVillemure

    2015-05-01

    Full Text Available Yoga combines postures, breathing, and meditation. Despite reported health benefits, yoga’s effects on the brain has received little study. We used magnetic resonance imaging to compare age-related gray matter (GM decline in yogis and controls. We also examined the effect of increasing yoga experience and weekly practice on GM volume and assessed which aspects of weekly practice contributed most to brain size. Controls displayed the well documented age-related global brain GM decline while yogis did not, suggesting that yoga contributes to protect the brain against age-related decline. Years of yoga experience correlated mostly with GM volume differences in the left hemisphere (insula, frontal operculum and orbitofrontal cortex suggesting that yoga tunes the brain towards a parasympatically-driven mode and positive states. The number of hours of weekly practice correlated with GM volume in the primary somatosensory cortex/superior parietal lobule (S1/SPL, precuneus/posterior cingulate cortex (PCC, hippocampus, and primary visual cortex (V1. Commonality analyses indicated that the combination of postures and meditation contributed the most to the size of the hippocampus, precuneus/PCC, and S1/SPL while the combination of meditation and breathing exercises contributed the most to V1 volume. Yoga’s potential neuroprotective effects may provide a neural basis for some of its beneficial effects.

  12. NMDA antagonists exert distinct effects in experimental organophosphate or carbamate poisoning in mice

    International Nuclear Information System (INIS)

    Dekundy, Andrzej; Kaminski, Rafal M.; Zielinska, Elzbieta; Turski, Waldemar A.

    2007-01-01

    Organophosphate (OP) and carbamate acetylcholinesterase (AChE) inhibitors produce seizures and lethality in mammals. Anticonvulsant and neuroprotective properties of N-methyl-D-aspartate (NMDA) antagonists encourage the investigation of their effects in AChE inhibitor-induced poisonings. In the present study, the effects of dizocilpine (MK-801, 1 mg/kg) or 3-((RS)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP, 10 mg/kg), alone or combined with muscarinic antagonist atropine (1.8 mg/kg), on convulsant and lethal properties of an OP pesticide dichlorvos or a carbamate drug physostigmine, were studied in mice. Both dichlorvos and physostigmine induced dose-dependent seizure activity and lethality. Atropine did not prevent the occurrence of convulsions but decreased the lethal effects of both dichlorvos and physostigmine. MK-801 or CPP blocked or attenuated, respectively, dichlorvos-induced convulsions. Contrariwise, NMDA antagonists had no effect in physostigmine-induced seizures or lethality produced by dichlorvos or physostigmine. Concurrent pretreatment with atropine and either MK-801 or CPP blocked or alleviated seizures produced by dichlorvos, but not by physostigmine. Both MK-801 and CPP co-administered with atropine enhanced its antilethal effects in both dichlorvos and physostigmine poisoning. In both saline- and AChE inhibitor-treated mice, no interaction of the investigated antidotes with brain cholinesterase was found. The data indicate that both muscarinic ACh and NMDA receptor-mediated mechanisms contribute to the acute toxicity of AChE inhibitors, and NMDA receptors seem critical to OP-induced seizures

  13. [Effect of dynamic hyperinflation on exertional dyspnea, exercise performance and quality of life in COPD].

    Science.gov (United States)

    Ozgur, Eylem Sercan; Atis, Sibel; Kanik, Arzu

    2008-01-01

    There is increasing evidence that dynamic hyperinflation (DH) have negative effects on exercise performance and quality of life in chronic obstructive pulmonary disease (COPD) patients. The aim of this study was to investigate effect of dynamic hyperinflation on exertional dyspnea, exercise performance and quality of life in patients with COPD. 72 clinically stable patients with moderate to severe COPD and 30 healthy age-matched control subjects were included in this study. Pulmonary function tests including lung volumes and maximal respiratory muscle forces, arterial blood gas analyses, evaluation of exertional dyspnea with the Borg scale, and The Saint George Respiratory Questionnaire (SGRQ, Turkish version) were performed at rest and after a 6-min walk test. We measured the change in inspiratory capacity (AlphaIC) after exercise to reflect DH. 80% of patients with COPD significantly decreased IC after exercise (DH). AlphaIC were -0.27 +/- 0.26 L in COPD and 0.8 +/- 0.17 L in controls (p= 0.001). A stepwise multiple regression analysis showed that to be a patient with COPD, Basal Dyspnea Index (BDI) and AlphaIC were the best predictors of 6 MWD (r(2)= 0.53, p< 0.001). FEV1 added an additinal 9% to the variance in 6 MWD. Exertional dyspnea (AlphaBorg) correlated with AlphaIC (r= -0.44, p= 0.0001) and BDI (r= 0.34, p= 0.02). AlphaIC significantly correlated with symptom (r= -0.36, p= 0.008), activity (r= -0.31, p= 0.03) and total scores (r= -0.30, p= 0.04) of SGRQ. Dynamic hyperinflation can often occur during exersice in patients with COPD. Extent of dynamic hyperinflation could able to explain exercise capacity limitation, exercise dyspnea, and poor quality of life in patients with COPD.

  14. Histamine exerts multiple effects on expression of genes associated with epidermal barrier function.

    Science.gov (United States)

    Gutowska-Owsiak, D; Salimi, M; Selvakumar, T A; Wang, X; Taylor, S; Ogg, G S

    2014-01-01

    The role of epidermal barrier genes in the pathogenesis of atopic skin inflammation has recently been highlighted. Cytokines that are abundant in the skin during inflammation have been shown to exert various effects on the expression of barrier genes, although the role of histamine in this area of skin biology is not yet fully understood. To assess the effect of stimulation with histamine on keratinocytes by analysis of the pathways involved in epidermal barrier integrity. We performed a gene expression analysis of histamine-stimulated keratinocytes. Functional changes were tested using the dye penetration assay. Differential changes in filaggrin and the filaggrin-processing enzyme bleomycin hydrolase (BLMH) were validated at the protein level, and expression was also assessed in filaggrin knock-down keratinocytes. Histamine altered expression of multiple barrier genes. Expression of filaggrin was downregulated, as was that of other markers, thus suggesting the presence of delayed/aberrant keratinocyte differentiation. Expression of genes involved in cellular adhesiveness and genes of protease expression was dysregulated, but expression of protease inhibitors was increased. BLMH was upregulated in keratinocytes subjected to histamine and filaggrin knockdown. Histamine exerts a dual effect on epidermal barrier genes; it suppresses keratinocyte differentiation and dysregulates genes of cellular adhesiveness, although it induces genes contributing to stratum corneum function. Upregulation of BLMH and protease inhibitors could support maintenance of the permeability barrier by enhanced generation of moisturizing compounds and suppressed desquamation. In contrast, in the case of stratum corneum damage, histamine could enhance transcutaneous sensitization.

  15. Neuroprotective Properties of Endocannabinoids N-Arachidonoyl Dopamine and N-Docosahexaenoyl Dopamine Examined in Neuronal Precursors Derived from Human Pluripotent Stem Cells.

    Science.gov (United States)

    Novosadova, E V; Arsenyeva, E L; Manuilova, E S; Khaspekov, L G; Bobrov, M Yu; Bezuglov, V V; Illarioshkin, S N; Grivennikov, I A

    2017-11-01

    Neuroprotective properties of endocannabinoids N-arachidonoyl dopamine (NADA) and N-docosahexaenoyl dopamine (DHDA) were examined in neuronal precursor cells differentiated from human induced pluripotent stem cells and subjected to oxidative stress. Both compounds exerted neuroprotective activity, which was enhanced by elevating the concentration of the endocannabinoids within the 0.1-10 µM range. However, both agents at 10 µM concentration showed a marked toxic effect resulting in death of ~30% of the cells. Finally, antagonists of cannabinoid receptors as well as the receptor of the TRPV1 endovanilloid system did not hamper the neuroprotective effects of these endocannabinoids.

  16. Neuroprotective effects of 20(S)-protopanaxatriol (PPT) on scopolamine-induced cognitive deficits in mice.

    Science.gov (United States)

    Lu, Cong; Lv, Jingwei; Dong, Liming; Jiang, Ning; Wang, Yan; Wang, Qiong; Li, Yinghui; Chen, Shanguang; Fan, Bei; Wang, Fengzhong; Liu, Xinmin

    2018-02-22

    20(S)-protopanaxatriol (PPT), one of the ginsenosides from Panax ginseng, has been reported to have neuroprotective effects and to improve memory. The present study was designed to investigate the protective effect of PPT on scopolamine-induced cognitive deficits in mice. Male Institute of Cancer Research mice were pretreated with 2 different doses of PPT (20 and 40 μmol/kg) for 27 days by intraperitoneal injection, and scopolamine (0.75 mg/kg) was injected intraperitoneally for 9 days to induce memory impairment. Thirty minutes after the last pretreatment, the locomotor activity was firstly examined to evaluate the motor function of mice. Then, memory-related behaviors were evaluated, and the related mechanism was further researched. It was founded that PPT treatment significantly reversed scopolamine-induced cognitive impairment in the object location recognition experiment, the Morris water maze test, and the passive avoidance task, showing memory-improving effects. PPT also significantly improved cholinergic system reactivity and suppressed oxidative stress, indicated by inhibition of acetylcholinesterase activity, elevation of acetylcholine levels, increasing superoxide dismutase activity and lowering levels of malondialdehyde in the hippocampus. In addition, the expression levels of Egr-1, c-Jun, and cAMP responsive element binding in the hippocampus were significantly elevated by PPT administration. These results suggest that PPT may be a potential drug candidate for the treatment of cognitive deficit in Alzheimer's disease. Copyright © 2018 John Wiley & Sons, Ltd.

  17. Neuro-protective effect of rutin against Cisplatin-induced neurotoxic rat model.

    Science.gov (United States)

    Almutairi, Mashal M; Alanazi, Wael A; Alshammari, Musaad A; Alotaibi, Moureq Rashed; Alhoshani, Ali R; Al-Rejaie, Salim Salah; Hafez, Mohamed M; Al-Shabanah, Othman A

    2017-09-29

    Cisplatin is widely used chemotherapeutic agent for cancer treatment with limited uses due to its neurotoxic side effect. The aim of this study was to determine the potential preventive effects of rutin on the brain of cisplatin- neurotoxic rat model. Forty rats were divided into four groups. Group-1 (control group) was intra-peritoneal (IP) injected with 2.5 ml/kg saline. Group-2 (rutin group) was orally administrated 30 mg/kg rutin dissolved in water for 14 days. Group-3 (cisplatin group) was IP received 5 mg/kg cisplatin single dose. Group-4 (rutin and cisplatin group) was orally administrated 30 mg/kg rutin dissolved in water for 14 days with a single dose of 5 mg/kg cisplatin IP on day ten. Brain tissues from frontal cortex was used to extract RNA, the gene expression levels of paraoxonase-1 (PON-1), PON-2, PON-3, peroxisome proliferator-activated receptor delta (PPAR-δ), and glutathione peroxidase (GPx) was investigated by Real-time PCR. Cisplatin significantly decreased the expression levels of PON-1, PON-3, PPAR-δ and GPX whereas significantly increased PON-2 expression levels. Co-administration of Rutin prevented the cisplatin-induced toxicity by restoring the alteration in the studied genes to normal values as in the control group. This study showed that Rutin has neuroprotective effect and reduces cisplatin- neurotoxicity with possible mechanism via the antioxidant pathway.

  18. Neuroprotective Effects of Centella asiatica against Intracerebroventricular Colchicine-Induced Cognitive Impairment and Oxidative Stress

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    Anil Kumar

    2009-01-01

    Full Text Available Oxidative stress appears to be an early event involved in the pathogenesis of Alzheimer's disease. The present study was designed to investigate the neuroprotective effects of Centella asiatica against colchicine-induced memory impairment and oxidative damage in rats. Colchicine (15 μg/5 μL was administered intracerebroventricularly in the lateral ventricle of male wistar rats. Morris water maze and plus-maze performance tests were used to assess memory performance tasks. Various biochemical parameters such as lipid peroxidation, nitrite, reduced glutathione, glutathione-S-transferase, superoxide dismutase, acetylcholinesterase were also assessed. ICV colchicine resulted marked memory impairment and oxidative damage. Chronic treatment with Centella asiatica extract (150 and 300 mg/kg, p.o. for a period of 25 days, beginning 4 days prior to colchicine administration, significantly attenuated colchicine-induced memory impairment and oxidative damage. Besides, Centella asiatica significantly reversed colchicines administered increase in acetylcholinesterase activity. Thus, present study indicates protective effect of Centella asiatica against colchicine-induced cognitive impairment and associated oxidative damage.

  19. Neuroprotective Effects of Centella asiatica against Intracerebroventricular Colchicine-Induced Cognitive Impairment and Oxidative Stress

    Science.gov (United States)

    Kumar, Anil; Dogra, Samrita; Prakash, Atish

    2009-01-01

    Oxidative stress appears to be an early event involved in the pathogenesis of Alzheimer's disease. The present study was designed to investigate the neuroprotective effects of Centella asiatica against colchicine-induced memory impairment and oxidative damage in rats. Colchicine (15 μg/5 μL) was administered intracerebroventricularly in the lateral ventricle of male wistar rats. Morris water maze and plus-maze performance tests were used to assess memory performance tasks. Various biochemical parameters such as lipid peroxidation, nitrite, reduced glutathione, glutathione-S-transferase, superoxide dismutase, acetylcholinesterase were also assessed. ICV colchicine resulted marked memory impairment and oxidative damage. Chronic treatment with Centella asiatica extract (150 and 300 mg/kg, p.o.) for a period of 25 days, beginning 4 days prior to colchicine administration, significantly attenuated colchicine-induced memory impairment and oxidative damage. Besides, Centella asiatica significantly reversed colchicines administered increase in acetylcholinesterase activity. Thus, present study indicates protective effect of Centella asiatica against colchicine-induced cognitive impairment and associated oxidative damage. PMID:20798885

  20. Neuroprotective Effects of Clostridium butyricum against Vascular Dementia in Mice via Metabolic Butyrate

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    Jiaming Liu

    2015-01-01

    Full Text Available Probiotics actively participate in neuropsychiatric disorders. However, the role of gut microbiota in brain disorders and vascular dementia (VaD remains unclear. We used a mouse model of VaD induced by a permanent right unilateral common carotid arteries occlusion (rUCCAO to investigate the neuroprotective effects and possible underlying mechanisms of Clostridium butyricum. Following rUCCAO, C. butyricum was intragastrically administered for 6 successive weeks. Cognitive function was estimated. Morphological examination was performed by electron microscopy and hematoxylin-eosin (H&E staining. The BDNF-PI3K/Akt pathway-related proteins were assessed by western blot and immunohistochemistry. The diversity of gut microbiota and the levels of butyrate in the feces and the brains were determined. The results showed that C. butyricum significantly attenuated the cognitive dysfunction and histopathological changes in VaD mice. C. butyricum not only increased the levels of BDNF and Bcl-2 and decreased level of Bax but also induced Akt phosphorylation (p-Akt and ultimately reduced neuronal apoptosis. Moreover, C. butyricum could regulate the gut microbiota and restore the butyrate content in the feces and the brains. These results suggest that C. butyricum might be effective in the treatment of VaD by regulating the gut-brain axis and that it can be considered a new therapeutic strategy against VaD.

  1. Neuroprotective Effect of Dexmedetomidine on Hyperoxia-Induced Toxicity in the Neonatal Rat Brain

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    Marco Sifringer

    2015-01-01

    Full Text Available Dexmedetomidine is a highly selective agonist of α2-receptors with sedative, anxiolytic, analgesic, and anesthetic properties. Neuroprotective effects of dexmedetomidine have been reported in various brain injury models. In the present study, we investigated the effects of dexmedetomidine on neurodegeneration, oxidative stress markers, and inflammation following the induction of hyperoxia in neonatal rats. Six-day-old Wistar rats received different concentrations of dexmedetomidine (1, 5, or 10 µg/kg bodyweight and were exposed to 80% oxygen for 24 h. Sex-matched littermates kept in room air and injected with normal saline or dexmedetomidine served as controls. Dexmedetomidine pretreatment significantly reduced hyperoxia-induced neurodegeneration in different brain regions of the neonatal rat. In addition, dexmedetomidine restored the reduced/oxidized glutathione ratio and attenuated the levels of malondialdehyde, a marker of lipid peroxidation, after exposure to high oxygen concentration. Moreover, administration of dexmedetomidine induced downregulation of IL-1β on mRNA and protein level in the developing rat brain. Dexmedetomidine provides protections against toxic oxygen induced neonatal brain injury which is likely associated with oxidative stress signaling and inflammatory cytokines. Our results suggest that dexmedetomidine may have a therapeutic potential since oxygen administration to neonates is sometimes inevitable.

  2. Neuroprotective effects of sulforaphane on cholinergic neurons in mice with Alzheimer's disease-like lesions.

    Science.gov (United States)

    Zhang, Rui; Zhang, Jingzhu; Fang, Lingduo; Li, Xi; Zhao, Yue; Shi, Wanying; An, Li

    2014-08-18

    Alzheimer's disease (AD) is a common neurodegenerative disease in elderly individuals, and effective therapies are unavailable. This study was designed to investigate the neuroprotective effects of sulforaphane (an activator of NF-E2-related factor 2) on mice with AD-like lesions induced by combined administration of aluminum and D-galactose. Step-down-type passive avoidance tests showed sulforaphane ameliorated cognitive impairment in AD-like mice. Immunohistochemistry results indicated sulforaphane attenuated cholinergic neuron loss in the medial septal and hippocampal CA1 regions in AD-like mice. However, spectrophotometry revealed no significant difference in acetylcholine level or the activity of choline acetyltransferase or acetylcholinesterase in the cerebral cortex among groups of control and AD-like mice with and without sulforaphane treatment. Sulforaphane significantly increased the numbers of 5-bromo-2'-deoxyuridine-positive neurons in the subventricular and subgranular zones in AD-like mice which were significantly augmented compared with controls. Atomic absorption spectrometry revealed significantly lower aluminum levels in the brains of sulforaphane-treated AD-like mice than in those that did not receive sulforaphane treatment. In conclusion, sulforaphane ameliorates neurobehavioral deficits by reducing cholinergic neuron loss in the brains of AD-like mice, and the mechanism may be associated with neurogenesis and aluminum load reduction. These findings suggest that phytochemical sulforaphane has potential application in AD therapeutics.

  3. Exercise preconditioning exhibits neuroprotective effects on hippocampal CA1 neuronal damage after cerebral ischemia

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    Nabi Shamsaei

    2015-01-01

    Full Text Available Recent evidence has suggested the neuroprotective effects of physical exercise on cerebral ischemic injury. However, the role of physical exercise in cerebral ischemia-induced hippocampal damage remains controversial. The aim of the present study was to evaluate the effects of pre-ischemia treadmill training on hippocampal CA1 neuronal damage after cerebral ischemia. Male adult rats were randomly divided into control, ischemia and exercise + ischemia groups. In the exercise + ischemia group, rats were subjected to running on a treadmill in a designated time schedule (5 days per week for 4 weeks. Then rats underwent cerebral ischemia induction through occlusion of common carotids followed by reperfusion. At 4 days after cerebral ischemia, rat learning and memory abilities were evaluated using passive avoidance memory test and rat hippocampal neuronal damage was detected using Nissl and TUNEL staining. Pre-ischemic exercise significantly reduced the number of TUNEL-positive cells and necrotic cell death in the hippocampal CA1 region as compared to the ischemia group. Moreover, pre-ischemic exercise significantly prevented ischemia-induced memory dysfunction. Pre-ischemic exercise mighct prevent memory deficits after cerebral ischemia through rescuing hippocampal CA1 neurons from ischemia-induced degeneration.

  4. Tamoxifen: an FDA approved drug with neuroprotective effects for spinal cord injury recovery

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    Jennifer M Colón

    2016-01-01

    Full Text Available Spinal cord injury (SCI is a condition without a cure, affecting sensory and/or motor functions. The physical trauma to the spinal cord initiates a cascade of molecular and cellular events that generates a non-permissive environment for cell survival and axonal regeneration. Among these complex set of events are damage of the blood-brain barrier, edema formation, inflammation, oxidative stress, demyelination, reactive gliosis and apoptosis. The multiple events activated after SCI require a multi-active drug that could target most of these events and produce a permissive environment for cell survival, regeneration, vascular reorganization and synaptic formation. Tamoxifen, a selective estrogen receptor modulator, is an FDA approved drug with several neuroprotective properties that should be considered for the treatment of this devastating condition. Various investigators using different animal models and injury parameters have demonstrated the beneficial effects of this drug to improve functional locomotor recovery after SCI. Results suggest that the mechanism of action of Tamoxifen administration is to modulate anti-oxidant, anti-inflammatory and anti-gliotic responses. A gap of knowledge exists regarding the sex differences in response to Tamoxifen and the therapeutic window available to administer this treatment. In addition, the effects of Tamoxifen in axonal outgrowth or synapse formation needs to be investigated. This review will address some of the mechanisms activated by Tamoxifen after SCI and the results recently published by investigators in the field.

  5. The new inhibitor of monoamine oxidase, M30, has a neuroprotective effect against dexamethasone-induced brain cell apoptosis

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    Shakevia Johnson

    2010-11-01

    Full Text Available Stress detrimentally affects the brain and body and can lead to or be accompanied by depression. Although stress and depression may contribute to each other, the exact molecular mechanism underlying the effects is unclear. However, there is a correlation between stress and an increase in glucocorticoid secretion which causes a subsequent increase in monoamine oxidase (MAO activity during stress. Consequently, MAO inhibitors have been used as traditional antidepressant drugs. Cellular treatment with the synthetic glucocorticoid, dexamethasone (a cellular stressor, has been reported to markedly increase both MAO A and MAO B catalytic activities, as well as apoptosis. This study compares the neuroprotective abilities of M30 (a new generation inhibitor of both MAO A and MAO B with rasagiline (Azilect®, another new MAO B inhibitor and selegiline (Deprenyl®, a traditional MAO B inhibitor in the prevention of dexamethasone-induced brain cell death and MAO activity in human neuroblastoma cells, SH-SY5Y. M30 demonstrated the highest inhibitory effect on MAO A; however, M30 showed the lowest inhibitory effect on MAO B enzymatic activity in comparison to rasagiline and selegiline. Although, M30 exhibited the greatest neuroprotective effect by decreasing cell death rates and apoptotic DNA damage compared to rasagiline and selegiline, these neuroprotective effects of M30 were, overall, similar to rasagiline. Summarily, M30 has a generally greater impact on neuroprotection than the MAO B inhibitors, selegiline and rasagiline. Our results suggest that M30 may have great potential in alleviating disorders involving increases in both MAO A and MAO B, such as stress-induced disorders.

  6. Indirect application of near infrared light induces neuro-protection in a mouse model of parkinsonism - an abscopal neuro-protective effective evaluation

    International Nuclear Information System (INIS)

    Johnstone, D.M.; Spana, S.; Purushothuman, S.; Stone, J.; Mitrofanis, J.; Johnstone, D.M.; Spana, S.; Purushothuman, S.; Stone, J.; El Massri, N.; Mitrofanis, J.; Moro, C.; Torres, N.; Chabrol, C.; De Jaeger, X.; Reinhart, F.; Benabid, A.L.; Wang, X.S.

    2014-01-01

    We have previously shown near infrared light (NIr), directed transcranially, mitigates the loss of dopaminergic cells in MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-treated mice, a model of parkinsonism. These findings complement others suggesting NIr treatment protects against damage from various insults. However one puzzling feature of NIr treatment is that unilateral exposure can lead to a bilateral healing response, suggesting NIr may have 'indirect' protective effects. We investigated whether remote NIr treatment is neuro-protective by administering different MPTP doses (50-, 75-, 100-mg/kg) to mice and treating with 670-nm light directed specifically at either the head or body. Our results show that, despite no direct irradiation of the damaged tissue, remote NIr treatment produces a significant rescue of tyrosine hydroxylase-positive cells in the substantia nigra pars compacta at the milder MPTP dose of 50-mg/kg (30% increase vs sham-treated MPTP mice, p≤ 0.05). However this protection did not appear as robust as that achieved by direct irradiation of the head (50% increase vs sham-treated MPTP mice, p ≤0.001). There was no quantifiable protective effect of NIr at higher MPTP doses, irrespective of the delivery mode. Astrocyte and microglia cell numbers in substantia nigra pars compacta were not influenced by either mode of NIr treatment. In summary, the findings suggest that treatment of a remote tissue with NIr is sufficient to induce protection of the brain, reminiscent of the 'abscopal effect' sometimes observed in radiation treatment of metastatic cancer. This discovery has implications for the clinical translation of light-based therapies, providing an improved mode of delivery over trans-cranial irradiation. (authors)

  7. Neuroprotective effects of Cassia tora against paraquat-induced neurodegeneration: relevance for Parkinson's disease.

    Science.gov (United States)

    Ravi, Sunil K; Narasingappa, Ramesh B; Joshi, Chandrashekar G; Girish, Talakatta K; Vincent, Bruno

    2017-07-16

    The aim of the present study was to determine whether Cassia tora extracts could reverse the oxidative stress-induced neurodegeneration in a Parkinson's disease in vitro model. The leaves were treated with ethyl acetate (CtEA) or methanol (CtME). The extracts were first analysed by HPLC for their phenolic content and then tested for their neuroprotective effects in human SK-N-SH neuroblastoma cells. Cells were pre-treated with various concentrations of extracts followed by incubation with paraquat (14 μM). Firstly, pre-treatment of SK-N-SH cells with 100 μg/mL of CtEA or CtME significantly reduced the paraquat-induced production of reactive oxygen species. Furthermore, both CtEA and CtME reduced the paraquat-induced apoptosis. Moreover, there was a significant reduction of paraquat-induced DNA damage in SK-N-SH cells pre-treated with CtEA or CtME. Finally, both extracts significantly inhibited paraquat-dependent lipid peroxidation. Altogether, these in vitro data establish C. tora as a possible anti-Parkinson natural remedy.

  8. The Neuroprotective Effect of Glycyrrhizic Acid on an Experimental Model of Focal Cerebral Ischemia in Rats.

    Science.gov (United States)

    Akman, Tarık; Guven, Mustafa; Aras, Adem Bozkurt; Ozkan, Adile; Sen, Halil Murat; Okuyucu, Ali; Kalkan, Yildiray; Sehitoglu, Ibrahim; Silan, Coskun; Cosar, Murat

    2015-08-01

    Cerebral ischemia is still one of the most important topics in neurosciences. Our study aimed to investigate the neuroprotective and anti-oxidant effects of glycyrrhizic acid on focal cerebral ischemia in rats. Twenty-four rats were divided equally into three groups. A middle cerebral artery occlusion model was performed in this study where sham and glycyrrhizic acid were administered intraperitoneally following middle cerebral artery occlusion. Group I was evaluated as control. Malondialdehyde (MDA), superoxide dismutase (SOD), and nuclear respiratory factor-1 (NRF1) levels were analyzed biochemically on the right cerebral hemisphere, while ischemic histopathological studies were completed to investigate the anti-oxidant status. Biochemical results showed that SOD and NRF1 levels were significantly increased in the glycyrrhizic acid group compared with the sham group while MDA levels were significantly decreased. On histopathological examination, cerebral edema, vacuolization, degeneration, and destruction of neurons were decreased in the glycyrrhizic acid group compared with the sham group. Cerebral ischemia was attenuated by glycyrrhizic acid administration. These observations indicate that glycyrrhizic acid may have potential as a therapeutic agent in cerebral ischemia by preventing oxidative stress.

  9. Neuroprotective effect of undecylenic acid extracted from Ricinus communis L. through inhibition of μ-calpain.

    Science.gov (United States)

    Lee, Eunyoung; Eom, Ji-Eun; Kim, Hye-Lin; Kang, Da-Hye; Jun, Kyu-Yeon; Jung, Duk Sang; Kwon, Youngjoo

    2012-05-12

    The key neuropathological features of Alzheimer's disease are abnormal deposition of Aβ plaques and insoluble Aβ peptides in extracellular brain and intracellular neurofibril tangles induced by abnormal tau hyperphosphorylation. μ-Calpain is one of the factors that bridge these Aβ- and hyperphosphorylated tau-mediated pathological pathways. Undecylenic acid (UDA), a naturally occurring unsaturated fatty acid, was discovered as a μ-calpain inhibitor by screening a chemical library using a substrate specific μ-calpain assay method. UDA inhibited Aβ oligomerization and Aβ fibrillation and reversed Aβ-induced neuronal cell death. In addition, UDA scavenged ROS and reversed the levels of proapoptotic proteins induced by ROS in SH-SY5Y cells. UDA inhibited μ-calpain activity with better potency than the known peptide-like μ-calpain inhibitor, MDL28170, in SH-SY5Y and HEK293T cells transfected with the catalytic subunit of μ-calpain. These results suggest that UDA is a novel non-peptide-like μ-calpain inhibitor with good cell permeability and potent neuroprotective effect. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Neuroprotective effects of riluzole: an electrophysiological and histological analysis in an in vitro model of ischemia.

    Science.gov (United States)

    Siniscalchi, A; Zona, C; Sancesario, G; D'Angelo, E; Zeng, Y C; Mercuri, N B; Bernardi, G

    1999-06-01

    The protective effects of riluzole against the neuronal damage caused by O2 and glucose deprivation (ischemia) was investigated in rat cortical slices by recording electrophysiologically the cortico-cortical field potential and by evaluating histologically the severity of neuronal death. Five minutes of ischemia determined an irreversible depression of the amplitude of the field potential. In addition, this insult caused a clear enhancement of the number of death cells that were specifically colored with trypan blue (a vital colorant which stains altered cells). We found that riluzole, which by itself depressed the synaptic transmission, neuroprotected when perfused 15-20 min before and during ischemia. In fact, due to the treatment with riluzole, the ischemia-induced irreversible depression of the field potential recovered and less cells were stained with trypan blue. These findings demonstrate that riluzole prevents neuronal death in an in vitro model of ischemia and suggest a therapeutic use of this drug in order to reduce the pathophysiological outcomes of stroke.

  11. Anti-Inflammatory and Neuroprotective Effects of Constituents Isolated from Rhodiola rosea

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    Yeonju Lee

    2013-01-01

    Full Text Available To determine the biological activity of Rhodiola rosea, the protein expression of iNOS and proinflammatory cytokines was measured after the activation of murine microglial BV2 cells by LPS under the exposure of constituents of Rhodiola rosea: crude extract, rosin, rosarin, and salidroside (each 1–50 μg/mL. The LPS-induced expression of iNOS and cytokines in BV2 cells was suppressed by the constituents of Rhodiola rosea in a concentration-dependent manner. Also the expression of the proinflammatory factors iNOS, IL-1β, and TNF-α in the kidney and prefrontal cortex of brain in mice was suppressed by the oral administration of Rhodiola rosea crude extract (500 mg/kg. To determine the neuroprotective effect of constituents of Rhodiola rosea, neuronal cells were activated by L-glutamate, and neurotoxicity was analyzed. The L-glutamate-induced neurotoxicity was suppressed by the treatment with rosin but not by rosarin. The level of phosphorylated MAPK, pJNK, and pp38 was increased by L-glutamate treatment but decreased by the treatment with rosin and salidroside. These results indicate that Rhodiola rosea may have therapeutic potential for the treatment of inflammation and neurodegenerative disease.

  12. Fluoxetine exerts age-dependent effects on behavior and amygdala neuroplasticity in the rat.

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    Judith R Homberg

    Full Text Available The selective serotonin reuptake inhibitor (SSRI Prozac® (fluoxetine is the only registered antidepressant to treat depression in children and adolescents. Yet, while the safety of SSRIs has been well established in adults, serotonin exerts neurotrophic actions in the developing brain and thereby may have harmful effects in adolescents. Here we treated adolescent and adult rats chronically with fluoxetine (12 mg/kg at postnatal day (PND 25 to 46 and from PND 67 to 88, respectively, and tested the animals 7-14 days after the last injection when (norfluoxetine in blood plasma had been washed out, as determined by HPLC. Plasma (norfluoxetine levels were also measured 5 hrs after the last fluoxetine injection, and matched clinical levels. Adolescent rats displayed increased behavioral despair in the forced swim test, which was not seen in adult fluoxetine treated rats. In addition, beneficial effects of fluoxetine on wakefulness as measured by electroencephalography in adults was not seen in adolescent rats, and age-dependent effects on the acoustic startle response and prepulse inhibition were observed. On the other hand, adolescent rats showed resilience to the anorexic effects of fluoxetine. Exploratory behavior in the open field test was not affected by fluoxetine treatment, but anxiety levels in the elevated plus maze test were increased in both adolescent and adult fluoxetine treated rats. Finally, in the amygdala, but not the dorsal raphe nucleus and medial prefrontal cortex, the number of PSA-NCAM (marker for synaptic remodeling immunoreactive neurons was increased in adolescent rats, and decreased in adult rats, as a consequence of chronic fluoxetine treatment. No fluoxetine-induced changes in 5-HT(1A receptor immunoreactivity were observed. In conclusion, we show that fluoxetine exerts both harmful and beneficial age-dependent effects on depressive behavior, body weight and wakefulness, which may relate, in part, to differential

  13. Epobis is a Nonerythropoietic and Neuroprotective Agonist of the Erythropoietin Receptor with Anti-Inflammatory and Memory Enhancing Effects

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    Oksana Dmytriyeva

    2016-01-01

    Full Text Available The cytokine erythropoietin (EPO stimulates proliferation and differentiation of erythroid progenitor cells. Moreover, EPO has neuroprotective, anti-inflammatory, and antioxidative effects, but the use of EPO as a neuroprotective agent is hampered by its erythropoietic activity. We have recently designed the synthetic, dendrimeric peptide, Epobis, derived from the sequence of human EPO. This peptide binds the EPO receptor and promotes neuritogenesis and neuronal cell survival. Here we demonstrate that Epobis in vitro promotes neuritogenesis in primary motoneurons and has anti-inflammatory effects as demonstrated by its ability to decrease TNF release from activated AMJ2-C8 macrophages and rat primary microglia. When administered systemically Epobis is detectable in both plasma and cerebrospinal fluid, demonstrating that the peptide crosses the blood-brain barrier. Importantly, Epobis is not erythropoietic, but systemic administration of Epobis in rats delays the clinical signs of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis, and the peptide has long-term, but not short-term, effects on working memory, detected as an improved social memory 3 days after administration. These data reveal Epobis to be a nonerythropoietic and neuroprotective EPO receptor agonist with anti-inflammatory and memory enhancing properties.

  14. Green tea supplementation produces better neuroprotective effects than red and black tea in Alzheimer-like rat model.

    Science.gov (United States)

    Schimidt, Helen L; Garcia, Alexandre; Martins, Alexandre; Mello-Carpes, Pamela B; Carpes, Felipe P

    2017-10-01

    Green tea from Camellia sinensis plays a neuroprotective role in different neurodegenerative conditions, such as memory deficits in Alzheimer disease (AD). However, whether other teas from Camellia sinensis present similar neuroprotective effect still is not clear. Here we investigate effects of green, red and black tea supplementation on memory and hippocampus oxidative status in a rat model of Alzheimer-like disease (AD-like). Wistar male rats were supplemented with green, red or black tea during 8weeks before Aβ intra-hippocampal injection (2μL of Aβ-25-35, CA1 region). AD and sham rats were submitted to memory tests. After euthanasia, oxidative status in the bilateral hippocampus was quantified. Green and red teas avoid memory deficits in AD rats, but only green tea also avoids oxidative stress and damage in the hippocampus. Green tea was more effective for neuroprotection than red and black teas from the Camellia sinensis in the AD rat model. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Amplexicaule A exerts anti-tumor effects by inducing apoptosis in human breast cancer

    Science.gov (United States)

    Shu, Guangwen; Wan, Dingrong; He, Feng; Loaec, Morgann; Ding, Yali; Li, Jun; Dovat, Sinisa; Yang, Gaungzhong; Song, Chunhua

    2016-01-01

    Chemotherapy is the main treatment for patients with breast cancer metastases, but natural alternatives have been receiving attention for their potential as novel anti-tumor reagents. Amplexicaule A (APA) is a flavonoid glucoside isolated from rhizomes of Polygonum amplexicaule D. Don var. sinense Forb (PADF). We found that APA has anti-tumor effects in a breast cancer xenograft mouse model and induces apoptosis in breast cancer cell lines. APA increased levels of cleaved caspase-3,-8,-9 and PARP, which resulted from suppression of MCL-1 and BCL-2 expression in the cells. APA also inactivated the Akt/mTOR pathway in breast cancer cells. Thus, APA exerts a strong anti-tumor effect on breast cancer cells, most likely through induction of apoptosis. Our study is the first to identify this novel anti-tumor compound and provides a new strategy for isolation and separation of single compounds from herbs. PMID:26943775

  16. Neuroprotective effects of 2,3,5,4'-tetrahydoxystilbene-2-O-β-D-glucoside from Polygonum multiflorum against glutamate-induced oxidative toxicity in HT22 cells.

    Science.gov (United States)

    Lee, Sun Young; Ahn, Sung Min; Wang, Ziyu; Choi, Young Whan; Shin, Hwa Kyoung; Choi, Byung Tae

    2017-01-04

    Since ancient times, Polygonum multiflorum Thunb. has been used to treat premature grey hair, dizziness, and blurred vision in East Asia. A major bioactive constituent of this medicinal herb, 2,3,5,4'-tetrahydoxystilbene-2-O-β-D-glucoside (THSG), has antioxidant activity and exerts beneficial effects on cognition and memory. The purpose of the current study was to determine if THSG affects hippocampal neuronal cell death and mitochondrial function following exposure to oxidative stress. HT22 hippocampal cells with or without THSG pretreatment were exposed to glutamate, and the effects on cell viability and expression of molecules related to apoptotic cell death were examined using biochemical techniques, flow cytometry, western immunoblotting, and real-time polymerase chain reaction. Pretreatment with THSG significantly attenuated glutamate-induced loss of cell viability and release of lactate dehydrogenase as well as apoptotic cell death. THSG inhibited generation of reactive oxygen species (ROS), expression of heme oxygenase-1, and activation of caspase-3 and calpain-1 proteases, all of which were increased by glutamate. THSG inhibited glutamate-induced disruption of mitochondrial membrane potential (MMP) and voltage-dependent anion channel-1. It also regulated the ratio of Bax to Bcl-2. These results indicate that THSG has a marked neuroprotective effect against glutamate-induced hippocampal damage by decreasing ROS production and stabilizing MMP. These findings suggest the potential of THSG as a new therapeutic agent for the treatment of cognitive disorders. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. Tetrahydroxystilbene Glucoside Produces Neuroprotection against 6-OHDA-Induced Dopamine Neurotoxicity

    Directory of Open Access Journals (Sweden)

    Chun Huang

    2018-01-01

    Full Text Available Parkinson’s disease (PD was one of the most common neurodegenerative diseases with a slow and progressive loss of dopamine (DA neurons in the midbrain substantia nigra (SN. Neuroinflammation was identified to be an important contributor to PD pathogenesis with the hallmark of microglia activation. Tetrahydroxystilbene glucoside (TSG was the main active component extracted from Polygonum multiflorum and held amounts of pharmacological activities including antioxidant, free radical-scavenging, anti-inflammation, and cardioprotective properties. Recent studies demonstrated that TSG exerted neuroprotection from several neurodegenerative disease models. However, the underlying mechanisms were not completely elucidated. In the present study, rat nigral stereotaxic injection of 6-hydroxydopamine- (6-OHDA- elicited DA neuronal injury was performed to investigate TSG-mediated neuroprotection on DA neurons. In addition, primary rat midbrain neuron-glia cocultures were applied to explore the mechanisms underlying TSG-exerted neuroprotection. Results showed that daily intraperitoneal injection of TSG for 14 consecutive days significantly protected DA neurons from 6-OHDA-induced neurotoxicity and suppressed microglia activation. Similar neuroprotection was shown in primary neuron-glia cocultures. In vitro studies further demonstrated that TSG inhibited microglia activation and subsequent release of proinflammatory factors. Moreover, TSG-mediated neuroprotection was closely related with the inactivation of mitogen-activated protein kinase (MAPK signaling pathway. Together, TSG protects DA neurons from 6-OHDA-induced neurotoxicity via the inhibition of microglia-elicited neuroinflammation. These findings suggest that TSG might hold potential therapeutic effects on PD.

  18. Exerting Capacity.

    Science.gov (United States)

    Leger, J Michael; Phillips, Carolyn A

    2017-05-01

    Patient safety has been at the forefront of nursing research since the release of the Institute of Medicine's report estimating the number of preventable adverse events in hospital settings; yet no research to date has incorporated the perspectives of bedside nurses using classical grounded theory (CGT) methodology. This CGT study explored the perceptions of bedside registered nurses regarding patient safety in adult acute care hospitals. Data analysis used three techniques unique to CGT-the constant comparative method, coding, and memoing-to explore the values, realities, and beliefs of bedside nurses about patient safety. The analysis resulted in a substantive theory, Exerting Capacity, which explained how bedside nurses balance the demands of keeping their patients safe. Exerting Capacity has implications for health care organization leaders, nursing leaders, and bedside nurses; it also has indications for future research into the concept of patient safety.

  19. Neuroprotective Effect and Molecular Mechanism of [6]-Gingerol against Scopolamine-Induced Amnesia in C57BL/6 Mice

    Directory of Open Access Journals (Sweden)

    Chang-Yul Kim

    2018-01-01

    Full Text Available We have investigated the neuroprotective and memory enhancing effect of [6]-gingerol (GIN, a pungent ingredient of ginger, using an animal model of amnesia. To determine the neuroprotective effect of GIN on cognitive dysfunction, scopolamine (SCO, 1 mg/kg, i.p. was injected into C57BL/6 mice, and a series of behavioral tests were conducted. SCO-induced behavior changes and memory impairments, such as decreased alteration (% in Y-maze test, increased mean escape latency in water maze test, diminished step-through latency in passive avoidance test, and shortened freezing time in fear condition test, were significantly prevented and restored by the oral administration of GIN (10 or 25 mg/kg/day. To further verify the neuroprotective mechanism of GIN, we have focused on the brain-derived neurotrophic factor (BDNF. The administration of GIN elevated the protein expression of BDNF, which was mediated via the activation of protein kinase B/Akt- and cAMP-response element binding protein (CREB signaling pathway. These results suggest that GIN may have preventive and/or therapeutic potentials in the management of memory deficit and cognitive impairment in mice with amnesia.

  20. The neuroprotective effects of α-iso-cubebene on dopaminergic cell death: involvement of CREB/Nrf2 signaling.

    Science.gov (United States)

    Park, Sun Young; Son, Beung Gu; Park, Young Hoon; Kim, Cheol-Min; Park, Geuntae; Choi, Young-Whan

    2014-09-01

    As a part of ongoing studies to elucidate pharmacologically active components of Schisandra chinensis, we isolated and studied α-iso-cubebene. The neuroprotective mechanisms of α-iso-cubebene in human neuroblastoma SH-SY5Y cells were investigated. α-Iso-cubebene significantly inhibited cytotoxicity and apoptosis due to 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in dopaminergic SH-SY5Y cells. Pretreatment of cells with α-iso-cubebene reduced intracellular accumulation of ROS and calcium in response to 6-OHDA. The neuroprotective effects of α-iso-cubebene were found to result from protecting the mitochondrial membrane potential. Notably, α-iso-cubebene inhibited the release of apoptosis-inducing factor from the mitochondria into the cytosol and nucleus after 6-OHDA treatment. α-Iso-cubebene also induced the activation of PKA/PKB/CREB/Nrf2 and suppressed 6-OHDA-induced neurotoxicity. α-Iso-cubebene was found to induce phosphorylation of PKA and PKB and activate Nrf2 and CREB signaling pathways in a dose-dependent manner. Additionally, α-iso-cubebene stimulated the expression of the antioxidant response genes NQO1 and HO-1. Finally, α-iso-cubebene-mediated neuroprotective effects were found to be reversible after transfection with CREB and Nrf2 small interfering RNAs.

  1. Neuroprotective effects of propofol, thiopental, etomidate, and midazolam in fetal rat brain in ischemia-reperfusion model.

    Science.gov (United States)

    Harman, Ferhat; Hasturk, Askin Esen; Yaman, Mehmet; Arca, Turkan; Kilinc, Kamer; Sargon, Mustafa Fevzi; Kaptanoglu, Erkan

    2012-07-01

    The aim of this study was to investigate the neuroprotective effects of propofol, thiopental, etomidate, and midazolam as anesthetic drugs in fetal rat brain in the ischemia-reperfusion (IR) model. Pregnant rats of day 19 were randomly allocated into eight groups. Fetal brain ischemia was induced by clamping the utero-ovarian artery bilaterally for 30 min and reperfusion was achieved by removing the clamps for 60 min. In the control group, fetal rat brains were obtained immediately after laparotomy. In the sham group, fetal rat brains were obtained 90 min after laparotomy. In the IR group, IR procedure was performed. No treatment was given in the IR group. One milliliter intralipid solution, 40 mg/kg propofol, 3 mg/kg thiopental, 0.1 mg/kg etomidate, and 3 mg/kg midazolam was administered intraperitoneally in the vehicle group, propofol group, thiopental group, etomidate group, and midazolam group, respectively, 20 min before IR procedure. At the end of the reperfusion period, the whole brains of the fetal rats were removed for evaluation of thiobarbituric acid reactive substances and for examination by electron microscopy. According to lipid peroxidation data, all the anesthetic drugs provide neuroprotection; however, ultrastructural findings and mitochondrial scoring confirms that only propofol and midazolam provides a strong neuroprotective effect. Propofol and midazolam may be used to protect fetal brain in case of acute fetal distress and hypoxic injury as a first choice anesthetic drug in cesarean delivery.

