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Sample records for prevent ischemic brain

  1. Pre-Ischemic Treadmill Training for Prevention of Ischemic Brain Injury via Regulation of Glutamate and Its Transporter GLT-1

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    Jingchun Guo

    2012-07-01

    Full Text Available Pre-ischemic treadmill training exerts cerebral protection in the prevention of cerebral ischemia by alleviating neurotoxicity induced by excessive glutamate release following ischemic stroke. However, the underlying mechanism of this process remains unclear. Cerebral ischemia-reperfusion injury was observed in a rat model after 2 weeks of pre-ischemic treadmill training. Cerebrospinal fluid was collected using the microdialysis sampling method, and the concentration of glutamate was determined every 40 min from the beginning of ischemia to 4 h after reperfusion with high-performance liquid chromatography (HPLC-fluorescence detection. At 3, 12, 24, and 48 h after ischemia, the expression of the glutamate transporter-1 (GLT-1 protein in brain tissues was determined by Western blot respectively. The effect of pre-ischemic treadmill training on glutamate concentration and GLT-1 expression after cerebral ischemia in rats along with changes in neurobehavioral score and cerebral infarct volume after 24 h ischemia yields critical information necessary to understand the protection mechanism exhibited by pre-ischemic treadmill training. The results demonstrated that pre-ischemic treadmill training up-regulates GLT-1 expression, decreases extracellular glutamate concentration, reduces cerebral infarct volume, and improves neurobehavioral score. Pre-ischemic treadmill training is likely to induce neuroprotection after cerebral ischemia by regulating GLT-1 expression, which results in re-uptake of excessive glutamate.

  2. Goreisan Prevents Brain Edema after Cerebral Ischemic Stroke by Inhibiting Aquaporin 4 Upregulation in Mice.

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    Nakano, Takafumi; Nishigami, Chisa; Irie, Keiichi; Shigemori, Yutaka; Sano, Kazunori; Yamashita, Yuta; Myose, Takayuki; Tominaga, Koji; Matsuo, Koichi; Nakamura, Yoshihiko; Ishikura, Hiroyasu; Kamimura, Hidetoshi; Egawa, Takashi; Mishima, Kenichi

    2018-03-01

    Aquaporin 4 (AQP4) is a water-selective transport protein expressed in astrocytes throughout the central nervous system. AQP4 level increases after cerebral ischemia and results in ischemic brain edema. Brain edema markedly influences mortality and motor function by elevating intracranial pressure that leads to secondary brain damage. Therefore, AQP4 is an important target to improve brain edema after cerebral ischemia. The Japanese herbal Kampo medicine, goreisan, is known to inhibit AQP4 activity. Here, we investigated whether goreisan prevents induction of brain edema by cerebral ischemia via AQP4 using 4-hour middle cerebral artery occlusion (4h MCAO) mice. Goreisan was orally administered at a dose of 500 mg/kg twice a day for 5 days before MCAO. AQP4 expression and motor coordination were measured by Western blotting and rotarod test, respectively. Brain water content of 4h MCAO mice was significantly increased at 24 hours after MCAO. Treatment with goreisan significantly decreased both brain water content and AQP4 expression in the ischemic brain at 24 hours after MCAO. In addition, treatment with goreisan alleviated motor coordination deficits at 24 hours after MCAO. The results of this study suggested that goreisan may be a useful new therapeutic option for ischemic brain edema. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  3. Ischemic preconditioning protects against ischemic brain injury

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    Xiao-meng Ma

    2016-01-01

    Full Text Available In this study, we hypothesized that an increase in integrin αv ß 3 and its co-activator vascular endothelial growth factor play important neuroprotective roles in ischemic injury. We performed ischemic preconditioning with bilateral common carotid artery occlusion for 5 minutes in C57BL/6J mice. This was followed by ischemic injury with bilateral common carotid artery occlusion for 30 minutes. The time interval between ischemic preconditioning and lethal ischemia was 48 hours. Histopathological analysis showed that ischemic preconditioning substantially diminished damage to neurons in the hippocampus 7 days after ischemia. Evans Blue dye assay showed that ischemic preconditioning reduced damage to the blood-brain barrier 24 hours after ischemia. This demonstrates the neuroprotective effect of ischemic preconditioning. Western blot assay revealed a significant reduction in protein levels of integrin αv ß 3, vascular endothelial growth factor and its receptor in mice given ischemic preconditioning compared with mice not given ischemic preconditioning 24 hours after ischemia. These findings suggest that the neuroprotective effect of ischemic preconditioning is associated with lower integrin αv ß 3 and vascular endothelial growth factor levels in the brain following ischemia.

  4. Totarol prevents neuronal injury in vitro and ameliorates brain ischemic stroke: Potential roles of Akt activation and HO-1 induction

    International Nuclear Information System (INIS)

    Gao, Yuanxue; Xu, Xiaojun; Chang, Sai; Wang, Yunjie; Xu, Yazhou; Ran, Siqi; Huang, Zhangjian; Li, Ping; Li, Jia; Zhang, Luyong; Saavedra, Juan M.; Liao, Hong; Pang, Tao

    2015-01-01

    The natural product totarol, a phenolic diterpenoid and a major constituent isolated from the sap of Podocarpus totara, has been reported to have a potent antimicrobial activity. In this study, we determined whether totarol possessed an additional neuroprotective activity in vitro and in vivo. We found that totarol prevented glutamate- and oxygen and glucose deprivation-induced neuronal death in primary rat cerebellar granule neuronal cells and cerebral cortical neurons. Totarol increased Akt and GSK-3β phosphorylation, Nrf2 and heme oxygenase-1 (HO-1) protein expressions and suppressed oxidative stress by increasing GSH and SOD activities. The PI3K/Akt inhibitor LY294002 prevented totarol neuroprotective effect by suppressing the totarol-induced changes in HO-1 expression and the activities of GSH and SOD. The HO-1 inhibitor ZnPPIX also prevented totarol-increased GSH and SOD activities. In a model of acute cerebral ischemic injury in Sprague–Dawley rats, produced by occlusion of the middle cerebral artery for 2 h followed by 22 h or 46 h of reperfusion, totarol significantly reduced infarct volume and improved the neurological deficit. In this model, totarol increased HO-1 expression and the activities of GSH and SOD. These observations suggest that totarol may be a novel activator of the Akt/HO-1 pathway protecting against ischemic stroke through reduction of oxidative stress. - Graphical abstract: It is unknown whether the natural product totarol has neuroprotective effects in vitro and in vivo. This study underscores that totarol prevents neuronal injury in vitro, not only by activating PI3K/Akt pathway, but also via induction of Nrf2, HO-1, GSH and SOD expressions. Totarol also ameliorated acute cerebral ischemic injury in a rat ischemic stroke model. The findings highlight that totarol may be exploited for protecting against ischemic stroke through Akt/HO-1 pathway. - Highlights: • Totarol protects glutamate- and OGD-induced neuronal injury in vitro.

  5. Ischemic Tolerance of the Brain and Spinal Cord: A Review.

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    Yunoki, Masatoshi; Kanda, Takahiro; Suzuki, Kenta; Uneda, Atsuhito; Hirashita, Koji; Yoshino, Kimihiro

    2017-11-15

    Ischemic tolerance is an endogenous neuroprotective phenomenon induced by sublethal ischemia. Ischemic preconditioning (IPC), the first discovered form of ischemic tolerance, is widely seen in many species and in various organs including the brain and the spinal cord. Ischemic tolerance of the spinal cord is less familiar among neurosurgeons, although it has been reported from the viewpoint of preventing ischemic spinal cord injury during aortic surgery. It is important for neurosurgeons to have opportunities to see patients with spinal cord ischemia, and to understand ischemic tolerance of the spinal cord as well as the brain. IPC has a strong neuroprotective effect in animal models of ischemia; however, clinical application of IPC for ischemic brain and spinal diseases is difficult because they cannot be predicted. In addition, one drawback of preconditioning stimuli is that they are also capable of producing injury with only minor changes to their intensity or duration. Numerous methods to induce ischemic tolerance have been discovered that vary in their timing and the site at which short-term ischemia occurs. These methods include ischemic postconditioning (IPoC), remote ischemic preconditioning (RIPC), remote ischemic perconditioning (RIPerC) and remote ischemic postconditioning (RIPoC), which has had a great impact on clinical approaches to treatment of ischemic brain and spinal cord injury. Especially RIPerC and RIPoC to induce spinal cord tolerance are considered clinically useful, however the evidence supporting these methods is currently insufficient; further experimental or clinical research in this area is thus necessary.

  6. B vitamins and magnetic resonance imaging-detected ischemic brain lesions in patients with recent transient ischemic attack or stroke: the VITAmins TO Prevent Stroke (VITATOPS) MRI-substudy.

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    Cavalieri, Margherita; Schmidt, Reinhold; Chen, Christopher; Mok, Vincent; de Freitas, Gabriel R; Song, Swithin; Yi, Qilong; Ropele, Stefan; Grazer, Anja; Homayoon, Nina; Enzinger, Christian; Loh, Katherine; Wong, Ka Sing Lawrence; Wong, Adrian; Xiong, Yunyun; Chang, Hui Meng; Wong, Meng Cheong; Fazekas, Franz; Eikelboom, John W; Hankey, Graeme J

    2012-12-01

    Elevated concentrations of homocysteine are associated with cerebral small vessel disease (CSVD). B-vitamin supplementation with folate and vitamins B12 and B6 reduces homocysteine concentrations. In a substudy of the VITAmins TO Prevent Stroke (VITATOPS) trial, we assessed the hypothesis that the addition of once-daily supplements of B vitamins would reduce the progression of CSVD-related brain lesions. A total of 359 patients with recent stroke or transient ischemic attack, who were randomly allocated to double-blind treatment with placebo or b vitamins, underwent brain MRI at randomization and after 2 years of B-vitamin supplementation. MR images were analyzed blinded to treatment allocation. Outcomes related to the prespecified hypothesis were progression of white matter hyperintensities and incident lacunes. We also explored the effect of B-vitamin supplementation on the incidence of other ischemic abnormalities. After 2 years of treatment with b vitamins or placebo, there was no significant difference in white matter hyperintensities volume change (0.08 vs 0.13 cm3; P=0.419) and incidence of lacunes (8.0% vs 5.9%, P=0.434; odds ratio=1.38). In a subanalysis of patients with MRI evidence of severe CSVD at baseline, b-vitamin supplementation was associated with a significant reduction in white matter hyperintensities volume change (0.3 vs 1.7 cm3; P=0.039). Daily B-vitamin supplementation for 2 years did not significantly reduce the progression of brain lesions resulting from presumed CSVD in all patients with recent stroke or transient ischemic attack but may do so in the subgroup of patients with recent stroke or transient ischemic attack and severe CSVD. http://vitatops.highway1.com.au/. Unique identifier: NCT00097669 and ISRCTN74743444.

  7. Neonatal ischemic brain injury: what every radiologist needs to know

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    Badve, Chaitra A.; Khanna, Paritosh C.; Ishak, Gisele E.

    2012-01-01

    We present a pictorial review of neonatal ischemic brain injury and look at its pathophysiology, imaging features and differential diagnoses from a radiologist's perspective. The concept of perinatal stroke is defined and its distinction from hypoxic-ischemic injury is emphasized. A brief review of recent imaging advances is included and a diagnostic approach to neonatal ischemic brain injury is suggested. (orig.)

  8. Tat-PRAS40 prevent hippocampal HT-22 cell death and oxidative stress induced animal brain ischemic insults.

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    Shin, Min Jea; Kim, Dae Won; Jo, Hyo Sang; Cho, Su Bin; Park, Jung Hwan; Lee, Chi Hern; Yeo, Eun Ji; Choi, Yeon Joo; Kim, Ji An; Hwang, Jung Soon; Sohn, Eun Jeong; Jeong, Ji-Heon; Kim, Duk-Soo; Kwon, Hyeok Yil; Cho, Yong-Jun; Lee, Keunwook; Han, Kyu Hyung; Park, Jinseu; Eum, Won Sik; Choi, Soo Young

    2016-08-01

    Proline rich Akt substrate (PRAS40) is a component of mammalian target of rapamycin complex 1 (mTORC1) and is known to play an important role against reactive oxygen species-induced cell death. However, the precise function of PRAS40 in ischemia remains unclear. Thus, we investigated whether Tat-PRAS40, a cell-permeable fusion protein, has a protective function against oxidative stress-induced hippocampal neuronal (HT-22) cell death in an animal model of ischemia. We showed that Tat-PRAS40 transduced into HT-22 cells, and significantly protected against cell death by reducing the levels of H2O2 and derived reactive species, and DNA fragmentation as well as via the regulation of Bcl-2, Bax, and caspase 3 expression levels in H2O2 treated cells. Also, we showed that transduced Tat-PARS40 protein markedly increased phosphorylated RRAS40 expression levels and 14-3-3σ complex via the Akt signaling pathway. In an animal ischemia model, Tat-PRAS40 effectively transduced into the hippocampus in animal brain and significantly protected against neuronal cell death in the CA1 region. We showed that Tat-PRAS40 protein effectively transduced into hippocampal neuronal cells and markedly protected against neuronal cell damage. Therefore, we suggest that Tat-PRAS40 protein may be used as a therapeutic protein for ischemia and oxidative stress-induced brain disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Effects of glycyrrhizin pre-treatment on transient ischemic brain ...

    African Journals Online (AJOL)

    Effects of glycyrrhizin pre-treatment on transient ischemic brain injury in mice. ... on transient ischemic brain injury in mice. Chiyeon Lim, Sehyun Lim, Young-Jun Lee, Bokcheul Kong, Byoungho Lee, Chang-Hyun Kim, Buyeo Kim, Suin Cho ... induced brain damage. Keywords: Glycyrrhizin, licorice, stroke, apoptosis ...

  10. Prevention of rt-PA induced blood-brain barrier component degradation by the poly(ADP-ribose)polymerase inhibitor PJ34 after ischemic stroke in mice.

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    Teng, Fei; Beray-Berthat, Virginie; Coqueran, Bérard; Lesbats, Clémentine; Kuntz, Mélanie; Palmier, Bruno; Garraud, Marie; Bedfert, Cyrielle; Slane, Niamh; Bérézowski, Vincent; Szeremeta, Frédéric; Hachani, Johan; Scherman, Daniel; Plotkine, Michel; Doan, Bich-Thuy; Marchand-Leroux, Catherine; Margaill, Isabelle

    2013-10-01

    Recombinant tissue plasminogen activator (rt-PA) is the only pharmacological treatment approved for thrombolysis in patients suffering from ischemic stroke, but its administration aggravates the risk of hemorrhagic transformations. Experimental data demonstrated that rt-PA increases the activity of poly(ADP-ribose)polymerase (PARP). The aim of the present study was to investigate whether PJ34, a potent (PARP) inhibitor, protects the blood-brain barrier components from rt-PA toxicity. In our mouse model of cerebral ischemia, administration of rt-PA (10 mg/kg, i.v.) 6h after ischemia aggravated the post-ischemic degradation of ZO-1, claudin-5 and VE-cadherin, increased the hemorrhagic transformations (assessed by brain hemoglobin content and magnetic resonance imaging). Furthermore, rt-PA also aggravated ischemia-induced functional deficits. Combining PJ34 with rt-PA preserved the expression of ZO-1, claudin-5 and VE-cadherin, reduced the hemorrhagic transformations and improved the sensorimotor performances. In vitro studies also demonstrated that PJ34 crosses the blood-brain barrier and may thus exert its protective effect by acting on endothelial and/or parenchymal cells. Thus, co-treatment with a PARP inhibitor seems to be a promising strategy to reduce rt-PA-induced vascular toxicity after stroke. © 2013.

  11. Neonatal ischemic brain injury: what every radiologist needs to know

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    Badve, Chaitra A.; Khanna, Paritosh C.; Ishak, Gisele E. [Seattle Children' s Hospital, University of Washington Medical Center, Department of Radiology, Seattle, WA (United States)

    2012-05-15

    We present a pictorial review of neonatal ischemic brain injury and look at its pathophysiology, imaging features and differential diagnoses from a radiologist's perspective. The concept of perinatal stroke is defined and its distinction from hypoxic-ischemic injury is emphasized. A brief review of recent imaging advances is included and a diagnostic approach to neonatal ischemic brain injury is suggested. (orig.)

  12. Prediction and prevention of ischemic placental disease.

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    Friedman, Alexander M; Cleary, Kirsten L

    2014-04-01

    Preeclampsia, intrauterine growth restriction (IUGR), and placental abruption are obstetrical conditions that constitute the syndrome of ischemic placental disease or IPD, the leading cause of indicated preterm birth and an important cause of neonatal morbidity and mortality. While the phenotypic manifestations vary significantly for preeclampsia, IUGR, and abruption, these conditions may share a common underlying etiology as evidenced by: (1) shared clinical risk factors, (2) increased recurrence risk across pregnancies as well as increased co-occurrence of IPD conditions within a pregnancy, and (3) findings that suggest the underlying pathophysiologic processes may be similar. IPD is of major clinical importance and accounts for a large proportion of indicated preterm delivery ranging from the periviable to late preterm period. Successful prevention of IPD and resultant preterm delivery could substantially improve neonatal and maternal outcomes. This article will review the following topics: (1) The complicated research literature on aspirin and the prevention of preeclampsia and IUGR. (2) Research evidence on other medical interventions to prevent IPD. (3) New clinical interventions currently under investigations, including statins. (4) Current clinical recommendations for prevention of ischemic placental disease. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. [Secondary prevention of ischemic non cardioembolic stroke].

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    Armario, Pedro; Pinto, Xavier; Soler, Cristina; Cardona, Pere

    2015-01-01

    Stroke patients are at high risk for recurrence or new occurrence of other cardiovascular events or cardiovascular mortality. It is estimated that a high percentage of non-cardioembolic ischemic stroke can be prevented by a suitable modification of lifestyle (diet and exercise), reducing blood pressure (BP) with antihypertensive medication, platelet aggregation inhibitors, statins and high intake reducing consumption of. Unfortunately the degree of control of the different risk factors in secondary prevention of stroke is low. The clinical practice guidelines show clear recommendations with corresponding levels of evidence, but only if implemented in a general way they will get a better primary and secondary stroke prevention. Copyright © 2014 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

  14. Involvement of CCR-2 chemokine receptor activation in ischemic preconditioning and postconditioning of brain in mice.

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    Rehni, Ashish K; Singh, Thakur Gurjeet

    2012-10-01

    The present study has been designed to investigate the potential role of CCR-2 chemokine receptor in ischemic preconditioning as well as postconditioning induced reversal of ischemia-reperfusion injury in mouse brain. Bilateral carotid artery occlusion of 17 min followed by reperfusion for 24h was employed in present study to produce ischemia and reperfusion induced cerebral injury in mice. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was evaluated using elevated plus-maze test and Morris water maze test. Rota rod test was employed to assess motor incoordination. Bilateral carotid artery occlusion followed by reperfusion produced cerebral infarction and impaired memory and motor co-ordination. Three preceding episodes of bilateral carotid artery occlusion for 1 min and reperfusion of 1 min were employed to elicit ischemic preconditioning of brain, while three episodes of bilateral carotid artery occlusion for 10s and reperfusion of 10s immediately after the completion of were employed to elicit ischemic postconditioning of brain. Both prior ischemic preconditioning as well as ischemic postconditioning immediately after global cerebral ischemia prevented markedly ischemia-reperfusion-induced cerebral injury as measured in terms of infarct size, loss of memory and motor coordination. RS 102895, a selective CCR-2 chemokine receptor antagonist, attenuated the neuroprotective effect of both the ischemic preconditioning as well as postconditioning. It is concluded that the neuroprotective effect of both ischemic preconditioning as well as ischemic postconditioning may involve the activation of CCR-2 chemokine receptors. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Ginkgo biloba Extract Prevents Female Mice from Ischemic Brain Damage and the Mechanism Is Independent of the HO1/Wnt Pathway.

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    Tulsulkar, Jatin; Glueck, Bryan; Hinds, Terry D; Shah, Zahoor A

    2016-04-01

    It is well known that gender differences exist in experimental or clinical stroke with respect to brain damage and loss of functional outcome. We have previously reported neuroprotective properties of Ginkgo biloba/EGb 761® (EGb 761) in transient and permanent mouse models of brain ischemia using male mice, and the mechanism of action was attributed to the upregulation of the heme oxygenase 1 (HO1)/Wnt pathway. Here, we sought to investigate whether EGb 761's protective effect in ovariectomized female mice following stroke is also mediated by the HO1/Wnt pathway. Female mice were ovariectomized (OVX) to remove the protective effect of estrogen and were treated with EGb 761 for 7 days prior to inducing permanent middle cerebral artery occlusion (pMCAO) and allowed to survive for an additional 7 days. At day 8, animals were sacrificed, and the brains were harvested for infarct volume analysis, western blots, and immunohistochemistry. The OVX female mice treated with EGb 761 showed significantly lower infarct size as compared to Veh/OVX animals. EGb 761 treatment in female mice inhibited apoptosis by preventing caspase-3 cleavage and blocking the extrinsic apoptotic pathway. EGb 761 pretreatment significantly enhanced neurogenesis in OVX mice as compared to the Veh/OVX group and significantly upregulated androgen receptor expression with no changes in HO1/Wnt signaling. These results suggest that EGb 761 prevented brain damage in OVX female mice by improving grip strength and neurological deficits, and the mechanism of action is not through HO1/Wnt but via blocking the extrinsic apoptotic pathway.

  16. Quantification of convection-enhanced delivery to the ischemic brain

    International Nuclear Information System (INIS)

    Haar, Peter J; Broaddus, William C; Chen, Zhi-jian; Gillies, George T; Fatouros, Panos P; Corwin, Frank D

    2010-01-01

    Convection-enhanced delivery (CED) could have clinical application in the delivery of neuroprotective agents following ischemic stroke. However, ischemic brain tissue changes such as cytotoxic edema, in which cellular swelling decreases the fractional volume of the extracellular space, would be expected to significantly alter the distribution of neuroprotective agents delivered by CED. We sought to predict and characterize these effects using the magnetic resonance contrast agent gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) as a model therapeutic agent. CED was observed using MRI in a normal rat brain and in a middle cerebral artery (MCA) occlusion rat model of brain ischemia. Gd-DTPA was infused to the caudate putamen in the normal rat (n = 6) and MCA occlusion model (n = 6). In each rat, baseline apparent diffusion coefficient images were acquired prior to infusion, and T1 maps were then acquired 13 times throughout the duration of the experiment. These T1 maps were used to compute Gd-DTPA concentrations throughout each brain. In the MCA occlusion group, CED delivered Gd-DTPA to a comparatively larger volume with lower average tissue concentrations. Following the infusion, the total content of Gd-DTPA decreased more slowly in the MCA occlusion group than in the normal group. This quantitative characterization confirms that edematous ischemic tissue changes alter the distribution of agents by CED. These findings may have important implications for CED in the treatment of brain injury, and will assist in future efforts to model the distribution of therapeutic agents

  17. Shear Stress Inhibits Apoptosis of Ischemic Brain Microvascular Endothelial Cells

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    Xiafeng Shen

    2013-01-01

    Full Text Available As a therapeutic strategy for ischemic stroke, to restore or increase cerebral blood flow (CBF is the most fundamental option. Laminar shear stress (LS, as an important force generated by CBF, mainly acts on brain microvascular endothelial cells (BMECs. In order to study whether LS was a protective factor in stroke, we investigated LS-intervented ischemic apoptosis of rat BMECs (rBMECs through PE Annexin V/7-AAD, JC-1 and Hoechst 33258 staining to observe the membranous, mitochondrial and nuclear dysfunction. Real-time PCR and western blot were also used to test the gene and protein expressions of Tie-2, Bcl-2 and Akt, which were respectively related to maintain membranous, mitochondrial and nuclear norm. The results showed that LS could be a helpful stimulus for ischemic rBMECs survival. Simultaneously, membranous, mitochondrial and nuclear regulation played an important role in this process.

  18. Silent ischemic brain lesions after transcatheter aortic valve replacement : lesion distribution and predictors

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    Samim, Mariam; Hendrikse, Jeroen; van der Worp, H. Bart; Agostoni, Pierfrancesco; Nijhoff, Freek; Doevendans, Pieter A.; Stella, Pieter R.

    Silent ischemic brain lesions and ischemic stroke are known complications of transcatheter aortic valve replacement (TAVR). We aimed to investigate the occurrence and distribution of TAVR-related silent ischemic brain lesions using diffusion-weighted magnetic resonance imaging (DWI). Consecutive

  19. Structural MRI markers of brain aging early after ischemic stroke.

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    Werden, Emilio; Cumming, Toby; Li, Qi; Bird, Laura; Veldsman, Michele; Pardoe, Heath R; Jackson, Graeme; Donnan, Geoffrey A; Brodtmann, Amy

    2017-07-11

    To examine associations between ischemic stroke, vascular risk factors, and MRI markers of brain aging. Eighty-one patients (mean age 67.5 ± 13.1 years, 31 left-sided, 61 men) with confirmed first-ever (n = 66) or recurrent (n = 15) ischemic stroke underwent 3T MRI scanning within 6 weeks of symptom onset (mean 26 ± 9 days). Age-matched controls (n = 40) completed identical testing. Multivariate regression analyses examined associations between group membership and MRI markers of brain aging (cortical thickness, total brain volume, white matter hyperintensity [WMH] volume, hippocampal volume), normalized against intracranial volume, and the effects of vascular risk factors on these relationships. First-ever stroke was associated with smaller hippocampal volume ( p = 0.025) and greater WMH volume ( p = 0.004) relative to controls. Recurrent stroke was in turn associated with smaller hippocampal volume relative to both first-ever stroke ( p = 0.017) and controls ( p = 0.001). These associations remained significant after adjustment for age, sex, education, and, in stroke patients, infarct volume. Total brain volume was not significantly smaller in first-ever stroke patients than in controls ( p = 0.056), but the association became significant after further adjustment for atrial fibrillation ( p = 0.036). Cortical thickness and brain volumes did not differ as a function of stroke type, infarct volume, or etiology. Brain structure is likely to be compromised before ischemic stroke by vascular risk factors. Smaller hippocampal and total brain volumes and increased WMH load represent proxies for underlying vascular brain injury. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

  20. Perinatal Hypoxic-Ischemic brain injury; MR findings

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    Park, Dong Woo; Seo, Chang Hye [Inje University Pusan Paik Hospital, Pusan (Korea, Republic of)

    1994-09-15

    To characterize the MR findings of hypoxic-ischemic brain injury and to assess the value of the MR imaging. SE T1-, T2-weighted, and IR brain MR images of 44 infants and children with the past history of perinatal hypoxic insults were reviewed. Abnormal brain MR findings of 8 patients with birth history of prematurity and 36 patients with birth history of full-term/posterm including 7 with severe anoxic insult history, were compared in regard to the location and the character of the lesions. MRI demonstrated the followings; (1)abnormal signal intensity lesions of subcortical and/or deep cerebral white matter, cortex, and deep gray matter, (2)atrophy of the cerebral white matter, cortex and corpus callosum, with/without ventriculomegaly, and (3)delay in myelination. Periventricular and deep white matter lesions were demonstrated in the prematurity, the deep white matter lesions and/ or subcortical white matter lesions in the term/post-term, and deep gray matter lesions in the 7 patients with severe anoxic insults history. MR imaging was useful in the diagnosis of the hypoxic-ischemic brain injury, and the white and gray matter lesions were correlated with the time of the injury and the severity of hypoxic insult.

  1. Population-based effectiveness and safety of different antiplatelet regimens as secondary prevention for ischemic stroke/Transient ischemic attack

    NARCIS (Netherlands)

    Noorsyahdy, Alfi; De Boer, Anthonius; Deneer, Vera H.M.; Ten Berg, Jurrien M.; Souverein, Patrick C.; Klungel, Olaf H.

    2016-01-01

    Background: Different antiplatelet regimens are used for secondary prevention after ischemic stroke (IS)/transient ischemic attack (TIA), but studies on the relative effectiveness and safety of each regimen in daily practice are lacking. Objectives: To assess the relative effectiveness and safety of

  2. Ischemic conditioning-induced endogenous brain protection: Applications pre-, per- or post-stroke.

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    Wang, Yuechun; Reis, Cesar; Applegate, Richard; Stier, Gary; Martin, Robert; Zhang, John H

    2015-10-01

    In the area of brain injury and neurodegenerative diseases, a plethora of experimental and clinical evidence strongly indicates the promise of therapeutically exploiting the endogenous adaptive system at various levels like triggers, mediators and the end-effectors to stimulate and mobilize intrinsic protective capacities against brain injuries. It is believed that ischemic pre-conditioning and post-conditioning are actually the strongest known interventions to stimulate the innate neuroprotective mechanism to prevent or reverse neurodegenerative diseases including stroke and traumatic brain injury. Recently, studies showed the effectiveness of ischemic per-conditioning in some organs. Therefore the term ischemic conditioning, including all interventions applied pre-, per- and post-ischemia, which spans therapeutic windows in 3 time periods, has recently been broadly accepted by scientific communities. In addition, it is extensively acknowledged that ischemia-mediated protection not only affects the neurons but also all the components of the neurovascular network (consisting of neurons, glial cells, vascular endothelial cells, pericytes, smooth muscle cells, and venule/veins). The concept of cerebroprotection has been widely used in place of neuroprotection. Intensive studies on the cellular signaling pathways involved in ischemic conditioning have improved the mechanistic understanding of tolerance to cerebral ischemia. This has added impetus to exploration for potential pharmacologic mimetics, which could possibly induce and maximize inherent protective capacities. However, most of these studies were performed in rodents, and the efficacy of these mimetics remains to be evaluated in human patients. Several classical signaling pathways involving apoptosis, inflammation, or oxidation have been elaborated in the past decades. Newly characterized mechanisms are emerging with the advances in biotechnology and conceptual renewal. In this review we are going to focus on

  3. Presumptive Ischemic Brain Infarction in a Dog with Evans’ Syndrome

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    Angelo Pasquale Giannuzzi

    2014-01-01

    Full Text Available A ten-year-old neutered female mixed breed dog was referred for pale mucous membrane and acute onset of right prosencephalic clinical signs. Brain magnetic resonance imaging was suggestive for right middle cerebral artery ischemic stroke. Based on cell blood count, serum biochemistry and serologic tests and flow cytometric detection of anti-platelets and anti-red blood cells antibodies, a diagnosis of immunomediated haemolytic anemia associated with thrombocytopenia of suspected immunomediated origin was done. Immunosuppresive therapy with prednisone was started and the dog clinically recovered. Two months later complete normalization of CBC and serum biochemistry was documented. The dog remained stable for 7 months without therapy; then she relapsed. CBC revealed mild regenerative anemia with spherocytosis and thrombocytopenia. A conclusive Evans’ syndrome diagnosis was done and prednisone and cyclosporine treatment led to normalization of physical and CBC parameters. The dog is still alive at the time the paper submitted. Possible thrombotic etiopathogenetic mechanisms are illustrated in the paper and the authors suggest introducing Evans’ syndrome in the differential diagnosis list for brain ischemic stroke in dogs.

  4. Ceftriaxone attenuates hypoxic-ischemic brain injury in neonatal rats

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    Huang Yen

    2011-09-01

    Full Text Available Abstract Background Perinatal brain injury is the leading cause of subsequent neurological disability in both term and preterm baby. Glutamate excitotoxicity is one of the major factors involved in perinatal hypoxic-ischemic encephalopathy (HIE. Glutamate transporter GLT1, expressed mainly in mature astrocytes, is the major glutamate transporter in the brain. HIE induced excessive glutamate release which is not reuptaked by immature astrocytes may induce neuronal damage. Compounds, such as ceftriaxone, that enhance the expression of GLT1 may exert neuroprotective effect in HIE. Methods We used a neonatal rat model of HIE by unilateral ligation of carotid artery and subsequent exposure to 8% oxygen for 2 hrs on postnatal day 7 (P7 rats. Neonatal rats were administered three dosages of an antibiotic, ceftriaxone, 48 hrs prior to experimental HIE. Neurobehavioral tests of treated rats were assessed. Brain sections from P14 rats were examined with Nissl and immunohistochemical stain, and TUNEL assay. GLT1 protein expression was evaluated by Western blot and immunohistochemistry. Results Pre-treatment with 200 mg/kg ceftriaxone significantly reduced the brain injury scores and apoptotic cells in the hippocampus, restored myelination in the external capsule of P14 rats, and improved the hypoxia-ischemia induced learning and memory deficit of P23-24 rats. GLT1 expression was observed in the cortical neurons of ceftriaxone treated rats. Conclusion These results suggest that pre-treatment of infants at risk for HIE with ceftriaxone may reduce subsequent brain injury.

  5. Stroke and Drug Delivery--In Vitro Models of the Ischemic Blood-Brain Barrier

    DEFF Research Database (Denmark)

    Tornabene, Erica; Brodin, Birger

    2016-01-01

    Stroke is a major cause of death and disability worldwide. Both cerebral hypoperfusion and focal cerebral infarcts are caused by a reduction of blood flow to the brain, leading to stroke and subsequent brain damage. At present, only few medical treatments of stroke are available, with the Food...... and Drug Administration-approved tissue plasminogen activator for treatment of acute ischemic stroke being the most prominent example. A large number of potential drug candidates for treatment of ischemic brain tissue have been developed and subsequently failed in clinical trials. A deeper understanding...... of permeation pathways across the barrier in ischemic and postischemic brain endothelium is important for development of new medical treatments. The blood-brain barrier, that is, the endothelial monolayer lining the brain capillaries, changes properties during an ischemic event. In vitro models of the blood-brain...

  6. Fetal stress and programming of hypoxic/ischemic-sensitive phenotype in the neonatal brain: mechanisms and possible interventions.

    Science.gov (United States)

    Li, Yong; Gonzalez, Pablo; Zhang, Lubo

    2012-08-01

    Growing evidence of epidemiological, clinical and experimental studies has clearly shown a close link between adverse in utero environment and the increased risk of neurological, psychological and psychiatric disorders in later life. Fetal stresses, such as hypoxia, malnutrition, and fetal exposure to nicotine, alcohol, cocaine and glucocorticoids may directly or indirectly act at cellular and molecular levels to alter the brain development and result in programming of heightened brain vulnerability to hypoxic-ischemic encephalopathy and the development of neurological diseases in the postnatal life. The underlying mechanisms are not well understood. However, glucocorticoids may play a crucial role in epigenetic programming of neurological disorders of fetal origins. This review summarizes the recent studies about the effects of fetal stress on the abnormal brain development, focusing on the cellular, molecular and epigenetic mechanisms and highlighting the central effects of glucocorticoids on programming of hypoxic-ischemic-sensitive phenotype in the neonatal brain, which may enhance the understanding of brain pathophysiology resulting from fetal stress and help explore potential targets of timely diagnosis, prevention and intervention in neonatal hypoxic-ischemic encephalopathy and other brain disorders. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Remote Ischemic Conditioning: A Novel Non-Invasive Approach to Prevent Post-Stroke Depression

    Directory of Open Access Journals (Sweden)

    Wenbo Zhao

    2017-08-01

    Full Text Available Post-stroke depression (PSD is a common neuropsychiatric complication of stroke. However, due to the high expense and side effects of pharmacotherapy and the difficult-to-achieve of psychotherapy, the prevention and treatment of PSD are still far from satisfaction. Inflammation hypothesis is now playing an essential role in the pathophysiological mechanism of PSD, and it may be a new preventive and therapeutic target. Remote ischemic conditioning (RIC is a non-invasive and easy-to-use physical strategy, which has been used to protect brain (including ischemic and hemorrhagic stroke, heart and many other organs in clinical trials. The underlying mechanisms of RIC include anti-inflammation, anti-oxidative stress, immune system regulation and other potential pathways. Our hypothesis is that RIC is a novel approach to prevent PSD. The important implications of this hypothesis are that: (1 RIC could be widely used in clinical practice to prevent PSD if our hypothesis were verified; and (2 RIC would be thoroughly explored to test its effects on other neurobehavioral disorders (e.g., cognitive impairment.

  8. Cannabidiol reduces lung injury induced by hypoxic-ischemic brain damage in newborn piglets.

    Science.gov (United States)

    Arruza, Luis; Pazos, Maria Ruth; Mohammed, Nagat; Escribano, Natalia; Lafuente, Hector; Santos, Martín; Alvarez-Díaz, Francisco J; Hind, William; Martínez-Orgado, Jose

    2017-07-01

    BackgroundBrain hypoxic-ischemic (HI) damage induces distant inflammatory lung damage in newborn pigs. We aimed to investigate the effects of cannabidiol (CBD) on lung damage in this scenario.MethodsNewborn piglets received intravenous vehicle, CBD, or CBD+WAY100635 (5-HT 1A receptor antagonist) after HI brain damage (carotid flow interruption and FiO 2 0.10 for 30 min). Total lung compliance (TLC), oxygenation index (OI), and extravascular lung water content (EVLW) were monitored for 6 h. Histological damage, interleukin (IL)-1β concentration, and oxidative stress were assessed in brain and lung tissue. Total protein content was determined in bronchoalveolar lavage fluid (BALF).ResultsCBD prevented HI-induced deleterious effects on TLC and OI and reduced lung histological damage, modulating inflammation (decreased leukocyte infiltration and IL-1 concentration) and reducing protein content in BALF and EVLW. These effects were related to CBD-induced anti-inflammatory changes in the brain. HI did not increase oxidative stress in the lungs. In the lungs, WAY100635 blunted the beneficial effects of CBD on histological damage, IL-1 concentration, and EVLW.ConclusionsCBD reduced brain HI-induced distant lung damage, with 5-HT 1A receptor involvement in these effects. Whether the effects of CBD on the lungs were due to the anti-inflammatory effects on the brain or due to the direct effects on the lungs remains to be elucidated.

  9. Caffeine prevents protection in two human models of ischemic preconditioning.

    NARCIS (Netherlands)

    Riksen, N.P.; Zhou, Z.; Oyen, W.J.G.; Jaspers, R.A.; Ramakers, B.P.; Brouwer, R.M.H.J.; Boerman, O.C.; Steinmetz, N.; Smits, P.; Rongen, G.A.

    2006-01-01

    OBJECTIVES: We studied whether caffeine impairs protection by ischemic preconditioning (IP) in humans. BACKGROUND: Ischemic preconditioning is critically dependent on adenosine receptor stimulation. We hypothesize that the adenosine receptor antagonist caffeine blocks the protective effect of IP.

  10. The distribution of N-isopropyl-p-iodoamphetamine in experimental ischemic brain of the mongolian gerbil

    International Nuclear Information System (INIS)

    Jinnouchi, Seishi; Hoshi, Hiroaki; Watanabe, Katsushi; Ueda, Takashi; Yamaguchi, Tadatoshi

    1988-01-01

    We studied the distribution of N-isopropyl-p-[I-131]-iodoamphetamine (IMP) in permanent and temporary ischemic brains of mongolian gerbils. For the permanent ischemic brain model, the right common carotid artery was ligated under ether anesthesia. For the temporary ischemic brain model, the right common carotid artery was clamped by a clip and recirculated at 3 hours thereafter. After given time intervals, 1.35 MBq (50 μCi) of IMP was injected intravenously into 17 gerbils (permanent ischemic brain model), 18 gerbils (temporary ischemic brain model) which had severe neurological symptoms, and 3 normal gerbils for controls. One minute, 10 minutes, 1 hour and 6 hours after the injection, gerbils were sacrified and autoradiography of the brain was performed. The activity of IMP in various parts of the brain was calculated from each autoradiogram. In permanent ischemic brains, low perfusion areas were observed in the right cerebral hemisphere, the brain stem (5 ∼ 20 % of normal value), and in the left hemisphere (40 ∼ 60 % of normal value). In temporary ischemic brains, focal areas of increased activity were observed in the right cerebral hemisphere and the thalamus from 10 minutes to 24 hours after recirculation. The high activity disappeared rapidly at 10 minutes after the injection. It seemed that this high activity represented luxury perfusion in the region with severe tissue damage. In the left hemisphere, almost complete recovery of perfusion occurred at 1 ∼ 3 days after recirculation. These results suggested the possibility of IMP to demonstrate cerebral ischemia, luxury perfusion and diaschisis. (author)

  11. Systemic evaluation of hypoxic-ischemic brain injury in neonatal rats.

    Science.gov (United States)

    Zhu, Ai-Hua; Hu, Yan-Rong; Liu, Wei; Gao, Feng; Li, Jian-Xin; Zhao, Li-Hui; Chen, Gang

    2014-06-01

    The objective of the study was to evaluate the systematically rat model of neonatal hypoxic-ischemic brain damage. The right carotid arteries of 7-day-old healthy Wistar rats were ligated, and then, the rats were subjected to an environment with 8 % of oxygen. Four weeks after the birth, neurobehavioral test, water maze test, and motor-evoked potential and neuropathologic examinations were performed. The footprint analysis showed significantly larger and instable paces in the hypoxic-ischemic group (P balance beam in the hypoxic-ischemic group was longer than the control group (P water maze test showed that the escape latency of hypoxic-ischemic group was significantly longer than that of control group (P neonatal hypoxic-ischemic brain damage and can be used for experimental research related to management of cerebral palsy.

  12. Role of Mitochondria in Neonatal Hypoxic-Ischemic Brain Injury.

    Science.gov (United States)

    Lu, Yujiao; Tucker, Donovan; Dong, Yan; Zhao, Ningjun; Zhuo, Xiaoying; Zhang, Quanguang

    Hypoxic-ischemia (HI) causes severe brain injury in neonates. It's one of the leading causes to neonatal death and pediatric disability, resulting in devastating consequences, emotionally and economically, to their families. A series of events happens in this process, e.g. excitatory transmitter release, extracelluar Ca 2+ influxing, mitochondrial dysfunction, energy failure, and neuron death. There are two forms of neuron death after HI insult: necrosis and apoptosis, apoptosis being the more prevalent form. Mitochondria handle a series of oxidative reactions, and yield energy for various cellular activities including the maintainance of membrane potential and preservation of intracellular ionic homeostasis. Therefore mitochondria play a critical role in neonatal neurodegeneration following HI, and mitochondrial dysfunction is the key point in neurodegenerative evolution. Because of this, exploring effective mitochondria-based clinical strategies is crucial. Today the only efficacious clinic treatment is hypothermia. However, due to its complex management, clinical complication and autoimmune decrease, its clinical application is limited. So far, many mitochondria-based strategies have been reported neuroprotective in animal models, which offers promise on neonatal therapy. However, since their clinical effectiveness are still unclear, plenty of studies need to be continued in the future. According to recent reports, two novel strategies have been proposed: methylene blue (MB) and melatonin. Although they are still in primary stage, the underlying mechanisms indicate promising clinical applications. Every neurological therapeutic strategy has its intrinsic deficit and limited efficacy, therefore in the long run, the perfect clinical therapy for hypoxic-ischemic neonatal brain injury will be based on the combination of multiple strategies.

  13. Transcriptomics and proteomics analyses of the PACAP38 influenced ischemic brain in permanent middle cerebral artery occlusion model mice

    Directory of Open Access Journals (Sweden)

    Hori Motohide

    2012-11-01

    Full Text Available Abstract Introduction The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP is considered to be a potential therapeutic agent for prevention of cerebral ischemia. Ischemia is a most common cause of death after heart attack and cancer causing major negative social and economic consequences. This study was designed to investigate the effect of PACAP38 injection intracerebroventrically in a mouse model of permanent middle cerebral artery occlusion (PMCAO along with corresponding SHAM control that used 0.9% saline injection. Methods Ischemic and non-ischemic brain tissues were sampled at 6 and 24 hours post-treatment. Following behavioral analyses to confirm whether the ischemia has occurred, we investigated the genome-wide changes in gene and protein expression using DNA microarray chip (4x44K, Agilent and two-dimensional gel electrophoresis (2-DGE coupled with matrix assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS, respectively. Western blotting and immunofluorescent staining were also used to further examine the identified protein factor. Results Our results revealed numerous changes in the transcriptome of ischemic hemisphere (ipsilateral treated with PACAP38 compared to the saline-injected SHAM control hemisphere (contralateral. Previously known (such as the interleukin family and novel (Gabra6, Crtam genes were identified under PACAP influence. In parallel, 2-DGE analysis revealed a highly expressed protein spot in the ischemic hemisphere that was identified as dihydropyrimidinase-related protein 2 (DPYL2. The DPYL2, also known as Crmp2, is a marker for the axonal growth and nerve development. Interestingly, PACAP treatment slightly increased its abundance (by 2-DGE and immunostaining at 6 h but not at 24 h in the ischemic hemisphere, suggesting PACAP activates neuronal defense mechanism early on. Conclusions This study provides a detailed inventory of PACAP influenced gene expressions

  14. Central role of maladapted astrocytic plasticity in ischemic brain edema formation

    Directory of Open Access Journals (Sweden)

    Yu-Feng eWang

    2016-05-01

    Full Text Available Brain edema formation and the ensuing brain damages are the major cause of high mortality and long term disability following the occurrence of ischemic stroke. In this process, oxygen and glucose deprivation and the ensuing reperfusion injury play primary roles. In response to the ischemic insult, the neurovascular unit experiences both intracellular and extracellular edemas; the two processes are interactive closely under the driving of maladapted astrocytic plasticity. The astrocytic plasticity includes both morphologic and functional plasticity. The former involves a reactive gliosis and the ensuing glial retraction. It relates to the capacity of astrocytes to buffer changes in extracellular chemical levels, particularly K+ and glutamate, as well as the integrity of the blood-brain barrier. The latter involves the expression and activity of a series of ion and water transport proteins. These molecules are grouped together around glial fibrillary acidic protein and water channel protein aquaporin 4 to form functional networks, regulate hydromineral balance across cell membranes and maintain the integrity of the blood-brain barrier. Intense ischemic challenges can disrupt these capacities of astrocytes and result in their maladaptation. The maladapted astrocytic plasticity in ischemic stroke cannot only disrupt the hydromineral homeostasis across astrocyte membrane and the blood-brain barrier, but also lead to disorders of the whole neurovascular unit. This review focuses on how the maladapted astrocytic plasticity in ischemic stroke plays the central role in the brain edema formation.

  15. Fetal Stress and Programming of Hypoxic/Ischemic-Sensitive Phenotype in the Neonatal Brain: Mechanisms and Possible Interventions

    Science.gov (United States)

    Li, Yong; Gonzalez, Pablo; Zhang, Lubo

    2012-01-01

    Growing evidence of epidemiological, clinical and experimental studies has clearly shown a close link between adverse in utero environment and the increased risk of neurological, psychological and psychiatric disorders in later life. Fetal stresses, such as hypoxia, malnutrition, and fetal exposure to nicotine, alcohol, cocaine and glucocorticoids may directly or indirectly act at cellular and molecular levels to alter the brain development and result in programming of heightened brain vulnerability to hypoxic-ischemic encephalopathy and the development of neurological diseases in the postnatal life. The underlying mechanisms are not well understood. However, glucocorticoids may play a crucial role in epigenetic programming of neurological disorders of fetal origins. This review summarizes the recent studies about the effects of fetal stress on the abnormal brain development, focusing on the cellular, molecular and epigenetic mechanisms and highlighting the central effects of glucocorticoids on programming of hypoxicischemic-sensitive phenotype in the neonatal brain, which may enhance the understanding of brain pathophysiology resulting from fetal stress and help explore potential targets of timely diagnosis, prevention and intervention in neonatal hypoxic-ischemic encephalopathy and other for brain disorders. PMID:22627492

  16. Dehydroascorbic Acid Attenuates Ischemic Brain Edema and Neurotoxicity in Cerebral Ischemia: An in vivo Study

    Science.gov (United States)

    Song, Juhyun; Park, Joohyun; Kim, Jae Hwan; Choi, Ja Yong; Kim, Jae Young; Lee, Kyoung Min

    2015-01-01

    Ischemic stroke results in the diverse phathophysiologies including blood brain barrier (BBB) disruption, brain edema, neuronal cell death, and synaptic loss in brain. Vitamin C has known as the potent anti-oxidant having multiple functions in various organs, as well as in brain. Dehydroascorbic acid (DHA) as the oxidized form of ascorbic acid (AA) acts as a cellular protector against oxidative stress and easily enters into the brain compared to AA. To determine the role of DHA on edema formation, neuronal cell death, and synaptic dysfunction following cerebral ischemia, we investigated the infarct size of ischemic brain tissue and measured the expression of aquaporin 1 (AQP-1) as the water channel protein. We also examined the expression of claudin 5 for confirming the BBB breakdown, and the expression of bcl 2 associated X protein (Bax), caspase-3, inducible nitric oxide synthase (iNOS) for checking the effect of DHA on the neurotoxicity. Finally, we examined postsynaptic density protein-95 (PSD-95) expression to confirm the effect of DHA on synaptic dysfunction following ischemic stroke. Based on our findings, we propose that DHA might alleviate the pathogenesis of ischemic brain injury by attenuating edema, neuronal loss, and by improving synaptic connection. PMID:25792869

  17. Relationships between brain and body temperature, clinical and imaging outcomes after ischemic stroke

    Science.gov (United States)

    Karaszewski, Bartosz; Carpenter, Trevor K; Thomas, Ralph G R; Armitage, Paul A; Lymer, Georgina Katherine S; Marshall, Ian; Dennis, Martin S; Wardlaw, Joanna M

    2013-01-01

    Pyrexia soon after stroke is associated with severe stroke and poor functional outcome. Few studies have assessed brain temperature after stroke in patients, so little is known of its associations with body temperature, stroke severity, or outcome. We measured temperatures in ischemic and normal-appearing brain using 1H-magnetic resonance spectroscopy and its correlations with body (tympanic) temperature measured four-hourly, infarct growth by 5 days, early neurologic (National Institute of Health Stroke Scale, NIHSS) and late functional outcome (death or dependency). Among 40 patients (mean age 73 years, median NIHSS 7, imaged at median 17 hours), temperature in ischemic brain was higher than in normal-appearing brain on admission (38.6°C-core, 37.9°C-contralateral hemisphere, P=0.03) but both were equally elevated by 5 days; both were higher than tympanic temperature. Ischemic lesion temperature was not associated with NIHSS or 3-month functional outcome; in contrast, higher contralateral normal-appearing brain temperature was associated with worse NIHSS, infarct expansion and poor functional outcome, similar to associations for tympanic temperature. We conclude that brain temperature is higher than body temperature; that elevated temperature in ischemic brain reflects a local tissue response to ischemia, whereas pyrexia reflects the systemic response to stroke, occurs later, and is associated with adverse outcomes. PMID:23571281

  18. Dabrafenib, an inhibitor of RIP3 kinase-dependent necroptosis, reduces ischemic brain injury

    Directory of Open Access Journals (Sweden)

    Shelly A Cruz

    2018-01-01

    Full Text Available Ischemic brain injury triggers neuronal cell death by apoptosis via caspase activation and by necroptosis through activation of the receptor-interacting protein kinases (RIPK associated with the tumor necrosis factor-alpha (TNF-α/death receptor. Recent evidence shows RIPK inhibitors are neuroprotective and alleviate ischemic brain injury in a number of animal models, however, most have not yet undergone clinical trials and safety in humans remains in question. Dabrafenib, originally identified as a B-raf inhibitor that is currently used to treat melanoma, was later revealed to be a potent RIPK3 inhibitor at micromolar concentrations. Here, we investigated whether Dabrafenib would show a similar neuroprotective effect in mice subjected to ischemic brain injury by photothrombosis. Dabrafenib administered intraperitoneally at 10 mg/kg one hour after photothrombosis-induced focal ischemic injury significantly reduced infarct lesion size in C57BL6 mice the following day, accompanied by a markedly attenuated upregulation of TNF-α. However, subsequent lower doses (5 mg/kg/day failed to sustain this neuroprotective effect after 4 days. Dabrafenib blocked lipopolysaccharides-induced activation of TNF-α in bone marrow-derived macrophages, suggesting that Dabrafenib may attenuate TNF-α-induced necroptotic pathway after ischemic brain injury. Since Dabrafenib is already in clinical use for the treatment of melanoma, it might be repurposed for stroke therapy.

  19. The role of oxidative stress in perinatal hypoxic-ischemic brain injury

    Directory of Open Access Journals (Sweden)

    Vasiljević Brankica

    2012-01-01

    Full Text Available Introduction. The pathogenesis of perinatal hypoxic-ischemic brain damage is highly complex. Objective. The aim of this study was to assess the role of oxidative stress in hypoxic-ischemic brain injury and subsequent abnormal neurological outcome in infants with perinatal hypoxic-ischemic encephalopathy (HIE. We estimated perinatal oxidative brain damage measuring activity of glutathione peroxidase (GPX in cerebrospinal fluid (CSF as an indirect biomarker of free radical production during cerebral hypoxia-ischemia in correlation with the level of intracellular enzyme neuron specific enolase (NSE in CSF as a biomarker of extend of brain injury. Methods. Ninety neonates (>32 GA with perinatal HIE were enrolled prospectively. HIE was categorized into three stages according Sarnat and Sarnat clinical scoring system and changes seen on amplitude integrated EEG. CSF for GPX analysis and NSE analysis was taken in the first 72 hours of life. Neurodevelopment outcome was assessed at 12 months of corrected gestational age. Results. GPX activity in CSF was in good relation with clinical stage of HIE (p<0.0001 and GA (p<0.0001 and significantly corresponded with subsequent neurodevelopment outcome (p<0.001. GPX activity in CSF showed a strong correlation with NSE levels in CSF (p<0.001 as the biomarker of extent of brain injury. Conclusion. Our results suggest that oxidative stress might be important contributing factor in perinatal hypoxic-ischemic brain damage, particularly in preterm neonates.

  20. In Vivo Bioimpedance Spectroscopy Characterization of Healthy, Hemorrhagic and Ischemic Rabbit Brain within 10 Hz–1 MHz

    Science.gov (United States)

    Yang, Lin; Liu, Wenbo; Chen, Rongqing; Zhang, Ge; Li, Weichen; Fu, Feng; Dong, Xiuzhen

    2017-01-01

    Acute stroke is a serious cerebrovascular disease and has been the second leading cause of death worldwide. Conventional diagnostic modalities for stroke, such as CT and MRI, may not be available in emergency settings. Hence, it is imperative to develop a portable tool to diagnose stroke in a timely manner. Since there are differences in impedance spectra between normal, hemorrhagic and ischemic brain tissues, multi-frequency electrical impedance tomography (MFEIT) shows great promise in detecting stroke. Measuring the impedance spectra of healthy, hemorrhagic and ischemic brain in vivo is crucial to the success of MFEIT. To our knowledge, no research has established hemorrhagic and ischemic brain models in the same animal and comprehensively measured the in vivo impedance spectra of healthy, hemorrhagic and ischemic brain within 10 Hz–1 MHz. In this study, the intracerebral hemorrhage and ischemic models were established in rabbits, and then the impedance spectra of healthy, hemorrhagic and ischemic brain were measured in vivo and compared. The results demonstrated that the impedance spectra differed significantly between healthy and stroke-affected brain (i.e., hemorrhagic or ischemic brain). Moreover, the rate of change in brain impedance following hemorrhagic and ischemic stroke with regard to frequency was distinct. These findings further validate the feasibility of using MFEIT to detect stroke and differentiate stroke types, and provide data supporting for future research. PMID:28387710

  1. Behavior outcome after ischemic and hemorrhagic stroke, with similar brain damage, in rats.

    Science.gov (United States)

    Mestriner, Régis Gemerasca; Miguel, Patrícia Maidana; Bagatini, Pamela Brambilla; Saur, Lisiani; Boisserand, Lígia Simões Braga; Baptista, Pedro Porto Alegre; Xavier, Léder Leal; Netto, Carlos Alexandre

    2013-05-01

    Stroke causes disability and mortality worldwide and is divided into ischemic and hemorrhagic subtypes. Although clinical trials suggest distinct recovery profiles for ischemic and hemorrhagic events, this is not conclusive due to stroke heterogeneity. The aim of this study was to produce similar brain damage, using experimental models of ischemic (IS) and hemorrhagic (HS) stroke and evaluate the motor spontaneous recovery profile. We used 31 Wistar rats divided into the following groups: Sham (n=7), ischemic (IS) (n=12) or hemorrhagic (HS) (n=12). Brain ischemia or hemorrhage was induced by endotelin-1 (ET-1) and collagenase type IV-S (collagenase) microinjections, respectively. All groups were evaluated in the open field, cylinder and ladder walk behavioral tests at distinct time points as from baseline to 30 days post-surgery (30 PS). Histological and morphometric analyses were used to assess the volume of lost tissue and lesion length. Present results reveal that both forms of experimental stroke had a comparable long-term pattern of damage, since no differences were found in volume of tissue lost or lesion size 30 days after surgery. However, behavioral data showed that hemorrhagic rats were less impaired at skilled walking than ischemic ones at 15 and 30 days post-surgery. We suggest that experimentally comparable stroke design is useful because it reduces heterogeneity and facilitates the assessment of neurobiological differences related to stroke subtypes; and that spontaneous skilled walking recovery differs between experimental ischemic and hemorrhagic insults. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Differential Temporal Evolution Patterns in Brain Temperature in Different Ischemic Tissues in a Monkey Model of Middle Cerebral Artery Occlusion

    Directory of Open Access Journals (Sweden)

    Zhihua Sun

    2012-01-01

    Full Text Available Brain temperature is elevated in acute ischemic stroke, especially in the ischemic penumbra (IP. We attempted to investigate the dynamic evolution of brain temperature in different ischemic regions in a monkey model of middle cerebral artery occlusion. The brain temperature of different ischemic regions was measured with proton magnetic resonance spectroscopy (1H MRS, and the evolution processes of brain temperature were compared among different ischemic regions. We found that the normal (baseline brain temperature of the monkey brain was 37.16°C. In the artery occlusion stage, the mean brain temperature of ischemic tissue was 1.16°C higher than the baseline; however, this increase was region dependent, with 1.72°C in the IP, 1.08°C in the infarct core, and 0.62°C in the oligemic region. After recanalization, the brain temperature of the infarct core showed a pattern of an initial decrease accompanied by a subsequent increase. However, the brain temperature of the IP and oligemic region showed a monotonously and slowly decreased pattern. Our study suggests that in vivo measurement of brain temperature could help to identify whether ischemic tissue survives.