  2. Neuroprotective effects of andrographolide in a rat model of permanent cerebral ischaemia

    Science.gov (United States)

    Chan, Su Jing; Wong, WS Fred; Wong, Peter TH; Bian, Jin-Song

    2010-01-01

    BACKGROUND AND PURPOSE Andrographolide is a diterpenoid lactone isolated from a traditional medicinal herb, Andrographis paniculata. It possesses potent anti-inflammatory activity. The present study examined potential therapeutic effects of andrographolide on cerebral ischaemia using a rat model with permanent middle cerebral artery occlusion (pMCAO). EXPERIMENTAL APPROACH The MCA in rats was permanently occluded (by cautery), and 24 h later neurological effects were assessed with behavioural scores. Infarct volume and microglial activation were determined histologically. The p65 form of the transcription factor, nuclear factor-κB (NF-κB), was measured by Western blot, and cytokines by immunoassay of brain extracts. KEY RESULTS Andrographolide, given i.p. 1 h after pMCAO, reduced infarct volume with a maximum reduction of approximately 50% obtained at 0.1 mg·kg−1. Neurological deficits were also reduced by andrographolide, reflecting a correlation between infarct volume and neurological deficits. pMCAO was found to induce activation of microglia and elevate tumour necrosis factor (TNF)-α, interleukin (IL)-1β and prostaglandin (PG)E2 in the ischaemic brain areas. Andrographolide (0.1 mg·kg−1) significantly attenuated or abolished these effects. In addition, andrographolide suppressed the translocation of p65 from cytosol to nucleus, indicating reduced NF-κB activation. CONCLUSIONS AND IMPLICATIONS Andrographolide exhibited neuroprotective effects, with accompanying suppression of NF-κB and microglial activation, and reduction in the production of cytokines including TNF-α and IL-1β, and pro-inflammatory factors such as PGE2. Our findings suggest that andrographolide may have therapeutic value in the treatment of stroke. PMID:20880404

  3. Neuroprotective Effects of Germinated Brown Rice in Rotenone-Induced Parkinson's-Like Disease Rats.

    Science.gov (United States)

    Chompoopong, Supin; Jarungjitaree, Sunit; Punbanlaem, Tideeporn; Rungruang, Thanaporn; Chongthammakun, Sukumal; Kettawan, Aikkarach; Taechowisan, Thongchai

    2016-09-01

    The effects of germinated brown rice (GBR) on the motor deficits and the dopaminergic (DA) cell death were investigated in Parkinson's-like disease (PD) rats. Reactive oxidative species generated by chronic subcutaneous injection of rotenone (RT) lead to neuronal apoptosis particularly in the nigrostriatal DA system and produce many features of PD, bradykinesis, postural instability and rigidity. In this study, 4-phenylbutyric acid (4-PBA), previously reported to inhibit RT-induced DA cell death, was used as the positive control. Results show that pretreatment with GBR as well as 4-PBA significantly enhanced the motor activity after RT injection, and GBR affected significantly in open field test, only in the ambulation but not the mobility duration, and ameliorated the time to orient down (t-turn) and total time to descend the pole (t-total) in pole test as compared to RT group, but significantly lowered both t-turn and t-total only in 4-PBA group. The percentage of apoptotic cells in brain measured by flow cytometry and the inflammatory effect measured by ELISA of TNF-α showed significant increase in RT group as compared to the control (CT) group at P < 0.05. Apoptotic cells in RT group (85.98 %) showed a significant (P < 0.05) increase versus CT group (17.50 %), and this effect was attenuated in GBR+RT group by decreasing apoptotic cells (79.32 %), whereas, increased viable cells (17.94 %) versus RT group (10.79 %). GBR in GBR + RT group could decrease TNF-α both in the serum and in brain. In summary, GBR showed a neuroprotective effect in RT-induced PD rats, and it may be useful as a value-added functional food to prevent neurodegenerative disease or PD.

  4. The effect of wearing jeans on maximum static lifting strength for men and women at various exertion heights.

    Science.gov (United States)

    Chen, Yi-Lang; Li, Chia-Ying; Wang, Chao-Hsuan; Hu, Shiun

    2018-03-13

    This study collected maximum static lifting strength (MSLS) data from 13 males and 13 females at an exertion height of 10-100 cm above the floor (in 10-cm increments) in wearing athletic shorts and wearing jeans conditions. Knee angles were also examined when participants performed the MSLS tasks. Results showed that gender, pant type and exertion height significantly affected participants' MSLS and corresponding knee angle. The effect of wearing jeans primarily occurred at 10-40 cm; meanwhile, male participants tended to stoop while exerting force. This substantially decreased their MSLS (55 N). For female participants in this exertion height range, no significant difference was found in knee angles; accordingly, wearing jeans only slightly affected their MSLS. In summary, wearing jeans had a noticeable effect on the MSLS of male participants, who should be particularly careful when performing lifting tasks at a height of less than 50 cm above the floor.

  5. Neuroprotective Effects of Pomegranate Peel Extract after Chronic Infusion with Amyloid-β Peptide in Mice

    Science.gov (United States)

    Morzelle, Maressa Caldeira; Salgado, Jocelem Mastrodi; Telles, Milena; Mourelle, Danilo; Bachiega, Patricia; Buck, Hudson Sousa

    2016-01-01

    Alzheimer’s disease is a chronic and degenerative condition that had no treatment until recently. The current therapeutic strategies reduce progression of the disease but are expensive and commonly cause side effects that are uncomfortable for treated patients. Functional foods to prevent and/or treat many conditions, including neurodegenerative diseases, represent a promising field of study currently gaining attention. To this end, here we demonstrate the effects of pomegranate (Punica granatum) peel extract (PPE) regarding spatial memory, biomarkers of neuroplasticity, oxidative stress and inflammation in a mouse model of neurodegeneration. Male C57Bl/6 mice were chronically infused for 35 days with amyloid-β peptide 1–42 (Aβ) or vehicle (control) using mini-osmotic pumps. Another group, also infused with Aβ, was treated with PPE (p.o.– βA+PPE, 800 mg/kg/day). Spatial memory was evaluated in the Barnes maze. Animals treated with PPE and in the control group exhibited a reduction in failure to find the escape box, a finding that was not observed in the Aβ group. The consumption of PPE reduced amyloid plaque density, increased the expression of neurotrophin BDNF and reduced the activity of acetylcholinesterase enzyme. A reduction in lipid peroxidation and in the concentration of the pro-inflammatory cytokine TNF-α was also observed in the PPE group. No hepatic lesions were observed in animals treated with PPE. In conclusion, administration of pomegranate peel extract has neuroprotective effects involving multiple mechanisms to prevent establishment and progression of the neurodegenerative process induced by infusion with amyloid-β peptide in mice. PMID:27829013

  6. Effects of the neuroprotective drugs somatostatin and brimonidine on retinal cell models of diabetic retinopathy.

    Science.gov (United States)

    Beltramo, Elena; Lopatina, Tatiana; Mazzeo, Aurora; Arroba, Ana I; Valverde, Angela M; Hernández, Cristina; Simó, Rafael; Porta, Massimo

    2016-12-01

    Diabetic retinopathy is considered a microvascular disease, but recent evidence has underlined early involvement of the neuroretina with interactions between microvascular and neural alterations. Topical administration of somatostatin (SST), a neuroprotective molecule with antiangiogenic properties, prevents diabetes-induced retinal neurodegeneration in animals. The α 2 -adrenergic receptor agonist brimonidine (BRM) decreases vitreoretinal vascular endothelial growth factor and inhibits blood-retinal barrier breakdown in diabetic rats. However, SST and BRM effects on microvascular cells have not yet been studied. We investigated the behaviour of these drugs on the crosstalk between microvasculature and neuroretina. Expression of SST receptors 1-5 in human retinal pericytes (HRP) was checked. We subsequently evaluated the effects of diabetic-like conditions (high glucose and/or hypoxia) with/without SST/BRM on HRP survival. Endothelial cells (EC) and photoreceptors were maintained in the above conditions and their conditioned media (CM) used to culture HRP. Vice versa, HRP-CM was used on EC and photoreceptors. Survival parameters were assessed. HRP express the SST receptor 1 (SSTR1). Glucose fluctuations mimicking those occurring in diabetic subjects are more damaging for pericytes and photoreceptors than stable high glucose and hypoxic conditions. SST/BRM added to HRP in diabetic-like conditions decrease EC apoptosis. However, neither SST nor BRM changed the response of pericytes and neuroretina-vascular crosstalk under diabetic-like conditions. Retinal pericytes express SSTR1, indicating that they can be a target for SST. Exposure to SST/BRM had no adverse effects, direct or mediated by the neuroretina, suggesting that these molecules could be safely evaluated for the treatment of ocular diseases.

  7. Effects of music and video on perceived exertion during high-intensity exercise

    Directory of Open Access Journals (Sweden)

    Enoch C. Chow

    2017-03-01

    Conclusion: Music and video in combination may result in lower perceived exertion during high-intensity exercise when compared to music or video in isolation. Future research will be necessary to test if reductions in perceived exertion in response to dissociative attentional stimuli have implications for exercise adherence.

  8. Neuroprotective effects of modafinil in a marmoset Parkinson model: behavioral and neurochemical aspects.

    Science.gov (United States)

    van Vliet, Sanneke A M; Vanwersch, Raymond A P; Jongsma, Marjan J; van der Gugten, Jan; Olivier, Berend; Philippens, Ingrid H C H M

    2006-09-01

    The vigilance-enhancing agent modafinil has neuroprotective properties: it prevents striatal ischemic injury, nigrostriatal pathway deterioration after partial transsection and intoxication with 1-methyl-1,2,3,6-tetrahydropyridine. The present study determines the protective effects of modafinil in the marmoset 1-methyl-1,2,3,6-tetrahydropyridine Parkinson model on behavior and on monoamine levels. Twelve marmoset monkeys were treated with a total dose of 6 mg/kg 1-methyl-1,2,3,6-tetrahydropyridine. Simultaneously, six animals received a daily oral dose of modafinil (100 mg/kg) and six animals received vehicle for 27 days. Behavior was observed daily and the locomotor activity, hand-eye coordination, small fast movements, anxiety-related behavior and startle response of the animals were tested twice a week for 3 weeks. Modafinil largely prevented the 1-methyl-1,2,3,6-tetrahydropyridine-induced change in observed behavior, locomotor activity, hand-eye coordination and small fast movements, whereas the vehicle could not prevent the devastating effects of 1-methyl-1,2,3,6-tetrahydropyridine. Dopamine levels in the striatum of the vehicle+1-methyl-1,2,3,6-tetrahydropyridine-treated animals were reduced to 5% of control levels, whereas the dopamine levels of the modafinil+1-methyl-1,2,3,6-tetrahydropyridine-treated animals were reduced to 41% of control levels. The present data suggest that modafinil prevents decrease of movement-related behavior and dopamine levels after 1-methyl-1,2,3,6-tetrahydropyridine intoxication and can be an efficaceous pharmacological intervention in the treatment of Parkinson's disease.

  9. Bariatric surgery may reduce the risk of Alzheimer's diseases through GLP-1 mediated neuroprotective effects.

    Science.gov (United States)

    Keshava, Hari B; Mowla, Ashkan; Heinberg, Leslie J; Schauer, Philip R; Brethauer, Stacy A; Aminian, Ali

    2017-07-01

    Obesity and diabetes are associated with deficits in multiple neurocognitive domains and increased risk for dementia. Over the last two decades, there has been a significant increase in bariatric and metabolic surgery worldwide, driven by rising intertwined pandemics of obesity and diabetes, along with improvement in surgical techniques. Patients undergoing bariatric surgery achieve a significant decrease in their excess weight and a multitude of sequela associated with obesity, diabetes, and metabolic syndrome. Glucagon-like peptide 1 (GLP-1) is an intestinal peptide that has been implicated as one of the weight loss-independent mechanisms in how bariatric surgery affects type 2 diabetes. GLP-1 improves insulin secretion, inhibits apoptosis and induce pancreatic islet neogenesis, promotes satiety, and can regulate heart rate and blood pressure. Moreover, numerous studies have demonstrated potential neuroprotective and neurotrophic effects of GLP-1. Increased GLP-1 activity has been shown to increase cortical activity, promote neuronal growth, and inhibit neuronal degeneration. Specifically, in experimental studies on Alzheimer's disease, GLP-1 decreases amyloid deposition and neurofibrillary tangles. Furthermore, recent studies have also suggested that GLP-1 based therapies, new class of antidiabetic drugs, have favorable effects on neurodegenerative disorders such as Alzheimer's disease. We present a hypothesis that bariatric surgery can help delay or even prevent the onset of Alzheimer's disease in long-term by increasing the levels of GLP-1. This hypothesis has a potential for many studies from basic science projects to large population studies to fully understand the neurological and cognitive consequences of bariatric surgery and associated rise in GLP-1. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Neuroprotective effect of Allium cepa L. in aluminium chloride induced neurotoxicity.

    Science.gov (United States)

    Singh, Tanveer; Goel, Rajesh Kumar

    2015-07-01

    The present study was envisaged to investigate the neuroprotective potential of Allium cepa (A. cepa) in aluminium chloride induced neurotoxicity. Aluminium chloride (50 mg/kg/day) was administered orally in mice supplemented with different doses of A. cepa hydroethanolic extract for a period of 60 days. Various behavioural, biochemical and histopathological parameters were estimated in aluminium exposed animals. Chronic aluminium administration resulted in significant motor incoordination and memory deficits, which were also endorsed biochemically as there was increased oxidative stress as well as elevated acetylcholinesterase (AChE) and aluminium levels in the brain. Supplementation with A. cepa in aluminium exposed animals significantly improved muscle coordination and memory deficits as well as reduced oxidative stress, AChE and decreased abnormal aluminium deposition in the brain. Histopathologically, there was marked deterioration visualized as decreased vacuolated cytoplasm as well as decreased pyramidal cells in the hippocampal area of mice brain which were found to be reversed with A. cepa supplementation. Administration of BADGE (PPARγ antagonist) in aluminium exposed animals reversed the neuroprotective potential of A. cepa as assessed with various behavioural, biochemical, neurochemical and histopathological estimations. In conclusion, finding of this study suggested significant neuroprotective potential of A. cepa in aluminium induced neurotoxicity. Further, the role of PPARγ receptor agonism has also been suggested as a putative neuroprotective mechanism of A. cepa, which needs further studies for confirmation. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Neuroprotective Effect of Zhen Tian Wan on Pial strip-Induced ...

    African Journals Online (AJOL)

    toshiba

    A variety of deficits in learning and memory function have been demonstrated in the brain of animals after injury ... memory in Pial Strip (lesion) –induced amnesia in rat using the Morris water maze. The neuroprotective ..... Hippocampectomy disrupts auditory trace fear conditioning and contextual fear conditioning in the rat.

  12. Neuroprotective and Therapeutic Effect of Caffeine on the Rat Model of Parkinson's Disease Induced by Rotenone.

    Science.gov (United States)

    Khadrawy, Yasser A; Salem, Ahmed M; El-Shamy, Karima A; Ahmed, Emad K; Fadl, Nevein N; Hosny, Eman N

    2017-09-03

    The present study aimed to investigate the protective and therapeutic effects of caffeine on rotenone-induced rat model of Parkinson's disease (PD). Rats were divided into control, PD model induced by rotenone (1.5 mg/kg intraperitoneally (i.p.) for 45 days), protected group injected with caffeine (30 mg/kg, i.p.) and rotenone for 45 days (during the development of PD model), and treated group injected with caffeine (30 mg/kg, i.p.) for 45 days after induction of PD model. The data revealed a state of oxidative and nitrosative stress in the midbrain and the striatum of animal model of PD as indicated from the increased lipid peroxidation and nitric oxide levels and the decreased reduced glutathione level and activities of glutathione-S-transferase and superoxide dismutase. Rotenone induced a decrease in acetylcholinesterase and Na + /K + -ATPase activities and an increase in tumor necrosis factor-α level in the midbrain and the striatum. Protection and treatment with caffeine ameliorated the oxidative stress and the changes in acetylcholinesterase and Na + /K + -ATPase activities induced by rotenone in the midbrain and the striatum. This was associated with improvement in the histopathological changes induced in the two areas of PD model. Caffeine protection and treatment restored the depletion of midbrain and striatal dopamine induced by rotenone and prevented decline in motor activities (assessed by open field test) and muscular strength (assessed by traction and hanging tests) and improved norepinephrine level in the two areas. The present study showed that caffeine offered a significant neuroprotection and treatment against neurochemical, histopathological, and behavioral changes in a rotenone-induced rat model of PD.

  13. Neuroprotective Effects of Theaflavins Against Oxidative Stress-Induced Apoptosis in PC12 Cells.

    Science.gov (United States)

    Zhang, Jing; Cai, Shuxian; Li, Juan; Xiong, Ligui; Tian, Lili; Liu, Jianjun; Huang, Jianan; Liu, Zhonghua

    2016-12-01

    Oxidative stress can induce neuronal apoptosis via the production of superoxide and hydroxyl radicals. This process is as a major pathogenic mechanism in neurodegenerative disorders. In this study, we aimed to clarify whether theaflavins protect PC12 cells from oxidative stress damage induced by H 2 O 2 . A cell model of PC12 cells undergoing oxidative stress was created by exposing cells to 200 μM H 2 O 2 in the presence or absence of varying concentrations of theaflavins (5, 10, and 20 μM). Cell viability was monitored using the MTT assay and Hoechst 33258 staining, showing that 10 μM theaflavins enhanced cell survival following 200 μM H 2 O 2 induced toxicity and increased cell viability by approximately 40 %. Additionally, we measured levels of intracellular reactive oxygen species (ROS) and antioxidant enzyme activity. This suggested that the neuroprotective effect of theaflavins against oxidative stress in PC12 cells is derived from suppression of oxidant enzyme activity. Furthermore, Western blot analyses indicated that theaflavins downregulated the ratio of pro-apoptosis/anti-apoptosis proteins Bax/Bcl-2. Theaflavins also downregulated the expression of caspase-3 compared with a H 2 O 2 -treated group that had not been treated with theaflavins. Interestingly, this is the first study to report that the four main components of theaflavins found in black tea can protect neural cells (PC12) from apoptosis induced by H 2 O 2 . These findings provide the foundations for a new field of using theaflavins or its source, black tea, in the treatment of neurodegenerative diseases caused by oxidative stress.

  14. Neuroprotective effects of Ganoderma lucidum polysaccharides against traumatic spinal cord injury in rats.

    Science.gov (United States)

    Gokce, Emre Cemal; Kahveci, Ramazan; Atanur, Osman Malik; Gürer, Bora; Aksoy, Nurkan; Gokce, Aysun; Sargon, Mustafa Fevzi; Cemil, Berker; Erdogan, Bulent; Kahveci, Ozan

    2015-11-01

    Ganoderma lucidum (G. lucidum) is a mushroom belonging to the polyporaceae family of Basidiomycota and has widely been used as a traditional medicine for thousands of years. G. lucidum has never been studied in traumatic spinal cord injury. The aim of this study is to investigate whether G. lucidum polysaccharides (GLPS) can protect the spinal cord after experimental spinal cord injury. Rats were randomized into five groups of eight animals each: control, sham, trauma, GLPS, and methylprednisolone. In the control group, no surgical intervention was performed. In the sham group, only a laminectomy was performed. In all the other groups, the spinal cord trauma model was created by the occlusion of the spinal cord with an aneurysm clip. In the spinal cord tissue, caspase-3 activity, tumour necrosis factor-alpha levels, myeloperoxidase activity, malondialdehyde levels, nitric oxide levels, and superoxide dismutase levels were analysed. Histopathological and ultrastructural evaluations were also performed. Neurological evaluation was performed using the Basso, Beattie, and Bresnahan locomotor scale and the inclined-plane test. After traumatic spinal cord injury, increases in caspase-3 activity, tumour necrosis factor-alpha levels, myeloperoxidase activity, malondialdehyde levels, and nitric oxide levels were detected. After the administration of GLPS, decreases were observed in tissue caspase-3 activity, tumour necrosis factor-alpha levels, myeloperoxidase activity, malondialdehyde levels, and nitric oxide levels. Furthermore, GLPS treatment showed improved results in histopathological scores, ultrastructural scores, and functional tests. Biochemical, histopathological, and ultrastructural analyses and functional tests reveal that GLPS exhibits meaningful neuroprotective effects against spinal cord injury. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Notochordal-cell derived extracellular vesicles exert regenerative effects on canine and human nucleus pulposus cells.

    Science.gov (United States)

    Bach, Frances; Libregts, Sten; Creemers, Laura; Meij, Björn; Ito, Keita; Wauben, Marca; Tryfonidou, Marianna

    2017-10-24

    During intervertebral disc ageing, chondrocyte-like cells (CLCs) replace notochordal cells (NCs). NCs have been shown to induce regenerative effects in CLCs. Since vesicles released by NCs may be responsible for these effects, we characterized NC-derived extracellular vesicles (EVs) and determined their effect on CLCs. EVs were purified from porcine NC-conditioned medium (NCCM) through size exclusion chromatography, ultracentrifugation or density gradient centrifugation. Additionally, the EVs were quantitatively analyzed by high-resolution flow cytometry. The effect of NCCM-derived EVs was studied on canine and human CLC micro-aggregates in vitro and compared with NCCM-derived proteins and unfractionated NCCM. Porcine NCCM contained a considerable amount of EVs. NCCM-derived EVs induced GAG deposition in canine CLCs to a comparable level as NCCM-derived proteins and unfractionated NCCM, and increased the DNA and glycosaminoglycan (GAG) content of human micro-aggregates, although to a lesser extent than unfractionated NCCM. The biological EV effects were not considerably influenced by ultracentrifugation compared with size exclusion-based purification. Upon ultracentrifugation, interfering GAGs, but not collagens, were lost. Nonetheless, collagen type I or II supplemented to CLCs in a concentration as present in NCCM induced no anabolic effects. Porcine NCCM-derived EVs exerted anabolic effects comparable to NCCM-derived proteins, while unfractionated NCCM was more potent in human CLCs. GAGs and collagens appeared not to mediate the regenerative EV effects. Thus, NC-derived EVs have regenerative potential, and their effects may be influenced by the proteins present in NCCM. The optimal combination of NC-secreted factors needs to be determined to fully exploit the regenerative potential of NC-based technology.

  16. Magnolol Enhances Hippocampal Neurogenesis and Exerts Antidepressant-Like Effects in Olfactory Bulbectomized Mice.

    Science.gov (United States)

    Matsui, Nobuaki; Akae, Haruka; Hirashima, Nana; Kido, Yuki; Tanabe, Satoshi; Koseki, Mayumi; Fukuyama, Yoshiyasu; Akagi, Masaaki

    2016-11-01

    Magnolol is the main constituent of Magnolia bark and has been reported to exhibit antidepressant effects in rodent models. Hippocampal neurogenesis and neurotrophins such as brain-derived neurotrophic factor are integrally involved in the action of conventional antidepressants. Here, we investigated the effects of magnolol on depressive behaviours, impaired hippocampal neurogenesis and neurotrophin-related signal transduction in an olfactory bulbectomy (OBX) mouse model of depression. Mice were submitted to OBX to induce depressive behaviour, which was evaluated in the tail suspension test. Magnolol was administered orally by gavage needle. Neurogenesis was assessed by analysis of cells expressing NeuN, a neuronal marker, and 5-bromo-2'-deoxyuridine (BrdU) uptake. Phosphorylation levels of protein kinase B (Akt), extracellular signal-regulated kinase and cyclic AMP-responsive element-binding protein were evaluated by Western blot. Fourteen day treatment with magnolol (50 or 100 mg/kg/day) significantly improved OBX-induced depressive behaviour in tail suspension test. In agreement, magnolol significantly rescued impairments of hippocampal neurogenesis. Moreover, single treatments with magnolol (50 mg/kg) significantly increased phosphorylation of Akt, extracellular signal-regulated kinase and cyclic AMP-responsive element-binding protein after 3 h. The present data indicate that magnolol exerts antidepressant-like effects on behaviours by enhancing hippocampal neurogenesis and neurotrophin-related intracellular signalling in OBX mice. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  17. Phloretin exerts hypoglycemic effect in streptozotocin-induced diabetic rats and improves insulin resistance in vitro

    Directory of Open Access Journals (Sweden)

    Shen X

    2017-02-01

    Full Text Available Xin Shen,1,* Nan Zhou,1,* Le Mi,1 Zishuo Hu,2 Libin Wang,1 Xueying Liu,1 Shengyong Zhang1 1Department of Medicinal Chemistry, School of Pharmacy, 2Student Brigade, The Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China *These authors contributed equally to this work Abstract: The present study investigated the possible antiobesity and hypoglycemic effects of phloretin (Ph. In an attempt to discover the hypoglycemic effect and potential mechanism of Ph, we used the streptozotocin-induced diabetic rats and (L6 myotubes. Daily oral treatment with Ph for 4 weeks significantly (P<0.05 reduced postprandial blood glucose and improved islet injury and lipid metabolism. Glucose consumption and glucose tolerance were improved by Ph via GOD–POD method. Western blot results revealed that the expression of Akt, PI3K, IRS-1, and GLUT4 were upregulated in skeletal muscle of T2D rats and in L6 myotubes by Ph. The immunofluorescence studies confirmed that Ph improved the translocation of GLUT4 in L6 myotubes. Ph exerted hypoglycemic effects in vivo and in vitro, hence it may play an important role in the management of diabetes. Keywords: phloretin, diabetes, insulin sensitivity, blood glucose consumption, skeletal muscle

  18. Nitrosonifedipine ameliorates the progression of type 2 diabetic nephropathy by exerting antioxidative effects.

    Directory of Open Access Journals (Sweden)

    Keisuke Ishizawa

    Full Text Available Diabetic nephropathy (DN is the major cause of end-stage renal failure. Oxidative stress is implicated in the pathogenesis of DN. Nitrosonifedipine (NO-NIF is a weak calcium channel blocker that is converted from nifedipine under light exposure. Recently, we reported that NO-NIF has potential as a novel antioxidant with radical scavenging abilities and has the capacity to treat vascular dysfunction by exerting an endothelial protective effect. In the present study, we extended these findings by evaluating the efficacy of NO-NIF against DN and by clarifying the mechanisms of its antioxidative effect. In a model of type 2 DN (established in KKAy mice, NO-NIF administration reduced albuminuria and proteinuria as well as glomerular expansion without affecting glucose metabolism or systolic blood pressure. NO-NIF also suppressed renal and systemic oxidative stress and decreased the expression of intercellular adhesion molecule (ICAM-1, a marker of endothelial cell injury, in the glomeruli of the KKAy mice. Similarly, NO-NIF reduced albuminuria, oxidative stress, and ICAM-1 expression in endothelial nitric oxide synthase (eNOS knockout mice. Moreover, NO-NIF suppressed urinary angiotensinogen (AGT excretion and intrarenal AGT protein expression in proximal tubular cells in the KKAy mice. On the other hand, hyperglycemia-induced mitochondrial superoxide production was not attenuated by NO-NIF in cultured endothelial cells. These findings suggest that NO-NIF prevents the progression of type 2 DN associated with endothelial dysfunction through selective antioxidative effects.

  19. Neuroprotective Effects of the Glucagon-Like Peptide-1 Analog Exenatide After Out-of-Hospital Cardiac Arrest

    DEFF Research Database (Denmark)

    Wiberg, Sebastian; Hassager, Christian; Schmidt, Henrik

    2016-01-01

    BACKGROUND: In-hospital mortality in comatose patients resuscitated from out-of-hospital cardiac arrest (OHCA) is ≈50%. In OHCA patients, the leading cause of death is neurological injury secondary to ischemia and reperfusion. Glucagon-like peptide-1 analogs are approved for type 2 diabetes...... mellitus; preclinical and clinical data have suggested their organ-protective effects in patients with ischemia and reperfusion injury. The aim of this trial was to investigate the neuroprotective effects of the glucagon-like peptide-1 analog exenatide in resuscitated OHCA patients. METHODS: We randomly...

  20. Effective range of reproductive interference exerted by an alien dandelion, Taraxacum officinale, on a native congener.

    Science.gov (United States)

    Takakura, Koh-Ichi; Matsumoto, Takashi; Nishida, Takayoshi; Nishida, Sachiko

    2011-03-01

    Reproductive interference (RI), defined as the fitness cost of interspecific sexual interactions, such as interspecific pollen transfer (IPT) in plants, is ecologically important. Theoretically, RI could result in competitive exclusion, as it operates in a frequency-dependent manner. Additionally, IPT may have a greater range than resource competition, although information about the range of IPT is lacking. In the present study, we measured the range of IPT exerted by Taraxacum officinale (an alien species) on a native dandelion, T. japonicum. We used two approaches. In one, we analyzed the RI effect on a native seed set at three spatial scales. In the second, we tracked IPT from alien to native flower heads using fluorescent pigments as markers. We estimated that pollination distances were in the order of several meters. These distances exceeded the mean distance from each native plant to the nearest alien. As hypothesized, the effect of RI reached farther than neighboring individuals. These data indicate the spatial range from which alien dandelions should be removed to allow the conservation of natives.

  1. The prozone effect exerted by the complement-binding anti-Lea on anti-D.

    Science.gov (United States)

    Joshi, Sanmukh R; Parekh, Kamlesh H

    2017-01-01

    Prozone phenomenon is seen with very high-titer antibodies in an immune serum. The prozone effect on anti-D by a low-titer anti-Le a was investigated associated with neonatal jaundice. Standard methods were used in investigations. The child was born at full-term developed mild jaundice. With weak direct antiglobulin test+, her indirect serum bilirubin was progressed to 27.5 mg/dL in 48 h. Anti-D and anti-Le a were detected in the mother. Both these antibodies were detected in the child's serum though the eluate from red blood cells (RBCs) contained only anti-D. Mother's anti-D was masked by anti-Le a if the RBCs possessed both the antigens together. Anti-D was revealed only with D-positive RBCs lacking Le a or if the serum was modified by mixing with Le a+ saliva or was heated at 56°C or fortified with citrate solution. An anti-D showed prozone effect exerted by the complement-fixing anti-Le a in the test.

  2. Melittin exerts an antitumor effect on non‑small cell lung cancer cells.

    Science.gov (United States)

    Zhang, Su-Fang; Chen, Zhe

    2017-09-01

    Lung cancer accounts for a significant percentage of all cancer‑associated mortalities in men and women, with non‑small cell lung cancer being the most frequently occurring type of lung cancer. Melittin is the principal active component of apitoxin (bee venom) that has been reported to exert anti‑chronic inflammatory and anti‑cancer effects. In the present study, the antitumor effect of melittin was evaluated using in vivo and in vitro analyses. The results demonstrated that melittin significantly inhibited the epidermal growth factor‑induced invasion and migration of non‑small cell lung cancer cells. Subcutaneous injection of melittin at doses of 1 and 10 mg/kg significantly suppressed non‑small cell lung cancer tumor growth by 27 and 61%, respectively. In addition, melittin significantly inhibited the secretion of vascular endothelial growth factor (VEGF) in non‑small cell lung cancer cells. Furthermore, melittin decreased the protein expression of VEGF and hypoxia‑inducible factor 1‑α. Therefore, the antitumor activity of melittin may be associated with the anti‑angiogenic actions of inhibiting the VEGF and hypoxia‑inducible factor signaling pathways.

  3. Fluoxetine and aripiprazole treatment following prenatal immune activation exert longstanding effects on rat locomotor response.

    Science.gov (United States)

    Richtand, Neil M; Ahlbrand, Rebecca; Horn, Paul; Tambyraja, Rabindra; Grainger, Molly; Bronson, Stefanie L; McNamara, Robert K

    2012-05-15

    Studies characterizing treatment interventions in a naturalistic setting suggest that antidepressant and antipsychotic medications may be equally effective in improving clinical outcome in individuals at high risk for first-episode psychosis. Of interest, both beneficial as well as potentially adverse effects have been observed following fluoxetine treatment in a mouse prenatal immune activation model of relevance to psychosis prevention. We sought to extend those findings by examining the effects of fluoxetine, as well as the antipsychotic medication aripiprazole, in a rat prenatal immune activation model. Pregnant Sprague-Dawley rats were injected with poly I:C or saline on gestational day 14. Offspring of poly I:C and saline-treated dams received fluoxetine (10.0 mg/kg/d), aripiprazole (0.66 mg/kg/d), or vehicle from postnatal days 35 to 70. Locomotor responses to novelty, saline injection, and amphetamine (1 and 5 mg/kg) were determined at three months, i.e., 21 days following drug discontinuation. Both fluoxetine and aripiprazole had beneficial effects on behavioral response to amphetamine (1 mg/kg) at 3 months, ameliorating the impact of prenatal immune activation on offspring of poly I:C-treated dams. Significantly, both drugs also exerted effects in offspring of control (saline-treated) dams on locomotor response to injection. Fluoxetine and aripiprazole pretreatment of poly I:C offspring from postnatal days 35 to 70 stabilized response to amphetamine exposure persisting through 3 months of age, similar to earlier findings in mice that fluoxetine treatment following prenatal immune activation prevented altered locomotor response to amphetamine. The current data also confirm earlier findings of potential adverse behavioral effects in offspring of control dams following treatment with fluoxetine and antipsychotic medications, highlighting the potential for both therapeutic as well as safety concerns with exposure to preventive pharmacological treatments over

  4. A novel macrolide solithromycin exerts superior anti-inflammatory effect via NF-κB inhibition.

    Science.gov (United States)

    Kobayashi, Yoshiki; Wada, Hiroo; Rossios, Christos; Takagi, Dai; Higaki, Manabu; Mikura, Shin'ichiro; Goto, Hajime; Barnes, Peter J; Ito, Kazuhiro

    2013-04-01

    Macrolides are reported to reduce exacerbation of chronic inflammatory respiratory disease, such as chronic obstructive pulmonary disease (COPD), and also show anti-inflammatory effects in vitro and in vivo. However the anti-inflammatory efficacies of current macrolides are relatively weak. Here we found that a novel macrolide/fluoroketolide solithromycin (CEM-101) showed superior anti-inflammatory effects to macrolides in current clinical use. The effects of solithromycin (SOL) on lipopolysaccharide-induced TNFα (tumor necrosis factor α) and/or CXCL8 (C-X-C motif chemokine ligand 8; interleukin-8) release, phorbol 12-myristate 13-acetate-induced MMP9 (matrix metalloproteinase 9) activity and NF-κB (nuclear factor-κB) activity under conditions of oxidative stress have been evaluated and compared with the effects of erythromycin, clarithromycin, azithromycin, and telithromycin in macrophage-like PMA-differentiated U937 cells and peripheral blood mononuclear cells (PBMC) obtained from COPD patients. We also examined effect of SOL on cigarette smoke-induced airway inflammation in mice. SOL exerted superior inhibitory effects on TNFα/CXCL8 production and MMP9 activity in monocytic U937 cells. In addition, SOL suppressed TNFα release and MMP9 activity in PBMC from COPD patients at 10 µM, which is 10 times more potent than the other macrolides tested. Activated NF-κB by oxidative stress was completely reversed by SOL. SOL also inhibited cigarette smoke-induced neutrophilia and pro-MMP9 production in vivo, although erythromycin did not inhibit them. Thus, SOL showed better anti-inflammatory profiles compared with macrolides currently used in the clinic and may be a promising anti-inflammatory and antimicrobial macrolide for the treatment of COPD in future.

  5. Differences in the Neuroprotective Effect of Orally Administered Virgin Olive Oil (Olea europaea) Polyphenols Tyrosol and Hydroxytyrosol in Rats.

    Science.gov (United States)

    De La Cruz, José Pedro; Ruiz-Moreno, Maria Isabel; Guerrero, Ana; Reyes, José Julio; Benitez-Guerrero, Adela; Espartero, José Luis; González-Correa, José Antonio

    2015-07-01

    The neuroprotective effect of virgin olive oil (VOO) polyphenols has been related to their antioxidant effect. The main objective was to analyze how tyrosol and hydroxytyrosol contribute to the antioxidant and neuroprotective effects of VOO in a model of hypoxia-reoxygenation in rat brain slices. Rats were treated per os (po) (10 or 20 mg/kg/day) with hydroxytyrosol ethyl ether (HTEE), tyrosol ethyl ether (TEE), or 3,4-di-o-methylidene-hydroxytyrosol ethyl ether (MHTEE), used as a negative control for antioxidant effects. Lipid peroxidation was inhibited with HTEE, TEE, and MHTEE (from 5.0 ± 1.5 to 2.6 ± 1.5, 4.5 ± 1.5, and 4.8 ± 1.5 nmol/mg protein, respectively). However, all three compounds had similar neuroprotective effects: from 2.8 ± 0.07 to 1.8 ± 0.02 arbitrary units for HTEE, 1.4 ± 0.09 arbitrary units for TEE, and 1.3 ± 0.2 arbitrary units for MHTEE. All three compounds inhibited 3-nitrotyrosine production (from 3.7 ± 0.3 to 1.2 ± 0.03 nmol/0.1 g tissue for HTEE, 1.0 ± 0.2 nmol/0.1 g tissue for TEE, and 1.3 ± 0.1 nmol/0.1 g tissue for MHTEE), prostaglandin E2 production (from 55.7 ± 2.2 to 46.4 ± 1.9 pg/0.1 g tissue for HTEE, 24.7 ± 1.3 pg/0.1 g tissue for TEE, and 27.6 ± 2.6 pg/0.1 g tissue for MHTEE), whereas only HTEE inhibited IL1β production (from 35.7 ± 1.5 to 21.6 ± 0.8 pg/0.1 g tissue). Pearson correlation coefficients related neuroprotective effect with an antioxidant effect for HTEE (R = 0.72, p < 0.001), and inhibition of nitrosative stress (R = 0.78, 0.67, and 0.66 for HTEE, TEE, and MHTEE, respectively, p < 0.001) and inflammatory mediators (R = 0.72, 0.79, and 0.64 for HTEE, TEE, and MHTEE, respectively, p < 0.001) with all three compounds.

  6. Neuroprotection in glaucoma

    Science.gov (United States)

    Vasudevan, Sushil K; Gupta, Viney; Crowston, Jonathan G

    2011-01-01

    Glaucoma is a neurodegenerative disease characterized by loss of retinal ganglion cells and their axons. Recent evidence suggests that intraocular pressure (IOP) is only one of the many risk factors for this disease. Current treatment options for this disease have been limited to the reduction of IOP; however, it is clear now that the disease progression continues in many patients despite effective lowering of IOP. In the search for newer modalities in treating this disease, much data have emerged from experimental research the world over, suggesting various pathological processes involved in this disease and newer possible strategies to treat it. This review article looks into the current understanding of the pathophysiology of glaucoma, the importance of neuroprotection, the various possible pharmacological approaches for neuroprotection and evidence of current available medications. PMID:21150020

  7. Fingolimod anti-inflammatory and neuroprotective effects modulation of RAGE axis in multiple sclerosis patients.

    Science.gov (United States)

    Sternberg, Zohara; Kolb, Channa; Chadha, Kailash; Nir, Adam; Nir, Raphael; George, Rayan; Johnson, Joseph; Yu, Jinhee; Hojnacki, David

    2018-03-01

    We investigated Fingolimod treatment effects on the RAGE (receptor for advanced glycation endproducts) axis in multiple sclerosis (MS) patients. The primary outcome of the study was whether Fingolimod treatment increases serum levels of the soluble RAGE isoforms, sRAGE and esRAGE - both being considered putative endogenous inhibitors of RAGE signaling. Additional variables were serum levels of RAGE ligands, the high mobility group box (HMGB)1 and pentosidine. Serum levels of the study variables were measured by ELISA, and compared between baseline (before Fingolimod treatment) and 6 and 12 months post-drug treatment in 17 relapsing MS patients. Fingolimod treatment effects on MS disease progression were assessed by comparing pre- and post-Fingolimod values of the EDSS and rate of clinical relapse, and changes in the T1-and T2-enahncing lesions on the MRI scan.methods RESULTS: Twelve months treatment with Fingolimod increased serum levels of sRAGE and esRAGE by 32.4% (P = 0.004) and 48.5% (P = 0.007) respectively. In addition, Fingolimod treatment reduced serum levels of HMGB1 by 71.6% (P = 0.02) and pentosidine serum levels by 41.3% (P = 0.12). EDSS remained stable (baseline: 3.57 ± 1.56; post-Fingolimod: 3.54 ± 1.2, P = 0.96) and the rate of clinical relapse decreased near significantly (P = 0.094). T1-and T2-enhancing lesions remained stable, showing no significant changes pre-vs. post-Fingolimod treatment. Fingolimod mediates modulation of the RAGE axis which apparently contributes to the Fingolimod's anti-inflammatory and neuroprotective effects. These findings may provide a rationale for the clinical efficacy of Fingolimod in pathological states other than MS, where dysregulation of the RAGE axis plays a role. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Prolactin mediates neuroprotection against excitotoxicity in primary cell cultures of hippocampal neurons via its receptor.

    Science.gov (United States)

    Vergara-Castañeda, E; Grattan, D R; Pasantes-Morales, H; Pérez-Domínguez, M; Cabrera-Reyes, E A; Morales, T; Cerbón, M

    2016-04-01

    Recently it has been reported that prolactin (PRL) exerts a neuroprotective effect against excitotoxicity in hippocampus in the rat in vivo models. However, the exact mechanism by which PRL mediates this effect is not completely understood. The aim of our study was to assess whether prolactin exerts neuroprotection against excitotoxicity in an in vitro model using primary cell cultures of hippocampal neurons, and to determine whether this effect is mediated via the prolactin receptor (PRLR). Primary cell cultures of rat hippocampal neurons were used in all experiments, gene expression was evaluated by RT-qPCR, and protein expression was assessed by Western blot analysis and immunocytochemistry. Cell viability was assessed by using the MTT method. The results demonstrated that PRL treatment of neurons from primary cultures did not modify cell viability, but that it exerted a neuroprotective effect, with cells treated with PRL showing a significant increase of viability after glutamate (Glu)--induced excitotoxicity as compared with neurons treated with Glu alone. Cultured neurons expressed mRNA for both PRL and its receptor (PRLR), and both PRL and PRLR expression levels changed after the excitotoxic insult. Interestingly, the PRLR protein was detected as two main isoforms of 100 and 40 kDa as compared with that expressed in hypothalamic cells, which was present only as a 30 kDa variant. On the other hand, PRL was not detected in neuron cultures, either by western blot or by immunohistochemistry. Neuroprotection induced by PRL was significantly blocked by specific oligonucleotides against PRLR, thus suggesting that the PRL role is mediated by its receptor expressed in these neurons. The overall results indicated that PRL induces neuroprotection in neurons from primary cell cultures. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Neuroprotective effects of the AMPA antagonist PNQX in oxygen-glucose deprivation in mouse hippocampal slice cultures and global cerebral ischemia in gerbils

    DEFF Research Database (Denmark)

    Montero, Maria; Nielsen, Marianne; Rønn, Lars Christian B

    2007-01-01

    PNQX (9-methyl-amino-6-nitro-hexahydro-benzo(F)quinoxalinedione) is a selective AMPA antagonist with demonstrated neuroprotective effects in focal ischemia in rats. Here we report corresponding effects in mouse hippocampal slice cultures subjected to oxygen and glucose deprivation (OGD) and in tr......PNQX (9-methyl-amino-6-nitro-hexahydro-benzo(F)quinoxalinedione) is a selective AMPA antagonist with demonstrated neuroprotective effects in focal ischemia in rats. Here we report corresponding effects in mouse hippocampal slice cultures subjected to oxygen and glucose deprivation (OGD....... For comparison, other cultures were exposed to the NMDA antagonist MK-801 using the same protocol. Both PNQX and MK-801 displayed significant neuroprotective effects in all hippocampal subfields when present during and after OGD. When added just after OGD, only PNQX retained some neuroprotective effect. When...... stained for the neurodegeneration marker Fluoro-Jade B and immunostained for the astroglial marker glial fibrillary acidic protein revealed a significant PNQX-induced decrease in neuronal cell death and astroglial activation. We conclude that, PNQX provided neuroprotection against both global cerebral...

  10. Neuroprotective effects of curcumin on endothelin-1 mediated cell death in hippocampal neurons.

    Science.gov (United States)

    Stankowska, Dorota L; Krishnamoorthy, Vignesh R; Ellis, Dorette Z; Krishnamoorthy, Raghu R

    2017-06-01

    Alzheimer's disease is a progressive neurodegenerative disease characterized by loss of hippocampal neurons leading to memory deficits and cognitive decline. Studies suggest that levels of the vasoactive peptide endothelin-1 (ET-1) are increased in the brain tissue of Alzheimer's patients. Curcumin, the main ingredient of the spice turmeric, has been shown to have anti-inflammatory, anti-cancer, and neuroprotective effects. However, the mechanisms underlying some of these beneficial effects are not completely understood. The objective of this study was to determine if curcumin could protect hippocampal neurons from ET-1 mediated cell death and examine the involvement of c-Jun in this pathway. Primary hippocampal neurons from rat pups were isolated using a previously published protocol. Viability of the cells was measured by the live/dead assay. Immunoblot and immunohistochemical analyses were performed to analyze c-Jun levels in hippocampal neurons treated with either ET-1 or a combination of ET-1 and curcumin. Apoptotic changes were evaluated by immunoblot detection of cleaved caspase-3, cleaved fodrin, and a caspase 3/7 activation assay. ET-1 treatment produced a 2-fold increase in the levels of c-Jun as determined by an immunoblot analysis in hippocampal neurons. Co-treatment with curcumin significantly attenuated the ET-1 mediated increase in c-Jun levels. ET-1 caused increased neuronal cell death of hippocampal neurons indicated by elevation of cleaved caspase-3, cleaved fodrin and an increased activity of caspases 3 and 7 which was attenuated by co-treatment with curcumin. Blockade of JNK, an upstream effector of c-Jun by specific inhibitor SP600125 did not fully protect from ET-1 mediated activation of pro-apoptotic enzymes in primary hippocampal cells. Our data suggests that one mechanism by which curcumin protects against ET-1-mediated cell death is through blocking an increase in c-Jun levels. Other possible mechanisms include decreasing pro

  11. The neuroprotective effects ofTao-Ren-Cheng-Qi Tangagainst embolic stroke in rats.

    Science.gov (United States)

    Hsu, Ling-Wei; Shiao, Wei-Cheng; Chang, Nen-Chung; Yu, Meng-Che; Yen, Ting-Lin; Thomas, Philip Aloysius; Jayakumar, Thanasekaran; Sheu, Joen-Rong

    2017-01-01

    Combinations of the traditional Chinese and Western medicines have been used to treat numerous diseases throughout the world, and there is a growing body of evidence showing that some of the herbs used in traditional Chinese medicine elicit significant pharmacological effects. The aim of this study was to demonstrate the neuroprotective effects of Tao - Ren - Cheng - Qi Tang (TRCQT) in combination with aspirin following middle cerebral artery occlusion (MCAO)-induced embolic stroke in rats. A blood clot was embolized into the middle cerebral artery of rats to induce focal ischemic brain injury. After 24 h of MCAO occlusion, the rats were arbitrarily separated into five groups and subjected to different oral treatment processes with TRCQT and aspirin for 30 days before being evaluated in terms of their neurological behavior using a four-point system. The rats were sacrificed at 30 days after drug treatment and the infarct volumes were measured using a 2,3,5-triphenyltetrazolium chloride staining method. Tumor necrosis factor-α (TNF-α), c-Jun N-terminal kinases (JNK), activated caspase-3 and Bax were detected by western blot analysis. The apoptotic cells were identified by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. ROS generation was also measured by electron spin resonance spectrometry. Rats treated with TRCQT alone or in combination with aspirin showed a significantly reduced infarct volume ( P  < 0.001) and improved neurological outcome compared with those treated with distilled water. Rats treated with TRCQT alone ( P  = 0.021) or in combination with aspirin ( P  = 0.02) also showed significantly reduced MCAO-induced expression levels of TNF-α and pJNK ( P  < 0.001) in their ischemic regions. Rats treated with TRCQT alone or in combination with aspirin showed decreased apoptosis by a reduction in the number of TUNEL positive cells, which inhibited the expression of activated caspase-3 ( P  = 0.038) and Bax ( P

  12. Acute effects of exercise and active video games on adults' reaction time and perceived exertion.

    Science.gov (United States)

    Guzmán, José F; López-García, Jesús

    2016-11-01

    The purpose of the present study was to examine the acute effects of resting, aerobic exercise practised alone, and aerobic exercise with active video games (AVG), on complex reaction time (CRT) and the post-exercise acute rate of perceived exertion (RPE) in young healthy adults. The experimental group was composed of 92 healthy young adults, 78 males and 13 females (age M = 21.9 ± 2.7 years) who completed two sessions, A and B. In session A, participants rode 30 min on an ergometer, while in session B they exercised for 30 min on an ergometer while playing an AVG on a Wii. The control group was composed of 30 young adults, 26 males and 4 females (age M = 21.4 ± 2.9 years) who rested for 30 min. In each session, a CRT task was performed before and after exercising or resting, and post-exercise global RPE was noted. Repeated measures general linear model (GLM) and Wilcoxon tests were performed. (1) Both aerobic exercise alone and aerobic exercise combined with AVG improved CRT, while resting did not; (2) aerobic exercise combined with AVG did not improve CRT more than aerobic exercise only; and (3) RPE was lower after aerobic exercise combined with AVG compared with aerobic exercise only. In young adults, exercise produces acute benefits on CRT, and practising exercise with AVG helps to decrease RPE.

  13. Acute Effect on Arterial Stiffness after Performing Resistance Exercise by Using the Valsalva Manoeuvre during Exertion

    Directory of Open Access Journals (Sweden)

    Wai Yip Vincent Mak

    2015-01-01

    Full Text Available Background. Performing resistance exercise could lead to an increase in arterial stiffness. Objective. We investigate the acute effect on arterial stiffness by performing Valsalva manoeuvre during resistance exercise. Materials and Methods. Eighteen healthy young men were assigned to perform bicep curls by using two breathing techniques (exhalation and Valsalva manoeuvre during muscle contraction on two separate study days. Carotid pulsed wave velocity (cPWV was measured as an indicator to reflect the body central arterial stiffness using a high-resolution ultrasound system, and its value was monitored repeatedly at three predefined time intervals: before resistance exercise, immediately after exercise, and 15 minutes after exercise. Results. At the 0th minute after resistance exercise was performed using the Valsalva manoeuvre during exertion, a significant increase in cPWV (4.91 m/s ± 0.52 compared with the baseline value (4.67 m/s ± 0.32, P=0.008 was observed, and then it nearly returned to its baseline value at the 15th minute after exercise (4.66 m/s ± 0.44, P=0.010. These findings persisted after adjusting for age, body mass index, and systolic blood pressure. Conclusion. Our result suggests short duration of resistance exercise may provoke a transient increase in central arterial stiffness in healthy young men.

  14. Biological effects of compressive forces exerted on particulate bone grafts during socket preservation: animal study.

    Science.gov (United States)

    Delgado-Ruiz, Rafael; Romanos, Georgios E; Alexandre Gerhke, Sergio; Gomez-Moreno, Gerardo; Maté-Sánchez de Val, José Eduardo; Calvo-Guirado, José Luis

    2016-08-02

    To compare different compressive forces exerted on a particulate graft material during socket preservation and their effects on bone regeneration. Six male dogs were used. The second, third, and fourth premolars, and the first molar were extracted bilaterally at the lower jaws. A particulate synthetic biphasic grafting material (60% HA and 40% β-tricalcium phosphate) was used. Three different standardized compressive forces were applied randomly during the socket preservation. The sample was divided into four experimental groups Test A (10 g), Test B (50 g), Test C (200 g), and Control (empty sockets). Collagen membranes were placed, and primary closure was obtained. Two months after the surgery the animals were sacrificed, and histomorphometric analysis of non-decalcified samples was performed at the coronal, middle, and apical thirds. Grafted sockets resulted in higher bony contour (3 ± 0.43 mm 2 ; P  0.05). Within the limitations of this experimental animal study, it might be concluded that grafted sockets compressed with 200 g force will have higher bony contours; higher compressive forces facilitate the penetration of the particulate graft material into the apical area of the socket and results in more bone formation at the coronal, middle, and apical thirds. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Sam68 exerts separable effects on cell cycle progression and apoptosis

    Directory of Open Access Journals (Sweden)

    Resnick Ross J

    2004-01-01

    Full Text Available Abstract Background The RNA-binding protein Sam68 has been implicated in a number of cellular processes, including transcription, RNA splicing and export, translation, signal transduction, cell cycle progression and replication of the human immunodeficiency virus and poliovirus. However, the precise impact it has on essential cellular functions remains largely obscure. Results In this report we show that conditional overexpression of Sam68 in fibroblasts results in both cell cycle arrest and apoptosis. Arrest in G1 phase of the cell cycle is associated with decreased levels of cyclins D1 and E RNA and protein, resulting in dramatically reduced Rb phosphorylation. Interestingly, cell cycle arrest does not require the specific RNA binding ability of Sam68. In marked contrast, induction of apoptosis by Sam68 absolutely requires a fully-functional RNA binding domain. Moreover, the anti-cancer agent trichostatin A potentiates Sam68-driven apoptosis. Conclusions For the first time we have shown that Sam68, an RNA binding protein with multiple apparent functions, exerts functionally separable effects on cell proliferation and survival, dependent on its ability to bind specifically to RNA. These findings shed new light on the ability of signal transducing RNA binding proteins to influence essential cell function. Moreover, the ability of a class of anti-cancer therapeutics to modulate its ability to promote apoptosis suggests that Sam68 status may impact some cancer treatments.

  16. Neuroprotective effects of Polygonum multiflorum extract against glutamate-induced oxidative toxicity in HT22 hippocampal cells.

    Science.gov (United States)

    Kim, Ha Neui; Kim, Yu Ri; Jang, Ji Yeon; Choi, Young Whan; Baek, Jin Ung; Hong, Jin Woo; Choi, Yung Hyun; Shin, Hwa Kyoung; Choi, Byung Tae

    2013-10-28

    Dried roots of Polygonum multiflorum have traditionally been used in the retarding of aging process in East Asian countries and its extracts exhibit anti-oxidative activities. Neuroprotective effects of ethyl acetate extract from Polygonum multiflorum (EEPM) were investigated against glutamate-induced oxidative cell death in HT22 hippocampal cells. Cell viability, cytotoxicity, morphological, flow cytometry, and Western blot assays were performed in order to observe alterations of neuronal cell survival or death related pathways. Pretreatment with EEPM resulted in significantly decreased glutamate-induced neurotoxicity and also resulted in drastically inhibited glutamate-induced apoptotic and necrotic neuronal death. To elucidate possible pathways of neuroprotection by EEPM, we explored the activation of mitogen activated protein kinases (MAPKs), phosphatidylinositol-3-kinase, and cAMP responsive element binding protein (CREB). Treatment with glutamate alone led to activation of extracellular regulated kinase (ERK), Jun N-terminal kinase, and p38 during the late phase after glutamate exposure, but pretreatment with EEPM resulted in significantly attenuated activation of these proteins. Pretreatment with EEPM resulted in increased activation of CREB. The specific inhibitors of ERK and p38, PD98059 and SB203580, abrogated the neuroprotective effects of EEPM. When we evaluated calpain I and striatal-enriched protein tyrosine phosphatase (STEP), active form of calpain I was significantly increased after glutamate exposure, and, along with this, active form of STEP showed a decrease. Pretreatment with EEPM resulted in significant recovery of pro-calpain I and active form of STEP caused by glutamate. Co-treatment with calpain inhibitor ALLN and EEPM had a synergistic effect on neuronal death and contributed to blockade of activation of both ERK and p38 with increased activation of CREB. These results suggest that Polygonum multiflorum extract may have neuroprotective

  17. Cellular and molecular mechanisms involved in the neuroprotective effects of VEGF on motoneurons

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    Jerònia eLladó

    2013-10-01

    Full Text Available Vascular endothelial growth factor (VEGF, originally described as a factor with a regulatory role in vascular growth and development, it is also known for its direct effects on neuronal cells. The discovery in the past decade that transgenic mice expressing reduced levels of VEGF developed late-onset motoneuron pathology, reminiscent of amyotrophic lateral sclerosis (ALS, opened a new field of research on this disease. VEGF has been shown to protect motoneurons from excitotoxic death, which is a relevant mechanism involved in motoneuron degeneration in ALS. Thus, VEGF delays motoneuron degeneration and increases survival in animal models of ALS. VEGF exerts its anti-excitotoxic effects on motoneurons through molecular mechanisms involving the VEGF receptor-2 resulting in the activation of the PI3-K/Akt signaling pathway, upregulation of GluR2 subunit of AMPA receptors, inhibition of p38MAPK and induction of the anti-apoptotic molecule Bcl-2. In addition, VEGF acts on astrocytes to reduce astroglial activation and to induce the release of growth factors. The potential use of VEGF as a therapeutic tool in ALS is counteracted by its vascular effects and by its short effective time frame. More studies are needed to assess the optimal isoform, route of administration and time frame for using VEGF in the treatment of ALS.

  18. Enzyme-treated asparagus extract promotes expression of heat shock protein and exerts antistress effects.

    Science.gov (United States)

    Ito, Tomohiro; Maeda, Takahiro; Goto, Kazunori; Miura, Takehito; Wakame, Koji; Nishioka, Hiroshi; Sato, Atsuya

    2014-03-01

    A novel enzyme-treated asparagus extract (ETAS) has been developed as a functional material produced from asparagus stem. Studies were conducted to determine the effect of ETAS on heat shock protein 70 (HSP70) expression and alleviation of stress. HeLa cells were treated with ETAS, and HSP70 mRNA and protein levels were measured using a reverse transcription-polymerase chain reaction (RT-PCR) assay and an enzyme-linked immunosorbent assay (ELISA), respectively. ETAS showed significant increases in HSP70 mRNA at more than 0.125 mg/mL and the protein at more than 1.0 mg/mL. The antistress effect was evaluated in a murine sleep-deprivation model. A sleep-deprivation stress load resulted in elevation of blood corticosterone and lipid peroxide concentrations, while supplementation with ETAS at 200 and 1000 mg/kg body weight was associated with significantly reduced levels of both stress markers, which were in the normal range. The HSP70 protein expression level in mice subjected to sleep-deprivation stress and supplemented with ETAS was significantly enhanced in stomach, liver, and kidney, compared to ETAS-untreated mice. A preliminary and small-sized human study was conducted among healthy volunteers consuming up to 150 mg/d of ETAS daily for 7 d. The mRNA expression of HSP70 in peripheral leukocytes was significantly elevated at intakes of 100 or 150 mg/d, compared to their baseline levels. Since HSP70 is known to be a stress-related protein and its induction leads to cytoprotection, the present results suggest that ETAS might exert antistress effects under stressful conditions, resulting from enhancement of HSP70 expression. © 2014 Institute of Food Technologists®

  19. Timing Effect on Training-Session Rating of Perceived Exertion in Top-Class Soccer Referees.

    Science.gov (United States)

    Castagna, Carlo; Bizzini, Mario; Póvoas, Susana Cristina Araújo; D'Ottavio, Stefano

    2017-10-01

    To examine the effect of recall timing on training-session rating of perceived exertion (sRPE) in a population of athletes well familiarized with the method and procedures during a 5-d training microcycle. Fifty-one top-class field referees (FRs) (age 38.4 ± 3.3 y, height 181 ± 5.6 cm, body mass 76.8 ± 6.8 kg, body-mass index 23.4 ± 1.7 kg/m 2 , body fat 20.4% ± 3.6%, international refereeing experience 5 ± 3.5 y) from 43 national football associations worldwide, preselected by the FIFA refereeing department for officiating during the FIFA World Cup 2014 Brazil, volunteered for this study. The FRs were randomly allocated into 3 assessment groups (n = 17 each), defined according to the timing of the sRPE, ie, immediately at the end of or 30 min or 7 h after the training sessions' end. The CR10 Borg scale was used to rate the training sessions (n = 5). All FRs again rated each training session of the 5-d training microcycle on the next morning (~20 h after) for confirmation (absolute and relative reliability). No significant timing effect was found between or within groups. Relative reliability ranged from large to very large with trivial within- and between-groups differences. This study showed no effect of recall timing on postexercise RPE when well-familiarized athletes are submitted to training during a weekly microcycle. Posttraining RPE was reported to be a reliable subjective measure; however, specific timing is advisable to reduce difference in RPE values.

  20. Triterpenoids and Polysaccharide Fractions of Ganoderma tsugae Exert Different Effects on Antiallergic Activities

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    Miaw-Ling Chen

    2015-01-01

    Full Text Available This study was to investigate antiallergic effects of triterpenoids (Gt-TRE and polysaccharide (Gt-PS extracts from Ganoderma tsugae, using mast cell line RBL-2H3, T cell line EL4, primary T cells, and transfected RAW264.7 macrophage cells. The results showed that histamine secreted from activated RBL-2H3 mast cells was significantly suppressed by Gt-TRE but not Gt-PS. Interleukin- (IL- 4 secreted from activated EL4 cells was significantly suppressed by Gt-TRE but not Gt-PS. Further primary CD4+ T cells cultures also confirmed that Gt-TRE (5~50 µg/mL significantly suppressed Th2 cytokines IL-4 and IL-5 secretions but had no effect on Th1 cytokines IL-2 and interferon (IFN-γ. Gt-PS did not affect IL-4 and IL-5 secretions until higher doses (400, 500 µg/mL and significantly suppressed IFNγ secretions but enhanced IL-2 at these high doses. The reporter gene assay indicated that Gt-TRE inhibited but Gt-PS enhanced the transcriptional activity of NF-κB in activated transfected RAW264.7 cells and transfected EL4 cells. IL-4 secreted by this transfected EL-4 cells was also significantly decreased by Gt-TRE but not by Gt-PS, suggesting that these two fractions may exert different effects on NF-κB related cytokines expression. These data suggested that triterpenoids fraction of Ganoderma tsugae might be the main constituents to alleviate allergic asthma.

  1. Novel small-molecule AMPK activator orally exerts beneficial effects on diabetic db/db mice

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yuan-Yuan; Yu, Li-Fang; Zhang, Li-Na; Qiu, Bei-Ying; Su, Ming-Bo; Wu, Fang; Chen, Da-Kai; Pang, Tao; Gu, Min; Zhang, Wei; Ma, Wei-Ping; Jiang, Hao-Wen; Li, Jing-Ya, E-mail: jyli@mail.shcnc.ac.cn; Nan, Fa-Jun, E-mail: fjnan@mail.shcnc.ac.cn; Li, Jia, E-mail: jli@mail.shcnc.ac.cn

    2013-12-01

    AMP-activated protein kinase (AMPK), which is a pivotal guardian of whole-body energy metabolism, has become an attractive therapeutic target for metabolic syndrome. Previously, using a homogeneous scintillation proximity assay, we identified the small-molecule AMPK activator C24 from an optimization based on the original allosteric activator PT1. In this paper, the AMPK activation mechanism of C24 and its potential beneficial effects on glucose and lipid metabolism on db/db mice were investigated. C24 allosterically stimulated inactive AMPK α subunit truncations and activated AMPK heterotrimers by antagonizing autoinhibition. In primary hepatocytes, C24 increased the phosphorylation of AMPK downstream target acetyl-CoA carboxylase dose-dependently without changing intracellular AMP/ATP ratio, indicating its allosteric activation in cells. Through activating AMPK, C24 decreased glucose output by down-regulating mRNA levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) in primary hepatocytes. C24 also decreased the triglyceride and cholesterol contents in HepG2 cells. Due to its improved bioavailability, chronic oral treatment with multiple doses of C24 significantly reduced blood glucose and lipid levels in plasma, and improved the glucose tolerance of diabetic db/db mice. The hepatic transcriptional levels of PEPCK and G6Pase were reduced. These results demonstrate that this orally effective activator of AMPK represents a novel approach to the treatment of metabolic syndrome. - Highlights: • C24 activates AMPK through antagonizing autoinhibition within α subunit. • C24 activates AMPK in hepatocytes and decreases glucose output via AMPK. • C24 exerts beneficial effects on diabetic db/db mice. • C24 represents a novel therapeutic for treatment of metabolic syndrome.

  2. Novel small-molecule AMPK activator orally exerts beneficial effects on diabetic db/db mice

    International Nuclear Information System (INIS)

    Li, Yuan-Yuan; Yu, Li-Fang; Zhang, Li-Na; Qiu, Bei-Ying; Su, Ming-Bo; Wu, Fang; Chen, Da-Kai; Pang, Tao; Gu, Min; Zhang, Wei; Ma, Wei-Ping; Jiang, Hao-Wen; Li, Jing-Ya; Nan, Fa-Jun; Li, Jia

    2013-01-01

    AMP-activated protein kinase (AMPK), which is a pivotal guardian of whole-body energy metabolism, has become an attractive therapeutic target for metabolic syndrome. Previously, using a homogeneous scintillation proximity assay, we identified the small-molecule AMPK activator C24 from an optimization based on the original allosteric activator PT1. In this paper, the AMPK activation mechanism of C24 and its potential beneficial effects on glucose and lipid metabolism on db/db mice were investigated. C24 allosterically stimulated inactive AMPK α subunit truncations and activated AMPK heterotrimers by antagonizing autoinhibition. In primary hepatocytes, C24 increased the phosphorylation of AMPK downstream target acetyl-CoA carboxylase dose-dependently without changing intracellular AMP/ATP ratio, indicating its allosteric activation in cells. Through activating AMPK, C24 decreased glucose output by down-regulating mRNA levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) in primary hepatocytes. C24 also decreased the triglyceride and cholesterol contents in HepG2 cells. Due to its improved bioavailability, chronic oral treatment with multiple doses of C24 significantly reduced blood glucose and lipid levels in plasma, and improved the glucose tolerance of diabetic db/db mice. The hepatic transcriptional levels of PEPCK and G6Pase were reduced. These results demonstrate that this orally effective activator of AMPK represents a novel approach to the treatment of metabolic syndrome. - Highlights: • C24 activates AMPK through antagonizing autoinhibition within α subunit. • C24 activates AMPK in hepatocytes and decreases glucose output via AMPK. • C24 exerts beneficial effects on diabetic db/db mice. • C24 represents a novel therapeutic for treatment of metabolic syndrome

  3. Exploring the neuroprotective effects of modafinil in a marmoset Parkinson model with immunohistochemistry, magnetic resonance imaging and spectroscopy.

    Science.gov (United States)

    van Vliet, S A M; van Vlieta, S A M; Blezer, E L A; Jongsma, M J; Vanwersch, R A P; Olivier, B; Philippens, I H C H M

    2008-01-16

    Neuroprotective therapeutics stop or slow down the degeneration process in animal models of Parkinson's disease (PD). Neuronal survival in PD animal models is often measured by immunohistochemistry. However, dynamic changes in the pathology of the brain cannot be explored with this technique. Application of proton magnetic resonance (MR) imaging (MRI) and spectroscopy (MRS) can cover this lacuna as these techniques are non-invasive and can be repeated over time in the same animal. Therefore, the sensitivity of both techniques to measure changes in PD-pathology was explored in an experiment studying the neuroprotective effects of the vigilance enhancer modafinil in a marmoset PD model. Eleven marmoset monkeys were treated with the neurotoxin 1-methyl-1,2,3,6-tetrahydropyridine (MPTP). Six of these 11 animals, simultaneously, received a daily oral dose of modafinil (100 mg/kg) and five received vehicle for 27 days. MR experiments were performed at baseline and 1 and 3.5 weeks after the MPTP intoxication period after which brains were analyzed with immunohistochemistry. Tyrosine hydroxylase immunoreactive (TH-IR) staining of dopamine neurons of the substantia nigra pars compacta confirmed that modafinil was able to partially prevent the MPTP-induced neuronal damage. In MRS, N-acetylaspartate (NAA)/phosphocreatine (tCR) ratios confirmed the protective effect indicating that this is a sensitive measure to detect neuroprotection in the MPTP marmoset model. Furthermore, the number of TH-IR positive neurons and the NAA/tCR ratio were significantly correlated to behavioral observations indicating that the changes measured in the brain are also reflected in the behavior and vice versa.

  4. Assessment of the neuroprotective effects of Lavandula angustifolia extract on the contusive model of spinal cord injury in Wistar rats

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    Gholamreza eKaka

    2016-02-01

    Full Text Available IntroductionSpinal cord injury (SCI involves a primary trauma and secondary cellular processes that can lead to severe damage to the nervous system, resulting in long-term spinal deficits. At the cellular level, SCI causes astrogliosis, of which glial fibrillary acidic protein (GFAP is a major index. ObjectiveThe aim of this study was to investigate the neuroprotective effects of Lavandula angustifolia (Lav on the repair of spinal cord injuries in Wistar rats.Materials and MethodsForty-five female rats were randomly divided into six groups of seven rats each: the intact, sham, control (SCI, Lav 100, Lav 200, and Lav 400 groups. Every week after SCI onset, all animals were evaluated for behavior outcomes by the Basso, Beattie, and Bresnahan (BBB score. H&E staining was performed to examine the lesions post-injury. GFAP expression was assessed for astrogliosis. Somatosensory evoked potential (SEP testing was performed to detect the recovery of neural conduction.Results BBB scores were significantly increased and delayed responses on sensory tests were significantly decreased in the Lav 200 and Lav 400 groups compared to the control group. The greatest decrease of GFAP was evident in the Lav 200 and Lav 400 groups. EMG results showed significant improvement in the hindlimbs in the Lav 200 and Lav 400 groups compared to the control group. Cavity areas significantly decreased and the number of ventral motor neurons significantly increased in the Lav 200 and Lav 400 groups.ConclusionLav at doses of 200 mg/kg and 400 mg/kg can promote structural and functional recovery after SCI. The neuroprotective effects of L. angustifolia can lead to improvement in the contusive model of spinal cord injury in Wistar rats.Keywords Spinal cord injury (SCI; Lavandula angustifolia; neuroprotection; Basso, Beattie, and Bresnahan (BBB; glial fibrillary acidic protein (GFAP; somatosensory evoked potential (SEP

  5. Comparison of Nootropic and Neuroprotective Features of Aryl-Substituted Analogs of Gamma-Aminobutyric Acid.

    Science.gov (United States)

    Tyurenkov, I N; Borodkina, L E; Bagmetova, V V; Berestovitskaya, V M; Vasil'eva, O S

    2016-02-01

    GABA analogs containing phenyl (phenibut) or para-chlorophenyl (baclofen) substituents demonstrated nootropic activity in a dose of 20 mg/kg: they improved passive avoidance conditioning, decelerated its natural extinction, and exerted antiamnestic effect on the models of amnesia provoked by scopolamine or electroshock. Tolyl-containing GABA analog (tolibut, 20 mg/kg) exhibited antiamnestic activity only on the model of electroshock-induced amnesia. Baclofen and, to a lesser extent, tolibut alleviated seizures provoked by electroshock, i.e. both agents exerted anticonvulsant effect. All examined GABA aryl derivatives demonstrated neuroprotective properties on the maximum electroshock model: they shortened the duration of coma and shortened the period of spontaneous motor activity recovery. In addition, these agents decreased the severity of passive avoidance amnesia and behavioral deficit in the open field test in rats exposed to electroshock. The greatest neuroprotective properties were exhibited by phenyl-containing GABA analog phenibut.

  6. Neurotropic and neuroprotective activities of the earthworm peptide Lumbricusin

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    Kim, Dae Hong; Lee, Ik Hwan; Nam, Seung Taek; Hong, Ji; Zhang, Peng [Department of Life Science, College of Natural Science, Daejin University, Pocheon, Gyeonggido 487-711 (Korea, Republic of); Hwang, Jae Sam [Department of Agricultural Biology, National Academy of Agricultural Science, RDA, Suwon 441-707 (Korea, Republic of); Seok, Heon [Department of Biomedical Engineering, Jungwon University, Goesan, Chungcheongbukdo 367-700 (Korea, Republic of); Choi, Hyemin; Lee, Dong Gun [School of Life Sciences, KNU Creative Bioresearch Group (BK21 Plus Program), College of Natural Sciences, Kyungpook National University, Daehak-ro 80, Buk-gu, Daegu 702-701 (Korea, Republic of); Kim, Jae Il [School of Life Sciences, Gwangju Institute of Science and Technology, Oryong-dong, Buk-gu, Gwangju 500-712 (Korea, Republic of); Kim, Ho, E-mail: hokim@daejin.ac.kr [Department of Life Science, College of Natural Science, Daejin University, Pocheon, Gyeonggido 487-711 (Korea, Republic of)

    2014-06-06

    Highlights: • 11-mer peptide Lumbricusin, a defensin like peptide, is isolated from earthworm. • We here demonstrated that Lumbricusin has neurotropic and neuroprotective effects. • p27 degradation by Lumbricusin mediates effects of Lumbricusin on neuronal cells. - Abstract: We recently isolated a polypeptide from the earthworm Lumbricus terrestris that is structurally similar to defensin, a well-known antibacterial peptide. An 11-mer antibacterial peptide (NH{sub 2}-RNRRWCIDQQA), designated Lumbricusin, was synthesized based on the amino acid sequence of the isolated polypeptide. Since we previously reported that CopA3, a dung beetle peptide, enhanced neuronal cell proliferation, we here examined whether Lumbricusin exerted neurotropic and/or neuroprotective effects. Lumbricusin treatment induced a time-dependent increase (∼51%) in the proliferation of human neuroblastoma SH-SY5Y cells. Lumbricusin also significantly inhibited the apoptosis and decreased viability induced by treatment with 6-hydroxy dopamine, a Parkinson’s disease-mimicking agent. Immunoblot analyses revealed that Lumbricusin treatment increased ubiquitination of p27{sup Kip1} protein, a negative regulator of cell-cycle progression, in SH-SY5Y cells, and markedly promoted its degradation. Notably, adenoviral-mediated over-expression of p27{sup Kip1} significantly blocked the antiapoptotic effect of Lumbricusin in 6-hydroxy dopamine-treated SH-SY5Y cells. These results suggest that promotion of p27{sup Kip1} degradation may be the main mechanism underlying the neuroprotective and neurotropic effects of Lumbricusin.

  7. Neurotropic and neuroprotective activities of the earthworm peptide Lumbricusin

    International Nuclear Information System (INIS)

    Kim, Dae Hong; Lee, Ik Hwan; Nam, Seung Taek; Hong, Ji; Zhang, Peng; Hwang, Jae Sam; Seok, Heon; Choi, Hyemin; Lee, Dong Gun; Kim, Jae Il; Kim, Ho

    2014-01-01

    Highlights: • 11-mer peptide Lumbricusin, a defensin like peptide, is isolated from earthworm. • We here demonstrated that Lumbricusin has neurotropic and neuroprotective effects. • p27 degradation by Lumbricusin mediates effects of Lumbricusin on neuronal cells. - Abstract: We recently isolated a polypeptide from the earthworm Lumbricus terrestris that is structurally similar to defensin, a well-known antibacterial peptide. An 11-mer antibacterial peptide (NH 2 -RNRRWCIDQQA), designated Lumbricusin, was synthesized based on the amino acid sequence of the isolated polypeptide. Since we previously reported that CopA3, a dung beetle peptide, enhanced neuronal cell proliferation, we here examined whether Lumbricusin exerted neurotropic and/or neuroprotective effects. Lumbricusin treatment induced a time-dependent increase (∼51%) in the proliferation of human neuroblastoma SH-SY5Y cells. Lumbricusin also significantly inhibited the apoptosis and decreased viability induced by treatment with 6-hydroxy dopamine, a Parkinson’s disease-mimicking agent. Immunoblot analyses revealed that Lumbricusin treatment increased ubiquitination of p27 Kip1 protein, a negative regulator of cell-cycle progression, in SH-SY5Y cells, and markedly promoted its degradation. Notably, adenoviral-mediated over-expression of p27 Kip1 significantly blocked the antiapoptotic effect of Lumbricusin in 6-hydroxy dopamine-treated SH-SY5Y cells. These results suggest that promotion of p27 Kip1 degradation may be the main mechanism underlying the neuroprotective and neurotropic effects of Lumbricusin

  8. Neuroprotective effect of licochalcone A against oxygen-glucose deprivation/reperfusion in rat primary cortical neurons by attenuating oxidative stress injury and inflammatory response via the SIRT1/Nrf2 pathway.

    Science.gov (United States)

    Liu, Xiaohong; Ma, Ying; Wei, Xiaodi; Fan, Ting

    2018-04-01

    Perinatal hypoxic-ischemic encephalopathy (HIE) is a leading cause of neonatal death and neurological disability. Oxidative stress and neuroinflammation are typical pathogenic factors of HIE. Licochalcone A (LCA) exerts various biological properties, including anti-inflammatory and antioxidant activities. However, no data have been reported to elucidate the role of LCA in the development of HIE. In the present study, primary cultured rat cortical neurons were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro to simulate the in vivo situation of neonatal HIE. Interestingly, LCA significantly antagonized cell injury under OGD/R by increasing cell survival, inhibiting lactate dehydrogenase (LDH) release and cell apoptosis. Furthermore, treatment with LCA suppressed oxidative stress by decreasing reactive oxygen species (ROS) production and malondialdehyde (MDA) content, and increasing superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities in primary rat cortical neurons after OGD/R. LCA stimulation also restrained OGD/R-triggered increase in pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production. Importantly, LCA treatment effectively counteracts OGD/R-mediated downregulation of silent information regulator 1 (SIRT1), nuclear factor erythroid2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1), and upregulation of nuclear factor kappa B p65 (NF-κB p65). Moreover, administration with SIRT1 inhibitor EX527 partly abolished LCA-induced neuroprotective effects on rat cortical neurons exposed to OGD/R. In conclusion, our study indicates that LCA exerts a neuroprotective effect against OGD/R-induced neuronal injury in rat primary cortical neurons, suggesting that LCA might act as a candidate therapeutic target drug used for HIE and related diseases. © 2017 Wiley Periodicals, Inc.

  9. The effects of superset configuration on kinetic, kinematic, and perceived exertion in the barbell bench press.

    Science.gov (United States)

    Weakley, Jonathon Js; Till, Kevin; Read, Dale B; Phibbs, Padraic J; Roe, Gregory; Darrall-Jones, Joshua; Jones, Ben L

    2017-08-04

    Training that is efficient and effective is of great importance to an athlete. One method of improving efficiency is by incorporating supersets into resistance training routines. However, the structuring of supersets is still unexplored. Therefore, the purpose of this study was to assess the effects of agonist-antagonist (A-A), alternate peripheral (A-P), and similar biomechanical (SB) superset configurations on rate of perceived exertion (RPE), kinetic and kinematic changes during the bench press. 10 subjects performed resistance training protocols in a randomized-crossover design, with magnitude-based inferences assessing changes/differences within and between protocols. Changes in RPE were very likely and almost certainly greater in the A-P and SB protocols when compared with the A-A, while all superset protocols had very likely to almost certain reductions in mean velocity and power from baseline. Reductions in mean velocity and power were almost certainly greater in the SB protocol, with differences between the A-A and A-P protocols being unclear. Decreases in peak force were likely and almost certain in the A-A and SB protocols respectively, with changes in A-P being unclear. Differences between these protocols showed likely greater decreases in SB peak forces when compared to A-A, with all other superset comparisons being unclear. This study demonstrates the importance of exercise selection when incorporating supersets into a training routine. It is suggested that the practitioner uses A-A supersets when aiming to improve training efficiency and minimize reductions in kinetic and kinematic output of the agonist musculature while completing the barbell bench press.

  10. Effect of Complex Working Conditions on Nurses Who Exert Coercive Measures in Forensic Psychiatric Care.

    Science.gov (United States)

    Gustafsson, Niclas; Salzmann-Erikson, Martin

    2016-09-01

    Nurses who exert coercive measures on patients within psychiatric care are emotionally affected. However, research on their working conditions and environment is limited. The purpose of the current study was to describe nurses' experiences and thoughts concerning the exertion of coercive measures in forensic psychiatric care. The investigation was a qualitative interview study using unstructured interviews; data were analyzed with inductive content analysis. Results described participants' thoughts and experiences of coercive measures from four main categories: (a) acting against the patients' will, (b) reasoning about ethical justifications, (c) feelings of compassion, and (d) the need for debriefing. The current study illuminates the working conditions of nurses who exert coercive measures in clinical practice with patients who have a long-term relationship with severe symptomatology. The findings are important to further discuss how nurses and leaders can promote a healthier working environment. [Journal of Psychosocial Nursing and Mental Health Services, 54(9), 37-43.]. Copyright 2016, SLACK Incorporated.

  11. Neuro-protective effects of growth hormone (GH) after hypoxia-ischemia injury in embryonic chicken cerebellum.

    Science.gov (United States)

    Alba-Betancourt, Clara; Luna-Acosta, José Luis; Ramírez-Martínez, Candy Elizabeth; Avila-González, Daniela; Granados-Ávalos, Estefany; Carranza, Martha; Martínez-Coria, Hilda; Arámburo, Carlos; Luna, Maricela

    2013-03-01

    Neuroprotection is a mechanism within the central nervous system (CNS) that protects neurons from damage as a result of a severe insult. It is known that growth hormone (GH) is involved in cell survival and may inhibit apoptosis in several cell types, including those of the CNS. Both GH and GH-receptor (GHR) genes are expressed in the cerebellum. Thus, we investigated the possible neuroprotective role of GH in this organ, which is very sensitive to hypoxic/ischemic conditions. Endogenous GH levels increased in the brain and cerebellum (30% and 74%, respectively) of 15-day-old chicken embryos exposed to hypoxia during 24h compared to normoxia. In primary embryonic cerebellar neuron cultures treated under hypoxia (0.5% O(2)) and low glucose (1g/L) conditions (HLG) for 1h, GH levels increased 1.16-fold compared to the control. The addition of 1nM recombinant chicken GH (rcGH) to cultures during HLG increased cell viability (1.7-fold) and the expression of Bcl-2 (1.67-fold); in contrast the caspase-3 activity and the proportion of apoptotic cells decreased (37% and 54.2%, respectively) compared to HLG. rcGH activated the PI3K/Akt pathway both under normoxic and HLG conditions, increasing the proportion of phosphorylated Akt (1.7- and 1.4-fold, respectively). These effects were abolished by wortmannin and by immunoneutralization, indicating that GH acts through this signaling pathway. Furthermore, the 15-kDa GH variant (10nM) significantly increased cell viability and decreased caspase-3 activity during HLG condition. Thus GH may act as a paracrine/autocrine neuroprotective factor that preserves cellular viability and inhibits apoptotic cell death. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Neuroprotective effects of Dioscorea opposita on scopolamine-induced memory impairment in in vivo behavioral tests and in vitro assays.

    Science.gov (United States)

    Yang, Min Hye; Yoon, Kee Dong; Chin, Young-Won; Park, Ju Hyun; Kim, Seung Hyun; Kim, Young Choong; Kim, Jinwoong

    2009-01-12

    Plants belong to the genus Dioscorea have long been used as edible tuber crops in many tropical and subtropical areas and as a traditional herbal medicine in oriental countries including China, Japan and Korea. In this study, in vivo and in vitro tests were carried out to evaluate the cognitive enhancing effects of CHCl(3)-soluble extract from Dioscorea opposita against scopolamine-induced amnesic mice and glutamate- and H(2)O(2)-treated cortical neurons of rats. Acute treatment (200 mg/kg body weight, p.o.) and 10 days' daily administration (50 mg/kg body weight, p.o.) of CHCl(3)-soluble extract showed significant spatial learning and memory improvement on mice. Furthermore, the neuroprotective effects on glutamate- and H(2)O(2)-induced neurotoxicity in primary cultured cortical neurons of rats were assessed. Pretreatment with the extract was found to impart significant protection against neurotoxicity. These in vivo and in vitro results suggest that the Dioscorea opposita has neuroprotective effects on memory impairment related neurodegenerative diseases.

  13. Improvement in regional CBF by L-serine contributes to its neuroprotective effect in rats after focal cerebral ischemia.

    Directory of Open Access Journals (Sweden)

    Tao-Jie Ren

    Full Text Available To investigate the mechanisms underlying the neuroprotective effect of L-serine, permanent focal cerebral ischemia was induced by occlusion of the middle cerebral artery while monitoring cerebral blood flow (CBF. Rats were divided into control and L-serine-treated groups after middle cerebral artery occlusion. The neurological deficit score and brain infarct volume were assessed. Nissl staining was used to quantify the cortical injury. L-serine and D-serine levels in the ischemic cortex were analyzed with high performance liquid chromatography. We found that L-serine treatment: 1 reduced the neurological deficit score, infarct volume and cortical neuron loss in a dose-dependent manner; 2 improved CBF in the cortex, and this effect was inhibited in the presence of apamin plus charybdotoxin while the alleviation of both neurological deficit score and infarct volume was blocked; and 3 increased the amount of L-serine and D-serine in the cortex, and inhibition of the conversion of L-serine into D-serine by aminooxyacetic acid did not affect the reduction of neurological deficit score and infarct volume by L-serine. In conclusion, improvement in regional CBF by L-serine may contribute to its neuroprotective effect on the ischemic brain, potentially through vasodilation which is mediated by the small- and intermediate-conductance Ca(2+-activated K(+ channels on the cerebral blood vessel endothelium.

  14. Neuroprotective effects of salidroside through PI3K/Akt pathway activation in Alzheimer’s disease models

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    Zhang B

    2016-04-01

    Full Text Available Bei Zhang,1,2 Ying Wang,1 Hui Li,1 Ran Xiong,1 Zongbo Zhao,1 Xingkun Chu,2 Qiongqiong Li,1 Suya Sun,1 Shengdi Chen1,2 1Department of Neurology, Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Laboratory of Neurodegenerative Diseases, The Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China Abstract: Alzheimer’s disease (AD is a devastating neurodegenerative disorder characterized by deposits of aggregated amyloid-β (Aβ peptide and neurofibrillary tangles in the brain parenchyma. Despite considerable research to elucidate the pathological mechanisms and identify therapeutic strategies for AD, effective treatments are still lacking. In the present study, we found that salidroside (Sal, a phenylpropanoid glycoside isolated from Rhodiola rosea L., can protect against Aβ-induced neurotoxicity in four transgenic Drosophila AD models. Both longevity and locomotor activity were improved in Sal-fed Drosophila. Sal also decreased Aβ levels and Aβ deposition in brain and ameliorated toxicity in Aβ-treated primary neuronal culture. The neuroprotective effect of Sal was associated with upregulated phosphatidylinositide 3-kinase (PI3K/Akt signaling. Our findings identify a compound that may possess potential therapeutic benefits for AD and other forms of neurodegeneration. Keywords: Alzheimer’s disease, amyloid-β, salidroside, Drosophila, neuroprotective effect

  15. Marked over expression of uncoupling protein-2 in beta cells exerts minor effects on mitochondrial metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Hals, Ingrid K., E-mail: ingrid.hals@ntnu.no [Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim (Norway); Ogata, Hirotaka; Pettersen, Elin [Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim (Norway); Ma, Zuheng; Bjoerklund, Anneli [Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm (Sweden); Skorpen, Frank [Department of Laboratory Medicine, NTNU, Trondheim (Norway); Egeberg, Kjartan Wollo [Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim (Norway); Grill, Valdemar [Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim (Norway); Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm (Sweden)

    2012-06-29

    positive findings. A fourfold induction of UCP-2 was required to exert minor metabolic effects. These findings question an impact of moderately elevated UCP-2 levels in beta cells as seen in diabetes.

  16. Ethanol-Extracted Brazilian Propolis Exerts Protective Effects on Tumorigenesis in Wistar Hannover Rats.

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    Anna Kakehashi

    Full Text Available The present study was conducted over a course of 104 weeks to estimate the carcinogenicity of ethanol-extracted Brazilian green propolis (EEP. Groups of 50 male and 50 female Wistar Hannover rats, 6-week-old at commencement were exposed to EEP at doses of 0, 0.5 or 2.5% in the diet. Survival rates of 0.5% and 2.5% EEP-treated male and female rats, respectively, were significantly higher than those of respective control groups. Overall histopathological evaluation of neoplasms in rat tissues after 2 years showed no significant increase of tumors or preneoplastic lesions in any organ of animals administered EEP. Significantly lower incidences of pituitary tumors in 0.5% EEP male and 2.5% EEP female groups, malignant lymphoma/leukemia in both 2.5% EEP-treated males and females and total thyroid tumors in 0.5% EEP male group were found. Administration of EEP caused significant decreases of lymphoid hyperplasia of the thymus and lymph nodes in 2.5% EEP-treated rats, tubular cell hyperplasia of kidneys in all EEP groups, and cortical hyperplasia of adrenals in EEP-treated females. In the blood, significant reduction of neutrophils in all EEP-treated males and band neutrophils in 2.5% EEP-treated females was found indicating lower levels of inflammation. Total cholesterol and triglicerides levels were significantly lower in the blood of 2.5% EEP-treated female rats. In conclusion, under the conditions of the 2-year feeding experiment, EEP was not carcinogenic, did not induce significant histopathological changes in any organ, and further exerted anti-inflammatory and antitumorigenic effects resulting in increase of survival of Wistar Hannover rats.

  17. Adiponectin and plant-derived mammalian adiponectin homolog exert a protective effect in murine colitis

    KAUST Repository

    Arsenescu, Violeta

    2011-04-11

    Background: Hypoadiponectinemia has been associated with states of chronic inflammation in humans. Mesenteric fat hypertrophy and low adiponectin have been described in patients with Crohn\\'s disease. We investigated whether adiponectin and the plant-derived homolog, osmotin, are beneficial in a murine model of colitis. Methods: C57BL/6 mice were injected (i.v.) with an adenoviral construct encoding the full-length murine adiponectin gene (AN+DSS) or a reporter-LacZ (Ctr and V+DSS groups) prior to DSS colitis protocol. In another experiment, mice with DSS colitis received either osmotin (Osm+DSS) or saline (DSS) via osmotic pumps. Disease progression and severity were evaluated using body weight, stool consistency, rectal bleeding, colon lengths, and histology. In vitro experiments were carried out in bone marrow-derived dendritic cells. Results: Mice overexpressing adiponectin had lower expression of proinflammatory cytokines (TNF, IL-1β), adipokines (angiotensin, osteopontin), and cellular stress and apoptosis markers. These mice had higher levels of IL-10, alternative macrophage marker, arginase 1, and leukoprotease inhibitor. The plant adiponectin homolog osmotin similarly improved colitis outcome and induced robust IL-10 secretion. LPS induced a state of adiponectin resistance in dendritic cells that was reversed by treatment with PPARγ agonist and retinoic acid. Conclusion: Adiponectin exerted protective effects during murine DSS colitis. It had a broad activity that encompassed cytokines, chemotactic factors as well as processes that assure cell viability during stressful conditions. Reducing adiponectin resistance or using plant-derived adiponectin homologs may become therapeutic options in inflammatory bowel disease. © 2011 Springer Science+Business Media, LLC.

  18. Prostacyclin mediates endothelial COX-2-dependent neuroprotective effects during excitotoxic brain injury

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    An Y

    2014-05-01

    Full Text Available Ying An,1,2 Natalya Belevych,1,2 Yufen Wang,1,2 Hao Zhang,1 Jason S Nasse,3 Harvey Herschman,4 Qun Chen,1,2 Andrew Tarr,1,2 Xiaoyu Liu,1,2 Ning Quan1,21Institute for Behavior Medicine Research, 2Department of Oral Biology, College of Dentistry, 3Neuroscience Graduate Studies Program, The Ohio State University, Columbus, OH, USA; 4Department of Molecular and Medical Pharmacology, UCLA, Los Angeles, CA, USAAbstract: In a previous study, we found that intracerebral administration of excitotoxin (RS-(tetrazole-5yl glycine caused increased neural damage in the brain in an endothelial COX-2 deleted mouse line (Tie2Cre COX-2flox/flox. In this study, we investigated whether prostacyclin might mediate this endothelial COX-2-dependent neuroprotection. Administration of excitotoxin into the striatum induced the production of prostacyclin (PGI2 in wild type, but not in endothelial COX-2 deleted mice. Inhibition of PGI2 synthase exacerbated brain lesions induced by the excitotoxin in wild type, but not in endothelial COX-2 deleted mice. Administration of a PGI2 agonist reduced neural damage in both wild type and endothelial COX-2 deleted mice. Increased PGI2 synthase expression was found in infiltrating neutrophils. In an ex vivo assay, PGI2 reduced the excitotoxin-induced calcium influx into neurons, suggesting a cellular mechanism for PGI2 mediated neuroprotection. These results reveal that PGI2 mediates endothelial COX-2 dependent neuroprotection.Keywords: neural injury, prostaglandins, neutrophil, conditional COX-2 deletion, PGI2

  19. Chemical and pharmacological evaluation of the effectiveness of enalapril maleate in exertional angina pectoris in elderly and senile patients

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    I. M. Belay

    2013-06-01

    Full Text Available The long-term administration of enalapril maleate in complex therapy of exertional angina pectoris in elderly persons showed antiischemic, antiarrhythmic effects of angiotensin converting enzyme inhibitors. Using chemical-pharmacological analysis the administration of enalapril against the background of basic therapy in patients with ischemic heart disease was grounded.

  20. Fluoxetine Exerts Age-Dependent Effects on Behavior and Amygdala Neuroplasticity in the Rat

    NARCIS (Netherlands)

    Homberg, J.R.; Olivier, J.D.A.; Blom, T.; Arentsen, T.; Brunschot, C. van; Schipper, P.; Korte-Bouws, G.A.; Luijtelaar, E.L.J.M. van; Reneman, L.

    2011-01-01

    The selective serotonin reuptake inhibitor (SSRI) Prozac® (fluoxetine) is the only registered antidepressant to treat depression in children and adolescents. Yet, while the safety of SSRIs has been well established in adults, serotonin exerts neurotrophic actions in the developing brain and thereby

  1. Fluoxetine Exerts Age-Dependent Effects on Behavior and Amygdala Neuroplasticity in the Rat

    NARCIS (Netherlands)

    Homberg, J.R.; Olivier, J.D.A.; Blom, T.; Arentsen, T.; van Brunschot, C.; Schipper, P.; Korte-Bouws, G.; van Luijtelaar, G.; Reneman, L.

    2011-01-01

    The selective serotonin reuptake inhibitor (SSRI) Prozac (R) (fluoxetine) is the only registered antidepressant to treat depression in children and adolescents. Yet, while the safety of SSRIs has been well established in adults, serotonin exerts neurotrophic actions in the developing brain and

  2. Fluoxetine exerts age-dependent effects on behavior and amygdala neuroplasticity in the rat.

    NARCIS (Netherlands)

    Homberg, J.R.; Olivier, J.D.A.; Blom, T.; Arentsen, T.; Brunschot, C. van; Schipper, P.; Korte-Bouws, G.A.; Luijtelaar, E.L.J.M. van; Reneman, L.