  3. Role of ischemic modified albumin in the early diagnosis of increased intracranial pressure and brain death.

    Science.gov (United States)

    Kara, I; Pampal, H K; Yildirim, F; Dilekoz, E; Emmez, G; U, F P; Kocabiyik, M; Demirel, C B

    Increased intracranial pressure following trauma and subsequent possible development of brain death are important factors for morbidity and mortality due to ischemic changes. We aimed to establish the role of ischemic modified albumin (IMA) in the early diagnosis of the process, starting with increased intracranial pressure and ending with brain death. Eighteen Wistar-Albino rats were divided into three groups; control (CG, n = 6), increased intracranial pressure (ICPG, n = 6), and brain death (BDG, n = 6). Intracranial pressure elevation and brain death were constituted with the inflation of a balloon of a Fogarty catheter in the epidural space. In all three groups, blood samples were drawn before the procedure, and at minutes 150 and 240 for IMA and malondialdehyde (MDA) analysis. Serum IMA levels at 150 and 240 minutes were higher in ICPG than in CG (p intracranial pressure elevation and ending at brain death (Tab. 3, Fig. 5, Ref. 31).

  4. Ginsenoside Rg1 improves ischemic brain injury by balancing ...

    African Journals Online (AJOL)

    Purpose: To study the effects of ginsenoside Rg1 on mitochondrial dysfunction induced by ischemic stroke. Methods: Human neuroblastoma SK-N-SH cells, subjected to oxygen-glucose deprivation (OGD), were divided into six groups: control group, OGD group, 3 OGD + Rg1 groups (6.25, 12.5 and 25 μM), and Rg1 (25 ...

  5. Edaravone Enhances Brain-Derived Neurotrophic Factor Production in the Ischemic Mouse Brain

    Directory of Open Access Journals (Sweden)

    Satoshi Okuyama

    2015-04-01

    Full Text Available Edaravone, a clinical drug used to treat strokes, protects against neuronal cell death and memory loss in the ischemic brains of animal models through its antioxidant activity. In the present study, we subcutaneously administrated edaravone to mice (3 mg/kg/day for three days immediately after bilateral common carotid artery occlusion, and revealed through an immunohistochemical analysis that edaravone (1 accelerated increases in the production of brain-derived neurotrophic factor (BDNF in the hippocampus; (2 increased the number of doublecortin-positive neuronal precursor cells in the dentate gyrus subgranular zone; and (3 suppressed the ischemia-induced inactivation of calcium-calmodulin-dependent protein kinase II in the hippocampus. We also revealed through a Western blotting analysis that edaravone (4 induced the phosphorylation of cAMP response element-binding (CREB, a transcription factor that regulates BDNF gene expression; and (5 induced the phosphorylation of extracellular signal-regulated kinases 1/2, an upstream signal factor of CREB. These results suggest that the neuroprotective effects of edaravone following brain ischemia were mediated not only by the elimination of oxidative stress, but also by the induction of BDNF production.

  6. Type 2 diabetes is not a risk factor for asymptomatic ischemic brain lesion. The Funagata study

    Energy Technology Data Exchange (ETDEWEB)

    Saitoh, Tamotsu; Daimon, Makoto; Eguchi, Hideyuki; Hosoya, Takaaki; Kawanami, Toru; Kurita, Keiji; Tominaga, Makoto; Kato, Takeo [Yamagata Univ. (Japan). School of Medicine

    2002-05-01

    The purpose of this study is to clarify whether type 2 diabetes (DM) is a risk factor for asymptomatic (silent) ischemic brain lesion, which is controversial at present. The subjects (n=187), who showed normal results on both neurological and neuropsychological examinations, underwent a 75-g OGTT and were examined by brain MRI on T1-weighted, T2-weighted, and FLAIR (fluid-attenuated inversion recovery) images. Their brain MRIs were evaluated quantitatively with the ischemia rating scale defined here. The subjects were grouped based on their glucose tolerance: normal glucose tolerance (NGT) (n=48), impaired glucose tolerance (IGT) (n=62), and DM (n=65). The subjects with DM were further divided based on their duration of illness: 20 with short duration (short DM: 1.3{+-}0.8 years) and 45 with long duration (long DM; 8.9{+-}5.4 years). Ages were matched among the groups. The percentages of individuals with asymptomatic ischemic brain lesion were 81% in NGT, 74% in IGT, 65% in short DM, and 78% in long DM. No significant difference was observed among the groups in terms of the percentage. Namely, even in individuals with a long history of DM without clinical stroke, the prevalence of asymptomatic ischemic brain lesion was not different from that of the other groups. Multiple regression and multiple logistic regression analyses showed that age and hypertension were significant independent risk factors for asymptomatic ischemic brain lesion, whereas hypercholesterolemia, smoking, and glucose intolerance, including IGT, short DM and long DM, were not. DM is not a risk factor for asymptomatic ischemic brain lesion. (author)

  7. Modeling the ischemic blood-brain barrier; the effects of oxygen-glucose deprivation (OGD) on endothelial cells in culture

    DEFF Research Database (Denmark)

    Tornabene, Erica; Helms, Hans Christian Cederberg; Berndt, Philipp

    their passage through the capillary endothelium. An ischemic insult and the subsequent restoration of blood flow, defined as reperfusion, dramatically impair the BBB integrity, resulting in increased BBB permeability, modified transport pathways, edema and tissue damage. A deeper understanding of the permeation......Introduction - The blood-brain barrier (BBB) is a physical, transport and metabolic barrier which plays a key role in preventing uncontrolled exchanges between blood and brain, ensuring an optimal environment for neurons activity. This extent interface is created by the endothelial cells forming...... the wall of brain capillaries. The restrictive nature of the BBB is due to the tight junctions (TJs), which seal the intercellular clefts, limiting the paracellular diffusion, efflux transporters, which extrude xenobiotics, and metabolizing enzymes, which may break down or convert molecules during...

  8. Regional cerebral blood perfusion SPECT imaging in brain ischemic injury due to cerebral hemorrhage

    International Nuclear Information System (INIS)

    Zhang Chunyin; Chen Yue; Li Zuoxiao; Tan Hua; Li Xiaohong

    2006-01-01

    Objective: To explore the clinical value of SPECT perfusion imaging in brain ischemic injury due to cerebral hemorrhage before and after treatment. Methods: Sixty cases of cerebral hemorrhage were randomly divided into nimodipine treated group and routine treated group. The volume of primary ischemic focus, changes of regional cerebral blood perfusion around hematoma and other cerebral areas were observed by SPECT imaging. Results: Volume of the primary focus was reduced apparently in both groups, but much more in nimodipine treated group (P<0.01). Also the regional cerebral blood flow in ischemic focus and remote areas increased much more in nimodipine treated group than routine treated group (P< 0.01). Conclusions: Brain SPECT imaging can sensitively reflect the regional cerebral blood flow before and after treatment. Thereby, it is useful for therapeutic monitoring. (authors)

  9. Modulation of Intestinal Microbiome Prevents Intestinal Ischemic Injury

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    Alessandra Bertacco

    2017-12-01

    Full Text Available Background: Butyrate protects against ischemic injury to the small intestine by reducing inflammation and maintaining the structure of the intestinal barrier, but is expensive, short-lived, and cannot be administered easily due to its odor. Lactate, both economical and more palatable, can be converted into butyrate by the intestinal microbiome. This study aimed to assess in a rat model whether lactate perfusion can also protect against intestinal ischemia.Materials and Methods: Rat intestinal segments were loaded in an in vitro bowel perfusion device, and water absorption or secretion was assessed based on fluorescence of FITC-inulin, a fluorescent marker bound to a biologically inert sugar. Change in FITC concentration was used as a measure of ischemic injury, given the tendency of ischemic cells to retain water. Hematoxylin and eosin-stained sections at light level microscopy were examined to evaluate intestinal epithelium morphology. Comparisons between the data sets were paired Student t-tests or ANOVA with p < 0.05 performed on GraphPad.Results: Lactate administration resulted in a protective effect against intestinal ischemia of similar magnitude to that observed with butyrate. Both exhibited approximately 1.5 times the secretion exhibited by control sections (p = 0.03. Perfusion with lactate and methoxyacetate, a specific inhibitor of lactate-butyrate conversion, abolished this effect (p = 0.09. Antibiotic treatment also eliminated this effect, rendering lactate-perfused sections similar to control sections (p = 0.72. Perfusion with butyrate and methoxyacetate did not eliminate the observed increased secretion, which indicates that ischemic protection was mediated by microbial conversion of lactate to butyrate (p = 0.71.Conclusions: Lactate's protective effect against intestinal ischemia due to microbial conversion to butyrate suggests possible applications in the transplant setting for reducing ischemic injury and ameliorating intestinal

  10. Computed tomography and brain scintigraphy in ischemic stroke

    International Nuclear Information System (INIS)

    Chiu, L.C.; Fodor, L.B.; Cornell, S.H.; Christie, J.H.

    1976-01-01

    Radionuclide and computed tomographic (CT) scans were reviewed in 215 patients with ischemic stroke. The findings vary depending on the site of vascular occlusion. In middle cerebral artery occlusion, four distinct patterns may be seen on the scintigrams. The CT scans show little variation in appearance. The tentorial confluence sign is an important finding on scintigrams of patients with occipital infarction; the absence of this sign should suggest another diagnosis. During the first week and after the fourth week following an ischemic stroke, the scintigram is usually negative, whereas the lesion is visible by CT. However, there are a significant number of false negative CT scans; therefore, both examinations are advocated in difficult cases

  11. Neuroinflammation and Neuroimmune Dysregulation After Acute Hypoxic-Ischemic Injury of Developing Brain

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    Utpal S Bhalala

    2015-01-01

    Full Text Available Hypoxic-ischemic injury to developing brain results from birth asphyxia in neonates and from cardiac arrest in infants and children. It is associated with varying degrees of neurologic sequelae, depending upon the severity and length of hypoxia-ischemia. Global hypoxia-ischemia triggers a series of cellular and biochemical pathways that lead to neuronal injury. One of the key cellular pathways of neuronal injury is inflammation. The inflammatory cascade comprises activation and migration of microglia—the so-called brain macrophages, infiltration of peripheral macrophages into the brain, and release of cytotoxic, proinflammatory cytokines. In this article, we review the inflammatory and immune mechanisms of secondary neuronal injury after global hypoxic-ischemic injury to developing brain. Specifically, we highlight the current literature on microglial activation in relation to neuronal injury, proinflammatory and anti-inflammatory/restorative pathways, the role of peripheral immune cells, and the potential use of immunomodulators as neuroprotective compounds.

  12. Neuroprotective actions of taurine on hypoxic-ischemic brain damage in neonatal rats.

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    Zhu, Xiao-Yun; Ma, Peng-Sheng; Wu, Wei; Zhou, Ru; Hao, Yin-Ju; Niu, Yang; Sun, Tao; Li, Yu-Xiang; Yu, Jian-Qiang

    2016-06-01

    Taurine is an abundant amino acid in the nervous system, which has been proved to possess antioxidation, osmoregulation and membrane stabilization. Previously it has been demonstrated that taurine exerts ischemic brain injury protective effect. This study was designed to investigate whether the protective effect of taurine has the possibility to be applied to treat neonatal hypoxic-ischemic brain damage. Seven-day-old Sprague-Dawley rats were treated with left carotid artery ligation followed by exposure to 8% oxygen to generate the experimental group. The cerebral damage area was measured after taurine post-treatment with 2,3,5-triphenyltetrazolium chloride (TTC) staining, Hematoxyline-Eosin (HE) staining and Nissl staining. The activities of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), myeloperoxtidase (MPO), ATP and Lactic Acid productions were assayed with ipsilateral hemisphere homogenates. Western-blot and immunofluorescence assay were processed to detect the expressions of AIF, Cyt C, Bax, Bcl-2 in brain. We found that taurine significantly reduced brain infarct volume and ameliorated morphological injury obviously reversed the changes of SOD, MDA, GSH-Px, T-AOC, ATP, MPO, and Lactic Acid levels. Compared with hypoxic-ischemic group, it showed marked reduction of AIF, Cyt C and Bax expressions and increase of Bcl-2 after post-treatment. We conclude that taurine possesses an efficacious neuroprotective effect after cerebral hypoxic-ischemic damage in neonatal rats. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Postconditioning with repeated mild hypoxia protects neonatal hypoxia-ischemic rats against brain damage and promotes rehabilitation of brain function.

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    Deng, Qingqing; Chang, Yanqun; Cheng, Xiaomao; Luo, Xingang; Zhang, Jing; Tang, Xiaoyuan

    2018-02-06

    Mild hypoxia conditioning induced by repeated episodes of transient ischemia is a clinically applicable method for protecting the brain against injury after hypoxia-ischemic brain damage. To assess the effect of repeated mild hypoxia postconditioning on brain damage and long-term neural functional recovery after hypoxia-ischemic brain damage. Rats received different protocols of repeated mild hypoxia postconditioning. Seven-day-old rats with hypoxia ischemic brain damage (HIBD) from the left carotid ligation procedure plus 2 h hypoxic stress (8% O 2 at 37 °C) were further receiving repeated mild hypoxia intermittently. The gross anatomy, functional analyses, hypoxia inducible factor 1 alpha (HIF-1a) expression, and neuronal apoptosis of the rat brains were subsequently examined. Compared to the HIBD group, rats postconditioned with mild hypoxia had elevated HIF-1a expression, more Nissl-stain positive cells in their brain tissue and their brains functioned better in behavioral analyses. The recovery of the brain function may be directly linked to the inhibitory effect of HIF-1α on neuronal apoptosis. Furthermore, there were significantly less neuronal apoptosis in the hippocampal CA1 region of the rats postconditioned with mild hypoxia, which might also be related to the higher HIF-1a expression and better brain performance. Overall, these results suggested that postconditioning of neonatal rats after HIBD with mild hypoxia increased HIF-1a expression, exerted a neuroprotective effect and promoted neural functional recovery. Repeated mild hypoxia postconditioning protects neonatal rats with HIBD against brain damage and improves neural functional recovery. Our results may have clinical implications for treating infants with HIBD. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. 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.

  15. Matrix Metalloproteinases and Blood-Brain Barrier Disruption in Acute Ischemic Stroke

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    Shaheen E. Lakhan

    2013-04-01

    Full Text Available Ischemic stroke continues to be one of the most challenging diseases in translational neurology. Tissue plasminogen activator (tPA remains the only approved treatment for acute ischemic stroke, but its use is limited to the first hours after stroke onset due to an increased risk of hemorrhagic transformation over time resulting in enhanced brain injury. In this review we discuss the role of matrix metalloproteinases (MMPs in blood-brain barrier (BBB disruption as a consequence of ischemic stroke. MMP-9 in particular appears to play an important role in tPA-associated hemorrhagic complications. Reactive oxygen species can enhance the effects of tPA on MMP activation through the loss of caveolin-1 (cav-1, a protein encoded in the cav-1 gene that serves as a critical determinant of BBB permeability. This review provides an overview of MMPs’ role in BBB breakdown during acute ischemic stroke. The possible role of MMPs in combination treatment of acute ischemic stroke is also examined.

  16. Regional brain structural abnormality in ischemic stroke patients: a voxel-based morphometry study

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    Ping Wu

    2016-01-01

    Full Text Available Our previous study used regional homogeneity analysis and found that activity in some brain areas of patients with ischemic stroke changed significantly. In the current study, we examined structural changes in these brain regions by taking structural magnetic resonance imaging scans of 11 ischemic stroke patients and 15 healthy participants, and analyzing the data using voxel-based morphometry. Compared with healthy participants, patients exhibited higher gray matter density in the left inferior occipital gyrus and right anterior white matter tract. In contrast, gray matter density in the right cerebellum, left precentral gyrus, right middle frontal gyrus, and left middle temporal gyrus was less in ischemic stroke patients. The changes of gray matter density in the middle frontal gyrus were negatively associated with the clinical rating scales of the Fugl-Meyer Motor Assessment (r = -0.609, P = 0.047 and the left middle temporal gyrus was negatively correlated with the clinical rating scales of the nervous functional deficiency scale (r = -0.737, P = 0.010. Our findings can objectively identify the functional abnormality in some brain regions of ischemic stroke patients.

  17. Regional brain structural abnormality in ischemic stroke patients: a voxel-based morphometry study.

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    Wu, Ping; Zhou, Yu-Mei; Zeng, Fang; Li, Zheng-Jie; Luo, Lu; Li, Yong-Xin; Fan, Wei; Qiu, Li-Hua; Qin, Wei; Chen, Lin; Bai, Lin; Nie, Juan; Zhang, San; Xiong, Yan; Bai, Yu; Yin, Can-Xin; Liang, Fan-Rong

    2016-09-01

    Our previous study used regional homogeneity analysis and found that activity in some brain areas of patients with ischemic stroke changed significantly. In the current study, we examined structural changes in these brain regions by taking structural magnetic resonance imaging scans of 11 ischemic stroke patients and 15 healthy participants, and analyzing the data using voxel-based morphometry. Compared with healthy participants, patients exhibited higher gray matter density in the left inferior occipital gyrus and right anterior white matter tract. In contrast, gray matter density in the right cerebellum, left precentral gyrus, right middle frontal gyrus, and left middle temporal gyrus was less in ischemic stroke patients. The changes of gray matter density in the middle frontal gyrus were negatively associated with the clinical rating scales of the Fugl-Meyer Motor Assessment ( r = -0.609, P = 0.047) and the left middle temporal gyrus was negatively correlated with the clinical rating scales of the nervous functional deficiency scale ( r = -0.737, P = 0.010). Our findings can objectively identify the functional abnormality in some brain regions of ischemic stroke patients.

  18. Hyper-attenuating brain lesions on CT after ischemic stroke and thrombectomy are associated with final brain infarction.

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    Cabral, F B; Castro-Afonso, L H; Nakiri, G S; Monsignore, L M; Fábio, Src; Dos Santos, A C; Pontes-Neto, O M; Abud, D G

    2017-12-01

    Purpose Hyper-attenuating lesions, or contrast staining, on a non-contrast brain computed tomography (NCCT) scan have been investigated as a predictor for hemorrhagic transformation after endovascular treatment of acute ischemic stroke (AIS). However, the association of hyper-attenuating lesions and final ischemic areas are poorly investigated in this setting. The aim of the present study was to assess correlations between hyper-attenuating lesions and final brain infarcted areas after thrombectomy for AIS. Methods Data from patients with AIS of the anterior circulation who underwent endovascular treatment were retrospectively assessed. Images of the brain NCCT scans were analyzed in the first hours and late after treatment. The hyper-attenuating areas were compared to the final ischemic areas using the Alberta Stroke Program Early CT Score (ASPECTS). Results Seventy-one of the 123 patients (65.13%) treated were included. The association between the hyper-attenuating region in the post-thrombectomy CT scan and final brain ischemic area were sensitivity (58.3% to 96.9%), specificity (42.9% to 95.6%), positive predictive values (71.4% to 97.7%), negative predictive values (53.8% to 79.5%), and accuracy values (68% to 91%). The highest sensitivity values were found for the lentiform (96.9%) and caudate nuclei (80.4%) and for the internal capsule (87.5%), and the lowest values were found for the M1 (58.3%) and M6 (66.7%) cortices. Conclusions Hyper-attenuating lesions on head NCCT scans performed after endovascular treatment of AIS may predict final brain infarcted areas. The prediction appears to be higher in the deep brain regions compared with the cortical regions.

  19. Krebs cycle metabolites and preferential succinate oxidation following neonatal hypoxic-ischemic brain injury in mice.

    Science.gov (United States)

    Sahni, Prateek V; Zhang, Jimmy; Sosunov, Sergey; Galkin, Alexander; Niatsetskaya, Zoya; Starkov, Anatoly; Brookes, Paul S; Ten, Vadim S

    2018-02-01

    BackgroundReverse electron transport (RET) driven by the oxidation of succinate has been proposed as the mechanism of accelerated production of reactive oxygen species (ROS) in post-ischemic mitochondria. However, it remains unclear whether upon reperfusion, mitochondria preferentially oxidase succinate.MethodsNeonatal mice were subjected to Rice-Vannucci model of hypoxic-ischemic brain injury (HI) followed by assessment of Krebs cycle metabolites, mitochondrial substrate preference, and H 2 O 2 generation rate in the ischemic brain.ResultsWhile brain mitochondria from control mice exhibited a rotenone-sensitive complex-I-dependent respiration, HI-brain mitochondria, at the initiation of reperfusion, demonstrated complex-II-dependent respiration, as rotenone minimally affected, but inhibition of complex-II ceased respiration. This was associated with a 30-fold increase of cerebral succinate concentration and significantly elevated H 2 O 2 emission rate in HI-mice compared to controls. At 60 min of reperfusion, cerebral succinate content and the mitochondrial response to rotenone did not differ from that in controls.ConclusionThese data are the first ex vivo evidence, that at the initiation of reperfusion, brain mitochondria transiently shift their metabolism from complex-I-dependent oxidation of NADH toward complex II-linked oxidation of succinate. Our study provides a critical piece of support for existence of the RET-dependent mechanism of elevated ROS production in reperfusion.

  20. [Brain repair after ischemic stroke: role of neurotransmitters in post-ischemic neurogenesis].

    Science.gov (United States)

    Sánchez-Mendoza, Eduardo; Bellver-Landete, Víctor; González, María Pilar; Merino, José Joaquín; Martínez-Murillo, Ricardo; Oset-Gasque, María Jesús

    2012-11-01

    Brain ischemia and reperfusion produce alterations in the microenvironment of the parenchyma, including ATP depletion, ionic homeostasis alterations, inflammation, release of multiple cytokines and abnormal release of neurotransmitters. As a consequence, the induction of proliferation and migration of neural stem cells towards the peri-infarct region occurs. The success of new neurorestorative treatments for damaged brain implies the need to know, with greater accuracy, the mechanisms in charge of regulating adult neurogenesis, both under physiological and pathological conditions. Recent evidence demonstrates that many neurotransmitters, glutamate in particular, control the subventricular zone, thus being part of the complex signalling network that influences the production of new neurons. Neurotransmitters provide a link between brain activity and subventricular zone neurogenesis. Therefore, a deeper knowledge of the role of neurotransmitters systems, such as glutamate and its transporters, in adult neurogenesis, may provide a valuable tool to be used as a neurorestorative therapy in this pathology.

  1. MECHANISMS OF SECONDARY BRAIN DAMAGE IN COMA DEVELOPED IN ACUTE PERIOD OF ISCHEMIC STROKE

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    Константин Владимирович Лукашев

    2017-06-01

    Conclusions. One of the mechanisms of secondary brain damage in patients in coma in acute period of ischemic stroke is a worsening dysfunction of the brain stem followed bythe cerebral autoregulationdisturbance in the absence of a significant increase of intracranial pressure.This causes disturbances of the central hemodynamics, the mechanical and gas exchange properties,the accumulation of extravascular lung water.These processesresult in acute lung injury, itbeing a critical element in the development and progression of systemic hypoxia as a key mechanism of secondary brain damage.

  2. Whole-Brain CT Perfusion to Quantify Acute Ischemic Penumbra and Core.

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    Lin, Longting; Bivard, Andrew; Krishnamurthy, Venkatesh; Levi, Christopher R; Parsons, Mark W

    2016-06-01

    Purpose To validate the use of perfusion computed tomography (CT) with whole-brain coverage to measure the ischemic penumbra and core and to compare its performance to that of limited-coverage perfusion CT. Materials and Methods Institutional ethics committee approval and informed consent were obtained. Patients (n = 296) who underwent 320-detector CT perfusion within 6 hours of the onset of ischemic stroke were studied. First, the ischemic volume at CT perfusion was compared with the penumbra and core reference values at magnetic resonance (MR) imaging to derive CT perfusion penumbra and core thresholds. Second, the thresholds were tested in a different group of patients to predict the final infarction at diffusion-weighted imaging 24 hours after CT perfusion. Third, the change in ischemic volume delineated by the optimal penumbra and core threshold was determined as the brain coverage was gradually reduced from 160 mm to 20 mm. The Wilcoxon signed-rank test, concordance correlation coefficient (CCC), and analysis of variance were used for the first, second, and third steps, respectively. Results CT perfusion at penumbra and core thresholds resulted in the least volumetric difference from MR imaging reference values with delay times greater than 3 seconds and delay-corrected cerebral blood flow of less than 30% (P = .34 and .33, respectively). When the thresholds were applied to the new group of patients, prediction of the final infarction was allowed with delay times greater than 3 seconds in patients with no recanalization of the occluded artery (CCC, 0.96 [95% confidence interval: 0.92, 0.98]) and with delay-corrected cerebral blood flow less than 30% in patients with complete recanalization (CCC, 0.91 [95% confidence interval: 0.83, 0.95]). However, the ischemic volume with a delay time greater than 3 seconds was underestimated when the brain coverage was reduced to 80 mm (P = .04) and the core volume measured as cerebral blood flow less than 30% was

  3. Ischemic brain injury: New insights on the protective role of melatonin.

    Science.gov (United States)

    Ramos, Eva; Patiño, Paloma; Reiter, Russel J; Gil-Martín, Emilio; Marco-Contelles, José; Parada, Esther; de Los Rios, Cristobal; Romero, Alejandro; Egea, Javier

    2017-03-01

    Stroke represents one of the most common causes of brain's vulnerability for many millions of people worldwide. The plethora of physiopathological events associated with brain ischemia are regulate through multiple signaling pathways leading to the activation of oxidative stress process, Ca 2+ dyshomeostasis, mitochondrial dysfunction, proinflammatory mediators, excitotoxicity and/or programmed neuronal cell death. Understanding this cascade of molecular events is mandatory in order to develop new therapeutic strategies for stroke. In this review article, we have highlighted the pleiotropic effects of melatonin to counteract the multiple processes of the ischemic cascade. Additionally, experimental evidence supports its actions to ameliorate ischemic long-term behavioural and neuronal deficits, preserving the functional integrity of the blood-brain barrier, inducing neurogenesis and cell proliferation through receptor-dependent mechanism, as well as improving synaptic transmission. Consequently, the synthesis of melatonin derivatives designed as new multitarget-directed products has focused a great interest in this area. This latter has been reinforced by the low cost of melatonin and its reduced toxicity. Furthermore, its spectrum of usages seems to be wide and with the potential for improving human health. Nevertheless, the molecular and cellular mechanisms underlying melatonin´s actions need to be further exploration and accordingly, new clinical studies should be conducted in human patients with ischemic brain pathologies. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Ferulic acid prevents cerebral ischemic injury-induced reduction of hippocalcin expression.

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    Koh, Phil-Ok

    2013-07-01

    Intracellular calcium overload is a critical pathophysiological factor in ischemic injury. Hippocalcin is a neuronal calcium sensor protein that buffers intracellular calcium levels and protects cells from apoptotic stimuli. Ferulic acid exerts a neuroprotective effect in cerebral ischemia through its anti-oxidant and anti-inflammation activity. This study investigated whether ferulic acid contributes to hippocalcin expression during cerebral ischemia and glutamate exposure-induced neuronal cell death. Rats were immediately treated with vehicle or ferulic acid (100 mg/kg, i.v.) after middle cerebral artery occlusion (MCAO). Brain tissues were collected 24 h after MCAO and followed by assessment of cerebral infarct. Ferulic acid reduced MCAO-induced infarct regions. A proteomics approach elucidated a decrease in hippocalcin in MCAO-operated animals, ferulic acid attenuates the injury-induced decrease in hippocalcin expression. Reverse transcription-polymerase chain reaction and Western blot analyses confirmed that ferulic acid prevents the injury-induced decrease in hippocalcin. In cultured HT22 hippocampal cells, glutamate exposure increased the intracellular Ca(2+) levels, whereas ferulic acid attenuated this increase. Moreover, ferulic acid attenuated the glutamate toxicity-induced decrease in hippocalcin expression. These findings can suggest the possibility that ferulic acid exerts a neuroprotective effect through modulating hippocalcine expression and regulating intracellular calcium levels. Copyright © 2013 Wiley Periodicals, Inc.

  5. Correlation between Nerve Growth Factor (NGF with Brain Derived Neurotropic Factor (BDNF in Ischemic Stroke Patient

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    Joko Widodo

    2016-05-01

    Full Text Available Background: The neurotrophins nerve growth factor (NGF and brain-derived neurotrophic factor (BDNF is a family of polypeptides that play critical role during neuronal development, appear to mediate protective role on neurorepair in ischemic stroke. Naturally in adult brain neurorepair process consist of: angiogenesis, neurogenesis, and neuronal plasticity, it can also be stimulated by endogenous neurorepair. In this study we observed correlation between NGF and BDNF ischemic stroke patient’s onset: 7-30 and over 30 days. Methods: This is cross sectional study on 46 subjects aged 38 – 74 years old with ischemic stroke from The Indonesian Central Hospital of Army Gatot Subroto Jakarta. Diagnosis of ischemic stroke was made using clinical examination and magnetic resonance imaging (MRI by neurologist. Subjects were divided into 2 groups based on stroke onset: 7 – 30 days (Group A: 19 subjects and > 30 days (Group B: 27 Subjects. Serum NGF levels were measured with ELISA method and BDNF levels were measured using multiplex method with Luminex Magpix. Results: Levels of NGF and BDNF were significantly different between onset group A and B (NGF p= 0.022, and BDNF p=0.008, with mean levels NGF in group A higher than group B, indicating that BDNF levels is lower in group A than group B. There was no significant correlation between NGF and BDNF levels in all groups. Conclusion: The variations in neurotrophic factor levels reflect an endogenous attempt at neuroprotection against biochemical and molecular changes after ischemic stroke. NGF represents an early marker of brain injury while BDNF recovery is most prominent during the first 14 days after onsite but continuous for more than 30 days. There is no significant correlation between NGF and BDNF in each group.  

  6. The influence of general anesthesia on the brain in aged patients with previous ischemic cerebrovascular disease

    International Nuclear Information System (INIS)

    Kokubo, Yasuaki; Kayama, Takamasa; Kondo, Rei; Oki, Masato; Takaoka, Seiji

    2008-01-01

    Whenever we discuss the overall results of surgical treatment for unruptured cerebral aneurysms, especially in aged patients, we tend to consider advanced age or general anesthesia as causes for unfavorable results. There are no reports concerning ischemic stroke events following general anesthesia in aged patients with a prior history of cerebrovascular disease. The purpose of this study is to clarify the influence of general anesthesia on the brats in aged patients with a previous history of ischemic cerebrovascular disease. The subjects were 30 consecutive patients over 70 years of age with previous ischemic cerebrovascular disease who underwent various surgeries except brain and cardiac surgery under general anesthesia. The patients were 70 to 85 years old, with a mean age of 76. Twenty-three were men and 7 were women. Surgical procedures were 12 gastrointestinal, 6 orthopedic and 4 urogenital and others. The type of cerebrovascular disease evaluated by neuroradiologist and anesthesiologist based on MR imaging was devided as follows: 16 patients had minor stroke, 7 had transient ischemic attack/reversible ischemic neurological deficit (TIA/RIND) and 7 had asymptomatic cerebral infarction. MR angiography was also assessed to evaluate the main artery in the brain. Blood pressure and arterial blood gas (PaCO 2 ) during general anesthesia were analyzed, and the rate of systemic and neurological complications following general anesthesia were evaluated. MR angiography revealed no occlusion or severe stenosis of the main artery in the brain of any of the patients. The minimum systolic blood pressure showed less than 100 mmHg transiently for 5-20 minutes in 28 of 30 patients during general anesthesia. The minimum value was 65 mmHg maintained for 5 minutes. The minimum PaCO 2 during general anesthesia was as follows: 1 case 36 mmHg. There were no neurological complications following general anesthesia in this study. One of 30 patients (3.3%) had suffered from pneumonia

  7. Anti-ischemic effect of curcumin in rat brain.

    Science.gov (United States)

    Shukla, Pradeep K; Khanna, Vinay K; Ali, Mohd M; Khan, Mohd Y; Srimal, Rikhab C

    2008-06-01

    Turmeric has been in use since ancient times as a condiment and due to its medicinal properties. Curcumin, the yellow colouring principle in turmeric, is polyphenolic and major active constituent. Besides anti-inflammatory, thrombolytic and anticarcinogenic activities, curcumin also possesses strong antioxidant property. In view of the novel combination of properties, neuroprotective efficacy of curcumin was studied in rat middle cerebral artery occlusion (MCAO) model. Rats were subjected to 2 h of focal ischemia followed by 72 h of reperfusion. They were pre-treated with curcumin (100 mg/kg, po) for 5 days prior to MCAO and for another 3 days after MCAO. The parameters studied were behavioural, biochemical and histological. Treatment with curcumin could significantly improve neurobehavioral performance compared to untreated ischemic rats as judged by its effect on rota-rod performance and grid walking. A significant inhibition in lipid peroxidation and an increase in superoxide dismutase (SOD) activity in corpus striatum and cerebral cortex was observed following treatment with curcumin in MCAO rats as compared to MCAO group. Intracellular calcium levels were decreased following treatment with curcumin in MCAO rats. Histologically, a reduction in the infarct area from 33% to 24% was observed in MCAO rats treated with curcumin. The study demonstrates the protective efficacy of curcumin in rat MCAO model.

  8. Ischemic Postconditioning Alleviates Brain Edema After Focal Cerebral Ischemia Reperfusion in Rats Through Down-Regulation of Aquaporin-4.

    Science.gov (United States)

    Han, Dong; Sun, Miao; He, Ping-Ping; Wen, Lu-Lu; Zhang, Hong; Feng, Juan

    2015-07-01

    Cerebral edema is a serious complication associated with cerebral ischemia/reperfusion (I/R). Aquaporin-4 (AQP4) plays a role in generating postischemic edema after reperfusion. Recently, ischemic postconditioning (Postcond) has been shown to produce neuroprotective effects and reduce brain edema in rats after cerebral I/R. It is unclear if ischemic Postcond alleviates brain edema injury through regulation of AQP4. In this study, middle cerebral artery occlusion (MCAO) was induced in rats by filament insertion for 2 h following 24-h reperfusion: ischemic Postcond treatment was performed before reperfusion in the experimental group. We used the wet-dry weight ratio and transmission electron microscopy to evaluate brain edema after 24 h of reperfusion. We used immunohistochemistry and Western blot analyses to evaluate the distribution and expression of AQP4. Ischemic Postcond significantly reduced the water content of the brain tissue and swelling of the astrocytic foot processes. AQP4 expression increased in the I/R and Postcond groups compared to the sham group, but it decreased in the Postcond group compared to the I/R group. The results of our study suggest that ischemic Postcond effectively reduces brain edema after reperfusion by inhibiting AQP4 expression. The data in this study support the use of ischemic Postcond for alleviating brain edema after cerebral I/R.

  9. Memory deficit associated with increased brain proinflammatory cytokine levels and neurodegeneration in acute ischemic stroke

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    Bruno Silva

    2015-08-01

    Full Text Available The present study aimed to investigate behavioral changes and neuroinflammatory process following left unilateral common carotid artery occlusion (UCCAO, a model of cerebral ischemia. Post-ischemic behavioral changes following 15 min UCCAO were recorded 24 hours after reperfusion. The novel object recognition task was used to assess learning and memory. After behavioral test, brains from sham and ischemic mice were removed and processed to evaluate central nervous system pathology by TTC and H&E techniques as well as inflammatory mediators by ELISA. UCCAO promoted long-term memory impairment after reperfusion. Infarct areas were observed in the cerebrum by TTC stain. Moreover, the histopathological analysis revealed cerebral necrotic cavities surrounded by ischemic neurons and hippocampal neurodegeneration. In parallel with memory dysfunction, brain levels of TNF-a, IL-1b and CXCL1 were increased post ischemia compared with sham-operated group. These findings suggest an involvement of central nervous system inflammatory mediators and brain damage in cognitive impairment following unilateral acute ischemia.

  10. Increased oligodendrogenesis by humanin promotes axonal remyelination and neurological recovery in hypoxic/ischemic brains.

    Science.gov (United States)

    Chen, Jing; Sun, Miao; Zhang, Xia; Miao, Zhigang; Chua, Balvin H L; Hamdy, Ronald C; Zhang, Quan-Guang; Liu, Chun-Feng; Xu, Xingshun

    2015-01-01

    Oligodendrocytes are the predominant cell type in white matter and are highly vulnerable to ischemic injury. The role of oligodendrocyte dysfunction in ischemic brain injury is unknown. In this study, we used a 24-amino acid peptide S14G-Humanin (HNG) to examine oligodendrogenesis and neurological functional recovery in a hypoxic/ischemic (H/I) neonatal model. Intraperitoneal HNG pre-treatment decreased infarct volume following H/I injury. Delayed HNG treatment 24 h after H/I injury did not reduce infarct volume but did decrease neurological deficits and brain atrophy. Delayed HNG treatment did not attenuate axonal demyelination at 48 h after H/I injury. However, at 14 d after H/I injury, delayed HNG treatment increased axonal remyelination, the thickness of corpus callosum at the midline, the number of Olig2(+) /BrdU(+) cells, and levels of brain-derived neurotrophic factor (BDNF). Our results suggest that targeting oligodendrogenesis via delayed HNG treatment may represent a promising approach for the treatment of stroke. © 2014 Wiley Periodicals, Inc.

  11. The role in thanatogenesis of generalized brain edema in ischemic cerebral infarction (computer-morphometric research

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    E. A. Dyadyk

    2012-12-01

    Full Text Available This work presents the results of computer-morphometric study of perivascular and pericellular free (oedematous spaces in brain cortex at death from the ischemic cerebral infarction and from reasons unconnected directly with cerebral pathology. It was revealed, that the mean area of perivascular spaces (vasogenic edema index at brain infarction in 13 times exceeds such at extracerebral pathology, and mean area of pericellular spaces (cytotoxic edema index – almost in 12 times, but also it substantially differs on the degree of variation (in 2,5 times higher, than area of perivascular spaces.

  12. Hypertensive patients using thiazide diuretics as primary stroke prevention make better functional outcome after ischemic stroke.

    Science.gov (United States)

    Shih, Hong-Mo; Lin, Wei Chun; Wang, Cheng-Hsien; Lin, Leng-Chieh

    2014-10-01

    Thiazides have been used for the control of blood pressure and primary prevention of ischemic stroke. No previous studies have assessed the influence of thiazides on functional prognosis after ischemic stroke. Demographics, prestroke conditions, poststroke National Institutes of Health Stroke Scale score, and clinical and laboratory parameters were prospectively registered in 216 Taiwanese patients. One hundred forty patients who completed follow-up 3 months after experiencing ischemic stroke were assessed with the modified Rankin scale as functional prognoses. Twenty-one patients used thiazide to control hypertension before experiencing ischemic stroke. No differences of stroke subtypes and comorbidities before stroke were observed between the 2 groups. The emergency department National Institutes of Health Stroke Scale was lesser among thiazide users (4 [2-7] versus 6 [4-16], P = .02). Among 140 patients who completed follow-up in 90 days, thiazide users had more favorable functional status (modified Rankin scale ≤2: 42.4% versus 26.9%, P = .02, odds ratio 3.34, 95%, confidence interval .130-.862). Hypertensive patients treated with thiazides long term had a lesser severity of stroke and better functional outcomes after ischemic stroke. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  13. Ferulic Acid Attenuates the Injury-Induced Decrease of Protein Phosphatase 2A Subunit B in Ischemic Brain Injury

    Science.gov (United States)

    Koh, Phil-Ok

    2013-01-01

    Background Ferulic acid provides a neuroprotective effect during cerebral ischemia through its anti-oxidant function. Protein phosphatase 2A (PP2A) is a serine and threonine phosphatase that contributes broadly to normal brain function. This study investigated whether ferulic acid regulates PP2A subunit B in a middle cerebral artery occlusion (MCAO) animal model and glutamate toxicity-induced neuronal cell death. Methodology/Principal Findings MCAO was surgically induced to yield permanent cerebral ischemic injury in rats. The rats were treated with either vehicle or ferulic acid (100 mg/kg, i.v.) immediately after MCAO, and cerebral cortex tissues were collected 24 h after MCAO. A proteomics approach, RT-PCR, and Western blot analyses performed to identification of PP2A subunit B expression levels. Ferulic acid significantly reduced the MCAO-induced infarct volume of the cerebral cortex. A proteomics approach elucidated the reduction of PP2A subunit B in MCAO-induced animals, and ferulic acid treatment prevented the injury-induced reduction in PP2A subunit B levels. RT-PCR and Western blot analyses also showed that ferulic acid treatment attenuates the injury-induced decrease in PP2A subunit B levels. Moreover, the number of PP2A subunit B-positive cells was reduced in MCAO-induced animals, and ferulic acid prevented these decreases. In cultured neuronal cells, ferulic acid treatment protected cells against glutamate toxicity and prevented the glutamate-induced decrease in PP2A subunit B. Conclusions/Significance These results suggest that the maintenance of PP2A subunit B by ferulic acid in ischemic brain injury plays an important role for the neuroprotective function of ferulic acid. PMID:23349830

  14. How study patients who receive fluo pyrimidines to prevent ischemic events

    International Nuclear Information System (INIS)

    Saldombide, L.

    2010-01-01

    Introduction: Ischemic heart disease is the main cause of death in Uruguay and cancer is the second. The pillar of the systemic treatment of colorectal cancer are fluo pyrimidines and cause acute ischemic events in 3-8% of t rated patients. The 5 fluorouracil is the third anticancer drug most used Objective: Due to the high incidence of the two diseases and the risk of death caused by the ischemic treatment complications, the literature is analyzed to define how to study patients who receive fluo pyrimidines as a medium of preventing the same. Development: fluo pyrimidines cardio-toxicity can occur by myocardial toxicity, vasospasm, dihydropyrimidine dehydrogenase deficiency, autoimmune phenomena, platelet hyper aggregability, etc. The clinic is varied and underestimated: angina, abnormal ST silent and reversible, arrhythmias, heart failure, hypertension and heart failure. It is the most common complication with continuous infusion of 5 Fu and its equivalent capecitabine with bolus f lou pyrimidines. It is common that ischemic heart disease prioritises the risk increase of complications, but their absence does not exist. Without ischemic heart disease it is difficult to prevent ischemic events, however proposes that the older higher risk. Results: No uniform guidelines is advised: detailed history, determine if risk factors such as smoking, hypertension, diabetes and dyslipidemia and They are present electrocardiogram and cardiac evaluation. Warn the patient about angina l pain as early symptom and monitor symptoms during chemotherapy including cardio-vascular hypotension. Discontinue the medication and perform classic anti-angina l symptoms and / or signs of ischemia. Not reintroduce unless it is the only therapeutic option, since mortality may exceed

  15. Association of reduced folate carrier-1 (RFC-1) polymorphisms with ischemic stroke and silent brain infarction.

    Science.gov (United States)

    Cho, Yunkyung; Kim, Jung O; Lee, Jeong Han; Park, Hye Mi; Jeon, Young Joo; Oh, Seung Hun; Bae, Jinkun; Park, Young Seok; Kim, Ok Joon; Kim, Nam Keun

    2015-01-01

    Stroke is the second leading cause of death in the world and in South Korea. Ischemic stroke and silent brain infarction (SBI) are complex, multifactorial diseases influenced by multiple genetic and environmental factors. Moderately elevated plasma homocysteine levels are a major risk factor for vascular diseases, including stroke and SBI. Folate and vitamin B12 are important regulators of homocysteine metabolism. Reduced folate carrier (RFC), a bidirectional anion exchanger, mediates folate delivery to a variety of cells. We selected three known RFC-1 polymorphisms (-43C>T, 80A>G, 696T>C) and investigated their relationship to cerebral infarction in the Korean population. We used the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to analyze associations between the three RFC-1 polymorphisms, disease status, and folate and homocysteine levels in 584 ischemic stroke patients, 353 SBI patients, and 505 control subjects. The frequencies of the RFC-1 -43TT, 80GG, and 696CC genotypes differed significantly between the stroke and control groups. The RFC-1 80A>G substitution was also associated with small artery occlusion and SBI. In a gene-environment analysis, the RFC-1 -43C>T, 80A>G, and 696T>C polymorphisms in the ischemic stroke group had combined effects with all environmental factors. In summary, we found that the RFC-1 -43C>T, 80A>G, and 696T>C polymorphisms may be risk factors for ischemic stroke.

  16. Evidence that the EphA2 receptor exacerbates ischemic brain injury.

    Directory of Open Access Journals (Sweden)

    John Thundyil

    Full Text Available Ephrin (Eph signaling within the central nervous system is known to modulate axon guidance, synaptic plasticity, and to promote long-term potentiation. We investigated the potential involvement of EphA2 receptors in ischemic stroke-induced brain inflammation in a mouse model of focal stroke. Cerebral ischemia was induced in male C57Bl6/J wild-type (WT and EphA2-deficient (EphA2(-/- mice by middle cerebral artery occlusion (MCAO; 60 min, followed by reperfusion (24 or 72 h. Brain infarction was measured using triphenyltetrazolium chloride staining. Neurological deficit scores and brain infarct volumes were significantly less in EphA2(-/- mice compared with WT controls. This protection by EphA2 deletion was associated with a comparative decrease in brain edema, blood-brain barrier damage, MMP-9 expression and leukocyte infiltration, and higher expression levels of the tight junction protein, zona occludens-1. Moreover, EphA2(-/- brains had significantly lower levels of the pro-apoptotic proteins, cleaved caspase-3 and BAX, and higher levels of the anti-apoptotic protein, Bcl-2 as compared to WT group. We confirmed that isolated WT cortical neurons express the EphA2 receptor and its ligands (ephrin-A1-A3. Furthermore, expression of all four proteins was increased in WT primary cortical neurons following 24 h of glucose deprivation, and in the brains of WT mice following stroke. Glucose deprivation induced less cell death in primary neurons from EphA2(-/- compared with WT mice. In conclusion, our data provide the first evidence that the EphA2 receptor directly contributes to blood-brain barrier damage and neuronal death following ischemic stroke.

  17. Dystrophin proteolysis: a potential target for MMP-2 and its prevention by ischemic preconditioning.

    Science.gov (United States)

    Buchholz, Bruno; Perez, Virginia; Siachoque, Nadezda; Miksztowicz, Verónica; Berg, Gabriela; Rodríguez, Manuel; Donato, Martín; Gelpi, Ricardo J

    2014-07-01

    Dystrophin is responsible for the mechanical stabilization of the sarcolemma, and it has been shown that it is one of the most sensitive proteins to ischemic injury. However, the enzyme responsible for this proteolysis is still unknown. Isolated rabbit hearts were subjected to 30 min of global ischemia with and without reperfusion (180 min) to determine whether dystrophin is cleaved by matrix metalloproteinase (MMP)-2 during acute ischemia and whether ischemic preconditioning (PC) prevents dystrophin breakdown through MMP-2 inhibition. The activity of MMP-2 was evaluated by zymography and using doxycycline as an inhibitor. Also, to stimulate MMP-2 activity without ischemia, SIN-1 was administered in the absence and presence of doxycycline. Finally, we considered the PC effect on MMP-2 activity and dystrophin expression. The dystrophin level decreased during ischemia, reaching 21% of control values (P dystrophin breakdown. In normoxic hearts, SIN-1 increased thiobarbituric acid-reactive substances by 33% (P dystrophin level to 23% of control values (P dystrophin breakdown by inhibiting MMP-2 activity, and the dystrophin level reached 89% of control values (P dystrophin. Thus, dystrophin emerges as a possible novel substrate for MMP-2 in the context of ischemic injury. Furthermore, our results demonstrate that ischemic PC prevents dystrophin breakdown most likely by inhibiting MMP-2 activity. Copyright © 2014 the American Physiological Society.

  18. Low-level light emitting diode (LED) therapy suppresses inflammasome-mediated brain damage in experimental ischemic stroke.

    Science.gov (United States)

    Lee, Hae In; Lee, Sae-Won; Kim, Nam Gyun; Park, Kyoung-Jun; Choi, Byung Tae; Shin, Yong-Il; Shin, Hwa Kyoung

    2017-11-01

    Use of photostimulation including low-level light emitting diode (LED) therapy has broadened greatly in recent years because it is compact, portable, and easy to use. Here, the effects of photostimulation by LED (610 nm) therapy on ischemic brain damage was investigated in mice in which treatment started after a stroke in a clinically relevant setting. The mice underwent LED therapy (20 min) twice a day for 3 days, commencing at 4 hours post-ischemia. LED therapy group generated a significantly smaller infarct size and improvements in neurological function based on neurologic test score. LED therapy profoundly reduced neuroinflammatory responses including neutrophil infiltration and microglia activation in the ischemic cortex. LED therapy also decreased cell death and attenuated the NLRP3 inflammasome, in accordance with down-regulation of pro-inflammatory cytokines IL-1β and IL-18 in the ischemic brain. Moreover, the mice with post-ischemic LED therapy showed suppressed TLR-2 levels, MAPK signaling and NF-kB activation. These findings suggest that by suppressing the inflammasome, LED therapy can attenuate neuroinflammatory responses and tissue damage following ischemic stroke. Therapeutic interventions targeting the inflammasome via photostimulation with LED may be a novel approach to ameliorate brain injury following ischemic stroke. Effect of post-ischemic low-level light emitting diode therapy (LED-T) on infarct reduction was mediated by inflammasome suppression. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Transient Ischemic Attack Results in Delayed Brain Atrophy and Cognitive Decline.

    Science.gov (United States)

    Bivard, Andrew; Lillicrap, Thomas; Maréchal, Bénédicte; Garcia-Esperon, Carlos; Holliday, Elizabeth; Krishnamurthy, Venkatesh; Levi, Christopher R; Parsons, Mark

    2018-02-01

    Transient ischemic attack (TIA) initiates an ischemic cascade without resulting in frank infarction and, as such, represents a novel model to study the effects of this ischemic cascade and secondary neurodegeneration in humans. Patients with suspected TIA underwent acute brain perfusion imaging, and those with acute ischemia were enrolled into a prospective observational study. We collected baseline and 90-day magnetic resonance imaging, including MP-RAGE (high-resolution T1 sequence) and cognitive assessment with the Montreal Cognitive Assessment. Brain morphometry and within patient statistical analysis were performed to identify changes between baseline and 90-day imaging and clinical assessments. Fifty patients with TIA with acute perfusion lesions were studied. All patients experienced a decrease in global cortical gray matter ( P =0.005). Patients with anterior circulation TIA (n=31) also had a significant reduction in the volume of the pons ( P atrophy ( R 2 =0.28; P =0.009). In a prospective observational study, patients with TIA confirmed by acute perfusion imaging experienced a significant reduction in global gray matter and focal structural atrophy related to the area of acute ischemia. The atrophy also resulted in a proportional decreased cognitive performance on the Montreal Cognitive Assessment. Further studies are required to identify the mechanisms of this atrophy. © 2018 American Heart Association, Inc.

  20. Rationale for ischemic conditioning to prevent stroke in patients with intracranial arterial stenosis

    Directory of Open Access Journals (Sweden)

    Sami Al Kasab

    2016-01-01

    Full Text Available Intracranial atherosclerotic arterial stenosis (ICAS is one of the most common causes of stroke worldwide and is associated with particularly a high risk of recurrent stroke. Although aggressive medical management, consisting of dual antiplatelet therapy and intensive control of vascular risk factors, has improved the prognosis of patients with ICAS, subgroups of patients remain at very high risk of stroke. More effective therapies for these high-risk patients are urgently needed. One promising treatment is remote limb ischemic conditioning, which involves producing repetitive, transient ischemia of a limb by inflating a blood pressure cuff with the intention of protecting the brain from subsequent ischemia. In this study, we review the limitations of currently available treatments, discuss the potential mechanisms of action of ischemic conditioning, describe the preclinical and clinical data suggesting a possible role of ischemic conditioning in treating patients with ICAS, and outline the questions that still need to be answered in future studies of ischemic conditioning in subjects with ICAS.

  1. Endothelium-targeted overexpression of heat shock protein 27 ameliorates blood–brain barrier disruption after ischemic brain injury

    Science.gov (United States)

    Jiang, Xiaoyan; Zhang, Lili; Pu, Hongjian; Hu, Xiaoming; Zhang, Wenting; Cai, Wei; Gao, Yanqin; Leak, Rehana K.; Keep, Richard F.; Bennett, Michael V. L.; Chen, Jun

    2017-01-01

    The damage borne by the endothelial cells (ECs) forming the blood–brain barrier (BBB) during ischemic stroke and other neurological conditions disrupts the structure and function of the neurovascular unit and contributes to poor patient outcomes. We recently reported that structural aberrations in brain microvascular ECs—namely, uncontrolled actin polymerization and subsequent disassembly of junctional proteins, are a possible cause of the early onset BBB breach that arises within 30–60 min of reperfusion after transient focal ischemia. Here, we investigated the role of heat shock protein 27 (HSP27) as a direct inhibitor of actin polymerization and protectant against BBB disruption after ischemia/reperfusion (I/R). Using in vivo and in vitro models, we found that targeted overexpression of HSP27 specifically within ECs—but not within neurons—ameliorated BBB impairment 1–24 h after I/R. Mechanistically, HSP27 suppressed I/R-induced aberrant actin polymerization, stress fiber formation, and junctional protein translocation in brain microvascular ECs, independent of its protective actions against cell death. By preserving BBB integrity after I/R, EC-targeted HSP27 overexpression attenuated the infiltration of potentially destructive neutrophils and macrophages into brain parenchyma, thereby improving long-term stroke outcome. Notably, early poststroke administration of HSP27 attached to a cell-penetrating transduction domain (TAT-HSP27) rapidly elevated HSP27 levels in brain microvessels and ameliorated I/R-induced BBB disruption and subsequent neurological deficits. Thus, the present study demonstrates that HSP27 can function at the EC level to preserve BBB integrity after I/R brain injury. HSP27 may be a therapeutic agent for ischemic stroke and other neurological conditions involving BBB breakdown. PMID:28137866

  2. Parameterized entropy analysis of EEG following hypoxic-ischemic brain injury

    International Nuclear Information System (INIS)

    Tong Shanbao; Bezerianos, Anastasios; Malhotra, Amit; Zhu Yisheng; Thakor, Nitish

    2003-01-01

    In the present study Tsallis and Renyi entropy methods were used to study the electric activity of brain following hypoxic-ischemic (HI) injury. We investigated the performances of these parameterized information measures in describing the electroencephalogram (EEG) signal of controlled experimental animal HI injury. The results show that (a): compared with Shannon and Renyi entropy, the parameterized Tsallis entropy acts like a spatial filter and the information rate can either tune to long range rhythms or to short abrupt changes, such as bursts or spikes during the beginning of recovery, by the entropic index q; (b): Renyi entropy is a compact and predictive indicator for monitoring the physiological changes during the recovery of brain injury. There is a reduction in the Renyi entropy after brain injury followed by a gradual recovery upon resuscitation

  3. Randomized Controlled Trial of Sildenafil for Preventing Recurrent Ischemic Priapism in Sickle Cell Disease

    Science.gov (United States)

    Burnett, Arthur L.; Anele, Uzoma A.; Trueheart, Irene N.; Strouse, John J.; Casella, James F.