    2011-01-01

    The selective serotonin reuptake inhibitor (SSRI) Prozac(R) (fluoxetine) is the only registered antidepressant to treat depression in children and adolescents. Yet, while the safety of SSRIs has been well established in adults, serotonin exerts neurotrophic actions in the developing brain and

  3. Neuroprotective effect of the active components of three Chinese herbs on brain iron load in a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Dong, Xian-Hui; Gao, Wei-Juan; Kong, Wei-Na; Xie, Hong-Lin; Peng, Yan; Shao, Tie-Mei; Yu, Wen-Guo; Chai, Xi-Qing

    2015-04-01

    Alzheimer's disease (AD) is a neurodegenerative brain disorder and the most common cause of dementia. New treatments for AD are required due to its increasing prevalence in aging populations. The present study evaluated the effects of the active components of Epimedium , Astragalus and Radix Puerariae on learning and memory impairment, β-amyloid (Aβ) reduction and brain iron load in an APP swe /PS1 ΔE9 transgenic mouse model of AD. Increasing evidence indicates that a disturbance of normal iron homeostasis may contribute to the pathology of AD. However, the underlying mechanisms resulting in abnormal iron load in the AD brain remain unclear. It has been hypothesized that the brain iron load is influenced by the deregulation of certain proteins associated with brain iron metabolism, including divalent metal transporter 1 (DMT1) and ferroportin 1 (FPN1). The present study investigated the effects of the active components of Epimedium , Astragalus and Radix Puerariae on the expression levels of DMT1 and FPN1. The treatment with the active components reduced cognitive deficits, inhibited Aβ plaque accumulation, reversed Aβ burden and reduced the brain iron load in AD model mice. A significant increase was observed in the levels of DMT1-iron-responsive element (IRE) and DMT1-nonIRE in the hippocampus of the AD mouse brain, which was reduced by treatment with the active components. In addition, the levels of FPN1 were significantly reduced in the hippocampus of the AD mouse brain compared with those of control mice, and these levels were increased following treatment with the active components. Thus, the present study indicated that the active components of Epimedium , Astragalus and Radix Puerariae may exert a neuroprotective effect against AD by reducing iron overload in the AD brain and may provide a novel approach for the development of drugs for the treatment of AD.

  4. Oxicam structure in non-steroidal anti-inflammatory drugs is essential to exhibit Akt-mediated neuroprotection against 1-methyl-4-phenyl pyridinium-induced cytotoxicity.

    Science.gov (United States)

    Tasaki, Yoshikazu; Yamamoto, Joe; Omura, Tomohiro; Noda, Toshihiro; Kamiyama, Naoya; Yoshida, Koichi; Satomi, Machiko; Sakaguchi, Tomoki; Asari, Masaru; Ohkubo, Tomoko; Shimizu, Keiko; Matsubara, Kazuo

    2012-02-15

    In the treatment of Parkinson's disease, potent disease-modifying drugs are still needed to halt progressive dopaminergic neurodegeneration. We have previously shown that meloxicam, an oxicam non-steroidal anti-inflammatory drug (NSAID), elicits a potent neuroprotective effect against 1-methyl-4-phenyl pyridinium (MPP(+))-induced toxicity in human dopaminergic SH-SY5Y neuroblastoma cells. This cyclooxygenase-independent neuroprotection of meloxicam is mediated via the phosphatidylinositol 3-kinase (PI3K)/Akt pathway; however, the specific chemical structure involved in inducing neuroprotection remains unresolved. In this study, we therefore investigated the structure-specific for eliciting the neuroprotective effect by examining a series of NSAIDs against MPP(+) toxicity in SH-SY5Y cells. Three oxicam-bearing NSAIDs showed potent neuroprotective effects, although none of the other 10 oxicam-nonbearing NSAIDs (3 salicylates, 6 coxibs and 1 polyphenol) or 3 piroxicam analogs (including ampiroxicam, a precursor of piroxicam) exerted any neuroprotection. Tenoxicam and piroxicam prevented MPP(+)-induced reduction of phosphorylated Akt levels in cells: a protective mechanism similar to that of meloxicam. Therefore, the oxicam structure was likely to be responsible for exhibiting the neuroprotection by sustaining survival-signaling in dopaminergic cells. The present results raise the possibility that the oxicam-bearing NSAIDs may serve as potential therapeutic drugs to retard or terminate progression of Parkinson's disease via a novel mechanism. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. Nootropic, neuroprotective and neurotrophic effects of phloretin in scopolamine induced amnesia in mice.

    Science.gov (United States)

    Ghumatkar, Priya J; Patil, Sachin P; Jain, Pankaj D; Tambe, Rufi M; Sathaye, Sadhana

    2015-08-01

    Phloretin (PHL), a dihydrochalcone flavonoid usually present in the roots and leaves of apple tree. In vitro study on GT1-7 immortalized hypothalamic neurons exposed to amyloid beta (25-35), demonstrated that PHL significantly influenced membrane fluidity and potential. PHL also significantly decreased excitotoxicity by restoring the calcium homeostasis in the same. Thus, PHL proves to be a promising therapeutic moiety which should be further screened in the treatment of Alzheimer's disease. The objective of the present study was to evaluate the nootropic, neuroprotective and neurotrophic roles of PHL in the subacute scopolamine induced amnesia in mice. In this study, mice were pretreated with PHL 2.5mg/kg, 5mg/kg, 10mg/kg and Donepezil (DON) 1mg/kg intraperitoneally (i.p) for 14days. The last 7days of treatment regimen included daily injection of SCP 1.5mg/kg to induce cognitive deficits. Mice were subjected to behavioral analysis. Biochemical estimation of the brain homogenates for acetylcholinesterase and oxidative stress biomarkers were conducted. Furthermore, immunohistochemical analysis for the brain derived neurotrophic factor (BDNF) was carried out particularly in the hippocampus. PHL was found to significantly improve the performance of mice in Morris water maze test (Pnootropic, neuroprotective and neurotrophic activities in SCP induced memory impaired mice and hence, is a promising therapeutic moiety in the treatment of AD. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Epigenetic memory of oxidative stress: does nephrilin exert its protective effects via Rac1?

    Directory of Open Access Journals (Sweden)

    Mascarenhas DD

    2017-07-01

    Full Text Available Desmond D Mascarenhas,1,2 David N Herndon,3 Istvan Arany4 1Mayflower Organization for Research & Education, Sunnyvale, CA, 2Transporin, Inc., Sunnyvale, CA, 3Department of Surgery, The University of Texas Medical Branch, and Shriners Hospitals for Children, Galveston, TX, 4Department of Pediatrics, Division of Pediatric Nephrology, University of Mississippi Medical Center, Jackson, MS, USA Aim: Nephrilin peptide, a designed inhibitor of Rictor complex (mTORC2, exerts pleiotropic protective effects in metabolic, xenobiotic and traumatic stress models. Stress can generate enduring epigenetic changes in gene function. In this work we examine the possibility that nephrilin treatment protects against acute and enduring global changes in oxidative metabolism, with a focus on the Rictor-complex-mediated activation of Rac1, a subunit of NADPH oxidase (Nox via PKCs, Prex1 and p66shc. Methods: Given the wide range of animal models in which nephrilin peptide has previously demonstrated effectiveness in vivo, we chose three different experimental systems for this investigation: dermal fibroblasts, renal proximal tubule epithelial cells (PTECs, and kidney tissue and urine from an animal model of burn trauma in which nephrilin was previously shown to prevent loss of kidney function. Results: (1 Nephrilin protects dermal fibroblasts from loss of viability and collagen synthesis after ultraviolet A (UV-A or H2O2 insult. (2 Nephrilin reduces reactive oxygen species (ROS formation by H2O2–treated (PTECs with or without nicotine pretreatment. Using RNA arrays and pathway analysis we demonstrate that nicotine and H2O2-treated PTECs specifically induced Rac1 gene networks in these cells. (3 Using kidney tissue and urine from the burn trauma model we demonstrate significant elevations of [a] 8-aminoprostane in urine; [b] kidney tissue histone modification and DNA methylation; and [c] post-transcriptional phosphorylation events consistent with Rac1 activation in

  7. Neuroprotective Effects of Oxytocin Hormone after an Experimental Stroke Model and the Possible Role of Calpain-1.

    Science.gov (United States)

    Etehadi Moghadam, Sepideh; Azami Tameh, Abolfazl; Vahidinia, Zeinab; Atlasi, Mohammad Ali; Hassani Bafrani, Hassan; Naderian, Homayoun

    2018-03-01

    Different mechanisms will be activated during ischemic stroke. Calpain proteases play a pivotal role in neuronal death after ischemia damage through apoptosis. Anti-apoptotic activities of the oxytocin (OT) in different ischemic tissues were reported in previous studies. Recently, a limited number of studies have noted the protective effects of OT in the brain. In the present study, the neuroprotective potential of OT in an animal model of transient middle cerebral artery occlusion (tMCAO) and the possible role of calpain-1 in the penumbra region were assessed. Adult male Wistar rats underwent 1 hour of tMCAO and were treated with nasal administration of OT. After 24 hours of reperfusion, infarct size was evaluated by triphenyltetrazolium chloride. Immunohistochemical staining and Western blotting were used to examine the expression of calpain-1. Nissl staining was performed for brain tissue morphology evaluation. OT reduced the infarct volume of the cerebral cortex and striatum compared with the ischemia control group significantly (P < .05). Calpain-1 overexpression, which was caused by ischemia, decreased after OT administration (P < .05). The number of pyknotic nuclei in neurons increased dramatically in the ischemic area and OT attenuated the apoptosis of neurons in the penumbra region (P < .01). We provided evidence for the neuroprotective role of OT after tMCAO through calpain-1 attenuation. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  8. Neuroprotective and Anti-Inflammatory Effects of Rhus coriaria Extract in a Mouse Model of Ischemic Optic Neuropathy

    Directory of Open Access Journals (Sweden)

    Saba Khalilpour

    2018-04-01

    Full Text Available Modulating oxidative stresses and inflammation can potentially prevent or alleviate the pathological conditions of diseases associated with the nervous system, including ischemic optic neuropathy. In this study we evaluated the anti-neuroinflammatory and neuroprotective activities of Rhus coriaria (R. coriaria extract in vivo. The half maximal inhibitory concentration (IC50 for DPPH, ABTS and β–carotene were 6.79 ± 0.009 µg/mL, 10.94 ± 0.09 µg/mL, and 6.25 ± 0.06 µg/mL, respectively. Retinal ischemia was induced by optic nerve crush injury in albino Balb/c mice. The anti-inflammatory activity of ethanolic extract of R. coriaria (ERC and linoleic acid (LA on ocular ischemia was monitored using Fluorescence Molecular Tomography (FMT. Following optic nerve crush injury, the mice treated with 400 mg/kg of ERC and LA exhibited an 84.87% and 86.71% reduction of fluorescent signal (cathepsin activity respectively. The results of this study provide strong scientific evidence for the neuroprotective activity of the ERC, identifying LA as one of the main components responsible for the effect. ERC may be useful and worthy of further development for its adjunctive utilization in the treatment of optic neuropathy.

  9. In Vitro and in Vivo Neuroprotective Effects of Walnut (Juglandis Semen in Models of Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Jin Gyu Choi

    2016-01-01

    Full Text Available Monoamine oxidase (MAO catalyzes the oxidative deamination of monoamines including dopamine (DA. MAO expression is elevated in Parkinson’s disease (PD. An increase in MAO activity is closely related to age, and this may induce neuronal degeneration in the brain due to oxidative stress. MAO (and particularly monoamine oxidase B (MAO-B participates in the generation of reactive oxygen species (ROS, such as hydrogen peroxide that are toxic to dopaminergic cells and their surroundings. Although the polyphenol-rich aqueous walnut extract (JSE; an extract of Juglandis Semen has been shown to have various beneficial bioactivities, no study has been dedicated to see if JSE is capable to protect dopaminergic neurons against neurotoxic insults in models of PD. In the present study we investigated the neuroprotective potential of JSE against 1-methyl-4-phenylpyridinium (MPP+- or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP-induced neurotoxicities in primary mesencephalic cells and in a mouse model of PD. Here we show that JSE treatment suppressed ROS and nitric oxide productions triggered by MPP+ in primary mesencephalic cells. JSE also inhibited depletion of striatal DA and its metabolites in vivo that resulted in significant improvement in PD-like movement impairment. Altogether our results indicate that JSE has neuroprotective effects in PD models and may have potential for the prevention or treatment of PD.

  10. Neuroprotective effects of scutellarin against hypoxic-ischemic-induced cerebral injury via augmentation of antioxidant defense capacity.

    Science.gov (United States)

    Guo, Hong; Hu, Li-Min; Wang, Shao-Xia; Wang, Yu-Lin; Shi, Fang; Li, Hui; Liu, Yang; Kang, Li-Yuan; Gao, Xiu-Mei

    2011-12-31

    An increasing number of studies has indicated that hypoxic-ischemic-induced cerebral injury is partly mediated via oxidative stress. Recent researches have focused on searching for drug and herbal manipulations to protect against hypoxic-ischemic-induced oxidative cell damage. Scutellarin is a flavonoid derived from the Erigeron breviscapus (vant.) and has been reported to exhibit neuroprotective properties. However, its precise mechanism, particularly its antioxidation mechanism, remains elusive. In the present study, we investigated the neuroprotective effects of scutellarin on middle cerebral artery occlusion (MCAO)-induced brain damage in rats, and oxygen-glucose deprivation (OGD)-induced toxicity in primary culture of rat cortical neurons. In vivo, intraperitoneal injections of scutellarin (20 and 60 mg/kg) improved the neurological score and diminished the percentage of brain infarct volume. At the same time, scutellarin significantly increased superoxide dismutase (SOD), catalase (CAT) activities and glutathione (GSH) level in ischemic brain tissues, enhancing endogenous antioxidant activity. Moreover, pretreatment of scutellarin (25, 50 and 100 μM) protected neurons against lethal stimuli, decreased the percentage of apoptotic cells and inhibited reactive oxygen species (ROS) generation in OGD-induced primary cortical neurons in vitro. These results suggest that the preventive and therapeutic potential of scutellarin in cerebral injury patients is, at least in part, ascribed to augmentation of cellular antioxidant defense capacity.

  11. Neuroprotective effect of tempol (4 hydroxy-tempo) on neuronal death induced by sciatic nerve transection in neonatal rats.

    Science.gov (United States)

    Chiarotto, Gabriela Bortolança; Drummond, Luisa; Cavarretto, Gabriela; Bombeiro, André Luis; de Oliveira, Alexandre Leite Rodrigues

    2014-07-01

    Peripheral nerve injury in newborn rats triggers extensive neuronal death within the spinal cord. Because most neurodegeneration is related to oxidative stress and apoptosis, the use of antioxidants may be of therapeutic interest. Tempol is promising because of its ability to chelate reactive oxygen species and to minimize or even prevent tissue damage. Here, we evaluated neuroprotective effects of tempol following neonatal sciatic nerve transection. Two-day-old pups underwent sciatic nerve axotomy followed by tempol (12, 24 and 48 mg/kg) treatment (i.p.) at 10 min, 6 h, and every 24 h up to 1 week after injury. The rats were then killed for lumbar intumescence analysis. Nissl staining, TUNEL, synaptophysin immunolabeling and qRT-PCR (Caspase 3, Bax and Bcl2) were carried out. The results indicated that tempol treatment, at 24 mg/kg, increased up to 21% spinal cord motoneuron survival (ptempol-treated animals. qRT-PCR results indicated differential increase in Caspase 3 (3-fold), Bax (13-fold) and Bcl2 (28-fold) gene expression, after 12 h following axotomy and tempol treatment. In conclusion, tempol administration has proven to be neuroprotective after neonatal nerve injury, leading to improved motoneuron survival, synapse preservation and minimizing apoptosis. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Neuroprotective effect of Momordica charantia in global cerebral ischemia and reperfusion induced neuronal damage in diabetic mice.

    Science.gov (United States)

    Malik, Zafar Ahmad; Singh, Manjeet; Sharma, P L

    2011-01-27

    Momordica charantia L. (Cucurbitaceae) fruits have been used traditionally for centuries, especially for treating diabetes and associated complications. The present study was performed to evaluate neuroprotective effect of lyophilized M. charantia fruit juice against global cerebral ischemia and reperfusion induced neuronal injury in diabetic mice. Global cerebral ischemia induced by occluding both common carotid arteries for 10 min followed by 24 h reperfusion was used to induce neuronal injury. Ischemia-reperfusion induced neuronal injury was evaluated in terms of cerebral infarct size, generation of free radicals measured as thiobarbaturic acid reactive substances (TBARS), and neurological functions measured as short term memory and motor activity. The cerebral oxidative stress and damage, and neurological deficits were dose dependently attenuated by pre-treatment with the lyophilized M. charantia juice (200-800 mg/kg, p.o., o.d.). Moreover, M. charantia also exhibited dose dependent antihyperglycemic activity in diabetic mice. These results suggest that M. charantia has potent neuroprotective activity against global cerebral ischemia-reperfusion induced neuronal injury and consequent neurological deficits in diabetic mice. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  13. Neuroprotective effects of germinated brown rice against hydrogen peroxide induced cell death in human SH-SY5Y cells.

    Science.gov (United States)

    Ismail, Norsharina; Ismail, Maznah; Fathy, Siti Farhana; Musa, Siti Nor Asma; Imam, Mustapha Umar; Foo, Jhi Biau; Iqbal, Shahid

    2012-01-01

    The neuroprotective and antioxidative effects of germinated brown rice (GBR), brown rice (BR) and commercially available γ-aminobutyric acid (GABA) against cell death induced by hydrogen peroxide (H(2)O(2)) in human neuroblastoma SH-SY5Y cells have been investigated. Results show that GBR suppressed H(2)O(2)-mediated cytotoxicity and induced G0/G1 phase cell cycle arrest in SH-SY5Y cells. Moreover, GBR reduced mitochondrial membrane potential (MMP) and prevented phosphatidylserine (PS) translocation in SH-SY5Y cells, key features of apoptosis, and subsequent cell death. GBR exhibited better neuroprotective and antioxidative activities as compared to BR and GABA. These results indicate that GBR possesses high antioxidative activities and suppressed cell death in SH-SY5Y cells by blocking the cell cycle re-entry and apoptotic mechanisms. Therefore, GBR could be developed as a value added functional food to prevent neurodegenerative diseases caused by oxidative stress and apoptosis.

  14. Neuroprotective Effects of Germinated Brown Rice against Hydrogen Peroxide Induced Cell Death in Human SH-SY5Y Cells

    Directory of Open Access Journals (Sweden)

    Shahid Iqbal

    2012-08-01

    Full Text Available The neuroprotective and antioxidative effects of germinated brown rice (GBR, brown rice (BR and commercially available γ-aminobutyric acid (GABA against cell death induced by hydrogen peroxide (H2O2 in human neuroblastoma SH-SY5Y cells have been investigated. Results show that GBR suppressed H2O2-mediated cytotoxicity and induced G0/G1 phase cell cycle arrest in SH-SY5Y cells. Moreover, GBR reduced mitochondrial membrane potential (MMP and prevented phosphatidylserine (PS translocation in SH-SY5Y cells, key features of apoptosis, and subsequent cell death. GBR exhibited better neuroprotective and antioxidative activities as compared to BR and GABA. These results indicate that GBR possesses high antioxidative activities and suppressed cell death in SH-SY5Y cells by blocking the cell cycle re-entry and apoptotic mechanisms. Therefore, GBR could be developed as a value added functional food to prevent neurodegenerative diseases caused by oxidative stress and apoptosis.

  15. Time dependent neuroprotection of mycophenolate mofetil: effects on temporal dynamics in glial proliferation, apoptosis, and scar formation

    Directory of Open Access Journals (Sweden)

    Ebrahimi Fahim

    2012-05-01

    Full Text Available Abstract Background Immunosuppressants such as mycophenolate mofetil (MMF have the capacity to inhibit microglial and astrocytic activation and to reduce the extent of cell death after neuronal injury. This study was designed to determine the effective neuroprotective time frame in which MMF elicits its beneficial effects, by analyzing glial cell proliferation, migration, and apoptosis. Methods Using organotypic hippocampal slice cultures (OHSCs, temporal dynamics of proliferation and apoptosis after N-methyl-D-aspartate (NMDA-mediated excitotoxicity were analyzed by quantitative morphometry of Ki-67 or cleaved caspase-3 immunoreactive glial cells. Treatment on NMDA-lesioned OHSCs with mycophenolate mofetil (MMF100 μg/mL was started at different time points after injury or performed within specific time frames, and the numbers of propidium iodide (PI+ degenerating neurons and isolectin (IB4+ microglial cells were determined. Pre-treatment with guanosine 100 μmol/l was performed to counteract MMF-induced effects. The effects of MMF on reactive astrocytic scar formation were investigated in the scratch-wound model of astrocyte monolayers. Results Excitotoxic lesion induction led to significant increases in glial proliferation rates between 12 and 36 hours after injury and to increased levels of apoptotic cells between 24 and 72 hours after injury. MMF treatment significantly reduced glial proliferation rates without affecting apoptosis. Continuous MMF treatment potently reduced the extent of neuronal cell demise when started within the first 12 hours after injury. A crucial time-frame of significant neuroprotection was identified between 12 and 36 hours after injury. Pre-treatment with the neuroprotective nucleoside guanosine reversed MMF-induced antiproliferative effects on glial cells. In the scratch-wound model, gap closure was reached within 48 hours in controls, and was potently inhibited by MMF. Conclusions Our data indicate that

  16. Anticonvulsive and neuroprotective effects of synergetic combination of phenytoin and gastrodin on the convulsion induced by penicillin in mice.

    Science.gov (United States)

    Zhou, Ziqi; Lin, Yanzhu; Zheng, Hongyi; He, Yuzhong; Xu, Haohua; Zhang, Siheng; Weng, Wen; Li, Wei; Zhu, Linyan; Yang, Haifeng

    2015-08-01

    Phenytoin (PHT) is a commonly prescribed first-line antiepileptic drug. However, long-term administration of PHT can cause memory loss and balance disturbance. Gastrodin (GD) is the major bioactive component in Tianma and has sedative, anticonvulsive, memory strengthening, and neuroprotective effects. To combine the two drugs seems attractive; however, little was known about the efficacy of combination therapy. In this study, convulsive attack was successfully induced by penicillin. Isobolographic analysis, memory and balance behavior test, histopathological examination, and Western blot analysis were used to investigate whether the combination therapy of GD and PHT can enhance anticonvulsive effect and reduce the side effects associated with PHT. The GD alone (950.60 mg/kg) and the PHT alone (45.50 mg/kg) could produce an anticonvulsive effect, while comparable effect could be produced by PHT : GD = 1 : 50 (8.59 : 429.27 mg/kg), which reduce the dose of PHT by 81% and GD by 55%. After the chronic anticonvulsive experiments of 16 days, the balance disturbance and short-/long-term memory loss were observed in the PHT group, while the PHT + GD therapy can protect the normal balance and memory function. The neuron morphology of hippocampus was preserved, and the number of surviving neurons after combination therapy was more than the model group. The amount of NF-κB (p65) expression was increased in combination group. All above suggested the potential of the combination of PHT and GD enhances the anticonvulsive effect and the neuroprotective effect and reduces the PHT-associated memory and balance disturbance. The PHT + GD strategy would provide new possibilities as a novel promising methodology to treat epileptic patients. © 2015 Société Française de Pharmacologie et de Thérapeutique.

  17. The administration of hydrogen sulphide prior to ischemic reperfusion has neuroprotective effects in an acute stroke model.

    Directory of Open Access Journals (Sweden)

    Chul-Woong Woo

    Full Text Available Emerging evidence has suggested that hydrogen sulfide (H2S may alleviate the cellular damage associated with cerebral ischemia/reperfusion (I/R injury. In this study, we assessed using 1H-magnetic resonance imaging/magnetic resonance spectroscopy (1H-MRI/MRS and histologic analysis whether H2S administration prior to reperfusion has neuroprotective effects. We also evaluated for differences in the effects of H2S treatment at 2 time points. 1H-MRI/MRS data were obtained at baseline, and at 3, 9, and 24 h after ischemia from 4 groups: sham, control (I/R injury, sodium hydrosulfide (NaHS-30 and NaHS-1 (NaHS delivery at 30 and 1 min before reperfusion, respectively. The total infarct volume and the midline shift at 24 h post-ischemia were lowest in the NaHS-1, followed by the NaHS-30 and control groups. Peri-infarct volume was significantly lower in the NaHS-1 compared to NaHS-30 and control animals. The relative apparent diffusion coefficient (ADC in the peri-infarct region showed that the NaHS-1 group had significantly lower values compared to the NaHS-30 and control animals and that NaHS-1 rats showed significantly higher relative T2 values in the peri-infarct region compared to the controls. The relative ADC value, relative T2 value, levels of N-acetyl-L-aspartate (NAA, and the NAA, glutamate, and taurine combination score (NGT in the ischemic core region at 24 h post-ischemia did not differ significantly between the 2 NaHS groups and the control except that the NAA and NGT values were higher in the peri-infarct region of the NaHS-1 animals at 9 h post-ischemia. In the ischemic core and peri-infarct regions, the apoptosis rate was lowest in the NaHS-1 group, followed by the NaHS-30 and control groups. Our results suggest that H2S treatment has neuroprotective effects on the peri-infarct region during the evolution of I/R injury. Furthermore, our findings indicate that the administration of H2S immediately prior to reperfusion produces the

  18. Arginine, N-carbamylglutamate, and glutamine exert protective effects against oxidative stress in rat intestine

    Directory of Open Access Journals (Sweden)

    Liang Xiao

    2016-09-01

    .05. Collectively, this study suggested that dietary supplementation with 1% GLN, 0.1% NCG, and 1% ARG was effective in enhancing the antioxidant status and maintaining the morphological structure of rat jejunum under oxidative stress; of these supplements, 1% GLN exerted the greatest effects on mitigating oxidative stress.

  19. Neuroprotective effect of melatonin against ischemia is partially mediated by alpha-7 nicotinic receptor modulation and HO-1 overexpression.

    Science.gov (United States)

    Parada, Esther; Buendia, Izaskun; León, Rafael; Negredo, Pilar; Romero, Alejandro; Cuadrado, Antonio; López, Manuela G; Egea, Javier

    2014-03-01

    Melatonin has been widely studied as a protective agent against oxidative stress. However, the molecular mechanisms underlying neuroprotection in neurodegeneration and ischemic stroke are not yet well understood. In this study, we evaluated the neuroprotective/antioxidant mechanism of action of melatonin in organotypic hippocampal cultures (OHCs) as well as in photothrombotic stroke model in vivo. Melatonin (0.1, 1, and 10 μM) incubated postoxygen and glucose deprivation (OGD) showed a concentration-dependent protection; maximum protection was achieved at 10 μM (90% protection). Next, OHCs were exposed to 10 μM melatonin at different post-OGD times; the protective effect of melatonin was maintained at 0, 1, and 2 hr post-OGD treatment, but it was lost at 6 hr post-OGD. The protective effect of melatonin and the reduction in OGD-induced ROS were prevented by luzindole (melatonin antagonist) and α-bungarotoxin (α-Bgt, a selective α7 nAChR antagonist). In Nrf2 knockout mice, the protective effect of melatonin was reduced by 40% compared with controls. Melatonin, incubated 0, 1, and 2 hr post-OGD, increased the expression of heme oxygenase-1 (HO-1), and this overexpression was prevented by luzindole and α-bungarotoxin. Finally, administration of 15 mg/kg melatonin following the induction of photothrombotic stroke in vivo, reduced infarct size (50%), and improved motor skills; this effect was partially lost in 0.1 mg/kg methyllycaconitine (MLA, selective α7 nAChR antagonist)-treated mice. Taken together, these results demonstrate that postincubation of melatonin provides a protective effect that, at least in part, depends on nicotinic receptor activation and overexpression of HO-1. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Neuroprotective Effects and Mechanisms of Curcumin–Cu(II and –Zn(II Complexes Systems and Their Pharmacological Implications

    Directory of Open Access Journals (Sweden)

    Fa-Shun Yan

    2017-12-01

    Full Text Available Alzheimer’s disease (AD is the main form of dementia and has a steadily increasing prevalence. As both oxidative stress and metal homeostasis are involved in the pathogenesis of AD, it would be interesting to develop a dual function agent, targeting the two factors. Curcumin, a natural compound isolated from the rhizome of Curcuma longa, is an antioxidant and can also chelate metal ions. Whether the complexes of curcumin with metal ions possess neuroprotective effects has not been evaluated. Therefore, the present study was designed to investigate the protective effects of the complexes of curcumin with Cu(II or Zn(II on hydrogen peroxide (H2O2-induced injury and the underlying molecular mechanisms. The use of rat pheochromocytoma (PC12 cells, a widely used neuronal cell model system, was adopted. It was revealed that curcumin–Cu(II complexes systems possessed enhanced O2·–-scavenging activities compared to unchelated curcumin. In comparison with unchelated curcumin, the protective effects of curcumin–Cu(II complexes systems were stronger than curcumin–Zn(II system. Curcumin–Cu(II or –Zn(II complexes systems significantly enhanced the superoxide dismutase, catalase, and glutathione peroxidase activities and attenuated the increase of malondialdehyde levels and caspase-3 and caspase-9 activities, in a dose-dependent manner. The curcumin–Cu(II complex system with a 2:1 ratio exhibited the most significant effect. Further mechanistic study demonstrated that curcumin–Cu(II or –Zn(II complexes systems inhibited cell apoptosis via downregulating the nuclear factor κB (NF-κB pathway and upregulating Bcl-2/Bax pathway. In summary, the present study found that curcumin–Cu(II or –Zn(II complexes systems, especially the former, possess significant neuroprotective effects, which indicates the potential advantage of curcumin as a promising agent against AD and deserves further study.

  1. Neuroprotective effects of lentivirus-mediated cystathionine-beta-synthase overexpression against 6-OHDA-induced parkinson's disease rats.

    Science.gov (United States)

    Yin, Wei-Lan; Yin, Wei-Guo; Huang, Bai-Sheng; Wu, Li-Xiang

    2017-09-14

    Parkinson's disease (PD) is age-related neurodegenerative disorder by a progressive loss of dopaminergic(DA) neurons in the substantia nigra (SN) and striatum, which is at least partly associated with α-synuclein protein accumulation in these neurons. Hydrogen sulfide (H 2 S) plays an important role in the nervous system. Studies have shown that H 2 S has a protective effect on PD. However, as a kind of gas molecules, H 2 S is lively, volatile, and not conducive to scientific research and clinical application. Cystathionine-beta-synthase(CBS) is the main enzymes of synthesis of H 2 S in the brain. In order to examine the neuroprotective effects of CBS on PD, we detected the effects of CBS overexpression on 6-Hydroxydopamine (6-OHDA)-lesioned PD rats using lentivirus-mediated gene transfection techniques. In the injured SN of 6-OHDA-induced PD rats, the CBS expression and the endogenous H 2 S level markedly decreased, while administration of lentivirus-mediated CBS overexpression increased the CBS expression and the endogenous H 2 S production.CBS overexpression dramatically reversed apomorphine-induced rotation of the 6-OHDA model rats, decreased the number of TUNEL-positive neurons and the loss of the nigral DA neurons,specifically inhibited 6-OHDA-induced oxidase stress injury, and down-regulated the expression of α-synuclein(α-SYN) in the injured SN. NaHS (an H 2 S donor) had similar effects to CBS overexpression, while Amino-oxyacetate(AOAA, a CBS inhibitor) had opposite effects on PD rats. In summary, we demonstrated that CBS overexpression was able to provide neuroprotective on PD rats and improving the expression of CBS may be a potential therapeutic method for PD. Copyright © 2017. Published by Elsevier B.V.

  2. Neuroprotective Effect of σ1-Receptors on the Cell Model of Huntington's Disease.

    Science.gov (United States)

    Bol'shakova, A V; Kraskovskaya, N A; Gainullina, A N; Kukanova, E O; Vlasova, O L; Bezprozvanny, I B

    2017-12-01

    Huntington's disease is a hereditary neurodegenerative disease that primarily affects striatal neurons. Recent studies demonstrated abnormalities in calcium regulation in striatal neurons in Huntington's disease, which leads to elimination of synaptic connections between cortical and striatal neurons. In the present study, we focused on the neuroprotective properties of σ1-receptor, because one of its main functions is associated with modulation of calcium homeostasis in cells. The application of selective σ1-receptor agonists to the corticostriatal cell culture restores synaptic connections between the cortical and striatal neurons. Based on the obtained data, we assume that σ1-receptor is a promising target for the development of drugs for the therapy of Huntington's disease.

  3. Neuroprotective effects of Rhodiola rosea extracts against excitotoxicity and oxygen-glucose deprivation in hippocampal slice cultures

    DEFF Research Database (Denmark)

    Gramsbergen, Jan Bert; Sindberg, J.; Lundberg, L.

    .g. salidroside) and phenylpropanoid glycosides (e.g. rosavin). Many of these compounds are considered potent antioxidants, but the significance of the various substances for the beneficial effects of roseroot is still largely unknown. Here we tested the neuroprotective effects of crude methanolic extracts of R......The medical plant Rhodiola rosea (roseroot, golden root) is known as a stimulant of mental and physical endurance, increasing resistance to chemical, biological, psychological and physical stressors. Extracts of R. rosea roots contain ?avonoids, phenolic acids, phenylethanol derivatives (e...... pups were grown for 2-3 weeks before exposure to N-methyl-D-aspartate (NMDA, 10 µM, 24 h) or oxygen-glucose deprivation (OGD, 30 or 35 min), with and without presence of R. rosea extracts or compounds during and 24 h after the insult. NMDA- or OGD-induced neuronal cell death was monitored...

  4. Neuroprotective Effect of Coptis chinensis in MPP[Formula: see text] and MPTP-Induced Parkinson's Disease Models.

    Science.gov (United States)

    Friedemann, Thomas; Ying, Yue; Wang, Weigang; Kramer, Edgar R; Schumacher, Udo; Fei, Jian; Schröder, Sven

    2016-01-01

    The rhizome of Coptis chinensis is commonly used in traditional Chinese medicine alone or in combination with other herbs to treat diseases characterized by causing oxidative stress including inflammatory diseases, diabetes mellitus and neurodegenerative diseases. In particular, there is emerging evidence that Coptis chinensis is effective in the treatment of neurodegenerative diseases associated with oxidative stress. Hence, the aim of this study was to investigate the neuroprotective effect of Coptis chinensis in vitro and in vivo using MPP[Formula: see text] and MPTP models of Parkinson's disease. MPP[Formula: see text] treated human SH-SY5Y neuroblastoma cells were used as a cell model of Parkinson's disease. A 24[Formula: see text]h pre-treatment of the cells with the watery extract of Coptis chinensis significantly increased cell viability, as well as the intracellular ATP concentration and attenuated apoptosis compared to the MPP[Formula: see text] control. Further experiments with the main alkaloids of Coptidis chinensis, berberine, coptisine, jaterorrhizine and palmatine revealed that berberine and coptisine were the main active compounds responsible for the observed neuroprotective effect. However, the full extract of Coptis chinensis was more effective than the tested single alkaloids. In the MPTP-induced animal model of Parkinson's disease, Coptis chinensis dose-dependently improved motor functions and increased tyrosine hydroxylase-positive neurons in the substantia nigra compared to the MPTP control. Based on the results of this work, Coptis chinensis and its main alkaloids could be considered potential candidates for the development of new treatment options for Parkinson's disease.

  5. Histological studies of neuroprotective effects of Curcuma longa Linn. on neuronal loss induced by dexamethasone treatment in the rat hippocampus.

    Science.gov (United States)

    Issuriya, Acharaporn; Kumarnsit, Ekkasit; Wattanapiromsakul, Chatchai; Vongvatcharanon, Uraporn

    2014-10-01

    Long term exposure to dexamethasone (Dx) is associated with brain damage especially in the hippocampus via the oxidative stress pathway. Previously, an ethanolic extract from Curcuma longa Linn. (CL) containing the curcumin constituent has been reported to produce antioxidant effects. However, its neuroprotective property on brain histology has remained unexplored. This study has examined the effects of a CL extract on the densities of cresyl violet positive neurons and glial fibrillary acidic protein immunoreactive (GFAP-ir) astrocytes in the hippocampus of Dx treated male rats. It showed that 21 days of Dx treatment (0.5mg/kg, i.p. once daily) significantly reduced the densities of cresyl violet positive neurons in the sub-areas CA1, CA3 and the dentate gyrus, but not in the CA2 area. However, CL pretreatment (100mg/kg, p.o.) was found to significantly restore neuronal densities in the CA1 and dentate gyrus. In addition, Dx treatment also significantly decreased the densities of the GFAP-ir astrocytes in the sub-areas CA1, CA3 and the dentate gyrus. However, CL pretreatment (100mg/kg, p.o.) failed to protect the loss of astrocytes in these sub-areas. These findings confirm the neuroprotective effects of the CL extract and indicate that the cause of astrocyte loss might be partially reduced by a non-oxidative mechanism. Moreover, the detection of neuronal and glial densities was suitable method to study brain damage and the effects of treatment. Copyright © 2014 Elsevier GmbH. All rights reserved.

  6. Neuroprotective effect of bee venom is mediated by reduced astrocyte activation in a subchronic MPTP-induced model of Parkinson's disease.

    Science.gov (United States)

    Kim, Mi Eun; Lee, Joo Yeon; Lee, Kyung Moon; Park, Hee Ra; Lee, Eunjin; Lee, Yujeong; Lee, Jun Sik; Lee, Jaewon

    2016-08-01

    Bee venom (BV), also known as apitoxin, is widely used in traditional oriental medicine to treat immune-related diseases. Recent studies suggest that BV could be beneficial for the treatment of neurodegenerative diseases. Parkinson's disease (PD) is the second most common neurodegenerative disease next to Alzheimer's disease, and PD pathologies are closely associated with neuroinflammation. Previous studies have suggested the neuroprotective effects of BV in animal models of PD are due to the modulation of inflammation. However, the molecular mechanisms responsible for the anti-neuroinflammatory effect of BV have not been elucidated in astrocytes. Here, the authors investigated the neuroprotective effects of BV and pramipexole (PPX; a positive control) in a subchronic MPTP-induced murine PD model. Both BV and PPX prevented MPTP-induced impairments in motor performance and reduced dopaminergic neuron loss, and furthermore, these neuroprotective effects of BV and PPX were found to be associated with reduced astroglial activation in vivo PD model. However, in MPP(+) treated primary cultured astrocytes, BV modulated astrocyte activation, whereas PPX did not, indicating that the neuroprotective effects of PPX were not mediated by neuroinflammation. These findings suggest that BV should be considered a potential therapeutic or preventive agent for PD and other neuroinflammatory associated disorders.

  7. Effects of 12 months aerobic exercise intervention on work ability, need for recovery, productivity and rating of exertion among cleaners

    DEFF Research Database (Denmark)

    Lidegaard, Mark; Søgaard, Karen; Krustrup, Peter

    2018-01-01

    PURPOSE: This study assessed the effects of a worksite aerobic exercise intervention among cleaners on: work ability, need for recovery, productivity, and rating of exertion. METHODS: In a monocentric randomised controlled trial in Denmark, 116, of 250 invited, cleaners were cluster-randomised (w......PURPOSE: This study assessed the effects of a worksite aerobic exercise intervention among cleaners on: work ability, need for recovery, productivity, and rating of exertion. METHODS: In a monocentric randomised controlled trial in Denmark, 116, of 250 invited, cleaners were cluster......-reported data on outcomes and sociodemographic information were collected at baseline, and at 4 and 12 month follow-up. All outcomes were analysed in a linear repeated-measures 2 × 2 mixed-model by an intention-to-treat analysis approach. RESULTS: Drop-out was 26 and 33% at 4 and 12 months, respectively...

  8. Neuroprotective effects of testosterone metabolites and dependency on receptor action on the morphology of somatic motoneurons following the death of neighboring motoneurons.

    Science.gov (United States)

    Cai, Yi; Chew, Cory; Muñoz, Fernando; Sengelaub, Dale R

    2017-06-01

    Partial depletion of spinal motoneuron populations induces dendritic atrophy in neighboring motoneurons, and treatment with testosterone is neuroprotective, attenuating induced dendritic atrophy. In this study we examined whether the protective effects of testosterone could be mediated via its androgenic or estrogenic metabolites. Furthermore, to assess whether these neuroprotective effects were mediated through steroid hormone receptors, we used receptor antagonists to attempt to prevent the neuroprotective effects of hormones after partial motoneuron depletion. Motoneurons innervating the vastus medialis muscles of adult male rats were selectively killed by intramuscular injection of cholera toxin-conjugated saporin. Simultaneously, some saporin-injected rats were treated with either dihydrotestosterone or estradiol, alone or in combination with their respective receptor antagonists, or left untreated. Four weeks later, motoneurons innervating the ipsilateral vastus lateralis muscle were labeled with cholera toxin-conjugated horseradish peroxidase, and dendritic arbors were reconstructed in three dimensions. Compared with intact normal animals, partial motoneuron depletion resulted in decreased dendritic length in remaining quadriceps motoneurons. Dendritic atrophy was attenuated with both dihydrotestosterone and estradiol treatment to a degree similar to that seen with testosterone, and attenuation of atrophy was prevented by receptor blockade. Together, these findings suggest that neuroprotective effects on motoneurons can be mediated by either androgenic or estrogenic hormones and require action via steroid hormone receptors, further supporting a role for hormones as neurotherapeutic agents in the injured nervous system. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 691-707, 2017. © 2016 Wiley Periodicals, Inc.

  9. Effect of traditional resistance and power training using rated perceived exertion for enhancement of muscle strength, power, and functional performance

    OpenAIRE

    Tiggemann, Carlos Leandro; Dias, Caroline Pieta; Radaelli, Regis; Massa, J?ssica Cassales; Bortoluzzi, Rafael; Schoenell, Maira Cristina Wolf; Noll, Matias; Alberton, Cristine Lima; Kruel, Luiz Fernando Martins

    2016-01-01

    The present study compared the effects of 12?weeks of traditional resistance training and power training using rated perceived exertion (RPE) to determine training intensity on improvements in strength, muscle power, and ability to perform functional task in older women. Thirty healthy elderly women (60?75?years) were randomly assigned to traditional resistance training group (TRT; n?=?15) or power training group (PT; n?=?15). Participants trained twice a week for 12?weeks using six exercises...

  10. Evidence for neuroprotective effect of sulbutiamine against oxygen-glucose deprivation in rat hippocampal CA1 pyramidal neurons.

    Science.gov (United States)

    Kwag, Jeehyun; Majid, Aman Shah Abdul; Kang, Kui Dong

    2011-01-01

    Hippocampus is one of the earliest brain regions that gets affected by ischemia, however, no pharmacological therapy exists yet that can fully counteract the ischemic damage. Here we study the effect of sulbutiamine, a synthetic thiamine analogue that can cross the blood-brain barrier easily, on hippocampal neurons under an in vitro model of ischemia, oxygen-glucose deprivation (OGD). We find that exposure to OGD in the presence of sulbutiamine significantly increases neuronal viability and enhances electrophysiological properties such as excitatory synaptic transmissions and intrinsic neuronal membrane input resistance in a concentration-dependent manner. Overall, here we report, for the first time, the neuroprotective evidence of sulbutiamine on hippocampal CA1 pyramidal neurons under OGD, which may have beneficial implications as a possible therapeutic agent/substance against ischemic insult.

  11. The effects of hand force variation on shoulder muscle activation during submaximal exertions.

    Science.gov (United States)

    Meszaros, Kimberly A; Vidt, Meghan E; Dickerson, Clark R

    2018-03-01

    Upper limb injuries are highly prevalent in the workplace and new tools are needed to proactively design workstations to reduce injury risk. The objective was to characterize spatial, load and direction dependency of muscle activity for hand exertions in the upper limb workspace. Electromyographic signals were collected from 14 upper limb muscles during exertions for all combinations of 4 submaximal hand forces (20/30/50/60 N) in 6 cardinal (up/down/left/right/forward/backward) directions at 5 hand locations. Linear muscle activity increases accompanied increased hand forces. Total muscle activity increases between 20 and 60 N hand forces ranged by direction from 92% (downward) to 189% (right). Prediction equations for all muscles depended on hand force, and linear, quadratic and interaction permutations of hand location. Muscle activity associated with manual tasks is load, direction and spatially dependent. Equations developed to describe these complex relationships can be used to better design future and evaluate current occupational activities.

  12. Neuroprotective Effect of(−)Δ9-Tetrahydrocannabinol and Cannabidiol in N-Methyl-d-Aspartate-Induced Retinal Neurotoxicity

    Science.gov (United States)

    El-Remessy, Azza B.; Khalil, Ibrahim E.; Matragoon, Suraporn; Abou-Mohamed, Gamal; Tsai, Nai-Jer; Roon, Penny; Caldwell, Ruth B.; Caldwell, Robert W.; Green, Keith; Liou, Gregory I.

    2003-01-01

    In glaucoma, the increased release of glutamate is the major cause of retinal ganglion cell death. Cannabinoids have been demonstrated to protect neuron cultures from glutamate-induced death. In this study, we test the hypothesis that glutamate causes apoptosis of retinal neurons via the excessive formation of peroxynitrite, and that the neuroprotective effect of the psychotropic Δ9-tetrahydroxycannabinol (THC) or nonpsychotropic cannabidiol (CBD) is via the attenuation of this formation. Excitotoxicity of the retina was induced by intravitreal injection of N-methyl-d-aspartate (NMDA) in rats, which also received 4-hydroxy-2,2,6,6-tetramethylpiperidine-n-oxyl (TEMPOL,a superoxide dismutase-mimetic), N-ω-nitro-l-arginine methyl ester (L-NAME, a nitric oxide synthase inhibitor), THC, or CBD. Retinal neuron loss was determined by TDT-mediated dUTP nick-end labeling assay, inner retinal thickness, and quantification of the mRNAs of ganglion cell markers. NMDA induced a dose- and time-dependent accumulation of nitrite/nitrate, lipid peroxidation, and nitrotyrosine (foot print of peroxynitrite), and a dose-dependent apoptosis and loss of inner retinal neurons. Treatment with L-NAME or TEMPOL protected retinal neurons and confirmed the involvement of peroxynitrite in retinal neurotoxicity. The neuroprotection by THC and CBD was because of attenuation of peroxynitrite. The effect of THC was in part mediated by the cannabinoid receptor CB1. These results suggest the potential use of CBD as a novel topical therapy for the treatment of glaucoma. PMID:14578199

  13. Neuroprotective effect of geraniol and curcumin in an acrylamide model of neurotoxicity in Drosophila melanogaster: relevance to neuropathy.

    Science.gov (United States)

    Prasad, Sathya N; Muralidhara

    2014-01-01

    Chronic exposure of acrylamide (ACR) leads to neuronal damage in both experimental animals and humans. The primary focus of this study was to assess the ameliorative effect of geraniol, (a natural monoterpene) against ACR-induced oxidative stress, mitochondrial dysfunction and neurotoxicity in a Drosophila model and compare its efficacy to that of curcumin, a spice active principle with pleiotropic biological activity. Adult male flies (8-10 days) were exposed (7 days) to ACR (5 mM) with or without geraniol and curcumin (5-10 μM) in the medium. Both phytoconstituents significantly reduced the incidence of ACR-induced mortality, rescued the locomotor phenotype and alleviated the enhanced levels of oxidative stress markers in head/body regions. The levels of reduced glutathione (GSH) and total thiols (TSH) resulting from ACR exposure was also restored with concomitant elevation in the activities of detoxifying enzymes. Interestingly, ACR induced mitochondrial dysfunctions (MTT reduction, activities of SDH and citrate synthase enzymes) were alleviated by both phytoconstituents. While ACR elevated the activity of acetylcholinesterase in head/body regions, marked diminution in enzyme activity ensued with co-exposure to phytoconstituents suggesting their potency to mitigate cholinergic function. Furthermore, phytoconstituents also restored the dopamine levels in head/body regions. The neuroprotective effect of geraniol was comparable to curcumin in terms of phenotypic and biochemical markers. Based on our evidences in fly model we hypothesise that geraniol possess significant neuromodulatory propensity and may be exploited for therapeutic application in human pathophysiology associated with neuropathy. However, the precise mechanism/s by which geraniol offers neuroprotection needs to be investigated in appropriate neuronal cell models. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Neuroprotective effects of xiao-xu-ming decoction against ischemic neuronal injury in vivo and in vitro.

    Science.gov (United States)

    Zhu, Xin-Hong; Li, Shu-Ji; Hu, Hong-Hai; Sun, Li-Rong; Das, Manas; Gao, Tian-Ming

    2010-01-08

    Xiao-Xu-Ming decoction (XXMD) has long been employed clinically to treat stroke in traditional Chinese Medicine. To investigate the neuroprotective effects of XXMD in vivo and in vitro stroke models and determine involved mechanisms. Two models (four-vessel occlusion in adult Wistar rats and oxygen-glucose deprivation primary cultured neurons) were employed to mimic ischemia-reperfusion damage, in vivo and in vitro, respectively. The effects of XXMD were investigated with respect to neuronal damage, activity of caspase-3 and expression of Bcl-2 in CA1 region of hippocampus after ischemia. The cognitive ability was measured 7 days after ischemia/reperfusion by using Morris water maze. Oral administration of XXMD significantly increased the density of neurons that survived in the CA1 region of hippocampus on the 3rd and 7th day after transient global ischemia was induced in a dose-dependent manner. XXMD ameliorated severe deficiencies in spatial cognitive performance induced by transient global ischemia. Inhibition of caspase-3 activity and up-regulation of Bcl-2 expression were induced in the high dose of XXMD-treated rats after ischemia. In oxygen-glucose deprivation model, both XXMD extract and drug-containing serum prepared from blood of high dose of XXMD-treated rats inhibited apoptotic neuronal death at 24h after reoxygenation. Our results clearly demonstrated that XXMD is neuroprotective and appears to influence deleterious pathological processes that are activated after the onset of ischemia. Crown Copyright 2009. Published by Elsevier Ireland Ltd. All rights reserved.

  15. Neuroprotective effects of orientin on oxygen-glucose deprivation/reperfusion-induced cell injury in primary culture of rat cortical neurons.

    Science.gov (United States)

    Tian, Tian; Zeng, Junan; Zhao, Guangyu; Zhao, Wenjing; Gao, Songyi; Liu, Li

    2018-01-01

    together, these results demonstrated that orientin has significant neuroprotective effects against OGD/RP-induced cell injury via JNK and ERK1/2 signaling pathways in primary culture of rat cortical neurons. Impact statement Orientin has been used in traditional eastern medicine and reported to possess antioxidant properties. However, the effects of orientin on neonatal ischemic brain injury and the underlying mechanisms involved have not been studied. Our results showed that orientin exerts significant neuroprotective effects on cell injury caused by oxygen-glucose deprivation/reperfusion via the JNK and ERK1/2 signaling pathways in primary culture of rat cortical neurons, implying the potential therapeutic application of orientin via the suppression of oxidative stress and cell apoptosis. This research suggested that orientin may be used as a therapeutic and preventive option for newborn cerebral ischemia/reperfusion injury.

  16. Neuroprotective effects of riluzole in early phase Parkinson's disease on clinically relevant parameters in the marmoset MPTP model.

    Science.gov (United States)

    Verhave, Peternella S; Jongsma, Marjan J; Van Den Berg, Roland M; Vanwersch, Raymond A P; Smit, August B; Philippens, Ingrid H C H M

    2012-03-01

    The present study evaluates neuroprotection in a marmoset MPTP (1-methyl-1,2,3,6-tetrahydropyridine) model representing early Parkinson's disease (PD). The anti-glutamatergic compound riluzole is used as a model compound for neuroprotection. The compound is one of the few protective compounds used in the clinic for a neurodegenerative disorder. Marmoset monkeys were randomized into three groups of six: 1) an MPTP group receiving a total MPTP dose of 7 mg/kg (4 injections over two weeks, s.c.) 2) a riluzole group receiving besides MPTP, a twice daily dose of riluzole (10 mg/kg, p.o.), starting one week before MPTP and continuing for one week after the final MPTP injection and 3) a control group receiving saline instead of MPTP and riluzole. The marmosets' Parkinsonian symptoms were scored daily and their activity level, hand-eye coordination, jumping behavior, axial turning and night sleep parameters were tested and recorded weekly. At three weeks following the last MPTP challenge, brains were dissected and dopamine levels in the striatum and the tyrosine hydroxylase (TH) expressing dopamine (DA) neurons in the substantia nigra (SN) were compared. MPTP affected all behavioral parameters and sleep architecture and induced a relatively mild (50%) decline of DA neurons in the substantia nigra (SN). Riluzole relieved the Parkinsonian signs, and improved the hand-eye coordination as well as turning ability. Moreover, riluzole prevented the impact of MPTP on sleep architecture and rapid eye movement behavioral disorder (RBD). Riluzole also increased the number of surviving DA neurons in MPTP-treated marmosets to 75%. However, riluzole did not prevent the MPTP-induced impairments on locomotor activity and jumping activity. In conclusion, reduction of excitotoxicity by riluzole appeared to be effective in reducing progressive neurodegeneration and relieved several clinically relevant PD symptoms in an animal model representing the early phase of PD. Copyright © 2011

  17. Neuroprotective Effects of Etidronate and 2,3,3-Trisphosphonate Against Glutamate-Induced Toxicity in PC12 Cells.

    Science.gov (United States)

    Li, Wen; Cheong, Yuen-Ki; Wang, Hui; Ren, Guogang; Yang, Zhuo

    2016-04-01

    Etidronate is one of the best known bisphosphonates (BP) derivatives. It is often used as a reference drug in research related to hypercalcaemia and other common bone diseases. 2,3,3-trisphosphonate (TrisPP) is brand new analogue of BP, that also contains a 'germinal bisphosphonate' unit with an additional phosphoryl group attached in proximity to the BP unit. It is known that BPs bind to calcium by chemisorptions to form Ca-BP complexes through (O)P-C-P(O) moiety and hydrogen coordinations, and so they suppress calcium flow by interfering with Ca(2+) channel operations. The mechanistic actions of BP, involving interactions and regulations of Ca(2+), are somewhat similar to the pathogenesis of well-known neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease and Huntington's disease. To investigate if neuroprotective effects are exhibited by the compounds of interests, we used a rat adrenal pheochromocytoma cell line (PC12) as our in vitro model to observe any occurrence of neuron inter-reflection. We pre-treated these PC12 cells with etidronate and TrisPP before challenging the cells with a high concentration of the neurotoxin, glutamate. Our data showed that pre-treatment with 100 μM etidronate partially ameliorated the glutamate-induced decrease in cell viability (47 %), whereas pre-treating cells with 10-100 μM TrisPP showed remarkable cell protection (78-86 %). Moreover, pre-treatments of the cells with etidronate or TrisPP attenuated cell apoptosis, reactive oxygen species generation, Ca(2+) overloading and caspase-3 protein expression, which were associated with a remarkable increase in superoxide dismutase activity in our glutamate-injured PC12 cells. Therefore, this study supports the notion that etidronate and TrisPP may be promising neuroprotective agents.

  18. Progesterone neuroprotection: The background of clinical trial failure.

    Science.gov (United States)

    Schumacher, Michael; Denier, Christian; Oudinet, Jean-Paul; Adams, David; Guennoun, Rachida

    2016-06-01

    Since the first pioneering studies in the 1990s, a large number of experimental animal studies have demonstrated the neuroprotective efficacy of progesterone for brain disorders, including traumatic brain injury (TBI). In addition, this steroid has major assets: it easily crosses the blood-brain-barrier, rapidly diffuses throughout the brain and exerts multiple beneficial effects by acting on many molecular and cellular targets. Moreover, progesterone therapies are well tolerated. Notably, increased brain levels of progesterone are part of endogenous neuroprotective responses to injury. The hormone thus emerged as a particularly promising protective candidate for TBI and stroke patients. The positive outcomes of small Phase 2 trials aimed at testing the safety and potential protective efficacy of progesterone in TBI patients then provided support and guidance for two large, multicenter, randomized and placebo-controlled Phase 3 trials, with more than 2000 TBI patients enrolled. The negative outcomes of both trials, named ProTECT III and SyNAPSE, came as a big disappointment. If these trials were successful, progesterone would have become the first efficient neuroprotective drug for brain-injured patients. Thus, progesterone has joined the numerous neuroprotective candidates that have failed in clinical trials. The aim of this review is a reappraisal of the preclinical animal studies, which provided the proof of concept for the clinical trials, and we critically examine the design of the clinical studies. We made efforts to present a balanced view of the strengths and limitations of the translational studies and of some serious issues with the clinical trials. We place particular emphasis on the translational value of animal studies and the relevance of TBI biomarkers. The probability of failure of ProTECT III and SyNAPSE was very high, and we present them within the broader context of other unsuccessful trials. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Early and moderate sensory stimulation exerts a protective effect on perilesion representations of somatosensory cortex after focal ischemic damage.

    Science.gov (United States)

    Xerri, Christian; Zennou-Azogui, Yoh'i

    2014-01-01

    Previous studies have shown that intensive training within an early critical time window after focal cortical ischemia increases the area of damaged tissue and is detrimental to behavioral recovery. We postulated that moderate stimulation initiated soon after the lesion could have protective effects on peri-infarct cortical somatotopic representations. Therefore, we have assessed the effects of mild cutaneous stimulation delivered in an attention-demanding behavioral context on the functional organization of the perilesion somatosensory cortex using high-density electrophysiological mapping. We compared the effects of 6-day training initiated on the 3rd day postlesion (early training; ET) to those of same-duration training started on the 8th day (delayed training; DT). Our findings confirm previous work showing that the absence of training aggravates representational loss in the perilesion zone. In addition, ET was found to be sufficient to limit expansion of the ischemic lesion and reduce tissue loss, and substantially maintain the neuronal responsiveness to tactile stimulation, thereby preserving somatotopic map arrangement in the peri-infarct cortical territories. By contrast, DT did not prevent tissue loss and only partially reinstated lost representations in a use-dependent manner within the spared peri-infarct cortical area. This study differentiates the effects of early versus delayed training on perilesion tissue and cortical map reorganization, and underscores the neuroprotective influence of mild rehabilitative stimulation on neuronal response properties in the peri-infarct cortex during an early critical period.

  20. Immunoregulatory Effects of Paeoniflorin Exerts Anti-asthmatic Effects via Modulation of the Th1/Th2 Equilibrium.

    Science.gov (United States)

    Zhang, Tianzhu; Yang, Zhaocong; Yang, Shihai; Du, Juan; Wang, Shumin

    2015-12-01

    Paeoniflorin has been demonstrated to exert anti-inflammatory and immunomodulatory effects in the animal study. In this study, we investigated immunoregulatory effects of paeoniflorin on anti-asthmatic effects and underlying mechanisms. Asthma model was established by ovalbumin-induced. A total of 50 mice were randomly assigned to five experimental groups: control, model, dexamethasone (2 mg/kg), and paeoniflorin (10 and 20 mg/kg). Airway resistance (Raw) were measured by the forced oscillation technique; histological studies were evaluated by the hematoxylin and eosin (HE) staining; Th1/Th2 cytokines were evaluated by enzyme-linked immunosorbent assay (ELISA); Th1/Th2 cells were evaluated by flow cytometry (FCM); and GATA3 and T-bet were evaluated by Western blot. Our study demonstrated that, compared with model group, paeoniflorin inhibited ovalbumin (OVA)-induced increases in Raw and eosinophil count; interleukin (IL)-4, IgE levels were recovered in bronchoalveolar lavage fluid compared; increased IFN-γ level in bronchoalveolar lavage fluid; histological studies demonstrated that paeoniflorin substantially inhibited OVA-induced eosinophilia in lung tissue and lung tissue compared with model group. Flow cytometry studies demonstrated that paeoniflorin can regulate Th1/Th2 balance. These findings suggest that paeoniflorin may effectively ameliorate the progression of asthma and could be used as a therapy for patients with allergic asthma.

  1. HER Specific TKIs Exert Their Antineoplastic Effects on Breast Cancer Cell Lines through the Involvement of STAT5 and JNK.

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    Daphne Gschwantler-Kaulich

    Full Text Available HER-targeted tyrosine kinase inhibitors (TKIs have demonstrated pro-apoptotic and antiproliferative effects in vitro and in vivo. The exact pathways through which TKIs exert their antineoplastic effects are, however, still not completely understood.Using Milliplex assays, we have investigated the effects of the three panHER-TKIs lapatinib, canertinib and afatinib on signal transduction cascade activation in SKBR3, T47D and Jurkat neoplastic cell lines. The growth-inhibitory effect of blockade of HER and of JNK and STAT5 signaling was measured by proliferation- and apoptosis-assays using formazan dye labeling of viable cells, Western blotting for cleaved PARP-1 and immunolabeling for active caspase 3, respectively.All three HER-TKIs clearly inhibited proliferation and increased apoptosis in HER2 overexpressing SKBR3 cells, while their effect was less pronounced on HER2 moderately expressing T47D cells where they exerted only a weak antiproliferative and essentially no pro-apoptotic effect. Remarkably, phosphorylation/activation of JNK and STAT5A/B were inhibited by HER-TKIs only in the sensitive, but not in the resistant cells. In contrast, phosphorylation/activation of ERK/MAPK, STAT3, CREB, p70 S6 kinase, IkBa, and p38 were equally affected by HER-TKIs in both cell lines. Moreover, we demonstrated that direct pharmacological blockade of JNK and STAT5 abrogates cell growth in both HER-TKI-sensitive as well as -resistant breast cancer cells, respectively.We have shown that HER-TKIs exert a HER2 expression-dependent anti-cancer effect in breast cancer cell lines. This involves blockade of JNK and STAT5A/B signaling, which have been found to be required for in vitro growth of these cell lines.

  2. Tert-buthylhydroquinone pre-conditioning exerts dual effects in old female rats exposed to 3-nitropropionic acid

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    Alejandro Silva-Palacios

    2017-08-01

    Full Text Available The brain is a very susceptible organ to structural and functional alterations caused by oxidative stress and its vulnerability increases with age. Understanding the antioxidant response activated by the transcription factor Nrf2 has become very important in the aging field in order to activate cellular protection. However, the role of Nrf2 inducers during old age has not been completely understood. Our aim was to activate the Nrf2 pathway by pre-treating old rats with a widely used Nrf2-inducer, tert-buthylhydroquinone (tBHQ, prior to 3-nitropropionic acid (3-NP insult, in order to evaluate its effects at a behavioral, morphological and biochemical levels. 3-NP has been used to reproduce the biochemical and pathophysiological characteristics of Huntington's disease due to an oxidative effect. Our results suggest that tBHQ confers an important protective effect against 3-NP toxicity; nevertheless, Nrf2 seems not to be the main protective pathway associated to neuroprotection. Hormetic responses include the activation of more than one transcription factor. Nrf2 and NFκB are known to simultaneously initiate different cellular responses against stress by triggering parallel mechanisms, therefore NFκB nuclear accumulation was also evaluated. Keywords: Aging, Nrf2 signaling, Tert-Buthylhydroquinone, Oxidative stress, 3-Nitropropionic acid

  3. Neuroprotective Potential of Mesenchymal Stem Cell-Based Therapy in Acute Stages of TNBS-Induced Colitis in Guinea-Pigs.

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    Ainsley M Robinson

    Full Text Available The therapeutic benefits of mesenchymal stem cells (MSCs, such as homing ability, multipotent differentiation capacity and secretion of soluble bioactive factors which exert neuroprotective, anti-inflammatory and immunomodulatory properties, have been attributed to attenuation of autoimmune, inflammatory and neurodegenerative disorders. In this study, we aimed to determine the earliest time point at which locally administered MSC-based therapies avert enteric neuronal loss and damage associated with intestinal inflammation in the guinea-pig model of colitis.At 3 hours after induction of colitis by 2,4,6-trinitrobenzene-sulfonate (TNBS, guinea-pigs received either human bone marrow-derived MSCs, conditioned medium (CM, or unconditioned medium by enema into the colon. Colon tissues were collected 6, 24 and 72 hours after administration of TNBS. Effects on body weight, gross morphological damage, immune cell infiltration and myenteric neurons were evaluated. RT-PCR, flow cytometry and antibody array kit were used to identify neurotrophic and neuroprotective factors released by MSCs.MSC and CM treatments prevented body weight loss, reduced infiltration of leukocytes into the colon wall and the myenteric plexus, facilitated repair of damaged tissue and nerve fibers, averted myenteric neuronal loss, as well as changes in neuronal subpopulations. The neuroprotective effects of MSC and CM treatments were observed as early as 24 hours after induction of inflammation even though the inflammatory reaction at the level of the myenteric ganglia had not completely subsided. Substantial number of neurotrophic and neuroprotective factors released by MSCs was identified in their secretome.MSC-based therapies applied at the acute stages of TNBS-induced colitis start exerting their neuroprotective effects towards enteric neurons by 24 hours post treatment. The neuroprotective efficacy of MSC-based therapies can be exerted independently to their anti

  4. Decreased extracellular adenosine levels lead to loss of hypoxia-induced neuroprotection after repeated episodes of exposure to hypoxia.

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    Mei Cui

    Full Text Available Achieving a prolonged neuroprotective state following transient ischemic attacks (TIAs is likely to effectively reduce the brain damage and neurological dysfunction associated with recurrent stroke. HPC is a phenomenon in which advanced exposure to mild hypoxia reduces the stroke volume produced by a subsequent TIA. However, this neuroprotection is not long-lasting, with the effects reaching a peak after 3 days. Therefore, in this study, we investigated the use of multiple episodes of hypoxic exposure at different time intervals to induce longer-term protection in a mouse stroke model. C57BL/6 mice were subjected to different hypoxic preconditioning protocols: a single episode of HPC or five identical episodes at intervals of 3 days (E3d HPC or 6 days (E6d HPC. Three days after the last hypoxic exposure, temporary middle cerebral artery occlusion (MCAO was induced. The effects of these HPC protocols on hypoxia-inducible factor (HIF regulated gene mRNA expression were measured by quantitative PCR. Changes in extracellular adenosine concentrations, known to exert neuroprotective effects, were also measured using in vivo microdialysis and high pressure liquid chromatography (HPLC. Neuroprotection was provided by E6d HPC but not E3d HPC. HIF-regulated target gene expression increased significantly following all HPC protocols. However, E3d HPC significantly decreased extracellular adenosine and reduced cerebral blood flow in the ischemic region with upregulated expression of the adenosine transporter, equilibrative nucleoside transporter 1 (ENT1. An ENT1 inhibitor, propentofylline increased the cerebral blood flow and re-established neuroprotection in E3d HPC. Adenosine receptor specific antagonists showed that adenosine mainly through A1 receptor mediates HPC induced neuroprotection. Our data indicate that cooperation of HIF-regulated genes and extracellular adenosine is necessary for HPC-induced neuroprotection.

  5. Male/female differences in neuroprotection and neuromodulation of brain dopamine.

    Directory of Open Access Journals (Sweden)

    Mélanie eBourque

    2011-09-01

    Full Text Available The existence of a sex difference in Parkinson’s disease is observed in several variables, including susceptibility of the disease, age at onset and symptoms. These differences between men and women represent a significant characteristic of Parkinson’s disease which suggests that estrogens may exert beneficial effects against the development and the progression of the disease. This paper reviews the neuroprotective and neuromodulator effect of 17β-estradiol and progesterone as compared to androgens in the nigrostriatal dopaminergic system of both female and male rodents. The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP mice model of Parkinson’s disease and methamphetamine toxicity faithfully reproduce the sex differences of Parkinson’s disease in that endogenous estrogen levels appear to influence the vulnerability to toxins targeting the nigrostriatal dopaminergic system. Exogenous 17β-estradiol and/or progesterone treatments show neuroprotective properties against nigrostriatal dopaminergic toxins while androgens fail to induce beneficial effect. Sex steroids treatments show males and females difference in their neuroprotective action against methamphetamine toxicity. Nigrostriatal dopaminergic structure and function, as well as the distribution of estrogen receptors, show sex difference and may influence the susceptibility to the toxins and the response to sex steroids. Genomic and non-genomic actions of 17β-estradiol converge to promote survival factors and the presence of both estrogen receptors α and β are critical to 17β-estradiol neuroprotective action against MPTP toxicity.

  6. Ultralow concentrations of bupivacaine exert anti-inflammatory effects on inflammation-reactive astrocytes

    Science.gov (United States)

    Block, Linda; Jörneberg, Per; Björklund, Ulrika; Westerlund, Anna; Biber, Björn; Hansson, Elisabeth

    2013-01-01

    Bupivacaine is a widely used, local anesthetic agent that blocks voltage-gated Na+ channels when used for neuro-axial blockades. Much lower concentrations of bupivacaine than in normal clinical use, bupivacaine exerts an influence on the Ca2+ signaling and interleukin-1β (IL-1β) secretion in inflammation-reactive astrocytes when used at ultralow concentrations, bupivacaine interacts with the opioid-, 5-hydroxytryptamine- (5-HT) and glutamate-receptor systems. With respect to the μ-opioid- and 5-HT-receptor systems, bupivacaine restored the inflammation-reactive astrocytes to their normal non-inflammatory levels. With respect to the glutamate-receptor system, bupivacaine, in combination with an ultralow concentration of the μ-opioid receptor antagonist naloxone and μ-opioid receptor agonists, restored the inflammation-reactive astrocytes to their normal non-inflammatory levels. Ultralow concentrations of bupivacaine attenuated the inflammation-induced upregulation of IL-1β secretion. The results indicate that bupivacaine interacts with the opioid-, 5-HT- and glutamate-receptor systems by affecting Ca2+ signaling and IL-1β release in inflammation-reactive astrocytes. These results suggest that bupivacaine may be used at ultralow concentrations as an anti-inflammatory drug, either alone or in combination with opioid agonists and ultralow concentrations of an opioid antagonist. PMID:24083665

  7. Effect of Music Tempo on Attentional Focus and Perceived Exertion during Self-selected Paced Walking.

    Science.gov (United States)

    Silva, Aldo Coelho; Dos Santos Ferreira, Sandro; Alves, Ragami Chaves; Follador, Lucio; DA Silva, Sergio Gregorio

    2016-01-01

    This study investigated the influence of music on the rating of perceived exertion (RPE) and attentional focus during walking at a self-selected pace. Fifteen overweight and obese women volunteered to participate in the study. They underwent four sessions: the first for incremental maximal test and anthropometric measurement followed by three experimental sessions. After the first session, they were exposed to three 30-minute walking sessions at a self-selected pace in a counterbalanced order: fast-tempo music (FT), medium-tempo music (MT) and no-music control (NM). Borg's RPE Scale and an Attentional Focus Questionnaire were used to measure the perceptual response and attentional focus, respectively. Results showed that the RPE was higher in the no-music control than in the medium-tempo music (12.05 ± 0.6 vs. 10.5 ± 0.5). Furthermore, dissociative attentional focus was greater for both conditions with music in comparison with the no-music control (NM= 39.0 ± 4.1; MT= 48.4 ± 4.1 and FT= 47.9 ± 4.5). The results indicated that the use of music during walking can modulate attentional focus, increasing dissociative thought, and medium-tempo music can reduce the RPE.

  8. Effect of magnesium sulfate administration for neuroprotection on latency in women with preterm premature rupture of membranes.

    LENUS (Irish Health Repository)

    Horton, Amanda L

    2015-03-01

    This study aims to evaluate whether magnesium sulfate administration for neuroprotection prolongs latency in women with preterm premature rupture of membranes (PPROM) between 24 and 31(6\\/7) weeks\\' gestation.

  9. Neuroprotective Effects of Bioactive Compounds and MAPK Pathway Modulation in “Ischemia”—Stressed PC12 Pheochromocytoma Cells

    Science.gov (United States)

    Lahiani, Adi; Brand-Yavin, Annette; Yavin, Ephraim

    2018-01-01

    This review surveys the efforts taken to investigate in vitro neuroprotective features of synthetic compounds and cell-released growth factors on PC12 clonal cell line temporarily deprived of oxygen and glucose followed by reoxygenation (OGD/R). These cells have been used previously to mimic some of the properties of in vivo brain ischemia-reperfusion-injury (IRI) and have been instrumental in identifying common mechanisms such as calcium overload, redox potential, lipid peroxidation and MAPKs modulation. In addition, they were useful for establishing the role of certain membrane penetrable cocktails of antioxidants as well as potential growth factors which may act in neuroprotection. Pharmacological mechanisms of neuroprotection addressing modulation of the MAPK cascade and increased redox potential by natural products, drugs and growth factors secreted by stem cells, in either undifferentiated or nerve growth factor-differentiated PC12 cells exposed to ischemic conditions are discussed for future prospects in neuroprotection studies. PMID:29419806

  10. Differential effects of ethanol antagonism and neuroprotection in peptide fragment NAPVSIPQ prevention of ethanol-induced developmental toxicity

    OpenAIRE

    Wilkemeyer, Michael F.; Chen, Shao-yu; Menkari, Carrie E.; Brenneman, Douglas E.; Sulik, Kathleen K.; Charness, Michael E.

    2003-01-01

    NAPVSIPQ (NAP), an active fragment of the glial-derived activity-dependent neuroprotective protein, is protective at femtomolar concentrations against a wide array of neural insults and prevents ethanol-induced fetal wastage and growth retardation in mice. NAP also antagonizes ethanol inhibition of L1-mediated cell adhesion (ethanol antagonism). We performed an Ala scanning substitution of NAP to determine the role of ethanol antagonism and neuroprotection in NAP preve...

  11. Nicotinamide riboside, a trace nutrient in foods, is a vitamin B3 with effects on energy metabolism and neuroprotection.

    Science.gov (United States)

    Chi, Yuling; Sauve, Anthony A

    2013-11-01

    This review focuses upon the biology and metabolism of a trace component in foods called nicotinamide riboside. Nicotinamide riboside is a precursor of nicotinamide adenine dinucleotide (NAD), and is a source of Vitamin B3. Evidence indicates that nicotinamide riboside has unique properties as a Vitamin B3. We review knowledge of the metabolism of this substance, as well as recent work suggesting novel health benefits that might be associated with nicotinamide riboside taken in larger quantities than is found naturally in foods. Recent work investigating the effects of nicotinamide riboside in yeast and mammals established that it is metabolized by at least two types of metabolic pathways. The first of these is degradative and produces nicotinamide. The second pathway involves kinases called nicotinamide riboside kinases (Nrk1 and Nrk2, in humans). The likely involvement of the kinase pathway is implicated in the unique effects of nicotinamide riboside in raising tissue NAD concentrations in rodents and for potent effects in eliciting insulin sensitivity, mitochondrial biogenesis, and enhancement of sirtuin functions. Additional studies with nicotinamide riboside in models of Alzheimer's disease indicate bioavailability to brain and protective effects, likely by stimulation of brain NAD synthesis. Initial studies have clarified the potential for a lesser-known Vitamin B3 called nicotinamide riboside that is available in selected foods, and possibly available to humans by supplements. It has properties that are insulin sensitizing, enhancing to exercise, resisting to negative effects of high-fat diet, and neuroprotecting.

  12. Acupuncture elicits neuroprotective effect by inhibiting NAPDH oxidase-mediated reactive oxygen species production in cerebral ischaemia.

    Science.gov (United States)

    Shi, Guang-Xia; Wang, Xue-Rui; Yan, Chao-Qun; He, Tian; Yang, Jing-Wen; Zeng, Xiang-Hong; Xu, Qian; Zhu, Wen; Du, Si-Qi; Liu, Cun-Zhi

    2015-12-10

    In the current study, we aimed to investigate whether NADPH oxidase, a major ROS-producing enzyme, was involved in the antioxidant effect of acupuncture on cognitive impairment after cerebral ischaemia. The cognitive function, infract size, neuron cell loss, level of superoxide anion and expression of NADPH oxidase subunit in hippocampus of two-vessel occlusion (2VO) rats were determined after 2-week acupuncture. Furthermore, the cognitive function and production of O2(-) were determined in the presence and absence of NADPH oxidase agonist (TBCA) and antagonist (Apocynin). The effect of acupuncture on cognitive function after cerebral ischaemia in gp91phox-KO mice was evaluated by Morris water maze. Acupuncture reduced infarct size, attenuated overproduction of O2(-), and reversed consequential cognitive impairment and neuron cell loss in 2VO rats. The elevations of gp91phox and p47phox after 2VO were significantly decreased after acupuncture treatment. However, no differences of gp91phox mRNA were found among any experimental groups. Furthermore, these beneficial effects were reversed by TBCA, whereas apocynin mimicked the effect of acupuncture by improving cognitive function and decreasing O2(-) generation. Acupuncture failed to improve the memory impairment in gp91phox KO mice. Full function of the NADPH oxidase enzyme plays an important role in neuroprotective effects against cognitive impairment via inhibition of NAPDH oxidase-mediated oxidative stress.

  13. Neuroprotective, Anti-Amyloidogenic and Neurotrophic Effects of Apigenin in an Alzheimer’s Disease Mouse Model

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    Lu Zhang

    2013-08-01

    Full Text Available Alzheimer’s disease (AD is a neurodegenerative disorder characterized by extracellular senile plaques and intracellular neurofibrillary tangles in the brain. Amyloid-β peptides (Aβ are considered to play a critical role in the onset and progression of AD. Apigenin (4',5,7-trihydroxyflavone is a pharmacologically active agent. Even though some evidence suggests that it has potential neuroprotective effects, no preexisting study has reported any therapeutic effects of apigenin in AD models. In the present study, we examined the effects of apigenin on cognitive function in APP/PS1 double transgenic AD mice and explored its mechanism(s of action. Three-month oral treatment with apigenin rescued learning deficits and relieved memory retention in APP/PS1 mice. Apigenin also showed effects affecting APP processing and preventing Aβ burden due to the down-regulation of BACE1 and β-CTF levels, the relief of Aβ deposition, and the decrease of insoluble Aβ levels. Moreover, apigenin exhibited superoxide anion scavenging effects and improved antioxidative enzyme activity of superoxide dismutase and glutathione peroxidase. In addition, apigenin restored neurotrophic ERK/CREB/BDNF pathway in the cerebral cortex. In conclusion, apigenin may ameliorate AD-associated learning and memory impairment through relieving Aβ burden, suppressing amyloidogenic process, inhibiting oxidative stress, and restoring ERK/CREB/BDNF pathway. Therefore, apigenin appears to represent an alternative medication for the prevention and/or therapy of AD.

  14. Progesterone Exerts a Neuromodulatory Effect on Turning Behavior of Hemiparkinsonian Male Rats: Expression of 3α-Hydroxysteroid Oxidoreductase and Allopregnanolone as Suggestive of GABAA Receptors Involvement

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    Roberto Yunes

    2015-01-01

    Full Text Available There is a growing amount of evidence for a neuroprotective role of progesterone and its neuroactive metabolite, allopregnanolone, in animal models of neurodegenerative diseases. By using a model of hemiparkinsonism in male rats, injection of the neurotoxic 6-OHDA in left striatum, we studied progesterone’s effects on rotational behavior induced by amphetamine or apomorphine. Also, in order to find potential explanatory mechanisms, we studied expression and activity of nigrostriatal 3α-hydroxysteroid oxidoreductase, the enzyme that catalyzes progesterone to its active metabolite allopregnanolone. Coherently, we tested allopregnanolone for a possible neuromodulatory effect on rotational behavior. Also, since allopregnanolone is known as a GABAA modulator, we finally examined the action of GABAA antagonist bicuculline. We found that progesterone, in addition to an apparent neuroprotective effect, also increased ipsilateral expression and activity of 3α-hydroxysteroid oxidoreductase. It was interesting to note that ipsilateral administration of allopregnanolone reversed a clear sign of motor neurodegeneration, that is, contralateral rotational behavior. A possible GABAA involvement modulated by allopregnanolone was shown by the blocking effect of bicuculline. Our results suggest that early administration of progesterone possibly activates genomic mechanisms that promote neuroprotection subchronically. This, in turn, could be partially mediated by fast, nongenomic, actions of allopregnanolone acting as an acute modulator of GABAergic transmission.

  15. Neuroprotective effect of combining tanshinone IIA with low-dose methylprednisolone following acute spinal cord injury in rats.

    Science.gov (United States)

    Yao, Nian-Wei; Lu, Yuan; Shi, Li-Qi; Xu, Feng; Cai, Xian-Hua

    2017-05-01

    The present study compared the potential neuroprotective effect of tanshinone IIA (TIIA) monotherapy, methylprednisolone (MP) monotherapy and combined treatment in an adult acute spinal cord injury (ASCI) rat model. The current study used the weight-drop method (Allen's Impactor) in the rat model and the mechanical scratch method in primary spinal cord neuron culture to determine whether the combined treatment was able to reduce the required dosage of MP in the treatment of ASCI to produce a similar or improved therapeutic effect. In vivo male Sprague Dawley rats (n=60) were randomly divided into 5 groups, of which 12 rats were selected for the sham group and T9-T11 laminectomies, leading to ASCI, were performed on 48 of the 60 rats using a 10 g ×25 mm weight-drop at the level of T10 spinal cord. Therefore, the ASCI group (n=12) included the 'laminectomy and weight-drop'. The remaining 36 ASCI model animals were subdivided into 3 groups (n=12 each group): TIIA group (30 mg/kg/day), MP group (30 mg/kg) and combined treatment group (TIIA 30 mg/kg/day + MP 20 mg/kg). Neuronal function following ASCI was evaluated using the Basso Beattie Bresnahan (BBB) locomotor rating scale. Levels of the anti-apoptotic factor B-cell lymphoma-2 (Bcl-2), the pro-apoptotic factors Bcl-2 associated protein X (Bax) and caspase-3, and the inflammatory associated factor nuclear factor-κB, were analyzed by western blot analysis. Immunohistochemistry was used to detect caspase-3. To investigate the underlying mechanism, the anti-oxidative effect of combination TIIA and MP treatment was assessed by measuring the activity of malondialdehyde (MDA) and superoxide dismutase (SOD) in ASCI. In agreement with the experiment in vivo , primary neurons were prepared from the spinal cord of one-day-old Sprague-Dawley rats' and co-cultured with astrocytes from the brain cortex. The injury of neurons was induced by mechanical scratch and levels of apoptosis factors were analyzed by western blot analysis

  16. Effect of wearing clothes on oxygen uptake and ratings of perceived exertion while swimming.

    Science.gov (United States)

    Choi, S W; Kurokawa, T; Ebisu, Y; Kikkawa, K; Shiokawa, M; Yamasaki, M

    2000-07-01

    For a comparative study between swimming in swimwear (control-sw) and swimming in clothes (clothes-sw), oxygen uptake (VO2) and ratings of perceived exertion (RPE) were measured. The subjects were six male members of a university swimming team. Three swimming strokes--the breaststroke, the front crawl stroke and the elementary backstroke--were applied. With regards to clothes-sw, swimmers wore T-shirts, sportswear (shirt and pants) over swimwear and running shoes. In both cases of control-sw and clothes-sw, the VO2 was increased exponentially with increased swimming speed. The VO2 of the subjects during the clothed tests did not exceed 1.4 times of that in the case of control-sw at swimming speeds below 0.3 m/s. As swimming speeds increased, VO2 difference in both cases increased. Consequently, VO2 in the clothed tests was equal to 1.5-1.6 times and 1.5-1.8 times of that in the swimwear tests at speeds of 0.5 and 0.7 m/s, respectively. At speeds below 0.6 m/s in clothes-sw, the breaststroke showed lower VO2 than the front crawl stroke, and the elementary backstroke showed higher VO2 than the other two swimming strokes. RPE increased linearly with %peak VO2. In addition, any RPE differences among the three swimming strokes were not shown in the control-sw tests. At an exercise intensity above 60 %peak VO2, clothed swimmers showed slightly higher RPE in the front crawl stroke compared to that in the two other swimming strokes.

  17. Neuroprotective Effects of α-Tocotrienol on Kainic Acid-Induced Neurotoxicity in Organotypic Hippocampal Slice Cultures

    Directory of Open Access Journals (Sweden)

    Bae Hwan Lee

    2013-09-01

    Full Text Available Vitamin E, such as alpha-tocopherol (ATPH and alpha-tocotrienol (ATTN, is a chain-breaking antioxidant that prevents the chain propagation step during lipid peroxidation. In the present study, we investigated the effects of ATTN on KA-induced neuronal death using organotypic hippocampal slice culture (OHSC and compared the neuroprotective effects of ATTN and ATPH. After 15 h KA (5 µM treatment, delayed neuronal death was detected in the CA3 region and reactive oxygen species (ROS formation and lipid peroxidation were also increased. Both co-treatment and post-treatment of ATPH (100 µM or ATTN (100 µM significantly increased the cell survival and reduced the number of TUNEL-positive cells in the CA3 region. Increased dichlorofluorescein (DCF fluorescence and levels of thiobarbiturate reactive substances (TBARS were decreased by ATPH and ATTN treatment. These data suggest that ATPH and ATTN treatment have protective effects on KA-induced cell death in OHSC. ATTN treatment tended to be more effective than ATPH treatment, even though there was no significant difference between ATPH and ATTN in co-treatment or post-treatment.

  18. Cognitive deficits and decreased locomotor activity induced by single-walled carbon nanotubes and neuroprotective effects of ascorbic acid

    Science.gov (United States)

    Liu, Xudong; Zhang, Yuchao; Li, Jinquan; Wang, Dong; Wu, Yang; Li, Yan; Lu, Zhisong; Yu, Samuel CT; Li, Rui; Yang, Xu

    2014-01-01

    Single-walled carbon nanotubes (SWCNTs) have shown increasing promise in the field of biomedicine, especially in applications related to the nervous system. However, there are limited studies available on the neurotoxicity of SWCNTs used in vivo. In this study, neurobehavioral changes caused by SWCNTs in mice and oxidative stress were investigated. The results of ethological analysis (Morris water maze and open-field test), brain histopathological examination, and assessments of oxidative stress (reactive oxygen species [ROS], malondialdehyde [MDA], and glutathione [GSH]), inflammation (nuclear factor κB, tumor necrosis factor α, interleukin-1β), and apoptosis (cysteine-aspartic acid protease 3) in brains showed that 6.25 and 12.50 mg/kg/day SWCNTs in mice could induce cognitive deficits and decreased locomotor activity, brain histopathological alterations, and increased levels of oxidative stress, inflammation, and apoptosis in mouse brains; however, 3.125 mg/kg/day SWCNTs had zero or minor adverse effects in mice, and these effects were blocked by concurrent administration of ascorbic acid. Down-regulation of oxidative stress, inflammation, and apoptosis were proposed to explain the neuroprotective effects of ascorbic acid. This work suggests SWCNTs could induce cognitive deficits and decreased locomotor activity, and provides a strategy to avoid the adverse effects. PMID:24596461

  19. Isolation of the sapogenin from defatted seeds of Camellia oleifera and its neuroprotective effects on dopaminergic neurons.

    Science.gov (United States)

    Ye, Yong; Fang, Fei; Li, Yue

    2014-07-02

    Sasanqua saponin is a major active compound in the defatted seeds of Camellia oleifera but is always discarded without effective utilization. The sapogenin from hydrolysis of sasanqua saponin was purified, and its amination derivative was investigated on its neuroprotective effects, which were evaluated by animal models of Parkinson disease in mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The results showed that the sapogenin and its derivative increased dopamine content in striatum and tyrosine hydroxylase (TH) positive cells in substantia nigra and relieved inflammation and behavioral disorder, but the effect on movement was reversed by dopamine receptor antagonist haloperidol and was not intervened by adenosine receptor antagonist CGS 15943. Molecular simulation showed the interaction between dopamine receptor and the sapogenin or its derivative. It is proven that the sapogenin can protect dopamine neurons through antineuroinflammation and activation of dopamine receptor rather than adenosine receptor, and its amination improves the effects. This research provides the prospective prodrugs for Parkinson disease and a new medicinal application of sasanqua saponin.

  20. The quaternary lidocaine derivative, QX-314, exerts biphasic effects on transient receptor potential vanilloid subtype 1 channels in vitro

    DEFF Research Database (Denmark)

    Rivera-Acevedo, Ricardo E; Pless, Stephan Alexander; Ahern, Christopher A

    2011-01-01

    BACKGROUND: Transient receptor potential vanilloid subfamily member 1 (TRPV1) channels are important integrators of noxious stimuli with pronounced expression in nociceptive neurons. The experimental local anesthetic, QX-314, a quaternary (i.e., permanently charged) lidocaine derivative, recently...... concentrations (less than 1 mM), QX-314 potently inhibited capsaicin-evoked TRPV1 currents with an IC₅₀ of 8.0 ± 0.6 μM. CONCLUSIONS: The results of this study show that the quaternary lidocaine derivative QX-314 exerts biphasic effects on TRPV1 channels, inhibiting capsaicin-evoked TRPV1 currents at lower...

  1. Effect of interval training intensity on fat oxidation, blood lactate and the rate of perceived exertion in obese men

    OpenAIRE

    Alkahtani, Shaea A; King, Neil A; Hills, Andrew P; Byrne, Nuala M

    2013-01-01

    Purpose The objectives of this study were to examine the effect of 4-week moderate- and high-intensity interval training (MIIT and HIIT) on fat oxidation and the responses of blood lactate (BLa) and rating of perceived exertion (RPE). Methods Ten overweight/obese men (age?=?29 ?3.7?years, BMI?=?30.7 ?3.4?kg/m2) participated in a cross-over study of 4-week MIIT and HIIT training. The MIIT training sessions consisted of 5-min cycling stages at mechanical workloads 20% above and 20% below 45%VO2...

  2. The effect of home-based inspiratory muscle training on exercise capacity, exertional dyspnea and pulmonary function in COPD patients.

    Science.gov (United States)

    Bavarsad, Maryam Bakhshandeh; Shariati, Abdolali; Eidani, Esmaeil; Latifi, Mahmud

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is currently the fourth cause of mortality worldwide. Patients with COPD experience periods of dyspnea, fatigue, and disability, which impact on their life. The objective of this study was to investigate the effect of short-term inspiratory muscle training on exercise capacity, exertional dyspnea, and pulmonary lung function. A randomized, controlled trial was performed. Thirty patients (27 males, 3 females) with mild to very severe COPD were randomly assigned to a training group (group T) or to a control group (group C). Patients in group T received training for 8 weeks (15 min/day for 6 days/week) with flow-volumetric inspiratory exerciser named (Respivol). Each patient was assessed before and after 8 weeks of training for the following clinical parameters: exercise capacity by 6-min walking test (6MWT), exertional dyspnea by Borg scale, and pulmonary lung function by spirometry. Patients used training together with medical treatment. The data were analyzed using paired t-test and independent t-test. Results showed statistically significant increase in 6MWT at the end of the training from 445.6 ± 22.99 to 491.06 ± 17.67 meters? (P training group but not in the control group. The values for exercise capacity and dyspnea improved after 8 weeks in group T in comparison with group C (P = 0.001 and P = 0.0001, respectively). No changes were observed in any measure of pulmonary function in both groups. Short-term inspiratory muscle training has beneficial effects on exercise capacity and exertional dyspnea in COPD patients.

  3. Tungsten carbide cobalt nanoparticles exert hypoxia-like effects on the gene expression level in human keratinocytes.

    Science.gov (United States)

    Busch, Wibke; Kühnel, Dana; Schirmer, Kristin; Scholz, Stefan

    2010-01-27

    Tungsten carbide (WC) and tungsten carbide cobalt (WC-Co) nanoparticles are of occupational health relevance because of the increasing usage in hard metal industries. Earlier studies showed an enhanced toxic potential for WC-Co compared to WC or cobalt ions alone. Therefore, we investigated the impact of these particles, compared to cobalt ions applied as CoCl(2), on the global gene expression level in human keratinocytes (HaCaT) in vitro. WC nanoparticles exerted very little effects on the transcriptomic level after 3 hours and 3 days of exposure. In contrast, WC-Co nanoparticles caused significant transcriptional changes that were similar to those provoked by CoCl(2). However, CoCl(2) exerted even more pronounced changes in the transcription patterns. Gene set enrichment analyses revealed that the differentially expressed genes were related to hypoxia response, carbohydrate metabolism, endocrine pathways, and targets of several transcription factors. The role of the transcription factor HIF1 (hypoxia inducible factor 1) is particularly highlighted and aspects of downstream events as well as the role of other transcription factors related to cobalt toxicity are considered. This study provides extensive data useful for the understanding of nanoparticle and cobalt toxicity. It shows that WC nanoparticles caused low transcriptional responses while WC-Co nanoparticles are able to exert responses similar to that of free cobalt ions, particularly the induction of hypoxia-like effects via interactions with HIF1alpha in human keratinocytes. However, the enhanced toxicity of WC-Co particles compared to CoCl(2) could not be explained by differences in gene transcription.

  4. Tungsten carbide cobalt nanoparticles exert hypoxia-like effects on the gene expression level in human keratinocytes

    Science.gov (United States)

    2010-01-01

    Background Tungsten carbide (WC) and tungsten carbide cobalt (WC-Co) nanoparticles are of occupational health relevance because of the increasing usage in hard metal industries. Earlier studies showed an enhanced toxic potential for WC-Co compared to WC or cobalt ions alone. Therefore, we investigated the impact of these particles, compared to cobalt ions applied as CoCl2, on the global gene expression level in human keratinocytes (HaCaT) in vitro. Results WC nanoparticles exerted very little effects on the transcriptomic level after 3 hours and 3 days of exposure. In contrast, WC-Co nanoparticles caused significant transcriptional changes that were similar to those provoked by CoCl2. However, CoCl2 exerted even more pronounced changes in the transcription patterns. Gene set enrichment analyses revealed that the differentially expressed genes were related to hypoxia response, carbohydrate metabolism, endocrine pathways, and targets of several transcription factors. The role of the transcription factor HIF1 (hypoxia inducible factor 1) is particularly highlighted and aspects of downstream events as well as the role of other transcription factors related to cobalt toxicity are considered. Conclusions This study provides extensive data useful for the understanding of nanoparticle and cobalt toxicity. It shows that WC nanoparticles caused low transcriptional responses while WC-Co nanoparticles are able to exert responses similar to that of free cobalt ions, particularly the induction of hypoxia-like effects via interactions with HIF1α in human keratinocytes. However, the enhanced toxicity of WC-Co particles compared to CoCl2 could not be explained by differences in gene transcription. PMID:20105288

  5. Neuroprotective and Antiamnesic Effects of Mitragyna inermis Willd (Rubiaceae on Scopolamine-Induced Memory Impairment in Mice

    Directory of Open Access Journals (Sweden)

    David Bougolla Pahaye

    2017-01-01

    Full Text Available Aim. To assess memory improvement and neuroprotective and antioxidant effects of Mitragyna inermis (M. inermis leaf decoction on the central nervous system. Methodology. Leaf decoction of M. inermis was tested on learning and memory in normal and scopolamine-induced cognitive impairment in mice using memory behavioral tests such as the Morris water maze, object recognition task, and elevated plus maze. Oxidative stress enzymes—catalase, superoxide dismutase, and the thiobarbituric acid reactive substance, a product of lipid peroxidation—were quantified. In each test, mice 18 to 25 g were divided into groups of 5. Results. The extract reversed the effects of scopolamine in mice. The extract significantly increased discrimination index in the object recognition task test and inflexion ratio in the elevated plus maze test. The times spent in target quadrant in MWM increased while the transfer latency decreased in mice treated by M. inermis at the dose of 196.5 mg/kg. The activity levels of superoxide dismutase and catalase were significantly increased, whereas the thiobarbituric acid reactive substance was significantly decreased after 8 consecutive days of treatment with M. inermis at the dose of 393 mg/kg. Conclusion. These results suggest that M. inermis leaf extract possess potential antiamnesic effects.