    2014-01-01

    BACKGROUND Successful preventive therapy for ischemic priapism, a disorder of penile erection with major physical and psychologic consequences, is limited. We conducted a randomized, double-blind, placebo-controlled clinical trial to assess the efficacy and safety of sildenafil by a systematic dosing protocol to prevent recurrent ischemic priapism associated with sickle cell disease. METHODS Thirteen patients with sickle cell disease reporting priapism recurrences at least twice weekly were randomized to receive sildenafil 50 mg or placebo daily, unassociated with sleep or sexual activity, for 8 weeks, followed by open-label use of this sildenafil regimen for an additional 8 weeks. RESULTS Priapism frequency reduction by 50% did not differ between sildenafil and placebo groups by intention-to-treat or per protocol analyses (P = 1.0). However, during open-label assessment, 5 of 8 patients (62.5%) by intention-to-treat analysis and 2 of 3 patients (66.7%) by per protocol analysis met this primary efficacy outcome. No significant differences were found between study groups in rates of adverse effects, although major priapism episodes were decreased 4-fold in patients monitored “on-treatment.” CONCLUSIONS Sildenafil use by systematic dosing may offer a strategy to prevent recurrent ischemic priapism in patients with sickle cell disease. PMID:24680796

  4. Brain hemorrhage after endovascular reperfusion therapy of ischemic stroke: a threshold-finding whole-brain perfusion CT study

    Science.gov (United States)

    Renú, Arturo; Laredo, Carlos; Tudela, Raúl; Urra, Xabier; Lopez-Rueda, Antonio; Llull, Laura; Oleaga, Laura; Chamorro, Ángel

    2015-01-01

    Endovascular reperfusion therapy is increasingly used for acute ischemic stroke treatment. The occurrence of parenchymal hemorrhage is clinically relevant and increases with reperfusion therapies. Herein we aimed to examine the optimal perfusion CT-derived parameters and the impact of the duration of brain ischemia for the prediction of parenchymal hemorrhage after endovascular therapy. A cohort of 146 consecutive patients with anterior circulation occlusions and treated with endovascular reperfusion therapy was analyzed. Recanalization was assessed at the end of reperfusion treatment, and the rate of parenchymal hemorrhage at follow-up neuroimaging. In regression analyses, cerebral blood volume and cerebral blood flow performed better than Delay Time maps for the prediction of parenchymal hemorrhage. The most informative thresholds (receiver operating curves) for relative cerebral blood volume and relative cerebral blood flow were values lower than 2.5% of normal brain. In binary regression analyses, the volume of regions with reduced relative cerebral blood volume and/or relative cerebral blood flow was significantly associated with an increased risk of parenchymal hemorrhage, as well as delayed vessel recanalization. These results highlight the relevance of the severity and duration of ischemia as drivers of blood-brain barrier disruption in acute ischemic stroke and support the role of perfusion CT for the prediction of parenchymal hemorrhage. PMID:26661254

  5. Deficiency in Serine Protease Inhibitor Neuroserpin Exacerbates Ischemic Brain Injury by Increased Postischemic Inflammation

    Science.gov (United States)

    Ludewig, Peter; Bernreuther, Christian; Krasemann, Susanne; Arunachalam, Priyadharshini; Gerloff, Christian; Glatzel, Markus; Magnus, Tim

    2013-01-01

    The only approved pharmacological treatment for ischemic stroke is intravenous administration of plasminogen activator (tPA) to re-canalize the occluded cerebral vessel. Not only reperfusion but also tPA itself can induce an inflammatory response. Microglia are the innate immune cells of the central nervous system and the first immune cells to become activated in stroke. Neuroserpin, an endogenous inhibitor of tPA, is up-regulated following cerebral ischemia. To examine neuroserpin-dependent mechanisms of neuroprotection in stroke, we studied neuroserpin deficient (Ns−/−) mice in an animal model of temporal focal ischemic stroke. Infarct size and neurological outcome were worse in neuroserpin deficient mice even though the fibrinolytic activity in the ischemic brain was increased. The increased infarct size was paralleled by a selective increase in proinflammatory microglia activation in Ns−/− mice. Our results show excessive microglial activation in Ns−/− mice mediated by an increased activity of tPA. This activation results in a worse outcome further underscoring the potential detrimental proinflammatory effects of tPA. PMID:23658802

  6. [Polymorphism of brain derived neurotrophic factor and recovery of functions after ischemic stroke].

    Science.gov (United States)

    Liepert, J; Heller, A; Behnisch, G; Schoenfeld, A

    2015-10-01

    After ischemic stroke, many factors influence the restitution of functions. In particular they include the patient age, the initial stroke severity and the presence of cognitive and neuropsychological deficits. In this study we investigated whether a polymorphism in the gene encoding for brain derived neurotrophic factor (BDNF) influences improvements of motor functions and everyday activities. Patients with subacute ischemic stroke (n = 67) were examined at the beginning of an inpatient neurological rehabilitation, after 4 weeks of treatment and after 6 months. The Barthel index (BI) and the Rivermead motor assessment (RMA) were used to measure motor functions and everyday activities. Patients were allocated to three groups (valine [Val]/valine, val/methionine [Met] and Met/Met) depending on the BDNF polymorphism at codon 66. The 3 groups (Val/Val, n = 34 patients, Val/Met, n = 26 and Met/Met, n = 7) showed significant improvements in BI and RMA after 4 weeks and after 6 months as compared to the preceding measurements. The BI and RMA were positively correlated. The three groups did not differ with respect to the extent of improvement. After ischemic stroke, motor functions and everyday activities improved continuously over a period of at least 6 months. The BDNF polymorphism did not influence this development.

  7. Systematic Analysis of RNA Regulatory Network in Rat Brain after Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Juan Liu

    2018-01-01

    Full Text Available Although extensive studies have identified large number of microRNAs (miRNAs and long noncoding RNAs (lncRNAs in ischemic stroke, the RNA regulation network response to focal ischemia remains poorly understood. In this study, we simultaneously interrogate the expression profiles of lncRNAs, miRNAs, and mRNAs changes during focal ischemia induced by transient middle cerebral artery occlusion. A set of 1924 novel lncRNAs were identified and may involve brain injury and DNA repair as revealed by coexpression network analysis. Furthermore, many short interspersed elements (SINE mediated lncRNA:mRNA duplexes were identified, implying that lncRNAs mediate Staufen1-mediated mRNA decay (SMD which may play a role during focal ischemia. Moreover, based on the competitive endogenous RNA (ceRNA hypothesis, a stroke regulatory ceRNA network which reveals functional lncRNA:miRNA:mRNA interactions was revealed in ischemic stroke. In brief, this work reports a large number of novel lncRNAs responding to focal ischemia and constructs a systematic RNA regulation network which highlighted the role of ncRNAs in ischemic stroke.

  8. RESVERATROL PRECONDITIONING INDUCES A NOVEL EXTENDED WINDOW OF ISCHEMIC TOLERANCE IN THE MOUSE BRAIN

    Science.gov (United States)

    Koronowski, Kevin B.; Dave, Kunjan R.; Saul, Isabel; Camarena, Vladimir; Thompson, John W.; Neumann, Jake T.; Young, Juan I.; Perez-Pinzon, Miguel A.

    2015-01-01

    Background and Purpose Prophylactic treatments that afford neuroprotection against stroke may emerge from the field of preconditioning. Resveratrol mimics ischemic preconditioning, reducing ischemic brain injury when administered two days prior to global ischemia in rats. This protection is linked to Sirt1 and enhanced mitochondrial function possibly through its repression of UCP2. BDNF is another neuroprotective protein associated with Sirt1. In this study we sought to identify the conditions of resveratrol preconditioning (RPC) that most robustly induce neuroprotection against focal ischemia in mice. Methods We tested four different RPC paradigms against a middle cerebral artery occlusion (MCAo) model of stroke. Infarct volume and neurological score were calculated 24 hours following MCAo. Sirt1-chromatin binding was evaluated by ChIP-qPCR. Percoll gradients were used to isolate synaptic fractions and changes in protein expression were determined via Western blot analysis. BDNF concentration was measured using a BDNF-specific ELISA assay. Results While repetitive RPC induced neuroprotection from MCAo, strikingly one application of RPC 14 days prior to MCAo showed the most robust protection, reducing infarct volume by 33% and improving neurological score by 28%. Fourteen days following RPC, Sirt1 protein was increased 1.5 fold and differentially bound to the UCP2 and BDNF promoter regions. Accordingly, synaptic UCP2 protein decreased by 23% and cortical BDNF concentration increased 26%. Conclusions RPC induces a novel extended window of ischemic tolerance in the brain that lasts for at least 14 days. Our data suggest that this tolerance may be mediated by Sirt1, through upregulation of BDNF and downregulation of UCP2. PMID:26159789

  9. Impaired cerebral autoregulation and brain injury in newborns with hypoxic-ischemic encephalopathy treated with hypothermia.

    Science.gov (United States)

    Massaro, An N; Govindan, R B; Vezina, Gilbert; Chang, Taeun; Andescavage, Nickie N; Wang, Yunfei; Al-Shargabi, Tareq; Metzler, Marina; Harris, Kari; du Plessis, Adre J

    2015-08-01

    Impaired cerebral autoregulation may contribute to secondary injury in newborns with hypoxic-ischemic encephalopathy (HIE). Continuous, noninvasive assessment of cerebral pressure autoregulation can be achieved with bedside near-infrared spectroscopy (NIRS) and systemic mean arterial blood pressure (MAP) monitoring. This study aimed to evaluate whether impaired cerebral autoregulation measured by NIRS-MAP monitoring during therapeutic hypothermia and rewarming relates to outcome in 36 newborns with HIE. Spectral coherence analysis between NIRS and MAP was used to quantify changes in the duration [pressure passivity index (PPI)] and magnitude (gain) of cerebral autoregulatory impairment. Higher PPI in both cerebral hemispheres and gain in the right hemisphere were associated with neonatal adverse outcomes [death or detectable brain injury by magnetic resonance imaging (MRI), P NIRS-MAP monitoring of cerebral autoregulation can provide an ongoing physiological biomarker that may help direct care in perinatal brain injury. Copyright © 2015 the American Physiological Society.

  10. Changes in cerebral oxidative metabolism during neonatal seizures following hypoxic ischemic brain injury

    Directory of Open Access Journals (Sweden)

    Subhabrata Mitra

    2016-08-01

    Full Text Available Seizures are common following hypoxic ischemic brain injury in newborn infants. Prolonged or recurrent seizures have been shown to exacerbate neuronal damage in the developing brain, however the precise mechanism is not fully understood. Cytochrome-c-oxidase is responsible for more than 90% of ATP production inside mitochondria. Using a novel broadband near-infrared spectroscopy system we measured the concentration changes in the oxidation state of cerebral cytochrome-c-oxidase (Δ[oxCCO] and hemodynamics during recurrent neonatal seizures following hypoxic ischemic encephalopathy in a newborn infant. A rapid increase in Δ[oxCCO] was noted at the onset of seizures along with a rise in the baseline of amplitude integrated electro-encephalogram (aEEG. Cerebral oxygenation and cerebral blood volume fell just prior to the seizure onset but recovered rapidly during seizures. Δ[oxCCO] during seizures correlated with changes in mean EEG voltage indicating an increase in neuronal activation and energy demand. The progressive decline in the Δ[oxCCO] baseline during seizures suggests a progressive decrease of mitochondrial oxidative metabolism.

  11. Multiple actions of the coumarine derivative cloricromene and its protective effects on ischemic brain injury.

    Science.gov (United States)

    Calapai, G; Squadrito, F; Rizzo, A; Marciano, M C; Campo, G M; Caputi, A P

    1995-02-01

    The effects of different doses (0.25, 0.5, 1 and 2 mg/kg i.p.) of cloricromene, a coumarine derivative, have been investigated on brain malondialdehyde levels, brain edema, myeloperoxidase activity, survival, locomotor hyperactivity and hippocampal neuronal loss following transient cerebral ischemia induced by temporary bilateral carotid occlusion in the Mongolian gerbil. Cloricromene reduced brain lipid peroxidation, measured through the evaluation of malondialdehyde (-82.9% with the highest dose), and the formation of post-ischemic brain edema, evaluated by water content. The increase in myeloperoxidase activity observed in the hippocampus of postischemic animals was also reduced: 0.7 +/- 0.3 U x 10(-3) vs. 3.3 +/- 0.3 U x 10(-3)/g tissue. The same treatment increased survival and reduced hyperactivity linked to neurodegeneration induced by cerebral ischemia and reperfusion. Histological observations of the pyramidal layer of CA1 showed a reduction of neuronal loss in animals that received the drug before occlusion but not in those that were treated after the occlusion. These results show that cloricromene, a drug with multiple actions, improves brain injury induced by transient cerebral ischemia.

  12. [Revelation of the circumstances of the accident vascular arterial ischemic brain in at term or near-term and referral].

    Science.gov (United States)

    Cneude, F; Diependaele, J-F; Chabernaud, J-L

    2017-09-01

    The neonatal arterial ischemic stroke is an emergency. Recurrent focal seizures, generally occurring in the first 24-72 hours after birth, are the commonest first clinical signs. When neonatal arterial ischemic stroke is suspected, optimal initial management involves careful supportive care including treatment of clinical and frequent or prolonged subclinical seizures, correction of the possible metabolic disorders and their prevention. Contrary to hypoxic ischemic encephalopathy, therapeutic hypothermia is not indicated. This newborn requires emergent transfer to a neonatal intensive care unit for the confirmation of the diagnosis by means of a specialized neonatal transport team. © 2017 Elsevier Masson SAS. Tous droits réservés.

  13. Neurobehavioral Assessments in a Mouse Model of Neonatal Hypoxic-ischemic Brain Injury.

    Science.gov (United States)

    Kim, MinGi; Yu, Ji Hea; Seo, Jung Hwa; Shin, Yoon-Kyum; Wi, Soohyun; Baek, Ahreum; Song, Suk-Young; Cho, Sung-Rae

    2017-11-24

    We performed unilateral carotid artery occlusion on CD-1 mice to create a neonatal hypoxic-ischemic (HI) model and investigated the effects of neonatal HI brain injury by studying neurobehavioral functions in these mice compared to non-operated (i.e., normal) mice. During the study, Rice-Vannucci's method was used to induce neonatal HI brain damage in postnatal day 7-10 (P7-10) mice. The HI operation was performed on the pups by unilateral carotid artery ligation and exposure to hypoxia (8% O2 and 92% N2 for 90 min). One week after the operation, the damaged brains were evaluated with the naked eye through the semi-transparent skull and were categorized into subgroups based on the absence ("no cortical injury" group) or presence ("cortical injury" group) of cortical injury, such as a lesion in the right hemisphere. On week 6, the following neurobehavioral tests were performed to evaluate the cognitive and motor functions: passive avoidance task (PAT), ladder walking test, and grip strength test. These behavioral tests are helpful in determining the effects of neonatal HI brain injury and are used in other mouse models of neurodegenerative diseases. In this study, neonatal HI brain injury mice showed motor deficits that corresponded to right hemisphere damage. The behavioral test results are relevant to the deficits observed in human neonatal HI patients, such as cerebral palsy or neonatal stroke patients. In this study, a mouse model of neonatal HI brain injury was established and showed different degrees of motor deficits and cognitive impairment compared to non-operated mice. This work provides basic information on the HI mouse model. MRI images demonstrate the different phenotypes, separated according to the severity of brain damage by motor and cognitive tests.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Non-Gaussian diffusion imaging for enhanced contrast of brain tissue affected by ischemic stroke.

    Science.gov (United States)

    Grinberg, Farida; Farrher, Ezequiel; Ciobanu, Luisa; Geffroy, Françoise; Le Bihan, Denis; Shah, N Jon

    2014-01-01

    Recent diffusion MRI studies of stroke in humans and animals have shown that the quantitative parameters characterising the degree of non-Gaussianity of the diffusion process are much more sensitive to ischemic changes than the apparent diffusion coefficient (ADC) considered so far as the "gold standard". The observed changes exceeded that of the ADC by a remarkable factor of 2 to 3. These studies were based on the novel non-Gaussian methods, such as diffusion kurtosis imaging (DKI) and log-normal distribution function imaging (LNDFI). As shown in our previous work investigating the animal stroke model, a combined analysis using two methods, DKI and LNDFI provides valuable complimentary information. In the present work, we report the application of three non-Gaussian diffusion models to quantify the deviations from the Gaussian behaviour in stroke induced by transient middle cerebral artery occlusion in rat brains: the gamma-distribution function (GDF), the stretched exponential model (SEM), and the biexponential model. The main goal was to compare the sensitivity of various non-Gaussian metrics to ischemic changes and to investigate if a combined application of several models will provide added value in the assessment of stroke. We have shown that two models, GDF and SEM, exhibit a better performance than the conventional method and allow for a significantly enhanced visualization of lesions. Furthermore, we showed that valuable information regarding spatial properties of stroke lesions can be obtained. In particular, we observed a stratified cortex structure in the lesions that were well visible in the maps of the GDF and SEM metrics, but poorly distinguishable in the ADC-maps. Our results provided evidence that cortical layers tend to be differently affected by ischemic processes.

  16. Non-Gaussian diffusion imaging for enhanced contrast of brain tissue affected by ischemic stroke.

    Directory of Open Access Journals (Sweden)

    Farida Grinberg

    Full Text Available Recent diffusion MRI studies of stroke in humans and animals have shown that the quantitative parameters characterising the degree of non-Gaussianity of the diffusion process are much more sensitive to ischemic changes than the apparent diffusion coefficient (ADC considered so far as the "gold standard". The observed changes exceeded that of the ADC by a remarkable factor of 2 to 3. These studies were based on the novel non-Gaussian methods, such as diffusion kurtosis imaging (DKI and log-normal distribution function imaging (LNDFI. As shown in our previous work investigating the animal stroke model, a combined analysis using two methods, DKI and LNDFI provides valuable complimentary information. In the present work, we report the application of three non-Gaussian diffusion models to quantify the deviations from the Gaussian behaviour in stroke induced by transient middle cerebral artery occlusion in rat brains: the gamma-distribution function (GDF, the stretched exponential model (SEM, and the biexponential model. The main goal was to compare the sensitivity of various non-Gaussian metrics to ischemic changes and to investigate if a combined application of several models will provide added value in the assessment of stroke. We have shown that two models, GDF and SEM, exhibit a better performance than the conventional method and allow for a significantly enhanced visualization of lesions. Furthermore, we showed that valuable information regarding spatial properties of stroke lesions can be obtained. In particular, we observed a stratified cortex structure in the lesions that were well visible in the maps of the GDF and SEM metrics, but poorly distinguishable in the ADC-maps. Our results provided evidence that cortical layers tend to be differently affected by ischemic processes.

  17. Blood flow and vascular reactivity in collaterally perfused brain tissue. Evidence of an ischemic penumbra in patients with acute stroke

    DEFF Research Database (Denmark)

    Olsen, T S; Larsen, B; Herning, M

    1983-01-01

    In a group of 48 patients with completed stroke, 8 patients had viable collaterally perfused brain tissue which was accessible for rCBF recordings with a two dimensional technique. All 8 had deep subcortical infarcts on CT-scan, and angiographic occlusion of the arteries normally supplying...... the infarcted territory. The brain tissue overlying the deep infarcts appeared normal on CT-scan and was supplied by collateral circulation. rCBF was measured in all within 72 hours after the stroke. The intra-carotid Xe-133 injection method and a 254 multidetector camera were used to study rCBF. Relatively...... ischemic low flow areas were a constant finding in the collaterally perfused tissue. In 6 of the patients, the collaterally perfused part of the brain had low flow values comparable to those of an "ischemic penumbra" (viable, but functionally depressed brain tissue due to inadequate perfusion...

  18. Permanent brain ischemia induces marked increments in hsp72 expression and local protein synthesis in synapses of the ischemic hemisphere.

    Science.gov (United States)

    Mariucci, Giuseppina; Tantucci, Michela; Giuditta, Antonio; Ambrosini, Maria Vittoria

    2007-03-19

    Transient focal ischemia induced in rat brain by occlusion of the middle cerebral artery (MCAo) elicits a generalized induction of the 72 kDa heat-shock protein (hsp72) heralding functional recovery. As this effect implies activation of protein synthesis, and local systems of protein synthesis are present in brain synapses, and may be analyzed in preparations of brain synaptosomes, we evaluated hsp72 expression and protein synthesis in synaptosomal fractions of spontaneously hypertensive rats (SHRs) subjected to permanent MCAo. SHRs were randomly divided in ischemics and sham controls, anaesthesia controls and passive controls. Focal ischemia was induced under chloral hydrate anaesthesia by unilateral permanent MCAo. Protein synthesis was determined by [35S]methionine incorporation into synaptosomal proteins from ischemic and contralateral cortex/striatum, and from cerebellum. Hsp72 expression was measured in the same fractions by immunoblotting. Our data demonstrate that under these conditions synaptic hsp72 markedly increases in the ischemic hemisphere 1 and 2 days after MCAo, progressively declining in the following 2 days, while no significant change occurs in control rats. In addition, in the ischemic hemisphere the rate of synaptic protein synthesis increases more than two-fold between 1 and 4 days after MCAo, without showing signs of an impending decline. The present data provide the first demonstration that synaptic protein synthesis is massively involved in brain plastic events elicited by permanent focal ischemia.

  19. Ubiquitin C-Terminal Hydrolase-L1 as a Biomarker for Ischemic and Traumatic Brain Injury in Rats

    Science.gov (United States)

    2010-01-01

    Mense, M., Bauman, R. & Tortella, F. (2003) The effect of voluntary exercise exposure on histological and neurobehavioral outcomes after ischemic brain...Proteomics analysis of the Alzheimer’s disease hippocampal proteome. J. Alzheimers Dis., 11, 153–164. Tongaonkar, P., Chen, L., Lambertson, D., Ko

  20. Hypoxic ischemic brain injury following in hospital cardiac arrest - lessons from autopsy.

    Science.gov (United States)

    Hinduja, Archana; Gupta, Harsh; Yang, Ju Dong; Onteddu, Sanjeeva

    2014-03-01

    Hypoxic ischemic brain injury (HIBI) is the most decisive factor in determining the outcome following a cardiac arrest. After an arrest, neuronal death may be early or delayed. The aim of our study is to determine the prevalence and predictors of HIBI on autopsy following an in hospital cardiac arrest. We retrospectively reviewed the medical records of patients who sustained an in hospital cardiorespiratory arrest and underwent autopsy following in hospital mortality at our tertiary care medical center from January 2004-June 2012. These patients were identified from the autopsy registry maintained by the Department of Pathology and were classified into two groups based on the presence or absence of HIBI on autopsy. We compared the baseline demographics, risk factors, total duration of cardiopulmonary resuscitation, number of resuscitative events and survival time between both groups. Multivariate logistic regression analysis was performed to identify predictors of hypoxic ischemic injury following cardiac arrest. Out of 71 patients identified during this study period, 21% had evidence of HIBI on autopsy. On univariate analysis, predictors of HIBI were prolonged hospital stay, prolonged survival time following an arrest and a slight increased trend following multiple resuscitative events. On multivariate analysis, prolonged survival time was the only significant predictor of HIBI. Similar to other prognostication cardiac arrest studies, there were minimal predictors of early neuronal injury even on autopsy. Published by Elsevier Ltd.

  1. Early Blood-Brain Barrier Disruption after Mechanical Thrombectomy in Acute Ischemic Stroke.

    Science.gov (United States)

    Shi, Zhong-Song; Duckwiler, Gary R; Jahan, Reza; Tateshima, Satoshi; Szeder, Viktor; Saver, Jeffrey L; Kim, Doojin; Sharma, Latisha K; Vespa, Paul M; Salamon, Noriko; Villablanca, J Pablo; Viñuela, Fernando; Feng, Lei; Loh, Yince; Liebeskind, David S

    2018-02-27

    The impact of blood-brain barrier (BBB) disruption can be detected by intraparenchymal hyperdense lesion on the computed tomography (CT) scan after endovascular stroke therapy. The purpose of this study was to determine whether early BBB disruption predicts intracranial hemorrhage and poor outcome in patients with acute ischemic stroke treated with mechanical thrombectomy. We analyzed patients with anterior circulation stroke treated with mechanical thrombectomy and identified BBB disruption on the noncontrast CT images immediately after endovascular treatment. Follow-up CT or magnetic resonance imaging scan was performed at 24 hours to assess intracranial hemorrhage. We dichotomized patients into those with moderate BBB disruption versus those with minor BBB disruption and no BBB disruption. We evaluated the association of moderate BBB disruption after mechanical thrombectomy with intracranial hemorrhage and clinical outcomes. Moderate BBB disruption after mechanical thrombectomy was found in 56 of 210 patients (26.7%). Moderate BBB disruption was independently associated with higher rates of hemorrhagic transformation (OR 25.33; 95% CI 9.93-64.65; P disruption with intracranial hemorrhage remained in patients with successful reperfusion after mechanical thrombectomy. The location of BBB disruption was not associated with intracranial hemorrhage and poor outcome. Moderate BBB disruption is common after mechanical thrombectomy in a quarter of patients with acute ischemic stroke and increases the risk of intracranial hemorrhage and poor outcome. Copyright © 2018 by the American Society of Neuroimaging.

  2. Molecular dialogues between the ischemic brain and the peripheral immune system: Dualistic roles in injury and repair

    Science.gov (United States)

    An, Chengrui; Shi, Yejie; Li, Peiying; Hu, Xiaoming; Gan, Yu; Stetler, Ruth A.; Leak, Rehana K.; Gao, Yanqin; Sun, Bao-Liang; Zheng, Ping; Chen, Jun

    2014-01-01

    Immune and inflammatory responses actively modulate the pathophysiological processes of acute brain injuries such as stroke. Soon after the onset of stroke, signals such as brain-derived antigens, danger-associated molecular patterns (DAMPs), cytokines, and chemokines are released from the injured brain into the systemic circulation. The injured brain also communicates with peripheral organs through the parasympathetic and sympathetic branches of the autonomic nervous system. Many of these diverse signals not only activate resident immune cells in the brain, but also trigger robust immune responses in the periphery. Peripheral immune cells then migrate toward the site of injury and release additional cytokines, chemokines, and other molecules, causing further disruptive or protective effects in the ischemic brain. Bidirectional communication between the injured brain and the peripheral immune system is now known to regulate the progression of stroke pathology as well as tissue repair. In the end, this exquisitely coordinated crosstalk helps determine the fate of animals after stroke. This article reviews the literature on ischemic brain-derived signals through which peripheral immune responses are triggered, and the potential impact of these peripheral responses on brain injury and repair. Pharmacological strategies and cell-based therapies that target the dialogue between the brain and peripheral immune system show promise as potential novel treatments for stroke. PMID:24374228

  3. Burden and outcome of prevalent ischemic brain disease in a national acute stroke registry.

    Science.gov (United States)

    Koton, Silvia; Tsabari, Rakefet; Molshazki, Noa; Kushnir, Moshe; Shaien, Radi; Eilam, Anda; Tanne, David

    2013-12-01

    Previous overt stroke and subclinical stroke are frequent in patients with stroke; yet, their clinical significance and effects on stroke outcome are not clear. We studied the burden and outcome after acute ischemic stroke by prevalent ischemic brain disease in a national registry of hospitalized patients with acute stroke. Patients with ischemic stroke in the National Acute Stroke Israeli prospective hospital-based registry (February to March 2004, March to April 2007, and April to May 2010) with information on previous overt stroke and subclinical stroke per computed tomography/MRI (n=3757) were included. Of them, a subsample (n=787) was followed up at 3 months. Logistic regression models were computed for outcomes in patients with prior overt stroke or subclinical stroke, compared with patients with first stroke, adjusting for age, sex, vascular risk factors, stroke severity, and clinical classification. Two-thirds of patients had a prior overt stroke or subclinical stroke. Death rates were similar for patients with and without prior stroke. Adjusted odds ratios (OR; 95% confidence interval [CI]) for disability were increased for patients with prior overt stroke (OR, 1.31; 95% CI, 1.03-1.66) and subclinical stroke (OR, 1.45; 95% CI, 1.16-1.82). Relative odds of Barthel Index≤60 for patients with prior overt stroke (OR, 2.04; 95% CI, 1.14-3.68) and with prior subclinical stroke (OR, 2.04; 95% CI, 1.15-3.64) were twice higher than for patients with a first stroke. ORs for dependency were significantly increased for patients with prior overt stroke (OR, 1.95; 95% CI, 1.19-3.20) but not for those with subclinical stroke (OR, 1.36; 95% CI, 0.84-2.19). In our national cohort of patients with acute ischemic stroke, nearly two thirds had a prior overt stroke or subclinical stroke. Risk of poor functional outcomes was increased for patients with prior stroke, both overt and subclinical.

  4. Role of brain natriuretic peptide as a novel prognostic biomarker in acute ischemic stroke

    Directory of Open Access Journals (Sweden)

    Bindu Menon

    2016-01-01

    Full Text Available Aim: We investigated to study the prognostic importance of brain natriuretic peptide (BNP in ischemic stroke. Materials and Methods: We prospectively enrolled 100 patients with acute ischemic stroke and measured plasma BNP levels and compared with age- and sex-matched healthy controls. Risk factors, biochemical parameters, lipid profile, carotid and vertebral Doppler, imaging, and cardiac evaluation were done. Stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS score on admission and functional disability by Barthel Index (BI at 3 months. Ischemic stroke subtype was classified according to the Oxfordshire Community Stroke Project (OCSP. Data were entered in MS Excel, and appropriate statistical analysis was done using the SPSS software version 21.0. A P = 0.05 was considered as significant. Results: Mean age of patients was 55.17 ± 11.37 years with a male:female ratio 3:1. OCSP showed total anterior circulation infarct (TACI 35, partial anterior circulation infarct 9, lacunar infarct 12, and posterior circulation infarct 44. NIHSS on admission was average 10 ± 7 and BI was 57 ± 30. BNP in patients (435 ng/ml was very high as compared to controls (<60 ng/ml (P < 0.001. There was a positive correlation between age and BNP (R2 = 0.34; P < 0.00; NIHSS and BNP (R2 = 0.255; P < 0.01, negative correlation between BI and BNP (R2 = −0.064; P < 0.01. Mean BNP levels across the OCSP showed higher values in TACI (F = 4.609 P = 0.005. Regression analysis showed that BNP can predict BI which was statistically significant. Conclusion: Plasma BNP levels was significantly elevated in patients with ischemic stroke. Our study concludes that high BNP levels are seen in large anterior circulation stroke and is a predictor for the poor functional outcome at 3 months. Determination of BNP levels as a biomarker could be helpful in predicting the outcome in stroke patients.

  5. Implications of MMP9 for Blood Brain Barrier Disruption And Hemorrhagic Transformation Following Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Renee Jade Turner

    2016-03-01

    Full Text Available Numerous studies have documented increases in matrix metalloproteinases (MMPs, specifically MMP-9 levels following stroke, with such perturbations associated with disruption of the blood brain barrier (BBB, increased risk of hemorrhagic complications and worsened outcome. Despite this, controversy remains as to which cells release MMP-9 at the normal and pathological BBB, with even less clarity in the context of stroke. This may be further complicated by the influence of tissue plasminogen activator (tPA treatment. The aim of the present review is to examine the relationship between neutrophils, MMP-9 and tPA following ischemic stroke to elucidate which cells are responsible for the increases in MMP-9 and resultant barrier changes and hemorrhage observed following stroke.

  6. Synergistic Association of Valproate and Resveratrol Reduces Brain Injury in Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Lara Faggi

    2018-01-01

    Full Text Available Histone deacetylation, together with altered acetylation of NF-κB/RelA, encompassing the K310 residue acetylation, occur during brain ischemia. By restoring the normal acetylation condition, we previously reported that sub-threshold doses of resveratrol and entinostat (MS-275, respectively, an activator of the AMP-activated kinase (AMPK-sirtuin 1 pathway and an inhibitor of class I histone deacetylases (HDACs, synergistically elicited neuroprotection in a mouse model of ischemic stroke. To improve the translational power of this approach, we investigated the efficacy of MS-275 replacement with valproate, the antiepileptic drug also reported to be a class I HDAC blocker. In cortical neurons previously exposed to oxygen glucose deprivation (OGD, valproate elicited neuroprotection at 100 nmol/mL concentration when used alone and at 1 nmol/mL concentration when associated with resveratrol (3 nmol/mL. Resveratrol and valproate restored the acetylation of histone H3 (K9/18, and they reduced the RelA(K310 acetylation and the Bim level in neurons exposed to OGD. Chromatin immunoprecipitation analysis showed that the synergistic drug association impaired the RelA binding to the Bim promoter, as well as the promoter-specific H3 (K9/18 acetylation. In mice subjected to 60 min of middle cerebral artery occlusion (MCAO, the association of resveratrol 680 µg/kg and valproate 200 µg/kg significantly reduced the infarct volume as well as the neurological deficits. The present study suggests that valproate and resveratrol may represent a promising ready-to-use strategy to treat post-ischemic brain damage.

  7. FLAIR lesion segmentation: Application in patients with brain tumors and acute ischemic stroke

    Energy Technology Data Exchange (ETDEWEB)

    Artzi, Moran, E-mail: artzimy@gmail.com [The Functional Brain Center, The Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel); Aizenstein, Orna, E-mail: ornaaize@gmail.com [The Functional Brain Center, The Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Jonas-Kimchi, Tali, E-mail: talijk@tlvmc.gov.il [Radiology Department, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Myers, Vicki, E-mail: vicki_myers@hotmail.com [The Functional Brain Center, The Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Hallevi, Hen, E-mail: hen.hallevi@gmail.com [Neurology Department, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Ben Bashat, Dafna, E-mail: dafnab@tlvmc.gov.il [The Functional Brain Center, The Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv (Israel)

    2013-09-15

    Background: Lesion size in fluid attenuation inversion recovery (FLAIR) images is an important clinical parameter for patient assessment and follow-up. Although manual delineation of lesion areas considered as ground truth, it is time-consuming, highly user-dependent and difficult to perform in areas of indistinct borders. In this study, an automatic methodology for FLAIR lesion segmentation is proposed, and its application in patients with brain tumors undergoing therapy; and in patients following stroke is demonstrated. Materials and methods: FLAIR lesion segmentation was performed in 57 magnetic resonance imaging (MRI) data sets obtained from 44 patients: 28 patients with primary brain tumors; 5 patients with recurrent-progressive glioblastoma (rGB) who were scanned longitudinally during anti-angiogenic therapy (18 MRI scans); and 11 patients following ischemic stroke. Results: FLAIR lesion segmentation was obtained in all patients. When compared to manual delineation, a high visual similarity was observed, with an absolute relative volume difference of 16.80% and 20.96% and a volumetric overlap error of 24.87% and 27.50% obtained for two raters: accepted values for automatic methods. Quantitative measurements of the segmented lesion volumes were in line with qualitative radiological assessment in four patients who received anti-anogiogenic drugs. In stroke patients the proposed methodology enabled identification of the ischemic lesion and differentiation from other FLAIR hyperintense areas, such as pre-existing disease. Conclusion: This study proposed a replicable methodology for FLAIR lesion detection and quantification and for discrimination between lesion of interest and pre-existing disease. Results from this study show the wide clinical applications of this methodology in research and clinical practice.

  8. Exploratory Use of Decision Tree Analysis in Classification of Outcome in Hypoxic–Ischemic Brain Injury

    Directory of Open Access Journals (Sweden)

    Thanh G. Phan

    2018-03-01

    Full Text Available BackgroundPrognostication following hypoxic ischemic encephalopathy (brain injury is important for clinical management. The aim of this exploratory study is to use a decision tree model to find clinical and MRI associates of severe disability and death in this condition. We evaluate clinical model and then the added value of MRI data.MethodThe inclusion criteria were as follows: age ≥17 years, cardio-respiratory arrest, and coma on admission (2003–2011. Decision tree analysis was used to find clinical [Glasgow Coma Score (GCS, features about cardiac arrest, therapeutic hypothermia, age, and sex] and MRI (infarct volume associates of severe disability and death. We used the area under the ROC (auROC to determine accuracy of model. There were 41 (63.7% males patients having MRI imaging with the average age 51.5 ± 18.9 years old. The decision trees showed that infarct volume and age were important factors for discrimination between mild to moderate disability and severe disability and death at day 0 and day 2. The auROC for this model was 0.94 (95% CI 0.82–1.00. At day 7, GCS value was the only predictor; the auROC was 0.96 (95% CI 0.86–1.00.ConclusionOur findings provide proof of concept for further exploration of the role of MR imaging and decision tree analysis in the early prognostication of hypoxic ischemic brain injury.

  9. FLAIR lesion segmentation: Application in patients with brain tumors and acute ischemic stroke

    International Nuclear Information System (INIS)

    Artzi, Moran; Aizenstein, Orna; Jonas-Kimchi, Tali; Myers, Vicki; Hallevi, Hen; Ben Bashat, Dafna

    2013-01-01

    Background: Lesion size in fluid attenuation inversion recovery (FLAIR) images is an important clinical parameter for patient assessment and follow-up. Although manual delineation of lesion areas considered as ground truth, it is time-consuming, highly user-dependent and difficult to perform in areas of indistinct borders. In this study, an automatic methodology for FLAIR lesion segmentation is proposed, and its application in patients with brain tumors undergoing therapy; and in patients following stroke is demonstrated. Materials and methods: FLAIR lesion segmentation was performed in 57 magnetic resonance imaging (MRI) data sets obtained from 44 patients: 28 patients with primary brain tumors; 5 patients with recurrent-progressive glioblastoma (rGB) who were scanned longitudinally during anti-angiogenic therapy (18 MRI scans); and 11 patients following ischemic stroke. Results: FLAIR lesion segmentation was obtained in all patients. When compared to manual delineation, a high visual similarity was observed, with an absolute relative volume difference of 16.80% and 20.96% and a volumetric overlap error of 24.87% and 27.50% obtained for two raters: accepted values for automatic methods. Quantitative measurements of the segmented lesion volumes were in line with qualitative radiological assessment in four patients who received anti-anogiogenic drugs. In stroke patients the proposed methodology enabled identification of the ischemic lesion and differentiation from other FLAIR hyperintense areas, such as pre-existing disease. Conclusion: This study proposed a replicable methodology for FLAIR lesion detection and quantification and for discrimination between lesion of interest and pre-existing disease. Results from this study show the wide clinical applications of this methodology in research and clinical practice

  10. MAFB prevents excess inflammation after ischemic stroke by accelerating clearance of damage signals through MSR1.

    Science.gov (United States)

    Shichita, Takashi; Ito, Minako; Morita, Rimpei; Komai, Kyoko; Noguchi, Yoshiko; Ooboshi, Hiroaki; Koshida, Ryusuke; Takahashi, Satoru; Kodama, Tatsuhiko; Yoshimura, Akihiko

    2017-06-01

    Damage-associated molecular patterns (DAMPs) trigger sterile inflammation after tissue injury, but the mechanisms underlying the resolution of inflammation remain unclear. In this study, we demonstrate that common DAMPs, such as high-mobility-group box 1 (HMGB1), peroxiredoxins (PRXs), and S100A8 and S100A9, were internalized through the class A scavenger receptors MSR1 and MARCO in vitro. In ischemic murine brain, DAMP internalization was largely mediated by MSR1. An elevation of MSR1 levels in infiltrating myeloid cells observed 3 d after experimental stroke was dependent on the transcription factor Mafb. Combined deficiency for Msr1 and Marco, or for Mafb alone, in infiltrating myeloid cells caused impaired clearance of DAMPs, more severe inflammation, and exacerbated neuronal injury in a murine model of ischemic stroke. The retinoic acid receptor (RAR) agonist Am80 increased the expression of Mafb, thereby enhancing MSR1 expression. Am80 exhibited therapeutic efficacy when administered, even at 24 h after the onset of experimental stroke. Our findings uncover cellular mechanisms contributing to DAMP clearance in resolution of the sterile inflammation triggered by tissue injury.

  11. Association between neuroserpin and molecular markers of brain damage in patients with acute ischemic stroke.

    Science.gov (United States)

    Rodríguez-González, Raquel; Sobrino, Tomás; Rodríguez-Yáñez, Manuel; Millán, Mónica; Brea, David; Miranda, Elena; Moldes, Octavio; Pérez, Juan; Lomas, David A; Leira, Rogelio; Dávalos, Antoni; Castillo, José

    2011-05-11

    Neuroserpin has shown neuroprotective effects in animal models of cerebral ischemia and has been associated with functional outcome after ischemic stroke. Our aim was to study whether neuroserpin serum levels could be associated to biomarkers of excitotoxicity, inflammation and blood brain barrier disruption. We prospectively included 129 patients with ischemic stroke (58.1% male; mean age, 72.4 ± 9.6 years) not treated with tPA within 12 hours (h) of symptoms onset (mean time, 4.7 ± 2.1 h). Poor functional outcome at 3 months was considered as a modified Rankin scale score >2. Serum levels of neuroserpin, Interleukin 6 (IL-6), Intercellular adhesion molecule-1 (ICAM-1), active Matrix metalloproteinase 9 (MMP-9), and cellular fibronectin (cFn) (determined by ELISA) and glutamate (determined by HPLC) were measured on admission, 24 and 72 h. The main variable was considered the decrease of neuroserpin levels within the first 24 h. ROC analysis was used to select the best predictive value for neuroserpin to predict poor functional outcome due to a lack of linearity. The decrease of neuroserpin levels within the first 24 h was negatively correlated with serum levels at 24 hours of glutamate (r = -0.642), IL-6 (r = -0.678), ICAM-1 (r = -0.345), MMP-9 (r = -0.554) and cFn (r = -0.703) (all P < 0.0001). In the multivariate analysis, serum levels of glutamate (OR, 1.04; CI95%, 1.01-1.06, p = 0.001); IL-6 (OR, 1.4; CI95%, 1.1-1.7, p = 0.001); and cFn (OR, 1.3; CI95%, 1.1-1.6, p = 0.002) were independently associated with a decrease of neuroserpin levels <70 ng/mL at 24 h after adjusting for confounding factors. These findings suggest that neuroprotective properties of neuroserpin may be related to the inhibition of excitotoxicity, inflammation, as well as blood brain barrier disruption that occur after acute ischemic stroke.

  12. Diffusion-weighted MR imaging in animal modil with acute ischemic brain infarction : evaluation of reversible brain injury

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Woo Mok; Chang, Han Won; Cho, Inn Ho; Hah, Jung Sang; Sung, Eon Gi [Yeungnam Univ. College of Medicine, Taegu (Korea, Republic of)

    2001-04-01

    To determine whether the analysis of abnormally high signal intensities in ischemic tissue, as revealed by diffusion-weighted MR imaging (DWI) can be used to evaluate reversible brain lesions in a cat model of acute ischemia. Ten cats were divided into two groups of five (Group I and Group II), and in all animals the middle cerebral artery was temporarily occluded. Group I underwent T2-DWI 30 minutes after occlusion, and Group II 120 minutes after occlusion. In both groups, DWI was performed one hour and 24 hours after reperfusion (at one hour, non-T2-weighted; at 24 hours, T2-weighted). Both occlusion and reperfusion were monitored by {sup 99m}TC-ECD brain perfusion SPECT. All animals were sacrificed 24 hours later and their brain tissue was stained with TTC. Signal intensity ratios (SIR, signifying average signal intensity within the region of interest divided by that in the contralateral, nonischemic, homologous region) of the two groups, as seen on DWI were compared. The percentage of hemispheric lesions occurring in the two groups was also compared. SIR after occlusion of the middle cerebral artery was 1.29 in Group I and 1.59 in Group II. Twenty-four hours after reperfusion, SIR in Group I was higher than in Group II (p<0.01). After occlusion and reperfusion, the percentage of hemispheric lesions in Group I was less than in Group II. For the latter, the percentage of these lesions revealed by TTC staining and T2-weighted imaging was 48% and 59%, respectively, findings distinctly different from those for Group I. In addition, in group I, infarction was revealed by neither TTC staining nor T2-weighted imaging (p<0.01). The use of DWI to evaluate signal intensity ratios can help determine whether or not brain injury after temporary cerebral ischemia is reversible.

  13. Identifying the brain regions associated with acute spasticity in patients diagnosed with an ischemic stroke.

    Science.gov (United States)

    Barlow, Susan J

    2016-06-01

    Spasticity is a common impairment found in patients that have been diagnosed with a stroke. Little is known about the pathophysiology of spasticity at the level of the brain. This retrospective study was performed to identify an association between the area of the brain affected by an ischemic stroke and the presence of acute spasticity. Physical and occupational therapy assessments from all patients (n = 441) that had suffered a stroke and were admitted into a local hospital over a 4-year period were screened for inclusion in this study. Subjects that fit the inclusion criteria were grouped according to the presence (n = 42) or absence (n = 129) of acute spasticity by the Modified Ashworth Scale score given during the hospital admission assessment. Magnetic resonance images from 20 subjects in the spasticity group and 52 from the control group were then compared using lesion density plots and voxel-based lesion-symptom mapping. An association of acute spasticity with the gray matter regions of the insula, basal ganglia, and thalamus was found in this study. White matter tracts including the pontine crossing tract, corticospinal tract, internal capsule, corona radiata, external capsule, and the superior fronto-occipital fasciculus were also found to be significantly associated with acute spasticity. This is the first study to describe an association between a region of the brain affected by an infarct and the presence of acute spasticity. Understanding the regions associated with acute spasticity will aid in understanding the pathophysiology of this musculoskeletal impairment at the level of the brain.

  14. Impact of perinatal systemic hypoxic-ischemic injury on the brain of male offspring rats: an improved model of neonatal hypoxic-ischemic encephalopathy in early preterm newborns.

    Directory of Open Access Journals (Sweden)

    Yuejun Huang

    Full Text Available In this study, we attempted to design a model using Sprague-Dawley rats to better reproduce perinatal systemic hypoxic-ischemic encephalopathy (HIE in early preterm newborns. On day 21 of gestation, the uterus of pregnant rats were exposed and the blood supply to the fetuses of neonatal HIE groups were thoroughly abscised by hemostatic clamp for 5, 10 or 15 min. Thereafter, fetuses were moved from the uterus and manually stimulated to initiate breathing in an incubator at 37 °C for 1 hr in air. We showed that survival rates of offspring rats were decreased with longer hypoxic time. TUNEL staining showed that apoptotic cells were significant increased in the brains of offspring rats from the 10 min and 15 min HIE groups as compared to the offspring rats in the control group at postnatal day (PND 1, but there was no statistical difference between the offspring rats in the 5 min HIE and control groups. The perinatal hypoxic treatment resulted in decreased neurons and increased cleaved caspase-3 protein levels in the offspring rats from all HIE groups at PND 1. Platform crossing times and the percentage of the time spent in the target quadrant of Morris Water Maze test were significantly reduced in the offspring rats of all HIE groups at PND 30, which were associated with decreased brain-derived neurotrophic factor levels and neuronal cells in the hippocampus of offspring rats at PND 35. These data demonstrated that perinatal ischemic injury led to the death of neuronal cells and long-lasting impairment of memory. This model reproduced hypoxic ischemic encephalopathy in early preterm newborns and may be appropriate for investigating therapeutic interventions.

  15. [Mechanism of potassium channel in hypoxia-ischemic brain edema: experiment with neonatal rat astrocyte].

    Science.gov (United States)

    Fu, Xue-mei; Xiang, Long; Liao, Da-qing; Feng, Zhi-chun; Mu, De-zhi

    2008-11-04

    To investigate the mechanism of potassium channel in brain edema caused by hypoxia-ischemia (HI). Astrocytes were obtained from 3-day-old SD rats, cultured, and randomly divided into 2 groups: normoxia group, cultured under normoxic condition, and hypoxic-ischemic group, cultured under hypoxic-ischemic condition. The cell volume was measured by radiologic method. Patch-clamp technique was used to observe the electric physiological properties of the voltage-gated potassium channels (Kv) in a whole cell configuration, and the change of voltage-gated potassium channel current (IKv) was recorded in cultured neonatal rat astrocyte during HI. Aquaporin 4 (AQP4) expression vector was constructed from pSUPER vector and transfected into the astrocytes (AQP4 RNAi) to construct AQP4 knockdown (AQP4-/-) cells. cellular volume was determined using [3H]-3-O-methyl-D-glucose uptake in both AQP4-/- and AQP4+/+ cells under the condition of HI. Real time PCR and Western blotting were used to detect the mRNA and protein expression of AQP4. The percentages of the AQP4+/+ and AQP4-/- astrocyte volumes in the condition of HI for 0.5, 1, 2, and 4 h were 104+/-7, 109+/-6, 126+/-12, and 152+/-9 times, and 97+/-7, 105+/-9, 109+/-7, and 132+/-6 times as those of their corresponding control groups (all Pastrocytes significantly increased during HI and the degrees of edema mediated by AQP4 knockdown at different time points were all significantly milder (all Pastrocytes via aquaporin-4 and then cell swelling.

  16. [Importance of hypertensive left ventricular hypertrophy in patients with ischemic events of the heart or brain].

    Science.gov (United States)

    Castilla-Guerra, L; Fernández-Moreno, M C; Aguilera-Saborido, A; Solanella-Soler, J

    2016-01-01

    Hypertensive left ventricular hypertrophy (H-LVH) is a potentially modifiable vascular risk factor (VRF) often overlooked in clinical practice. We aimed to evaluate the frequency of H-LVH in patients with coronary heart disease (CHD) or ischemic stroke (IS). We retrospectively assessed all the echocardiography studies of patients admitted with the diagnosis CHD or IS over a 4-year period. We studied 533 patients, 330 with CHD and 203 with IS. Mean age was 69 (±11) years, 61.5% males. Hypertension was the most common RF: 362 patients (67.9%) (CHD vs. IS: 70 vs. 64.5%; P=NS). H-LVH was seen in 234 patients (43.9%) (CHD vs. IS: 44.8 vs. 42.3%; P=NS). Patients with H-LVH were older and received a greater number of antihypertensive drugs at discharge. Half of patients with hypertension presented H-LVH (184 patients; 50.8%), with similar frequency in both groups (CHD vs. IS: 50.6 vs. 51.1%; P=NS). Neither patients' characteristics nor VRF with the exception of hypertension (P=.0001) were associated with H-LVH. H-LVH is a major VRF in patients with ischemic events in the heart and brain. Nearly half the patients present H-LVH, with a similar frequency in both groups. It is important to identify H-LVH in these patients to optimize treatment and improve long-term prognosis. Copyright © 2015 SEHLELHA. Published by Elsevier España, S.L.U. All rights reserved.

  17. Effect of Dementia on the Use of Drugs for Secondary Prevention of Ischemic Heart Disease

    Directory of Open Access Journals (Sweden)

    Nicole R. Fowler

    2014-01-01

    Full Text Available Background. Dementia and cardiovascular disease (CVD are frequently comorbid. The presence of dementia may have an effect on how CVD is treated. Objective. To examine the effect of dementia on the use of four medications recommended for secondary prevention of ischemic heart disease (IHD: angiotensin-converting enzyme inhibitors, beta-blockers, lipid-lowering medications, and antiplatelet medications. Design. Retrospective analysis of data from the Cardiovascular Health Study: Cognition Study. Setting and Subjects. 1,087 older adults in four US states who had or developed IHD between 1989 and 1998. Methods. Generalized estimating equations to explore the association between dementia and the use of guideline-recommended medications for the secondary prevention of IHD. Results. The length of follow-up for the cohort was 8.7 years and 265 (24% had or developed dementia during the study. Use of medications for the secondary prevention of IHD for patients with and without dementia increased during the study period. In models, subjects with dementia were not less likely to use any one particular class of medication but were less likely to use two or more classes of medications as a group (OR, 0.60; 95% CI, 0.36–0.99. Conclusions. Subjects with dementia used fewer guideline-recommended medications for the secondary prevention of IHD than those without dementia.

  18. Clinical and Demographic Characteristics Associated With Suboptimal Primary Stroke and Transient Ischemic Attack Prevention: Retrospective Analysis.

    Science.gov (United States)

    Turner, Grace M; Calvert, Melanie; Feltham, Max G; Ryan, Ronan; Finnikin, Samuel; Marshall, Tom

    2018-03-01

    Primary prevention of stroke and transient ischemic attack (TIA) is important to reduce the burden of these conditions; however, prescribing of prevention drugs is suboptimal. We aimed to identify individual clinical and demographic characteristics associated with potential missed opportunities for prevention therapy with lipid-lowering, anticoagulant, or antihypertensive drugs before stroke/TIA. We analyzed anonymized electronic primary care records from a UK primary care database that covers 561 family practices. Patients with first-ever stroke/TIA, ≥18 years, with diagnosis between January 1, 2009, and December 31, 2013, were included. Missed opportunities for prevention were defined as people with clinical indications for lipid-lowering, anticoagulant, or antihypertensive drugs but not prescribed these drugs before their stroke/TIA. Mixed-effect logistic regression models evaluated the relationship between missed opportunities and individual clinical/demographic characteristics. The inclusion criteria were met by 29 043 people with stroke/TIA. Patients with coronary heart disease, chronic kidney disease, peripheral arterial disease, or diabetes mellitus were at less risk of a missed opportunity for prescription of lipid-lowering and antihypertensive drugs. However, patients with a 10-year cardiovascular disease risk ≥20% but without these diagnoses had increased risk of having a missed opportunity for prescription of lipid-lowering drugs or antihypertensive drugs. Women were less likely to be prescribed anticoagulants but more likely to be prescribed antihypertensive drugs. The elderly (≥85 years of age) were less likely to be prescribed all 3 prevention drugs, compared with people aged 75 to 79 years. Knowing the patient characteristics predictive of missed opportunities for stroke prevention may help primary care identify and appropriately manage these patients. Improving the management of these groups may reduce their risk and potentially prevent

  19. Clinical Updates in Women's Health Care Summary: Ischemic Heart Disease: Primary and Preventive Care Review.

    Science.gov (United States)

    Fuller, Brittany S; Carlyle, Lynn; Voeltz, Michele D

    2017-11-01

    Cardiovascular disease is the leading cause of death among women in the United States. Obstetrician-gynecologists often are the sole health care providers for otherwise healthy women. Therefore, they must be aware of risk factors, signs, and symptoms of cardiovascular disease and be prepared to recognize and treat this condition in patients as well as provide referrals when specialized care is indicated. Women with cardiac problems typically present with chest discomfort; however, they also are more likely than healthy women to present with other common symptoms, such as shortness of breath, back pain, jaw pain, or nausea and vomiting. This monograph, with a primary focus on ischemic heart disease (IHD), discusses the basic anatomy of the heart and coronary arteries; vascular biology; pathogenesis of atherosclerosis; and the screening, prevention, diagnosis, and treatment of IHD as well as the multiple risk factors associated with the development of IHD that contribute to both increased morbidity and mortality.

  20. Methylene blue prevents retinal damage in an experimental model of ischemic proliferative retinopathy.

    Science.gov (United States)

    Rey-Funes, Manuel; Larrayoz, Ignacio M; Fernández, Juan C; Contartese, Daniela S; Rolón, Federico; Inserra, Pablo I F; Martínez-Murillo, Ricardo; López-Costa, Juan J; Dorfman, Verónica B; Martínez, Alfredo; Loidl, César F

    2016-06-01

    Perinatal asphyxia induces retinal lesions, generating ischemic proliferative retinopathy, which may result in blindness. Previously, we showed that the nitrergic system was involved in the physiopathology of perinatal asphyxia. Here we analyze the application of methylene blue, a well-known soluble guanylate cyclase inhibitor, as a therapeutic strategy to prevent retinopathy. Male rats (n = 28 per group) were treated in different ways: 1) control group comprised born-to-term animals; 2) methylene blue group comprised animals born from pregnant rats treated with methylene blue (2 mg/kg) 30 and 5 min before delivery; 3) perinatal asphyxia (PA) group comprised rats exposed to perinatal asphyxia (20 min at 37°C); and 4) methylene blue-PA group comprised animals born from pregnant rats treated with methylene blue (2 mg/kg) 30 and 5 min before delivery, and then the pups were subjected to PA as above. For molecular studies, mRNA was obtained at different times after asphyxia, and tissue was collected at 30 days for morphological and biochemical analysis. Perinatal asphyxia produced significant gliosis, angiogenesis, and thickening of the inner retina. Methylene blue treatment reduced these parameters. Perinatal asphyxia resulted in a significant elevation of the nitrergic system as shown by NO synthase (NOS) activity assays, Western blotting, and (immuno)histochemistry for the neuronal isoform of NOS and NADPH-diaphorase activity. All these parameters were also normalized by the treatment. In addition, methylene blue induced the upregulation of the anti-angiogenic peptide, pigment epithelium-derived factor. Application of methylene blue reduced morphological and biochemical parameters of retinopathy. This finding suggests the use of methylene blue as a new treatment to prevent or decrease retinal damage in the context of ischemic proliferative retinopathy. Copyright © 2016 the American Physiological Society.