  6. Neuroprotective and Antiamnesic Effects ofMitragyna inermisWilld (Rubiaceae) on Scopolamine-Induced Memory Impairment in Mice.

    Science.gov (United States)

    Pahaye, David Bougolla; Bum, Elisabeth Ngo; Taïwé, Germain Sotoing; Ngoupaye, Gwladys Temkou; Sidiki, Neteydji; Moto, Fleur Clarisse Okomolo; Kouemou, Nadège; Njapdounke, Stephanie Jacqueline Kameni; Nkantchoua, Gisele; Kandeda, Antoine; Omam, Jean Pierre Omam; Mairaira, Veronique; Ojong, Josiane Lucie

    2017-01-01

    Aim . To assess memory improvement and neuroprotective and antioxidant effects of Mitragyna inermis ( M. inermis ) leaf decoction on the central nervous system. Methodology . Leaf decoction of M. inermis was tested on learning and memory in normal and scopolamine-induced cognitive impairment in mice using memory behavioral tests such as the Morris water maze, object recognition task, and elevated plus maze. Oxidative stress enzymes-catalase, superoxide dismutase, and the thiobarbituric acid reactive substance, a product of lipid peroxidation-were quantified. In each test, mice 18 to 25 g were divided into groups of 5. Results . The extract reversed the effects of scopolamine in mice. The extract significantly increased discrimination index in the object recognition task test and inflexion ratio in the elevated plus maze test. The times spent in target quadrant in MWM increased while the transfer latency decreased in mice treated by M. inermis at the dose of 196.5 mg/kg. The activity levels of superoxide dismutase and catalase were significantly increased, whereas the thiobarbituric acid reactive substance was significantly decreased after 8 consecutive days of treatment with M. inermis at the dose of 393 mg/kg. Conclusion . These results suggest that M. inermis leaf extract possess potential antiamnesic effects.

  7. The neuroprotective effects of taurine against nickel by reducing oxidative stress and maintaining mitochondrial function in cortical neurons.

    Science.gov (United States)

    Xu, Shangcheng; He, Mindi; Zhong, Min; Li, Li; Lu, Yonghui; Zhang, Yanwen; Zhang, Lei; Yu, Zhengping; Zhou, Zhou

    2015-03-17

    Previous studies have indicated that oxidative stress and mitochondrial dysfunction are involved in the toxicity of nickel. Taurine is recognized as an efficient antioxidant and is essential for mitochondrial function. To investigate whether taurine could protect against the neurotoxicity of nickel, we exposed primary cultured cortical neurons to various concentrations of nickel chloride (NiCl2; 0.5mM, 1mM and 2mM) for 24h or to 1mM NiCl2 for various periods (0 h, 12h, 24h and 48 h). Our results showed that taurine efficiently reduced lactate dehydrogenase (LDH) release induced by NiCl2. Along with this protective effect, taurine pretreatment not only significantly reversed the increase of ROS production and mitochondrial superoxide concentration, but also attenuated the decrease of superoxide dismutase (SOD) activity and glutathione (GSH) concentration in neurons exposed to NiCl2 for 24h. Moreover, nickel exposure reduced ATP production, disrupted the mitochondrial membrane potential and decreased mtDNA content. These types of oxidative damage in the mitochondria were efficiently ameliorated by taurine pretreatment. Taken together, our results indicate that the neuroprotective effects of taurine against the toxicity of nickel might largely depend on its roles in reducing oxidative stress and improving mitochondrial function. Taurine may have great pharmacological potential in treating the adverse effects of nickel in the nervous system. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. The neuroprotective effect of vitamin E on chronic sleep deprivation-induced memory impairment: the role of oxidative stress.

    Science.gov (United States)

    Alzoubi, Karem H; Khabour, Omar F; Rashid, Baraa Abu; Damaj, Imad M; Salah, Heba A

    2012-01-01

    Sleep deprivation induces oxidative stress and impairs learning and memory processes. Vitamin E, on the other hand, is a strong antioxidant that has neuroprotective effect on the brain. In this study, we examined the potential protective effect of chronic administration of vitamin E on chronic sleep deprivation-induced cognitive impairment. In addition, possible molecular targets for vitamin E effects on chronic sleep deprivation-induced cognitive impairment were determined. Sleep deprivation was induced in rats using modified multiple platform model. Vitamin E (100mg/kg) was administered to animals by oral gavage. Behavioral study was conducted to test the spatial learning and memory using the radial arm water maze (RAWM). In addition, the hippocampus was dissected out and antioxidant markers including glutathione (GSH), oxidized glutathione (GSSG) and GSH/GSSG, glutathione peroxidase (GPx), catalase, and superoxide dismutase (SOD) were assessed. The results of this project revealed that chronic sleep deprivation impaired both (short- and long-term) memories (Psleep deprivation-induced reduction in the hippocampus GSH/GSSG ratio, and activity of catalase, SOD, and GPx. In conclusion, sleep deprivation induces memory impairment, and treatment with vitamin E prevented this impairment probably through its antioxidant action in the hippocampus. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. A comparative study of neuroprotective effect of angiotensin converting enzyme inhibitors against scopolamine-induced memory impairments in rats

    Directory of Open Access Journals (Sweden)

    Talha Jawaid

    2015-01-01

    Full Text Available The comparative study of neuroprotective effect of angiotensin converting enzyme inhibitors against scopolamine-induced neuroinflammation in albino Wistar rats was studied. Male albino rats were administered with scopolamine to induce memory impairment. The standard nootropic agent, piracetam (200 mg/kg b.w., [i.p.], perindopril (0.1 mg/kg b.w., [i.p.], enalapril (0.1 mg/kg b.w., [i.p.], and ramipril (0.1 mg/kg b.w., [i.p.] were administered in different group of animals for 5 days. On 5 th day, scopolamine (1 mg/kg b.w., i.p. was administered after 60 min of the last dose of test drug. Memory function was evaluated in Morris water maze (MWM test and pole climbing test (PCT. Biochemical estimations like glutathione (GSH, malondialdehyde (MDA, and acetylcholinesterase activity in the brain were estimated after completion of behavior study. All three test groups shows improvement in learning and memory in comparison to control group. Perindopril treated group showed a more effective significant decrease in escape latency time and transfer latency time compared to enalapril and ramipril treated group on day 4 in MWM test and PCT, respectively. Perindopril shows a significant reduction in MDA level and acetylcholinesterase activity and a significant rise in GSH level compared to enalapril and ramipril. The finding of this study indicates that Perindopril is more effective in memory retention compared to enalapril and ramipril.

  10. Low Prevalence of Periodontitis in Acromegaly: Growth Hormone May Exert a Protective Effect

    Directory of Open Access Journals (Sweden)

    Hülya Serinsöz

    2015-06-01

    Full Text Available Purpose: To evaluate bone mineral density (BMD measurements and the presence of periodontitis in patients with acromegaly, as well as to inquire the impact of interfering factors. Material and Method: Forty-seven acromegalic patients with any accompanying condition known to affect calcium-bone metabolism and 60 age-matched healthy controls were included. Age, gender, duration and activity of acromegaly, past-present therapy options, pituitary hormone profiles, replacement therapies, and the results of periodontal analysis were recorded. Results: Eighteen patients were male (38.3%, 29 were female (61.7%. The mean age of the patients was 46.6±11.5 years, twenty-five (53.1% had active, 22 (46.8% had inactive acromegaly. The latter were older and had longer disease duration (p=0.04, p=0.003, respectively. Serum calcium and phosphorus levels, 24-hour urinary calcium excretion and BMD at the lumbar spine and femur neck insignificantly associated with disease activity (p>0.05. Osteoporosis was detected in 6 patients (12.76%. Periodontitis and advanced periodontitis were more common in control group (66.7% vs. 44.7%, (43.3% vs. 12.8% (p=0.022, p=0.0001, respectively. There was no difference in chronic periodontitis and severity between active and inactive groups (48% vs. 40.9%; p=0.279. No difference was noted in other study parameters, as well. Repeated measures analysis of variance demonstrated statistically insignificant distribution between GH change in time and periodontitis subgroups. Discussion: We demonstrated that acromegaly exerted no clear negative impact on vertebral BMD in the absence of overt hypogonadism. Regardless of disease activity, acromegaly cases exhibited lower rates of periodontitis with less severity which remained unchanged in the presence of accompanying metabolic disorders known to have negative impact on periodontal tissue. Chronic exposure to excess GH may have a protective role against periodontitis. Turk Jem 2015; 19: 42-48

  11. Tract-based spatial statistics to assess the neuroprotective effect of early erythropoietin on white matter development in preterm infants.

    Science.gov (United States)

    O'Gorman, Ruth L; Bucher, Hans U; Held, Ulrike; Koller, Brigitte M; Hüppi, Petra S; Hagmann, Cornelia F

    2015-02-01

    Despite improved survival, many preterm infants undergo subsequent neurodevelopmental impairment. To date, no neuroprotective therapies have been implemented into clinical practice. Erythropoietin, a haematopoietic cytokine used for treatment of anaemia of prematurity, has been shown to have neuroprotective and neuroregenerative effects on the brain in many experimental studies. The aim of the study was to assess the effect of recombinant human erythropoietin on the microstructural development of the cerebral white matter using tract-based spatial statistics performed at term equivalent age. A randomized, double-blind placebo-controlled, prospective multicentre study applying recombinant human erythropoietin in the first 42 h after preterm birth entitled 'Does erythropoietin improve outcome in preterm infant' was conducted in Switzerland (NCT00413946). Preterm infants were given recombinant human erythropoietin (3000 IU) or an equivalent volume of placebo (NaCl 0.9%) intravenously before 3 h of age after birth, at 12-18 h and at 36-42 h after birth. High resolution diffusion tensor imaging was obtained at 3 T in 58 preterm infants with mean (standard deviation) gestational age at birth 29.75 (1.44) weeks, and at scanning at 41.1 (2.09) weeks. Imaging was performed at a single centre. Voxel-wise statistical analysis of the fractional anisotropy data was carried out using tract-based spatial statistics to test for differences in fractional anisotropy between infants treated with recombinant human erythropoietin and placebo using a general linear model, covarying for the gestational age at birth and the corrected gestational age at the time of the scan. Preterm infants treated with recombinant human erythropoietin demonstrated increased fractional anisotropy in the genu and splenium of the corpus callosum, the anterior and posterior limbs of the internal capsule, and the corticospinal tract bilaterally. Mean fractional anisotropy was significantly higher in preterm

  12. Structure-activity relationships for flavone interactions with amyloid β reveal a novel anti-aggregatory and neuroprotective effect of 2',3',4'-trihydroxyflavone (2-D08).

    Science.gov (United States)

    Marsh, Dylan T; Das, Sukanya; Ridell, Jessica; Smid, Scott D

    2017-07-15

    Naturally-occurring flavonoids have well documented anti-aggregatory and neuroprotective properties against the hallmark toxic protein in Alzheimer's disease, amyloid β (Aβ). However the extensive diversity of flavonoids has limited the insight into the precise structure-activity relationships that confer such bioactive properties against the Aβ protein. In the present study we have characterised the Aβ binding properties, anti-aggregatory and neuroprotective effects of a discreet set of flavones, including the recently described novel protein sumoylation inhibitor 2',3',4'-trihydroxyflavone (2-D08). Quercetin, transilitin, jaceosidin, nobiletin and 2-D08 were incubated with human Aβ 1-42 for 48h in vitro and effects on Aβ fibrillisation kinetics and morphology measured using Thioflavin T (ThT) and electron microscopy respectively, in addition to effects on neuronal PC12 cell viability. Of the flavones studied, only quercetin, transilitin and 2-D08 significantly inhibited Aβ 1-42 aggregation and toxicity in PC12 cells. Of those, 2-D08 was the most effective inhibitor. The strong anti-amyloid activity of 2-D08 indicates that extensive hydroxylation in the B ring is the most important determinant of activity against β amyloid within the flavone scaffold. The lack of efficacy of jaceosidin and nobiletin indicate that extension of B ring hydroxylation with methoxyl groups result in an incremental loss of anti-fibrillar and neuroprotective activity, highlighting the constraint to vicinal hydroxyl groups in the B ring for effective inhibition of aggregation. These findings reveal further structural insights into anti-amyloid bioactivity of flavonoids in addition to a novel and efficacious anti-aggregatory and neuroprotective effect of the semi-synthetic flavone and sumoylation inhibitor 2',3',4'-trihydroxyflavone (2-D08). Such modified flavones may facilitate drug development targeting multiple pathways in neurodegenerative disease. Crown Copyright © 2017

  13. Neuroprotective Effect of Puerarin on Glutamate-Induced Cytotoxicity in Differentiated Y-79 Cells via Inhibition of ROS Generation and Ca(2+) Influx.

    Science.gov (United States)

    Wang, Ke; Zhu, Xue; Zhang, Kai; Wu, Zhifeng; Sun, Song; Zhou, Fanfan; Zhu, Ling

    2016-07-11

    Glutamate toxicity is estimated to be the key cause of photoreceptor degeneration in the pathogenesis of retinal degenerative diseases. Oxidative stress and Ca(2+) influx induced by glutamate are responsible for the apoptosis process of photoreceptor degeneration. Puerarin, a primary component of Kudzu root, has been widely used in the clinical treatment of retinal degenerative diseases in China for decades; however, the detailed molecular mechanism underlying this effect remains unclear. In this study, the neuroprotective effect of puerarin against glutamate-induced cytotoxicity in the differentiated Y-79 cells was first investigated through cytotoxicity assay. Then the molecular mechanism of this effect regarding anti-oxidative stress and Ca(2+) hemostasis was further explored with indirect immunofluorescence, flow cytometric analysis and western blot analysis. Our study showed that glutamate induced cell viability loss, excessive reactive oxygen species (ROS) generation, calcium overload and up-regulated cell apoptosis in differentiated Y-79 cells, which effect was significantly attenuated with the pre-treatment of puerarin in a dose-dependent manner. Furthermore, our data indicated that the neuroprotective effect of puerarin was potentially mediated through the inhibition of glutamate-induced activation of mitochondrial-dependent signaling pathway and calmodulin-dependent protein kinase II (CaMKII)-dependent apoptosis signal-regulating kinase 1(ASK-1)/c-Jun N-terminal kinase (JNK)/p38 signaling pathway. The present study supports the notion that puerarin may be a promising neuroprotective agent in the prevention of retinal degenerative diseases.

  14. Neuroprotective Effect and Mechanism of Thiazolidinedione on Dopaminergic Neurons In Vivo and In Vitro in Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Yanqin Wang

    2017-01-01

    Full Text Available The aim of the present study was to gain insight into the neuroprotection effects and mechanism of thiazolidinedione pioglitazone in both in vitro and in vivo MPP+/MPTP induced PD models. In vivo experimental results showed that oral treatment of pioglitazone resulted in significant improvements in behavior symptoms damaged by MPTP and increase in the survival of TH positive neurons in the pioglitazone intervention groups. In addition, oral treatment of pioglitazone increased the expression of peroxisome proliferator-activated receptor-γ coactivator of 1α (PGC-1α and increased the number of mitochondria, along with an observed improvement in mitochondrial ultrastructure. From in vitro studies, 2,4-thiazolidinedione resulted in increased levels of molecules regulated function of mitochondria, including PGC-1α, nuclear respiratory factor 1 (NRF1, NRF2, and mitochondria fusion 2 (Mfn2, and inhibited mitochondria fission 1 (Fis1. We show that protein levels of Bcl-2 and ERK were reduced in the MPP+-treated group compared with the control group. This effect was observed to be reversed upon treatment with 2,4-thiazolidinedione, as Bcl-2 and ERK expression levels were increased. We also observed that levels of the apoptotic protein Bax showed opposite changes compared to Bcl-2 and ERK levels. The results from this study confirm that pioglitazone/2,4-thiazolidinedione is able to activate PGC-1α and prevent damage of dopaminergic neurons and restore mitochondria ultrastructure through the regulation of mitochondria function.

  15. Neuroprotective Effects of Erucin against 6-Hydroxydopamine-Induced Oxidative Damage in a Dopaminergic-like Neuroblastoma Cell Line

    Directory of Open Access Journals (Sweden)

    Giorgio Cantelli-Forti

    2012-08-01

    Full Text Available Oxidative stress (OS contributes to the cascade leading to the dysfunction or death of dopaminergic neurons during Parkinson’s disease (PD. A strategy to prevent the OS of dopaminergic neurons may be the use of phytochemicals as inducers of endogenous antioxidants and phase 2 enzymes. In this study, we demonstrated that treatment of the dopaminergic-like neuroblastoma SH-SY5Y cell line with isothiocyanate erucin (ER, a compound of cruciferous vegetables, resulted in significant increases of both total glutathione (GSH levels and total antioxidant capacity at the cytosolic level. The increase of GSH levels was associated with an increase in the resistance of SH-SY5Y cells to neuronal death, in terms of apoptosis, induced by 6-hydroxydopamine (6-OHDA. The pretreatment of SH-SY5Y cells with ER was also shown to prevent the redox status impairment, in terms of intracellular ROS and O2•− formation, and loss of mitochondrial membrane potential, early events that are initiators of the apoptotic process, induced by 6-OHDA. Last, the antiapoptotic and antioxidant effects of ER were abolished by buthionine sulfoximine, supporting the main role of GSH in the neuroprotective effects recorded by ER. These results suggest that ER may prevent the oxidative damage induced by 6-OHDA.

  16. Inhibitory Effect on Cerebral Inflammatory Response following Traumatic Brain Injury in Rats: A Potential Neuroprotective Mechanism of N-Acetylcysteine

    Directory of Open Access Journals (Sweden)

    Gang Chen

    2008-01-01

    Full Text Available Although N-acetylcysteine (NAC has been shown to be neuroprotective for traumatic brain injury (TBI, the mechanisms for this beneficial effect are still poorly understood. Cerebral inflammation plays an important role in the pathogenesis of secondary brain injury after TBI. However, it has not been investigated whether NAC modulates TBI-induced cerebral inflammatory response. In this work, we investigated the effect of NAC administration on cortical expressions of nuclear factor kappa B (NF-κB and inflammatory proteins such as interleukin-1β (IL-1β, tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6, and intercellular adhesion molecule-1 (ICAM-1 after TBI. As a result, we found that NF-κB, proinflammatory cytokines, and ICAM-1 were increased in all injured animals. In animals given NAC post-TBI, NF-κB, IL-1β, TNF-α, and ICAM-1 were decreased in comparison to vehicle-treated animals. Measures of IL-6 showed no change after NAC treatment. NAC administration reduced brain edema, BBB permeability, and apoptotic index in the injured brain. The results suggest that post-TBI NAC administration may attenuate inflammatory response in the injured rat brain, and this may be one mechanism by which NAC ameliorates secondary brain damage following TBI.

  17. Neuroprotective effect of rapamycin on spinal cord injury via activation of the Wnt/β-catenin signaling pathway

    Directory of Open Access Journals (Sweden)

    Kai Gao

    2015-01-01

    Full Text Available The Wnt/β-catenin signaling pathway plays a crucial role in neural development, axonal guidance, neuropathic pain remission and neuronal survival. In this study, we initially examined the effect of rapamycin on the Wnt/β-catenin signaling pathway after spinal cord injury, by intraperitoneally injecting spinal cord injured rats with rapamycin over 2 days. Western blot analysis and immunofluorescence staining were used to detect the expression levels of β-catenin protein, ca-spase-3 protein and brain-derived neurotrophic factor protein, components of the Wnt/β-catenin signaling pathway. Rapamycin increased the levels of β-catenin and brain-derived neurotrophic factor in the injured spinal cord, improved the pathological morphology at the injury site, reduced the loss of motor neurons, and promoted motor functional recovery in rats after spinal cord injury. Our experimental findings suggest that the neuroprotective effect of rapamycin intervention is mediated through activation of the Wnt/β-catenin signaling pathway after spinal cord injury.

  18. Effect of inspiratory muscle training (IMT) on aerobic capacity, respiratory muscle strength and rate of perceived exertion in paraplegics.

    Science.gov (United States)

    Soumyashree, Sonali; Kaur, Jaskirat

    2018-04-18

    The purpose is to study the effect of inspiratory muscle training on aerobic capacity, respiratory muscle strength and rate of perceived exertion in paraplegics. Randomized controlled trial. Rehabilitation department in Indian Spinal Injuries Centre, New Delhi. A sample of 30 paraplegics (T1-T12) were randomly allocated into two groups: inspiratory muscle training (IMT) group and control group. The IMT group received inspiratory muscle training for 15 minutes 5 times a week for 4 weeks whereas the control group was given breathing exercises. Maximal inspiratory pressure(MIP), maximal expiratory pressure (MEP), modified Borg's scale (MBS), 12 minute wheelchair aerobic test (12MWAT), multistage fitness test (MSFT), and 6 minutes push test (6MPT). Out of 30 participants, 27 completed the study. The results show that after four weeks of IMT training, there were significant improvements in mean change scores of IMT group as compared to control group. Participants in IMT group performed better on 12MWAT (P = 0.001), MSFT (P = 0.001) and 6MPT (P = 0.001). Improvements in MIP scores (P = 0.001), MEP scores (P = 0.001) and MBS scores (P = 0.004) were also seen in IMT group. Both groups showed significant improvements, however inspiratory muscle training was seen to be more effective than deep breathing exercises for improving aerobic capacity, respiratory muscle strength and rate of perceived exertion in paraplegics.

  19. Mesenchymal stromal cell secreted sphingosine 1-phosphate (S1P exerts a stimulatory effect on skeletal myoblast proliferation.

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    Chiara Sassoli

    Full Text Available Bone-marrow-derived mesenchymal stromal cells (MSCs have the potential to significantly contribute to skeletal muscle healing through the secretion of paracrine factors that support proliferation and enhance participation of the endogenous muscle stem cells in the process of repair/regeneration. However, MSC-derived trophic molecules have been poorly characterized. The aim of this study was to investigate paracrine signaling effects of MSCs on skeletal myoblasts. It was found, using a biochemical and morphological approach that sphingosine 1-phosphate (S1P, a natural bioactive lipid exerting a broad range of muscle cell responses, is secreted by MSCs and represents an important factor by which these cells exert their stimulatory effects on C2C12 myoblast and satellite cell proliferation. Indeed, exposure to conditioned medium obtained from MSCs cultured in the presence of the selective sphingosine kinase inhibitor (iSK, blocked increased cell proliferation caused by the conditioned medium from untreated MSCs, and the addition of exogenous S1P in the conditioned medium from MSCs pre-treated with iSK further increased myoblast proliferation. Finally, we also demonstrated that the myoblast response to MSC-secreted vascular endothelial growth factor (VEGF involves the release of S1P from C2C12 cells. Our data may have important implications in the optimization of cell-based strategies to promote skeletal muscle regeneration.

  20. Mesenchymal Stromal Cell Secreted Sphingosine 1-Phosphate (S1P) Exerts a Stimulatory Effect on Skeletal Myoblast Proliferation

    Science.gov (United States)

    Tani, Alessia; Anderloni, Giulia; Pierucci, Federica; Matteini, Francesca; Chellini, Flaminia; Zecchi Orlandini, Sandra; Meacci, Elisabetta

    2014-01-01

    Bone-marrow-derived mesenchymal stromal cells (MSCs) have the potential to significantly contribute to skeletal muscle healing through the secretion of paracrine factors that support proliferation and enhance participation of the endogenous muscle stem cells in the process of repair/regeneration. However, MSC-derived trophic molecules have been poorly characterized. The aim of this study was to investigate paracrine signaling effects of MSCs on skeletal myoblasts. It was found, using a biochemical and morphological approach that sphingosine 1-phosphate (S1P), a natural bioactive lipid exerting a broad range of muscle cell responses, is secreted by MSCs and represents an important factor by which these cells exert their stimulatory effects on C2C12 myoblast and satellite cell proliferation. Indeed, exposure to conditioned medium obtained from MSCs cultured in the presence of the selective sphingosine kinase inhibitor (iSK), blocked increased cell proliferation caused by the conditioned medium from untreated MSCs, and the addition of exogenous S1P in the conditioned medium from MSCs pre-treated with iSK further increased myoblast proliferation. Finally, we also demonstrated that the myoblast response to MSC-secreted vascular endothelial growth factor (VEGF) involves the release of S1P from C2C12 cells. Our data may have important implications in the optimization of cell-based strategies to promote skeletal muscle regeneration. PMID:25264785

  1. Neuroprotective and axon growth-promoting effects following inflammatory stimulation on mature retinal ganglion cells in mice depend on ciliary neurotrophic factor and leukemia inhibitory factor.

    Science.gov (United States)

    Leibinger, Marco; Müller, Adrienne; Andreadaki, Anastasia; Hauk, Thomas G; Kirsch, Matthias; Fischer, Dietmar

    2009-11-11

    After optic nerve injury retinal ganglion cells (RGCs) normally fail to regenerate axons in the optic nerve and undergo apoptosis. However, lens injury (LI) or intravitreal application of zymosan switch RGCs into an active regenerative state, enabling these neurons to survive axotomy and to regenerate axons into the injured optic nerve. Several factors have been proposed to mediate the beneficial effects of LI. Here, we investigated the contribution of glial-derived ciliary neurotrophic factor (CNTF) to LI-mediated regeneration and neuroprotection using wild-type and CNTF-deficient mice. In wild-type mice, CNTF expression was strongly upregulated in retinal astrocytes, the JAK/STAT3 pathway was activated in RGCs, and RGCs were transformed into an active regenerative state after LI. Interestingly, retinal LIF expression was correlated with CNTF expression after LI. In CNTF-deficient mice, the neuroprotective and axon growth-promoting effects of LI were significantly reduced compared with wild-type animals, despite an observed compensatory upregulation of LIF expression in CNTF-deficient mice. The positive effects of LI and also zymosan were completely abolished in CNTF/LIF double knock-out mice, whereas LI-induced glial and macrophage activation was not compromised. In culture CNTF and LIF markedly stimulated neurite outgrowth of mature RGCs. These data confirm a key role for CNTF in directly mediating the neuroprotective and axon regenerative effects of inflammatory stimulation in the eye and identify LIF as an additional contributing factor.

  2. Supraphysiological Doses of Performance Enhancing Anabolic-Androgenic Steroids Exert Direct Toxic Effects on Neuron-like Cells

    Directory of Open Access Journals (Sweden)

    John Robert Basile

    2013-05-01

    Full Text Available Anabolic-androgenic steroids (AAS are lipophilic hormones often taken in excessive quantities by athletes and bodybuilders to enhance performance and increase muscle mass. AAS exert well known toxic effects on specific cell and tissue types and organ systems. The attention that androgen abuse has received lately should be used as an opportunity to educate both athletes and the general population regarding their adverse effects. Among numerous commercially available steroid hormones, very few have been specifically tested for direct neurotoxicity. We evaluated the effects of supraphysiological doses of methandienone and 17-α-methyltestosterone on sympathetic-like neuron cells. Vitality and apoptotic effects were analyzed, and immunofluorescence staining and western blot performed. In this study, we demonstrate that exposure of supraphysiological doses of methandienone and 17-α-methyltestosterone are toxic to the neuron-like differentiated pheochromocytoma cell line PC12, as confirmed by toxicity on neurite networks responding to nerve growth factor and the modulation of the survival and apoptosis-related proteins ERK, caspase-3, poly (ADP-ribose polymerase and heat-shock protein 90. We observe, in contrast to some previous reports but in accordance with others, expression of the androgen receptor (AR in neuron-like cells, which when inhibited mitigated the toxic effects of AAS tested, suggesting that the AR could be binding these steroid hormones to induce genomic effects. We also note elevated transcription of neuritin in treated cells, a neurotropic factor likely expressed in an attempt to resist neurotoxicity. Taken together, these results demonstrate that supraphysiological exposure to the AAS methandienone and 17-α-methyltestosterone exert neurotoxic effects by an increase in the activity of the intrinsic apoptotic pathway and alterations in neurite networks.

  3. Glucocorticoids exert context-dependent effects on cells of the joint in vitro

    DEFF Research Database (Denmark)

    Madsen, Suzi H; Andreassen, Kim V; Christensen, Søren T

    2011-01-01

    Glucocorticoids are known to attenuate bone formation in vivo leading to decreased bone volume and increased risk of fractures, whereas effects on the joint tissue are less characterized. However, glucocorticoids appear to have a reducing effect on inflammation and pain in osteoarthritis....... This study aimed at characterizing the effect of glucocorticoids on chondrocytes, osteoclasts, and osteoblasts....

  4. Neuroprotective effects of a novel single compound 1-methoxyoctadecan-1-ol isolated from Uncaria sinensis in primary cortical neurons and a photothrombotic ischemia model.

    Directory of Open Access Journals (Sweden)

    Ji Yeon Jang

    Full Text Available We identified a novel neuroprotective compound, 1-methoxyoctadecan-1-ol, from Uncaria sinensis (Oliv. Havil and investigated its effects and mechanisms in primary cortical neurons and in a photothrombotic ischemic model. In primary rat cortical neurons against glutamate-induced neurotoxicity, pretreatment with 1-methoxyoctadecan-1-ol resulted in significantly reduced neuronal death in a dose-dependent manner. In addition, treatment with 1-methoxyoctadecan-1-ol resulted in decreased neuronal apoptotic death, as assessed by nuclear morphological approaches. To clarify the neuroprotective mechanism of 1-methoxyoctadecan-1-ol, we explored the downstream signaling pathways of N-methyl-D-aspartate receptor (NMDAR with calpain activation. Treatment with glutamate leads to early activation of NMDAR, which in turn leads to calpain-mediated cleavage of striatal-enriched protein tyrosine phosphatase (STEP and subsequent activation of p38 mitogen activated protein kinase (MAPK. However, pretreatment with 1-methoxyoctadecan-1-ol resulted in significantly attenuated activation of GluN2B-NMDAR and a decrease in calpain-mediated STEP cleavage, leading to subsequent attenuation of p38 MAPK activation. We confirmed the critical role of p38 MAPK in neuroprotective effects of 1-methoxyoctadecan-1-ol using specific inhibitor SB203580. In the photothrombotic ischemic injury in mice, treatment with 1-methoxyoctadecan-1-ol resulted in significantly reduced infarct volume, edema size, and improved neurological function. 1-methoxyoctadecan-1-ol effectively prevents cerebral ischemic damage through down-regulation of calpain-mediated STEP cleavage and activation of p38 MAPK. These results suggest that 1-methoxyoctadecan-1-ol showed neuroprotective effects through down-regulation of calpain-mediated STEP cleavage with activation of GluN2B-NMDAR, and subsequent alleviation of p38 MAPK activation. In addition, 1-methoxyoctadecan-1-ol might be a useful therapeutic agent for

  5. Extracts from Lentinula edodes (Shiitake) Edible Mushrooms Enriched with Vitamin D Exert an Anti-Inflammatory Hepatoprotective Effect.

    Science.gov (United States)

    Drori, Ariel; Shabat, Yehudit; Ben Ya'acov, Ami; Danay, Ofer; Levanon, Dan; Zolotarov, Lidya; Ilan, Yaron

    2016-04-01

    Vitamin D has been known for its anti-inflammatory properties. Extracts derived from Lentinula edodes (Shiitake) edible mushroom exert an anti-inflammatory effect. These extracts contain high levels of ergosterol, which converts into ergocalciferol (vitamin D2) following exposure to ultraviolet light, followed by absorption and hydroxylation into the active form 25-hydroxyvitamin D [25(OH)D]. To determine the anti-inflammatory effect of overexpression of vitamin D in edible mushrooms, L. edodes mushrooms were exposed to ultraviolet-B light, freeze-dried, followed by measurement of vitamin D2 contents, in their dry weight. C57B1/6 mice were orally treated with vitamin D2-enriched or nonenriched mushroom extract prior and during concanavalin A-immune-mediated liver injury. Exposure to ultraviolet light increased vitamin D2 content in Shiitake edible mushrooms. Following feeding of vitamin D-enriched mushroom extracts to mice with immune-mediated hepatitis, a significant decrease in liver damage was noted. This was shown by a decrease in alanine aminotransferase and aspartate aminotransferase serum levels, a decrease in proportion of mice with severe liver injury, and by improvement in liver histology. These effects were associated with a decrease in serum interferon gamma levels. A synergistic effect was noted between the anti-inflammatory effect of the mushroom extracts and that of vitamin D. Oral administration of vitamin D-enriched L. edodes edible mushroom exerts a synergistic anti-inflammatory effect in the immune-mediated hepatitis. The data support its potential use as safe immunomodulatory adjuvant for the treatment of HCV and nonalcoholic steatohepatitis.

  6. Nitrite exerts antioxidant effects, inhibits the mTOR pathway and reverses hypertension-induced cardiac hypertrophy.

    Science.gov (United States)

    Guimaraes, Danielle A; Dos Passos, Madla A; Rizzi, Elen; Pinheiro, Lucas C; Amaral, Jefferson H; Gerlach, Raquel F; Castro, Michele M; Tanus-Santos, Jose E

    2018-03-09

    Cardiac hypertrophy is a common consequence of chronic hypertension and leads to heart failure and premature death. The anion nitrite is now considered as a bioactive molecule able to exert beneficial cardiovascular effects. Previous results showed that nitrite attenuates hypertension-induced increases in reactive oxygen species (ROS) production in the vasculature. Whether antioxidant effects induced by nitrite block critical signaling pathways involved in cardiac hypertrophy induced by hypertension has not been determined yet. The Akt/mTOR signaling pathway is responsible to activate protein synthesis during cardiac remodeling and is activated by increased ROS production, which is commonly found in hypertension. Here, we investigated the effects of nitrite treatment on cardiac remodeling and activation of this hypertrophic signaling pathway in 2 kidney-1 clip (2K1C) hypertension. Sham and 2K1C rats were treated with oral nitrite at 1 or 15mg/kg for four weeks. Nitrite treatment (15mg/kg) reduced systolic blood pressure and decreased ROS production in the heart tissue from hypertensive rats. This nitrite dose also blunted hypertension-induced activation of mTOR pathway and cardiac hypertrophy. While the lower nitrite dose (1mg/kg) did not affect blood pressure, it exerted antioxidant effects and tended to attenuate mTOR pathway activation and cardiac hypertrophy induced by hypertension. Our findings provide strong evidence that nitrite treatment decreases cardiac remodeling induced by hypertension as a result of its antioxidants effects and downregulation of mTOR signaling pathway. This study may help to establish nitrite as an effective therapy in hypertension-induced cardiac hypertrophic remodeling. Copyright © 2018. Published by Elsevier Inc.

  7. Neuroprotective Effects of Herbal Extract (Rosa canina, Tanacetum vulgare and Urtica dioica) on Rat Model of Sporadic Alzheimer's Disease.

    Science.gov (United States)

    Daneshmand, Parvaneh; Saliminejad, Kioomars; Dehghan Shasaltaneh, Marzieh; Kamali, Koorosh; Riazi, Gholam Hossein; Nazari, Reza; Azimzadeh, Pedram; Khorram Khorshid, Hamid Reza

    2016-01-01

    Sporadic Alzheimer's Disease (SAD) is caused by genetic risk factors, aging and oxidative stresses. The herbal extract of Rosa canina (R. canina), Tanacetum vulgare (T. vulgare) and Urtica dioica (U. dioica) has a beneficial role in aging, as an anti-inflammatory and anti-oxidative agent. In this study, the neuroprotective effects of this herbal extract in the rat model of SAD was investigated. The rats were divided into control, sham, model, herbal extract -treated and ethanol-treated groups. Drug interventions were started on the 21(st) day after modeling and each treatment group was given the drugs by intraperitoneal (I.P.) route for 21 days. The expression levels of the five important genes for pathogenesis of SAD including Syp, Psen1, Mapk3, Map2 and Tnf-α were measured by qPCR between the hippocampi of SAD model which were treated by this herbal extract and control groups. The Morris Water Maze was adapted to test spatial learning and memory ability of the rats. Treatment of the rat model of SAD with herbal extract induced a significant change in expression of Syp (p=0.001) and Psen1 (p=0.029). In Morris Water Maze, significant changes in spatial learning seen in the rat model group were improved in herbal-treated group. This herbal extract could have anti-dementia properties and improve spatial learning and memory in SAD rat model.

  8. Neuroprotective Effect of Ginkgolide B on Bupivacaine-Induced Apoptosis in SH-SY5Y Cells

    Science.gov (United States)

    Li, Le; Zhang, Qing-guo; Lai, Lu-ying; Wen, Xian-jie; Zheng, Ting; Cheung, Chi-wai; Zhou, Shu-qin; Xu, Shi-yuan

    2013-01-01

    Local anesthetics are used routinely and effectively. However, many are also known to activate neurotoxic pathways. We tested the neuroprotective efficacy of ginkgolide B (GB), an active component of Ginkgo biloba, against ROS-mediated neurotoxicity caused by the local anesthetic bupivacaine. SH-SY5Y cells were treated with different concentrations of bupivacaine alone or following preincubation with GB. Pretreatment with GB increased SH-SY5Y cell viability and attenuated intracellular ROS accumulation, apoptosis, mitochondrial dysfunction, and ER stress. GB suppressed bupivacaine-induced mitochondrial depolarization and mitochondria complex I and III inhibition and increased cleaved caspase-3 and Htra2 expression, which was strongly indicative of activation of mitochondria-dependent apoptosis with concomitantly enhanced expressions of Grp78, caspase-12 mRNA, protein, and ER stress. GB also improved ultrastructural changes indicative of mitochondrial and ER damage induced by bupivacaine. These results implicate bupivacaine-induced ROS-dependent mitochondria, ER dysfunction, and apoptosis, which can be attenuated by GB through its antioxidant property. PMID:24228138

  9. Neuroprotective effects of anthocyanin- and proanthocyanidin-rich extracts in cellular models of Parkinson’s disease

    Science.gov (United States)

    Strathearn, Katherine E.; Yousef, Gad G.; Grace, Mary H.; Roy, Susan L.; Tambe, Mitali A.; Ferruzzi, Mario G.; Wu, Qing-Li; Simon, James E.; Lila, Mary Ann; Rochet, Jean-Christophe

    2014-01-01

    Neuropathological evidence indicates that dopaminergic cell death in Parkinson’s disease (PD) involves impairment of mitochondrial complex I, oxidative stress, microglial activation, and the formation of Lewy bodies. Epidemiological findings suggest that the consumption of berries rich in anthocyanins and proanthocyanidins may reduce PD risk. In this study, we investigated whether extracts rich in anthocyanins, proanthocyanidins, or other polyphenols suppress the neurotoxic effects of rotenone in a primary cell culture model of PD. Dopaminergic cell death elicited by rotenone was suppressed by extracts prepared from blueberries, grape seed, hibiscus, blackcurrant, and Chinese mulberry. Extracts rich in anthocyanins and proanthocyanidins exhibited greater neuroprotective activity than extracts rich in other polyphenols, and a number of individual anthocyanins interfered with rotenone neurotoxicity. The blueberry and grape seed extracts rescued rotenone-induced defects in mitochondrial respiration in a dopaminergic cell line, and a purple basal extract attenuated nitrite release from microglial cells stimulated by lipopolysaccharide. These findings suggest that anthocyanin- and proanthocyanidin-rich botanical extracts may alleviate neurodegeneration in PD via enhancement of mitochondrial function. PMID:24502982

  10. Neuroprotective effects of aqueous extracts of Uncaria tomentosa: Insights from 6-OHDA induced cell damage and transgenic Caenorhabditis elegans model.

    Science.gov (United States)

    Shi, Zhenhua; Lu, Zhongbing; Zhao, Yashuo; Wang, Yueqi; Zhao-Wilson, Xi; Guan, Peng; Duan, Xianglin; Chang, Yan-Zhong; Zhao, Baolu

    2013-06-01

    Previous pharmacological studies have indicated that AC11 (a standardized aqueous extract of Uncaria tomentosa) has beneficial effects on DNA repair and immune function. However, its benefits go beyond this. The present study utilized electron spin resonance (ESR) and spin trapping technique, as well as the 6-OHDA-induced cell damage and transgenic Caenorhabditis elegans models, towards exploring the antioxidant and neuroprotective ability of AC11. Our results showed that AC11 could scavenge several types of free radicals, especially hydroxyl radicals (60% of hydroxyl radicals were scavenged by 30 μg/ml of AC11). In SH-SY5Y cells, we found that AC11 could dose dependently protect 6-OHDA induced cell damage by increase cell viability and mitochondrial membrane potential. AC11 pretreatment also significantly decreased the level of lipid peroxidation, intracellular reactive oxygen species and nitric oxide in 6-OHDA treated cells. In NL5901 C. elegans, 10 μg/ml AC11 could reduce the aggregation of α-synuclein by 40%. These findings encourage further investigation on AC11 and its active constituent compounds, as possible therapeutic intervention against Parkinson's disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Anticonvulsant and neuroprotective effects of the novel calcium antagonist NP04634 on kainic acid-induced seizures in rats.

    Science.gov (United States)

    Morales-Garcia, Jose A; Luna-Medina, Rosario; Martinez, Ana; Santos, Angel; Perez-Castillo, Ana

    2009-12-01

    Kainic acid (KA)-induced status epilepticus (SE) is a well-characterized model of excitotoxic neuronal injury. Excitotoxicity results from activation of specific glutamate receptors, with resultant elevation of intracellular Ca(2+). The CA1 and CA3 subregions of the hippocampus are especially vulnerable to KA, and this pattern of neuronal injury resembles that occurring in patients with temporal lobe epilepsy. Calcium plays an essential role in excitotoxicity, and accordingly calcium channel inhibitors have been shown to have protective effects in various experimental models of epilepsy and brain injury. Moreover, they also potentiate the antiseizure efficacy of conventional antiepileptic drugs. This study was undertaken to determine whether NP04634, a novel compound, reported as a non-L-type voltage-sensitive calcium channel (VSCC) inhibitor, could prevent the entrance in SE and the neuronal loss evoked by intraperitoneal injection of KA. Our results show that intragastrical administration of NP04634 reduced the percentage of rats that entered SE after KA injection, increased the latency of SE entry, and significantly reduced the mortality of rats that entered SE. Also, NP04634 prevented the loss of hippocampal CA1 and CA3 pyramidal neurons and reduced the gliosis induced by KA. These results point to a potential anticonvulsant and neuroprotective role for NP04634. Copyright 2009 Wiley-Liss, Inc.

  12. Neuroprotective effect of quercetin in a model of Parkinson’s disease in rat: A histochemical analysis

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    Mehdi Mehdizadeh

    2009-01-01

    Full Text Available AbstractIntroduction: Parkinson's disease (PD is a neuropathological disorder involving the degeneration of dopaminergic neurons in the substantia nigra, with the subsequent loss of their terminals in the striatum. Quercetin, a natural flavonoid, is a strong antioxidant and radical scavenger. Therefore, its neuroprotective effect in a model of Parkinson’s disease in rat was evaluated.Methods: For this purpose, unilateral intrastriatal 6-hydroxydopamine (6-OHDA-lesioned rats were pretreated with quercetin (20 mg/kg; i.p. 1 hour before surgery and treated once a day for one month. Nissl-stained neurons of substantia nigra pars compacta (SNC were counted. Results: Number of Nissl-stained neurons in left side of SNC of lesion group was lower relative to sham-operated group (p<0.005 and it was higher in quercetin-treated lesion group as compared to untreated lesion group (p<0.01.Discussion: Flavonoid quercetin administration for one month could protect the neurons of SNC against 6-OHDA toxicity. 

  13. Neuroprotective effect of quercetin in a model of Parkinson’s disease in rat: A histochemical analysis

    Directory of Open Access Journals (Sweden)

    Mehdi Mehdizadeh

    2009-01-01

    Full Text Available AbstractIntroduction: Parkinson's disease (PD is a neuropathological disorder involving the degeneration of dopaminergic neurons in the substantia nigra, with the subsequent loss of their terminals in the striatum. Quercetin, a natural flavonoid, is a strong antioxidant and radical scavenger. Therefore, its neuroprotective effect in a model of Parkinson’s disease in rat was evaluated.Methods: For this purpose, unilateral intrastriatal 6-hydroxydopamine (6-OHDA-lesioned rats were pretreated with quercetin (20 mg/kg i.p. 1 hour before surgery and treated once a day for one month. Nissl-stained neurons of substantia nigra pars compacta (SNC were counted. Results: Number of Nissl-stained neurons in left side of SNC of lesion group was lower relative to sham-operated group (p<0.005 and it was higher in quercetin-treated lesion group as compared to untreated lesion group (p<0.01.Discussion: Flavonoid quercetin administration for one month could protect the neurons of SNC against 6-OHDA toxicity.

  14. Neuroprotective effect of Buddleja cordata methanolic extract in the 1-methyl-4-phenylpyridinium Parkinson's disease rat model.

    Science.gov (United States)

    Pérez-Barrón, Gabriela; Avila-Acevedo, José Guillermo; García-Bores, Ana María; Montes, Sergio; García-Jiménez, Sara; León-Rivera, Ismael; Rubio-Osornio, Moisés; Monroy-Noyola, Antonio

    2015-01-01

    Parkinson's disease (PD) is a neurodegenerative disorder characterized by the irreversible loss of dopaminergic neurons in the nigrostriatal pathway with subsequent dopamine deficiency. Environmental causes have been proposed through molecules, such as 1-methyl-4-phenylpyridinium (MPP(+)), to induce oxidative stress. The methanolic extract of plants of the genus Buddleja has been reported to have in vitro and in vivo antioxidant properties to protect against neuronal death. In the present study, the neuroprotective effect of Buddleja cordata methanolic extract in the MPP(+) PD rat model was investigated. Animals were administered orally with 50 or 100 mg/kg of methanolic extract every 24 h for 14 days. Twenty hours later, rats were infused with an intrastriatal stereotaxic microinjection of 10 µg MPP(+) in 8 μl sterile saline solution. Six days later, the animals were treated with 1 mg/kg apomorphine to record ipsilateral rotations for 1 h. All the rats were killed by decapitation and the lesioned striatum was dissected for dopamine and lipid peroxidation quantifications. Both methanolic extract doses led to a significantly lower (P Buddleja cordata methanolic extract in the MPP(+) PD rat model, possibly due to the involvement of phenylpropanoids.

  15. Neuroprotective effect of humanin on cerebral ischemia/reperfusion injury is mediated by a PI3K/Akt pathway

    Science.gov (United States)

    Xu, Xingshun; Chua, Chu Chang; Gao, Jinping; Chua, Kao-Wei; Wang, Hong; Hamdy, Ronald C.; Chua, Balvin H.L.