  1. Motor-Evoked Potential Confirmation of Functional Improvement by Transplanted Bone Marrow Mesenchymal Stem Cell in the Ischemic Rat Brain

    Science.gov (United States)

    Jang, Dong-Kyu; Park, Sang-In; Han, Young-Min; Jang, Kyung-Sool; Park, Moon-Seo; Chung, Young-An; Kim, Min-Wook; Maeng, Lee-So; Huh, Pil-Woo; Yoo, Do-Sung; Jung, Seong-Whan

    2011-01-01

    This study investigated the effect of bone marrow mesenchymal stem cells (BMSCs) on the motor pathway in the transient ischemic rat brain that were transplanted through the carotid artery, measuring motor-evoked potential (MEP) in the four limbs muscle and the atlantooccipital membrane, which was elicited after monopolar and bipolar transcortical stimulation. After monopolar stimulation, the latency of MEP was significantly prolonged, and the amplitude was less reduced in the BMSC group in comparison with the control group (P < .05). MEPs induced by bipolar stimulation in the left forelimb could be measured in 40% of the BMSC group and the I wave that was not detected in the control group was also detected in 40% of the BMSC group. Our preliminary results imply that BMSCs transplanted to the ischemic rat brain mediate effects on the functional recovery of the cerebral motor cortex and the motor pathway. PMID:21772790

  2. Motor-Evoked Potential Confirmation of Functional Improvement by Transplanted Bone Marrow Mesenchymal Stem Cell in the Ischemic Rat Brain

    Directory of Open Access Journals (Sweden)

    Dong-Kyu Jang

    2011-01-01

    Full Text Available This study investigated the effect of bone marrow mesenchymal stem cells (BMSCs on the motor pathway in the transient ischemic rat brain that were transplanted through the carotid artery, measuring motor-evoked potential (MEP in the four limbs muscle and the atlantooccipital membrane, which was elicited after monopolar and bipolar transcortical stimulation. After monopolar stimulation, the latency of MEP was significantly prolonged, and the amplitude was less reduced in the BMSC group in comparison with the control group (<.05. MEPs induced by bipolar stimulation in the left forelimb could be measured in 40% of the BMSC group and the I wave that was not detected in the control group was also detected in 40% of the BMSC group. Our preliminary results imply that BMSCs transplanted to the ischemic rat brain mediate effects on the functional recovery of the cerebral motor cortex and the motor pathway.

  3. Hemostatic system changes predictive value in patients with ischemic brain disorders

    Directory of Open Access Journals (Sweden)

    Raičević Ranko

    2002-01-01

    Full Text Available The aim of this research was to determine the importance of tracking the dynamics of changes of the hemostatic system factors (aggregation of thrombocytes, D-dimer, PAI-1, antithrombin III, protein C and protein S, factor VII and factor VIII, fibrin degradation products, euglobulin test and the activated partial thromboplastin time – aPTPV in relation to the level of the severity of ischemic brain disorders (IBD and the level of neurological and functional deficiency in the beginning of IBD manifestation from 7 to 10 days, 19 to 21 day, and after 3 to 6 months. The research results confirmed significant predictive value of changes of hemostatic system with the predomination of procoagulant factors, together with the insufficiency of fibrinolysis. Concerning the IBD severity and it's outcome, the significant predictive value was shown in the higher levels of PAI-1 and the lower level of antithrombin III, and borderline significant value was shown in the accelerated aggregation of thrombocytes and the increased concentration of D-dimer. It could be concluded that the tracking of the dynamics of changes in parameters of hemostatic system proved to be an easily accessible method with the significant predictive value regarding the development of more severe. IBD cases and the outcome of the disease itself.

  4. 3D movement correction of CT brain perfusion image data of patients with acute ischemic stroke

    International Nuclear Information System (INIS)

    Fahmi, Fahmi; Marquering, Henk A.; Streekstra, Geert J.; Borst, Jordi; Beenen, Ludo F.M.; Majoie, Charles B.L.; Niesten, Joris M.; Velthuis, Birgitta K.; VanBavel, Ed

    2014-01-01

    Head movement during CT brain perfusion (CTP) acquisition can deteriorate the accuracy of CTP analysis. Most CTP software packages can only correct in-plane movement and are limited to small ranges. The purpose of this study is to validate a novel 3D correction method for head movement during CTP acquisition. Thirty-five CTP datasets that were classified as defective due to head movement were included in this study. All CTP time frames were registered with non-contrast CT data using a 3D rigid registration method. Location and appearance of ischemic area in summary maps derived from original and registered CTP datasets were qualitative compared with follow-up non-contrast CT. A quality score (QS) of 0 to 3 was used to express the degree of agreement. Furthermore, experts compared the quality of both summary maps and assigned the improvement score (IS) of the CTP analysis, ranging from -2 (much worse) to 2 (much better). Summary maps generated from corrected CTP significantly agreed better with appearance of infarct on follow-up CT with mean QS 2.3 versus mean QS 1.8 for summary maps from original CTP (P = 0.024). In comparison to original CTP data, correction resulted in a quality improvement with average IS 0.8: 17 % worsened (IS = -2, -1), 20 % remained unchanged (IS = 0), and 63 % improved (IS = +1, +2). The proposed 3D movement correction improves the summary map quality for CTP datasets with severe head movement. (orig.)

  5. Tissue-type plasminogen activator protects the postsynaptic density in the ischemic brain.

    Science.gov (United States)

    Jeanneret, Valerie; Ospina, Juan P; Diaz, Ariel; Manrique, Luis G; Merino, Paola; Gutierrez, Laura; Torre, Enrique; Wu, Fang; Cheng, Lihong; Yepes, Manuel

    2018-01-01

    Cerebral ischemia causes the presynaptic release of tissue-type plasminogen activator (tPA). The postsynaptic density (PSD) is a postsynaptic structure that provides a matrix where signaling transduction of excitatory synapses takes place. The postsynaptic density protein-95 (PSD-95) is the most abundant scaffolding protein in the postsynaptic density (PSD), where it modulates the postsynaptic response to the presynaptic release of glutamate by regulating the anchoring of glutamate receptors to the PSD. We found that tPA induces the local translation of PSD-95 mRNA and the subsequent recruitment of PSD-95 protein to the PSD, via plasminogen-independent activation of TrkB receptors. Our data show that PSD-95 is removed from the PSD during the early stages of cerebral ischemia, and that this effect is abrogated by either the release of neuronal tPA, or intravenous administration of recombinant tPA (rtPA). We report that the effect of tPA on PSD-95 is associated with inhibition of the phosphorylation and recruitment of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors to the PSD, known to amplify the effect of the excitotoxic injury, and that this is followed by TrkB-mediated protection of dendritic spines from the harmful effects of the hypoxic insult. These data reveal that tPA is a synaptic protector in the ischemic brain.

  6. 3D movement correction of CT brain perfusion image data of patients with acute ischemic stroke

    Energy Technology Data Exchange (ETDEWEB)

    Fahmi, Fahmi [Academic Medical Center, Department of Biomedical Engineering and Physics, Amsterdam (Netherlands); University of Sumatera Utara, Department of Electrical Engineering, Medan (Indonesia); Marquering, Henk A.; Streekstra, Geert J. [Academic Medical Center, Department of Biomedical Engineering and Physics, Amsterdam (Netherlands); Academic Medical Center, Department of Radiology, Amsterdam (Netherlands); Borst, Jordi; Beenen, Ludo F.M.; Majoie, Charles B.L. [Academic Medical Center, Department of Radiology, Amsterdam (Netherlands); Niesten, Joris M.; Velthuis, Birgitta K. [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); VanBavel, Ed [Academic Medical Center, Department of Biomedical Engineering and Physics, Amsterdam (Netherlands); Collaboration: on behalf of the DUST study

    2014-06-15

    Head movement during CT brain perfusion (CTP) acquisition can deteriorate the accuracy of CTP analysis. Most CTP software packages can only correct in-plane movement and are limited to small ranges. The purpose of this study is to validate a novel 3D correction method for head movement during CTP acquisition. Thirty-five CTP datasets that were classified as defective due to head movement were included in this study. All CTP time frames were registered with non-contrast CT data using a 3D rigid registration method. Location and appearance of ischemic area in summary maps derived from original and registered CTP datasets were qualitative compared with follow-up non-contrast CT. A quality score (QS) of 0 to 3 was used to express the degree of agreement. Furthermore, experts compared the quality of both summary maps and assigned the improvement score (IS) of the CTP analysis, ranging from -2 (much worse) to 2 (much better). Summary maps generated from corrected CTP significantly agreed better with appearance of infarct on follow-up CT with mean QS 2.3 versus mean QS 1.8 for summary maps from original CTP (P = 0.024). In comparison to original CTP data, correction resulted in a quality improvement with average IS 0.8: 17 % worsened (IS = -2, -1), 20 % remained unchanged (IS = 0), and 63 % improved (IS = +1, +2). The proposed 3D movement correction improves the summary map quality for CTP datasets with severe head movement. (orig.)

  7. Macro-to-micro cortical vascular imaging underlies regional differences in ischemic brain.

    Science.gov (United States)

    Dziennis, Suzan; Qin, Jia; Shi, Lei; Wang, Ruikang K

    2015-05-05

    The ability to non-invasively monitor and quantify hemodynamic responses down to the capillary level is important for improved diagnosis, treatment and management of neurovascular disorders, including stroke. We developed an integrated multi-functional imaging system, in which synchronized dual wavelength laser speckle contrast imaging (DWLS) was used as a guiding tool for optical microangiography (OMAG) to test whether detailed vascular responses to experimental stroke in male mice can be evaluated with wide range sensitivity from arteries and veins down to the capillary level. DWLS enabled rapid identification of cerebral blood flow (CBF), prediction of infarct area and hemoglobin oxygenation over the whole mouse brain and was used to guide the OMAG system to hone in on depth information regarding blood volume, blood flow velocity and direction, vascular architecture, vessel diameter and capillary density pertaining to defined regions of CBF in response to ischemia. OMAG-DWLS is a novel imaging platform technology to simultaneously evaluate multiple vascular responses to ischemic injury, which can be useful in improving our understanding of vascular responses under pathologic and physiological conditions, and ultimately facilitating clinical diagnosis, monitoring and therapeutic interventions of neurovascular diseases.

  8. Automated brain computed tomographic densitometry of early ischemic changes in acute stroke

    NARCIS (Netherlands)

    Stoel, Berend C.; Marquering, Henk A.; Staring, Marius; Beenen, Ludo F.; Slump, Cornelis H.; Roos, Yvo B.; Majoie, Charles B.

    2015-01-01

    The Alberta Stroke Program Early CT score (ASPECTS) scoring method is frequently used for quantifying early ischemic changes (EICs) in patients with acute ischemic stroke in clinical studies. Varying interobserver agreement has been reported, however, with limited agreement. Therefore, our goal was

  9. Tongxinluo reduces brain edema and inhibits post-ischemic inflammation after middle cerebral artery occlusion in rats.

    Science.gov (United States)

    Cai, Min; Yu, Zhonghai; Wang, Lili; Song, Xiaoling; Zhang, Jingsi; Zhang, Zhennian; Zhang, Wen; Li, Wenwei; Xiang, Jun; Cai, Dingfang

    2016-04-02

    Tongxinluo (TXL), a widely used traditional Chinese medicine, has been proved multiple therapeutic effects in cerebral ischemic infraction. The purpose of this study was to investigate the protective effects of TXL on the brain edema and post-ischemic inflammatory response. Middle cerebral artery occlusion in the rat was used as the ischemia model. Rats were treated with TXL. In the first stage, the best dosage was chosen based on functional assessment and infarct size. In the second stage, rats were randomly divided into 5 groups: sham control (sham), ischemia and reperfusion (IR) 24h, TXL24h, I/R72h, TXL72h. TXL(1.6g/kg/day) administration was pre-performed for 3 days in TXL groups, and was post-performed for 24h (TXL24h group) or 72h (TXL72h group). Brain edema was measured by water content, MRI and AQP4 expression. Iba1, HMGB1, TLR4, NF-κB expression were examined by immunofluorescence staining or Western blot. TNF-α was determined by enzyme-linked immunosorbent assay. High dose (1.6g/kg/day) of TXL remarkably reduced neurological deficit scores and cerebral infarct area. Compared with those results of I/R24h group, pre-post treatment with TXL for 3 days decreased brain water content, down-regulated AQP4 expression, lowered relative signal intensity of T2WI, reduced lesion volume ratio, and inhibited the activation of microglia, HMGB1, TLR4, NF-κB and TNF-α. These results indicated that the TXL pre-post treatment for 3 days could be an effective therapy for brain ischemia by inhibiting the development of brain edema and post-ischemic inflammation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Detection of hypoxic-ischemic brain injury with 3D-enhanced T2* weighted angiography (ESWAN) imaging

    Energy Technology Data Exchange (ETDEWEB)

    Gang, QiangQiang, E-mail: rousikang@163.com; Zhang, Jianing, E-mail: 1325916060@qq.com; Hao, Peng, E-mail: 1043600590@qq.com; Xu, Yikai, E-mail: yikaivip@163.com

    2013-11-01

    Objective: To demonstrate the use of 3D-enhanced T2* weighted angiography (ESWAN) imaging for the observation and quantification of the evolution of brain injury induced by a recently developed model of hypoxic-ischemic brain injury (HI/R) in neonatal piglets. Methods: For these experiments, newborn piglets were subjected to HI/R injury, during which ESWAN scanning was performed, followed by H and E staining and immunohistochemistry of AQP-4 expression. Results: In the striatum, values from T2* weighted magnetic resonance imaging (MRI) increased and reached their highest level at 3 days post injury, whereas T2* values increased and peaked at 24 h in the subcortical region. The change in T2* values was concordant with brain edema. Phase values in the subcortical border region were not dependent on time post-injury. Magnitude values were significantly different from the control group, and increased gradually over time in the subcortical border region. Susceptibility-weighted images (SWI) indicated small petechial hemorrhages in the striatum and thalamus, as well as dilated intramedullary veins. Conclusion: SWI images can be used to detect white and gray matter microhemorrhages and dilated intramedullary veins. The T2*, phase, and magnitude map can also reflect the development of brain injury. Our data illustrate that ESWAN imaging can increase the diagnostic sensitivity and specificity of MRI in neonatal hypoxic-ischemic encephalopathy.

  11. Detection of hypoxic-ischemic brain injury with 3D-enhanced T2* weighted angiography (ESWAN) imaging

    International Nuclear Information System (INIS)

    Gang, QiangQiang; Zhang, Jianing; Hao, Peng; Xu, Yikai

    2013-01-01

    Objective: To demonstrate the use of 3D-enhanced T2* weighted angiography (ESWAN) imaging for the observation and quantification of the evolution of brain injury induced by a recently developed model of hypoxic-ischemic brain injury (HI/R) in neonatal piglets. Methods: For these experiments, newborn piglets were subjected to HI/R injury, during which ESWAN scanning was performed, followed by H and E staining and immunohistochemistry of AQP-4 expression. Results: In the striatum, values from T2* weighted magnetic resonance imaging (MRI) increased and reached their highest level at 3 days post injury, whereas T2* values increased and peaked at 24 h in the subcortical region. The change in T2* values was concordant with brain edema. Phase values in the subcortical border region were not dependent on time post-injury. Magnitude values were significantly different from the control group, and increased gradually over time in the subcortical border region. Susceptibility-weighted images (SWI) indicated small petechial hemorrhages in the striatum and thalamus, as well as dilated intramedullary veins. Conclusion: SWI images can be used to detect white and gray matter microhemorrhages and dilated intramedullary veins. The T2*, phase, and magnitude map can also reflect the development of brain injury. Our data illustrate that ESWAN imaging can increase the diagnostic sensitivity and specificity of MRI in neonatal hypoxic-ischemic encephalopathy

  12. Magnetic resonance imaging of post-ischemic blood-brain barrier damage with PEGylated iron oxide nanoparticles

    Science.gov (United States)

    Liu, Dong-Fang; Qian, Cheng; An, Yan-Li; Chang, Di; Ju, Sheng-Hong; Teng, Gao-Jun

    2014-11-01

    Blood-brain barrier (BBB) damage during ischemia may induce devastating consequences like cerebral edema and hemorrhagic transformation. This study presents a novel strategy for dynamically imaging of BBB damage with PEGylated supermagnetic iron oxide nanoparticles (SPIONs) as contrast agents. The employment of SPIONs as contrast agents made it possible to dynamically image the BBB permeability alterations and ischemic lesions simultaneously with T2-weighted MRI, and the monitoring could last up to 24 h with a single administration of PEGylated SPIONs in vivo. The ability of the PEGylated SPIONs to highlight BBB damage by MRI was demonstrated by the colocalization of PEGylated SPIONs with Gd-DTPA after intravenous injection of SPION-PEG/Gd-DTPA into a mouse. The immunohistochemical staining also confirmed the leakage of SPION-PEG from cerebral vessels into parenchyma. This study provides a novel and convenient route for imaging BBB alteration in the experimental ischemic stroke model.

  13. Real-time monitoring of ischemic and contralateral brain pO2 during stroke by variable length multisite resonators.

    Science.gov (United States)

    Hou, Huagang; Li, Hongbin; Dong, Ruhong; Khan, Nadeem; Swartz, Harold

    2014-06-01

    Electron paramagnetic resonance (EPR) oximetry using variable length multi-probe implantable resonator (IR), was used to investigate the temporal changes in the ischemic and contralateral brain pO2 during stroke in rats. The EPR signal to noise ratio (S/N) of the IR with four sensor loops at a depth of up to 11 mm were compared with direct implantation of lithium phthalocyanine (LiPc, oximetry probe) deposits in vitro. These IRs were used to follow the temporal changes in pO2 at two sites in each hemisphere during ischemia induced by left middle cerebral artery occlusion (MCAO) in rats breathing 30% O2 or 100% O2. The S/N ratios of the IRs were significantly greater than the LiPc deposits. A similar pO2 at two sites in each hemisphere prior to the onset of ischemia was observed in rats breathing 30% O2. However, a significant decline in the pO2 of the left cortex and striatum occurred during ischemia, but no change in the pO2 of the contralateral brain was observed. A significant increase in the pO2 of only the contralateral non-ischemic brain was observed in the rats breathing 100% O2. No significant difference in the infarct volume was evident between the animals breathing 30% O2 or 100% O2 during ischemia. EPR oximetry with IRs can repeatedly assess temporal changes in the brain pO2 at four sites simultaneously during stroke. This oximetry approach can be used to test and develop interventions to rescue ischemic tissue by modulating cerebral pO2 during stroke. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Effect of antibodies to glutamate on the content of neurotransmitter amino acids in brain structures of rats with ischemic damage to the prefrontal cortex.

    Science.gov (United States)

    Romanova, G A; Kvashennikova, Yu N; Shakova, F M; Davydova, T V

    2012-05-01

    Experiments on the model of bilateral photothrombosis in the prefrontal cortex showed that antibodies to glutamate administered intranasally 1 h after ischemic damage to the brain cortex led to a decrease in glutamate content in the hippocampus and prefrontal cortex and had no effect on aspartate concentration in these structures of the brain.

  15. Remote ischemic preconditioning prevents reduction in brachial artery flow-mediated dilation after strenuous exercise.

    Science.gov (United States)

    Bailey, Tom G; Birk, Gurpreet K; Cable, N Timothy; Atkinson, Greg; Green, Daniel J; Jones, Helen; Thijssen, Dick H J

    2012-09-01

    Strenuous exercise is associated with an immediate decrease in endothelial function. Repeated bouts of ischemia followed by reperfusion, known as remote ischemic preconditioning (RIPC), is able to protect the endothelium against ischemia-induced injury beyond the ischemic area. We examined the hypothesis that RIPC prevents the decrease in endothelial function observed after strenuous exercise in healthy men. In a randomized, crossover study, 13 healthy men performed running exercise preceded by RIPC of the lower limbs (4 × 5-min 220-mmHg bilateral occlusion) or a sham intervention (sham; 4 × 5-min 20-mmHg bilateral occlusion). Participants performed a graded maximal treadmill running test, followed by a 5-km time trial (TT). Brachial artery endothelial function was examined before and after RIPC or sham, as well as after the 5-km TT. We measured flow-mediated dilation (FMD), an index of endothelium-dependent function, using high-resolution echo-Doppler. We also calculated the shear rate area-under-the-curve (from cuff deflation to peak dilatation; SR(AUC)). Data are described as mean and 95% confidence intervals. FMD changed by 0.30). In the sham trial, FMD changed from 5.1 (4.4-5.9) to 3.7% (2.6-4.8) following the 5-km TT (P = 0.02). In the RIPC trial, FMD changed negligibly from 5.4 (4.4-6.4) post-IPC and 5.7% (4.6-6.8) post 5-km TT (P = 0.60). Baseline diameter, SR(AUC), and time-to-peak diameter were all increased following the 5-km TT (P < 0.05), but these changes did not influence the IPC-mediated maintenance of FMD. In conclusion, these data indicate that strenuous lower-limb exercise results in an acute decrease in brachial artery FMD of ~1.4% in healthy men. However, we have shown for the first time that prior RIPC of the lower limbs maintains postexercise brachial artery endothelium-dependent function at preexercise levels.

  16. DIDS prevents ischemic membrane degradation in cultured hippocampal neurons by inhibiting matrix metalloproteinase release.

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    Matthew E Pamenter

    Full Text Available During stroke, cells in the infarct core exhibit rapid failure of their permeability barriers, which releases ions and inflammatory molecules that are deleterious to nearby tissue (the penumbra. Plasma membrane degradation is key to penumbral spread and is mediated by matrix metalloproteinases (MMPs, which are released via vesicular exocytosis into the extracellular fluid in response to stress. DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid preserves membrane integrity in neurons challenged with an in vitro ischemic penumbral mimic (ischemic solution: IS and we asked whether this action was mediated via inhibition of MMP activity. In cultured murine hippocampal neurons challenged with IS, intracellular proMMP-2 and -9 expression increased 4-10 fold and extracellular latent and active MMP isoform expression increased 2-22 fold. MMP-mediated extracellular gelatinolytic activity increased ∼20-50 fold, causing detachment of 32.1±4.5% of cells from the matrix and extensive plasma membrane degradation (>60% of cells took up vital dyes and >60% of plasma membranes were fragmented or blebbed. DIDS abolished cellular detachment and membrane degradation in neurons and the pathology-induced extracellular expression of latent and active MMPs. DIDS similarly inhibited extracellular MMP expression and cellular detachment induced by the pro-apoptotic agent staurosporine or the general proteinase agonist 4-aminophenylmercuric acetate (APMA. Conversely, DIDS-treatment did not impair stress-induced intracellular proMMP production, nor the intracellular cleavage of proMMP-2 to the active form, suggesting DIDS interferes with the vesicular extrusion of MMPs rather than directly inhibiting proteinase expression or activation. In support of this hypothesis, an antagonist of the V-type vesicular ATPase also inhibited extracellular MMP expression to a similar degree as DIDS. In addition, in a proteinase-independent model of vesicular exocytosis, DIDS

  17. Effect of 3-aminobenzamide, PARP inhibitor, on matrix metalloproteinase-9 level in plasma and brain of ischemic stroke model

    International Nuclear Information System (INIS)

    Koh, Seong-Ho; Chang, Dae-Il; Kim, Hee-Tae; Kim, Juhan; Kim, Myung-Ho; Kim, Kyung Suk; Bae, Inhee; Kim, Haekwon; Kim, Dong Won; Kim, Seung Hyun

    2005-01-01

    We investigated the effect of poly(ADP-ribose) polymerase (PARP) inhibitor on the levels of plasma and brain matrix metalloproteinase-9 (MMP-9) and the expression of nuclear factor kappa B (NF-κB) during experimental focal cerebral ischemia. The 3-aminobenzamide (3-AB), a PARP inhibitor, and saline were administered to 80 Sprague-Dawley rats [3-AB group; 5 rats for plasma sampling, 35 for brain sampling, and 40 for TTC staining] and to 85 rats (10, 35, and 40, respectively), respectively, 10 min before the occlusion of the left middle cerebral artery (MCAo) for 2 h. Infarct volume was measured by TTC staining, the serial levels of plasma and brain MMP-9 were measured by zymography just before and 2, 4, 8, 24, 48, and 72 h after MCAo, brain NF-κB activity was determined by Western blotting, and neutrophil infiltration was evaluated by assessing myeloperoxidase activity. Compared with control group, the levels of plasma and brain MMP-9, brain NF-κB, and MPO activities were significantly reduced in 3-AB group at each time point (p < 0.05). Plasma MMP-9 increased maximally at 4 h and then decreased rapidly, brain MMP-9 increased maximally at 24 h and persisted until 72 h, and NF-κB increased maximally at 24 h and then decreased slowly in both groups. Therefore, the PARP inhibitor reduces the expression of MMP-9 and NF-κB and the infiltration of neutrophils in ischemic stroke

  18. The neuroprotective effects of intramuscular insulin-like growth factor-I treatment in brain ischemic rats.

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    Heng-Chih Chang

    Full Text Available Brain ischemia leads to muscle inactivity-induced atrophy and may exacerbate motor function deficits. Intramuscular insulin-like growth factor I (IGF-I injection has been shown to alleviate the brain ischemia-induced muscle atrophy and thus improve the motor function. Motor function is normally gauged by the integrity and coordination of the central nervous system and peripheral muscles. Whether brain ischemic regions are adaptively changed by the intramuscular IGF-I injection is not well understood. In this study, the effect of intramuscular IGF-I injection was examined on the central nervous system of brain ischemic rats. Rats were divided into 4 groups: sham control, brain ischemia control, brain ischemia with IGF-I treatment, and brain ischemia with IGF-I plus IGF-I receptor inhibitor treatment. Brain ischemia was induced by right middle cerebral artery occlusion. IGF-I and an IGF-1 receptor inhibitor were injected into the affected calf and anterior tibialis muscles of the treated rats for 4 times. There was an interval of 2 days between each injection. Motor function was examined and measured at the 24 hours and 7 days following a brain ischemia. The affected hind-limb muscles, sciatic nerve, lumbar spinal cord, and motor cortex were collected for examination after euthanizing the rats. IGF-I expression in the central nervous system and affected muscles were significantly decreased after brain ischemia. Intramuscular IGF-I injection increased the IGF-I expression in the affected muscles, sciatic nerve, lumbar spinal cord, and motor cortex. It also increased the p-Akt expression in the affected motor cortex. Furthermore, intramuscular IGF-I injection decreased the neuronal apoptosis and improved the motor function. However, co-administration of the IGF-I receptor inhibitor eliminated these effects. Intramuscular IGF-I injection after brain ischemia attenuated or reversed the decrease of IGF-I in both central and peripheral tissues, and

  19. Melatonin alleviates brain and peripheral tissue edema in a neonatal rat model of hypoxic-ischemic brain damage: the involvement of edema related proteins.

    Science.gov (United States)

    Xu, Li-Xiao; Lv, Yuan; Li, Yan-Hong; Ding, Xin; Wang, Ying; Han, Xing; Liu, Ming-Hua; Sun, Bin; Feng, Xing

    2017-03-28

    Previous studies have indicated edema may be involved in the pathophysiology following hypoxic-ischemic encephalopathy (HIE), and melatonin may exhibit neuro-protection against brain insults. However, little is known regarding the mechanisms that involve the protective effects of melatonin in the brain and peripheral tissues after HIE. The present study aimed to examine the effects of melatonin on multiple organs, and the expression of edema related proteins in a neonatal rat model of hypoxic-ischemic brain damage (HIBD). One hundred ninety-two neonatal rats were randomly divided into three subgroups that underwent a sham surgery or HIBD. After the HIBD or sham-injury, the rats received an intraperitoneal injection of melatonin or an equal volume vehicle, respectively. We investigated the effects of melatonin on brain, kidney, and colon edema via histological examination and the expression of edema related proteins, including AQP-4, ZO-1 and occludin, via qPCR and western blot. Our data indicated (1) Melatonin reduced the histological injury in the brain and peripheral organs induced by HIBD as assessed via H-E staining and transmission electron microscopy. (2) Melatonin alleviated the HIBD-induced cerebral edema characterized by increased brain water content. (3) HIBD induced significant changes of edema related proteins, such as AQP-4, ZO-1 and occludin, and these changes were partially reversed by melatonin treatment. These findings provide substantial evidence that melatonin treatment has protective effects on the brain and peripheral organs after HIBD, and the edema related proteins, AQP4, ZO-1, and occludin, may indirectly contribute tothe mechanism of the edema protection by melatonin.

  20. Diffusion-weighted imaging in the evaluation of watershed hypoxic-ischemic brain injury in pediatric patients

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    Liu, A.Y.; Zimmerman, R.A.; Haselgrove, J.C.; Bilaniuk, L.T.; Hunter, J.V. [Hospital of the Univ. of Pennsylvania (HUP), Philadelphia (United States). Dept. of Radiology

    2001-11-01

    The purpose of our study was to determine the usefulness of echo-planar diffusion-weighted imaging (EPDI) in the evaluation of watershed hypoxic-ischemic brain injury in pediatric patients. Eighteen patients ranging in age from 3 weeks to 12 years were evaluated for evidence of ischemic/infarction changes on conventional MR and EPDI. Included in the study group were five patients with sickle cell disease, four with congenital heart disease, four with hypotensive episodes with various etiologies, three with sepsis, and two with encephalitis or meningitis. Patients were examined 2 h to 6 days after the initial insult, with follow-up studies in four patients at 1 to 62 days after the initial examination. After conventional MR imaging (T1, FSE T2, and FLAIR), diffusion-weighted MR imaging was performed using high-speed, single-shot EP techniques with TR 6000, TE 144, matrix 96 x 128, FOV 23.3 x 31 and five b values of 0, 160, 360, 640, and 1,000 s/mm{sup 2}. EPDI demonstrated abnormally increased signal in watershed ischemic/infarction zones in all initial cases. Apparent diffusion coefficients (ADC) were obtained in 59 lesions. When compared with radiographically normal (on EPDI) contralateral brain parenchyma, 45 demonstrated a relatively decreased ADC, while eight had normal ({+-} 10 %) and six had increased ADC. In four cases, signal abnormalities on EPDI were not seen or exceeded that seen with conventional MR imaging. In the remaining cases, signal abnormalities were obvious on EPDI and more subtle on conventional MR imaging. Follow-up studies demonstrated resolution of abnormal EPDI signal with persistent abnormalities on conventional imaging in some cases, while others revealed an increase in size or number of EPDI signal abnormalities, suggesting ongoing acute ischemic/infarctive changes. EPDI is a rapid, sensitive technique for detecting watershed ischemic/infarction changes in pediatric patients with hypoperfusion episodes, at times before such changes are

  1. Diagnosis, management and prevention of ischemic stroke for non-neurologists

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    Kavian Ghandehari

    2011-07-01

    Full Text Available Background: Stroke is the third common cause of disability and death. Diagnosis of stroke is based on its clinical manifestations and/or observation of infarct in the neuroimaging. Standard battery of diagnostic investigations and classification criteria is required for detection of stroke etiology. Materials and Method: This review article deals with the diagnosis and management of brain infarction particularly in our country and is provided for non-neurologists. Using online scientific search engines and in some parts referring to laboratory archives constituted base of this review article.Results: Acute stroke management is almost similar in its various etiologies. Neuroprotective drugs have little value in acute stroke management. At present time, a few Iranian medical centers have infrastructure of thrombolysis therapy. Prevention of stroke is based on the detection and control of its risk factors. Aspirin, 80 mg per day is the most common drug for stroke prevention. Co-administration of aspirin 80 mg/d and Dipyridamole 200-400 mg/d increases the preventive effects of aspirin. Clopidogrel 75 mg/d is the stroke preventive drug of choice in patients with peptic ulcer and coronary artery disease. Co-administration of aspirin and clopidogrel is more effective in stroke prevention but has more hemorrhagic complications. Using warfarin for stroke prevention is suggested only in patients who have facilities for repetitive coagulation tests. Carotid endarterectomy is indicated in symptomatic patients with more than 70% stenosis of extracranial internal carotid artery, if performed only by vascular surgeons experienced in carotid surgery.Conclusion: Many stroke patients are managed by general practitioners and non-neurologists, e.g. internists, cardiologists and neurosurgeons. This review article provides continuous medical education according to Iranian medical curriculum

  2. Efficacy of atorvastatin therapy in prevention of postoperative atrial fibrillation in patients with ischemic heart disease

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    O. A. Rubanenko

    2015-11-01

    Full Text Available Aim. To evaluate the efficacy of atorvastatin therapy in prevention of atrial fibrillation (AF development after coronary artery bypass graft (CABG surgery in patients with ischemic heart disease (IHD with the assessment of inflammation, sheer stress and myocardial injury indicators. Material and methods. The study included 105 patients with IHD who were divided into two groups: patients of group 1 were treated with atorvastatin (59 patients, 81% males, mean age 62.1±7.5 years; patients of group 2 received no HMG-CoA reductase inhibitors (46 patients, 89% males, and mean age 61.7±8.1 years. Results. Postoperative AF occurred more often in patients of group 2 (41.3% vs 16.9%; р=0.047. Laboratory analysis revealed the following: the levels of total leukocytes, interleukin-8, interleukin-10, C-reactive protein, fibrinogen, superoxide dismutase and troponin did not different significantly among the patients of two groups. Interleukin-6 level in preand postoperative period was significantly higher in patients of group 2 (35.4±28.5 pg/ml vs 24.1±14.8 pg/ml, р=0.03; 63.7±54.8 pg/ml vs 50.7±40.8 pg/ml, р=0.04, respectively. Conclusion. Our study has shown that atorvastatin therapy contributed to the reduction of number of new cases of AF after CABG in patients with IHD. At that, the efficacy of atorvastatin therapy correlated with the size of left atrium and the severity of inflammatory response. Patients with atorvastatin therapy had significantly lower interleukin-6 level, as a proinflammatory marker, in preand postoperational period as compared with the patients without such treatment.

  3. MRI patterns of hypoxic-ischemic brain injury in preterm and full term infants – classical and less common MR findings

    International Nuclear Information System (INIS)

    Cabaj, Astra; Bekiesińska-Figatowska, Monika; Mądzik, Jaroslaw

    2012-01-01

    Hypoxic-ischemic brain injury occurring in antenatal, perinatal or early postnatal period constitutes an important diagnostic problem in both term and prematurely born neonates. Over the past several years magnetic resonance imaging (MRI) has become relatively easily accessible in Poland. On the basis of the central nervous system MRI, the experienced radiologist are able to determine the location of the hypoxic-ischemic lesions, their extent and evolution. Therefore he can help clinicians to answer the question whether the brain damage of the newborn is responsible for its clinical condition and he can contribute to determining the prognosis of the infant’s future development. The aim of this study is to present the current knowledge of different types of hypoxic-ischemic brain lesions based on our personal experience and MR images from the archives of the Department of Diagnostic Imaging at the Institute of Mother and Child

  4. Effects of umbilical cord blood cells, and subtypes, to reduce neuroinflammation following perinatal hypoxic-ischemic brain injury.

    Science.gov (United States)

    McDonald, Courtney A; Penny, Tayla R; Paton, Madison C B; Sutherland, Amy E; Nekkanti, Lakshmi; Yawno, Tamara; Castillo-Melendez, Margie; Fahey, Michael C; Jones, Nicole M; Jenkin, Graham; Miller, Suzanne L

    2018-02-17

    It is well understood that hypoxic-ischemic (HI) brain injury during the highly vulnerable perinatal period can lead to cerebral palsy, the most prevalent cause of chronic disability in children. Recently, human clinical trials have reported safety and some efficacy following treatment of cerebral palsy using umbilical cord blood (UCB) cells. UCB is made up of many different cell types, including endothelial progenitor cells (EPCs), T regulatory cells (Tregs), and monocyte-derived suppressor cells (MDSCs). How each cell type contributes individually towards reducing neuroinflammation and/or repairing brain injury is not known. In this study, we examined whether human (h) UCB, or specific UCB cell types, could reduce peripheral and cerebral inflammation, and promote brain repair, when given early after perinatal HI brain injury. HI brain injury was induced in postnatal day (PND) 7 rat pups and cells were administered intraperitoneally on PND 8. Behavioral testing was performed 7 days post injury, and then, brains and spleens were collected for analysis. We found in vitro that all UCB cell types, except for EPCs, were immunomodulatory. Perinatal HI brain injury induced significant infiltration of CD4+ T cells into the injured cerebral hemisphere, and this was significantly reduced by all hUCB cell types tested. Compared to HI, UCB, Tregs, and EPCs were able to reduce motor deficits, reduce CD4+ T cell infiltration into the brain, and reduce microglial activation. In addition to the beneficial effects of UCB, EPCs also significantly reduced cortical cell death, returned CD4+ T cell infiltration to sham levels, and reduced the peripheral Th1-mediated pro-inflammatory shift. This study highlights that cells found in UCB is able to mediate neuroinflammation and is an effective neuroprotective therapy. Our study also shows that particular cells found in UCB, namely EPCs, may have an added advantage over using UCB alone. This work has the potential to progress towards

  5. Experimental model considerations for the study of protein-energy malnutrition co-existing with ischemic brain injury.

    Science.gov (United States)

    Prosser-Loose, Erin J; Smith, Shari E; Paterson, Phyllis G

    2011-05-01

    Protein-energy malnutrition (PEM) affects ~16% of patients at admission for stroke. We previously modeled this in a gerbil global cerebral ischemia model and found that PEM impairs functional outcome and influences mechanisms of ischemic brain injury and recovery. Since this model is no longer reliable, we investigated the utility of the rat 2-vessel occlusion (2-VO) with hypotension model of global ischemia for further study of this clinical problem. Male, Sprague-Dawley rats were exposed to either control diet (18% protein) or PEM induced by feeding a low protein diet (2% protein) for 7d prior to either global ischemia or sham surgery. PEM did not significantly alter the hippocampal CA1 neuron death (p = 0.195 by 2-factor ANOVA) or the increase in dendritic injury caused by exposure to global ischemia. Unexpectedly, however, a strong trend was evident for PEM to decrease the consistency of hippocampal damage, as shown by an increased incidence of unilateral or no hippocampal damage (p=0.069 by chi-square analysis). Although PEM caused significant changes to baseline arterial blood pH, pO(2), pCO(2), and fasting glucose (p0.269). Intra-ischemic tympanic temperature and blood pressure were strictly and equally controlled between ischemic groups. We conclude that co-existing PEM confounded the consistency of hippocampal injury in the 2-VO model. Although the mechanisms responsible were not identified, this model of brain ischemia should not be used for studying this co-morbidity factor. © 2011 Bentham Science Publishers Ltd.

  6. Cortical hypoxic-ischemic brain damage in shaken-baby (shaken impact) syndrome: value of diffusion-weighted MRI

    International Nuclear Information System (INIS)

    Parizel, Paul M.; Oezsarlak, Oezkan; Goethem, Johan W. van; Ceulemans, Berten; Laridon, Annick; Jorens, Philippe G.

    2003-01-01

    Shaken-baby syndrome (SBS) is a type of child abuse caused by violent shaking of an infant, with or without impact, and characterized by subdural hematomas, retinal hemorrhages, and occult bone fractures. Parenchymal brain lesions in SBS may be missed or underestimated on CT scans, but can be detected at an earlier stage with diffusion-weighted MRI (DW-MRI) as areas of restricted diffusion. We demonstrate the value of DW-MRI in a 2-month-old baby boy with suspected SBS. The pattern of diffusion abnormalities indicates that the neuropathology of parenchymal lesions in SBS is due to hypoxic-ischemic brain injuries, and not to diffuse axonal injury. (orig.)

  7. Cortical hypoxic-ischemic brain damage in shaken-baby (shaken impact) syndrome: value of diffusion-weighted MRI

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    Parizel, Paul M.; Oezsarlak, Oezkan; Goethem, Johan W. van [Department of Radiology, University of Antwerp, Wilrijkstraat 10, 2650, Edegem (Belgium); Ceulemans, Berten; Laridon, Annick [Department of Pediatric Neurology, University of Antwerp, Wilrijkstraat 10, 2650, Edegem (Belgium); Jorens, Philippe G. [Department of Pediatric Intensive Care Medicine, University of Antwerp, Wilrijkstraat 10, 2650, Edegem (Belgium)

    2003-12-01

    Shaken-baby syndrome (SBS) is a type of child abuse caused by violent shaking of an infant, with or without impact, and characterized by subdural hematomas, retinal hemorrhages, and occult bone fractures. Parenchymal brain lesions in SBS may be missed or underestimated on CT scans, but can be detected at an earlier stage with diffusion-weighted MRI (DW-MRI) as areas of restricted diffusion. We demonstrate the value of DW-MRI in a 2-month-old baby boy with suspected SBS. The pattern of diffusion abnormalities indicates that the neuropathology of parenchymal lesions in SBS is due to hypoxic-ischemic brain injuries, and not to diffuse axonal injury. (orig.)

  8. Multiplex Brain Proteomic Analysis Revealed the Molecular Therapeutic Effects of Buyang Huanwu Decoction on Cerebral Ischemic Stroke Mice.

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    Hong-Jhang Chen

    Full Text Available Stroke is the second-leading cause of death worldwide, and tissue plasminogen activator (TPA is the only drug used for a limited group of stroke patients in the acute phase. Buyang Huanwu Decoction (BHD, a traditional Chinese medicine prescription, has long been used for improving neurological functional recovery in stroke. In this study, we characterized the therapeutic effect of TPA and BHD in a cerebral ischemia/reperfusion (CIR injury mouse model using multiplex proteomics approach. After the iTRAQ-based proteomics analysis, 1310 proteins were identified from the mouse brain with <1% false discovery rate. Among them, 877 quantitative proteins, 10.26% (90/877, 1.71% (15/877, and 2.62% (23/877 of the proteins was significantly changed in the CIR, BHD treatment, and TPA treatment, respectively. Functional categorization analysis showed that BHD treatment preserved the integrity of the blood-brain barrier (BBB (Alb, Fga, and Trf, suppressed excitotoxicity (Grm5, Gnai, and Gdi, and enhanced energy metabolism (Bdh, thereby revealing its multiple effects on ischemic stroke mice. Moreover, the neurogenesis marker doublecortin was upregulated, and the activity of glycogen synthase kinase 3 (GSK-3 and Tau was inhibited, which represented the neuroprotective effects. However, TPA treatment deteriorated BBB breakdown. This study highlights the potential of BHD in clinical applications for ischemic stroke.

  9. Cerebral ischemic injury decreases α-synuclein expression in brain tissue and glutamate-exposed HT22 cells.

    Science.gov (United States)

    Koh, Phil-Ok

    2017-09-01

    α-Synuclein is abundantly expressed in neuronal tissue, plays an essential role in the pathogenesis of neurodegenerative disorders, and exerts a neuroprotective effect against oxidative stress. Cerebral ischemia causes severe neurological disorders and neuronal dysfunction. In this study, we examined α-synuclein expression in middle cerebral artery occlusion (MCAO)-induced cerebral ischemic injury and neuronal cells damaged by glutamate treatment. MCAO surgical operation was performed on male Sprague-Dawley rats, and brain samples were isolated 24 hours after MCAO. We confirmed neurological behavior deficit, infarction area, and histopathological changes following MCAO injury. A proteomic approach and Western blot analysis demonstrated a decrease in α-synuclein in the cerebral cortices after MCAO injury. Moreover, glutamate treatment induced neuronal cell death and decreased α-synuclein expression in a hippocampal-derived cell line in a dose-dependent manner. It is known that α-synuclein regulates neuronal survival, and low levels of α-synuclein expression result in cytotoxicity. Thus, these results suggest that cerebral ischemic injury leads to a reduction in α-synuclein and consequently causes serious brain damage.

  10. MRI at 3 Tesla detects no evidence for ischemic brain damage in intensively treated patients with homozygous familial hypercholesterolemia

    Energy Technology Data Exchange (ETDEWEB)

    Schmitz, Stephan A.; O' Regan, Declan P.; Fitzpatrick, Julie; Hajnal, Joseph V. [Hammersmith Hospital Campus, Imaging Sciences Department, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, London (United Kingdom); Neuwirth, Clare; Potter, Elizabeth; Tosi, Isabella; Naoumova, Rossi P. [MRC Clinical Sciences Centre, Clinical Research Facility, London (United Kingdom); Hammersmith Hospital, Lipid Clinic, London (United Kingdom)

    2007-11-15

    Homozygous familial hypercholesterolemia (FH) is considered a model disease for excessive plasma cholesterol levels. Patients with untreated homozygous FH have a markedly increased risk for premature atherosclerosis. The frequency and extent of ischemic brain damage detectable by high-field magnetic resonance imaging (MRI) after long-term intensive treatment are unknown. In a case control study, five patients with homozygous FH (one male and four females; mean age: 23.6 {+-} 9.2, range: 12-36 years; mean pre-treatment serum total cholesterol level: 26.9 {+-} 3.24 mmol/L; all patients with documented atherosclerotic plaques in the carotid arteries) and five age- and sex-matched healthy controls were studied. All patients had been on maximal lipid-lowering medication since early childhood, and four of them were also on treatment with low-density lipoprotein (LDL) apheresis at bi-weekly intervals. Brain MRI was performed at 3 Tesla field strength with fluid-attenuated T2-weighted inversion recovery and T1-weighted spin-echo MR pulse sequences and subsequently evaluated by two independent readers. The maximal lipid-lowering treatment reduced the total serum cholesterol by more than 50% in the patients, but their serum concentrations were still 3.6-fold higher than those found in the controls (11.9 {+-} 4.2 vs. 4.5 {+-} 0.5 mmol/L; p < 0.0047). No brain abnormality was observed in any of the patients with homozygous FH. Homozygous FH patients on intensive cholesterol-lowering therapy have no evidence of ischemic brain damage at 3 Tesla MRI despite the remaining high cholesterol levels. (orig.)

  11. MRI at 3 Tesla detects no evidence for ischemic brain damage in intensively treated patients with homozygous familial hypercholesterolemia

    International Nuclear Information System (INIS)

    Schmitz, Stephan A.; O'Regan, Declan P.; Fitzpatrick, Julie; Hajnal, Joseph V.; Neuwirth, Clare; Potter, Elizabeth; Tosi, Isabella; Naoumova, Rossi P.

    2007-01-01

    Homozygous familial hypercholesterolemia (FH) is considered a model disease for excessive plasma cholesterol levels. Patients with untreated homozygous FH have a markedly increased risk for premature atherosclerosis. The frequency and extent of ischemic brain damage detectable by high-field magnetic resonance imaging (MRI) after long-term intensive treatment are unknown. In a case control study, five patients with homozygous FH (one male and four females; mean age: 23.6 ± 9.2, range: 12-36 years; mean pre-treatment serum total cholesterol level: 26.9 ± 3.24 mmol/L; all patients with documented atherosclerotic plaques in the carotid arteries) and five age- and sex-matched healthy controls were studied. All patients had been on maximal lipid-lowering medication since early childhood, and four of them were also on treatment with low-density lipoprotein (LDL) apheresis at bi-weekly intervals. Brain MRI was performed at 3 Tesla field strength with fluid-attenuated T2-weighted inversion recovery and T1-weighted spin-echo MR pulse sequences and subsequently evaluated by two independent readers. The maximal lipid-lowering treatment reduced the total serum cholesterol by more than 50% in the patients, but their serum concentrations were still 3.6-fold higher than those found in the controls (11.9 ± 4.2 vs. 4.5 ± 0.5 mmol/L; p < 0.0047). No brain abnormality was observed in any of the patients with homozygous FH. Homozygous FH patients on intensive cholesterol-lowering therapy have no evidence of ischemic brain damage at 3 Tesla MRI despite the remaining high cholesterol levels. (orig.)

  12. Fibroblast growth factor-2 induced by enriched environment enhances angiogenesis and motor function in chronic hypoxic-ischemic brain injury.

    Science.gov (United States)

    Seo, Jung Hwa; Yu, Ji Hea; Suh, Hwal; Kim, Myung-Sun; Cho, Sung-Rae

    2013-01-01

    This study aimed to investigate the effects of enriched environment (EE) on promoting angiogenesis and neurobehavioral function in an animal model of chronic hypoxic-ischemic (HI) brain injury. HI brain damage was induced in seven day-old CD-1® mice by unilateral carotid artery ligation and exposure to hypoxia (8% O2 for 90 min). At six weeks of age, the mice were randomly assigned to either EE or standard cages (SC) for two months. Rotarod, forelimb-use asymmetry, and grip strength tests were performed to evaluate neurobehavioral function. In order to identify angiogenic growth factors regulated by EE, an array-based multiplex ELISA assay was used to measure the expression in frontal cortex, striatum, and cerebellum. Among the growth factors, the expression of fibroblast growth factor-2 (FGF-2) was confirmed using western blotting. Platelet endothelial cell adhesion molecule-1 (PECAM-1) and α-smooth muscle actin (α-SMA) were also evaluated using immunohistochemistry. As a result, mice exposed to EE showed significant improvements in rotarod and ladder walking performances compared to SC controls. The level of FGF-2 was significantly higher in the frontal cortex of EE mice at 8 weeks after treatment in multiplex ELISA and western blot. On the other hand, FGF-2 in the striatum significantly increased at 2 weeks after exposure to EE earlier than in the frontal cortex. Expression of activin A was similarly upregulated as FGF-2 expression pattern. Particularly, all animals treated with FGF-2 neutralizing antibody abolished the beneficial effect of EE on motor performance relative to mice not given anti-FGF-2. Immunohistochemistry showed that densities of α-SMA(+) and PECAM-1(+) cells in frontal cortex, striatum, and hippocampus were significantly increased following EE, suggesting the histological findings exhibit a similar pattern to the upregulation of FGF-2 in the brain. In conclusion, EE enhances endogenous angiogenesis and neurobehavioral functions mediated by

  13. Long-term survival of human neural stem cells in the ischemic rat brain upon transient immunosuppression.

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    Laura Rota Nodari

    Full Text Available Understanding the physiology of human neural stem cells (hNSCs in the context of cell therapy for neurodegenerative disorders is of paramount importance, yet large-scale studies are hampered by the slow-expansion rate of these cells. To overcome this issue, we previously established immortal, non-transformed, telencephalic-diencephalic hNSCs (IhNSCs from the fetal brain. Here, we investigated the fate of these IhNSC's immediate progeny (i.e. neural progenitors; IhNSC-Ps upon unilateral implantation into the corpus callosum or the hippocampal fissure of adult rat brain, 3 days after global ischemic injury. One month after grafting, approximately one fifth of the IhNSC-Ps had survived and migrated through the corpus callosum, into the cortex or throughout the dentate gyrus of the hippocampus. By the fourth month, they had reached the ipsilateral subventricular zone, CA1-3 hippocampal layers and the controlateral hemisphere. Notably, these results could be accomplished using transient immunosuppression, i.e administering cyclosporine for 15 days following the ischemic event. Furthermore, a concomitant reduction of reactive microglia (Iba1+ cells and of glial, GFAP+ cells was also observed in the ipsilateral hemisphere as compared to the controlateral one. IhNSC-Ps were not tumorigenic and, upon in vivo engraftment, underwent differentiation into GFAP+ astrocytes, and β-tubulinIII+ or MAP2+ neurons, which displayed GABAergic and GLUTAmatergic markers. Electron microscopy analysis pointed to the formation of mature synaptic contacts between host and donor-derived neurons, showing the full maturation of the IhNSC-P-derived neurons and their likely functional integration into the host tissue. Thus, IhNSC-Ps possess long-term survival and engraftment capacity upon transplantation into the globally injured ischemic brain, into which they can integrate and mature into neurons, even under mild, transient immunosuppressive conditions. Most notably

  14. Attenuation of reactive gliosis does not affect infarct volume in neonatal hypoxic-ischemic brain injury in mice.

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    Katarina Järlestedt

    2010-04-01

    Full Text Available Astroglial cells are activated following injury and up-regulate the expression of the intermediate filament proteins glial fibrillary acidic protein (GFAP and vimentin. Adult mice lacking the intermediate filament proteins GFAP and vimentin (GFAP(-/-Vim(-/- show attenuated reactive gliosis, reduced glial scar formation and improved regeneration of neuronal synapses after neurotrauma. GFAP(-/-Vim(-/- mice exhibit larger brain infarcts after middle cerebral artery occlusion suggesting protective role of reactive gliosis after adult focal brain ischemia. However, the role of astrocyte activation and reactive gliosis in the injured developing brain is unknown.We subjected GFAP(-/-Vim(-/- and wild-type mice to unilateral hypoxia-ischemia (HI at postnatal day 9 (P9. Bromodeoxyuridine (BrdU; 25 mg/kg was injected intraperitoneally twice daily from P9 to P12. On P12 and P31, the animals were perfused intracardially. Immunohistochemistry with MAP-2, BrdU, NeuN, and S100 antibodies was performed on coronal sections. We found no difference in the hemisphere or infarct volume between GFAP(-/-Vim(-/- and wild-type mice at P12 and P31, i.e. 3 and 22 days after HI. At P31, the number of NeuN(+ neurons in the ischemic and contralateral hemisphere was comparable between GFAP(-/-Vim(-/- and wild-type mice. In wild-type mice, the number of S100(+ astrocytes was lower in the ipsilateral compared to contralateral hemisphere (65.0+/-50.1 vs. 85.6+/-34.0, p<0.05. In the GFAP(-/-Vim(-/- mice, the number of S100(+ astrocytes did not differ between the ischemic and contralateral hemisphere at P31. At P31, GFAP(-/-Vim(-/- mice showed an increase in NeuN(+BrdU(+ (surviving newly born neurons in the ischemic cortex compared to wild-type mice (6.7+/-7.7; n = 29 versus 2.9+/-3.6; n = 28, respectively, p<0.05, but a comparable number of S100(+BrdU(+ (surviving newly born astrocytes.Our results suggest that attenuation of reactive gliosis in the developing brain does not affect

  15. Rest/stress myocardial perfusion imaging: A means to prevent missed acute ischemic coronary syndrome diagnoses

    International Nuclear Information System (INIS)

    Fink-Bennett, D.; Pattekar, A.M.

    2002-01-01

    Aim: The sensitivity and specificity of rest/stress (R/S) myocardial perfusion imaging (MPI) in detecting an acute ischemic coronary syndrome (AICS) was determined in 100 consecutive patients (pts) admitted to the Chest Pain Clinic-Observation Unit (CPC-OU) with chest pain (CP) of suspected cardiac etiology and a negative (neg) or non diagnostic (dx) EKG. There were 57 females and 43 males, 30-83 years of age. 50 studies were performed from 1/15/98 to 4/2/98; 50 from 11/19/99 to 1/10/00. Material and Methods: An AICS was deemed present if a reversible perfusion defect was demonstrated scintigraphically; a ?50% luminal narrow angiographically. No AICS if the pt had a normal R/S MPI, a fixed defect with normal wall motion and thickening, a neg cardiac catheterization, or was free of cardiac symptoms and had no history of a vascular event for 2-3 years post CPC-OU admission. 13 pts with a positive MPI had a cardiac catheterization, none with a neg MPI. SPECT rest MPI's were performed 30-90 minutes (mins) post 10.0 mCi of technetium 99m Sestamibi. SPECT stress MPI's were performed following a 6-8 hour acute myocardial infarction enzyme (CP-MB/Troponin 1) rule out and 30-90 mins post 30.0 mCi of technetium 99m Sestamibi. Results: 29 pts were lost to follow-up. There were 12 true positive, 5 false positive, 54 true negative and 0 false negative studies. The sensitivity, specificity, positive and negative predictive value of a R/S MPI in detecting an AICS is 100%, 91%, 70% and 100%, respectively. An AICS was detected in 12% of pts admitted to the CPC-OU; a finding that correlates with its reported incidence of 2-12%. 6 were managed medically, 3 required emergent bypass surgery, 3 were stented. Conclusion: R/S MPI should be included in the CPC-OU dx work-up of pts with CP of suspected cardiac etiology to prevent missed AICS diagnoses. Patient care will be optimized and health care and medical malpractice awards for failure to diagnosis an acute myocardial infarction

  16. Risk of stroke and cardiovascular events after ischemic stroke or transient ischemic attack in patients with type 2 diabetes or metabolic syndrome: secondary analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial

    DEFF Research Database (Denmark)

    Callahan, Alfred; Amarenco, Pierre; Goldstein, Larry B

    2011-01-01

    To perform a secondary analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial, which tested the effect of treatment with atorvastatin in reducing stroke in subjects with a recent stroke or transient ischemic attack, to explore the effects of treatment...

  17. Overexpression of HIF-1α in mesenchymal stem cells contributes to repairing hypoxic-ischemic brain damage in rats.

    Science.gov (United States)

    Lin, Deju; Zhou, Liping; Wang, Biao; Liu, Lizhen; Cong, Li; Hu, Chuanqin; Ge, Tingting; Yu, Qin

    2017-01-01

    Preclinical researches on mesenchymal stem cells (MSCs) transplantation, which is used to treat hypoxic-ischemic (HI) brain damage, have received inspiring achievements. However, the insufficient migration of active cells to damaged tissues has limited their potential therapeutic effects. There are some evidences that hypoxia inducible factor-1 alpha (HIF-1α) promotes the viability and migration of the cells. Here, we aim to investigate whether overexpression of HIF-1α in MSCs could improve the viability and migration capacity of cells, and its therapeutic efficiency on HI brain damage. In the study, MSCs with HIF-1α overexpression was achieved by recombinant lentiviral vector and transplanted to the rats subsequent to HI. Our data indicated that overexpression of HIF-1α promoted the viability and migration of MSCs, HIF-1α overexpressed MSCs also had a stronger therapeutic efficiency on HI brain damaged treatment by mitigating the injury on behavioral and histological changes evoked by HI insults, accompanied with more MSCs migrating to cerebral damaged area. This study demonstrated that HIF-1α overexpression could increase the MSCs' therapeutic efficiency in HI and the promotion of the cells' directional migration to cerebral HI area by overexpression may be responsible for it, which showed that transplantation of MSCs with HIF-1α overexpression is an attractive therapeutic option to treat HI-induced brain injury in the future. Copyright © 2016 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  18. Acupuncture at Waiguan (TE5) influences activation/deactivation of functional brain areas in ischemic stroke patients and healthy people: A functional MRI study.