    2008-01-01

    Humanin (HN) is an anti-apoptotic peptide that suppresses neuronal cell death induced by Alzheimer's disease, prion protein fragments, and serum deprivation. Recently, we demonstrated that Gly14-HN (HNG), a variant of HN in which the 14th amino acid serine is replaced with glycine, can decrease apoptotic neuronal death and reduce infarct volume in a focal cerebral ischemia/reperfusion mouse model. In this study, we postulate that the mechanism of HNG's neuroprotective effect is mediated by the PI3K/Akt pathway. Oxygen-glucose deprivation (OGD) was performed in cultured mouse primary cortical neurons for 60 min. The effect of HNG and PI3K/Akt inhibitors on OGD-induced cell death was examined at 24 h after reperfusion. HNG increased cell viability after OGD in primary cortical neurons, whereas the PI3K/Akt inhibitors wortmannin and Akti-1/2 attenuated the protective effect of HNG. HNG rapidly increased Akt phosphorylation, an effect that was inhibited by wortmannin and Akti-1/2. Mouse brains were injected intraventricularly with HNG before being subjected to middle cerebral artery occlusion (MCAO) for 75 min followed by 24 h reperfusion. HNG treatment significantly elevated p-Akt levels after cerebral I/R injury and decreased infarct volume. The protective effect of HNG on infarct size was attenuated by wortmannin and Akti-1/2. Taken as a whole, these results suggest that PI3K/Akt activation mediates HNG's protective effect against hypoxia/ischemia reperfusion injury. PMID:18590709

  16. Sodium Butyrate Upregulates miR-203 Expression to Exert Anti-Proliferation Effect on Colorectal Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ruirui Han

    2016-10-01

    Full Text Available Background: As the end product of the bacterial fermentation of dietary fiber in the colonic lumen, sodium butyrate (NaBt has been reported to exert antitumor effects on colorectal cancer (CRC. In addition to functioning as a histone deacetylase (HDAC inhibitor, NaBt also regulates the expression of microRNAs (miRNAs to inhibit CRC cell proliferation. Yet, the mechanisms involved are not completely understood. Here we investigate whether NaBt regulates miR-203 to inhibit CRC growth and explore the promising target gene of miR-203 in CRC cells. Methods: We conducted qRT-PCR and Western blotting assays to evaluate the effects of NaBt on the expression of miR-203 and NEDD9 in HT-29 and Caco-2 cell lines. The promising target gene of miR-203 was predicted by miRNA target prediction and dual luciferase reporter assay. CRC Cell proliferation, colony formation, cell apoptosis and cell invasion assays were performed to explore the effect of NaBt, miR-203 and NEDD9 on HT-29 and Caco-2 cell lines. Results: The results showed that NaBt increased the expression of miR-203 to induce CRC cell apoptosis as well as inhibit cell proliferation, colony formation and cell invasion. Moreover, we determined that the NEDD9 was a target gene of miR-203. NEDD9 partially overcame the inhibitory effects of miR-203 on CRC cell colony formation and invasion. Conclusions: NaBt could induce CRC cell apoptosis, inhibit CRC cell proliferation, colony formation and invasion through miR-203/NEDD9 cascade. The present study may enrich the mechanisms underlying the process that NaBt exerts anti-tumor effects on CRC cells.

  17. Perfluorononanoic acid in combination with 14 chemicals exerts low-dose mixture effects in rats

    DEFF Research Database (Denmark)

    Hadrup, Niels; Pedersen, Mikael; Skov, Kasper

    2016-01-01

    . An increase in testosterone and dihydrotestosterone plasma concentrations was observed for Low PFNA + Mix. This effect was considered non-monotonic, as higher doses did not cause this effect. Reduced LH plasma concentrations together with increased androgen concentrations indicate a disturbed pituitary...

  18. Notochordal-cell derived extracellular vesicles exert regenerative effects on canine and human nucleus pulposus cells

    NARCIS (Netherlands)

    Bach, Frances; Libregts, Sten; Creemers, Laura; Meij, Björn P; Ito, Keita; Wauben, Marca H M; Tryfonidou, Marianna A

    2017-01-01

    During intervertebral disc ageing, chondrocyte-like cells (CLCs) replace notochordal cells (NCs). NCs have been shown to induce regenerative effects in CLCs. Since vesicles released by NCs may be responsible for these effects, we characterized NC-derived extracellular vesicles (EVs) and determined

  19. Effects of ladder parameters on asymmetric patterns of force exertion during below-knee amputees climbing ladders.

    Science.gov (United States)

    Li, Weidong; Li, Shiqi; Fu, Yan; Chen, Jacon

    2017-03-01

    Different from walking, ladder climbing requires four-limb coordination and more energy exertion for below-knee amputees (BKAs). We hypothesized that functional deficiency of a disabled limb shall be compensated by the other three intact limbs, showing an asymmetry pattern among limbs. Hand and foot forces of six below-knee amputees and six able-bodied people were collected. Hand, foot and hand/foot sum force variances between groups (non-BKA, intact side and prosthetic side) were carefully examined. Our hypothesis was validated that there is asymmetry between prosthetic and intact side. Results further showed that the ipsilateral hand of the prosthetic leg is stronger than the hand on the intact side, compensating weakness of the prosthetic leg. Effects of ladder rung separations and ladder slant on asymmetric force distribution of BKAs were evaluated, indicating that rung separation has a more significant interactive effect on hand/foot force of BKAs than ladder slant.

  20. Hippocampal insulin signaling and neuroprotection mediated by physical exercise in Alzheimer´s Disease

    Directory of Open Access Journals (Sweden)

    Gabriel Keine Kuga

    2017-05-01

    Full Text Available Abstract Epidemiological studies indicate continuous increases in the prevalence of Alzheimer’s Disease (AD in the next few decades. The key feature of this disease is hippocampal neurodegeneration. This structure has an important role in learning and memory. Intense research efforts have sought to elucidate neuroprotective mechanisms responsible for hippocampal integrity. Insulin signaling seems to be a very promising pathway for the prevention and treatment of AD. This hormone has been described as a powerful activator of neuronal survival. Recent research showed that reduced insulin sensitivity leads to low-grade inflammation, and both phenomena are closely related to AD genesis. Concomitantly, exercise has been shown to exert anti-inflammatory effects and to promote improvement in insulin signaling in the hippocampus, which supports neuronal survival and constitutes an interesting non-pharmacological alternative for the prevention and treatment of AD. This review examines recent advances in understanding the molecular mechanisms involved in hippocampal neuroprotection mediated by exercise.

  1. Salvianolic acid A exerts antiamnesic effect on diazepam-induced anterograde amnesia in mice.

    Science.gov (United States)

    Wang, T; Shan, S Y; Han, B; Zhang, L M; Fu, F H

    2011-01-01

    Benzodiazepine was known to produce amnesia. Salvianolic acid A extracted from Salvia miltiorrhiza was an effective antioxidant. The objective of the study was to evaluate the effect of salvianolic acid A on diazepam-induced amnesia in mice. C57BL/6 mice were treated with salvianolic acid A at doses of 10, 20 and 40 mg/kg following administration with diazepam at a dose of 3 mg/kg. Morris water maze was performed to evaluate the effect of salvianolic acid A on amnesia. The antioxidative parameters in hippocampus were measured. The results showed that salvianolic acid A decreased the mean escape latency and increased the percentage of time spent in target quadrant. Salvianolic acid A reduced the content of malondialdehyde and increased the activities of superoxide dismutase, catalase and glutathione peroxidase in hippocampus. The findings demonstrated that salvianolic acid A had antiamnesic effects on diazepam-induced anterograde amnesia in mice, by augmenting the antioxidative capacity of hippocampus.

  2. Subliminal messages exert long-term effects on decision-making

    OpenAIRE

    Ruch Simon; Züst Marc Alain; Henke Katharina

    2016-01-01

    Subliminal manipulation is often considered harmless because its effects typically decay within a second. So far, subliminal long-term effects on behavior were only observed in studies which repeatedly presented highly familiar information such as single words. These studies suggest that subliminal messages are only slowly stored and might not be stored at all if they provide novel, unfamiliar information. We speculated that subliminal messages might affect delayed decision making especially ...

  3. An antipsychotic drug exerts anti-prion effects by altering the localization of the cellular prion protein.

    Directory of Open Access Journals (Sweden)

    Claudia Stincardini

    Full Text Available Prion diseases are neurodegenerative conditions characterized by the conformational conversion of the cellular prion protein (PrPC, an endogenous membrane glycoprotein of uncertain function, into PrPSc, a pathological isoform that replicates by imposing its abnormal folding onto PrPC molecules. A great deal of evidence supports the notion that PrPC plays at least two roles in prion diseases, by acting as a substrate for PrPSc replication, and as a mediator of its toxicity. This conclusion was recently supported by data suggesting that PrPC may transduce neurotoxic signals elicited by other disease-associated protein aggregates. Thus, PrPC may represent a convenient pharmacological target for prion diseases, and possibly other neurodegenerative conditions. Here, we sought to characterize the activity of chlorpromazine (CPZ, an antipsychotic previously shown to inhibit prion replication by directly binding to PrPC. By employing biochemical and biophysical techniques, we provide direct experimental evidence indicating that CPZ does not bind PrPC at biologically relevant concentrations. Instead, the compound exerts anti-prion effects by inducing the relocalization of PrPC from the plasma membrane. Consistent with these findings, CPZ also inhibits the cytotoxic effects delivered by a PrP mutant. Interestingly, we found that the different pharmacological effects of CPZ could be mimicked by two inhibitors of the GTPase activity of dynamins, a class of proteins involved in the scission of newly formed membrane vesicles, and recently reported as potential pharmacological targets of CPZ. Collectively, our results redefine the mechanism by which CPZ exerts anti-prion effects, and support a primary role for dynamins in the membrane recycling of PrPC, as well as in the propagation of infectious prions.

  4. SH3-binding protein 5 mediates the neuroprotective effect of the secreted bioactive peptide humanin by inhibiting c-Jun NH2-terminal kinase.

    Science.gov (United States)

    Takeshita, Yuji; Hashimoto, Yuichi; Nawa, Mikiro; Uchino, Hiroyuki; Matsuoka, Masaaki

    2013-08-23

    Humanin is a secreted bioactive peptide that suppresses cell toxicity caused by a variety of insults. The neuroprotective effect of Humanin against Alzheimer disease (AD)-related death is mediated by the binding of Humanin to its heterotrimeric Humanin receptor composed of ciliary neurotrophic receptor α, WSX-1, and gp130, as well as the activation of intracellular signaling pathways including a JAK2 and STAT3 signaling axis. Despite the elucidation of the signaling pathways by which Humanin mediates its neuroprotection, the transcriptional targets of Humanin that behaves as effectors of Humanin remains undefined. In the present study, Humanin increased the mRNA and protein expression of SH3 domain-binding protein 5 (SH3BP5), which has been known to be a JNK interactor, in neuronal cells. Similar to Humanin treatment, overexpression of SH3BP5 inhibited AD-related neuronal death, while siRNA-mediated knockdown of endogenous SH3BP5 expression attenuated the neuroprotective effect of Humanin. These results indicate that SH3BP5 is a downstream effector of Humanin. Furthermore, biochemical analysis has revealed that SH3BP5 binds to JNK and directly inhibits JNK through its two putative mitogen-activated protein kinase interaction motifs (KIMs).

  5. SH3-binding Protein 5 Mediates the Neuroprotective Effect of the Secreted Bioactive Peptide Humanin by Inhibiting c-Jun NH2-terminal Kinase*

    Science.gov (United States)

    Takeshita, Yuji; Hashimoto, Yuichi; Nawa, Mikiro; Uchino, Hiroyuki; Matsuoka, Masaaki

    2013-01-01

    Humanin is a secreted bioactive peptide that suppresses cell toxicity caused by a variety of insults. The neuroprotective effect of Humanin against Alzheimer disease (AD)-related death is mediated by the binding of Humanin to its heterotrimeric Humanin receptor composed of ciliary neurotrophic receptor α, WSX-1, and gp130, as well as the activation of intracellular signaling pathways including a JAK2 and STAT3 signaling axis. Despite the elucidation of the signaling pathways by which Humanin mediates its neuroprotection, the transcriptional targets of Humanin that behaves as effectors of Humanin remains undefined. In the present study, Humanin increased the mRNA and protein expression of SH3 domain-binding protein 5 (SH3BP5), which has been known to be a JNK interactor, in neuronal cells. Similar to Humanin treatment, overexpression of SH3BP5 inhibited AD-related neuronal death, while siRNA-mediated knockdown of endogenous SH3BP5 expression attenuated the neuroprotective effect of Humanin. These results indicate that SH3BP5 is a downstream effector of Humanin. Furthermore, biochemical analysis has revealed that SH3BP5 binds to JNK and directly inhibits JNK through its two putative mitogen-activated protein kinase interaction motifs (KIMs). PMID:23861391

  6. Glucocorticoids exert context-dependent effects on cells of the joint in vitro.

    Science.gov (United States)

    Madsen, Suzi H; Andreassen, Kim V; Christensen, Søren T; Karsdal, Morten A; Sverdrup, Francis M; Bay-Jensen, Anne-Christine; Henriksen, Kim

    2011-12-11

    Glucocorticoids are known to attenuate bone formation in vivo leading to decreased bone volume and increased risk of fractures, whereas effects on the joint tissue are less characterized. However, glucocorticoids appear to have a reducing effect on inflammation and pain in osteoarthritis. This study aimed at characterizing the effect of glucocorticoids on chondrocytes, osteoclasts, and osteoblasts. We used four model systems to investigate how glucocorticoids affect the cells of the joint; two intact tissues (femoral head- and cartilage-explants), and two separate cell cultures of osteoblasts (2T3-pre-osteoblasts) and osteoclasts (CD14(+)-monocytes). The model systems were cultured in the presence of two glucocorticoids; prednisolone or dexamethasone. To induce anabolic and catabolic conditions, cultures were activated by insulin-like growth factor I/bone morphogenetic protein 2 and oncostatin M/tumor necrosis factor-α, respectively. Histology and markers of bone- and cartilage-turnover were used to evaluate effects of glucocorticoid treatment. Prednisolone treatment decreased collagen type-II degradation in immature cartilage, whereas glucocorticoids did not affect collagen type-II in mature cartilage. Glucocorticoids had an anti-catabolic effect on catabolic-activated cartilage from a bovine stifle joint and murine femoral heads. Glucocorticoids decreased viability of all bone cells, leading to a reduction in osteoclastogenesis and bone resorption; however, bone morphogenetic protein 2-stimulated osteoblasts increased bone formation, as opposed to non-stimulated osteoblasts. Using highly robust in vitro models of bone and cartilage turnover, we suggest that effects of glucocorticoids highly depend on the activation and differential stage of the cell targeted in the joint. Present data indicated that glucocorticoid treatment may be beneficial for articular cartilage, although detrimental effects on bone should be taken into account. Copyright © 2011 Elsevier Inc

  7. The DHEA metabolite 7β-hydroxy-epiandrosterone exerts anti-estrogenic effects on breast cancer cell lines.

    Science.gov (United States)

    Sandra, Niro; Ester, Pereira; Marie-Agnès, Pélissier; Robert, Morfin; Olivier, Hennebert

    2012-04-01

    7β-Hydroxy-epiandrosterone (7β-OH-EpiA), an endogenous androgenic derivative of dehydroepiandrosterone, has previously been shown to exert anti-inflammatory action in vitro and in vivo via a shift from prostaglandin E2 (PGE2) to 15-deoxy-Δ(12,14)-PGJ2 production. This modulation in prostaglandin production was obtained with low concentrations of 7β-OH-EpiA (1-100nM) and suggested that it might act through a specific receptor. Inflammation and prostaglandin synthesis is important in the development and survival of estrogen-dependent mammary cancers. Estrogen induced PGE2 production and cell proliferation via its binding to estrogen receptors (ERs) in these tumors. Our objective was to test the effects of 7β-OH-EpiA on the proliferation (by counting with trypan blue exclusion), cell cycle and cell apoptosis (by flow cytometry) of breast cancer cell lines MCF-7 (ERα+, ERβ+, G-protein coupled receptor 30: GPR30+) and MDA-MB-231 (ERα-, ERβ+, GPR30+) and to identify a potential target of this steroid in these cell lineages (by transactivations) and in the nuclear ER-negative SKBr3 cells (GPR30+) (by proliferation assays). 7β-OH-EpiA exerted anti-estrogenic effects in MCF-7 and MDA-MB-231 cells associated with cell proliferation inhibition and cell cycle arrest. Moreover, transactivation and proliferation with ER agonists assays indicated that 7β-OH-EpiA interacted with ERβ. Data from proliferation assays on the MCF-7, MDA-MB-231 and SKBr3 cell lines suggested that 7β-OH-EpiA may also act through the membrane GPR30 receptor. These results support that this androgenic steroid acts as an anti-estrogenic compound. Moreover, this is the first evidence that low doses of androgenic steroid exert antiproliferative effects in these mammary cancer cells. Further investigations are needed to improve understanding of the observed actions of endogenous 7β-OH-EpiA. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. R-Modafinil exerts weak effects on spatial memory acquisition and dentate gyrus synaptic plasticity.

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    Bharanidharan Shanmugasundaram

    Full Text Available Modafinil is a wake promoting drug approved for clinical use and also has cognitive enhancing properties. Its enantiomer R-Modafinil (R-MO is not well studied in regard to cognitive enhancing properties. Hence we studied its effect in a spatial memory paradigm and its possible effects on dentate gyrus long-term potentiation (DG-LTP. Clinically relevant doses of R-MO, vehicle dimethyl sulfoxide (DMSO or saline were administered for three days during the hole-board test and in in vivo DG-LTP. Synaptic levels of dopamine receptors D1R, D2R, dopamine transporter (DAT, and its phosphorylated form (ph-DAT in DG tissue 4 h after LTP induction were quantified by western blot analysis. Monoamine reuptake and release assays were performed by using transfected HEK-293 cells. Possible neurotoxic side effects on general behaviour were also studied. R-MO at both doses significantly enhanced spatial reference memory during the last training session and during memory retrieval compared to DMSO vehicle but not when compared to saline treated rats. Similarly, R-MO rescues DG-LTP from impairing effects of DMSO. DMSO reduced memory performance and LTP magnitude when compared to saline treated groups. The synaptic DR1 levels in R-MO groups were significantly decreased compared to DMSO group but were comparable with saline treated animals. We found no effect of R-MO in neurotoxicity tests. Thus, our results support the notion that LTP-like synaptic plasticity processes could be one of the factors contributing to the cognitive enhancing effects of spatial memory traces. D1R may play an important regulatory role in these processes.

  9. Crambescin C1 Exerts a Cytoprotective Effect on HepG2 Cells through Metallothionein Induction

    Science.gov (United States)

    Roel, María; Rubiolo, Juan A.; Ternon, Eva; Thomas, Olivier P.; Vieytes, Mercedes R.; Botana, Luis M.

    2015-01-01

    The Mediterranean marine sponge Crambe crambe is the source of two families of guanidine alkaloids known as crambescins and crambescidins. Some of the biological effects of crambescidins have been previously reported while crambescins have undergone little study. Taking this into account, we performed comparative transcriptome analysis to examine the effect of crambescin-C1 (CC1) on human tumor hepatocarcinoma cells HepG2 followed by validation experiments to confirm its predicted biological activities. We report herein that, while crambescin-A1 has a minor effect on these cells, CC1 protects them against oxidative injury by means of metallothionein induction even at low concentrations. Additionally, at high doses, CC1 arrests the HepG2 cell cycle in G0/G1 and thus inhibits tumor cell proliferation. The findings presented here provide the first detailed approach regarding the different effects of crambescins on tumor cells and provide a basis for future studies on other possible cellular mechanisms related to these bioactivities. PMID:26225985

  10. Native herbivore exerts contrasting effects on fire regime and vegetation structure

    Science.gov (United States)

    Jose L. Hierro; Kenneth L. Clark; Lyn C. Branch; Diego. Villarreal

    2011-01-01

    Although native herbivores can alter fire regimes by consuming herbaceous vegetation that serves as fine fuel and, less commonly, accumulating fuel as nest material and other structures, simultaneous considerations of contrasting effects of herbivores on fire have scarcely been addressed. We proposed that a colonial rodent, vizcacha (Lagostomus maximus...

  11. Cannabidiol exerts anti-convulsant effects in animal models of temporal lobe and partial seizures.

    Science.gov (United States)

    Jones, Nicholas A; Glyn, Sarah E; Akiyama, Satoshi; Hill, Thomas D M; Hill, Andrew J; Weston, Samantha E; Burnett, Matthew D A; Yamasaki, Yuki; Stephens, Gary J; Whalley, Benjamin J; Williams, Claire M

    2012-06-01

    Cannabis sativa has been associated with contradictory effects upon seizure states despite its medicinal use by numerous people with epilepsy. We have recently shown that the phytocannabinoid cannabidiol (CBD) reduces seizure severity and lethality in the well-established in vivo model of pentylenetetrazole-induced generalised seizures, suggesting that earlier, small-scale clinical trials examining CBD effects in people with epilepsy warrant renewed attention. Here, we report the effects of pure CBD (1, 10 and 100mg/kg) in two other established rodent seizure models, the acute pilocarpine model of temporal lobe seizure and the penicillin model of partial seizure. Seizure activity was video recorded and scored offline using model-specific seizure severity scales. In the pilocarpine model CBD (all doses) significantly reduced the percentage of animals experiencing the most severe seizures. In the penicillin model, CBD (≥ 10 mg/kg) significantly decreased the percentage mortality as a result of seizures; CBD (all doses) also decreased the percentage of animals experiencing the most severe tonic-clonic seizures. These results extend the anti-convulsant profile of CBD; when combined with a reported absence of psychoactive effects, this evidence strongly supports CBD as a therapeutic candidate for a diverse range of human epilepsies. Copyright © 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  12. Ginsenoside Rg1 exerts synergistic anti-inflammatory effects with low doses of glucocorticoids in vitro.

    Science.gov (United States)

    Song, Yanqin; Zhao, Feng; Zhang, Leiming; Du, Yuan; Wang, Tian; Fu, Fenghua

    2013-12-01

    Glucocorticoids (GCs) are usually used to treat inflammatory diseases. However, they cause severe and irreversible side effects, which limit the use of these compounds. Ginsenoside Rg1 had been demonstrated to possess anti-inflammatory and anti-cancer effects. The present study was designed to investigate whether Rg1 exhibits synergistic anti-inflammatory effects when combined with glucocorticoids. After stimulated by lipopolysaccharide (LPS), murine macrophagic RAW264.7 cells were treated with Rg1, corticosterone (Cort) or Rg1 and Cort. Then nitric oxide (NO), tumor necrosis factor-α (TNF-α) and glucocorticoid receptor (GR) expression were measured. The results showed that Rg1 or Cort could reduce the production of NO and TNF-α, and Rg1 dose-dependently up-regulated GR expression, while Cort dose-dependently down-regulated GR expression. The combination of low concentrations of Rg1 with Cort, which alone could not markedly inhibit the release of inflammatory factors, inhibited the secretion of NO and TNF-α in LPS-stimulated RAW264.7 macrophage cells, and up-regulated the expression of GR. The findings suggested Rg1 can synergize with glucocorticoid to enhance its anti-inflammatory effect. © 2013.

  13. Bifidobacteria exert species-specific effects on constipation in BALB/c mice.

    Science.gov (United States)

    Wang, Linlin; Hu, Lujun; Xu, Qi; Jiang, Tian; Fang, Shuguang; Wang, Gang; Zhao, Jianxin; Zhang, Hao; Chen, Wei

    2017-10-18

    Constipation is one of the most common gastrointestinal complaints worldwide. The aim of this study was to determine whether edible bifidobacteria (Bifidobacterium longum, B. infantis, B. animalis, B. bifidum, B. adolescentis or B. breve) exhibit interspecies differences in alleviating constipation induced by loperamide in BALB/c mice and to analyse the main reasons for the interspecies differences. BALB/c mice were given bifidobacteria by gavage once per day for 8 days. The primary outcome measures, which included related constipation indicators, and the secondary outcome measures, which included changes in the concentration of short-chain fatty acids in faeces and changes in the faecal flora, were used to evaluate the therapeutic effects of the edible bifidobacteria on constipation. The findings show that the six species of Bifidobacterium differed in their ability to relieve constipation. B. longum, B. infantis and B. bifidum were the most effective in relieving constipation, B. adolescentis and B. breve were partially effective and B. animalis was not effective. Furthermore, edible Bifidobacterium treated constipation by increasing the abundance of Lactobacillus and decreasing the abundance of Alistipes, Odoribacter and Clostridium. Higher concentrations of short-chain fatty acids were found in the faecal samples from the edible Bifidobacterium treatment groups. Meanwhile, an increased concentration of acetic acid could alleviate constipation. In conclusion, edible bifidobacteria exhibit interspecies differences in the alleviation of constipation. Meanwhile, bifidobacteria improved constipation symptoms by increasing the concentration of acetic acid and the relative abundance of Lactobacillus and reducing the content of Alistipes, Odoribacter and Clostridium.

  14. Vinpocetine and piracetam exert antinociceptive effect in visceral pain model in mice.

    Science.gov (United States)

    Abdel Salam, Omar M E

    2006-01-01

    The effect of vinpocetine or piracetam on thermal and visceral pain was studied in mice. In the hot plate test, vinpocetine (0.9 and 1.8 mg/kg), but not piracetam, produced a reduction in nociceptive response. Vinpocetine (0.45-1.8 mg/kg, ip) or piracetam (75-300 mg/kg, ip) caused dose-dependent inhibition of the abdominal constrictions evoked by ip injection of acetic acid. The effect of vinpocetine or piracetam was markedly potentiated by co-administration of propranolol, guanethidine, atropine, naloxone, yohimbine or prazosin. The marked potentiation of antinociception occurred upon a co-administration of vinpocetine and baclofen (5 or 10 mg/kg). In contrast, piracetam antagonized antinociception caused by the low (5 mg/kg), but not the high (10 mg/kg) dose of baclofen. The antinociception caused by vinpocetine was reduced by sulpiride; while that of piracetam was enhanced by haloperidol or sulpiride. Either vinpocetine or piracetam enhanced antinociception caused by imipramine. The antinociceptive effects of vinpocetine or piracetam were blocked by prior administration of theophylline. Low doses of either vinpocetine or piracetam reduced immobility time in the Porsolt's forced-swimming test. This study indicates that vinpocetine and piracetam possess visceral antinociceptive properties. This effect depends on activation of adenosine receptors. Piracetam in addition inhibits GABA-mediated antinociception.

  15. NHBA isolated from Gastrodia elata exerts sedative and hypnotic effects in sodium pentobarbital-treated mice.

    Science.gov (United States)

    Zhang, Ying; Li, Min; Kang, Rui-Xia; Shi, Jian-Gong; Liu, Geng-Tao; Zhang, Jian-Jun

    2012-09-01

    The rhizomes of Gastrodia elata have been used for the treatment of insomnia in oriental countries. N⁶-(4-hydroxybenzyl) adenine riboside (NHBA) was originally isolated from G. elata. For the first time we report a detailed study on the effects and mechanisms of NHBA on its sedative and hypnotic activity. Adenosine, an endogenous sleep factor, regulates sleep-wake cycle via interacting with adenosine A₁/A(2A) receptors. Using radioligand binding studies and cAMP accumulation assays, our results show that NHBA may be a functional ligand for the adenosine A₁ and A(2A) receptors. NHBA significantly decreases spontaneous locomotor activity and potentiates the hypnotic effect of sodium pentobarbital in mice. Sleep architecture analyses reveal that NHBA significantly decreases wakefulness time and increases NREM sleep times. However, NHBA does not affect the amount of REM sleep. Pretreatment with the adenosine A₁ receptor antagonist DPCPX or the A(2A) receptor antagonist SCH 58261 significantly reverses the increase in sleeping time induced by NHBA in sodium pentobarbital treated mice. Immunohistochemical studies show that NHBA increases c-Fos expression in GABAergic neurons of the ventrolateral preoptic area (VLPO), which suggests that NHBA activates the sleep center in the anterior hypothalamus. Altogether, these results indicate that NHBA produces significant sedative and hypnotic effects. Such effects might be mediated by the activation of adenosine A₁/A(2A) receptors and stimulation of the sleep center VLPO. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Meglumine exerts protective effects against features of metabolic syndrome and type II diabetes.

    Directory of Open Access Journals (Sweden)

    Arturo Bravo-Nuevo

    Full Text Available Metabolic syndrome, diabetes and diabetes complications pose a growing medical challenge worldwide, accentuating the need of safe and effective strategies for their clinical management. Here we present preclinical evidence that the sorbitol derivative meglumine (N-methyl-D-glucamine can safely protect against several features of metabolic syndrome and diabetes, as well as elicit enhancement in muscle stamina. Meglumine is a compound routinely used as an approved excipient to improve drug absorption that has not been ascribed any direct biological effects in vivo. Normal mice (SV129 administered 18 mM meglumine orally for six weeks did not display any gastrointestinal or other observable adverse effects, but had a marked effect on enhancing muscle stamina and at longer times in limiting weight gain. In the established KK.Cg-Ay/J model of non-insulin dependent diabetes, oral administration of meglumine significantly improved glycemic control and significantly lowered levels of plasma and liver triglycerides. Compared to untreated control animals, meglumine reduced apparent diabetic nephropathy. Sorbitol can improve blood glucose uptake by liver and muscle in a manner associated with upregulation of the AMPK-related enzyme SNARK, but with undesirable gastrointestinal side effects not seen with meglumine. In murine myoblasts, we found that meglumine increased steady-state SNARK levels in a dose-dependent manner more potently than sorbitol. Taken together, these findings provide support for the clinical evaluation of meglumine as a low-cost, safe supplement offering the potential to improve muscle function, limit metabolic syndrome and reduce diabetic complications.

  17. Tanshinone IIA Exerts an Antinociceptive Effect in Rats with Cancer-induced Bone Pain.

    Science.gov (United States)

    Hao, Wei; Chen, Lei; Wu, Li-Fang; Yang, Fan; Niu, Jian-Xiang; Kaye, Alan D; Xu, Shi-Yuan

    2016-01-01

    Cancer-induced bone pain (CIBP) is a common chronic pain characterized by 2 components, ongoing pain and breakthrough pain. Tanshinone IIA (TSN IIA) is a bioactive constituent of the traditional Chinese medicine Danshen, which has been reported to have an antinociceptive effect on neuropathic and inflammatory pain through downregulation of the late proinflammatory cytokine high-mobility group protein B1 (HMGB1). To assess the antinociceptive effect of TSN IIA on CIBP. A randomized, double-blind, controlled animal trial was performed. University lab in China. A rat CIBP model was established by injecting Walker 256 mammary gland carcinoma cells into the intramedullary cavity of the tibia. Both ongoing pain, e.g., flinching and guarding, and breakthrough pain, e.g., limb use and von Frey threshold, were evaluated. The effects of intraperitoneally administered TSN IIA on pain behavior and the expression levels of spinal HMGB1, interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, and IL-6 were determined. The effect of TSN IIA on the electrically evoked response of spinal wide-dynamic range (WDR) neurons was performed in vivo. TSN IIA dose-dependently inhibited cancer-induced ongoing pain and breakthrough pain. The expression levels of spinal HMGB1 and other inflammatory factors (IL-1beta, TNF-alpha, and IL-6) were increased in the rat model, but they were suppressed by TSN IIA in a dose-dependent manner. Moreover, TSN IIA significantly inhibited the neuronal responses of WDR neurons in spinal deep layers. Further studies are warranted to ascertain how TSN IIA attenuates cancer-induced ongoing pain. Our results indicate that TSN IIA attenuates cancer-induced ongoing pain and breakthrough pain, possibly via suppression of central sensitization in CIBP rats. Therefore, we have provided strong evidence supporting TSN IIA as a potential and effective therapy for relieving CIBP. Cancer-induced bone pain, high-mobility group protein B1, Tanshinone IIA, ongoing pain

  18. Does combined therapy of curcumin and epigallocatechin gallate have a synergistic neuroprotective effect against spinal cord injury?

    Directory of Open Access Journals (Sweden)

    Jiri Ruzicka

    2018-01-01

    Full Text Available Systematic inflammatory response after spinal cord injury (SCI is one of the factors leading to lesion development and a profound degree of functional loss. Anti-inflammatory compounds, such as curcumin and epigallocatechin gallate (EGCG are known for their neuroprotective effects. In this study, we investigated the effect of combined therapy of curcumin and EGCG in a rat model of acute SCI induced by balloon compression. Immediately after SCI, rats received curcumin, EGCG, curcumin + EGCG or saline [daily intraperitoneal doses (curcumin, 6 mg/kg; EGCG 17 mg/kg] and weekly intramuscular doses (curcumin, 60 mg/kg; EGCG 17 mg/kg] for 28 days. Rats were evaluated using behavioral tests (the Basso, Beattie, and Bresnahan (BBB open-field locomotor test, flat beam test. Spinal cord tissue was analyzed using histological methods (Luxol Blue-cresyl violet staining and immunohistochemistry (anti-glial fibrillary acidic protein, anti-growth associated protein 43. Cytokine levels (interleukin-1β, interleukin-4, interleukin-2, interleukin-6, macrophage inflammatory protein 1-alpha, and RANTES were measured using Luminex assay. Quantitative polymerase chain reaction was performed to determine the relative expression of genes (Sort1, Fgf2, Irf5, Mrc1, Olig2, Casp3, Gap43, Gfap, Vegf, NfκB, Cntf related to regenerative processes in injured spinal cord. We found that all treatments displayed significant behavioral recovery, with no obvious synergistic effect after combined therapy of curcumin and ECGC. Curcumin and EGCG alone or in combination increased axonal sprouting, decreased glial scar formation, and altered the levels of macrophage inflammatory protein 1-alpha, interleukin-1β, interleukin-4 and interleukin-6 cytokines. These results imply that although the expected synergistic response of this combined therapy was less obvious, aspects of tissue regeneration and immune responses in severe SCI were evident.

  19. Neuroprotective effect of the natural iron chelator, phytic acid in a cell culture model of Parkinson's disease

    International Nuclear Information System (INIS)

    Xu Qi; Kanthasamy, Anumantha G.; Reddy, Manju B.

    2008-01-01

    Disrupted iron metabolism and excess iron accumulation has been reported in the brains of Parkinson's disease (PD) patients. Because excessive iron can induce oxidative stress subsequently causing degradation of nigral dopaminergic neurons in PD, we determined the protective effect of a naturally occurring iron chelator, phytic acid (IP6), on 1-methyl-4-phenylpyridinium (MPP + )-induced cell death in immortalized rat mesencephalic/dopaminergic cells. Cell death was induced with MPP + in normal and iron-excess conditions and cytotoxicity was measured by thiazolyl blue tetrazolium bromide (MTT assay) and trypan blue staining. Apoptotic cell death was also measured with caspase-3 activity, DNA fragmentation, and Hoechst nuclear staining. Compared to MPP + treatment, IP6 (30 μmol/L) increased cell viability by 19% (P + treatment was decreased by 55% (P < 0.01) and 52% (P < 0.05), respectively with IP6. Cell survival was increased by 18% (P < 0.05) and 42% (P < 0.001) with 30 and 100 μmol/L of IP6, respectively in iron-excess conditions. A 40% and 52% (P < 0.001) protection was observed in caspase-3 activity with 30 and 100 μmol/L IP6, respectively in iron-excess condition. Similarly, a 45% reduction (P < 0.001) in DNA fragmentation was found with 100 μmol/L IP6. In addition, Hoechst nuclear staining results confirmed the protective effect of IP6 against apoptosis. Similar protection was also observed with the differentiated cells. Collectively, our results demonstrate a significant neuroprotective effect of phytate in a cell culture model of PD

  20. Neuroprotective effect of bexarotene in the SOD1G93A mouse model of amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Javier eRiancho

    2015-07-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a neurodegenerative disease characterized by progressive weakness and muscle atrophy related to the loss of upper and lower motor neurons (MNs without a curative treatment. There is experimental evidence suggesting that retinoids may be involved in ALS pathogenesis. Bexarotene (Bxt is a retinoid-X receptor agonist used in the treatment of cutaneous lymphoma with a favourable safety profile whose effects have been recently investigated in other neurodegenerative diseases. In this study, we analyze the potential therapeutic effect of Bxt in the SOD1G93A mouse model of ALS.Mice were treated with Bxt or vehicle five times per week from day 60 onwards. Survival, weight and neuromuscular function studies together with histological and biochemical analyses were performed. Bxt significantly delayed motor function deterioration, ameliorated the loss of body weight and extended mice survival up to 30% of the symptomatic period. Histological analyses of the lumbosacral spinal cord revealed that Bxt markedly delayed the early motor-neuron degeneration occurring at presymptomatic stages in ALS-transgenic mice. Bxt treatment contributed to preserve the MN homeostasis in the SOD1G93A mice. Particularly, it reduced the neuronal loss and the chromatolytic response, induced nucleolar hypertrophy, decreased the formation of ubiquitylated inclusions and modulated the lysosomal response. As an agonist of the retinoic-X receptor pathway (RXR, Bxt notably increased the nuclear expression of the RXRα throughout transcriptionally active euchromatin domains. Bxt also contributed to protect the MN environment by reducing reactive astrogliosis and preserving perisomatic synapsis. Overall, these neuroprotective effects suggest that treatment with Bxt could be useful in ALS, particularly in those cases related to SOD1 mutations.

  1. Neuroprotective Effect of Bexarotene in the SOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis

    Science.gov (United States)

    Riancho, Javier; Ruiz-Soto, María; Berciano, María T.; Berciano, José; Lafarga, Miguel

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive weakness and muscle atrophy related to the loss of upper and lower motor neurons (MNs) without a curative treatment. There is experimental evidence suggesting that retinoids may be involved in ALS pathogenesis. Bexarotene (Bxt) is a retinoid-X receptor agonist used in the treatment of cutaneous lymphoma with a favorable safety profile whose effects have been recently investigated in other neurodegenerative diseases. In this study, we analyze the potential therapeutic effect of Bxt in the SOD1G93A mouse model of ALS. Mice were treated with Bxt or vehicle five times per week from day 60 onward. Survival, weight, and neuromuscular function studies together with histological and biochemical analyses were performed. Bxt significantly delayed motor function deterioration, ameliorated the loss of body weight, and extended mice survival up to 30% of the symptomatic period. Histological analyses of the lumbosacral spinal cord revealed that Bxt markedly delayed the early motor-neuron degeneration occurring at presymptomatic stages in ALS-transgenic mice. Bxt treatment contributed to preserve the MN homeostasis in the SOD1G93A mice. Particularly, it reduced the neuronal loss and the chromatolytic response, induced nucleolar hypertrophy, decreased the formation of ubiquitylated inclusions, and modulated the lysosomal response. As an agonist of the retinoic-X receptor (RXR) pathway, Bxt notably increased the nuclear expression of the RXRα throughout transcriptionally active euchromatin domains. Bxt also contributed to protect the MN environment by reducing reactive astrogliosis and preserving perisomatic synapsis. Overall, these neuroprotective effects suggest that treatment with Bxt could be useful in ALS, particularly in those cases related to SOD1 mutations. PMID:26190974

  2. The KCNE1 beta-subunit exerts a transient effect on the KCNQ1 K+ channel

    DEFF Research Database (Denmark)

    Poulsen, Asser Nyander; Klærke, Dan Arne

    2007-01-01

      The KCNE1 beta-subunit is a modulatory one-trans-membrane segment accessory protein that alters KCNQ1 K(+) channel current characteristics, though it is not required for channel expression. The KCNE1 and KCNQ1 interaction was investigated by looking for effects of expression time on channel...... currents in Xenopus laevis oocytes. We found that long-time expression of KCNQ1+KCNE1 (2-14 days) resulted in gradual changes in current characteristics resembling a disappearance of KCNE1 from the oocyte plasma membrane. Towards the end of the expression period the current of oocytes expressing KCNQ1+KCNE......1 was indistinguishable from those expressing KCNQ1 alone. No time dependent effect was seen in oocytes expressing KCNQ1 alone or a concatamer of KCNQ1 and KCNE1. Brefeldin A was tested, showing that measured current was independent of exocytosis (decreased capacitance) thus eliminating a continuous...

  3. Calcitriol exerts an anti-tumor effect in osteosarcoma by inducing the endoplasmic reticulum stress response.

    Science.gov (United States)

    Shimizu, Takatsune; Kamel, Walied A; Yamaguchi-Iwai, Sayaka; Fukuchi, Yumi; Muto, Akihiro; Saya, Hideyuki

    2017-09-01

    Osteosarcoma is the most common type of primary bone tumor, and novel therapeutic approaches for this disease are urgently required. To identify effective agents, we screened a panel of Food and Drug Administration (FDA)-approved drugs in AXT cells, our newly established mouse osteosarcoma line, and identified calcitriol as a candidate compound with therapeutic efficacy for this disease. Calcitriol inhibited cell proliferation in AXT cells by blocking cell cycle progression. From a mechanistic standpoint, calcitriol induced endoplasmic reticulum (ER) stress, which was potentially responsible for downregulation of cyclin D1, activation of p38 MAPK, and intracellular production of reactive oxygen species (ROS). Knockdown of Atf4 or Ddit3 restored cell viability after calcitriol treatment, indicating that the ER stress response was indeed responsible for the anti-proliferative effect in AXT cells. Notably, the ER stress response was induced to a lesser extent in human osteosarcoma than in AXT cells, consistent with the weaker suppressive effect on cell growth in the human cells. Thus, the magnitude of ER stress induced by calcitriol might be an index of its anti-osteosarcoma effect. Although mice treated with calcitriol exhibited weight loss and elevated serum calcium levels, a single dose was sufficient to decrease osteosarcoma tumor size in vivo. Our findings suggest that calcitriol holds therapeutic potential for treatment of osteosarcoma, assuming that techniques to diminish its toxicity could be established. In addition, our results show that calcitriol could still be safely administered to osteosarcoma patients for its original purposes, including treatment of osteoporosis. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  4. Chlorpyrifos exerts opposing effects on axonal and dendritic growth in primary neuronal cultures

    International Nuclear Information System (INIS)

    Howard, Angela S.; Bucelli, Robert; Jett, David A.; Bruun, Donald; Yang, Dongren; Lein, Pamela J.

    2005-01-01

    Evidence that children are widely exposed to organophosphorus pesticides (OPs) and that OPs cause developmental neurotoxicity in animal models raises significant concerns about the risks these compounds pose to the developing human nervous system. Critical to assessing this risk is identifying specific neurodevelopmental events targeted by OPs. Observations that OPs alter brain morphometry in developing rodents and inhibit neurite outgrowth in neural cell lines suggest that OPs perturb neuronal morphogenesis. However, an important question yet to be answered is whether the dysmorphogenic effect of OPs reflects perturbation of axonal or dendritic growth. We addressed this question by quantifying axonal and dendritic growth in primary cultures of embryonic rat sympathetic neurons derived from superior cervical ganglia (SCG) following in vitro exposure to chlorpyrifos (CPF) or its metabolites CPF-oxon (CPFO) and trichloropyridinol (TCP). Axon outgrowth was significantly inhibited by CPF or CPFO, but not TCP, at concentrations ≥0.001 μM or 0.001 nM, respectively. In contrast, all three compounds enhanced BMP-induced dendritic growth. Acetylcholinesterase was inhibited only by the highest concentrations of CPF (≥1 μM) and CPFO (≥1 nM); TCP had no effect on this parameter. In summary, these compounds perturb neuronal morphogenesis via opposing effects on axonal and dendritic growth, and both effects are independent of acetylcholinesterase inhibition. These findings have important implications for current risk assessment practices of using acetylcholinesterase inhibition as a biomarker of OP neurotoxicity and suggest that OPs may disrupt normal patterns of neuronal connectivity in the developing nervous system

  5. Epigeic Earthworms Exert a Bottleneck Effect on Microbial Communities through Gut Associated Processes

    OpenAIRE

    Gómez-Brandón, María; Aira, Manuel; Lores, Marta; Domínguez, Jorge

    2011-01-01

    BACKGROUND: Earthworms play a critical role in organic matter decomposition because of the interactions they establish with microorganisms. The ingestion, digestion, assimilation of organic material in the gut and then casting is the first step in earthworm-microorganism interactions. The current knowledge of these direct effects is still limited for epigeic earthworm species, mainly those living in man-made environments. Here we tested whether and to what extent the earthworm Eisenia andrei ...

  6. Bixa orellana (annatto) exerts a sustained hypoglycemic effect in experimental diabetes mellitus in rats

    OpenAIRE

    Teles, Flávio; Anjos, Felipe Silveira dos; Machado, Tarcilo; Lima, Roberta

    2014-01-01

    OBJECTIVE: Bixa orellana (annatto) is a natural pigment and food colorant that has been used for a variety of therapeutic purposes. It has been suggested that annatto could have the property of reducing blood glucose levels. However, most previous studies have demonstrated a hypoglycemic effect in non-diabetic animals. We evaluated the impact of annatto on blood glucose levels in an experimental model of diabetes mellitus. METHOD: Male Wistar rats were made diabetic by a single dose of60 mg/...

  7. Dexamethasone loaded nanoparticles exert protective effects against Cisplatin-induced hearing loss by systemic administration.

    Science.gov (United States)

    Sun, Changling; Wang, Xueling; Chen, Dongye; Lin, Xin; Yu, Dehong; Wu, Hao

    2016-04-21

    Ototoxicity is one of the most important adverse effects of cisplatin chemotherapy. As a common treatment of acute sensorineural hearing loss, systemic administration of steroids was demonstrated ineffective against cisplatin-induced hearing loss (CIHL) in published studies. The current study aimed to evaluate the potential protective effect of dexamethasone (DEX) encapsulated in polyethyleneglycol-coated polylactic acid (PEG-PLA) nanoparticles (DEX-NPs) against cisplatin-induced hearing loss following systemic administration. DEX was fabricated into PEG-PLA nanoparticles using emulsion and evaporation technique as previously reported. DEX or DEX-NPs was administered intraperitoneally to guinea pigs 1h before cisplatin administration. Auditory brainstem response (ABR) threshold shifts were measured at four frequencies (4, 8, 16, and 24kHz) 1 day before and three days after cisplatin injection. Cochlear morphology was examined to evaluate inner ear injury induced by cisplatin exposure. A single dose of DEX-NPs 1h before cisplatin treatment resulted in a significant preservation of the functional and structural properties of the cochlea, which was equivalent to the effect of multidose (3 days) DEX injection. In contrast, no significant protective effect was observed by single dose injection of DEX. The results of histological examination of the cochleae were consistent with the functional measurements. In conclusion, a single dose DEX-NPs significantly attenuated cisplatin ototoxicity in guinea pigs after systemic administration at both histological and functional levels indicating the potential therapeutic benefits of these nanoparticles for enhancing the delivery of DEX in acute sensorineural hearing loss. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Fucoidan Does Not Exert Anti-Tumorigenic Effects on Uveal Melanoma Cell Lines.