    Science.gov (United States)

    Chen, Junqi; Huang, Yong; Lai, Xinsheng; Tang, Chunzhi; Yang, Junjun; Chen, Hua; Zeng, Tongjun; Wu, Junxian; Qu, Shanshan

    2013-01-25

    In the present study, 10 patients with ischemic stroke in the left hemisphere and six healthy controls were subjected to acupuncture at right Waiguan (TE5). In ischemic stroke subjects, functional MRI showed enhanced activation in Broadmann areas 5, 6, 7, 18, 19, 24, 32, the hypothalamic inferior lobe, the mamillary body, and the ventral posterolateral nucleus of the left hemisphere, and Broadmann areas 4, 6, 7, 18, 19 and 32 of the right hemisphere, but attenuated activation of Broadmann area 13, the hypothalamic inferior lobe, the posterior lobe of the tonsil of cerebellum, and the culmen of the anterior lobe of hypophysis, in the left hemisphere and Broadmann area 13 in the right hemisphere. In ischemic stroke subjects, a number of deactivated brain areas were enhanced, including Broadmann areas 6, 11, 20, 22, 37, and 47, the culmen of the anterior lobe of hypophysis, alae lingulae cerebella, and the posterior lobe of the tonsil of cerebellum of the left hemisphere, and Broadmann areas 8, 37, 45 and 47, the culmen of the anterior lobe of hypophysis, pars tuberalis adenohypophyseos, inferior border of lentiform nucleus, lateral globus pallidus, inferior temporal gyrus, and the parahippocampal gyrus of the right hemisphere. These subjects also exhibited attenuation of a number of deactivated brain areas, including Broadmann area 7. These data suggest that acupuncture at Waiguan specifically alters brain function in regions associated with sensation, vision, and motion in ischemic stroke patients. By contrast, in normal individuals, acupuncture at Waiguan generally activates brain areas associated with insomnia and other functions.

  19. Basic fibroblast growth factor enhances cell proliferation in the dentate gyrus of neonatal rats following hypoxic-ischemic brain damage.

    Science.gov (United States)

    Zhu, Huan; Qiao, Lixing; Sun, Yao; Yin, Liping; Huang, Li; Jiang, Li; Li, Jiaqing

    2018-04-23

    Perinatal hypoxic-ischemic insult is considered a major contributor to child mortality and morbidity and leads to neurological deficits in newborn infants. There has been a lack of promising neurotherapeutic interventions for hypoxic-ischemic brain damage (HIBD) for clinical application in infants. The present study aimed to investigate the correlation between neurogenesis and basic fibroblast growth factor (bFGF) in the hippocampal dentate gyrus (DG) region in neonatal rats following HIBD. Cell proliferation was examined by detecting BrdU signals, and the role of bFGF in cell proliferation in the DG region following neonatal HIBD was investigated. Cell proliferation was induced by HIBD in the hippocampal DG of neonatal rats. Furthermore, bFGF gene expression was upregulated in the hippocampus in neonatal rats, particularly between 7 and 14 days after HIBD. Moreover, intraperitoneal injection of exogenous bFGF enhanced cell proliferation in the hippocampal DG following neonatal HIBD. Taken together, these data indicate that cell proliferation in the DG could be induced by neonatal HIBD, and bFGF promotes proliferation following neonatal HIBD. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Cannabidiol reduces brain damage and improves functional recovery in a neonatal rat model of arterial ischemic stroke.

    Science.gov (United States)

    Ceprián, Maria; Jiménez-Sánchez, Laura; Vargas, Carlos; Barata, Lorena; Hind, Will; Martínez-Orgado, Jose

    2017-04-01

    and purpose: Currently there is no effective treatment for neonatal arterial ischemic stroke (AIS). Cannabidiol (CBD) is neuroprotective in models of newborn hypoxic-ischemic brain damage and adult stroke. The purpose of this work was to study the protective effect of CBD in a neonatal rat model of AIS. Middle Cerebral Artery Occlusion (MCAO) was achieved in neonatal Wistar rats by introducing a nylon filament to the left MCA for 3 h; 15 min after removing the occluder vehicle (MCAO-V) or CBD single dose 5 mg/kg (MCAO-C) were administered i. p. Similarly manipulated but non-occluded rats served as controls (SHM). A set of behavioral tests was then conducted one week (P15) or one month (P38) after MCAO. Brain damage was then assessed by magnetic resonance imaging (MRI), proton magnetic resonance spectroscopy (H + -MRS) and histologic (TUNEL for cell death, immunohistochemistry for neuron, astrocyte and microglia identification) studies. CBD administration improved neurobehavioral function regarding strength, hemiparesis, coordination and sensorimotor performance as assessed at P15 and P38. MRI indicated that CBD did not reduce the volume of infarct but reduced the volume of perilesional gliosis. H + -MRS indicated that CBD reduced metabolic derangement and excitotoxicty, and protected astrocyte function. Histologic studies indicated that CBD reduced neuronal loss and apoptosis, and modulated astrogliosis and microglial proliferation and activation. CBD administration after MCAO led to long-term functional recovery, reducing neuronal loss and astrogliosis, and modulating apoptosis, metabolic derangement, excitotoxicity and neuro-inflammation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Picroside II Inhibits Neuronal Apoptosis and Improves the Morphology and Structure of Brain Tissue following Cerebral Ischemic Injury in Rats.

    Directory of Open Access Journals (Sweden)

    Tingting Wang

    Full Text Available This paper aimed to explore the protective effects of picroside II against the neuronal apoptosis and changes in morphology and structure that follow cerebral ischemic injury in rats. A focal cerebral ischemic model was established by inserting a monofilament thread to achieve middle cerebral artery occlusion (MCAO in 60 Wistar rats, and intraperitoneal injections of picroside II (20 mg/kg were administered. The neurobehavioral functions were evaluated with the modified neurological severity score (mNSS test. The cerebral infarct volumes were measured with tetrazolium chloride (TTC staining. The morphology and ultrastructure of the cortical brain tissues were observed with hematoxylin-eosin staining and transmission electron microscopy, respectively. The apoptotic cells were counted with terminal deoxynucleotidyl transferase dUTP nick-end labeling and flow cytometry, and pERK1/2 expression was determined by immunohistochemical assay and Western blot. The results indicated that neurological behavioral malfunctions and cerebral infarcts were present in the MCAO rats. In the model group, the damage to the structures of the neurons and the blood brain barrier (BBB in the cortex was more severe, and the numbers of apoptotic cells, the early apoptotic ratio (EAR and pERK1/2 expression were significantly increased in this group compared to the control group (P<0.05. In the treatment group, the neurological behavioral function and the morphology and ultrastructure of the neurons and the BBB were improved including the number of Mi increased and relative area of condensed chromosome and basement (BM thickness descreased, and the cerebral infarct volume, the number of apoptotic cells, the EAR and pERK1/2 expression were significantly decreased compared to the model group (P<0.05. These results suggest that picroside II reduced apoptosis and improved the morphology and ultrastructure of the neurons and the BBB and that these effects resulted in the

  2. Behavioral and neuroanatomical outcomes in a rat model of preterm hypoxic-ischemic brain Injury: Effects of caffeine and hypothermia.

    Science.gov (United States)

    Potter, Molly; Rosenkrantz, Ted; Fitch, R Holly

    2018-02-21

    The current study investigated behavioral and post mortem neuroanatomical outcomes in Wistar rats with a neonatal hypoxic-ischemic (HI) brain injury induced on postnatal day 6 (P6; Rice-Vannucci HI method; Rice et al., 1981). This preparation models brain injury seen in premature infants (gestational age (GA) 32-35 weeks) based on shared neurodevelopmental markers at time of insult, coupled with similar neuropathologic sequelae (Rice et al., 1981; Workman et al., 2013). Clinically, HI insult during this window is associated with poor outcomes that include attention deficit hyperactivity disorder (ADHD), motor coordination deficits, spatial memory deficits, and language/learning disabilities. To assess therapies that might offer translational potential for improved outcomes, we used a P6 HI rat model to measure the behavioral and neuroanatomical effects of two prospective preterm neuroprotective treatments - hypothermia and caffeine. Hypothermia (aka "cooling") is an approved and moderately efficacious intervention therapy for fullterm infants with perinatal hypoxic-ischemic (HI) injury, but is not currently approved for preterm use. Caffeine is a respiratory stimulant used during removal of infants from ventilation but has shown surprising long-term benefits, leading to consideration as a therapy for HI of prematurity. Current findings support caffeine as a preterm neuroprotectant; treatment significantly improved some behavioral outcomes in a P6 HI rat model and partially rescued neuropathology. Hypothermia treatment (involving core temperature reduction by 4 °C over 5 hours), conversely, was found to be largely ineffective and even deleterious for some measures in both HI and sham rats. These results have important implications for therapeutic intervention in at-risk preterm populations, and promote caution in the application of hypothermia protocols to at-risk premature infants without further research. Copyright © 2018 ISDN. Published by Elsevier Ltd. All

  3. Ischemic brain extract increases SDF-1 expression in astrocytes through the CXCR2/miR-223/miR-27b pathway.

    Science.gov (United States)

    Shin, Jin Hee; Park, Young Mi; Kim, Dong Hee; Moon, Gyeong Joon; Bang, Oh Young; Ohn, Takbum; Kim, Hyeon Ho

    2014-09-01

    Ischemic cerebral stroke is one of the leading global causes of mortality and morbidity. Ischemic preconditioning (IPC) refers to a sublethal ischemia and resulting in tolerance to subsequent severe ischemic injury. Although several pathways are reportedly involved in IPC-mediated neuroprotection, the functional role of astrocytes is not fully understood. Stromal cell-derived factor-1 (SDF-1), a CXC chemokine produced mainly in astrocytes, is a ligand for chemokine receptor CXCR4. SDF-1 is reported to play a critical role in neuroprotection after stroke by mediating the migration of neuronal progenitor cells. We hypothesized that stimuli derived from ischemic brain were involved in the protective effects of IPC. To investigate this hypothesis, the mechanism in which ischemic brain extract (IBE) induced SDF-1 expression was investigated in C6 astrocytoma cells. IBE treatment of C6 cells increased SDF-1 expression compared to that in untreated or normal brain extract (NBE)-treated cells by downregulating SDF-1 targeting miRNA, miR-27b. MiR-223 was inversely upregulated in IBE-treated cells; overexpression of miR-223 decreased the expression of miR-27b by suppressing IKKα expression. Analysis of cytokine array data revealed an IBE associated enhanced expression of CINC-1 (CXCL1) and LIX1 (CXCL5). Knockdown or inhibition of their receptor, CXCR2, abolished IBE-mediated increased expression of SDF-1. These results were confirmed in primary cultured astrocytes. Taken together, the data demonstrate that IBE-elicited signals increase SDF-1 expression through the CXCR2/miR-223/miR-27b pathway in C6 astrocytoma cells and primary astrocytes, supporting the view that increased expression of SDF-1 by ischemic insults is a possible mechanism underlying therapeutic application of IPC. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Head movement during CT brain perfusion acquisition of patients with suspected acute ischemic stroke

    International Nuclear Information System (INIS)

    Fahmi, F.; Beenen, L.F.M.; Streekstra, G.J.; Janssen, N.Y.; Jong, H.W. de; Riordan, A.; Roos, Y.B.; Majoie, C.B.; Bavel, E. van; Marquering, H.A.

    2013-01-01

    Objective: Computed Tomography Perfusion (CTP) is a promising tool to support treatment decision for acute ischemic stroke patients. However, head movement during acquisition may limit its applicability. Information of the extent of head motion is currently lacking. Our purpose is to qualitatively and quantitatively assess the extent of head movement during acquisition. Methods: From 103 consecutive patients admitted with suspicion of acute ischemic stroke, head movement in 220 CTP datasets was qualitatively categorized by experts as none, minimal, moderate, or severe. The movement was quantified using 3D registration of CTP volume data with non-contrast CT of the same patient; yielding 6 movement parameters for each time frame. The movement categorization was correlated with National Institutes of Health Stroke Scale (NIHSS) score and baseline characteristic using multinomial logistic regression and student's t-test respectively. Results: Moderate and severe head movement occurred in almost 25% (25/103) of all patients with acute ischemic stroke. The registration technique quantified head movement with mean rotation angle up to 3.6° and 14°, and mean translation up to 9.1 mm and 22.6 mm for datasets classified as moderate and severe respectively. The rotation was predominantly in the axial plane (yaw) and the main translation was in the scan direction. There was no statistically significant association between movement classification and NIHSS score and baseline characteristics. Conclusions: Moderate or severe head movement during CTP acquisition of acute stroke patients is quite common. The presented registration technique can be used to automatically quantify the movement during acquisition, which can assist identification of CTP datasets with excessive head movement

  5. Hot topics in research: Preventive neuroradiology in brain aging and cognitive decline

    NARCIS (Netherlands)

    C.A. Raji; H. Eyre; S.H. Wei; D.E. Bredesen; S. Moylan (Steven); M. Law; G. Small; P.M. Thompson (Paul); R.M. Friedlander; D.H. Silverman; B.T. Baune; T.A. Hoang; N. Salamon; A.W. Toga (Arthur); M.W. Vernooij (Meike)

    2015-01-01

    textabstractPreventive neuroradiology is a new concept supported by growing literature. The main rationale of preventive neuroradiology is the application of multimodal brain imaging toward early and subclinical detection of brain disease and subsequent preventive actions through identification of

  6. Ginkgo biloba extract neuroprotective action is dependent on heme oxygenase 1 in ischemic reperfusion brain injury.

    Science.gov (United States)

    Saleem, Sofiyan; Zhuang, Hean; Biswal, Shyam; Christen, Yves; Doré, Sylvain

    2008-12-01

    Ginkgo biloba extracts are now prescribed in several countries for their reported health benefits, particularly for medicinal properties in the brain. The standardized Ginkgo extract, EGb761, has been reported to protect neurons against oxidative stress, but the underlying mechanisms are not fully understood. To characterize the oral consumption of EGb761 in transient ischemia, we performed the middle cerebral artery occlusion (MCAO) filament model in wild-type and heme oxygenase 1 (HO-1) knockouts. Mice were pretreated for 7 days before the transient occlusion or posttreated acutely during reperfusion; then neurobehavioral scores and infarct volumes were assessed. Furthermore, primary cortical neuronal cultures were used to investigate the contribution of the antioxidant enzyme HO-1 in the EGb761-associated cytoprotection. Mice that were pretreated with EGb761 had 50.9+/-5.6% less neurological dysfunction and 48.2+/-5.3% smaller infarct volumes than vehicle-treated mice; this effect was abolished in HO-1 knockouts. In addition to the prophylactic properties of EGb761, acute posttreatment 5 minutes and 4.5 hours after reperfusion also led to significant reduction in infarct size (P<0.01). After our previous demonstration that EGb761 significantly induced HO-1 levels in a dose- and time-dependent manner in neuronal cultures, here we revealed that this de novo HO-1 induction was required for neuroprotection against free radical damage and excitotoxicity as it was significantly attenuated by the enzyme inhibitor. These results demonstrate that EGb761 could be used as a preventive or therapeutic agent in cerebral ischemia and suggest that HO-1 contributes, at least in part, to EGb761 neuroprotection.

  7. PET/CT imaging of striatal dopamine transporters in a newborn piglet model of hypoxic-ischemic brain injury

    International Nuclear Information System (INIS)

    Zhang Yanfen; Wang Xiaoming; Wang Xiaoyu; Cao Li; Guo Qiyong

    2013-01-01

    Objective: To investigate changes of striatal DAT following hypoxic ischemic (HI) brain injury in newborn piglets using 11 C-N-2-carbomethoxy-3-(4-fluorophenyl)-tropane (CFT) PET/CT, and to evaluate the value of 11 C-CFT PET/CT in brain injury. Methods: Newborn piglets with HI brain injury (n=20) were taken as a model group,and five piglets were used as a control group. Radioligand 11 C-CFT (55.5-74.0 MBq) was injected through the jugular vein, and PET/CT imaging was performed to observe the changes of striatal DAT in newborn piglets. The ST/occipital lobe (OC) ratio was calculated. Model group was divided into 0-6 h, 20-24 h, 44-48 h and 68-72 h sub-groups after HI in accordance with the imaging time. The piglets were sacrificed immediately after 11 C-CFT PET/CT scanning, and then the brains were removed for pathological analysis. Data analysis was performed with one-way analysis of variance and Pearson linear correlation analysis. Results: After intravenous injection of 11 C-CFT, the radioactivity accumulation in cortical, striatum, and cerebellum was shown clearly in the control and model groups. The radioactivity accumulation was lower in the white matter. The radioactivity in cortical and cerebellum exhibited decreased with time, while the striatum was still clear. After HI, the ST/OC activity ratio in the striatum was initially increased, and the ratio of 0-6 h group (1.34 ± 0.04) was statistically significant compared with that of the control group (1.18 ± 0.06; F=4.658, P<0.05), followed by a gradual decrease. ST/OC ratios of other HI subgroups were 1.27 ±0.01, 1.27 ±0.10 and 1.18 ±0.05, respectively. There was a positive correlation between the number of DAT positive neurons ((13 ± 3), (13 ± 4), (8 ±3) and (4 ±4)/high power field) and 11 C-CFT ST/OC activity ratios (r=0.844, P<0.05). Conclusion: 11 C-CFT PET/CT study can accurately reflect the changes of DAT in the striatum, and the amount of DAT is related to the severity of the ischemic insult

  8. DETERMINANTS OF PREVENTIVE BEHAVIOR REGARDING CARDIOVASCULAR DISEASES AND RISK FACTORS IN PATIENTS WITH ESSENTIAL HYPERTENSION AND CHRONIC ISCHEMIC HEART DISEASE

    Directory of Open Access Journals (Sweden)

    D. Yu. Platonov

    2011-01-01

    Full Text Available Aim. To analyze potential determinants of preventive behavior (PB in patients with essential hypertension (HT and chronic ischemic heart disease (CIHD, and to establish their significance and hierarchy. Material and methods. Patients with HT (n=285 and CIHD (n=223 were studied. Questioning of all patients was performed to assess the characteristics of their PB. Differentiated multivariate analysis of activity and efficacy of PB determinants was performed in HT and CIHD patients by the method of step-by-step backward logistic regression. Results. Awareness of the cardiovascular diseases (CVD and its prevention (odds ratio [OR] 6.08 as well as high level of general education (OR=2.29 were the most significant determinants of active PB in HT patients. Sufficient social support (OR=3.77, awareness of CVD and its prevention (OR=3.16 were the most significant determinants of active PB in patients with CIHD. Efficacy of PB in patients with HT and CIHD mostly depends on satisfaction of medical service (OR=10.2 and 6.63, respectively, social support (OR=6.25 and 10.5, respectively, adequate awareness of CVD and its prevention (OR, 6.92 and 6.64, respectively. Conclusion. PB activity and efficacy in patients with HT and CIHD depends on many contributing and impeding factors. Disregarding these factors can result in failure in preventive efforts at both individual and population levels.

  9. Transient ischemic attacks and presence of an acute brain lesion in diffusion-weighted MRI: study of 50 patients

    Directory of Open Access Journals (Sweden)

    Sabeti M

    2012-10-01

    Full Text Available Background: Finding an acute brain lesion by diffusion-weighted (DW MRI upon an episode of transient ischemic attack (TIA is a predictor of imminent stroke in the near future. Therefore, exploring risk factors associated with lesions in DW-MRI of the brain is important in adopting an approach to TIA management. In the current study, we tried to determine the risk factors associated with lesions in DW-MRI of the brain in patients experiencing TIA episodes.Methods: Fifty patients with TIA were recruited consecutively in Sina Hospital, Tehran, Iran, over a 6-month period between July 2008 and January 2009. All of the patients underwent a complete neurological examination and laboratory tests. Brain DW-MRIs were performed for all the patients within 72 hours of a TIA episode.Results: DW-MRI revealed an acute lesion in 16% of the participants. There was a significant correlation between presence of an acute lesion in DW-MRI and TIA duration, history of diabetes mellitus and presence of unilateral facial palsy (P=0.0003, P=0.02 and P=0.008, respectively. Other variables such as age, hypertension, hyperlipidemia, past history of TIA, headache, vertigo, and sensory or visual disturbances had no significant relation with the presence of an acute lesion in DW-MRI.Conclusion: Duration of TIA, presence of diabetes mellitus and unilateral facial palsy are risk factors for an acute lesion in DW-MRI, meaning that patients with such risk factors are at risk for stroke in the near future.

  10. Relevance of blood-brain barrier disruption after endovascular treatment of ischemic stroke: dual-energy computed tomographic study.

    Science.gov (United States)

    Renú, Arturo; Amaro, Sergio; Laredo, Carlos; Román, Luis San; Llull, Laura; Lopez, Antonio; Urra, Xabier; Blasco, Jordi; Oleaga, Laura; Chamorro, Ángel

    2015-03-01

    Computed tomographic (CT) high attenuation (HA) areas after endovascular therapy for acute ischemic stroke are a common finding indicative of blood-brain barrier disruption. Dual-energy CT allows an accurate differentiation between HA areas related to contrast staining (CS) or to brain hemorrhage (BH). We sought to evaluate the prognostic significance of the presence of CS and BH after endovascular therapy. A prospective cohort of 132 patients treated with endovascular therapy was analyzed. According to dual-energy CT findings, patients were classified into 3 groups: no HA areas (n=53), CS (n=32), and BH (n=47). The rate of new hemorrhagic transformations was recorded at follow-up neuroimaging. Clinical outcome was evaluated at 90 days with the modified Rankin Scale (poor outcome, 3-6). Poor outcome was associated with the presence of CS (odds ratio [OR], 11.3; 95% confidence interval, 3.34-38.95) and BH (OR, 10.4; 95% confidence interval, 3.42-31.68). The rate of poor outcome despite complete recanalization was also significantly higher in CS (OR, 9.7; 95% confidence interval, 2.55-37.18) and BH (OR, 15.1; 95% confidence interval, 3.85-59.35) groups, compared with the no-HA group. Patients with CS disclosed a higher incidence of delayed hemorrhagic transformation at follow-up (OR, 4.5; 95% confidence interval, 1.22-16.37) compared with no-HA patients. Blood-brain barrier disruption, defined as CS and BH on dual-energy CT, was associated with poor clinical outcomes in patients with stroke treated with endovascular therapies. Moreover, isolated CS was associated with delayed hemorrhagic transformation. These results support the clinical relevance of blood-brain barrier disruption in acute stroke. © 2015 American Heart Association, Inc.

  11. Induction of hemeoxygenase-1 expression after inhibition of hemeoxygenase activity promotes inflammation and worsens ischemic brain damage in mice.

    Science.gov (United States)

    Pérez-de-Puig, I; Martín, A; Gorina, R; de la Rosa, X; Martinez, E; Planas, A M

    2013-07-23

    Hemeoxygenase (HO) is an enzymatic system that degrades heme. HO-1 is an inducible isoform whereas HO-2 is constitutive. Stroke strongly induces HO-1 expression but the underlying mechanisms are not fully elucidated. Cytokines that are up-regulated after ischemia, like interleukin (IL)-10, can induce HO-1 gene expression, which is positively regulated by the transcriptional activator nuclear factor erythroid 2-related factor 2 (Nrf2) and negatively regulated by the transcriptional repressor breast cancer type 1 susceptibility protein (BRCA1) associated C-terminal helicase 1 (Bach-1). While Nrf2 is activated after ischemia and drugs promoting Nrf2 activation increase HO-1 and are beneficial, the involvement of Bach-1 is unknown. Here we investigated mechanisms involved in HO-1 induction and evaluated the effects of HO activity inhibition in mouse permanent middle cerebral artery occlusion (pMCAO). HO-1 was induced after ischemia in IL-10-deficient mice suggesting that post-ischemic HO-1 induction was IL-10-independent. Attenuation of Bach-1 gene repression after ischemia was associated to enhanced HO-1 induction. Administration of the HO activity inhibitor zinc proto-porphyrin IX (ZnPP) i.p. 24h before pMCAO exacerbated ischemia-induced tumor necrosis factor-α (TNF-α) and IL-1β, nitro-oxidative stress, and the presence of neutrophils at 8h, and increased infarct volume at day 4. However, ZnPP did not worsen ischemic damage when given 30min before pMCAO. ZnPP induced HO-1 expression in the cerebral vasculature at 24h, when it was still detected by high-performance liquid chromatography (HPLC) in plasma. While ZnPP was not found in brain tissue extracts of controls, it could be detected after ischemia, supporting that a small fraction of the injected drug can reach the tissue following blood-brain barrier breakdown. The deleterious effect of inhibiting HO activity in ischemia became apparent in the presence of ZnPP-induced HO-1, which is known to exert effects

  12. Linoleic acid participates in the response to ischemic brain injury through oxidized metabolites that regulate neurotransmission.

    Science.gov (United States)

    Hennebelle, Marie; Zhang, Zhichao; Metherel, Adam H; Kitson, Alex P; Otoki, Yurika; Richardson, Christine E; Yang, Jun; Lee, Kin Sing Stephen; Hammock, Bruce D; Zhang, Liang; Bazinet, Richard P; Taha, Ameer Y

    2017-06-28

    Linoleic acid (LA; 18:2 n-6), the most abundant polyunsaturated fatty acid in the US diet, is a precursor to oxidized metabolites that have unknown roles in the brain. Here, we show that oxidized LA-derived metabolites accumulate in several rat brain regions during CO 2 -induced ischemia and that LA-derived 13-hydroxyoctadecadienoic acid, but not LA, increase somatic paired-pulse facilitation in rat hippocampus by 80%, suggesting bioactivity. This study provides new evidence that LA participates in the response to ischemia-induced brain injury through oxidized metabolites that regulate neurotransmission. Targeting this pathway may be therapeutically relevant for ischemia-related conditions such as stroke.

  13. Pharmacological targeting of secondary brain damage following ischemic or hemorrhagic stroke, traumatic brain injury, and bacterial meningitis - a systematic review and meta-analysis.

    Science.gov (United States)

    Beez, Thomas; Steiger, Hans-Jakob; Etminan, Nima

    2017-12-07

    The effectiveness of pharmacological strategies exclusively targeting secondary brain damage (SBD) following ischemic stroke, aneurysmal subarachnoid hemorrhage, aSAH, intracerebral hemorrhage (ICH), traumatic brain injury (TBI) and bacterial meningitis is unclear. This meta-analysis studied the effect of SBD targeted treatment on clinical outcome across the pathological entities. Randomized, controlled, double-blinded trials on aforementioned entities with 'death' as endpoint were identified. Effect sizes were analyzed and expressed as pooled risk ratio (RR) estimates with 95% confidence intervals (CI). 123 studies fulfilled the criteria, with data on 66,561 patients. In the pooled analysis, there was a minor reduction of mortality for aSAH [RR 0.93 (95% CI:0.85-1.02)], ICH [RR 0.92 (95% CI:0.82-1.03)] and bacterial meningitis [RR 0.86 (95% CI:0.68-1.09)]. No reduction of mortality was found for ischemic stroke [RR 1.05 (95% CI:1.00-1.11)] and TBI [RR 1.03 (95% CI:0.93-1.15)]. Additional analysis of "poor outcome" as endpoint gave similar results. Subgroup analysis with respect to effector mechanisms showed a tendency towards a reduced mortality for the effector mechanism category "oxidative metabolism/stress" for aSAH with a risk ratio of 0.86 [95% CI: 0.73-1.00]. Regarding specific medications, a statistically significant reduction of mortality and poor outcome was confirmed only for nimodipine for aSAH and dexamethasone for bacterial meningitis. Our results show that only a few selected SBD directed medications are likely to reduce the rate of death and poor outcome following aSAH, and bacterial meningitis, while no convincing evidence could be found for the usefulness of SBD directed medications in ischemic stroke, ICH and TBI. However, a subtle effect on good or excellent outcome might remain undetected. These results should lead to a new perspective of secondary reactions following cerebral injury. These processes should not be seen as suicide mechanisms

  14. In Vivo Expression of Reprogramming Factors Increases Hippocampal Neurogenesis and Synaptic Plasticity in Chronic Hypoxic-Ischemic Brain Injury

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    Soohyun Wi

    2016-01-01

    Full Text Available Neurogenesis and synaptic plasticity can be stimulated in vivo in the brain. In this study, we hypothesized that in vivo expression of reprogramming factors such as Klf4, Sox2, Oct4, and c-Myc would facilitate endogenous neurogenesis and functional recovery. CD-1® mice were induced at 1 week of age by unilaterally carotid artery ligation and exposure to hypoxia. At 6 weeks of age, mice were injected GFP only or both four reprogramming factors and GFP into lateral ventricle. Passive avoidance task and open field test were performed to evaluate neurobehavioral function. Neurogenesis and synaptic activity in the hippocampus were evaluated using immunohistochemistry, qRT-PCR, and/or western blot analyses. Whereas BrdU+GFAP+ cells in the subgranular zone of the hippocampus were not significantly different, the numbers of BrdU+βIII-tubulin+ and BrdU+NeuN+ cells were significantly higher in treatment group than control group. Expressions of synaptophysin and PSD-95 were also higher in treatment group than control group. Importantly, passive avoidance task and open field test showed improvement in long-term memory and decreased anxiety in treatment group. In conclusion, in vivo expression of reprogramming factors improved behavioral functions in chronic hypoxic-ischemic brain injury. The mechanisms underlying these repair processes included endogenous neurogenesis and synaptic plasticity in the hippocampus.

  15. Elevation of brain-enriched miRNAs in cerebrospinal fluid of patients with acute ischemic stroke

    DEFF Research Database (Denmark)

    Sorensen, Sofie Solvsten; Nygaard, Ann-Britt; Carlsen, Anting Liu

    2017-01-01

    RNA qPCR assays, and 3) validation of 24 selected miRNAs with Norgen Biotek RNA extraction protocol and Applied Biosystems qPCR assays. ResultsNGS detected 71 frequently expressed miRNAs in CSF of which brain-enriched miR-9-5p and miR-128-3p were significantly higher in CSF of stroke patients compared...... to controls. When dividing stroke patients into groups according to infarct size several brain-enriched miRNAs (miR-9-5p, miR-9-3p, miR-124-3p, and miR-128-3p) were elevated in patients with infarcts >2 cm3. This trend appeared in data from both NGS, qPCR (Exiqon), and qPCR (Applied Biosystems) but was only......BackgroundThe purpose of this study was to investigate the potential of cerebrospinal fluid miRNAs as diagnostic biomarkers of acute ischemic stroke using three different profiling techniques in order to identify and bypass any influence from technical variation. MethodsCerebrospinal fluid (CSF...

  16. Astroglial Activation by an Enriched Environment after Transplantation of Mesenchymal Stem Cells Enhances Angiogenesis after Hypoxic-Ischemic Brain Injury

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    Sung-Rae Cho

    2016-09-01

    Full Text Available Transplantation of mesenchymal stem cells (MSCs has paracrine effects; however, the effects are known to be largely limited. Here we investigated the combination effects of cell transplantation and enriched environment (EE in a model of hypoxic-ischemic brain injury. Brain damage was induced in seven-day-old mice by unilateral carotid artery ligation and exposure to hypoxia (8% O2 for 90 min. At six weeks of age, the mice were randomly assigned to four groups: phosphate-buffered saline (PBS-control (CON, PBS-EE, MSC-CON, and MSC-EE. Rotarod and grip strength tests were performed to evaluate neurobehavioral functions. Histologic evaluations were also performed to confirm the extent of astrocyte activation and endogenous angiogenesis. An array-based multiplex ELISA and Western blot were used to identify growth factors in vivo and in vitro. Two weeks after treatment, levels of astrocyte density and angiogenic factors were increased in MSC-EE mice, but glial scarring was not increased. Eight weeks after treatment, angiogenesis was increased, and behavioral outcomes were synergistically improved in the MSC-EE group. Astrocytes co-cultured with MSCs expressed higher levels of angiogenic factors than astrocytes cultured alone. The mechanisms of this synergistic effect included enhanced repair processes, such as increased endogenous angiogenesis and upregulation of angiogenic factors released from activated astrocytes.

  17. The Traditional Herbal Medicine, Dangkwisoo-San, Prevents Cerebral Ischemic Injury through Nitric Oxide-Dependent Mechanisms

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    Ji Hyun Kim

    2011-01-01

    Full Text Available Dangkwisoo-San (DS is an herbal extract that is widely used in traditional Korean medicine to treat traumatic ecchymosis and pain by promoting blood circulation and relieving blood stasis. However, the effect of DS in cerebrovascular disease has not been examined experimentally. The protective effects of DS on focal ischemic brain were investigated in a mouse model. DS stimulated nitric oxide (NO production in human brain microvascular endothelial cells (HBMECs. DS (10–300 μg/mL produced a concentration-dependent relaxation in mouse aorta, which was significantly attenuated by the nitric oxide synthase (NOS inhibitor L-NAME, suggesting that DS causes vasodilation via a NO-dependent mechanism. DS increased resting cerebral blood flow (CBF, although it caused mild hypotension. To investigate the effect of DS on the acute cerebral injury, C57/BL6J mice received 90 min of middle cerebral artery occlusion followed by 22.5 h of reperfusion. DS administered 3 days before arterial occlusion significantly reduced cerebral infarct size by 53.7% compared with vehicle treatment. However, DS did not reduce brain infarction in mice treated with the relatively specific endothelial NOS (eNOS inhibitor, N5-(1-iminoethyl-L-ornithine, suggesting that the neuroprotective effect of DS is primarily endothelium-dependent. This correlated with increased phosphorylation of eNOS in the brains of DS-treated mice. DS acutely improves CBF in eNOS-dependent vasodilation and reduces infarct size in focal cerebral ischemia. These data provide causal evidence that DS is cerebroprotective via the eNOS-dependent production of NO, which ameliorates blood circulation.

  18. PACAP38 differentially effects genes and CRMP2 protein expression in ischemic core and penumbra regions of permanent middle cerebral artery occlusion model mice brain.

    Science.gov (United States)

    Hori, Motohide; Nakamachi, Tomoya; Shibato, Junko; Rakwal, Randeep; Tsuchida, Masachi; Shioda, Seiji; Numazawa, Satoshi

    2014-09-23

    Pituitary adenylate-cyclase activating polypeptide (PACAP) has neuroprotective and axonal guidance functions, but the mechanisms behind such actions remain unclear. Previously we examined effects of PACAP (PACAP38, 1 pmol) injection intracerebroventrically in a mouse model of permanent middle cerebral artery occlusion (PMCAO) along with control saline (0.9% NaCl) injection. Transcriptomic and proteomic approaches using ischemic (ipsilateral) brain hemisphere revealed differentially regulated genes and proteins by PACAP38 at 6 and 24 h post-treatment. However, as the ischemic hemisphere consisted of infarct core, penumbra, and non-ischemic regions, specificity of expression and localization of these identified molecular factors remained incomplete. This led us to devise a new experimental strategy wherein, ischemic core and penumbra were carefully sampled and compared to the corresponding contralateral (healthy) core and penumbra regions at 6 and 24 h post PACAP38 or saline injections. Both reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were used to examine targeted gene expressions and the collapsin response mediator protein 2 (CRMP2) protein profiles, respectively. Clear differences in expression of genes and CRMP2 protein abundance and degradation product/short isoform was observed between ischemic core and penumbra and also compared to the contralateral healthy tissues after PACAP38 or saline treatment. Results indicate the importance of region-specific analyses to further identify, localize and functionally analyse target molecular factors for clarifying the neuroprotective function of PACAP38.

  19. PACAP38 Differentially Effects Genes and CRMP2 Protein Expression in Ischemic Core and Penumbra Regions of Permanent Middle Cerebral Artery Occlusion Model Mice Brain

    Directory of Open Access Journals (Sweden)

    Motohide Hori

    2014-09-01

    Full Text Available Pituitary adenylate-cyclase activating polypeptide (PACAP has neuroprotective and axonal guidance functions, but the mechanisms behind such actions remain unclear. Previously we examined effects of PACAP (PACAP38, 1 pmol injection intracerebroventrically in a mouse model of permanent middle cerebral artery occlusion (PMCAO along with control saline (0.9% NaCl injection. Transcriptomic and proteomic approaches using ischemic (ipsilateral brain hemisphere revealed differentially regulated genes and proteins by PACAP38 at 6 and 24 h post-treatment. However, as the ischemic hemisphere consisted of infarct core, penumbra, and non-ischemic regions, specificity of expression and localization of these identified molecular factors remained incomplete. This led us to devise a new experimental strategy wherein, ischemic core and penumbra were carefully sampled and compared to the corresponding contralateral (healthy core and penumbra regions at 6 and 24 h post PACAP38 or saline injections. Both reverse transcription-polymerase chain reaction (RT-PCR and Western blotting were used to examine targeted gene expressions and the collapsin response mediator protein 2 (CRMP2 protein profiles, respectively. Clear differences in expression of genes and CRMP2 protein abundance and degradation product/short isoform was observed between ischemic core and penumbra and also compared to the contralateral healthy tissues after PACAP38 or saline treatment. Results indicate the importance of region-specific analyses to further identify, localize and functionally analyse target molecular factors for clarifying the neuroprotective function of PACAP38.

  20. Demyelinating and ischemic brain diseases: detection algorithm through regular magnetic resonance images

    Science.gov (United States)

    Castillo, D.; Samaniego, René; Jiménez, Y.; Cuenca, L.; Vivanco, O.; Rodríguez-Álvarez, M. J.

    2017-09-01

    This work presents the advance to development of an algorithm for automatic detection of demyelinating lesions and cerebral ischemia through magnetic resonance images, which have contributed in paramount importance in the diagnosis of brain diseases. The sequences of images to be used are T1, T2, and FLAIR. Brain demyelination lesions occur due to damage of the myelin layer of nerve fibers; and therefore this deterioration is the cause of serious pathologies such as multiple sclerosis (MS), leukodystrophy, disseminated acute encephalomyelitis. Cerebral or cerebrovascular ischemia is the interruption of the blood supply to the brain, thus interrupting; the flow of oxygen and nutrients needed to maintain the functioning of brain cells. The algorithm allows the differentiation between these lesions.

  1. Glutamate receptors in NG2-glial cells: gene profiling and functional changes after ischemic brain injury

    OpenAIRE

    Waloschková, Eliška

    2017-01-01

    Glutamate is the main excitatory neurotransmitter in the mammalian brain and its transmission is responsible for higher brain functions, such as learning, memory and cognition. Glutamate action is mediated by a variety of glutamate receptors, though their properties were until now studied predominantly in neurons. Glutamate receptors are expressed also in NG2-glia, however their role under physiological conditions as well as in pathological states of the central nervous system is not fully un...

  2. Glucocorticoids and Preterm Hypoxic-Ischemic Brain Injury: The Good and the Bad

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    Laura Bennet

    2012-01-01

    Full Text Available Fetuses at risk of premature delivery are now routinely exposed to maternal treatment with synthetic glucocorticoids. In randomized clinical trials, these substantially reduce acute neonatal systemic morbidity, and mortality, after premature birth and reduce intraventricular hemorrhage. However, the overall neurodevelopmental impact is surprisingly unclear; worryingly, postnatal glucocorticoids are consistently associated with impaired brain development. We review the clinical and experimental evidence on how glucocorticoids may affect the developing brain and highlight the need for systematic research.

  3. Zingiber officinale Mitigates Brain Damage and Improves Memory Impairment in Focal Cerebral Ischemic Rat

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    Jintanaporn Wattanathorn

    2011-01-01

    Full Text Available Cerebral ischemia is known to produce brain damage and related behavioral deficits including memory. Recently, accumulating lines of evidence showed that dietary enrichment with nutritional antioxidants could reduce brain damage and improve cognitive function. In this study, possible protective effect of Zingiber officinale, a medicinal plant reputed for neuroprotective effect against oxidative stress-related brain damage, on brain damage and memory deficit induced by focal cerebral ischemia was elucidated. Male adult Wistar rats were administrated an alcoholic extract of ginger rhizome orally 14 days before and 21 days after the permanent occlusion of right middle cerebral artery (MCAO. Cognitive function assessment was performed at 7, 14, and 21 days after MCAO using the Morris water maze test. The brain infarct volume and density of neurons in hippocampus were also determined. Furthermore, the level of malondialdehyde (MDA, superoxide dismutase (SOD, catalase (CAT, and glutathione peroxidase (GSH-Px in cerebral cortex, striatum, and hippocampus was also quantified at the end of experiment. The results showed that cognitive function and neurons density in hippocampus of rats receiving ginger rhizome extract were improved while the brain infarct volume was decreased. The cognitive enhancing effect and neuroprotective effect occurred partly via the antioxidant activity of the extract. In conclusion, our study demonstrated the beneficial effect of ginger rhizome to protect against focal cerebral ischemia.

  4. Value of fluid-attenuated inversion recovery sequences in early MRI of the brain in neonates with a perinatal hypoxic-ischemic encephalopathy

    Energy Technology Data Exchange (ETDEWEB)

    Sie, L.T.L.; Knaap, M.S. van der [Vrije Univ. Hospital, Amsterdam (Netherlands). Dept. of Neurology; Barkhof, F.; Valk, J. [Amsterdam Univ. (Netherlands). Dept. of Diagnostic Radiology, Pathology and Gastroenterology; Lafeber, H.N. [Univ. Hospital ' Vrije Universiteit' , Amsterdam (Netherlands). Dept. of Neonatology

    2000-10-01

    The aim of our study was to assess the usefulness of fluid-attenuated inversion recovery (FLAIR) sequences in comparison with conventional spin-echo and inversion MR imaging in neonates for evaluation of myelination and for detection of hypoxic-ischemic brain injury. We reviewed early MR scans of 18 neonates with suspected hypoxic-ischemic brain damage. Myelination could be evaluated with confidence using conventional MR imaging in all but 2 infants; however, the presence of myelin was very difficult to assess on FLAIR images. Overall, 53 lesions or groups of lesions were identified. The FLAIR technique was more sensitive in 11 of the lesions; especially (pre)cystic lesions could be identified much better and more cysts were found. Conventional MR imaging failed to identify 2 of the lesions and was more sensitive in 14 of the lesions; especially punctate hemorrhages and lesions in basal ganglia or thalami could be better determined. The FLAIR technique missed 3 of these lesions. In the remaining 28 lesions conventional MR and FLAIR images were equally diagnostic. The FLAIR technique and conventional MR imaging are complementary in detecting early sequelae of hypoxic-ischemic brain injury in neonates. The FLAIR technique is not suitable for assessing myelination of the neonatal brain; therefore, FLAIR cannot replace conventional MR imaging. (orig.)

  5. Ex-Vivo Characterization of Bioimpedance Spectroscopy of Normal, Ischemic and Hemorrhagic Rabbit Brain Tissue at Frequencies from 10 Hz to 1 MHz.

    Science.gov (United States)

    Yang, Lin; Zhang, Ge; Song, Jiali; Dai, Meng; Xu, Canhua; Dong, Xiuzhen; Fu, Feng

    2016-11-18

    Stroke is a severe cerebrovascular disease and is the second greatest cause of death worldwide. Because diagnostic tools (CT and MRI) to detect acute stroke cannot be used until the patient reaches the hospital setting, a portable diagnostic tool is urgently needed. Because biological tissues have different impedance spectra under normal physiological conditions and different pathological states, multi-frequency electrical impedance tomography (MFEIT) can potentially detect stroke. Accurate impedance spectra of normal brain tissue (gray and white matter) and stroke lesions (ischemic and hemorrhagic tissue) are important elements when studying stroke detection with MFEIT. To our knowledge, no study has comprehensively measured the impedance spectra of normal brain tissue and stroke lesions for the whole frequency range of 1 MHz within as short as possible an ex vivo time and using the same animal model. In this study, we established intracerebral hemorrhage and ischemic models in rabbits, then measured and analyzed the impedance spectra of normal brain tissue and stroke lesions ex vivo within 15 min after animal death at 10 Hz to 1 MHz. The results showed that the impedance spectra of stroke lesions significantly differed from those of normal brain tissue; the ratio of change in impedance of ischemic and hemorrhagic tissue with regard to frequency was distinct; and tissue type could be discriminated according to its impedance spectra. These findings further confirm the feasibility of detecting stroke with MFEIT and provide data supporting further study of MFEIT to detect stroke.

  6. Effect of atropine and gammahydroxybutyrate on ischemically induced changes in the level of radioactivity in [3H]inositol phosphates in gerbil brain in vivo

    International Nuclear Information System (INIS)

    Wikiel, H.; Halat, G.; Strosznajder, J.

    1988-01-01

    Brain ischemia in gerbils was induced by ligation of both common carotid arteries for 1 min or 10 min. Sham-operated animals served as controls. Intracerebral injection of [3H]inositol into gerbil brain 16 hr before ischemic insult resulted in equilibration of the label between inositol lipids and water-soluble inositol phosphate. A short ischemic period (1 min) resulted in a statistically significant increase in the radioactivity of inositol triphosphate (IP3) and inositol monophosphate (IP), by about 48% and 79%, respectively, with little change in that of the intermediate inositol biphosphate (IP2), which increased by about 16%. When the ischemic period was prolonged (10 min), an increase in the radioactivity of inositol monophosphate exclusively, by about 84%, was observed. The level of radioactivity in inositol phosphates IP2 and IP3 decreased by about 50%, probably as a consequence of phosphatase activation by the ischemic insult. The agonist of the cholinergic receptor, carbachol, injected intracerebrally (40 micrograms per animal) increased accumulation of radioactivity in all inositol phosphates. The level of radioactivity in IP3, IP2, and IP was elevated by about 40, 23, and 147%, respectively. The muscarinic cholinergic antagonist, atropine, injected intraperitoneally in doses of 100 mg/kg body wt. depressed phosphoinositide metabolism in control animals. The level of radioactivity in water-soluble inositol metabolites in the brain of animals pretreated with atropine was evidently about 32% lower than in untreated animals. Pretreatment with atropine decreased the radioactivity of all inositol phosphates in the brain of animals subjected to 1-min ischemia and the radioactivity of IP in the case of 10-min brain ischemia

  7. Vascular expression of angiopoietin1, α5β1 integrin and tight junction proteins is tightly regulated during vascular remodeling in the post-ischemic brain.

    Science.gov (United States)

    Sun, Jialan; Yu, Liming; Huang, Shu; Lai, Xiaoyin; Milner, Richard; Li, Longxuan

    2017-10-24

    The post-stroke angiogenic response is accompanied by changes of tight junctions (TJs) of the blood-brain barrier (BBB). However, the precise dynamic change of TJ proteins (TJPs) in the different stages of stroke-induced vascular remodeling and the molecules mediating these processes have yet to be fully defined. To investigate the temporal relationship between changes in TJPs, the pro-angiogenic factor α5β1 integrin and the anti-permeability factor Ang1 in cerebral vessels following cerebral ischemic stroke, male C57Bl/6 mice were subject to 90min of ischemia by temporary occlusion of the middle cerebral artery followed by reperfusion and their brains analyzed 0, 1, 2, 4, 7 and 14days post-ischemia. Immunofluorescent studies demonstrated that in the ischemic penumbra, TJPs claudin-5 and ZO-1 levels decreased during the early stages of vascular remodeling, but then increased in the later stages. In contrast, within the ischemic core, TJPs levels decreased over the 14-day time-course, plateaued at day 4, and remained at low levels up to day 14. In the penumbra, Ang1 expression was induced, peaking at the same time point as α5β1 expression. Consistent with these findings, oxygen glucose deprivation/reperfusion induced expression of α5β1 and Ang1 on brain endothelial cell (BEC) in a similar manner in vitro, which correlated closely with BEC proliferation and increased expression of TJPs. Our results demonstrate that in the post-ischemic penumbra, a tight temporal correlation exists between the angiogenic markers α5β1 and Ang1 and the TJPs, suggesting a potential role for Ang1 and α5β1 in promoting BBB integrity following ischemic stroke. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. Chemical exchange-sensitive spin-lock MRI of glucose analog 3-O-methyl-d-glucose in normal and ischemic brain.

    Science.gov (United States)

    Jin, Tao; Mehrens, Hunter; Wang, Ping; Kim, Seong-Gi

    2018-05-01

    Glucose transport is important for understanding brain glucose metabolism. We studied glucose transport with a presumably non-toxic and non-metabolizable glucose analog, 3-O-methyl-d-glucose, using a chemical exchange-sensitive spin-lock MRI technique at 9.4 Tesla. 3-O-methyl-d-glucose showed comparable chemical exchange properties with d-glucose and 2-deoxy-d-glucose in phantoms, and higher and lower chemical exchange-sensitive spin-lock sensitivity than Glc and 2-deoxy-d-glucose in in vivo experiments, respectively. The changes of the spin-lattice relaxation rate in the rotating frame (Δ R 1 ρ) in normal rat brain peaked at ∼15 min after the intravenous injection of 1 g/kg 3-O-methyl-d-glucose and almost maintained a plateau for >1 h. Doses up to 4 g/kg 3-O-methyl-d-glucose were linearly correlated with Δ R 1 ρ. In rats with focal ischemic stroke, chemical exchange-sensitive spin-lock with 3-O-methyl-d-glucose injection at 1 h after stroke onset showed reduced Δ R 1 ρ in the ischemic core but higher Δ R 1 ρ in the peri-core region compared to normal tissue, which progressed into the ischemic core at 3 h after stroke onset. This suggests that the hyper-chemical exchange-sensitive spin-lock region observed at 1 h is the ischemic penumbra at-risk of infarct. In summary, 3-O-methyl-d-glucose-chemical exchange-sensitive spin-lock can be a sensitive MRI technique to probe the glucose transport in normal and ischemic brains.

  9. Protective Effects of L-902,688, a Prostanoid EP4 Receptor Agonist, against Acute Blood-Brain Barrier Damage in Experimental Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Kelly M. DeMars

    2018-02-01

    Full Text Available Ischemic stroke occurs when a clot forms in the brain vasculature that starves downstream tissue of oxygen and nutrients resulting in cell death. The tissue immediately downstream of the blockage, the core, dies within minutes, but the surrounding tissue, the penumbra is potentially salvageable. Prostaglandin E2 binds to four different G-protein coupled membrane receptors EP1–EP4 mediating different and sometimes opposing responses. Pharmacological activation of the EP4 receptor has already been established as neuroprotective in stroke, but the mechanism(s of protection are not well-characterized. In this study, we hypothesized that EP4 receptor activation reduces ischemic brain injury by reducing matrix metalloproteinase (MMP-3/-9 production and blood-brain barrier (BBB damage. Rats underwent transient ischemic stroke for 90 min. Animals received an intravenous injection of either the vehicle or L-902,688, a highly specific EP4 agonist, at the onset of reperfusion. Brain tissue was harvested at 24 h. We established a dose-response curve and used the optimal dose that resulted in the greatest infarct reduction to analyze BBB integrity compared to vehicle-treated rats. The presence of IgG, a blood protein, in the brain parenchyma is a marker of BBB damage, and L-902,688 (1 mg/kg; i.v. dramatically reduced IgG extravasation (P < 0.05. Consistent with these data, we assessed zona occludens-1 and occludin, tight junction proteins integral to the maintenance of the BBB, and found reduced degradation with L-902,688 administration. With immunoblotting, qRT-PCR, and/or a fluorescence resonance energy transfer (FRET-based activity assay, we next measured MMP-3/-9 since they are key effectors of BBB breakdown in stroke. In the cerebral cortex, not only was MMP-3 activity significantly decreased (P < 0.05, but L-902,688 treatment also reduced MMP-9 mRNA, protein, and enzymatic activity (P < 0.001. In addition, post-ischemic administration of the EP4

  10. Age dependent accumulation of N-acyl-ethanolamine phospholipids in ischemic rat brain

    DEFF Research Database (Denmark)

    Moesgaard, B.; Petersen, G.; Hansen, Harald S.

    2000-01-01

    of various age (1, 6, 12, 19, 30, and ~70 days) by the use of P NMR spectroscopy of lipid extracts. This ability to accumulate NAPE was compared with the activity of N-acyltransferase and of NAPE-hydrolyzing phospholipase D (NAPE-PLD) in brain microsomes. These two enzymes are involved in the formation...... brains NAPE accumulation could not be detected (detection limit 0.09 %)]; and 2) this age pattern of accumulation can be explained by a combination of the decreased activity of N- acyltransferase and the increased activity of NAPE-PLD during development. These results point out that it would......N-acyl-ethanolamine phospholipids (NAPE) can be formed as a stress response during neuronal injury, and they are precursors for N-acyl- ethanolamines (NAE), some of which are endocannabinoids. The levels of NAPE accumulated during post-decapitative ischemia (6 h at 37°C) were studied in rat brains...

  11. [Effect of a new derivative of glutamic and apovincaminic acids on brain metabolism in post-ischemic period].

    Science.gov (United States)

    Makarova, L M; Prikhod'ko, M A; Pogorelyĭ, V E; Skachilova, S Ia; Mirzoian, R S

    2014-01-01

    Neuroprotective properties of the new derivative of glutamic and apovincaminic acids, ethyl -(3-alpha,16-alpha)-eburnamenin-14-carbopxylate of 2-aminopentadionic acid (LHT 1-02) were studied on a model of acute brain ischemia in cats. LHT 1-02 has proved to be more effective than the reference drugs vinpocetin and glycine in preventing the reperfusive damage, which was manifested by decreased postischemic hyperglycemia, activated utilization of oxygen in the brain, and suppressed postischemic metabolic lactate acidosis. Thus, the results of this comparative study show expediency of further investigations of LHT 1 - 02 as a potential neuroprotective drug.

  12. Tissue is more important than time: insights into acute ischemic stroke from modern brain imaging.

    Science.gov (United States)

    Bivard, Andrew; Parsons, Mark

    2018-02-01

    The clinical practice of acute ischemic stroke treatment has undergone a major change over the last 5 years, as multimodal imaging becomes more accessible, and evidence mounts that individualized treatment is possible. Multimodal imaging performed before treatment provides invaluable information to treating clinicians, which includes confirmation of the diagnosis, and provides guidance on the appropriateness and the likely outcome of intravenous or endovascular treatment for individual patients (and their families). However, often health systems struggle to keep pace with science; thus, a one-size fits all protocol-driven basic imaging approach is still the norm in many stroke centers. Comprehensive multimodal computed tomography (CT) (incorporating noncontrast CT, CT angiography, and perfusion CT) provides rapid, reliable information about stroke pathophysiology that cannot be provided by more limited imaging prior to treatment. Multimodal CT identifies treatment responders for both intravenous thrombolysis and endovascular therapy. Now we are in the era of thrombectomy, the use of multimodal imaging routinely to guide treatment can no longer be avoided. In light of the ground breaking thrombectomy trial results and previous studies validating the use of multimodal imaging, there is now a strong rationale for performing comprehensive multimodal CT assessments before treatment as a standard of care for all stroke patients.

  13. The effect of whole-body cooling on brain metabolism following perinatal hypoxic-ischemic injury.

    Science.gov (United States)

    Corbo, Elizabeth T; Bartnik-Olson, Brenda L; Machado, Sandra; Merritt, T Allen; Peverini, Ricardo; Wycliffe, Nathaniel; Ashwal, Stephen

    2012-01-01

    Magnetic resonance imaging (MRI) and spectroscopy (MRS) have proven valuable in evaluating neonatal hypoxic-ischemic injury (HII). MRI scores in the basal ganglia of HII/HT(+) neonates were significantly lower than HII/HT(-) neonates, indicating less severe injury and were associated with lower discharge encephalopathy severity scores in the HII/HT(+) group (P = 0.01). Lactate (Lac) was detected in the occipital gray matter (OGM) and thalamus (TH) of significantly more HII/HT(-) neonates (31.6 and 35.3%) as compared to the HII/HT(+) group (10.5 and 15.8%). In contrast, the -N-acetylaspartate (NAA)-based ratios in the OGM and TH did not differ between the HII groups. Our data show that the HT was associated with a decrease in the number of HII neonates with detectable cortical and subcortical Lac as well as a decrease in the number of MRI-detectable subcortical lesions. We retrospectively compared the medical and neuroimaging data of 19 HII neonates who received 72 h of whole-body cooling (HII/HT(+)) with those of 19 noncooled HII neonates (HII/HT(-)) to determine whether hypothermia was associated with improved recovery from the injury as measured by MRI and MRS within the first 14 days of life. MRI scores and metabolite ratios of HII/HT(+) and HII/HT(-) neonates were also compared with nine healthy, nonasphyxiated "control" neonates.

  14. Macrophage-derived osteopontin induces reactive astrocyte polarization and promotes re-establishment of the blood brain barrier after ischemic stroke.

    Science.gov (United States)

    Gliem, Michael; Krammes, Kristina; Liaw, Lucy; van Rooijen, Nico; Hartung, Hans-Peter; Jander, Sebastian

    2015-12-01

    Infarcted regions of the brain after stroke are segregated from the intact brain by scar tissue comprising both fibrous and glial components. The extent and quality of scarring is influenced by inflammation. The matricellular glycoprotein osteopontin (OPN) is strongly induced in myeloid cells after stroke and may contribute to repair of ischemic brain lesions. To elucidate the role of OPN in scar formation, we induced photothrombotic brain infarction, characterized by circumscribed cortical infarctions with a well-defined border zone toward the intact brain parenchyma. The cellular source and functional role of OPN was addressed by studies in OPN null (OPN(-/-) ) mice, wild-type mice depleted of hematogenous monocytes/macrophages by clodronate-filled liposome treatment, and CCR2(-/-) bone marrow chimeric mice characterized by impaired hematogenous macrophage influx into the infarctions. OPN was mainly produced by hematogenous macrophages infiltrating into the inner border zone of the infarcts whereas astrocyte activation occurred in the outer border zone. In OPN(-/-) as well as macrophage-depleted mice, reactive astrocytes failed to properly extend processes from the periphery toward the center of the infarctions. This was associated with incomplete coverage of neovessels by astrocytic endfeet and persistent leakiness of the damaged blood brain barrier. In conclusion, OPN produced by hematogenous macrophages induces astrocyte process extension toward the infarct border zone, which may contribute to repair of the ischemic neurovascular unit. © 2015 Wiley Periodicals, Inc.

  15. Acupuncture at Waiguan (SJ5) and sham points influences activation of functional brain areas of ischemic stroke patients: a functional magnetic resonance imaging study

    OpenAIRE

    Qi, Ji; Chen, Junqi; Huang, Yong; Lai, Xinsheng; Tang, Chunzhi; Yang, Junjun; Chen, Hua; Qu, Shanshan

    2014-01-01

    Most studies addressing the specificity of meridians and acupuncture points have focused mainly on the different neural effects of acupuncture at different points in healthy individuals. This study examined the effects of acupuncture on brain function in a pathological context. Sixteen patients with ischemic stroke were randomly assigned to true point group (true acupuncture at right Waiguan (SJ5)) and sham point group (sham acupuncture). Results of functional magnetic resonance imaging revea...

  16. Acupuncture at Waiguan (TE5) influences activation/deactivation of functional brain areas in ischemic stroke patients and healthy people: A functional MRI study☆

    Science.gov (United States)

    Chen, Junqi; Huang, Yong; Lai, Xinsheng; Tang, Chunzhi; Yang, Junjun; Chen, Hua; Zeng, Tongjun; Wu, Junxian; Qu, Shanshan

    2013-01-01

    In the present study, 10 patients with ischemic stroke in the left hemisphere and six healthy controls were subjected to acupuncture at right Waiguan (TE5). In ischemic stroke subjects, functional MRI showed enhanced activation in Broadmann areas 5, 6, 7, 18, 19, 24, 32, the hypothalamic inferior lobe, the mamillary body, and the ventral posterolateral nucleus of the left hemisphere, and Broadmann areas 4, 6, 7, 18, 19 and 32 of the right hemisphere, but attenuated activation of Broadmann area 13, the hypothalamic inferior lobe, the posterior lobe of the tonsil of cerebellum, and the culmen of the anterior lobe of hypophysis, in the left hemisphere and Broadmann area 13 in the right hemisphere. In ischemic stroke subjects, a number of deactivated brain areas were enhanced, including Broadmann areas 6, 11, 20, 22, 37, and 47, the culmen of the anterior lobe of hypophysis, alae lingulae cerebella, and the posterior lobe of the tonsil of cerebellum of the left hemisphere, and Broadmann areas 8, 37, 45 and 47, the culmen of the anterior lobe of hypophysis, pars tuberalis adenohypophyseos, inferior border of lentiform nucleus, lateral globus pallidus, inferior temporal gyrus, and the parahippocampal gyrus of the right hemisphere. These subjects also exhibited attenuation of a number of deactivated brain areas, including Broadmann area 7. These data suggest that acupuncture at Waiguan specifically alters brain function in regions associated with sensation, vision, and motion in ischemic stroke patients. By contrast, in normal individuals, acupuncture at Waiguan generally activates brain areas associated with insomnia and other functions. PMID:25206592

  17. Age dependent accumulation of N-acyl-ethanolamine phospholipids in ischemic rat brain

    DEFF Research Database (Denmark)

    Moesgaard, B.; Petersen, G.; Hansen, Harald S.

    2000-01-01

    N-acyl-ethanolamine phospholipids (NAPE) can be formed as a stress response during neuronal injury, and they are precursors for N-acyl- ethanolamines (NAE), some of which are endocannabinoids. The levels of NAPE accumulated during post-decapitative ischemia (6 h at 37°C) were studied in rat brains...

  18. The Neuroprotective Effects of Flaxseed Oil Supplementation on Functional Motor Recovery in a Model of Ischemic Brain Stroke: Upregulation of BDNF and GDNF.

    Science.gov (United States)

    Bagheri, Abolqasem; Talei, Sahand; Hassanzadeh, Negar; Mokhtari, Tahmineh; Akbari, Mohammad; Malek, Fatemeh; Jameie, Seyed Behnamedin; Sadeghi, Yousef; Hassanzadeh, Gholamreza

    2017-12-01

    Cerebral ischemic stroke is a common leading cause of disability. Flaxseed is a richest plant-based source of antioxidants. In this study, the effects of flaxseed oil (FSO) pretreatment on functional motor recovery and gene expression and protein content of neurotrophic factors in motor cortex area in rat model of brain ischemia/reperfusion (I/R) were assessed. Transient middle cerebral artery occlusion (tMCAo) in rats was used as model brain I/R. Rats (6 in each group) were randomly divided into four groups of Control (Co+normal saline [NS]), Sham (Sh+NS), tMCAo+NS and tMCAo+FSO. After three weeks of pretreatment with vehicle or FSO (0.2 ml~800 mg/kg body weight), the rats were operated in sham and ischemic groups. Ischemia was induced for 1 h and then reperfused. After 24 h of reperfusion, neurological examination was performed, and animals were sacrificed, and their brains were used for molecular and histopathological studies. FSO significantly improved the functional motor recovery compared with tMCAo+NS group (Pmotor cortex area following cerebral ischemic stroke by increasing the neurotrophic factors (BDNF, GDNF).

  19. HO1 and Wnt expression is independently regulated in female mice brains following permanent ischemic brain injury.

    Science.gov (United States)

    Tulsulkar, Jatin; Ward, Alicia; Shah, Zahoor A

    2017-05-01

    A gender difference in stroke is observed throughout epidemiologic studies, pathophysiology, treatment and outcomes. We investigated the neuroprotective role of hemeoxygenase (HO) enzyme, which catabolizes free heme to bilirubin, carbon monoxide and biliverdin in the female brain after permanent ischemia. We have previously reported in male mice that genetic deletion of HO1 exacerbates the brain damage after permanent ischemia, and the mechanism of neuroprotection is dependent on the HO1/Wnt pathway; however, the role of HO1/Wnt mediated neuroprotection in the female brain is yet to be investigated. We subjected ovary intact female mice, HO1 -/- intact, HO1 inhibitor tin mesoporphyrin (SnMP) treated intact and/or ovariectomized female mice to permanent ischemia (pMCAO), and the animals were sacrificed after 7days. The SnMP treatment for 7days significantly reduced the HO1 enzyme activity as compared to that of vehicle treated group. Infarct volume analysis showed significantly lower infarct in intact, HO1 -/- intact, and SnMP treated group as compared to the OVX group, suggesting the role of estrogen in neuroprotection. However, there were no differences in infarct volume observed between the intact, HO1 -/- and SnMP treated group, suggesting a sexually dimorphic role of HO1 neuroprotection. Western blot analysis on intact and SnMP-treated groups subjected to pMCAO suggested no significant differences in Wnt expression. Together, these results suggest that HO1 neuroprotection is sexually dimorphic and Wnt expression is independently regulated in the female brain following permanent ischemia. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. [Isoflurane provides neuroprotection in neonatal hypoxic ischemic brain injury by suppressing apoptosis].

    Science.gov (United States)

    Zhao, De-An; Bi, Ling-Yun; Huang, Qian; Zhang, Fang-Min; Han, Zi-Ming

    Isoflurane is halogenated volatile ether used for inhalational anesthesia. It is widely used in clinics as an inhalational anesthetic. Neonatal hypoxic ischemia injury ensues in the immature brain that results in delayed cell death via excitotoxicity and oxidative stress. Isoflurane has shown neuroprotective properties that make a beneficial basis of using isoflurane in both cell culture and animal models, including various models of brain injury. We aimed to determine the neuroprotective effect of isoflurane on hypoxic brain injury and elucidated the underlying mechanism. A hippocampal slice, in artificial cerebrospinal fluid with glucose and oxygen deprivation, was used as an in vitro model for brain hypoxia. The orthodromic population spike and hypoxic injury potential were recorded in the CA1 and CA3 regions. Amino acid neurotransmitters concentration in perfusion solution of hippocampal slices was measured. Isoflurane treatment caused delayed elimination of population spike and improved the recovery of population spike; decreased frequency of hypoxic injury potential, postponed the onset of hypoxic injury potential and increased the duration of hypoxic injury potential. Isoflurane treatment also decreased the hypoxia-induced release of amino acid neurotransmitters such as aspartate, glutamate and glycine induced by hypoxia, but the levels of γ-aminobutyric acid were elevated. Morphological studies showed that isoflurane treatment attenuated edema of pyramid neurons in the CA1 region. It also reduced apoptosis as evident by lowered expression of caspase-3 and PARP genes. Isoflurane showed a neuro-protective effect on hippocampal neuron injury induced by hypoxia through suppression of apoptosis. Copyright © 2016 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  1. Isoflurane provides neuroprotection in neonatal hypoxic ischemic brain injury by suppressing apoptosis.

    Science.gov (United States)

    Zhao, De-An; Bi, Ling-Yun; Huang, Qian; Zhang, Fang-Min; Han, Zi-Ming

    Isoflurane is halogenated volatile ether used for inhalational anesthesia. It is widely used in clinics as an inhalational anesthetic. Neonatal hypoxic ischemia injury ensues in the immature brain that results in delayed cell death via excitotoxicity and oxidative stress. Isoflurane has shown neuroprotective properties that make a beneficial basis of using isoflurane in both cell culture and animal models, including various models of brain injury. We aimed to determine the neuroprotective effect of isoflurane on hypoxic brain injury and elucidated the underlying mechanism. A hippocampal slice, in artificial cerebrospinal fluid with glucose and oxygen deprivation, was used as an in vitro model for brain hypoxia. The orthodromic population spike and hypoxic injury potential were recorded in the CA1 and CA3 regions. Amino acid neurotransmitters concentration in perfusion solution of hippocampal slices was measured. Isoflurane treatment caused delayed elimination of population spike and improved the recovery of population spike; decreased frequency of hypoxic injury potential, postponed the onset of hypoxic injury potential and increased the duration of hypoxic injury potential. Isoflurane treatment also decreased the hypoxia-induced release of amino acid neurotransmitters such as aspartate, glutamate and glycine induced by hypoxia, but the levels of γ-aminobutyric acid were elevated. Morphological studies showed that isoflurane treatment attenuated edema of pyramid neurons in the CA1 region. It also reduced apoptosis as evident by lowered expression of caspase-3 and PARP genes. Isoflurane showed a neuro-protective effect on hippocampal neuron injury induced by hypoxia through suppression of apoptosis. Copyright © 2016 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

  2. Isoflurane anesthesia initiated at the onset of reperfusion attenuates oxidative and hypoxic-ischemic brain injury.

    Science.gov (United States)

    Sosunov, Sergey A; Ameer, Xavier; Niatsetskaya, Zoya V; Utkina-Sosunova, Irina; Ratner, Veniamin I; Ten, Vadim S

    2015-01-01

    This study demonstrates that in mice subjected to hypoxia-ischemia (HI) brain injury isoflurane anesthesia initiated upon reperfusion limits a release of mitochondrial oxidative radicals by inhibiting a recovery of complex-I dependent mitochondrial respiration. This significantly attenuates an oxidative stress and reduces the extent of HI brain injury. Neonatal mice were subjected to HI, and at the initiation of reperfusion were exposed to isoflurane with or without mechanical ventilation. At the end of HI and isoflurane exposure cerebral mitochondrial respiration, H2O2 emission rates were measured followed by an assessment of cerebral oxidative damage and infarct volumes. At 8 weeks after HI navigational memory and brain atrophy were assessed. In vitro, direct effect of isoflurane on mitochondrial H2O2 emission was compared to that of complex-I inhibitor, rotenone. Compared to controls, 15 minutes of isoflurane anesthesia inhibited recovery of the compex I-dependent mitochondrial respiration and decreased H2O2 production in mitochondria supported with succinate. This was associated with reduced oxidative brain injury, superior navigational memory and decreased cerebral atrophy compared to the vehicle-treated HI-mice. Extended isoflurane anesthesia was associated with sluggish recovery of cerebral blood flow (CBF) and the neuroprotection was lost. However, when isoflurane anesthesia was supported with mechanical ventilation the CBF recovery improved, the event associated with further reduction of infarct volume compared to HI-mice exposed to isoflurane without respiratory support. Thus, in neonatal mice brief isoflurane anesthesia initiated at the onset of reperfusion limits mitochondrial release of oxidative radicals and attenuates an oxidative stress. This novel mechanism contributes to neuroprotective action of isoflurane. The use of mechanical ventilation during isoflurane anesthesia counterbalances negative effect of isoflurane anesthesia on recovery of

  3. Isoflurane anesthesia initiated at the onset of reperfusion attenuates oxidative and hypoxic-ischemic brain injury.

    Directory of Open Access Journals (Sweden)

    Sergey A Sosunov

    Full Text Available This study demonstrates that in mice subjected to hypoxia-ischemia (HI brain injury isoflurane anesthesia initiated upon reperfusion limits a release of mitochondrial oxidative radicals by inhibiting a recovery of complex-I dependent mitochondrial respiration. This significantly attenuates an oxidative stress and reduces the extent of HI brain injury. Neonatal mice were subjected to HI, and at the initiation of reperfusion were exposed to isoflurane with or without mechanical ventilation. At the end of HI and isoflurane exposure cerebral mitochondrial respiration, H2O2 emission rates were measured followed by an assessment of cerebral oxidative damage and infarct volumes. At 8 weeks after HI navigational memory and brain atrophy were assessed. In vitro, direct effect of isoflurane on mitochondrial H2O2 emission was compared to that of complex-I inhibitor, rotenone. Compared to controls, 15 minutes of isoflurane anesthesia inhibited recovery of the compex I-dependent mitochondrial respiration and decreased H2O2 production in mitochondria supported with succinate. This was associated with reduced oxidative brain injury, superior navigational memory and decreased cerebral atrophy compared to the vehicle-treated HI-mice. Extended isoflurane anesthesia was associated with sluggish recovery of cerebral blood flow (CBF and the neuroprotection was lost. However, when isoflurane anesthesia was supported with mechanical ventilation the CBF recovery improved, the event associated with further reduction of infarct volume compared to HI-mice exposed to isoflurane without respiratory support. Thus, in neonatal mice brief isoflurane anesthesia initiated at the onset of reperfusion limits mitochondrial release of oxidative radicals and attenuates an oxidative stress. This novel mechanism contributes to neuroprotective action of isoflurane. The use of mechanical ventilation during isoflurane anesthesia counterbalances negative effect of isoflurane anesthesia on

  4. Nicotine exacerbates brain edema during in vitro and in vivo focal ischemic conditions.

    Science.gov (United States)

    Paulson, Jennifer R; Yang, Tianzhi; Selvaraj, Pradeep K; Mdzinarishvili, Alexander; Van der Schyf, Cornelis J; Klein, Jochen; Bickel, Ulrich; Abbruscato, Thomas J

    2010-02-01

    We have previously shown that nicotine, the addictive component of tobacco products, alters the blood-brain barrier (BBB) Na(+),K(+),2Cl(-) cotransporter (NKCC) during in vitro hypoxia-aglycemia exposure. Attenuation of abluminal NKCC suggests that accumulation of ions in the brain extracellular fluid would result in an increase of fluid or cytotoxic edema in the brain during hypoxia-aglycemia or stroke conditions. To further investigate whether nicotine products have the potential to worsen stroke outcome by increasing edema formation, two separate models to mimic stroke conditions were utilized to decipher the effects of short-term and long-term administrations of nicotine products on brain edema following stroke. Oxygen glucose deprivation (OGD) was studied in rat hippocampal slices with short-term or long-term exposure to nicotine and cigarette smoke constituents. During short-term exposure, the presence of nicotine at a concentration mimicking heavy smokers increased water content of hippocampal slices during OGD. Furthermore, long-term 1-week administration of nicotine increased water content in hippocampal slices that could be attenuated with nicotine acetylcholine receptor (nAChR) antagonists, suggesting nicotine increase edema during OGD via nAChRs. A second model of focal ischemia, middle cerebral artery occlusion, showed an increase of infarct size during short-term exposure to nicotine and an increase of edema during both short-term and long-term administration of nicotine, compared with saline controls. These findings support the paradigm that nicotine products not only increase the incidence of stroke but also have the potential to worsen stroke outcome by increased edema formation.

  5. [Control of major cardiovascular risk factors of ischemic heart disease in secondary prevention in Aragón: COCINA study].

    Science.gov (United States)

    Cucalon Arenal, J M; Buisac Ramón, C; Marin Ibáñez, A; Castan Ruiz, S; Blay Cortes, M G; Barrasa Villar, J I

    2016-01-01

    Ischemic heart disease remains a leading cause of death in Spain. According to the American Heart Association/American College of Cardiology (AHA/ACC) and European national societies, secondary prevention for these patients consists of control of major cardiovascular risk factors (CVRF) and suitable lifestyle habits. To determine the degree of control of CVRF in the Aragonese population in secondary prevention. Cross-sectional study of a sample of 705 patients of Aragon who had suffered a cardiac event, selected opportunistically in consultations of family physicians participating in the 3 provinces of Aragon. The study was conducted in the second half of 2012. To measure the degree of control of different FRVC and lifestyle habits in this population. Anthropometric, different cardiovascular risk factors, treatment and lifestyle. 58% of men and 52% of women met criteria for monitoring of measured variables. The best result was obtained with smoking cessation and the worst with BMI. Hypertension, Dyslipidemia and Diabetes Mellitus achieve poor control results. The results show that the degree of control of CVRF is still low, especially in variables such as dyslipidemia and Diabetes Mellitus. Only 16.5% of control patients met criteria given the pharmacologically-modifiable cardiovascular risk factors. Copyright © 2015 SEHLELHA. Published by Elsevier España, S.L.U. All rights reserved.

  6. SDF-1α/CXCR4 Axis Mediates The Migration of Mesenchymal Stem Cells to The Hypoxic-Ischemic Brain Lesion in A Rat Model.

    Science.gov (United States)

    Yu, Qin; Liu, Lizhen; Lin, Jie; Wang, Yan; Xuan, Xiaobo; Guo, Ying; Hu, Shaojun

    2015-01-01

    Transplantation of mesenchymal stem cells (MSCs) can promote functional recovery of the brain after hypoxic-ischemic brain damage (HIBD). However, the mechanism regulating MSC migration to a hypoxic-ischemic lesion is poorly understood. Interaction between stromal cell-derived factor-1α (SDF-1α) and its cognate receptor CXC chemokine receptor 4 (CXCR4) is crucial for homing and migration of multiple stem cell types. In this study, we investigate the potential role of SDF-1α/CXCR4 axis in mediating MSC migration in an HIBD model. In this experimental study, we first established the animal model of HIBD using the neonatal rat. Bone marrow MSCs were cultured and labeled with 5-bromo-21-deoxyuridine (BrdU) after which 6×10(6) cells were intravenously injected into the rat. BrdU positive MSCs in the hippocampus were detected by immunohistochemical analyses. The expression of hypoxia-inducible factor-1α (HIF-1α) and SDF-1α in the hippocampus of hypoxic-ischemic rats was detected by Western blotting. To investigate the role of hypoxia and SDF-1α on migration of MSCs in vitro, MSCs isolated from normal rats were cultured in a hypoxic environment (PO2=1%). Migration of MSCs was detected by the transwell assay. The expression of CXCR4 was tested using Western blotting and flow cytometry. BrdU-labeled MSCs were found in the rat brain, which suggested that transplanted MSCs migrated to the site of the hypoxic-ischemic brain tissue. HIF-1α and SDF-1α significantly increased in the hippocampal formations of HIBD rats in a time-dependent manner. They peaked on day 7 and were stably expressed until day 21. Migration of MSCs in vitro was promoted by SDF-1α under hypoxia and inhibited by the CXCR4 inhibitor AMD3100. The expression of CXCR4 on MSCs was elevated by hypoxia stimulation as well as microdosage treatment of SDF-1α. This observation illustrates that SDF-1α/CXCR4 axis mediate the migration of MSCs to a hypoxic-ischemic brain lesion in a rat model.

  7. Know your tools - concordance of different methods for measuring brain volume change after ischemic stroke

    Energy Technology Data Exchange (ETDEWEB)

    Yassi, Nawaf; Campbell, Bruce C.V.; Davis, Stephen M.; Bivard, Andrew [The University of Melbourne, Departments of Medicine and Neurology, Melbourne Brain Centre rate at The Royal Melbourne Hospital, Parkville, Victoria (Australia); Moffat, Bradford A.; Steward, Christopher; Desmond, Patricia M. [The University of Melbourne, Department of Radiology, The Royal Melbourne Hospital, Parkville (Australia); Churilov, Leonid [The University of Melbourne, The Florey Institute of Neurosciences and Mental Health, Parkville (Australia); Parsons, Mark W. [University of Newcastle and Hunter Medical Research Institute, Priority Research Centre for Translational Neuroscience and Mental Health, Newcastle (Australia)

    2015-07-15

    Longitudinal brain volume changes have been investigated in a number of cerebral disorders as a surrogate marker of clinical outcome. In stroke, unique methodological challenges are posed by dynamic structural changes occurring after onset, particularly those relating to the infarct lesion. We aimed to evaluate agreement between different analysis methods for the measurement of post-stroke brain volume change, and to explore technical challenges inherent to these methods. Fifteen patients with anterior circulation stroke underwent magnetic resonance imaging within 1 week of onset and at 1 and 3 months. Whole-brain as well as grey- and white-matter volume were estimated separately using both an intensity-based and a surface watershed-based algorithm. In the case of the intensity-based algorithm, the analysis was also performed with and without exclusion of the infarct lesion. Due to the effects of peri-infarct edema at the baseline scan, longitudinal volume change was measured as percentage change between the 1 and 3-month scans. Intra-class and concordance correlation coefficients were used to assess agreement between the different analysis methods. Reduced major axis regression was used to inspect the nature of bias between measurements. Overall agreement between methods was modest with strong disagreement between some techniques. Measurements were variably impacted by procedures performed to account for infarct lesions. Improvements in volumetric methods and consensus between methodologies employed in different studies are necessary in order to increase the validity of conclusions derived from post-stroke cerebral volumetric studies. Readers should be aware of the potential impact of different methods on study conclusions. (orig.)

  8. Quantitative analysis of brain metabolites concentrations using MR spectroscopy in acute hypoxia ischemic encephalopathy

    International Nuclear Information System (INIS)

    Xiao Yeyu; Wang HaiYu; Shen Zhiwei; Lin Yan; Chen Yaowen; Xiao Gang; Wu Renhua

    2010-01-01

    Objective: To evaluate the absolute quantification of brain metabolites concentrations using external standard MRS in acute hypoxia ischemia encephalopathy (HIE) piglet model. Method: Eight 7-day-old healthy piglets were subjected to insult of hypoxia ischemia (HI). The animals and an external standard phantom containing detectable metabolites of known concentrations were studied on a 1.5 T GE Signa scanner. The single-voxel proton magnetic resonance spectroscopy ( 1 H-MRS) data were processed using LCModel software, and the quantification of N-acetylaspartate (NAA), creatine (Cr) and lactate (Lac) were accomplished. Multivariate analysis of variance was performed to compare the NAA, Cr, Lac concentration differences in the brains of piglets pre- and post-HI (0h). In addition, the dynamic changes of brain metabolites concentrations of 2 HIE piglets were observed at the time points of 0 h and 2 h. Results: One piglet was excluded because it was over anesthetized to death. Seven piglets' data were analyzed. The concentrations of NAA pre- and post-HI were (6.86±0.49) mmol/kg and (5.73±0.88) mmol/kg respectively, they were (4.65±0.73) mmol/kg and (4.40±0.80) mmol/kg for Cr; and were 0.00 mmol/kg and (0.43±0.39) mmol/kg for Lac. After HI, decreased NAA concentration immediately was observed, and it was of statistical significance (F=8.608, P=0.013). The concentration of Cr was insignificantly decreased (F=0.379, P=0.550). The concentration of Lac was increased, and the difference was of statistical significance (F=8.600, P=0.013). Dynamic observation showed a Lac peak immediately after HI and it decreased after 2 h post-HI. Conclusions: External standard MRS using LCModel has great value in the quantitative analysis of brain metabolites. The changes of NAA and Lac concentrations are sensitive to reflect the early metabolic change of acute HIE. (authors)

  9. HILIC-MS rat brain analysis, a new approach for the study of ischemic attack

    Directory of Open Access Journals (Sweden)

    Miękus Natalia

    2017-08-01

    Full Text Available Clinicians often rely on selected small molecular compounds from body fluids for the detection, screening or monitoring of numerous life-threatening diseases. Among others, important monoamines – biogenic amines (BAs – and their metabolites serve as sensitive biomarkers to study the progression or even early detection of on-going brain pathologies or tumors of neuroendocrine origins. Undertaking the task to optimize a reliable method for the simultaneous analysis of the most relevant BAs in biological matrices is of utmost importance for scientists.

  10. Sevoflurane preconditioning induced endogenous neurogenesis against ischemic brain injury by promoting microglial activation.

    Science.gov (United States)

    Li, Li; Saiyin, Hexige; Xie, Jingmo; Ma, Lixiang; Xue, Lei; Wang, Wei; Liang, Weimin; Yu, Qiong

    2017-04-25

    Brain ischemia causes irreversible damage to functional neurons in cases of infarct. Promoting endogenous neurogenesis to replace necrotic neurons is a promising therapeutic strategy for ischemia patients. The neuroprotective role of sevoflurane preconditioning implies that it might also enhance endogenous neurogenesis and functional restoration in the infarct region. By using a transient middle cerebral artery occlusion (tMCAO) model, we discovered that endogenous neurogenesis was enhanced by sevoflurane preconditioning. This enhancement process is characterized by the promotion of neuroblast proliferation within the subventricular zone (SVZ), migration and differentiation into neurons, and the presence of astrocytes and oligodendrocytes at the site of infarct. The newborn neurons in the sevoflurane preconditioning group showed miniature excitatory postsynaptic currents (mEPSCs), increased synaptophysin and PSD95 staining density, indicating normal neuronal function. Furthermore, long-term behavioral improvement was observed in the sevoflurane preconditioning group consistent with endogenous neurogenesis. Further histological analyses showed that sevoflurane preconditioning accelerated microglial activation, including migration, phagocytosis and secretion of brain-derived neurotrophic factor (BDNF). Intraperitoneal injection of minocycline, a microglial inhibitor, suppressed microglial activation and reversed neurogenesis. Our data showed that sevoflurane preconditioning promoted microglial activities, created a favorable microenvironment for endogenous neurogenesis and accelerated functional reconstruction in the infarct region.

  11. Soluble epoxide hydrolase inhibitors might prevent ischemic arrhythmias via microRNA-1 repression in primary neonatal mouse ventricular myocytes.

    Science.gov (United States)

    Liu, Qiong; Zhao, Xuan; Peng, Ran; Wang, Mi; Zhao, Wang; Gui, Ya-Jun; Liao, Cai-Xiu; Xu, Dan-Yan

    2017-02-28

    Ischemic arrhythmias are the main causes of sudden cardiac death. It has been reported that soluble epoxide hydrolase inhibitors (sEHis) could prevent arrhythmias; however, the underlying molecular mechanisms remain unclear. In recent years, the proarrhythmic role of microRNA-1 (miR-1) has been investigated. This study aimed to elucidate whether sEHis prevented ischemic arrhythmias by suppressing miR-1. The primary neonatal mouse ventricular myocyte model of miR-1 overexpression was established by incubating with agonist microONTM mmu-miR-1a-3p agomir (DAEDstain TM Dye) (agomiR-1). The sEHi, trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB), was administered following miR-1 overexpression. Quantitative real-time PCR (qPCR) and western blotting were used to test alterations in the expression of miR-1 and its target mRNAs GJA1 and KCNJ2 and their respective encoded proteins connexin 43 (Cx43) and the K + channel subunit (Kir2.1). The whole-cell patch-clamp technique was used to record the alterations of the inward rectifying K + current (I K1 ). Compared with the control group, miR-1 levels were significantly increased in the agomiR-1 group (p < 0.05), which suggested the successful construction of the miR-1 overexpression model. Compared with the control group, the levels of GJA1 and KCNJ2 mRNAs and Cx43 and Kir2.1 proteins in the agomiR-1 group were significantly decreased, and I K1 was significantly impaired (all p < 0.05). The miR-1 levels were dose-dependently decreased by t-AUCB, whereas t-AUCB dose-dependently increased the levels of GJA1 and KCNJ2 mRNAs and Cx43 and Kir2.1 proteins. Furthermore, t-AUCB restored the impaired I K1 (all p < 0.05). In conclusion, the sEHi t-AUCB has the ability to down-regulate proarrhythmic miR-1 and up-regulate its target genes and proteins, eventually restoring I K1 .

  12. Zinc transporter 8 (ZnT8 expression is reduced by ischemic insults: a potential therapeutic target to prevent ischemic retinopathy.

    Directory of Open Access Journals (Sweden)

    Michael Deniro

    Full Text Available The zinc (Zn(++ transporter ZnT8 plays a crucial role in zinc homeostasis. It's been reported that an acute decrease in ZnT8 levels impairs β cell function and Zn(++ homeostasis, which contribute to the pathophysiology of diabetes mellitus (DM. Although ZnT8 expression has been detected in the retinal pigment epithelium (RPE, its expression profile in the retina has yet to be determined. Furthermore, the link between diabetes and ischemic retinopathy is well documented; nevertheless, the molecular mechanism(s of such link has yet to be defined. Our aims were to; investigate the expression profile of ZnT8 in the retina; address the influence of ischemia on such expression; and evaluate the influence of YC-1; (3-(50-hydroxymethyl-20-furyl-1-benzyl indazole, a hypoxia inducible factor-1 (HIF-1 inhibitor, on the status of ZnT8 expression. We used real-time RT-PCR, immunohistochemistry, and Western blot in the mouse model of oxygen-induced retinopathy (OIR and Müller cells to evaluate the effects of ischemia/hypoxia and YC-1 on ZnT8 expression. Our data indicate that ZnT8 was strongly expressed in the outer nuclear layer (ONL, outer plexiform layer (OPL, ganglion cell layer (GCL, and nerve fiber layer (NFL, whereas the photoreceptor layer (PRL, inner nuclear layer (INL and inner plexiform layer (IPL showed moderate ZnT8 immunoreactivity. Furthermore, we demonstrate that retinal ischemic insult induces a significant downregulation of ZnT8 at the message and protein levels, YC-1 rescues the injured retina by restoring the ZnT8 to its basal homeostatic levels in the neovascular retinas. Our data indicate that ischemic retinopathy maybe mediated by aberrant Zn(++ homeostasis caused by ZnT8 downregulation, whereas YC-1 plays a neuroprotective role against ischemic insult. Therefore, targeting ZnT8 provides a therapeutic strategy to combat neovascular eye diseases.

  13. Uric Acid Therapy Prevents Early Ischemic Stroke Progression: A Tertiary Analysis of the URICO-ICTUS Trial (Efficacy Study of Combined Treatment With Uric Acid and r-tPA in Acute Ischemic Stroke).

    Science.gov (United States)

    Amaro, Sergio; Laredo, Carlos; Renú, Arturo; Llull, Laura; Rudilosso, Salvatore; Obach, Víctor; Urra, Xabier; Planas, Anna M; Chamorro, Ángel

    2016-11-01

    Identification of neuroprotective therapies in acute ischemic stroke is imperative. We report a predefined analysis of the URICO-ICTUS trial (Efficacy Study of Combined Treatment With Uric Acid and r-tPA in Acute Ischemic Stroke) assessing the efficacy of uric acid (UA) compared with placebo to prevent early ischemic worsening (EIW) and the relevance of collateral circulation. URICO-ICTUS was a double-blind, placebo-controlled, phase 2b trial where a total of 411 patients treated with alteplase within 4.5 hours of stroke onset were randomized (1:1) to receive UA 1000 mg (n=211) or placebo (n=200) before the end of alteplase infusion. EIW defined an increment ≥4 points in the National Institutes of Health Stroke Scale score within 72 hours of treatment in the absence of hemorrhage or recurrent stroke. Logistic regression models assessed the interaction between therapy and the collateral circulation in 112 patients who had a pretreatment computed tomographic angiography. EIW occurred in 2 of 149 (1%) patients with good outcome and 23 of 262 (9%) patients with poor outcome (χ 2 ; P=0.002). EIW occurred in 7 of 204 (3%) patients treated with UA and in 18 of 200 (9%) patients treated with placebo (χ 2 ; P=0.01). There was a significant interaction between the efficacy of UA to prevent EIW and collaterals (P=0.029), with lower incidence in patients with good collaterals treated with UA compared with placebo (2% versus 15%, respectively; P=0.048). UA therapy may prevent EIW after acute stroke in thrombolysed patients. Optimal access of UA to its molecular targets through appropriate collaterals may modify the magnitude of the neuroprotective effect. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00860366. © 2016 American Heart Association, Inc.

  14. Red photon treatment inhibits apoptosis via regulation of bcl-2 proteins and ROS levels, alleviating hypoxic-ischemic brain damage.

    Science.gov (United States)

    Jiang, W; Chen, L; Zhang, X J; Chen, J; Li, X C; Hou, W S; Xiao, N

    2014-05-30

    Therapeutic options for hypoxic-ischemic brain damage (HIBD) are scarce and inefficient. Recently, many studies have demonstrated that red photon plays an important role in anti-inflammatory processes as well as apoptosis, the main trait of HIBD. In this study, we investigated whether red photon can protect from HIBD in SD rats and oxygen-glucose deprivation (OGD) in PC12 cells. Apoptosis, mitochondrial transmembrane potential (MMP), and reactive oxygen species (ROS) rates were assessed in PC12 cells. We found that 6-h irradiation resulted in decreased MMP, ROS and apoptosis rates, although these changes were reversible with prolonged irradiation. Importantly, these effects were sustained for 2-8h upon quenching of the red photon. Similar trends were observed for protein and mRNA expression of bax and bcl-2, with short-term irradiation (6h) inhibiting apoptosis in PC12 Cells. However, long-term (>6h) irradiation caused cell damage. In vivo experiments, bax mRNA and protein levels were reduced after 7days in HIBD model rats treated with red photon, in contrast to bcl-2. Furthermore, we found that bax and bcl-2 were mainly expressed in pyramidal cells of the hippocampus CA1 and CA3. Importantly, Morris Water Maze test results revealed an improvement in learning ability and spatial memory in rats after irradiation. Overall, our data showed that short-term irradiation with red photon in the acute phase inhibits the mitochondrial apoptotic pathway via regulation of bcl-2-related proteins and reduction of ROS levels, thereby decreasing apoptosis in nerve cells and improving the neurological prognosis of HIBD. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. Large field-of-view and depth-specific cortical microvascular imaging underlies regional differences in ischemic brain

    Science.gov (United States)

    Qin, Jia; Shi, Lei; Dziennis, Suzan; Wang, Ruikang K.

    2014-02-01

    Ability to non-invasively monitor and quantify of blood flow, blood vessel morphology, oxygenation and tissue morphology is important for improved diagnosis, treatment and management of various neurovascular disorders, e.g., stroke. Currently, no imaging technique is available that can satisfactorily extract these parameters from in vivo microcirculatory tissue beds, with large field of view and sufficient resolution at defined depth without any harm to the tissue. In order for more effective therapeutics, we need to determine the area of brain that is damaged but not yet dead after focal ischemia. Here we develop an integrated multi-functional imaging system, in which SDW-LSCI (synchronized dual wavelength laser speckle imaging) is used as a guiding tool for OMAG (optical microangiography) to investigate the fine detail of tissue hemodynamics, such as vessel flow, profile, and flow direction. We determine the utility of the integrated system for serial monitoring afore mentioned parameters in experimental stroke, middle cerebral artery occlusion (MCAO) in mice. For 90 min MCAO, onsite and 24 hours following reperfusion, we use SDW-LSCI to determine distinct flow and oxygenation variations for differentiation of the infarction, peri-infarct, reduced flow and contralateral regions. The blood volumes are quantifiable and distinct in afore mentioned regions. We also demonstrate the behaviors of flow and flow direction in the arterials connected to MCA play important role in the time course of MCAO. These achievements may improve our understanding of vascular involvement under pathologic and physiological conditions, and ultimately facilitate clinical diagnosis, monitoring and therapeutic interventions of neurovascular diseases, such as ischemic stroke.

  16. Ethnic differences in ischemic stroke subtypes in young-onset stroke: the Stroke Prevention in Young Adults Study.

    Science.gov (United States)

    Trivedi, Megh M; Ryan, Kathleen A; Cole, John W

    2015-10-29

    Prior studies indicate that young African-Americans (AA) have a greater frequency of ischemic stroke than similarly aged European-Americans (EA). We hypothesized that differences in stroke subtype frequency mediated through sex and differing risk factor profiles may play a role in ethnicity-specific stroke. Utilizing our biracial young-onset stroke population, we explored these relationships. Fifty nine hospitals in the Baltimore-Washington area participated in a population-based study of young-onset stroke in men (218-AA, 291-EA) and women (219-AA, 222-EA) aged 16-49. Data on age, sex, ethnicity and stroke risk factors (hypertension (HTN) and smoking) were gathered through standardized interview. A pair of vascular neurologists adjudicated each case to determine TOAST subtype. Logistic regression analyses evaluating for differences in stroke risk factors by TOAST subtype were performed. Analyses controlling for age and sex demonstrated that AA were more likely to have a lacunar stroke than EA (OR = 1.61; 95% CI = 1.12-2.32; p = 0.011) when utilizing the other TOAST subtypes as the reference group. This effect was mediated by HTN, which increases the risk of lacunar stroke (OR = 2.03; 95% CI = 1.38-2.98; p = 0.0003) and large artery stroke (OR = 1.70; 95% CI = 1.01-2.88; p = 0.048) when controlling for sex, ethnicity, and age. Cases below age 40 were more likely to have a cardioembolic stroke than those above age 40 (OR = 1.62; 95% CI = 1.15-2.27; p = 0.006), controlling for sex and ethnicity. Lastly, current smokers were more likely to have a large artery stroke than non-smokers (OR = 1.79; 95% CI = 1.08-2.98; p = 0.024). Our population-based data demonstrate ethnic differences in ischemic stroke subtypes. These findings may help clarify mechanisms of stroke in young adults which may in part be driven by ethnic-specific differences in early-onset traditional risk factors, thereby indicating differing emphasis on workup and prevention.

  17. Endogenous calcitonin gene-related peptide suppresses ischemic brain injuries and progression of cognitive decline.

    Science.gov (United States)

    Zhai, Liuyu; Sakurai, Takayuki; Kamiyoshi, Akiko; Ichikawa-Shindo, Yuka; Kawate, Hisaka; Tanaka, Megumu; Xian, Xian; Hirabayashi, Kazutaka; Dai, Kun; Cui, Nanqi; Tanimura, Keiya; Liu, Teng; Wei, Yangxuan; Tanaka, Masaaki; Tomiyama, Haruka; Yamauchi, Akihiro; Igarashi, Kyoko; Shindo, Takayuki

    2018-04-01

    Calcitonin gene-related peptide (CGRP) is a 37-amino acid peptide and produced by alternative splicing of the transcript of the calcitonin/CGRP gene. Originally identified as a strong vasodilatory and hypotensive peptide, CGRP is now known to be a pleiotropic molecule distributed in various organs, including the brain. In this study, we used CGRP knockout mice (CGRP-/-) to examine the actions of endogenous CGRP during cerebral ischemia. To induce acute and chronic cerebral ischemia, mice were subjected to middle cerebral artery occlusion (MCAO) and bilateral common carotid artery stenosis (BCAS). In the cerebral cortex of wild-type mice, CGRP expression was upregulated after acute infarction. In CGRP-/- subjected to MCAO or BCAS, recovery of cerebral blood flow was slower and exhibited more extensive neuronal cell death. Expression of the inflammatory cytokines was higher in CGRP-/- than wild type in the acute phase of ischemia. Pathological analysis during the chronic phase revealed more extensive neuronal cell loss and demyelination and higher levels of oxidative stress in CGRP-/- than wild-type. CGRP-/- also showed less compensatory capillary growth. In an eight-arm radial maze test, CGRP-/- exhibited poorer reference memory than wild-type. On the other hand, CGRP administration promoted cerebral blood flow recovery after cerebral ischemia. We also found that CGRP directly inhibited the cell death of primary cortical neurons. These results indicate endogenous CGRP is protective against ischemia-induced neuronal cell injury. CGRP could, thus, be a novel candidate for use in the treatment of both cerebral ischemia and progression of cognitive decline.

  18. Sorting out the clinical consequences of ischemic lesions in brain aging: a clinicopathological approach.

    Science.gov (United States)

    Gold, Gabriel; Kovari, Enikö; Hof, Patrick R; Bouras, Constantin; Giannakopoulos, Panteleimon

    2007-06-15

    Vascular lesions are particularly common in the aged brain. However, it is still unclear whether all such lesions affect cognition. To better explore relationships between specific characteristics of vascular lesions (type, size and location) and cognitive status. We performed a review of currently available neuroimaging and post-mortem studies taking into account several recent clinicopathological reports in elderly individuals with varying levels of cognitive impairment. New data reveals the significant impact of cortical microinfarcts on intellectual function, in contrast to focal cortical and white matter gliosis which are not significantly associated with cognitive status. Structural neuroimaging studies show inconsistent data regarding the cognitive consequences of WML. Neuropathological analyses reveal that both periventricular and subcortical demyelination are associated with cognitive status in the absence of macrovascular pathology. When lacunes are present, these microvascular lesions have no independent effect on intellectual impairment. The relationship between lacunes and cognition is highly dependent on localization. Basal ganglia and thalamic lacunes correlate with cognitive decline but not lacunes in the frontal, temporal and parietal deep white matter. Recent studies suggest that some cases of dementia might be misclassified: 1. Cases with typical Alzheimer course and moderate lacunes in subcortical white matter should probably be considered pure Alzheimer's disease. 2. The presence of microscopic infarcts can markedly impact cognition but is not detectable by currently available neuroimaging techniques and the vascular component of such mixed cases may go undiagnosed. The development of urgently needed new criteria for vascular dementia should take into account the relative contribution of various types of vascular lesions that can impact cognitive function.

  19. BRAIN NATRIURETIC PEPTIDE (BNP: BIOMARKER FOR RISK STRATIFICATION AND FUNCTIONAL RECOVERY PREDICTION IN ISCHEMIC STROKE

    Directory of Open Access Journals (Sweden)

    STANESCU Ioana

    2015-02-01

    Full Text Available Functional outcome after cardiovascular and cerebrovascular events is traditionally predicted using demographic and clinical variables like age, gender, blood pressure, cholesterol levels, diabetes status, smoking habits or pre-existing morbidity. Identification of new variables will improve the risk stratification of specific categories of patients. Numerous blood-based biomarkers associated with increased cardiovascular risk have been identified; some of them even predict cardiovascular events. Investigators have tried to produce prediction models by incorporating traditional risk factors and biomarkers. (1. Widely-available, rapidly processed and less expensive biomarkers could be used in the future to guide management of complex cerebrovascular patients in order to maximize their recovery (2 Recently, studies have demonstrated that biomarkers can predict not only the risk for a specific clinical event, but also the risk of death of vascular cause and the functional outcome after cardiovascular or cerebrovascular events. Early prediction of fatal outcome after stroke may improve therapeutic strategies (such as the use of more aggressive treatments or inclusion of patients in clinical trials and guide decision-making processes in order to maximize patient’s chances for survival and recovery. (3 Long term functional outcome after stroke is one of the most difficult variables to predict. Elevated serum levels of brain natriuretic peptide (BNP are powerful predictor of outcomes in patients with cardiovascular disease (heart failure, atrial fibrillation. Potential role of BNP in predicting atrial fibrillation occurrence, cardio-embolic stroke and post-stroke mortality have been proved in many studies. However, data concerning the potential role of BNP in predicting short term and long term functional outcomes after stroke remain controversial.

  20. Comprehensive Cardiac Rehabilitation for Secondary Prevention After Transient Ischemic Attack or Mild Stroke: PSYCHOLOGICAL PROFILE AND OUTCOMES.

    Science.gov (United States)

    Prior, Peter L; Hachinski, Vladimir; Chan, Richard; Unsworth, Karen; Mytka, Sharon; Harnadek, Michael; OʼCallaghan, Christina; Suskin, Neville

    2017-11-01

    Having previously reported that comprehensive cardiac rehabilitation (CCR) is effective for secondary prevention post-transient ischemic attack (TIA)/mild nondisabling stroke (MNDS), we present psychometric findings for the same sample that elucidate subacute TIA/MNDS psychological outcomes and test whether CCR would be independently associated with psychological improvements. In this prospective cohort trial patients with ≥1 risk factor, recruited from a stroke prevention clinic within 12 months (mean = 11.5 weeks) post-TIA/MNDS, entered CCR. Of the 110 recruited patients, 100 (mean age = 65.4 years; 46 females) entered CCR and 80 completed CCR (mean duration = 7.6 months). At CCR entry, 16.5% and 39.2% screened positively for depression and anxiety, decreasing nonsignificantly at exit to 4.2%, and significantly to 16.9% (P = .008), respectively. Age-corrected deficits occurred more frequently than expected (P ≤ .03); at entry, mental health status (13.3%), clock-drawing (31.6%), oral-verbal fluency (16.9%), word-list learning (11.2%), and recall (12.6%); at exit, clock-drawing (30.0%). Entry-to-exit, mean depression, anxiety, mental and physical health status, word-list learning, memory, digit-symbol coding, and oral-verbal fluency scores improved significantly (P ≤ .031). No reliable change indices were significant. Psychological service recipients improved significantly more than nonrecipients in depression (P = .049). Baseline North American Adult Reading Test score predicted exercise attendance (R = 0.275; P = .044); New York Heart Association (NYHA) class and depression score predicted exit physical health status (R = 0.770, P psychological improvements. CCR psychological treatment may benefit depression. Subacute NYHA class and depression may later affect quality of life.

  1. Short-duration hypothermia after ischemic stroke prevents delayed intracranial pressure rise.

    Science.gov (United States)

    Murtha, L A; McLeod, D D; McCann, S K; Pepperall, D; Chung, S; Levi, C R; Calford, M B; Spratt, N J

    2014-07-01

    Intracranial pressure elevation, peaking three to seven post-stroke is well recognized following large strokes. Data following small-moderate stroke are limited. Therapeutic hypothermia improves outcome after cardiac arrest, is strongly neuroprotective in experimental stroke, and is under clinical trial in stroke. Hypothermia lowers elevated intracranial pressure; however, rebound intracranial pressure elevation and neurological deterioration may occur during rewarming. (1) Intracranial pressure increases 24 h after moderate and small strokes. (2) Short-duration hypothermia-rewarming, instituted before intracranial pressure elevation, prevents this 24 h intracranial pressure elevation. Long-Evans rats with two hour middle cerebral artery occlusion or outbred Wistar rats with three hour middle cerebral artery occlusion had intracranial pressure measured at baseline and 24 h. Wistars were randomized to 2·5 h hypothermia (32·5°C) or normothermia, commencing 1 h after stroke. In Long-Evans rats (n = 5), intracranial pressure increased from 10·9 ± 4·6 mmHg at baseline to 32·4 ± 11·4 mmHg at 24 h, infarct volume was 84·3 ± 15·9 mm(3) . In normothermic Wistars (n = 10), intracranial pressure increased from 6·7 ± 2·3 mmHg to 31·6 ± 9·3 mmHg, infarct volume was 31·3 ± 18·4 mm(3) . In hypothermia-treated Wistars (n = 10), 24 h intracranial pressure did not increase (7·0 ± 2·8 mmHg, P intracranial pressure elevation 24 h after stroke in two rat strains, even after small strokes. Short-duration hypothermia prevented the intracranial pressure rise, an effect sustained for at least 18 h after rewarming. The findings have potentially important implications for design of future clinical trials. © 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.

  2. Prognostic value of brain proton MR spectroscopy and diffusion tensor imaging in newborns with hypoxic-ischemic encephalopathy treated by brain cooling

    Energy Technology Data Exchange (ETDEWEB)

    Ancora, G. [Neonatal Intensive Care Unit, Department of Mother and Infant Infermi Hospital of Rimini, Rimini (Italy); Testa, C.; Tonon, C.; Manners, D.N.; Gramegna, L.L.; Lodi, R. [Department of Biomedical and Neuromotor Sciences University of Bologna, MR Functional Unit, Bologna (Italy); Grandi, S.; Sbravati, F.; Savini, S.; Corvaglia, L.T.; Faldella, G. [University of Bologna, Neonatology Unit, Department of Woman, Child and Adolescent Health, Bologna (Italy); Tani, G. [University of Bologna, Radiology Unit, Department of Woman, Child and Adolescent Health, Bologna (Italy); Malucelli, E. [University of Bologna, Department of Pharmacy and Biotechnologies, Bologna (Italy)

    2013-08-15

    MRI, proton magnetic resonance spectroscopy ({sup 1}H-MRS), and diffusion tensor imaging (DTI) have been shown to be of great prognostic value in term newborns with moderate-severe hypoxic-ischemic encephalopathy (HIE). Currently, no data are available on {sup 1}H-MRS and DTI performed in the subacute phase after hypothermic treatment. The aim of the present study was to assess their prognostic value in newborns affected by moderate-severe HIE and treated with selective brain cooling (BC). Twenty infants treated with BC underwent conventional MRI and {sup 1}H-MRS at a mean (SD) age of 8.3 (2.8) days; 15 also underwent DTI. Peak area ratios of metabolites and DTI variables, namely mean diffusivity (MD), axial and radial diffusivity, and fractional anisotropy (FA), were calculated. Clinical outcome was monitored until 2 years of age. Adverse outcome was observed in 6/20 newborns. Both {sup 1}H-MRS and DTI variables showed higher prognostic accuracy than conventional MRI. N-acetylaspartate/creatine at a basal ganglia localisation showed 100 % PPV and 93 % NPV for outcome. MD showed significantly decreased values in many regions of white and gray matter, axial diffusivity showed the best predictive value (PPV and NPV) in the genu of corpus callosum (100 and 91 %, respectively), and radial diffusivity was significantly decreased in fronto white matter (FWM) and fronto parietal (FP) WM. The decrement of FA showed the best AUC (0.94) in the FPWM. Selective BC in HIE neonates does not affect the early and accurate prognostic value of {sup 1}H-MRS and DTI, which outperform conventional MRI. (orig.)

  3. A high-affinity, dimeric inhibitor of PSD-95 bivalently interacts with PDZ1-2 and protects against ischemic brain damage

    DEFF Research Database (Denmark)

    Bach, Anders*; Clausen, Bettina H; Møller, Magda

    2012-01-01

    Inhibition of the ternary protein complex of the synaptic scaffolding protein postsynaptic density protein-95 (PSD-95), neuronal nitric oxide synthase (nNOS), and the N-methyl-d-aspartate (NMDA) receptor is a potential strategy for treating ischemic brain damage, but high-affinity inhibitors are ...... of Tat-N-dimer (3 nmol/g) to mice subjected to focal cerebral ischemia reduces infarct volume with 40% and restores motor functions. Thus, Tat-N-dimer is a highly efficacious neuroprotective agent with therapeutic potential in stroke....

  4. Magnetic resonance imaging of blood-brain barrier permeability in ischemic stroke using diffusion-weighted arterial spin labeling in rats.

    Science.gov (United States)

    Tiwari, Yash V; Lu, Jianfei; Shen, Qiang; Cerqueira, Bianca; Duong, Timothy Q

    2017-08-01

    Diffusion-weighted arterial spin labeling magnetic resonance imaging has recently been proposed to quantify the rate of water exchange (K w ) across the blood-brain barrier in humans. This study aimed to evaluate the blood-brain barrier disruption in transient (60 min) ischemic stroke using K w magnetic resonance imaging with cross-validation by dynamic contrast-enhanced magnetic resonance imaging and Evans blue histology in the same rats. The major findings were: (i) at 90 min after stroke (30 min after reperfusion), group K w magnetic resonance imaging data showed no significant blood-brain barrier permeability changes, although a few animals showed slightly abnormal K w . Dynamic contrast-enhanced magnetic resonance imaging confirmed this finding in the same animals. (ii) At two days after stroke, K w magnetic resonance imaging revealed significant blood-brain barrier disruption. Regions with abnormal K w showed substantial overlap with regions of hyperintense T 2 (vasogenic edema) and hyperperfusion. Dynamic contrast-enhanced magnetic resonance imaging and Evans blue histology confirmed these findings in the same animals. The K w values in the normal contralesional hemisphere and the ipsilesional ischemic core two days after stroke were: 363 ± 17 and 261 ± 18 min -1 , respectively (P < 0.05, n = 9). K w magnetic resonance imaging is sensitive to blood-brain barrier permeability changes in stroke, consistent with dynamic contrast-enhanced magnetic resonance imaging and Evans blue extravasation. K w magnetic resonance imaging offers advantages over existing techniques because contrast agent is not needed and repeated measurements can be made for longitudinal monitoring or averaging.

  5. No improvement of neuronal metabolism in the reperfusion phase with melatonin treatment after hypoxic-ischemic brain injury in the neonatal rat.

    Science.gov (United States)

    Berger, Hester R; Morken, Tora Sund; Vettukattil, Riyas; Brubakk, Ann-Mari; Sonnewald, Ursula; Widerøe, Marius

    2016-01-01

    Mitochondrial impairment is a key feature underlying neonatal hypoxic-ischemic (HI) brain injury and melatonin is potentially neuroprotective through its effects on mitochondria. In this study, we have used (1) H and (13) C NMR spectroscopy after injection of [1-(13) C]glucose and [1,2-(13) C]acetate to examine neuronal and astrocytic metabolism in the early reperfusion phase after unilateral HI brain injury in 7-day-old rat pups, exploring the effects of HI on mitochondrial function and the potential protective effects of melatonin on brain metabolism. One hour after hypoxia-ischemia, astrocytic metabolism was recovered and glycolysis was normalized, whereas mitochondrial metabolism in neurons was clearly impaired. Pyruvate carboxylation was also lower in both hemispheres after HI. The transfer of glutamate from neurons to astrocytes was higher whereas the transfer of glutamine from astrocytes to neurons was lower 1 h after HI in the contralateral hemisphere. Neuronal metabolism was equally affected in pups treated with melatonin (10 mg/kg) immediately after HI as in vehicle treated pups indicating that the given dose of melatonin was not capable of protecting the neuronal mitochondria in this early phase after HI brain injury. However, any beneficial effects of melatonin might have been masked by modulatory effects of the solvent dimethyl sulfoxide on cerebral metabolism. Neuronal and astrocytic metabolism was examined by (13) C and (1) H NMR spectroscopy in the early reperfusion phase after unilateral hypoxic-ischemic brain injury and melatonin treatment in neonatal rats. One hour after hypoxia-ischemia astrocytic mitochondrial metabolism had recovered and glycolysis was normalized, whereas mitochondrial metabolism in neurons was impaired. Melatonin treatment did not show a protective effect on neuronal metabolism. © 2015 International Society for Neurochemistry.

  6. Delphi-consensus weights for ischemic and bleeding events to be included in a composite outcome for RCTs in thrombosis prevention.