    Science.gov (United States)

    Dithmer, Michaela; Kirsch, Anna-Maria; Richert, Elisabeth; Fuchs, Sabine; Wang, Fanlu; Schmidt, Harald; Coupland, Sarah E; Roider, Johann; Klettner, Alexa

    2017-06-22

    The polysaccharide fucoidan is widely investigated as an anti-cancer agent. Here, we tested the effect of fucoidan on uveal melanoma cell lines. The effect of 100 µM fucoidan was investigated on five cell lines (92.1, Mel270 OMM1, OMM2.3, OMM2.5) and of 1 µg/mL-1 mg/mL fucoidan in two cell lines (OMM1, OMM2.3). Cell proliferation and viability were investigated with a WST-1 assay, migration in a wound healing (scratch) assay. Vascular Endothelial Growth Factor (VEGF) was measured in ELISA. Angiogenesis was evaluated in co-cultures with endothelial cells. Cell toxicity was induced by hydrogen-peroxide. Protein expression (Akt, ERK1/2, Bcl-2, Bax) was investigated in Western blot. Fucoidan increased proliferation in two and reduced it in one cell line. Migration was reduced in three cell lines. The effect of fucoidan on VEGF was cell type and concentration dependent. In endothelial co-culture with 92.1, fucoidan significantly increased tubular structures. Moreover, fucoidan significantly protected all tested uveal melanoma cell lines from hydrogen-peroxide induced cell death. Under oxidative stress, fucoidan did not alter the expression of Bcl-2, Bax or ERK1/2, while inducing Akt expression in 92.1 cells but not in any other cell line. Fucoidan did not show anti-tumorigenic effects but displayed protective and pro-angiogenic properties, rendering fucoidan unsuitable as a potential new drug for the treatment of uveal melanoma.

  9. Fucoidan Does Not Exert Anti-Tumorigenic Effects on Uveal Melanoma Cell Lines

    Directory of Open Access Journals (Sweden)

    Michaela Dithmer

    2017-06-01

    Full Text Available Background. The polysaccharide fucoidan is widely investigated as an anti-cancer agent. Here, we tested the effect of fucoidan on uveal melanoma cell lines. Methods. The effect of 100 µM fucoidan was investigated on five cell lines (92.1, Mel270 OMM1, OMM2.3, OMM2.5 and of 1 µg/mL–1 mg/mL fucoidan in two cell lines (OMM1, OMM2.3. Cell proliferation and viability were investigated with a WST-1 assay, migration in a wound healing (scratch assay. Vascular Endothelial Growth Factor (VEGF was measured in ELISA. Angiogenesis was evaluated in co-cultures with endothelial cells. Cell toxicity was induced by hydrogen-peroxide. Protein expression (Akt, ERK1/2, Bcl-2, Bax was investigated in Western blot. Results. Fucoidan increased proliferation in two and reduced it in one cell line. Migration was reduced in three cell lines. The effect of fucoidan on VEGF was cell type and concentration dependent. In endothelial co-culture with 92.1, fucoidan significantly increased tubular structures. Moreover, fucoidan significantly protected all tested uveal melanoma cell lines from hydrogen-peroxide induced cell death. Under oxidative stress, fucoidan did not alter the expression of Bcl-2, Bax or ERK1/2, while inducing Akt expression in 92.1 cells but not in any other cell line. Conclusion. Fucoidan did not show anti-tumorigenic effects but displayed protective and pro-angiogenic properties, rendering fucoidan unsuitable as a potential new drug for the treatment of uveal melanoma.

  10. Fucoidan Does Not Exert Anti-Tumorigenic Effects on Uveal Melanoma Cell Lines

    Science.gov (United States)

    Dithmer, Michaela; Kirsch, Anna-Maria; Richert, Elisabeth; Fuchs, Sabine; Wang, Fanlu; Schmidt, Harald; Coupland, Sarah E.; Roider, Johann; Klettner, Alexa

    2017-01-01

    Background. The polysaccharide fucoidan is widely investigated as an anti-cancer agent. Here, we tested the effect of fucoidan on uveal melanoma cell lines. Methods. The effect of 100 µM fucoidan was investigated on five cell lines (92.1, Mel270 OMM1, OMM2.3, OMM2.5) and of 1 µg/mL–1 mg/mL fucoidan in two cell lines (OMM1, OMM2.3). Cell proliferation and viability were investigated with a WST-1 assay, migration in a wound healing (scratch) assay. Vascular Endothelial Growth Factor (VEGF) was measured in ELISA. Angiogenesis was evaluated in co-cultures with endothelial cells. Cell toxicity was induced by hydrogen-peroxide. Protein expression (Akt, ERK1/2, Bcl-2, Bax) was investigated in Western blot. Results. Fucoidan increased proliferation in two and reduced it in one cell line. Migration was reduced in three cell lines. The effect of fucoidan on VEGF was cell type and concentration dependent. In endothelial co-culture with 92.1, fucoidan significantly increased tubular structures. Moreover, fucoidan significantly protected all tested uveal melanoma cell lines from hydrogen-peroxide induced cell death. Under oxidative stress, fucoidan did not alter the expression of Bcl-2, Bax or ERK1/2, while inducing Akt expression in 92.1 cells but not in any other cell line. Conclusion. Fucoidan did not show anti-tumorigenic effects but displayed protective and pro-angiogenic properties, rendering fucoidan unsuitable as a potential new drug for the treatment of uveal melanoma. PMID:28640204

  11. Labdanolic acid methyl ester (LAME) exerts anti-inflammatory effects through inhibition of TAK-1 activation

    International Nuclear Information System (INIS)

    Cuadrado, Irene; Cidre, Florencia; Herranz, Sandra; Estevez-Braun, Ana; Heras, Beatriz de las; Hortelano, Sonsoles

    2012-01-01

    Labdane derivatives obtained from the diterpenoid labdanediol suppressed NO and PGE 2 production in LPS-stimulated RAW 264.7 macrophages. However, mechanisms involved in these inhibitory effects are not elucidated. In this study, we investigated the signaling pathways involved in the anti-inflammatory effects of labdanolic acid methyl ester (LAME) in peritoneal macrophages and examined its therapeutic effect in a mouse endotoxic shock model. LAME reduced the production of NO and PGE 2 in LPS-activated macrophages. This effect involved the inhibition of NOS-2 and COX-2 gene expression, acting at the transcription level. Examination of the effects of the diterpene on NF-κB signaling showed that LAME inhibits the phosphorylation of IκBα and IκBβ, preventing their degradation and the nuclear translocation of the NF-κB p65 subunit. Moreover, inhibition of MAPK signaling was also observed. A further experiment revealed that LAME inhibited the phosphorylation of transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1), an upstream signaling molecule required for IKK and mitogen-activated protein kinases (MAPKs) activation. Inflammatory cytokines such as IL-6, TNF-α and IP-10 were downregulated in the presence of this compound after stimulation with LPS. Additionally, LAME also improved survival in a mouse model of endotoxemia and reduced the circulatory levels of cytokines (IL-6, TNF-α). In conclusion, these results indicate that labdane diterpene LAME significantly attenuates the pro-inflammatory response induced by LPS both in vivo and in vitro. Highlights: ► LAME reduced the production of NO and PGE 2 in LPS-activated macrophages. ► IL-6, TNF-α and IP-10 were also inhibited by LAME. ► Inhibition of TAK-1 activation is the mechanism involved in this process. ► LAME improved survival in a mouse model of endotoxemia. ► LAME reduced the circulatory levels of cytokines (IL-6, TNF-α).

  12. Labdanolic acid methyl ester (LAME) exerts anti-inflammatory effects through inhibition of TAK-1 activation

    Energy Technology Data Exchange (ETDEWEB)

    Cuadrado, Irene [Departamento de Farmacología, Facultad de Farmacia, Universidad Complutense, Plaza Ramón y Cajal s/n, 28040 Madrid (Spain); Cidre, Florencia; Herranz, Sandra [Unidad de Inflamación y Cáncer. Área de Biología Celular y Desarrollo. Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid (Spain); Estevez-Braun, Ana [Instituto Universitario de Bio-Orgánica “Antonio González”. Universidad de La Laguna. Avda. Astrofísico Fco. Sánchez 2. 38206. La Laguna, Tenerife (Spain); Instituto Canario de Investigaciones del Cáncer (ICIC) (Spain); Heras, Beatriz de las, E-mail: lasheras@farm.ucm.es [Departamento de Farmacología, Facultad de Farmacia, Universidad Complutense, Plaza Ramón y Cajal s/n, 28040 Madrid (Spain); Hortelano, Sonsoles, E-mail: shortelano@isciii.es [Unidad de Inflamación y Cáncer. Área de Biología Celular y Desarrollo. Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid (Spain)

    2012-01-01

    Labdane derivatives obtained from the diterpenoid labdanediol suppressed NO and PGE{sub 2} production in LPS-stimulated RAW 264.7 macrophages. However, mechanisms involved in these inhibitory effects are not elucidated. In this study, we investigated the signaling pathways involved in the anti-inflammatory effects of labdanolic acid methyl ester (LAME) in peritoneal macrophages and examined its therapeutic effect in a mouse endotoxic shock model. LAME reduced the production of NO and PGE{sub 2} in LPS-activated macrophages. This effect involved the inhibition of NOS-2 and COX-2 gene expression, acting at the transcription level. Examination of the effects of the diterpene on NF-κB signaling showed that LAME inhibits the phosphorylation of IκBα and IκBβ, preventing their degradation and the nuclear translocation of the NF-κB p65 subunit. Moreover, inhibition of MAPK signaling was also observed. A further experiment revealed that LAME inhibited the phosphorylation of transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1), an upstream signaling molecule required for IKK and mitogen-activated protein kinases (MAPKs) activation. Inflammatory cytokines such as IL-6, TNF-α and IP-10 were downregulated in the presence of this compound after stimulation with LPS. Additionally, LAME also improved survival in a mouse model of endotoxemia and reduced the circulatory levels of cytokines (IL-6, TNF-α). In conclusion, these results indicate that labdane diterpene LAME significantly attenuates the pro-inflammatory response induced by LPS both in vivo and in vitro. Highlights: ► LAME reduced the production of NO and PGE{sub 2} in LPS-activated macrophages. ► IL-6, TNF-α and IP-10 were also inhibited by LAME. ► Inhibition of TAK-1 activation is the mechanism involved in this process. ► LAME improved survival in a mouse model of endotoxemia. ► LAME reduced the circulatory levels of cytokines (IL-6, TNF-α).

  13. Neuroprotective and Cytotoxic Phthalides from Angelicae Sinensis Radix

    Directory of Open Access Journals (Sweden)

    Wenxia Gong

    2016-04-01

    Full Text Available Seven phthalides, including a new dimeric one named tokinolide C (7, were isolated from Angelicae Sinensis Radix and characterized. The structures of these compounds were elucidated on the basis of comprehensive analysis of spectroscopic data and comparison with literature data. All of the compounds were evaluated for their cytotoxic activities against the A549, HCT-8, and HepG2 cancer cell lines. Riligustilide (4 showed cytotoxicity against three cancer cell lines, with IC50 values of 13.82, 6.79, and 7.92 μM, respectively. Tokinolide A (6 and tokinolide C (6 exerted low cytotoxicity in these cancer cell lines, while the remaining compounds were inactive. Flow cytometry analysis was employed to evaluate the possible mechanism of cytotoxic action of riligustilide (4. We observed that compound 4 was able to arrest the cell cycle in the G1, S phases and induce apoptosis in a time-dependent manner in HCT-8 cell lines. In addition, these compounds were evaluated for neuroprotective effect against SH-SY5Y cells injured by glutamate. The result showed that ligustilide (1, Z-butylidenephthalide (3 and tokinolide A (6 exhibited significant neuroprotective effects.

  14. Epigeic earthworms exert a bottleneck effect on microbial communities through gut associated processes.

    Science.gov (United States)

    Gómez-Brandón, María; Aira, Manuel; Lores, Marta; Domínguez, Jorge

    2011-01-01

    Earthworms play a critical role in organic matter decomposition because of the interactions they establish with microorganisms. The ingestion, digestion, assimilation of organic material in the gut and then casting is the first step in earthworm-microorganism interactions. The current knowledge of these direct effects is still limited for epigeic earthworm species, mainly those living in man-made environments. Here we tested whether and to what extent the earthworm Eisenia andrei is capable of altering the microbiological properties of fresh organic matter through gut associated processes; and if these direct effects are related to the earthworm diet. To address these questions we determined the microbial community structure (phospholipid fatty acid profiles) and microbial activity (fluorescein diacetate hydrolysis) in the earthworm casts derived from three types of animal manure (cow, horse and pig manure), which differed in microbial composition. The passage of the organic material through the gut of E. andrei reduced the total microbial biomass irrespective of the type of manure, and resulted in a decrease in bacterial biomass in all the manures; whilst leaving the fungi unaffected in the egested materials. However, unlike the microbial biomass, no such reduction was detected in the total microbial activity of cast samples derived from the pig manure. Moreover, no differences were found between cast samples derived from the different types of manure with regards to microbial community structure, which provides strong evidence for a bottleneck effect of worm digestion on microbial populations of the original material consumed. Our data reveal that earthworm gut is a major shaper of microbial communities, thereby favouring the existence of a reduced but more active microbial population in the egested materials, which is of great importance to understand how biotic interactions within the decomposer food web influence on nutrient cycling.

  15. Epigeic earthworms exert a bottleneck effect on microbial communities through gut associated processes.

    Directory of Open Access Journals (Sweden)

    María Gómez-Brandón

    Full Text Available BACKGROUND: Earthworms play a critical role in organic matter decomposition because of the interactions they establish with microorganisms. The ingestion, digestion, assimilation of organic material in the gut and then casting is the first step in earthworm-microorganism interactions. The current knowledge of these direct effects is still limited for epigeic earthworm species, mainly those living in man-made environments. Here we tested whether and to what extent the earthworm Eisenia andrei is capable of altering the microbiological properties of fresh organic matter through gut associated processes; and if these direct effects are related to the earthworm diet. METHODOLOGY: To address these questions we determined the microbial community structure (phospholipid fatty acid profiles and microbial activity (fluorescein diacetate hydrolysis in the earthworm casts derived from three types of animal manure (cow, horse and pig manure, which differed in microbial composition. PRINCIPAL FINDINGS: The passage of the organic material through the gut of E. andrei reduced the total microbial biomass irrespective of the type of manure, and resulted in a decrease in bacterial biomass in all the manures; whilst leaving the fungi unaffected in the egested materials. However, unlike the microbial biomass, no such reduction was detected in the total microbial activity of cast samples derived from the pig manure. Moreover, no differences were found between cast samples derived from the different types of manure with regards to microbial community structure, which provides strong evidence for a bottleneck effect of worm digestion on microbial populations of the original material consumed. CONCLUSIONS/SIGNIFICANCE: Our data reveal that earthworm gut is a major shaper of microbial communities, thereby favouring the existence of a reduced but more active microbial population in the egested materials, which is of great importance to understand how biotic interactions

  16. RAM, an RGDS analog, exerts potent anti-melanoma effects in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Maria Simona Aguzzi

    Full Text Available Peptides containing the RGD sequence are under continuous investigation given their ability to control cell adhesion and apoptosis. Since small peptides are quickly metabolized and degraded in vivo, developing analogs resistant to serum-induced degradation is a challenging task. RGD analogs developed so far are known as molecules mostly inhibiting cell adhesion; this feature may reduce cell proliferation and tumor development but may not induce regression of tumors or metastases already formed. In the current study, carried out in melanoma in vitro and in vivo models, we show that RAM, an RGD-non-peptide Analog-Molecule, strongly inhibits cells adhesion onto plastic, vitronectin, fibronectin, laminin and von Willebrand Factor while it does not inhibit cell adhesion onto collagen IV, similarly to the RGDS template peptide. It also strongly inhibits in vitro cell proliferation, migration and DNA-synthesis, increases melanoma cells apoptosis and reduces survivin expression. All such effects were observed in collagen IV seeded cells, therefore are most likely independent from the anti adhesive properties. Further, RAM is more stable than the template RGDS; in fact it maintains its anti-proliferation and anti-adhesion effects after long serum exposure while RGDS almost completely loses its effects upon serum exposure. In a mouse metastatic melanoma in vivo model, increasing doses of RAM significantly reduce up to about 80% lung metastases development, while comparable doses of RGDS are less potent. In conclusion these data show that RAM is a potent inhibitor of melanoma growth in vitro, strongly reduces melanoma metastases development in vivo and represents a novel candidate for further in vivo investigations in the cancer treatment field.

  17. Placental extract ameliorates non-alcoholic steatohepatitis (NASH by exerting protective effects on endothelial cells

    Directory of Open Access Journals (Sweden)

    Akihiro Yamauchi

    2017-09-01

    Full Text Available Non-alcoholic steatohepatitis (NASH is a severe form of fatty liver disease that is defined by the presence of inflammation and fibrosis, ultimately leading to cirrhosis and hepatocellular carcinoma. Treatment with human placental extract (HPE reportedly ameliorates the hepatic injury. We evaluated the effect of HPE treatment in a mouse model of NASH. In the methione- and choline-deficient (MCD diet-induced liver injury model, fibrosis started from regions adjacent to the sinusoids. We administered the MCD diet with high-salt loading (8% NaCl in the drinking water to mice deficient in the vasoprotective molecule RAMP2 for 5 weeks, with or without HPE. In both the HPE and control groups, fibrosis was seen in regions adjacent to the sinusoids, but the fibrosis was less pronounced in the HPE-treated mice. Levels of TNF-α and MMP9 expression were also significantly reduced in HPE-treated mice, and oxidative stress was suppressed in the perivascular region. In addition, HPE dose-dependently increased survival of cultured endothelial cells exposed to 100 μM H2O2, and it upregulated expression of eNOS and the anti-apoptotic factors bcl-2 and bcl-xL. From these observations, we conclude that HPE ameliorates NASH-associated pathologies by suppressing inflammation, oxidative stress and fibrosis. These beneficially effects of HPE are in part attributable to its protective effects on liver sinusoidal endothelial cells. HPE could thus be an attractive therapeutic candidate with which to suppress progression from simple fatty liver to NASH.

  18. Intranasal Delivery of Recombinant NT4-NAP/AAV Exerts Potential Antidepressant Effect.

    Science.gov (United States)

    Ma, Xian-Cang; Chu, Zheng; Zhang, Xiao-Ling; Jiang, Wen-Hui; Jia, Min; Dang, Yong-Hui; Gao, Cheng-Ge

    2016-06-01

    The present study was designed to construct a recombinant adeno-associated virus (rAAV) which can express NAP in the brain and examine whether this virus can produce antidepressant effects on C57 BL/6 mice that had been subjected to open field test and forced swimming test, via nose-to-brain pathway. When the recombinant plasmid pGEM-T Easy/NT4-NAP was digested by EcoRI, 297 bp fragments can be obtained and NT4-NAP sequence was consistent with the designed sequence confirmed by DNA sequencing. When the recombinant plasmid pSSCMV/NT4-NAP was digested by EcoRI, 297 bp fragments is visible. Immunohistochemical staining of fibroblasts revealed that expression of NAP was detected in NT4-NAP/AAV group. Intranasal delivery of NT4-NAP/AAV significantly reduced immobility time when the FST was performed after 1 day from the last administration. The effects observed in the FST could not be attributed to non-specific increases in activity since intranasal delivery of NT4-NAP/AAV did not alter the behavior of the mice during the open field test. The results indicated that a recombinant AAV vector which could express NAP in cells was successfully constructed and NAP may be a potential target for therapeutic action of antidepressant treatment.

  19. Garlic exerts allelopathic effects on pepper physiology in a hydroponic co-culture system

    Directory of Open Access Journals (Sweden)

    Haiyan Ding

    2016-05-01

    Full Text Available A hydroponic co-culture system was adopted to determine the allelopathic potential of garlic on the growth of pepper plants. Different numbers of garlic plants (0, 2, 4, 8 and 12 were hydroponically co-cultured with two pepper plants to investigate allelopathic effects on the growth attributes and antioxidative defense system of the test pepper plants. The responses of the pepper plants depended on the number of garlic plants included in the co-culture system, indicating an association of pepper growth with the garlic root exudate concentration. When grown at a pepper/garlic ratio of 1:1 or 1:2, the pepper plant height, chlorophyll content, and peroxidase (POD, catalase (CAT and phenylalanine ammonia-lyase (PAL activities were significantly increased after 30 days of co-culture; in contrast, reduction in methane dicarboxylic aldehyde (MDA content was observed. However, when the pepper/garlic ratio was 1:4 or higher, these morphological indices and protective enzyme activities were significantly inhibited, whereas MDA levels in the pepper leaves were significantly increased due to severe membrane lipid peroxidation. The results indicate that although low concentrations of garlic root exudates appear to induce protective enzyme systems and promote pepper growth, high concentrations have deleterious effects. These findings suggest that further investigations should optimize the co-culture pepper/garlic ratio to reduce continuous cropping obstacles in pepper production.

  20. Native herbivore exerts contrasting effects on fire regime and vegetation structure.

    Science.gov (United States)

    Hierro, José L; Clark, Kenneth L; Branch, Lyn C; Villarreal, Diego

    2011-08-01

    Although native herbivores can alter fire regimes by consuming herbaceous vegetation that serves as fine fuel and, less commonly, accumulating fuel as nest material and other structures, simultaneous considerations of contrasting effects of herbivores on fire have scarcely been addressed. We proposed that a colonial rodent, vizcacha (Lagostomus maximus), reduces and increases fire intensity at different stages in its population cycle in the semiarid scrub of Argentina. Specifically, we hypothesized that, when colonies are active, vizcachas create natural fire-breaks through intense grazing, generating over time patches of large unburned shrubs in grazed zones. In contrast, when colonies are abandoned, recovery of fine fuels and previous accumulation of coarse wood on colonies during territorial displays increases fire intensity, creating patches of high shrub mortality. To test these hypotheses, we estimated stem age of the dominant shrub (Larrea divaricata) and measured aboveground biomass in zones actively grazed by vizcachas and in ungrazed zones, and compared densities of live and dead shrubs on abandoned colonies and adjacent zones following fire. In active colonies, age and biomass of shrubs were much greater in grazed than ungrazed zones. In abandoned colonies that had been burnt, density of dead, burned shrubs was higher and density of live shrubs was lower than in adjacent zones. These results support our hypotheses and reveal a new interaction between native herbivores and fire, in which herbivores augment fire intensity by gathering fuel. Our findings indicate that, through opposing effects on fire, native herbivores enhance the heterogeneity of vegetation in woody-dominated ecosystems.

  1. Plant Identity Exerts Stronger Effect than Fertilization on Soil Arbuscular Mycorrhizal Fungi in a Sown Pasture.

    Science.gov (United States)

    Zheng, Yong; Chen, Liang; Luo, Cai-Yun; Zhang, Zhen-Hua; Wang, Shi-Ping; Guo, Liang-Dong

    2016-10-01

    Arbuscular mycorrhizal (AM) fungi play key roles in plant nutrition and plant productivity. AM fungal responses to either plant identity or fertilization have been investigated. However, the interactive effects of different plant species and fertilizer types on these symbiotic fungi remain poorly understood. We evaluated the effects of the factorial combinations of plant identity (grasses Avena sativa and Elymus nutans and legume Vicia sativa) and fertilization (urea and sheep manure) on AM fungi following 2-year monocultures in a sown pasture field study. AM fungal extraradical hyphal density was significantly higher in E. nutans than that in A. sativa and V. sativa in the unfertilized control and was significantly increased by urea and manure in A. sativa and by manure only in E. nutans, but not by either fertilizers in V. sativa. AM fungal spore density was not significantly affected by plant identity or fertilization. Forty-eight operational taxonomic units (OTUs) of AM fungi were obtained through 454 pyrosequencing of 18S rDNA. The OTU richness and Shannon diversity index of AM fungi were significantly higher in E. nutans than those in V. sativa and/or A. sativa, but not significantly affected by any fertilizer in all of the three plant species. AM fungal community composition was significantly structured directly by plant identity only and indirectly by both urea addition and plant identity through soil total nitrogen content. Our findings highlight that plant identity has stronger influence than fertilization on belowground AM fungal community in this converted pastureland from an alpine meadow.

  2. Low power millimeter wave irradiation exerts no harmful effect on human keratinocytes in vitro.

    Science.gov (United States)

    Szabo, Imre; Manning, Michael R; Radzievsky, Alexander A; Wetzel, Michele A; Rogers, Thomas J; Ziskin, Marvin C

    2003-04-01

    Low power millimeter wave (LP-MW) irradiation has been successfully used in clinical practice as an independent and/or supplemental therapy in patients with various diseases. It is still not clear, however, whether exposed skin is directly affected by repeated LP-MW irradiation and whether cells of the epidermis can be activated by the absorbed energy. Keratinocytes, the most numerous component of the epidermis are believed to manifest functional responses to physical stimuli. In this study we analyzed whether LP-MW irradiation modulated the production of chemokines, including RANTES and IP-10 of keratinocytes in vitro. We also investigated whether LP-MW irradiation induces a heat stress reaction in keratinocytes, and stimulates heat shock protein 70 (Hsp70) production. Vital staining of keratinocytes with carboxyfluorescein succinimidyl ester and ethidium bromide was used to analyze the MW effect on the viability of adherent cells. In addition, we studied the effect of LP-MW irradiation on intercellular gap junctional communication in keratinocyte monolayers by Lucifer yellow dye transfer. We found no significant changes in constitutive RANTES and inducible IP-10 production following LP-MW irradiation. LP-MW exposure of keratinocyte monolayers did not alter Hsp70 production, unlike exposure to higher power MWs (HP-MW) or hyperthermia (43 degrees C; 1 h). LP-MW irradiation and hyperthermia did not alter the viability of adherent keratinocytes, while HP-MW irradiation induced cellular damage within the beam area. Finally, we found no alteration in the gap junctional intercellular communication of keratinocytes following LP-MW irradiation, which on the other hand, was significantly increased by hyperthermia. In summary, we detected no harmful effect of LP-MW irradiation on both keratinocyte function and structure in vitro, although these cells were sensitive to higher MW power that developed heat stress reaction and cellular damage. Our results provide further

  3. Ocean acidification exerts negative effects during warming conditions in a developing Antarctic fish.

    Science.gov (United States)

    Flynn, Erin E; Bjelde, Brittany E; Miller, Nathan A; Todgham, Anne E

    2015-01-01

    Anthropogenic CO2 is rapidly causing oceans to become warmer and more acidic, challenging marine ectotherms to respond to simultaneous changes in their environment. While recent work has highlighted that marine fishes, particularly during early development, can be vulnerable to ocean acidification, we lack an understanding of how life-history strategies, ecosystems and concurrent ocean warming interplay with interspecific susceptibility. To address the effects of multiple ocean changes on cold-adapted, slowly developing fishes, we investigated the interactive effects of elevated partial pressure of carbon dioxide (pCO2) and temperature on the embryonic physiology of an Antarctic dragonfish (Gymnodraco acuticeps), with protracted embryogenesis (∼10 months). Using an integrative, experimental approach, our research examined the impacts of near-future warming [-1 (ambient) and 2°C (+3°C)] and ocean acidification [420 (ambient), 650 (moderate) and 1000 μatm pCO2 (high)] on survival, development and metabolic processes over the course of 3 weeks in early development. In the presence of increased pCO2 alone, embryonic mortality did not increase, with greatest overall survival at the highest pCO2. Furthermore, embryos were significantly more likely to be at a later developmental stage at high pCO2 by 3 weeks relative to ambient pCO2. However, in combined warming and ocean acidification scenarios, dragonfish embryos experienced a dose-dependent, synergistic decrease in survival and developed more slowly. We also found significant interactions between temperature, pCO2 and time in aerobic enzyme activity (citrate synthase). Increased temperature alone increased whole-organism metabolic rate (O2 consumption) and developmental rate and slightly decreased osmolality at the cost of increased mortality. Our findings suggest that developing dragonfish are more sensitive to ocean warming and may experience negative physiological effects of ocean acidification only in

  4. Regulation of the endoplasmic reticulum stress response and neuroprotective effects of acupuncture on brain injury caused by heroin addiction.

    Science.gov (United States)

    Gao, Yong-Long; Zhang, Yang; Cao, Jiang-Peng; Wu, Sheng-Bing; Cai, Xing-Hui; Zhang, Yan-Chun; Zhang, Rong-Jun; Song, Xiao-Ge; Zhang, Li-Da

    2017-10-01

    To evaluate regulation of the endoplasmic reticulum stress (ERS) response by acupuncture and to investigate its neuroprotective effect on brain injury caused by heroin addiction. A total of 48 male Sprague-Dawley rats were randomly divided into a healthy control group (Control), an untreated heroin exposed group (Heroin) and a heroin exposed group receiving electroacupuncture (EA) treatment at GV14 and GV20 (Heroin+acupuncture) with n=16 rats per group. A rat model of heroin addiction was established by intramuscular injection of incremental doses of heroin for 8 consecutive days. A rat model of heroin relapse was established according to the exposure (addiction) → detoxification method. Apoptotic changes in nerve cells in the hippocampus and ventral tegmental area (VTA) were evaluated in each group of rats using terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay. PERK, eIF2a, CHOP, IRE1 and JNK gene expression and protein expression were measured using quantitative real-time PCR (RT-qPCR) assay and immunohistochemical assay, respectively. The total number of positive nerve cells in the hippocampus and VTA was significantly lower in the Heroin+acupuncture group than in the Heroin group (pHeroin group, mRNA and protein expression of PERK, eIF2a, CHOP, IRE1 and JNK in the hippocampus and VTA were significantly downregulated in the Heroin+acupuncture group (pheroin-addicted rats with brain injury. Inhibition of CHOP and JNK upregulation and reduction of nerve cell apoptosis may be the main mechanisms underlying the effects of acupuncture on heroin addiction-induced brain injury. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  5. Neuroprotective effects of chloroform and petroleum ether extracts of Nigella sativa seeds in stroke model of rat

    Science.gov (United States)

    Akhtar, Mohammad; Maikiyo, Aliyu Muhammad; Najmi, Abul Kalam; Khanam, Razia; Mujeeb, Mohd; Aqil, Mohd

    2013-01-01

    PURPOSE: Stroke still remains a challenge for the researchers and scientists for developing ideal drug. Several new drugs are being evaluated showing excellent results in preclinical studies but when tested in clinical trials, they failed. Many herbal drugs in different indigenous system of medicine claim to have beneficial effects but not extensively evaluated for stroke (cerebral ischemia). AIM: The present study was undertaken to evaluate chloroform and petroleum ether extract of Nigella sativa seeds administered at a dose of 400 mg/kg, per orally for seven days in middle cerebral artery occluded (MCAO) rats for its neuroprotective role in cerebral ischemia. MATERIALS AND METHODS: Focal cerebral ischemia was induced by middle cerebral artery occlusion for two hours followed by reperfusion for 22 hours. After 24 hours, grip strength, locomotor activity tests were performed in different treatment groups of rats. After completing behavioral tests, animals were sacrificed; brains were removed for the measurement of infarct volume followed by the estimation of markers of oxidative stress. RESULTS: Both chloroform and petroleum ether extracts-pretreated rats showed improvement in locomotor activity and grip strength, reduced infarct volume when compared with MCAO rats. MCA occlusion resulted in the elevation of levels of thiobarbituric acid reactive substance (TBARS), while a reduction in the levels of glutathione (GSH) and antioxidant enzymes viz. superoxide dismutase (SOD) and catalase levels were observed. Pre-treatment of both extracts of Nigella sativa showed reduction in TBARS, elevation in glutathione, SOD, and catalase levels when compared with MCAO rats. CONCLUSION: The chloroform and petroleum ether extract of Nigella sativa showed the protective effects in cerebral ischemia. The present study confirms the antioxidant, free radical scavenging, and anti-inflammatory properties of Nigella sativa already reported. PMID:23833517

  6. Neuroprotective effects of JGK-263 in transgenic SOD1-G93A mice of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Ahn, Suk-Won; Jeon, Gye Sun; Kim, Myung-Jin; Shon, Jee-Heun; Kim, Jee-Eun; Shin, Je-Young; Kim, Sung-Min; Kim, Seung Hyun; Ye, In-Hae; Lee, Kwang-Woo; Hong, Yoon-Ho; Sung, Jung-Joon

    2014-05-15

    Glycogen synthase kinase-3β (GSK-3β) activity plays a central role in motor neuron degeneration. GSK-3β inhibitors have been shown to prolong motor neuron survival and suppress disease progression in amyotrophic lateral sclerosis (ALS). In this study, we evaluated the therapeutic effects of a new GSK-3b inhibitor, JGK-263, on ALS in G93A SOD1 transgenic mice. Previously, biochemical efficacy of JGK-263 was observed in normal and mutant (G93A) hSOD1-transfected motor neuronal cell lines (NSC34). Based on these previous results, we administered JGK-263 orally to 93 transgenic mice with the human G93A-mutated SOD1 gene. The mice were divided into three groups: a group administered 20mg/kg JGK-263, a group administered 50mg/kg JGK-263, and a control group not administered with JGK-263. Clinical status, rotarod test, and survival rates of transgenic mice with ALS were evaluated. Sixteen mice from each group were selected for further biochemical study that involved examination of motor neuron count, apoptosis, and cell survival signals. JGK-263 administration remarkably improved motor function and prolonged the time until symptom onset, rotarod failure, and death in transgenic mice with ALS compared to control mice. In JGK-263 groups, choline acetyltransferase (ChAT) staining in the ventral horn of the lower lumbar spinal cord showed a large number of motor neurons, suggesting normal morphology. The neuroprotective effects of JGK-263 in ALS mice were also suggested by western blot analysis of spinal cord tissues in transgenic mice. These results suggest that JGK-263, an oral GSK-3β inhibitor, is promising as a novel therapeutic agent for ALS. Still, further biochemical studies on the underlying mechanisms and safety of JGK-263 are necessary. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. The effect of body armor on performance, thermal stress, and exertion: a critical review.

    Science.gov (United States)

    Larsen, Brianna; Netto, Kevin; Aisbett, Brad

    2011-11-01

    Armed forces worldwide utilize some form of body armor as part of their personal protective system. This is particularly essential in recent times because of the increased sophistication of weapons employed during modern warfare and the advent of unconventional combat methods (such as the increased use of improvised explosive devices). There is some evidence to show, however, that the usage of military body armor impairs physical performance. This review of the literature will focus on the effect of body armor on the performance of, and physiological and subjective responses during, military-style physical tasks. Because of the paucity of research investigating body armor, this review will also draw upon more generalized personal protective clothing and equipment literature from a range of physically demanding occupations (i.e., firefighting and other emergency services). The review will conclude with suggested directions for future research in this area.

  8. Lutein exerts anti-inflammatory effects in patients with coronary artery disease.

    Science.gov (United States)

    Chung, Rosanna W S; Leanderson, Per; Lundberg, Anna K; Jonasson, Lena

    2017-07-01

    Many coronary artery disease (CAD) patients exhibit chronic low-grade inflammation. Carotenoids are anti-oxidants with potential anti-inflammatory properties. Here, we first assessed relationships between interleukin (IL)-6 and individual carotenoids in plasma from CAD patients. Based on the results, we proceeded to assess anti-inflammatory effects of one carotenoid, lutein, in peripheral blood mononuclear cells (PBMCs) from CAD patients. Lutein + zeaxanthin (isomers with lutein being dominant), β-cryptoxanthin, lycopene, α- and β-carotene and IL-6 were measured in plasma from 134 patients with stable angina (SA) and 59 patients with acute coronary syndrome. In 42 patients, plasma measurements were also performed 3 months after coronary intervention. PBMCs from SA patients were pre-treated with lutein (1, 5 and 25 μM) for 24 h followed by 24 h incubation ± lipopolysaccharide (LPS). Cell pellets were collected for IL-6, IL-1β and TNF mRNA and intracellular lutein. Cytokine secretion was measured in cell media. Only lutein + zeaxanthin were inversely correlated with IL-6 in SA patients at baseline (r = -0.366, p lutein was taken up by PBMCs from SA patients in a dose- and time-dependent manner. Pre-treatment with lutein dose-dependently lowered LPS-induced secretion of IL-6, IL-1β (p lutein and IL-6 in CAD patients. Anti-inflammatory effects of lutein in PBMCs from CAD patients were consolidated in ex vivo experiments. Taken together, these results show that lutein has the potential to play a role in resolution of chronic inflammation in CAD patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. The chalcone compound isosalipurposide (ISPP) exerts a cytoprotective effect against oxidative injury via Nrf2 activation

    International Nuclear Information System (INIS)

    Han, Jae Yun; Cho, Seung Sik; Yang, Ji Hye; Kim, Kyu Min; Jang, Chang Ho; Park, Da Eon; Bang, Joon Seok; Jung, Young Suk; Ki, Sung Hwan

    2015-01-01

    The chalcone compound isosalipurposide (ISPP) has been successfully isolated from the native Korean plant species Corylopsis coreana Uyeki (Korean winter hazel). However, the therapeutic efficacy of ISPP remains poorly understood. This study investigated whether ISPP has the capacity to activate NF-E2-related factor (Nrf2)-antioxidant response element (ARE) signaling and induce its target gene expression, and to determined the protective role of ISPP against oxidative injury of hepatocytes. In HepG2 cells, nuclear translocation of Nrf2 is augmented by ISPP treatment. Consistently, ISPP increased ARE reporter gene activity and the protein levels of glutamate cysteine ligase (GCL) and hemeoxygenase (HO-1), resulting in increased intracellular glutathione levels. Cells pretreated with ISPP were rescued from tert-butylhydroperoxide-induced reactive oxygen species (ROS) production and glutathione depletion and consequently, apoptotic cell death. Moreover, ISPP ameliorated the mitochondrial dysfunction and apoptosis induced by rotenone which is an inhibitor of complex 1 of the mitochondrial respiratory chain. The specific role of Nrf2 activation by ISPP was demonstrated using an ARE-deletion mutant plasmid and Nrf2-knockout cells. Finally, we observed that extracellular signal-regulated kinase (ERK) and AMP-activated protein kinase (AMPK), but not protein kinase C (PKC)-δ or other mitogen-activated protein kinases (MAPKs), are involved in the activation of Nrf2 by ISPP. Taken together, our results demonstrate that ISPP has a cytoprotective effect against oxidative damage mediated through Nrf2 activation and induction of its target gene expression in hepatocytes. - Highlights: • We investigated the effect of ISPP on Nrf2 activation. • ISPP increased Nrf2 activity and its target gene expression. • ISPP inhibited the mitochondrial dysfunction and ROS production. • Nrf2 activation by ISPP is dependent on ERK1/2 and AMPK phosphorylation. • ISPP may be a promising

  10. Rose hip exerts antidiabetic effects via a mechanism involving downregulation of the hepatic lipogenic program.

    Science.gov (United States)

    Andersson, Ulrika; Henriksson, Emma; Ström, Kristoffer; Alenfall, Jan; Göransson, Olga; Holm, Cecilia

    2011-01-01

    The aim of this study was to investigate the metabolic effects of a dietary supplement of powdered rose hip to C57BL/6J mice fed a high-fat diet (HFD). Two different study protocols were used; rose hip was fed together with HFD to lean mice for 20 wk (prevention study) and to obese mice for 10 wk (intervention study). Parameters related to obesity and glucose tolerance were monitored, and livers were examined for lipids and expression of genes and proteins related to lipid metabolism and gluconeogenesis. A supplement of rose hip was capable of both preventing and reversing the increase in body weight and body fat mass imposed by a HFD in the C57BL/6J mouse. Oral and intravenous glucose tolerance tests together with lower basal levels of insulin and glucose showed improved glucose tolerance in mice fed a supplement of rose hip compared with control mice. Hepatic lipid accumulation was reduced in mice fed rose hip compared with control, and the expression of lipogenic proteins was downregulated, whereas AMP-activated protein kinase and other proteins involved in fatty acid oxidation were unaltered. Rose hip intake lowered total plasma cholesterol as well as the low-density lipoprotein-to-high-density lipoprotein ratio via a mechanism not involving altered gene expression of sterol regulatory element-binding protein 2 or 3-hydroxymethylglutaryl-CoA reductase. Taken together, these data show that a dietary supplement of rose hip prevents the development of a diabetic state in the C57BL/6J mouse and that downregulation of the hepatic lipogenic program appears to be at least one mechanism underlying the antidiabetic effect of rose hip.

  11. Sulfated galactans from the red seaweed Gracilaria fisheri exerts anti-migration effect on cholangiocarcinoma cells.

    Science.gov (United States)

    Sae-Lao, Thannicha; Luplertlop, Natthanej; Janvilisri, Tavan; Tohtong, Rutaiwan; Bates, David O; Wongprasert, Kanokpan

    2017-12-01

    Seaweeds have a long history of use in Asian countries as functional foods, medicinal herbs, and the treatment of cancer. Polysaccharides from various seaweeds have shown anti-tumor activity. Cholangiocarcinoma (CCA), often with metastatic disease, is highly prevalent in Thailand as a consequence of liver fluke infection. Recently, we extracted sulfated galactans (SG) from Gracilaria fisheri (G. fisheri), a south east Asian seaweed, and found it exhibited anti-proliferation effect on CCA cells. In the present study, we evaluated the anti-migration activity of SG on CCA cells and its underlined mechanism. CCA cells were treated with SG alone or drugs targeting to epidermal growth factor (EGF) receptor (EGFR) or pretreated with SG prior to incubation with EGF. Anti-migration activity was determined using a scratch wound-healing assay and zymography. Immunofluorescence staining and western blotting were used to investigate EGFR signaling mediators. Under basal condition, SG reduced the migration rate of CCA, which was correlated with a decrease in the active-form of matrix metalloproteinases-9. SG decreased expression of phosphorylated focal adhesion kinase (FAK), but increased expression of E-cadherin to promote cells stasis. Moreover, phosphorylation of EGFR and extracellular signal-regulated kinases (ERK), known to stimulate growth of cancer cells, was blocked in a comparable way to EGFR inhibitors Cetuximab and Erlotinib. Pretreatment cells with SG attenuated EGF induced phosphorylation of EGFR, ERK and FAK. This study reveals that SG from G. fisheri retards migration of CCA cells, and its mechanism of inhibition is mediated, to some extent, by inhibitory effects on MAPK/ERK signal transduction pathway. Our findings suggest that there may be a therapeutic potential of SG in CCA treatment. Copyright © 2017 Elsevier GmbH. All rights reserved.

  12. Proton pump inhibitors exert anti-allergic effects by reducing TCTP secretion.

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    Sunghee Choi

    Full Text Available BACKGROUND: Extracellular translationally controlled tumor protein (TCTP is known to play a role in human allergic responses. TCTP has been identified outside of macrophages, in activated mononuclear cells, and in biological fluids from allergic patients. Even TCTP devoid of signal sequences, is secreted to extracellular environment by an yet undefined mechanism. This study is aimed at understanding the mechanism of TCTP release and its regulation. A secondary goal is to see if inhibitors of TCTP release can serve as potential anti-allergic asthmatic drugs. METHODOLOGY/PRINCIPAL FINDINGS: Using Western blotting assay in HEK293 and U937 cells, we found that TCTP secretion is reduced by omeprazole and pantoprazole, both of which are proton pump inhibitors. We then transfected HEK293 cells with proton pump expression vectors to search for the effects of exogeneously overexpressed H(+/K(+-ATPase on the TCTP secretion. Based on these in vitro data we checked the in vivo effects of pantoprazole in a murine model of ovalbumin-induced allergy. Omeprazole and pantoprazole reduced TCTP secretion from HEK293 and U937 cells in a concentration-dependent fashion and the secretion of TCTP from HEK293 cells increased when they over-expressed H(+/K(+-ATPase. In a murine model of ovalbumin-induced allergy, pretreatment with pantoprazole reduced infiltration of inflammatory cells, increased goblet cells, and increased TCTP secretion induced by OVA challenge. CONCLUSION: Since Omeprazole and pantoprazole decrease the secretion of TCTP which is associated with the development of allergic reaction, they may have the potential to serve as anti-allergic (asthmatic drugs.

  13. The chalcone compound isosalipurposide (ISPP) exerts a cytoprotective effect against oxidative injury via Nrf2 activation

    Energy Technology Data Exchange (ETDEWEB)

    Han, Jae Yun [College of Pharmacy, Chosun University, Gwangju 501-759 (Korea, Republic of); Cho, Seung Sik [College of Pharmacy, Mokpo National University, Muan, Jeonnam 535-729 (Korea, Republic of); Yang, Ji Hye; Kim, Kyu Min; Jang, Chang Ho [College of Pharmacy, Chosun University, Gwangju 501-759 (Korea, Republic of); Park, Da Eon [College of Pharmacy, Mokpo National University, Muan, Jeonnam 535-729 (Korea, Republic of); Bang, Joon Seok [Graduate School of Clinical Pharmacy, Sookmyung Women' s University, Seoul (Korea, Republic of); Jung, Young Suk [College of Pharmacy, Pusan National University, Busan (Korea, Republic of); Ki, Sung Hwan, E-mail: shki@chosun.ac.kr [College of Pharmacy, Chosun University, Gwangju 501-759 (Korea, Republic of)

    2015-08-15

    The chalcone compound isosalipurposide (ISPP) has been successfully isolated from the native Korean plant species Corylopsis coreana Uyeki (Korean winter hazel). However, the therapeutic efficacy of ISPP remains poorly understood. This study investigated whether ISPP has the capacity to activate NF-E2-related factor (Nrf2)-antioxidant response element (ARE) signaling and induce its target gene expression, and to determined the protective role of ISPP against oxidative injury of hepatocytes. In HepG2 cells, nuclear translocation of Nrf2 is augmented by ISPP treatment. Consistently, ISPP increased ARE reporter gene activity and the protein levels of glutamate cysteine ligase (GCL) and hemeoxygenase (HO-1), resulting in increased intracellular glutathione levels. Cells pretreated with ISPP were rescued from tert-butylhydroperoxide-induced reactive oxygen species (ROS) production and glutathione depletion and consequently, apoptotic cell death. Moreover, ISPP ameliorated the mitochondrial dysfunction and apoptosis induced by rotenone which is an inhibitor of complex 1 of the mitochondrial respiratory chain. The specific role of Nrf2 activation by ISPP was demonstrated using an ARE-deletion mutant plasmid and Nrf2-knockout cells. Finally, we observed that extracellular signal-regulated kinase (ERK) and AMP-activated protein kinase (AMPK), but not protein kinase C (PKC)-δ or other mitogen-activated protein kinases (MAPKs), are involved in the activation of Nrf2 by ISPP. Taken together, our results demonstrate that ISPP has a cytoprotective effect against oxidative damage mediated through Nrf2 activation and induction of its target gene expression in hepatocytes. - Highlights: • We investigated the effect of ISPP on Nrf2 activation. • ISPP increased Nrf2 activity and its target gene expression. • ISPP inhibited the mitochondrial dysfunction and ROS production. • Nrf2 activation by ISPP is dependent on ERK1/2 and AMPK phosphorylation. • ISPP may be a promising

  14. DNA, histones and neutrophil extracellular traps exert anti-fibrinolytic effects in a plasma environment.

    Science.gov (United States)

    Varjú, Imre; Longstaff, Colin; Szabó, László; Farkas, Ádám Zoltán; Varga-Szabó, Veronika Judit; Tanka-Salamon, Anna; Machovich, Raymund; Kolev, Krasimir

    2015-06-01

    In response to various inflammatory stimuli, neutrophils secrete neutrophil extracellular traps (NETs), web-like meshworks of DNA, histones and granular components forming supplementary scaffolds in venous and arterial thrombi. Isolated DNA and histones are known to promote thrombus formation and render fibrin clots more resistant to mechanical forces and tissue-type plasminogen activator (tPA)-induced enzymatic digestion. The present study extends our earlier observations to a physiologically more relevant environment including plasma cl