    Directory of Open Access Journals (Sweden)

    Agnes Dechartres

    2011-04-01

    Full Text Available To weight ischemic and bleeding events according to their severity to be used in a composite outcome in RCTs in the field of thrombosis prevention.Using a Delphi consensus method, a panel of anaesthesiology and cardiology experts rated the severity of thrombotic and bleeding clinical events. The ratings were expressed on a 10-point scale. The median and quartiles of the ratings of each item were returned to the experts. Then, the panel members evaluated the events a second time with knowledge of the group responses from the first round. Cronbach's a was used as a measure of homogeneity for the ratings. The final rating for each event corresponded to the median rating obtained at the last Delphi round.Of 70 experts invited, 32 (46% accepted to participate. Consensus was reached at the second round as indicated by Cronbach's a value (0.99 (95% CI 0.98-1.00 so the Delphi was stopped. Severity ranged from under-popliteal venous thrombosis (median = 3, Q1 = 2; Q3 = 3 to ischemic stroke or intracerebral hemorrhage with severe disability at 7 days and massive pulmonary embolism (median = 9, Q1 = 9; Q3 = 9. Ratings did not differ according to the medical specialty of experts.These ratings could be used to weight ischemic and bleeding events of various severity comprising a composite outcome in the field of thrombosis prevention.

  7. Impact of shocks on mortality in patients with ischemic or dilated cardiomyopathy and defibrillators implanted for primary prevention.

    Directory of Open Access Journals (Sweden)

    Florian Streitner

    Full Text Available BACKGROUND: Emerging interest is seen in the paradox of defibrillator shocks for ventricular tachyarrhythmia and increased mortality risk. Particularly in patients with dilated cardiomyopathy (DCM, the prognostic importance of shocks is unclear. The purpose of this study was to compare the outcome after shocks in patients with ischemic cardiomyopathy (ICM or DCM and defibrillators (ICD implanted for primary prevention. METHODS AND RESULTS: Data of 561 patients were analyzed (mean age 68.6±10.6 years, mean left ventricular ejection fraction 28.6±7.3%. During a median follow-up of 49.3 months, occurrence of device therapies and all-cause mortality were recorded. 74 out of 561 patients (13.2% experienced ≥1 appropriate and 51 out of 561 patients (9.1% ≥1 inappropriate shock. All-cause mortality was 24.2% (136 out of 561 subjects. Appropriate shock was associated with a trend to higher mortality in the overall patient population (HR 1.48, 95% CI 0.96-2.28, log rank p = 0.072. The effect was significant in ICM patients (HR 1.61, 95% CI 1.00-2.59, log rank p = 0.049 but not in DCM patients (HR 1.03, 95% CI 0.36-2.96, log rank p = 0.96. Appropriate shocks occurring before the median follow-up revealed a much stronger impact on mortality (HR for the overall patient population 2.12, 95% CI 1.24-3.63, p = 0.005. The effect was driven by ICM patients (HR 2.48, 95% CI 1.41-4.37, p = 0.001, as appropriate shocks again did not influence survival of DCM patients (HR 0.63, 95% CI 0.083-4.75, p = 0.65. Appropriate shocks occurring after the median follow-up and inappropriate shocks occurring at any time revealed no impact on survival in any of the groups (p = ns. CONCLUSION: Appropriate shocks are associated with reduced survival in patients with ICM but not in patients with DCM and ICDs implanted for primary prevention. Furthermore, the negative effect of appropriate shocks on survival in ICM patients is only evident within the

  8. Effects of hypoxic–ischemic brain injury on striatal dopamine transporter in newborn piglets: evaluation of 11C-CFT PET/CT for DAT quantification

    International Nuclear Information System (INIS)

    Zhang Yanfen; Wang Xiaoyu; Cao Li; Guo Qiyong; Wang Xiaoming

    2011-01-01

    Introduction: Alterations of dopamine in striatal presynaptic terminals play an important role in the hypoxic–ischemic (HI) brain injury. Quantification of DAT levels in the presynaptic site using 11 C-N-2-carbomethoxy-3-(4-fluorophenyl)-tropane ( 11 C-CFT) with positron emission tomography (PET) was applied in studies for Parkinson's disease. The current study investigated the changes in striatal DAT following HI brain injury in newborn piglets using 11 C-CFT PET. Methods: Newborn piglets were subjected to occlusion of bilateral common carotid arteries for 30 min and simultaneous peripheral hypoxia. Brain DAT imaging was performed using PET/CT with 11 C-CFT as the probe in each group (including the control group and HI insult groups). Brain tissues were collected for DAT immunohistochemical (IHC) analysis at each time point post the PET/CT procedure. Sham controls had some operation without HI procedure. Results: A few minutes after intravenous injection of 11 C-CFT, radioactive signals for DAT clearly appeared in the cortical area, striatum and cerebellum of newborn piglets of sham control group and HI insult groups. HI brain insult markedly increased striatal DAT at an early period (P 11 C-CFT PET imaging data and IHC DAT staining data were highly correlated (r=0.844, P 11 C-CFT PET/CT imaging data reflected the dynamic changes of DAT in the striatum in vivo.

  9. Blood-Brain Barrier Permeability Assessed by Perfusion CT Predicts Symptomatic Hemorrhagic Transformation and Malignant Edema in Acute Ischemic Stroke

    NARCIS (Netherlands)

    Hom, J.; Dankbaar, J. W.; Soares, B. P.; Schneider, T.; Cheng, S. -C.; Bredno, J.; Lau, B. C.; Smith, W.; Dillon, W. P.; Wintermark, M.

    BACKGROUND AND PURPOSE: SHT and ME are feared complications in patients with acute ischemic stroke. They occur >10 times more frequently in tPA-treated versus placebo-treated patients. Our goal was to evaluate the sensitivity and specificity of admission BBBP measurements derived from PCT in

  10. Unraveling the Specific Ischemic Core and Penumbra Transcriptome in the Permanent Middle Cerebral Artery Occlusion Mouse Model Brain Treated with the Neuropeptide PACAP38.

    Science.gov (United States)

    Hori, Motohide; Nakamachi, Tomoya; Shibato, Junko; Rakwal, Randeep; Shioda, Seiji; Numazawa, Satoshi

    2015-01-21

    Our group has been systematically investigating the effects of the neuropeptide pituitary adenylate-cyclase activating polypeptide (PACAP) on the ischemic brain. To do so, we have established and utilized the permanent middle cerebral artery occlusion (PMCAO) mouse model, in which PACAP38 (1 pmol) injection is given intracerebroventrically and compared to a control saline (0.9% sodium chloride, NaCl) injection, to unravel genome‑wide gene expression changes using a high-throughput DNA microarray analysis approach. In our previous studies, we have accumulated a large volume of data (gene inventory) from the whole brain (ipsilateral and contralateral hemispheres) after both PMCAO and post-PACAP38 injection. In our latest research, we have targeted specifically infarct or ischemic core (hereafter abbreviated IC) and penumbra (hereafter abbreviated P) post-PACAP38 injections in order to re-examine the transcriptome at 6 and 24 h post injection. The current study aims to delineate the specificity of expression and localization of differentially expressed molecular factors influenced by PACAP38 in the IC and P regions. Utilizing the mouse 4 × 44 K whole genome DNA chip we show numerous changes (≧/≦ 1.5/0.75-fold) at both 6 h (654 and 456, and 522 and 449 up- and down-regulated genes for IC and P, respectively) and 24 h (2568 and 2684, and 1947 and 1592 up- and down-regulated genes for IC and P, respectively) after PACAP38 treatment. Among the gene inventories obtained here, two genes, brain-derived neurotrophic factor (Bdnf) and transthyretin (Ttr) were found to be induced by PACAP38 treatment, which we had not been able to identify previously using the whole hemisphere transcriptome analysis. Using bioinformatics analysis by pathway- or specific-disease-state focused gene classifications and Ingenuity Pathway Analysis (IPA) the differentially expressed genes are functionally classified and discussed. Among these, we specifically discuss some novel and previously

  11. Unraveling the Specific Ischemic Core and Penumbra Transcriptome in the Permanent Middle Cerebral Artery Occlusion Mouse Model Brain Treated with the Neuropeptide PACAP38

    Directory of Open Access Journals (Sweden)

    Motohide Hori

    2015-01-01

    Full Text Available Our group has been systematically investigating the effects of the neuropeptide pituitary adenylate-cyclase activating polypeptide (PACAP on the ischemic brain. To do so, we have established and utilized the permanent middle cerebral artery occlusion (PMCAO mouse model, in which PACAP38 (1 pmol injection is given intracerebroventrically and compared to a control saline (0.9% sodium chloride, NaCl injection, to unravel genome‑wide gene expression changes using a high-throughput DNA microarray analysis approach. In our previous studies, we have accumulated a large volume of data (gene inventory from the whole brain (ipsilateral and contralateral hemispheres after both PMCAO and post-PACAP38 injection. In our latest research, we have targeted specifically infarct or ischemic core (hereafter abbreviated IC and penumbra (hereafter abbreviated P post-PACAP38 injections in order to re-examine the transcriptome at 6 and 24 h post injection. The current study aims to delineate the specificity of expression and localization of differentially expressed molecular factors influenced by PACAP38 in the IC and P regions. Utilizing the mouse 4 × 44 K whole genome DNA chip we show numerous changes (≧/≦ 1.5/0.75-fold at both 6 h (654 and 456, and 522 and 449 up- and down-regulated genes for IC and P, respectively and 24 h (2568 and 2684, and 1947 and 1592 up- and down-regulated genes for IC and P, respectively after PACAP38 treatment. Among the gene inventories obtained here, two genes, brain-derived neurotrophic factor (Bdnf and transthyretin (Ttr were found to be induced by PACAP38 treatment, which we had not been able to identify previously using the whole hemisphere transcriptome analysis. Using bioinformatics analysis by pathway- or specific-disease-state focused gene classifications and Ingenuity Pathway Analysis (IPA the differentially expressed genes are functionally classified and discussed. Among these, we specifically discuss some novel and

  12. Relationship between hypertensive cerebral hemorrhage and ischemic lesions

    International Nuclear Information System (INIS)

    Yamaguchi, Shinya; Tsuchiya, Takashi; Yamaguchi, Takenori

    1991-01-01

    Patchy parenchymal lesions of increased intensity were frequently identified in patients with cerebral hemorrhage in T2-weighted image of high-fields MR imaging. We studied 64 patients with brain hemorrhage to determine the frequency and distribution of those lesions. We defined an area with high intensity in T2 weighted and low or iso-intensity area in T1 weighted images smaller than 1.5 cm in diameter to be 'ischemic lesion'. Ishemic lesions were found in 48 (75%) of all cases; in 25 (75%) of 32 patients with putaminal hemorrhage, in 15 (100%) of 15 with thalamic hemorrhage, in 3 (33%) of 9 with subcortical hemorrhage. Multiple ischemic lesions were more frequently seen in thalamic hemorrhage than in putaminal hemorrhage. Only 5 (10%) of 48 cases with associated ischemic lesions had a previous history related to those lesions. Multivariable regression analysis identified hypertension as the major predictor of the presence of ischemic lesions. Patients with brain hemorrhage frequently accompanied with incidental ischemic lesions, making it difficult to establish a guideline of blood pressure control for prevention of recurrent stroke. (author)

  13. Tc99m-HMPAO Neuro--SPECT Assessment of Ischemic Penumbra in Acute Brain Infarct: Control of Intra-arterial Thrombolysis Treatment

    International Nuclear Information System (INIS)

    Mena, Francisco; Mena, Ismael; Ducci, Hector; Soto, Francisco; Pedraza, Luis; Contreras, Andrea; Miranda, Marcelo; Basaez, Esteban; Fruns, Manuel

    2004-01-01

    Acute brain infarct is a medical emergency potentially reversible if treated with thrombolysis, an approved therapy, if performed in the first 3 to 6 hours of evolution. Thrombolysis has many benefits, but it also has associated risks, mainly development of intracranial hemorrhage. The selection of which patient should receive this type of treatment had been an important research topic over the last decade. As a consequence neuroimaging of brain infarct has significantly improved during the last few years. A variety of diagnostic studies are now available in the evaluation of brain infarct and in particular of potentially reversible brain ischemia, including magnetic resonance imaging (MRI) diffusion-perfusion, perfusion computed tomography (CT) and functional neuroimaging techniques includes positron emission tomography (PET) and single-photon emission tomography (SPECT). The aim of this study is to present our experience with a group of patients that presented with acute brain ischemia and had a NeuroSPECT evaluation before and after intra-arterial thrombolysis and/or possible stent placement, in the treatment of acute brain infarct. Methods: 16 patients were treated acutely for a significant ischemic stroke with the following protocol. 1) Admission, and complete neurological evaluation. 2) Brain CT scan performed to rule out hemorrhage or established infarct. 3) IV injection of 1100MBq Tc 99m HMPAO (Ceretec tm ) 4) Conventional cerebral angiography and intra-arterial thrombolysis with tPA and /or angioplasty/stent if necessary. 5) NeuroSPECT assessment of ischemic penumbra (Pre-therapy results). 6) 14 of 16 patients received a NeuroSPECT (Post-therapy results) control at 24 hours. NeuroSPECT image acquisition was performed immediately following arterial thrombolysis with a dual Head Camera, Siemens ECAM, SHR collimators and conventional protocol. Image processing was performed using the Neurogam, Segami Corp. Software as previously reported in Alasbimn Journal 2

  14. Shear Stress Induces Differentiation of Endothelial Lineage Cells to Protect Neonatal Brain from Hypoxic-Ischemic Injury through NRP1 and VEGFR2 Signaling

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    Chia-Wei Huang

    2015-01-01

    Full Text Available Neonatal hypoxic-ischemic (HI brain injuries disrupt the integrity of neurovascular structure and lead to lifelong neurological deficit. The devastating damage can be ameliorated by preserving the endothelial network, but the source for therapeutic cells is limited. We aim to evaluate the beneficial effect of mechanical shear stress in the differentiation of endothelial lineage cells (ELCs from adipose-derived stem cells (ASCs and the possible intracellular signals to protect HI injury using cell-based therapy in the neonatal rats. The ASCs expressed early endothelial markers after biochemical stimulation of endothelial growth medium. The ELCs with full endothelial characteristics were accomplished after a subsequential shear stress application for 24 hours. When comparing the therapeutic potential of ASCs and ELCs, the ELCs treatment significantly reduced the infarction area and preserved neurovascular architecture in HI injured brain. The transplanted ELCs can migrate and engraft into the brain tissue, especially in vessels, where they promoted the angiogenesis. The activation of Akt by neuropilin 1 (NRP1 and vascular endothelial growth factor receptor 2 (VEGFR2 was important for ELC migration and following in vivo therapeutic outcomes. Therefore, the current study demonstrated importance of mechanical factor in stem cell differentiation and showed promising protection of brain from HI injury using ELCs treatment.

  15. Effect of brain-derived neurotrophic factor on mesenchymal stem cell-seeded electrospinning biomaterial for treating ischemic diabetic ulcers via milieu-dependent differentiation mechanism.

    Science.gov (United States)

    He, Siyi; Shen, Lei; Wu, Yangxiao; Li, Li; Chen, Wen; Hou, Chunli; Yang, Mingcan; Zeng, Wen; Zhu, Chuhong

    2015-03-01

    Great challenges in transplantation of mesenchymal stem cells (MSCs) for treating ischemic diabetic ulcers (IDUs) are to find a suitable carrier and create a beneficial microenvironment. Brain-derived neurotrophic factor (BDNF), a member of neurotrophin family, is considered angiogenic and neuroprotective. Given that IDUs are caused by vascular disease and peripheral neuropathy, we used BDNF as a stimulant, and intended to explore the role of new biomaterials complex with MSCs in wound healing. BDNF promoted the proliferation and migration of MSCs using MTT, transwell, and cell scratch assays. The activity of human umbilical vein endothelial cells (HUVECs) was also enhanced by the MSC-conditioned medium in the presence of BDNF, via a vascular endothelial growth factor-independent pathway. Since proliferated HUVECs in the BDNF group made the microenvironment more conducive to endothelial differentiation of MSCs, by establishing co-culture systems with the two cell types, endothelial cells derived from MSCs increased significantly. A new biomaterial made of polylactic acid, silk and collagen was used as the carrier dressing. After transplantation of the BDNF-stimulated MSC/biomaterial complex, the ulcers in hindlimb ischemic mice healed prominently. More blood vessel formation was observed in the wound tissue, and more MSCs were co-stained with some endothelial-specific markers such as cluster of differentiation (CD)31 and von Willebrand Factor (vWF) in the treatment group than in the control group. These results demonstrated that BDNF could improve microenvironment in the new biomaterial, and induce MSCs to differentiate into endothelial cells indirectly, thus accelerating ischemic ulcer healing.

  16. Intracranial atherosclerosis: Causes of ischemic stroke, diagnosis, and treatment

    Directory of Open Access Journals (Sweden)

    V.A Sorokoumov

    2014-01-01

    Full Text Available The paper reviews the literature on the identification of the causes of ischemic stroke and transient ischemic attacks in intracranial atherosclerosis. Symptomatic intracranial atherosclerosis is the cause of an ischemic focus in not only the cortical and subcortical structures due to hypoperfusion or arterio-arterial embolism, but also in the deep structures of the cerebral hemispheres and brainstem. Major artery dolichoectasia may make an accurate diagnosis and treatment choice difficult.Progress in the treatment of patients with symptomatic intracranial atherosclerosis depends on the availability of current brain and vessel imaging techniques and cranial artery angioplasty and stenting methods. The efficiency of aggressive medical prevention, primarily blood pressure reduction and different combinations of antiplatelet drugs, is being intensively investigated.

  17. Protective effect of Kombucha tea on brain damage induced by transient cerebral ischemia and reperfusion in rat

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    Najmeh Kabiri

    2016-09-01

    Full Text Available The aim of study was to investigate the potential neuroprotective effects of Kombucha on cerebral damage induced by ischemia in rats (n=99. Cerebral infarct volume in the ischemic rats received Kombucha solution showed no significance alteration. However, the permeability of blood-brain barrier significantly decreased in both ischemic rats received 15 mg/kg Kombucha tea and Sham group. In addition, brain water content in the ischemic groups treated with Kombucha solution was significantly higher than the Sham group, although right hemispheres in all of the treated groups illustrated higher brain water content than the left ones. Brain anti-oxidant capacity elevated in the ischemic rats treated with Kombucha and in the Sham group. Brain and plasma malondialdehyde concentrations significantly decreased in both of the ischemic groups injected with Kombucha. The findings suggest that Kombucha tea could be useful for the prevention of cerebral damage.

  18. Ischemic stroke risk, smoking, and the genetics of inflammation in a biracial population: the stroke prevention in young women study

    OpenAIRE

    Cole, John W; Brown, David W; Giles, Wayne H; Stine, Oscar C; O'Connell, Jeffrey R; Mitchell, Braxton D; Sorkin, John D; Wozniak, Marcella A; Stern, Barney J; Sparks, Mary J; Dobbins, Mark T; Shoffner, Latasha T; Zappala, Nancy K; Reinhart, Laurie J; Kittner, Steven J

    2008-01-01

    Abstract Background Although cigarette smoking is a well-established risk factor for vascular disease, the genetic mechanisms that link cigarette smoking to an increased incidence of stroke are not well understood. Genetic variations within the genes of the inflammatory pathways are thought to partially mediate this risk. Here we evaluate the association of several inflammatory gene single nucleotide polymorphisms (SNPs) with ischemic stroke risk among young women, further stratified by curre...

  19. Regional mild hypothermia in the protection of the ischemic brain A hipotermia regional moderada na proteção do encéfalo isquêmico

    Directory of Open Access Journals (Sweden)

    Mirto Nelso Prandini

    2002-08-01

    Full Text Available Objective: To demonstrate that mild hypothermia can be a protective element when an ischemic onset occurs in rabbit brains. Methods: A rabbit model of focal ischemia was used to test the protection provided by mild hypothermia regionally produced by means of the placement of ice bag on the scalp of a hemicranium which has had previously its bone removed. Twenty New Zealand White rabbits were divided into two groups as follows: (A a control group where an ischemic lesion was produced by coagulation of the middle cerebral artery and (B a brain protected group where mild hypothermia was provided during 80 to 100 minutes after the same ischemic lesion. The brains slices were stained with 2,3,5-Triphenyletrazolium (TTC. The sections were photographed with a digital camera and the infarct volume was measured through a computer program. Results: The average of infarct volume was 70.53 mm³ in the control group. In the protected group, the average of infarct volume was 41,30 mm³ only in five animals. Five animals of this group did not demonstrate macroscopically and microscopically infarct area. Conclusions: We concluded that mild hypothermia regionally produced may protect ischemic brains of rabbits.Objetivo: Demonstrar a proteção que a hipotermia moderada pode fornecer em casos de isquemia em encéfalos de coelhos. Métodos: Foi utilizado um modelo de isquemia focal em coelhos, para avaliar a proteção fornecida por meio de hipotermia moderada, produzida através da colocação de pedras de gelo contidas no interior de um pequeno saco plástico, em contato com o couro cabeludo de um hemicrânio onde a tábua óssea foi previamente removida. Vinte coelhos da raça Nova Zelândia Branca, pesando de 3,100 Kg a 3,750 Kg foram divididos em dois grupos: (A um grupo controle onde foi produzida uma lesão isquêmica por meio da coagulação da artéria cerebral média e (B um grupo submetido a neuroproteção por hipotermia moderada regional durante 80 a

  20. NOX Inhibitors - A Promising Avenue for Ischemic Stroke.

    Science.gov (United States)

    Kim, Jong Youl; Park, Joohyun; Lee, Jong Eun; Yenari, Midori A

    2017-08-01

    NADPH-oxidase (NOX) mediated superoxide originally found on leukocytes, but now recognized in several types of cells in the brain. It has been shown to play an important role in the progression of stroke and related cerebrovascular disease. NOX is a multisubunit complex consisting of 2 membrane-associated and 4 cytosolic subunits. NOX activation occurs when cytosolic subunits translocate to the membrane, leading to transport electrons to oxygen, thus producing superoxide. Superoxide produced by NOX is thought to function in long-term potentiation and intercellular signaling, but excessive production is damaging and has been implicated to play an important role in the progression of ischemic brain. Thus, inhibition of NOX activity may prove to be a promising treatment for ischemic brain as well as an adjunctive agent to prevent its secondary complications. There is mounting evidence that NOX inhibition in the ischemic brain is neuroprotective, and targeting NOX in circulating immune cells will also improve outcome. This review will focus on therapeutic effects of NOX assembly inhibitors in brain ischemia and stroke. However, the lack of specificity and toxicities of existing inhibitors are clear hurdles that will need to be overcome before this class of compounds could be translated clinically.

  1. Increased Brain-Specific MiR-9 and MiR-124 in the Serum Exosomes of Acute Ischemic Stroke Patients.

    Directory of Open Access Journals (Sweden)

    Qiuhong Ji

    Full Text Available The aims of this study were to examine the alternation in serum exosome concentrations and the levels of serum exosomal miR-9 and miR-124, two brain-specific miRNAs, in acute ischemic stroke (AIS patients and to explore the predictive values of these miRNAs for AIS diagnosis and damage evaluation. Sixty-five patients with AIS at the acute stage were enrolled and 66 non-stroke volunteers served as controls. Serum exosomes isolated by ExoQuick precipitations were characterized by transmission electron microscopy, nanoparticle-tracking analysis and western blotting. The levels of exosomal miR-9 and miR-124 were determined by real-time quantitative PCR. Compared with controls, the concentration of serum exosomes and the median levels of serum exosomal miR-9 and miR-124 were significantly higher in AIS patients (p<0.01. The levels of both miR-9 and miR-124 were positively correlated with National Institutes of Health Stroke Scale (NIHSS scores, infarct volumes and serum concentrations of IL-6. The areas under the curve for exosomal miR-9 and miR-124 were 0.8026 and 0.6976, respectively. This proof of concept study suggests that serum exosomal miR-9 and miR-124 are promising biomarkers for diagnosing AIS and evaluating the degree of damage caused by ischemic injury. However, further studies are needed to explore the potential roles of the exosomes released from brain tissues in post stroke complications.

  2. The neuroblast and angioblast chemotaxic factor SDF-1 (CXCL12 expression is briefly up regulated by reactive astrocytes in brain following neonatal hypoxic-ischemic injury

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    Walker Aisha L

    2005-10-01

    Full Text Available Abstract Background Stromal cell-derived factor 1 (SDF-1 or CXCL12 is chemotaxic for CXCR4 expressing bone marrow-derived cells. It functions in brain embryonic development and in response to ischemic injury in helping guide neuroblast migration and vasculogenesis. In experimental adult stroke models SDF-1 is expressed perivascularly in the injured region up to 30 days after the injury, suggesting it could be a therapeutic target for tissue repair strategies. We hypothesized that SDF-1 would be expressed in similar temporal and spatial patterns following hypoxic-ischemic (HI injury in neonatal brain. Results Twenty-five 7-day-old C57BL/J mice underwent HI injury. SDF-1 expression was up regulated up to 7 days after the injury but not at the later time points. The chief sites of SDF-1 up regulation were astrocytes, their foot processes along blood vessels and endothelial cells. Conclusion The localization of SDF-1 along blood vessels in the HI injury zone suggests that these perivascular areas are where chemotaxic signaling for cellular recruitment originates and that reactive astrocytes are major mediators of this process. The associated endothelium is likely to be the site for vascular attachment and diapedesis of CXCR4 receptor expressing cells to enter the injured tissue. Here we show that, relative to adults, neonates have a significantly smaller window of opportunity for SDF-1 based vascular chemotaxic recruitment of bone marrow-derived cells. Therefore, without modification, following neonatal HI injury there is only a narrow period of time for endogenous SDF-1 mediated chemotaxis and recruitment of reparative cells, including exogenously administered stem/progenitor cells.

  3. Ischemic Stroke: MedlinePlus Health Topic

    Science.gov (United States)

    ... Clots) (American Stroke Association) Let's Talk about Ischemic Stroke (American Heart Association) Also in Spanish Prevention and Risk Factors Carotid Endarterectomy (National Heart, Lung, and Blood Institute) ...

  4. Electroacupuncture stimulation of the brachial plexus trunk on the healthy side promotes brain-derived neurotrophic factor mRNA expression in the ischemic cerebral cortex of a rat model of cerebral ischemia/reperfusion injury.

    Science.gov (United States)

    Guo, Zongjun; Wang, Lumin

    2012-07-25

    A rat model of cerebral ischemia/reperfusion was established by suture occlusion of the left middle cerebral artery. In situ hybridization results showed that the number of brain-derived neurotrophic factor mRNA-positive cells in the ischemic rat cerebral cortex increased after cerebral ischemia/ reperfusion injury. Low frequency continuous wave electroacupuncture (frequency 2-6 Hz, current intensity 2 mA) stimulation of the brachial plexus trunk on the healthy (right) side increased the number of brain-derived neurotrophic factor mRNA-positive cells in the ischemic cerebral cortex 14 days after cerebral ischemia/reperfusion injury. At the same time, electroacupuncture stimulation of the healthy brachial plexus truck significantly decreased neurological function scores and alleviated neurological function deficits. These findings suggest that electroacupuncture stimulation of the brachial plexus trunk on the healthy (right) side can greatly increase brain-derived neurotrophic factor mRNA expression and improve neurological function.

  5. Ischemic Colitis

    Science.gov (United States)

    ... Leiden, may increase the risk of ischemic colitis. High cholesterol, which can lead to atherosclerosis. Reduced blood flow, due to heart failure, low blood pressure and shock. Previous abdominal surgery. Scar tissue that forms after surgery may cause ...

  6. Sestrin2 induced by hypoxia inducible factor1 alpha protects the blood-brain barrier via inhibiting VEGF after severe hypoxic-ischemic injury in neonatal rats.

    Science.gov (United States)

    Shi, Xudan; Doycheva, Desislava Met; Xu, Liang; Tang, Jiping; Yan, Min; Zhang, John H

    2016-11-01

    Hypoxic ischemic (HI) encephalopathy remains the leading cause of perinatal brain injury resulting in long term disabilities. Stabilization of blood brain barrier (BBB) after HI is an important target, therefore, in this study we aim to determine the role of sestrin2, a stress inducible protein which is elevated after various insults, on BBB stabilization after moderate and severe HI injuries. Rat pups underwent common carotid artery ligation followed by either 150min (severe model) or 100min (moderate model) of hypoxia. 1h post HI, rats were intranasally administered with recombinant human sestrin2 (rh-sestrin2) and sacrificed for infarct area, brain water content, righting reflex and geotaxis reflex. Sestrin2 was silenced using siRNA and an activator/inhibitor of hypoxia inducible factor1α (HIF1α) was used to examine their roles on BBB permeability. Rats subjected to severe HI exhibited larger infarct area and higher sestrin2 expression compared to rats in the moderate HI group. rh-sestrin2 attenuated brain infarct and edema, while silencing sestrin2 reversed these protective effects after severe HI. HIF1α induced sestrin2 activation in severe HI but not in moderate HI groups. A HIF1a agonist was shown to increase permeability of the BBB via vascular endothelial growth factor (VEGF) after moderate HI. However, after severe HI, HIF1α activated both VEGF and sestrin2. But HIF1α dependent sestrin2 activation was the predominant pathway after severe HI which inhibited VEGF and attenuated BBB permeability. rh-sestrin2 attenuated BBB permeability via upregulation of endogenous sestrin2 which was induced by HIF1α after severe HI. However, HIF1α's effects as a prodeath or prosurvival signal were influenced by the severity of HI injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Near-infrared spectroscopy versus magnetic resonance imaging to study brain perfusion in newborns with hypoxic-ischemic encephalopathy treated with hypothermia.

    Science.gov (United States)

    Wintermark, P; Hansen, A; Warfield, S K; Dukhovny, D; Soul, J S

    2014-01-15

    The measurement of brain perfusion may provide valuable information for assessment and treatment of newborns with hypoxic-ischemic encephalopathy (HIE). While arterial spin labeled perfusion (ASL) magnetic resonance imaging (MRI) provides noninvasive and direct measurements of regional cerebral blood flow (CBF) values, it is logistically challenging to obtain. Near-infrared spectroscopy (NIRS) might be an alternative, as it permits noninvasive and continuous monitoring of cerebral hemodynamics and oxygenation at the bedside. The purpose of this study is to determine the correlation between measurements of brain perfusion by NIRS and by MRI in term newborns with HIE treated with hypothermia. In this prospective cohort study, ASL-MRI and NIRS performed during hypothermia were used to assess brain perfusion in these newborns. Regional cerebral blood flow (CBF) values, measured from 1-2 MRI scans for each patient, were compared to mixed venous saturation values (SctO2) recorded by NIRS just before and after each MRI. Analysis included groupings into moderate versus severe HIE based on their initial background pattern of amplitude-integrated electroencephalogram. Twelve concomitant recordings were obtained of seven neonates. Strong correlation was found between SctO2 and CBF in asphyxiated newborns with severe HIE (r=0.88; p value=0.0085). Moreover, newborns with severe HIE had lower CBF (likely lower oxygen supply) and extracted less oxygen (likely lower oxygen demand or utilization) when comparing SctO2 and CBF to those with moderate HIE. NIRS is an effective bedside tool to monitor and understand brain perfusion changes in term asphyxiated newborns, which in conjunction with precise measurements of CBF obtained by MRI at particular times, may help tailor neuroprotective strategies in term newborns with HIE. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Intravenous renal cell transplantation with SAA1-positive cells prevents the progression of chronic renal failure in rats with ischemic-diabetic nephropathy.

    Science.gov (United States)

    Kelly, Katherine J; Zhang, Jizhong; Han, Ling; Wang, Mingsheng; Zhang, Shaobo; Dominguez, Jesus H

    2013-12-15

    Diabetic nephropathy, the most common cause of progressive chronic renal failure and end-stage renal disease, has now reached global proportions. The only means to rescue diabetic patients on dialysis is renal transplantation, a very effective therapy but severely limited by the availability of donor kidneys. Hence, we tested the role of intravenous renal cell transplantation (IRCT) on obese/diabetic Zucker/SHHF F1 hybrid (ZS) female rats with severe ischemic and diabetic nephropathy. Renal ischemia was produced by bilateral renal clamping of the renal arteries at 10 wk of age, and IRCT with genetically modified normal ZS male tubular cells was given intravenously at 15 and 20 wk of age. Rats were euthanized at 34 wk of age. IRCT with cells expressing serum amyloid A had strong and long-lasting beneficial effects on renal function and structure, including tubules and glomeruli. However, donor cells were found engrafted only in renal tubules 14 wk after the second infusion. The results indicate that IRCT with serum amyloid A-positive cells is effective in preventing the progression of chronic kidney disease in rats with diabetic and ischemic nephropathy.

  9. Synchrotron Radiation X-Ray Phase-Contrast Tomography Visualizes Microvasculature Changes in Mice Brains after Ischemic Injury

    Directory of Open Access Journals (Sweden)

    Peng Miao

    2016-01-01

    Full Text Available Imaging brain microvasculature is important in plasticity studies of cerebrovascular diseases. Applying contrast agents, traditional μCT and μMRI methods gain imaging contrast for vasculature. The aim of this study is to develop a synchrotron radiation X-ray inline phase-contrast tomography (SRXPCT method for imaging the intact mouse brain (microvasculature in high resolution (~3.7 μm without contrast agent. A specific preparation protocol was proposed to enhance the phase contrast of brain vasculature by using density difference over gas-tissue interface. The CT imaging system was developed and optimized to obtain 3D brain vasculature of adult male C57BL/6 mice. The SRXPCT method was further applied to investigate the microvasculature changes in mouse brains (n=14 after 14-day reperfusion from transient middle cerebral artery occlusion (tMCAO. 3D reconstructions of brain microvasculature demonstrated that the branching radius ratio (post- to preinjury of small vessels (radius < 7.4 μm in the injury group was significantly smaller than that in the sham group (p<0.05. This result revealed the active angiogenesis in the recovery brain after stroke. As a high-resolution and contrast-agent-free method, the SRXPCT method demonstrates higher potential in investigations of functional plasticity in cerebrovascular diseases.

  10. Hemorrhagic transformation in ischemic stroke and its treatment during thrombolysis

    Directory of Open Access Journals (Sweden)

    Maurizio Paciaroni

    2011-08-01

    Full Text Available Haemorrhagic transformation (HT of brain infarction or hemorrhagic infarction is a complication of acute ischemic stroke, especially in cardioembolic stroke, and represents the most feared complication of thrombolysis. HT is a multifocal secondary bleeding into brain infarcts with innumerable foci of capillary and venular extravasation either remaining as discrete petechiae or emerging to form confluent purpura. HT is evidenced as a parenchymal area of increased density within an area of low attenuation in a typical vascular distribution on non-contrasted CT scans and is subdivided into two major categories on the basis of standardised definition: haemorrhagic infarct (HI and parenchymal haematoma (PH. PH has been associated to poor outcome in ischemic stroke patients. Thus, its prevention, early detection and adequate treatment represent key points in the management of acute stroke.

  11. Ischemic stroke risk, smoking, and the genetics of inflammation in a biracial population: the stroke prevention in young women study

    Directory of Open Access Journals (Sweden)

    Sorkin John D

    2008-08-01

    Full Text Available Abstract Background Although cigarette smoking is a well-established risk factor for vascular disease, the genetic mechanisms that link cigarette smoking to an increased incidence of stroke are not well understood. Genetic variations within the genes of the inflammatory pathways are thought to partially mediate this risk. Here we evaluate the association of several inflammatory gene single nucleotide polymorphisms (SNPs with ischemic stroke risk among young women, further stratified by current cigarette smoking status. Methods A population-based case-control study of stroke among women aged 15–49 identified 224 cases of first ischemic stroke (47.3% African-American and 211 age-comparable control subjects (43.1% African-American. Several inflammatory candidate gene SNPs chosen through literature review were genotyped in the study population and assessed for association with stroke and interaction with smoking status. Results Of the 8 SNPs (across 6 genes analyzed, only IL6 SNP rs2069832 (allele C, African-American frequency = 92%, Caucasian frequency = 55% was found to be significantly associated with stroke using an additive model, and this was only among African-Americans (age-adjusted: OR = 2.2, 95% CI = 1.0–5.0, p = 0.049; risk factor adjusted: OR = 2.5, 95% CI = 1.0–6.5, p = 0.05. When stratified by smoking status, two SNPs demonstrated statistically significant gene-environment interactions. First, the T allele (frequency = 5% of IL6 SNP rs2069830 was found to be protective among non-smokers (OR = 0.30, 95% CI = 0.11–.082, p = 0.02, but not among smokers (OR = 1.63, 95% CI = 0.48–5.58, p = 0.43; genotype by smoking interaction (p = 0.036. Second, the C allele (frequency = 39% of CD14 SNP rs2569190 was found to increase risk among smokers (OR = 2.05, 95% CI = 1.09–3.86, p = 0.03, but not among non-smokers (OR = 0.93, 95% CI = 0.62–1.39, p = 0.72; genotype by smoking interaction (p = 0.039. Conclusion This study demonstrates

  12. Magnesium Sulfate Prevents Placental Ischemia-Induced Increases in Brain Water Content and Cerebrospinal Fluid Cytokines in Pregnant Rats

    Science.gov (United States)

    Zhang, Linda W.; Warrington, Junie P.

    2016-01-01

    Magnesium sulfate (MgSO4) is the most widely used therapy in the clinic to prevent the progression of preeclampsia, a hypertensive disorder of pregnancy, to eclampsia. Eclampsia, manifested as unexplained seizures and/or coma during pregnancy or postpartum, accounts for ~13% of maternal deaths worldwide. While MgSO4 continues to be used in the clinic, the mechanisms by which it exerts its protective actions are not well understood. In this study, we tested the hypothesis that MgSO4 protects against placental ischemia-induced increases in brain water content and cerebrospinal fluid cytokines. To test this hypothesis, MgSO4 was administered via mini-osmotic pump (60 mg/day, i.p.) to pregnant and placental ischemic rats, induced by mechanical reduction of uterine perfusion pressure, from gestational day 14–19. This treatment regimen of MgSO4 led to therapeutic level of 2.8 ± 0.6 mmol/L Mg in plasma. MgSO4 had no effect on improving placental ischemia-induced changes in mean arterial pressure, number of live fetuses, or fetal and placental weight. Placental ischemia increased, while MgSO4 prevented the increase in water content in the anterior cerebrum. Cytokine and chemokine levels were measured in the cerebrospinal fluid using a multi-plex assay. Results demonstrate that cerebrospinal fluid, obtained via the cisterna magna, had reduced protein, albumin, interleukin (IL)-17A, IL-18, IL-2, eotaxin, fractalkine, interferon gamma, vascular endothelial growth factor (VEGF), and macrophage inflammatory protein (MIP)-2 following MgSO4 treatment. These data support the hypothesis that MgSO4 offers neuroprotection by preventing placental ischemia-induced cerebral edema and reducing levels of cytokines/chemokines in the cerebrospinal fluid. PMID:28008305

  13. Design and Rationale of the Intima-Medial Thickness Sub-Study of the PreventIon of CArdiovascular Events in iSchemic Stroke Patients with High Risk of Cerebral hemOrrhage (PICASSO-IMT) Study.

    Science.gov (United States)

    Seo, Woo-Keun; Kim, Yong Jae; Lee, Juneyoung; Kwon, Sun U

    2017-09-01

    Atherosclerosis is one of the main mechanisms of stroke and cardiovascular diseases and is associated with increased risk of recurrent stroke and cardiovascular events. Intima-medial thickness (IMT) is a well-known surrogate marker of atherosclerosis and has been used to predict stroke and cardiovascular events. However, the clinical significance of IMT and IMT change in stroke has not been investigated in well-designed studies. The PreventIon of CArdiovascular events in iSchemic Stroke patients with high risk of cerebral hemOrrhage-Intima-Media Thickness (PICASSO-IMT) sub-study is designed to investigate the effects of cilostazol, probucol, or both on IMT in patients with stroke. PICASSO-IMT is a prospective sub-study of the PICASSO study designed to measure IMT and plaque score at 1, 13, 25, 37, and 49 months after randomization. The primary outcome is the change in mean carotid IMT, which is defined as the mean of the far-wall IMTs of the right and left common carotid arteries, between baseline and 13 months after randomization. PICASSO-IMT will provide the largest IMT data set in a stroke population and will provide valuable information about the clinical significance of IMT in patients with ischemic stroke. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  14. Hot Topics in Research: Preventive Neuroradiology in Brain Aging and Cognitive Decline.

    Science.gov (United States)

    Raji, C A; Eyre, H; Wei, S H; Bredesen, D E; Moylan, S; Law, M; Small, G; Thompson, P M; Friedlander, R M; Silverman, D H; Baune, B T; Hoang, T A; Salamon, N; Toga, A W; Vernooij, M W

    2015-10-01

    Preventive neuroradiology is a new concept supported by growing literature. The main rationale of preventive neuroradiology is the application of multimodal brain imaging toward early and subclinical detection of brain disease and subsequent preventive actions through identification of modifiable risk factors. An insightful example of this is in the area of age-related cognitive decline, mild cognitive impairment, and dementia with potentially modifiable risk factors such as obesity, diet, sleep, hypertension, diabetes, depression, supplementation, smoking, and physical activity. In studying this link between lifestyle and cognitive decline, brain imaging markers may be instrumental as quantitative measures or even indicators of early disease. The purpose of this article is to provide an overview of the major studies reflecting how lifestyle factors affect the brain and cognition aging. In this hot topics review, we will specifically focus on obesity and physical activity. © 2015 by American Journal of Neuroradiology.

  15. Hypoxic-Ischemic Brain Damage in 7-Days-Old Rats: Early Neuronal Changes and the Long-Term Outcome

    OpenAIRE

    Ota Nakasone, Arturo; Departamento de Ginecología y Obstetricia Escuela de Medicina de Miyazaki Miyazaki, Japón; Ikeda, Tomoaki; Departamento de Ginecología y Obstetricia Escuela de Medicina de Miyazaki Miyazaki, Japón; Sameshima, Hiroshi; Departamento de Ginecología y Obstetricia Escuela de Medicina de Miyazaki Miyazaki, Japóni; Ikenoue, Tsuyomu; Departamento de Ginecología y Obstetricia Escuela de Medicina de Miyazaki Miyazaki, Japón; Toshimori, Kiyotaka; Departamento de Anatomía Escuela de Medicina de Miyazaki Miyazaki, Japón

    2014-01-01

    OBJECTIVES: To study the changes after hypoxia-ischemia (HI), and to observe both, the vulnerability of the different regions of the brain to HI and the heat shock protein-72 kDa (HSP72) induction and its efects on the neuronal cell. MATERIAL AND METHODS: 7-days-old rats were exposed to left carotid artery ligation followed by 2 h of HI and then they were sacrificed at different time points. Brains extracted at 1-72 h were immunohistochemically study using the HSP-72 and the microtubule assoc...

  16. Coronary heart disease risk in patients with stroke or transient ischemic attack and no known coronary heart disease: findings from the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial

    DEFF Research Database (Denmark)

    Amarenco, Pierre; Goldstein, Larry B; Sillesen, Henrik

    2010-01-01

    Noncoronary forms of atherosclerosis (including transient ischemic attacks or stroke of carotid origin or >50% stenosis of the carotid artery) are associated with a 10-year vascular risk of >20% and are considered as a coronary heart disease (CHD) -risk equivalent from the standpoint of lipid...... management. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial included patients with stroke or transient ischemic attack and no known CHD regardless of the presence of carotid atherosclerosis. We evaluated the risk of developing clinically recognized CHD in SPARCL patients....

  17. Mitochondrial Optic Atrophy (OPA) 1 Processing Is Altered in Response to Neonatal Hypoxic-Ischemic Brain Injury

    Science.gov (United States)

    Baburamani, Ana A.; Hurling, Chloe; Stolp, Helen; Sobotka, Kristina; Gressens, Pierre; Hagberg, Henrik; Thornton, Claire

    2015-01-01

    Perturbation of mitochondrial function and subsequent induction of cell death pathways are key hallmarks in neonatal hypoxic-ischemic (HI) injury, both in animal models and in term infants. Mitoprotective therapies therefore offer a new avenue for intervention for the babies who suffer life-long disabilities as a result of birth asphyxia. Here we show that after oxygen-glucose deprivation in primary neurons or in a mouse model of HI, mitochondrial protein homeostasis is altered, manifesting as a change in mitochondrial morphology and functional impairment. Furthermore we find that the mitochondrial fusion and cristae regulatory protein, OPA1, is aberrantly cleaved to shorter forms. OPA1 cleavage is normally regulated by a balanced action of the proteases Yme1L and Oma1. However, in primary neurons or after HI in vivo, protein expression of YmelL is also reduced, whereas no change is observed in Oma1 expression. Our data strongly suggest that alterations in mitochondria-shaping proteins are an early event in the pathogenesis of neonatal HI injury. PMID:26393574

  18. Relationship Between Cerebral Oxygenation and Metabolism During Rewarming in Newborn Infants After Therapeutic Hypothermia Following Hypoxic-Ischemic Brain Injury.

    Science.gov (United States)

    Mitra, Subhabrata; Bale, Gemma; Meek, Judith; Uria-Avellanal, Cristina; Robertson, Nicola J; Tachtsidis, Ilias

    2016-01-01

    Therapeutic hypothermia (TH) has become a standard of care following hypoxic ischemic encephalopathy (HIE). After TH, body temperature is brought back to 37 °C over 14 h. Lactate/N-acetylasperatate (Lac/NAA) peak area ratio on proton magnetic resonance spectroscopy ((1)H MRS) is the best available outcome biomarker following HIE. We hypothesized that broadband near infrared spectroscopy (NIRS) measured changes in the oxidation state of cytochrome-c-oxidase concentration (Δ[oxCCO]) and cerebral hemodynamics during rewarming would relate to Lac/NAA. Broadband NIRS and systemic data were collected during rewarming from 14 infants following HIE over a mean period of 12.5 h. (1)H MRS was performed on day 5-9. Heart rate increased by 20/min during rewarming while blood pressure and peripheral oxygen saturation (SpO2) remained stable. The relationship between mitochondrial metabolism and oxygenation (measured as Δ[oxCCO] and Δ[HbD], respectively) was calculated by linear regression analysis. This was reviewed in three groups: Lac/NAA values 1. Mean regression coefficient (r (2)) values in these groups were 0.41 (±0.27), 0.22 (±0.21) and 0.01, respectively. The relationship between mitochondrial metabolism and oxygenation became impaired with rising Lac/NAA. Cardiovascular parameters remained stable during rewarming.

  19. Mitochondrial Optic Atrophy (OPA) 1 Processing Is Altered in Response to Neonatal Hypoxic-Ischemic Brain Injury.

    Science.gov (United States)

    Baburamani, Ana A; Hurling, Chloe; Stolp, Helen; Sobotka, Kristina; Gressens, Pierre; Hagberg, Henrik; Thornton, Claire

    2015-09-17

    Perturbation of mitochondrial function and subsequent induction of cell death pathways are key hallmarks in neonatal hypoxic-ischemic (HI) injury, both in animal models and in term infants. Mitoprotective therapies therefore offer a new avenue for intervention for the babies who suffer life-long disabilities as a result of birth asphyxia. Here we show that after oxygen-glucose deprivation in primary neurons or in a mouse model of HI, mitochondrial protein homeostasis is altered, manifesting as a change in mitochondrial morphology and functional impairment. Furthermore we find that the mitochondrial fusion and cristae regulatory protein, OPA1, is aberrantly cleaved to shorter forms. OPA1 cleavage is normally regulated by a balanced action of the proteases Yme1L and Oma1. However, in primary neurons or after HI in vivo, protein expression of YmelL is also reduced, whereas no change is observed in Oma1 expression. Our data strongly suggest that alterations in mitochondria-shaping proteins are an early event in the pathogenesis of neonatal HI injury.

  20. Neuroprotection of the leaf and stem of Vitis amurensis and their active compounds against ischemic brain damage in rats and excitotoxicity in cultured neurons.

    Science.gov (United States)

    Kim, Joo Youn; Jeong, Ha Yeon; Lee, Hong Kyu; Kim, SeungHwan; Hwang, Bang Yeon; Bae, KiHwan; Seong, Yeon Hee

    2012-01-15

    Vitis amurensis (Vitaceae) has been reported to have anti-oxidant and anti-inflammatory activities. The present study investigated a methanol extract from the leaf and stem of V. amurensis for neuroprotective effects on cerebral ischemic damage in rats and on excitotoxicity induced by glutamate in cultured rat cortical neurons. Transient focal cerebral ischemia was induced by 2h middle cerebral artery occlusion followed by 24h reperfusion (MCAO/reperfusion) in rats. Orally administered V. amurensis (25-100 mg/kg) reduced MCAO/reperfusion-induced infarct and edema formation, neurological deficits, and neuronal death. Depletion of glutathione (GSH) level and lipid peroxidation induced by MCAO/reperfusion was inhibited by administration of V. amurensis. The increase of phosphorylated mitogen-activated protein kinases (MAPKs), cyclooxygenase-2 (COX-2), and pro-apoptotic proteins and the decrease of anti-apoptotic protein in MCAO/reperfusion rats were significantly inhibited by treatment with V. amurensis. Exposure of cultured cortical neurons to 500 μM glutamate for 12h induced neuronal cell death. V. amurensis (1-50 μg/ml) and (+)-ampelopsin A, γ-2-viniferin, and trans-ε-viniferin isolated from the leaf and stem of V. amurensis inhibited glutamate-induced neuronal death, the elevation of intracellular calcium ([Ca(2+)](i)), the generation of reactive oxygen species (ROS), and changes of apoptosis-related proteins in cultured cortical neurons, suggesting that the neuroprotective effect of V. amurensis may be partially attributed to these compounds. These results suggest that the neuroprotective effect of V. amurensis against focal cerebral ischemic injury might be due to its anti-apoptotic effect, resulting from anti-excitotoxic, anti-oxidative, and anti-inflammatory effects and that the leaf and stem of V. amurensis have possible therapeutic roles for preventing neurodegeneration in stroke. Copyright © 2011 Elsevier GmbH. All rights reserved.

  1. Aging of the Brain: How Can We Prevent It?

    Science.gov (United States)

    Jarvik, Lissy F.

    1988-01-01

    Contends distinction between normal and abnormal aging of the brain changes as data emerge which identify as pathology what had previously been considered the norm. Reviews research on effects of aging in twins begun in 1940s, focusing on facts related to intellectual decline, neuropsychological test performance relationship to dementia, and…

  2. Prostacyclin infusion may prevent secondary damage in pericontusional brain tissue

    DEFF Research Database (Denmark)

    Reinstrup, Peter; Nordström, Carl-Henrik

    2011-01-01

    Prostacyclin is a potent vasodilator, inhibitor of leukocyte adhesion, and platelet aggregation, and has been suggested as therapy for cerebral ischemia. A case of focal traumatic brain lesion that was monitored using intracerebral microdialysis, and bedside analysis and display is reported here........ When biochemical signs of cerebral ischemia progressed, i.v. infusion of prostacyclin was started....

  3. Humanin prevents brain mitochondrial dysfunction in a cardiac ischaemia-reperfusion injury model.

    Science.gov (United States)

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

    2016-06-01

    What is the central question of this study? Myocardial ischaemia-reperfusion (I/R) injury causes interference in the systemic circulation and damages not only the heart but also several vital organs, including the brain. Recently, a novel peptide called humanin has been shown to exert potent neuroprotective effects. However, the effect of humanin on the brain during cardiac I/R injury has not yet been investigated. What is the main finding and its importance? The I/R injury caused blood-brain barrier breakdown, increased brain oxidative stress and resulted in mitochondrial dysfunction. Only the humanin treatment before ischaemia attenuated brain mitochondrial dysfunction, but it did not prevent blood-brain barrier breakdown or brain oxidative stress. Humanin treatment during ischaemia and in the reperfusion period provided no neuroprotection. These findings indicate that humanin exerted neuroprotection during cardiac I/R injury via improved brain mitochondrial function. Myocardial ischaemia-reperfusion (I/R) injury causes interference in the systemic circulation and damages not only the heart but also several vital organs, including the brain. Nevertheless, limited information is available regarding the effect of cardiac I/R injury on the brain, including blood-brain barrier (BBB) breakdown, brain oxidative stress and mitochondrial function. Recently, a novel peptide called humanin has been shown to exert potent neuroprotective effects. However, the effect of humanin on the brain during cardiac I/R injury has not yet been investigated. Forty-two male Wistar rats were divided into the following two groups: an I/R group, which was subjected to a 30 min left anterior descending coronary artery occlusion followed by 120 min reperfusion (I/R group; n = 36); and a sham group (n = 6). The I/R group was divided into six subgroups. Each subgroup was given either vehicle or humanin analogue (84 μg kg(-1) , i.v.) at three different time points, namely before

  4. THE USE OF ATORVASTATIN FOR THE PREVENTION OF RECURRENT ATRIAL FIBRILLATION AFTER ELECTRICAL CARDIOVERSION IN PATIENTS WITH ISCHEMIC HEART DISEASE

    Directory of Open Access Journals (Sweden)

    S. N. Tereshchenko

    2010-01-01

    Full Text Available Aim. To study the effect of atorvastatin on the rate of atrial fibrillation (AF recurrence after electrical cardioversion in patients with ischemic heart disease (IHD and paroxysmal AF.Material and Methods. Sixty outpatients and inpatients (aged 30-70 y.o. with IHD and paroxysmal AF were included into the open controlled randomized study immediately after the restoration of sinus rhythm by electrical cardioversion. Patients were randomized into 2 groups. Patients in Group 1 (n=30 received standard therapy recommended for maintenance of sinus rhythm in paroxysmal AF and atorvastatin (average dose 23.5±3.7 mg/day, and patients in Group 2 (n=30 had only the standard therapy. Routine blood analysis, blood chemistry (transaminases, creatine phosphokinase, creatinine, bilirubin, glucose, lipid profile, daily ECG monitoring, treatment safety evaluation were performed. AF relapse was considered as a primary endpoint.Results. Significant reduction in the rate of AF recurrence in was revealed in patients treated with atorvastatin. According to daily ECG monitoring AF relapse was recorded in 8.3 and 48% of patients in Group 1 and Group 2, respectively (p<0.001. Episodes of sinus tachycardia decreased on 52.3% (p<0.001 and 48,5% (p<0.01 in patients of the 1st and the 2 nd group, respectively.Conclusion. The addition of atorvastatin to the standard therapy for maintenance of sinus rhythm reduces effectively the rate of AF recurrence in patients with IHD and paroxysmal AF.

  5. Tanshinone I alleviates motor and cognitive impairments via suppressing oxidative stress in the neonatal rats after hypoxic-ischemic brain damage.

    Science.gov (United States)

    Dai, Chunfang; Liu, Yannan; Dong, Zhifang

    2017-11-14

    Neonatal hypoxia-ischemia is one of the main reasons that cause neuronal damage and neonatal death. Several studies have shown that tanshinone I (TsI), one of the major ingredients of Danshen, exerts potential neuroprotective effect in adult mice exposed to permanent left cerebral ischemia. However, it is unclear whether administration of TsI has neuroprotective effect on neonatal hypoxic-ischemic brain damage (HIBD), and if so, the potential mechanisms also remain unclear. Here, we reported that treatment with TsI (5 mg/kg, i.p.) significantly alleviated the deficits of myodynamia and motor functions as well as the spatial learning and memory in the rat model of HIBD. These behavioral changes were accompanied by a significant decrease in the number of neuronal loss in the CA1 area of hippocampus. Moreover, ELISA assay showed that TsI significantly increased the production of antioxidants including total antioxidant capacity (T-AOC), glutathione (GSH), total superoxide dismutase (T-SOD) and catalase (CAT), and reduced the production of pro-oxidants including hydrogen peroxide (H 2 O 2 ), total nitric oxide synthase (T-NOS) and inducible nitric oxide synthase (iNOS). Taken together, these results indicate that TsI presents potential neuroprotection against neuronal damage via exerting significantly antioxidative activity and against pro-oxidant challenge, thereby ameliorating hypoxia-ischemia-induced motor and cognitive impairments in the neonatal rats, suggesting that TsI may be a potential therapeutic agent against HIBD.

  6. Acupuncture at Waiguan (SJ5) and sham points influences activation of functional brain areas of ischemic stroke patients: a functional magnetic resonance imaging study.

    Science.gov (United States)

    Qi, Ji; Chen, Junqi; Huang, Yong; Lai, Xinsheng; Tang, Chunzhi; Yang, Junjun; Chen, Hua; Qu, Shanshan

    2014-02-01

    Most studies addressing the specificity of meridians and acupuncture points have focused mainly on the different neural effects of acupuncture at different points in healthy individuals. This study examined the effects of acupuncture on brain function in a pathological context. Sixteen patients with ischemic stroke were randomly assigned to true point group (true acupuncture at right Waiguan (SJ5)) and sham point group (sham acupuncture). Results of functional magnetic resonance imaging revealed activation in right parietal lobe (Brodmann areas 7 and 19), the right temporal lobe (Brodmann area 39), the right limbic lobe (Brodmann area 23) and bilateral occipital lobes (Brodmann area 18). Furthermore, inhibition of bilateral frontal lobes (Brodmann area 4, 6, and 45), right parietal lobe (Brodmann areas 1 and 5) and left temporal lobe (Brodmann area 21) were observed in the true point group. Activation in the precuneus of right parietal lobe (Brodmann area 7) and inhibition of the left superior frontal gyrus (Brodmann area 10) was observed in the sham group. Compared with sham acupuncture, acupuncture at Waiguan in stroke patients inhibited Brodmann area 5 on the healthy side. Results indicated that the altered specificity of sensation-associated cortex (Brodmann area 5) is possibly associated with a central mechanism of acupuncture at Waiguan for stroke patients.

  7. Harmful effect of kainic acid on brain ischemic damage is not related to duration of status epilepticus

    OpenAIRE

    Hasson, Henry; Malhotra, Samit; Giorgi, Filippo S.; Rosenbaum, Daniel M.; Moshé, Solomon L.

    2009-01-01

    Status epilepticus is common in infants and may have long-term consequences on the brain persisting into adulthood. Vascular ischemia is a common cause of stroke in adulthood. The extent of stroke in 15-day-old rats is larger when previously exposed to kainic acid-induced status epilepticus. In this paper, we assess whether shortening the duration of seizures modifies subsequent susceptibility to middle cerebral artery occlusion. We administered pentobarbital 50 mg/kg to abort seizures after ...

  8. Glial-Restricted Precursors Protect Neonatal Brain Slices from Hypoxic-Ischemic Cell Death Without Direct Tissue Contact.

    Science.gov (United States)

    Sweda, Romy; Phillips, Andre W; Marx, Joel; Johnston, Michael V; Wilson, Mary Ann; Fatemi, Ali

    2016-07-01

    Glial-Restricted Precursors (GRPs) are tripotential progenitors that have been shown to exhibit beneficial effects in several preclinical models of neurological disorders, including neonatal brain injury. The mechanisms of action of these cells, however, require further study, as do clinically relevant questions such as timing and route of cell administration. Here, we explored the effects of GRPs on neonatal hypoxia-ischemia during acute and subacute stages, using an in vitro transwell co-culture system with organotypic brain slices exposed to oxygen-glucose deprivation (OGD). OGD-exposed slices that were then co-cultured with GRPs without direct cell contact had decreased tissue injury and cortical cell death, as evaluated by lactate dehydrogenase (LDH) release and propidium iodide (PI) staining. This effect was more pronounced when cells were added during the subacute phase of the injury. Furthermore, GRPs reduced the amount of glutamate in the slice supernatant and changed the proliferation pattern of endogenous progenitor cells in brain slices. In summary, we show that GRPs exert a neuroprotective effect on neonatal hypoxia-ischemia without the need for direct cell-cell contact, thus confirming the rising view that beneficial actions of stem cells are more likely attributable to trophic or immunomodulatory support rather than to long-term integration.

  9. Baicalin Attenuates Blood-Brain Barrier Disruption and Hemorrhagic Transformation and Improves Neurological Outcome in Ischemic Stroke Rats with Delayed t-PA Treatment: Involvement of ONOO--MMP-9 Pathway.

    Science.gov (United States)

    Chen, Hansen; Guan, Binghe; Chen, Xi; Chen, Xingmiao; Li, Caiming; Qiu, Jinhua; Yang, Dan; Liu, Ke Jian; Qi, Suhua; Shen, Jiangang

    2017-12-23

    Tissue plasminogen activator (t-PA) has a restrictive therapeutic window within 4.5 h after ischemic stroke with the risk of hemorrhagic transformation (HT) and neurotoxicity when it is used beyond the time window. In the present study, we tested the hypothesis that baicalin, an active compound of medicinal plant, could attenuate HT in cerebral ischemia stroke with delayed t-PA treatment. Male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 4.5 h and then continuously received t-PA infusion (10 mg/kg) for 0.5 h and followed by 19-h reperfusion. Baicalin (50, 100, 150 mg/kg) was administrated via femoral vein at 4.5 h after MCAO cerebral ischemia. Delayed t-PA infusion significantly increased the mortality rate, induced HT, blood-brain barrier (BBB) damage, and apoptotic cell death in the ischemic brains and exacerbated neurological outcomes in cerebral ischemia-reperfusion rats at 24 h after MCAO cerebral ischemia. Co-treatment of baicalin significantly reduced the mortality rates, ameliorated the t-PA-mediated BBB disruption and HT. Furthermore, baicalin showed to directly scavenge peroxynitrite and inhibit MMP-9 expression and activity in the ischemic brains with the delayed t-PA treatment. Baicalin had no effect on the t-PA fibrinolytic function indicated by t-PA activity assay. Taken together, baicalin could attenuate t-PA-mediated HT and improve the outcomes of ischemic stroke treatment possibly via inhibiting peroxynitrite-mediated MMP-9 activation.

  10. Recent Trends in Neuro-endovascular Treatment for Acute Ischemic Stroke, Cerebral Aneurysms, Carotid Stenosis, and Brain Arteriovenous Malformations.

    Science.gov (United States)

    Matsumaru, Yuji; Ishikawa, Eiichi; Yamamoto, Tetsuya; Matsumura, Akira

    2017-06-15

    The efficacy of mechanical thrombectomy with stent retrievers for emergent large vessel occlusion has been proved by randomized trials. Mechanical thrombectomy is increasingly being adopted in Japan since stent retrievers were first approved in 2014. An urgent clinical task is to offer structured systems of care to provide this treatment in a timely fashion to all patients with emergent large vessel occlusion. Treatment with flow-diverting stents is currently a preferred treatment option worldwide for large and giant unruptured aneurysms. Initial studies reported high rates of complete aneurysm occlusion, even in large and giant aneurysms, without delayed aneurysmal recanalization and/or growth. The Pipeline Embolic Device is a flow diverter recently approved in Japan for the treatment of large and giant wide-neck unruptured aneurysms in the internal carotid artery, from the petrous to superior hypophyseal segments. Carotid artery stenting is the preferred treatment approach for carotid stenosis in Japan, whereas it remains an alternative for carotid endarterectomy in Europe and the United States. Carotid artery stenting with embolic protection and plaque imaging is effective in achieving favorable outcomes. The design and conclusions of a randomized trial of unruptured brain arteriovenous malformations (ARUBA) trial, which compared medical management alone and medical management with interventional therapy in patients with an unruptured arteriovenous brain malformation, are controversial. However, the annual bleeding rate (2.2%) of the medical management group obtained from this study is worthy of consideration when deciding treatment strategy.

  11. Integrating Health Promotion Into Physical Therapy Practice to Improve Brain Health and Prevent Alzheimer Disease.

    Science.gov (United States)

    McGough, Ellen; Kirk-Sanchez, Neva; Liu-Ambrose, Teresa

    2017-07-01

    Alzheimer disease is the most common cause of dementia, and brain pathology appears years before symptoms are evident. Primary prevention through health promotion can incorporate lifestyle improvement across the lifespan. Risk factor assessment and identifying markers of disease might also trigger preventive measures needed for high-risk individuals and groups. Many potential risk factors are modifiable through exercise, and may be responsive to early intervention strategies to reduce the downward slope toward disability. Through the use of common clinical tests to identify cognitive and noncognitive functional markers of disease, detection and intervention can occur at earlier stages, including preclinical stages of disease. Physical activity and exercise interventions to address modifiable risk factors and impairments can play a pivotal role in the prevention and delay of functional decline, ultimately reducing the incidence of dementia. This article discusses prevention, prediction, plasticity, and participation in the context of preserving brain health and preventing Alzheimer disease and related dementias in aging adults. Rehabilitation professionals have opportunities to slow disease progression through research, practice, and education initiatives. From a clinical perspective, interventions that target brain health through lifestyle changes and exercise interventions show promise for preventing stroke and associated neurovascular diseases in addition to dementia. Physical therapists are well positioned to integrate primary health promotion into practice for the prevention of dementia and other neurological conditions in older adults.

  12. Tempol, a superoxide dismutase-mimetic drug, prevents chronic ischemic renal injury in two-kidney, one-clip hypertensive rats.

    Science.gov (United States)

    Nunes, Douglas Vq; Costa, Cristiane A; De Bem, Graziele F; Cordeiro, Viviane Sc; Santos, Izabelle B; Carvalho, Lenize Crm; Jordão, Alessandro K; Cunha, Anna C; Ferreira, Vitor F; Moura, Roberto S; Resende, Angela C; Ognibene, Dayane T

    2018-01-23

    Tempol, a superoxide dismutase-mimetic drug, has been shown to attenuate radical-induced damage, exerting beneficial effects in the animal models of oxidative stress and hypertension. This study evaluated the effect of Tempol on renal structural and functional alterations in two-Kidney, one-Clip hypertensive rats. In this study, young male Wistar rats had the left kidney clipped (2K1C), and sham-operated animals (Sham) were used as controls. Animals received Tempol (1mmol/L in drinking water) or vehicle for 5 weeks. Systolic blood pressure was evaluated once a week. At the end of the experimental protocol, the animals were placed in metabolic cages to collect urine (24h) and then anesthetized with thiopental (70mg/kg i.p.) to collect blood by puncturing the descending aorta for biochemical analysis, and the clipped kidney for morphological and immunohistochemical analyses. The vasodilator effect of Tempol was evaluated in mesenteric arterial bed (MAB) isolated from adult Wistar rats. The chronic treatment with Tempol prevented the development of hypertension and the increased plasma levels of urea, creatinine, and 8-isoprostane in 2K1C animals. Tempol also improved both glomeruli number and kidney volume to normal levels in the 2K1C+Tempol group. In addition, the treatment prevented the increased collagen deposition and immunostaining for renin, caspase-3, and 8-isoprostane in the stenotic kidney of 2K1C animals. Moreover, Tempol induced a dose-dependent vasodilator response in MAB from Wistar rats. These results suggest that Tempol protects the stenotic kidney against chronic ischemic renal injury and prevents renal dysfunction in the 2K1C model, probably through its antioxidant, vasodilator and antihypertensive actions.

  13. Peptidylarginine deiminases: novel drug targets for prevention of neuronal damage following hypoxic ischemic insult (HI) in neonates.

    Science.gov (United States)

    Lange, Sigrun; Rocha-Ferreira, Eridan; Thei, Laura; Mawjee, Priyanka; Bennett, Kate; Thompson, Paul R; Subramanian, Venkataraman; Nicholas, Anthony P; Peebles, Donald; Hristova, Mariya; Raivich, Gennadij

    2014-08-01

    Neonatal hypoxic ischaemic (HI) injury frequently causes neural impairment in surviving infants. Our knowledge of the underlying molecular mechanisms is still limited. Protein deimination is a post-translational modification caused by Ca(+2) -regulated peptidylarginine deiminases (PADs), a group of five isozymes that display tissue-specific expression and different preference for target proteins. Protein deimination results in altered protein conformation and function of target proteins, and is associated with neurodegenerative diseases, gene regulation and autoimmunity. In this study, we used the neonatal HI and HI/infection [lipopolysaccharide (LPS) stimulation] murine models to investigate changes in protein deimination. Brains showed increases in deiminated proteins, cell death, activated microglia and neuronal loss in affected brain areas at 48 h after hypoxic ischaemic insult. Upon treatment with the pan-PAD inhibitor Cl-amidine, a significant reduction was seen in microglial activation, cell death and infarct size compared with control saline or LPS-treated animals. Deimination of histone 3, a target protein of the PAD4 isozyme, was increased in hippocampus and cortex specifically upon LPS stimulation and markedly reduced following Cl-amidine treatment. Here, we demonstrate a novel role for PAD enzymes in neural impairment in neonatal HI Encephalopathy, highlighting their role as promising new candidates for drug-directed intervention in neurotrauma. Hypoxic Ischaemic Insult (HI) results in activation of peptidylarginine deiminases (PADs) because of calcium dysregulation. Target proteins undergo irreversible changes of protein bound arginine to citrulline, resulting in protein misfolding. Infection in synergy with HI causes up-regulation of TNFα, nuclear translocation of PAD4 and change in gene regulation as a result of histone deimination. Pharmacological PAD inhibition significantly reduced HI brain damage. © 2014 The Authors. Journal of Neurochemistry

  14. [Effects of electric stimulation at the cerebellar fastigial nucleus on astrocytes in the hippocampus of neonatal rats with hypoxic-ischemic brain damage].

    Science.gov (United States)

    Li, Xiao-Li; Jia, Tian-Ming; Luan, Bin; Liu, Tao; Yuan, Yan

    2011-04-01

    To study the effects of electric stimulation at the cerebellar fastigial nucleus on astrocytes in the hippocampus of neonatal rats with hypoxic-ischemic brain damage (HIBD) and the possible mechanism. One hundred and eighty 7-day-old neonatal Sprague-Dawley rats were randomly divided into three groups: sham-operation (control group) and HIBD with and without electric stimulation (n=60 each). The HIBD model of neonatal rats was prepared by the Rice-Vennucci method. Electric stimulation at the cerebellar fastigial nucleus was given 24 hrs after the operation in the electric stimulation group once daily and lasted for 30 minutes each time. The other two groups were not subjected to electric stimulation but captured to fix in corresponding periods. Rats were sacrificed 3, 7, 14 and 21 days after stimulations to observe the glial fibrillary acidic protein (GFAP) expression by immunohistochemisty and the ultrastructural changes of astrocytes in the hippocampus under an electron microscope. Immunohistochemical analysis showed the expression of GFAP in the HIBD groups with and without electric stimulation increased significantly compared with the control group on day 3, reached the peak on day 7, and the increased expression remained till to day 21. The GFAP expression in the electric stimulation group was significantly lower than that in the untreated HIBD group at all time points. Under the electron microscope, the astrocytes in the untreated HIBD group were swollen and the amount of organelles was reduced, while the swelling of astrocytes was alleviated and the organelles remained in integrity in the electric stimulation group. The electric stimulation at the cerebellar fastigial nucleus can inhibit the excessive proliferation of astrocytes and relieve the structural damage of astrocytes in neonatal rats following HIBD.

  15. [Priorities of secondary prevention of ischemic heart disease in conditions of a depressive region: preliminary results of the North Caucasian project].

    Science.gov (United States)

    Mamedov, M N; Didigova, R T; Ugurchieva, Z O; Inarokova, A M

    2011-01-01

    was detection of behavioral factors, main risk factors of development of cardiovascular diseases (CVD), assessment of adequacy of their management, as well as assessment of quality of life in a cohort of patients with ischemic heart disease from three republics of the North Caucasian region. A sample of patients with ischemic heart disease (IHD) aged 40-69 years (n=1500) from 3 republics of the North Caucasian Federal Okrug (Ingushetia, Kabardino-Balkaria, and North Ossetia - Alania) were included in a clinico-epidemiological project. In this work we present results obtained in three towns and districts of the Republic Ingushetia (300 men and 230 women with IHD and class II-III effort angina). Socio-demographic factors, family history of CVD, disturbances of nutrition, and physical activity were assessed by standard WHO questionnaires. For assessment of anthropometric deviations we measured height, body mass, and waist circumference. With the aim of detection of hyperlipidemia and disturbances of carbohydrate metabolism we measured levels of total cholesterol and fasting glucose in venous blood. Quality of life was assessed by EQ-5D questionnaire which comprised 5 points: movement, self service, everyday activity, pain/discomfort, and anxiety/depression. Each forth men (24.3%) smoked, and 12% were alcohol abusers. Each forth patient had severe disturbance of nutrition. Disturbances of nutrition of medium degree were detected twice more often. Way of life was sedentary in 63% of women and 46% of men. Abdominal obesity was detected in 46% of men and 72.6% of women. Prevalence of hypercholesterolemia was 96.7% among men and 90.7% among women. Every fifth patient with IHD had diabetes, in 10% of patients diabetes was newly detected. Quality of life changed in every second IHD patient with angina because of limitation in carrying out everyday work, movement and presence of chest discomfort, this was associated with presence of anxiety/depression. Main priority of

  16. Selective A2A receptor antagonist prevents microglia-mediated neuroinflammation and protects retinal ganglion cells from high intraocular pressure-induced transient ischemic injury.

    Science.gov (United States)

    Madeira, Maria H; Boia, Raquel; Elvas, Filipe; Martins, Tiago; Cunha, Rodrigo A; Ambrósio, António Francisco; Santiago, Ana Raquel

    2016-03-01

    Glaucoma is a leading cause of vision loss and blindness worldwide, characterized by chronic and progressive neuronal loss. Reactive microglial cells have been recognized as a neuropathologic feature, contributing to local inflammation and retinal neurodegeneration. In a recent in vitro work (organotypic cultures), we demonstrated that blockade of adenosine A2A receptor (A2AR) prevents the neuroinflammatory response and affords protection to retinal ganglion cells (RGCs) against exposure to elevated hydrostatic pressure (EHP), to mimic elevated intraocular pressure (IOP), the main risk factor for glaucoma development. Herein, we investigated whether a selective A2AR antagonist (SCH 58261) could modulate retinal microglia reactivity and their inflammatory response. Furthermore, we took advantage of the high IOP-induced transient ischemia (ischemia-reperfusion, I-R) animal model to evaluate the protective role of A2AR blockade in the control of retinal neuroinflammation and neurodegeneration. Primary microglial cell cultures were challenged either with lipopolysaccharide or with EHP, in the presence or absence of A2AR antagonist SCH 58261 (50 nM). In addition, I-R injury was induced in adult Wistar rats after intravitreal administration of SCH 58261 (100 nM, 5 μL). Our results showed that SCH 58261 attenuated microglia reactivity and the increased expression and release of proinflammatory cytokines. Moreover, intravitreal administration of SCH 58261 prevented I-R-induced cell death and RGC loss, by controlling microglial-mediated neuroinflammatory response. These results prompt the proposal that A2AR blockade may have great potential in the management of retinal neurodegenerative diseases characterized by microglia reactivity and RGC death, such as glaucoma and ischemic diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Grape seed and skin extract prevents high-fat diet-induced brain lipotoxicity in rat.

    Science.gov (United States)

    Charradi, Kamel; Elkahoui, Salem; Karkouch, Ines; Limam, Ferid; Hassine, Fethy Ben; Aouani, Ezzedine

    2012-09-01

    Obesity is related to an elevated risk of dementia and the physiologic mechanisms whereby fat adversely affects the brain are poorly understood. The present investigation analyzed the effect of a high fat diet (HFD) on brain steatosis and oxidative stress and the intracellular mediators involved in signal transduction, as well as the protection offered by grape seed and skin extract (GSSE). HFD induced ectopic deposition of cholesterol and phospholipid but not triglyceride. Moreover brain lipotoxicity is linked to an oxidative stress characterized by increased lipoperoxidation and carbonylation, inhibition of glutathione peroxidase and superoxide dismutase activities, depletion of manganese and a concomitant increase in ionizable calcium and acetylcholinesterase activity. Importantly GSSE alleviated all the deleterious effects of HFD treatment. Altogether our data indicated that HFD could find some potential application in the treatment of manganism and that GSSE should be used as a safe anti-lipotoxic agent in the prevention and treatment of fat-induced brain injury.

  18. Spatial Working Memory Deficits in Male Rats Following Neonatal Hypoxic Ischemic Brain Injury Can Be Attenuated by Task Modifications

    Directory of Open Access Journals (Sweden)

    Amanda L. Smith

    2014-04-01

    Full Text Available Hypoxia-ischemia (HI; reduction in blood/oxygen supply is common in infants with serious birth complications, such as prolonged labor and cord prolapse, as well as in infants born prematurely (<37 weeks gestational age; GA. Most often, HI can lead to brain injury in the form of cortical and subcortical damage, as well as later cognitive/behavioral deficits. A common domain of impairment is working memory, which can be associated with heightened incidence of developmental disorders. To further characterize these clinical issues, the current investigation describes data from a rodent model of HI induced on postnatal (P7, an age comparable to a term (GA 36–38 human. Specifically, we sought to assess working memory using an eight-arm radial water maze paradigm. Study 1 used a modified version of the paradigm, which requires a step-wise change in spatial memory via progressively more difficult tasks, as well as multiple daily trials for extra learning opportunity. Results were surprising and revealed a small HI deficit only for the final and most difficult condition, when a delay before test trial was introduced. Study 2 again used the modified radial arm maze, but presented the most difficult condition from the start, and only one daily test trial. Here, results were expected and revealed a robust and consistent HI deficit across all weeks. Combined results indicate that male HI rats can learn a difficult spatial working memory task if it is presented in a graded multi-trial format, but performance is poor and does not appear to remediate if the task is presented with high initial memory demand. Male HI rats in both studies displayed impulsive characteristics throughout testing evidenced as reduced choice latencies despite more errors. This aspect of behavioral results is consistent with impulsiveness as a core symptom of ADHD—a diagnosis common in children with HI insult. Overall findings suggest that task specific behavioral modifications are

  19. Program of rehabilitative exercise and education to avert vascular events after non-disabling stroke or transient ischemic attack (PREVENT Trial: a multi-centred, randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Thompson Kara

    2010-12-01

    Full Text Available Abstract Background Despite lack of outward signs, most individuals after non-disabling stroke (NDS and transient ischemic attack (TIA have significant cardiovascular and cerebrovascular disease and are at high risk of a major stroke, hospitalization for other vascular events, or death. Most have multiple modifiable risk factors (e.g., hypertension, physical inactivity, hyperlipidaemia, diabetes, tobacco consumption, psychological stress. In addition, accelerated rates of depression, cognitive decline, and poor quality of sleep have been reported following TIA, which correlate with poor functional outcomes and reduced quality of life. Thus, NSD and TIA are important warning signs that should not be overlooked. The challenge is not unlike that facing other 'silent' conditions - to identify a model of care that is effective in changing people's current behaviors in order to avert further morbidity. Methods/Design A single blind, randomized controlled trial will be conducted at two sites to compare the effectiveness of a program of rehabilitative exercise and education versus usual care in modifying vascular risk factors in adults after NDS/TIA. 250 adults within 90 days of being diagnosed with NDS/TIA will be randomly allocated to a 12-week program of exercise and education (PREVENT or to an outpatient clinic assessment and discussion of secondary prevention recommendations with return clinic visits as indicated (USUAL CARE. Primary outcome measures will include blood pressure, waist circumference, 12-hour fasting lipid profile, and 12-hour fasting glucose/hemoglobin A1c. Secondary measures will include exercise capacity, walking endurance, physical activity, cognitive function, depression, goal attainment and health-related quality of life. Outcome assessment will be conducted at baseline, post-intervention, and 6- and 12-month follow-ups. Direct health care costs incurred over one year by PREVENT versus USUAL CARE participants will also be

  20. Chronic Treatment with a Water-Soluble Extract from the Culture Medium of Ganoderma lucidum Mycelia Prevents Apoptosis and Necroptosis in Hypoxia/Ischemia-Induced Injury of Type 2 Diabetic Mouse Brain

    Directory of Open Access Journals (Sweden)

    Meiyan Xuan

    2015-01-01

    Full Text Available Type 2 diabetes mellitus has been known to increase systemic oxidative stress by chronic hyperglycemia and visceral obesity and aggravate cerebral ischemic injury. On the basis of our previous study regarding a water-soluble extract from the culture medium of Ganoderma lucidum mycelia (designed as MAK, which exerts antioxidative and neuroprotective effects, the present study was conducted to evaluate the preventive effects of MAK on apoptosis and necroptosis (a programmed necrosis induced by hypoxia/ischemia (H/I in type 2 diabetic KKAy mice. H/I was induced by a combination of unilateral common carotid artery ligation with hypoxia (8% O2 for 20 min and subsequent reoxygenation. Pretreatment with MAK (1 g/kg, p.o. for a week significantly reduced H/I-induced neurological deficits and brain infarction volume assessed at 24 h of reoxygenation. Histochemical analysis showed that MAK significantly suppressed superoxide production, neuronal cell death, and vacuolation in the ischemic penumbra, which was accompanied by a decrease in the numbers of TUNEL- or cleaved caspase-3-positive cells. Furthermore, MAK decreased the expression of receptor-interacting protein kinase 3 mRNA and protein, a key molecule for necroptosis. These results suggest that MAK confers resistance to apoptotic and necroptotic cell death and relieves H/I-induced cerebral ischemic injury in type 2 diabetic mice.

  1. Early behavioral intervention, brain plasticity, and the prevention of autism spectrum disorder.

    Science.gov (United States)

    Dawson, Geraldine

    2008-01-01

    Advances in the fields of cognitive and affective developmental neuroscience, developmental psychopathology, neurobiology, genetics, and applied behavior analysis have contributed to a more optimistic outcome for individuals with autism spectrum disorder (ASD). These advances have led to new methods for early detection and more effective treatments. For the first time, prevention of ASD is plausible. Prevention will entail detecting infants at risk before the full syndrome is present and implementing treatments designed to alter the course of early behavioral and brain development. This article describes a developmental model of risk, risk processes, symptom emergence, and adaptation in ASD that offers a framework for understanding early brain plasticity in ASD and its role in prevention of the disorder.

  2. Intracranial Pressure Elevation 24 Hours after Ischemic Stroke in Aged Rats is Prevented by Early, Short Hypothermia Treatment

    Directory of Open Access Journals (Sweden)

    Lucy Anne Murtha

    2016-05-01

    Full Text Available Stroke is predominantly a senescent disease, yet most preclinical studies investigate treatment in young animals. We recently demonstrated that short-duration hypothermia-treatment completely prevented the dramatic intracranial pressure (ICP rise seen post-stroke in young rats. Here, our aim was to investigate whether a similar ICP rise occurs in aged rats and to determine whether short-duration hypothermia is an effective treatment in aged animals. Experimental Middle Cerebral Artery occlusion (MCAo - 3 hour occlusion was performed on male Wistar rats aged 19-20 months. At one hour after stroke-onset, rats were randomized to 2.5 hours hypothermia-treatment (32.5 °C or normothermia (37 °C. ICP was monitored at baseline, for 3.5 hours post-occlusion, and at 24 hours post-stroke. Infarct and edema volumes were calculated from histology. Baseline pre-stroke ICP was 11.2 ± 3.3 mmHg across all animals. Twenty-four hours post-stroke, ICP was significantly higher in normothermic animals compared to hypothermia-treated animals (27.4 ± 18.2 mmHg vs. 8.0 ± 5.0 mmHg, p = 0.03. Infarct and edema volumes were not significantly different between groups. These data demonstrate ICP may also increase 24 hours post-stroke in aged rats, and that short-duration hypothermia treatment has a profound and sustained preventative effect. These findings may have important implications for the use of hypothermia in clinical trials of aged stroke patients.

  3. Neutrophil proteomic analysis reveals the participation of antioxidant enzymes, motility and ribosomal proteins in the prevention of ischemic effects by preconditioning

    DEFF Research Database (Denmark)

    Arshid, S; Tahir, M; Fontes, B

    2017-01-01

    reperfusion and ischemic preconditioning. After neutrophil separation, proteins were extracted, trypsin digested and the resulting peptides were iTRAQ labeled followed by HILIC fractionation and nLC-MS/MS analysis. After database searches, normalization and statistical analysis our proteomic analysis resulted...... and proteasome, after intestinal ischemic preconditioning. Furthermore, enzyme prediction analysis revealed the regulation of some important antioxidant enzymes and having their role in reactive oxygen species production. To our knowledge, this work describes the most comprehensive and detailed quantitative...

  4. Coronary heart disease risk in patients with stroke or transient ischemic attack and no known coronary heart disease: findings from the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial.

    Science.gov (United States)

    Amarenco, Pierre; Goldstein, Larry B; Sillesen, Henrik; Benavente, Oscar; Zweifler, Richard M; Callahan, Alfred; Hennerici, Michael G; Zivin, Justin A; Welch, K Michael A

    2010-03-01

    Noncoronary forms of atherosclerosis (including transient ischemic attacks or stroke of carotid origin or >50% stenosis of the carotid artery) are associated with a 10-year vascular risk of >20% and are considered as a coronary heart disease (CHD) -risk equivalent from the standpoint of lipid management. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial included patients with stroke or transient ischemic attack and no known CHD regardless of the presence of carotid atherosclerosis. We evaluated the risk of developing clinically recognized CHD in SPARCL patients. A total of 4731 patients (mean age, 63 years) was randomized to 80 mg/day atorvastatin placebo. The rates of major coronary event, any CHD event, and any revascularization procedure were evaluated. After 4.9 years of follow-up, the risks of a major coronary event and of any CHD end point in the placebo group were 5.1% and 8.6%, respectively. The rate of outcome of stroke decreased over time, whereas the major coronary event rate was stable. Relative to those having a large vessel-related stroke at baseline, those having a transient ischemic attack, hemorrhagic stroke, small vessel stroke, or a stroke of unknown cause had similar absolute rates for a first major coronary event and for any CHD event; transient ischemic attack, small vessel, and unknown cause groups had lower absolute revascularization procedure rates. Major coronary event, any CHD event, and any revascularization procedure rates were similarly reduced in all baseline stroke subtypes in the atorvastatin arm compared with placebo with no heterogeneity between groups. CHD risk can be substantially reduced by atorvastatin therapy in patients with recent stroke or transient ischemic attack regardless of stroke subtype.

  5. Brain irradiation for metastasis prevention and radiation treatment of small cell lung cancer metastases into the brain

    International Nuclear Information System (INIS)

    Mikhina, Z.P.; Motorina, L.I.; Glekov, I.V.

    1985-01-01

    The report presents the results of cranial irradiation of 44 small cell lung cancer patients with clinically-identified intracranial metastases and 40 patients - for metastatic spread prevention. Whole brain irradiation was carried out with single doses of 2-4 Gy (total dose - 30-40 Gy) in both groups 5 times weekly. Patients irradiated for metastasis prevention revealed a 3.3 - fold decrease in intracranial metastasis frequency and a good post-treatment tolerance. In the other group, radiation failed to reach tumor lesions in 20%; treatment produced a poor effect in 30%. There was a correlation between survival time, initial expansion of process and tumor response to primary treatment. No relationship was observed between survival time and procedure and duration of cranial irradiation. Prophylactic irradiation may be beneficial in responders to therapy

  6. Dosimetric analysis of the alopecia preventing effect of hippocampus sparing whole brain radiation therapy

    International Nuclear Information System (INIS)

    Mahadevan, Anand; Sampson, Carrie; LaRosa, Salvatore; Floyd, Scott R.; Wong, Eric T.; Uhlmann, Erik J.; Sengupta, Soma; Kasper, Ekkehard M.

    2015-01-01

    Whole brain radiation therapy (WBRT) is widely used for the treatment of brain metastases. Cognitive decline and alopecia are recognized adverse effects of WBRT. Recently hippocampus sparing whole brain radiation therapy (HS-WBRT) has been shown to reduce the incidence of memory loss. In this study, we found that multi-field intensity modulated radiation therapy (IMRT), with strict constraints to the brain parenchyma and to the hippocampus, reduces follicular scalp dose and prevents alopecia. Suitable patients befitting the inclusion criteria of the RTOG 0933 trial received Hippocampus sparing whole brain radiation. On follow up, they were noticed to have full scalp hair preservation. 5 mm thickness of follicle bearing scalp in the radiation field was outlined in the planning CT scans. Conventional opposed lateral WBRT radiation fields were applied to these patient-specific image sets and planned with the same nominal dose of 30 Gy in 10 fractions. The mean and maximum dose to follicle bearing skin and Dose Volume Histogram (DVH) data were analyzed for conventional and HS-WBRT. Paired t-test was used to compare the means. All six patients had fully preserved scalp hair and remained clinically cognitively intact 1–3 months after HS-WBRT. Compared to conventional WBRT, in addition to the intended sparing of the Hippocampus, HS-WBRT delivered significantly lower mean dose (22.42 cGy vs. 16.33 cGy, p < 0.0001), V 24 (9 cc vs. 44 cc, p < 0.0000) and V 30 (9 cc vs. 0.096 cc, p = 0.0106) to follicle hair bearing scalp and prevented alopecia. There were no recurrences in the Hippocampus area. HS-WBRT, with an 11-field set up as described, while attempting to conserve hippocampus radiation and maintain radiation dose to brain inadvertently spares follicle-bearing scalp and prevents alopecia

  7. Acute ischemic stroke update.

    Science.gov (United States)

    Baldwin, Kathleen; Orr, Sean; Briand, Mary; Piazza, Carolyn; Veydt, Annita; McCoy, Stacey

    2010-05-01

    Stroke is the third most common cause of death in the United States and is the number one cause of long-term disability. Legislative mandates, largely the result of the American Heart Association, American Stroke Association, and Brain Attack Coalition working cooperatively, have resulted in nationwide standardization of care for patients who experience a stroke. Transport to a skilled facility that can provide optimal care, including immediate treatment to halt or reverse the damage caused by stroke, must occur swiftly. Admission to a certified stroke center is recommended for improving outcomes. Most strokes are ischemic in nature. Acute ischemic stroke is a heterogeneous group of vascular diseases, which makes targeted treatment challenging. To provide a thorough review of the literature since the 2007 acute ischemic stroke guidelines were developed, we performed a search of the MEDLINE database (January 1, 2004-July 1, 2009) for relevant English-language studies. Results (through July 1, 2009) from clinical trials included in the Internet Stroke Center registry were also accessed. Results from several pivotal studies have contributed to our knowledge of stroke. Additional data support the efficacy and safety of intravenous alteplase, the standard of care for acute ischemic stroke since 1995. Due to these study results, the American Stroke Association changed its recommendation to extend the time window for administration of intravenous alteplase from within 3 hours to 4.5 hours of symptom onset; this recommendation enables many more patients to receive the drug. Other findings included clinically useful biomarkers, the role of inflammation and infection, an expanded role for placement of intracranial stents, a reduced role for urgent carotid endarterectomy, alternative treatments for large-vessel disease, identification of nontraditional risk factors, including risk factors for women, and newly published pediatric stroke guidelines. In addition, new devices for

  8. Preventive geriatrics the cross-talk between arterial and brain aging: A lifelong condition.

    Science.gov (United States)

    Scuteri, Angelo; Tesauro, Manfredi; Di Daniele, Nicola

    2017-01-01

    Arterial aging - clinically evaluable noninvasively as carotid-femoral Pulse Wave Velocity (PWV), an index of arterial stiffness - has emerged as a risky condition for cardiovascular events and cognitive decline. With advancing age, arterial aging is less and less dependent on blood pressure levels. We propose a life-course approach to the cross-talking between arterial and brain aging aimed at preventing disabling conditions at older ages. This vision is supported by growing evidence that "silent" alteration in large artery as well as in brain structure and function are already detectable at young ages. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Defining the Collateral Flow of Posterior Tibial Artery and Dorsalis Pedis Artery in Ischemic Foot Disease: Is It a Preventing Factor for Ischemia?

    International Nuclear Information System (INIS)

    Tutar, Onur; Yildirim, Duzgun; Samanci, Cesur; Rafiee, Babak; Inan, Kaan; Dikici, Suleyman; Ustabasioglu, Fethi Emre; Kuyumcu, Gokhan

    2016-01-01

    Critical limb ischemia, a worldwide prevalent morbidity cause, is mostly secondary to vascular insufficiency due to atherosclerosis. The disease presents with intermittent claudication, which can progress to critical limb ischemia requiring amputation. Research has emphasized that the quality or existence of the pedal arch have a direct effect on wound healing and, therefore, on limb salvage, through the mechanism of collateral vascularization to the ischemic regions. This study aimed to determine the existence and, if present, grade of retrograde blood flow from plantar arch to dorsal foot artery (dorsalis pedis artery, DPA). The correlation between clinical symptoms and presence of collateral flow were also investigated. Study group consisted of 34 cases, which included patient group (n = 17, all male, mean age: 68 years) and control group (n = 17, all male, mean age: 66 years). After physical examination and lower extremity Doppler examination, spectral morphology of DPA flow was recorded, before and during manual compression of posterior tibial artery (PTA), for a period of 5 seconds. At the end, findings of Doppler ultrasound, computed tomography angiography, magnetic resonance angiography and, physical examination finding and symptomatology were gathered and analyzed. In the patient group, 31 lower limb arteries, of total of 17 cases, were included. After compression maneuver, DPA in 11 cases (six right, five left) showed retrograde filling from plantar arch. This retrograde flow support was triphasic in three cases, biphasic in five cases, and monophasic in three cases. In other DPAs of these 20 limbs, PTA based retrograde collateral flow was not determined. In nine of these 20 limbs, with no or diminished retrograde filling, symptoms were worse than in other cases. Contrarily, only two of 11 limbs, with retrograde collaterals, have claudication during walking. In cases with critical atherosclerotic disease of anterior tibial artery, PTA-based biphasic or

  10. Temporal delta wave and ischemic lesions on MRI

    International Nuclear Information System (INIS)

    Inui, Koji; Kawamoto, Hozumi; Kawakita, Masahiko; Wako, Kazuhisa; Nakashima, Hiromichi; Kamihara, Masanori; Nomura, Junichi

    1994-01-01

    The present study was designed to determine the clinical significance of a temporal low-voltage irregular delta wave (TLID) on EEG. Among 808 EEG records examined during one year at our hospital, the TLID was commonly detected in patients with clinically diagnosed ischemic brain diseases such as multiple infarction. Subsequently, a relation of the TLID to ischemic lesions on MRI was examined in 50 elderly depressive patients. It was found that there was a close correlation between the occurrence of the TLID and small ischemic lesions on MRI (p<0.001). These results suggest that the TLID is a valuable indicator of minor ischemic changes of the brain. (author)

  11. Transient central diabetes insipidus following ischemic stroke

    Directory of Open Access Journals (Sweden)

    Muthukrishnan Jayaraman

    2013-01-01

    Full Text Available Central Diabetes Insipidus (CDI following ischemic infarction of the brain has been described as a rare presentation. Posterior pituitary ischemia has also been postulated as a possible cause of idiopathic CDI. We encountered a young male with bilateral extensive ischemic infarction sustained at high altitude, who had transient polyuria due to central diabetes insipidus, requiring desmopressin therapy. DI completely resolved during the course of his neurological recovery.

  12. Deep brain stimulation during early adolescence prevents microglial alterations in a model of maternal immune activation.

    Science.gov (United States)

    Hadar, Ravit; Dong, Le; Del-Valle-Anton, Lucia; Guneykaya, Dilansu; Voget, Mareike; Edemann-Callesen, Henriette; Schweibold, Regina; Djodari-Irani, Anais; Goetz, Thomas; Ewing, Samuel; Kettenmann, Helmut; Wolf, Susanne A; Winter, Christine

    2017-07-01

    In recent years schizophrenia has been recognized as a neurodevelopmental disorder likely involving a perinatal insult progressively affecting brain development. The poly I:C maternal immune activation (MIA) rodent model is considered as a neurodevelopmental model of schizophrenia. Using this model we and others demonstrated the association between neuroinflammation in the form of altered microglia and a schizophrenia-like endophenotype. Therapeutic intervention using the anti-inflammatory drug minocycline affected altered microglia activation and was successful in the adult offspring. However, less is known about the effect of preventive therapeutic strategies on microglia properties. Previously we found that deep brain stimulation of the medial prefrontal cortex applied pre-symptomatically to adolescence MIA rats prevented the manifestation of behavioral and structural deficits in adult rats. We here studied the effects of deep brain stimulation during adolescence on microglia properties in adulthood. We found that in the hippocampus and nucleus accumbens, but not in the medial prefrontal cortex, microglial density and soma size were increased in MIA rats. Pro-inflammatory cytokine mRNA was unchanged in all brain areas before and after implantation and stimulation. Stimulation of either the medial prefrontal cortex or the nucleus accumbens normalized microglia density and soma size in main projection areas including the hippocampus and in the area around the electrode implantation. We conclude that in parallel to an alleviation of the symptoms in the rat MIA model, deep brain stimulation has the potential to prevent the neuroinflammatory component in this disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Reducing cannabinoid abuse and preventing relapse by enhancing endogenous brain levels of kynurenic acid

    Science.gov (United States)

    Justinova, Zuzana; Mascia, Paola; Wu, Hui-Qiu; Secci, Maria E.; Redhi, Godfrey H.; Panlilio, Leigh V.; Scherma, Maria; Barnes, Chanel; Parashos, Alexandra; Zara, Tamara; Fratta, Walter; Solinas, Marcello; Pistis, Marco; Bergman, Jack; Kangas, Brian D.; Ferré, Sergi; Tanda, Gianluigi; Schwarcz, Robert; Goldberg, Steven R.

    2013-01-01

    In the reward circuitry of the brain, alpha-7-nicotinic acetylcholine receptors (α7nAChRs) modulate effects of delta-9-tetrahydrocannabinol (THC), marijuana’s main psychoactive ingredient. Kynurenic acid (KYNA) is an endogenous negative allosteric modulator of α7nAChRs. Here we report that the kynurenine 3-monooxygenase (KMO) inhibitor Ro 61-8048 increases brain KYNA levels and attenuates cannabinoid-induced increases in extracellular dopamine in reward-related brain areas. In the self-administration model of drug abuse, Ro 61-8048 reduced the rewarding effects of THC and the synthetic cannabinoid WIN 55,212-2 in squirrel monkeys and rats, respectively, and it also prevented relapse to drug-seeking induced by re-exposure to cannabinoids or cannabinoid-associated cues. The effects of enhancing endogenous KYNA levels with Ro 61-8048 were prevented by positive allosteric modulators of α7nAChRs. Despite a clear need, there are currently no medications approved for treatment of marijuana dependence. Modulation of KYNA provides a novel pharmacological strategy for achieving abstinence from marijuana and preventing relapse. PMID:24121737

  14. Ischemic stroke and incomplete infarction

    DEFF Research Database (Denmark)

    Garcia, Javier; Lassen, N A; Weiller, C

    1996-01-01

    The concept of selective vulnerability or selective loss o f individual neurons, with survival of glial and vascular elements as one of the consequences of a systemic ischemic-hypoxic insult (eg, transient cardiac arrest or severe hypotension), has been recognized for decades. In contrast, select......, selective neuronal death as one of the lesions that may develop in the brain after occluding an intracranial artery is an idea not readily acknowledged in the current medical literature dealing with human stroke....

  15. Pathophysiology of repetitive head injury in sports. Prevention against catastrophic brain damage

    International Nuclear Information System (INIS)

    Mori, Tatsuro; Kawamata, Tatsuro; Katayama, Yoichi

    2008-01-01

    The most common head injury in sports is concussion and experiencing multiple concussions in a short period of time sometimes can cause severe brain damage. In this paper, we investigate severe brain damage due to repeated head injury in sports and discuss the pathophysiology of repeated sports injury. The majority of these severe cases are usually male adolescents or young adults that suffer a second head injury before they have recovered from the first head injury. All cases that could be confirmed by brain CT scan after the second injury revealed brain swelling associated with a thin subdural hematoma. We suggested that the existence of subdural hematoma is one of the major causes of brain swelling after repeated head injury in sports. Since repeated concussions occurring within a short period may have a risk for severe brain damage, the diagnosis for initial cerebral concussion should be done appropriately. To prevent catastrophic brain damage, the player who suffered from concussion should not engage in any sports before recovery. The american Academy of Neurology and Colorado Medical Society set a guideline to return to play after cerebral concussion. An international conference on concussion in sports was held at Prague in 2004. The summary and agreement of this meeting was published and the Sports Concussion Assessment Tool (SCAT) was introduced to treat sports-related concussion. In addition, a number of computerized cognitive assessment tests and test batteries have been developed to allow athletes to return to play. It is important that coaches, as well as players and trainers, understand the medical issues involved in concussion. (author)

  16. Targeting brain-health from "cradle to grave": Can we prevent or delay dementia?

    Directory of Open Access Journals (Sweden)

    Bhaskara P. Shelley

    2014-01-01

    Full Text Available Dementia or the "silver tsunami" is a public health challenge of epidemic proportions of the 21 st century. It imposes enormous burden in terms of economic and social impact on the health care systems and the quality of life of people with dementia, their families and caregivers. For a number of decades, clinicians, researchers, and pharmaceutical companies have laid emphasis on the development of a drug armamentarium for fighting dementia. However, the neurotherapy of dementia targeting the "pathogenesis model" still remains disappointing with no breakthrough in-sight. The cure for dementia is worthy, but an elusive and frustrating goal. On the contrary, epidemiological research does spell optimism and provides a substantial amount of evidence of modifiable risk and protective factors to delay, prevent or shorten dementia. Thus time has come for a "strategic vision for the future" to move away from the current paradigm of curative therapies to a strategy of "preemptive medicine" that identifies disease processes at the earliest stages and prevents rather than attempting to reverse disability. Such a strategy is not only a safer, more dignified option, but also a step forward for a sustainable society in an aging world in order to preserve the mental capital and brain well-being of nations. This would reiterate the concept of "anthroposophical medicine," neurocentric health and preventive neurology strategies to promote healthy brain aging and brain protection. The need to rethink and redefine dementia from a "salutogenesis" perspective as a "lifestyle disorder" and implement multiple preventative life-course approaches through well-designed randomized controlled trials is quintessential to delay, prevent or keep dementia at bay.

  17. SECONDARY BRAIN INJURY

    Directory of Open Access Journals (Sweden)

    Ida Ayu Basmatika

    2013-03-01

    Full Text Available Secondary brain injury is a condision that occurs at some times after the primary impact and can be largely prevented and treated. Most brain injury ends with deadly consequences which is caused by secondary damage to the brain. Traumatic brain injured still represents the leading cause of morbidity and mortality in individuals under the age of 45 years in the world. The classification of secondary brain injured is divided into extracranial and intracranial causes. The cause of extracranial such as hipoxia, hypotensi, hyponatremia, hypertermia, hypoglycemia or hyperglycemia. The cause of intracranial such as extradural, subdural, intraserebral, intraventrikular, dan subarachnoid hemorrhage. Beside that secondary injury can also be caused by edema and infection. Post-traumatic cerebral injured is characterized by direct tissue damage, impaired regulation of cerebral blood flow (cerebral blood flow / CBF, and disruption of metabolism. Manifestations of secondary brain injured include increased intracranial pressure, ischemic brain damage, cerebral hypoxia and hypercarbi, as well as disruption of cerebral autoregulation. The first priority is to stabilize the patient's cervical spine injury, relieve and maintain airway, ensure adequate ventilation (breathing, and making venous access for fluid resuscitation pathways (circulation and assessing the level of awareness and disability. This steps is crucial in patients with head injured to prevent hypoxia and hypotension, which is the main cause of secondary brain injury.

  18. Melatonin prevented spatial deficits and increases in brain asymmetric dimethylarginine in young bile duct ligation rats.

    Science.gov (United States)

    Hsu, Mei-Hsin; Chen, Yu-Chieh; Sheen, Jiunn-Ming; Li, Shih-Wen; Huang, Li-Tung

    2018-01-30

    Bile duct ligation (BDL) in young rats can cause impaired liver function and cognition deficits. Nitric oxide is implicated in hepatic encephalopathy and is also involved in cognition. In this study, we examined the role of brain asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, in young BDL rats with spatial deficits. Young male Sprague-Dawley rats aged 17 days were assigned to four groups: laparotomy (SHAM), laparotomy plus 5 mg melatonin delivered through a pellet (SHAMM) for 4 weeks, BDL for 4 weeks, and BDL plus 5 mg melatonin delivered through a pellet (BDLM) for 4 weeks. Their spatial memory was assessed using a Morris water-maze task. Plasma and brains were collected for biochemical and ADMA analyses. We found that the BDL group had significantly elevated levels of ADMA in the plasma, the prefrontal cortex, and the dorsal hippocampus, and worse spatial performance than that of the control groups. Melatonin administration prevented an increase in the ADMA levels in the plasma, prefrontal cortex, and dorsal hippocampus, and prevented spatial deficits in BDL rats. In addition, melatonin maintained brain-derived neurotrophic factor in the dorsal hippocampus at a level comparable with controls. We concluded that melatonin is effective in preventing spatial deficits and decreasing ADMA levels in the plasma, prefrontal cortex, and dorsal hippocampus in young BDL rats. Brain ADMA levels might play a role in BDL-induced spatial deficits.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/.

  19. Characteristics of Misclassified CT Perfusion Ischemic Core in Patients with Acute Ischemic Stroke.

    Science.gov (United States)

    Geuskens, Ralph R E G; Borst, Jordi; Lucas, Marit; Boers, A M Merel; Berkhemer, Olvert A; Roos, Yvo B W E M; van Walderveen, Marianne A A; Jenniskens, Sjoerd F M; van Zwam, Wim H; Dippel, Diederik W J; Majoie, Charles B L M; Marquering, Henk A

    2015-01-01

    CT perfusion (CTP) is used to estimate the extent of ischemic core and penumbra in patients with acute ischemic stroke. CTP reliability, however, is limited. This study aims to identify regions misclassified as ischemic core on CTP, using infarct on follow-up noncontrast CT. We aim to assess differences in volumetric and perfusion characteristics in these regions compared to areas that ended up as infarct on follow-up. This study included 35 patients with >100 mm brain coverage CTP. CTP processing was performed using Philips software (IntelliSpace 7.0). Final infarct was automatically segmented on follow-up noncontrast CT and used as reference. CTP and follow-up noncontrast CT image data were registered. This allowed classification of ischemic lesion agreement (core on CTP: rMTT≥145%, aCBVCT) and misclassified ischemic core (core on CTP, not identified on follow-up noncontrast CT) regions. False discovery ratio (FDR), defined as misclassified ischemic core volume divided by total CTP ischemic core volume, was calculated. Absolute and relative CTP parameters (CBV, CBF, and MTT) were calculated for both misclassified CTP ischemic core and ischemic lesion agreement regions and compared using paired rank-sum tests. Median total CTP ischemic core volume was 49.7ml (IQR:29.9ml-132ml); median misclassified ischemic core volume was 30.4ml (IQR:20.9ml-77.0ml). Median FDR between patients was 62% (IQR:49%-80%). Median relative mean transit time was 243% (IQR:198%-289%) and 342% (IQR:249%-432%) for misclassified and ischemic lesion agreement regions, respectively. Median absolute cerebral blood volume was 1.59 (IQR:1.43-1.79) ml/100g (P<0.01) and 1.38 (IQR:1.15-1.49) ml/100g (P<0.01) for misclassified ischemic core and ischemic lesion agreement, respectively. All CTP parameter values differed significantly. For all patients a considerable region of the CTP ischemic core is misclassified. CTP parameters significantly differed between ischemic lesion agreement and

  20. Characteristics of Misclassified CT Perfusion Ischemic Core in Patients with Acute Ischemic Stroke.

    Directory of Open Access Journals (Sweden)

    Ralph R E G Geuskens

    Full Text Available CT perfusion (CTP is used to estimate the extent of ischemic core and penumbra in patients with acute ischemic stroke. CTP reliability, however, is limited. This study aims to identify regions misclassified as ischemic core on CTP, using infarct on follow-up noncontrast CT. We aim to assess differences in volumetric and perfusion characteristics in these regions compared to areas that ended up as infarct on follow-up.This study included 35 patients with >100 mm brain coverage CTP. CTP processing was performed using Philips software (IntelliSpace 7.0. Final infarct was automatically segmented on follow-up noncontrast CT and used as reference. CTP and follow-up noncontrast CT image data were registered. This allowed classification of ischemic lesion agreement (core on CTP: rMTT≥145%, aCBV<2.0 ml/100g and infarct on follow-up noncontrast CT and misclassified ischemic core (core on CTP, not identified on follow-up noncontrast CT regions. False discovery ratio (FDR, defined as misclassified ischemic core volume divided by total CTP ischemic core volume, was calculated. Absolute and relative CTP parameters (CBV, CBF, and MTT were calculated for both misclassified CTP ischemic core and ischemic lesion agreement regions and compared using paired rank-sum tests.Median total CTP ischemic core volume was 49.7ml (IQR:29.9ml-132ml; median misclassified ischemic core volume was 30.4ml (IQR:20.9ml-77.0ml. Median FDR between patients was 62% (IQR:49%-80%. Median relative mean transit time was 243% (IQR:198%-289% and 342% (IQR:249%-432% for misclassified and ischemic lesion agreement regions, respectively. Median absolute cerebral blood volume was 1.59 (IQR:1.43-1.79 ml/100g (P<0.01 and 1.38 (IQR:1.15-1.49 ml/100g (P<0.01 for misclassified ischemic core and ischemic lesion agreement, respectively. All CTP parameter values differed significantly.For all patients a considerable region of the CTP ischemic core is misclassified. CTP parameters significantly

  1. Hypophosphorylation of ribosomal protein S6 is a molecular mechanism underlying ischemic tolerance induced by either hibernation or preconditioning.

    Science.gov (United States)

    Miyake, Shin-ichi; Wakita, Hideaki; Bernstock, Joshua D; Castri, Paola; Ruetzler, Christl; Miyake, Junko; Lee, Yang-Ja; Hallenbeck, John M

    2015-12-01

    Thirteen-lined ground squirrels (Ictidomys tridecemlineatus) have an extraordinary capacity to withstand prolonged and profound reductions in blood flow and oxygen delivery to the brain without incurring any cellular damage. As such, the hibernation torpor of I. tridecemlineatus provides a valuable model of tolerance to ischemic stress. Herein, we report that during hibernation torpor, a marked reduction in the phosphorylation of the ribosomal protein S6 (rpS6) occurs within the brains of I. tridecemlineatus. Of note, rpS6 phosphorylation was shown to increase in the brains of rats that underwent an occlusion of the middle cerebral artery. However, such an increase was attenuated after the implementation of an ischemic preconditioning paradigm. In addition, cultured cortical neurons treated with the rpS6 kinase (S6K) inhibitors, D-glucosamine or PF4708671, displayed a decrease in rpS6 phosphorylation and a subsequent increase in tolerance to oxygen/glucose deprivation, an in vitro model of ischemic stroke. Collectively, such evidence suggests that the down-regulation of rpS6 signal transduction may account for a substantial part of the observed increase in cellular tolerance to brain ischemia that occurs during hibernation torpor and after ischemic preconditioning. Further identification and characterization of the mechanisms used by hibernating species to increase ischemic tolerance may eventually clarify how the loss of homeostatic control that occurs during and after cerebral ischemia in the clinic can ultimately be minimized and/or prevented. Mammalian hibernation provides a valuable model of tolerance to ischemic stress. Herein, we demonstrate that marked reductions in the phosphorylation of ribosomal protein S6 (rpS6), extracellular signal-regulated kinase family of mitogen-activated protein (MAP) kinase p44/42 (p44/42MAPK) and ribosomal protein S6 kinase (S6K) occur within the brains of both hibernating squirrels and rats, which have undergone an ischemic

  2. Heart rate is a prognostic risk factor for myocardial infarction: a post hoc analysis in the PERFORM (Prevention of cerebrovascular and cardiovascular Events of ischemic origin with teRutroban in patients with a history oF ischemic strOke or tRansient ischeMic attack) study population.

    Science.gov (United States)

    Fox, Kim; Bousser, Marie-Germaine; Amarenco, Pierre; Chamorro, Angel; Fisher, Marc; Ford, Ian; Hennerici, Michael G; Mattle, Heinrich P; Rothwell, Peter M

    2013-10-09

    Elevated resting heart rate is known to be detrimental to morbidity and mortality in cardiovascular disease, though its effect in patients with ischemic stroke is unclear. We analyzed the effect of baseline resting heart rate on myocardial infarction (MI) in patients with a recent noncardioembolic cerebral ischemic event participating in PERFORM. We compared fatal or nonfatal MI using adjusted Cox proportional hazards models for PERFORM patients with baseline heart rate heart rate was analyzed as a continuous variable. Other cerebrovascular and cardiovascular outcomes were also explored. Heart rate ≥70 bpm was associated with increased relative risk for fatal or nonfatal MI (HR 1.32, 95% CI 1.03-1.69, P=0.029). For every 5-bpm increase in heart rate, there was an increase in relative risk for fatal and nonfatal MI (11.3%, P=0.0002). Heart rate ≥70 bpm was also associated with increased relative risk for a composite of fatal or nonfatal ischemic stroke, fatal or nonfatal MI, or other vascular death (excluding hemorrhagic death) (Pheart rate, there were increases in relative risk for fatal or nonfatal ischemic stroke, fatal or nonfatal MI, or other vascular death (4.7%, Pheart rate ≥70 bpm places patients with a noncardioembolic cerebral ischemic event at increased risk for MI. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  3. Acute Administration of Diazepam Provokes Redox Homeostasis Imbalance in the Rat Brain: Prevention by Simvastatin.

    Science.gov (United States)

    Eger, Guilherme André; Ferreira, Vinícius Vialle; Batista, Camila Ribeiro; Bonde, Henrique LuisPetrek; de Lima, Daniela Delwing; Rodrigues, André Felipe; da Cruz, José Geraldo Pereira; Magro, Débora Delwing Dal

    2016-10-01

    We investigated the effects of acute diazepam (DZP) administration on thiobarbituric acid-reactive substance (TBARS) levels, protein carbonyl content, and on the activities of the antioxidant enzymes catalase, glutathione peroxidase, and superoxide dismutase in the brain of rats. Additionally, we investigated the antioxidant role of chronic pretreatment with simvastatin on the effects provoked by DZP. Simvastatin was administered (1 or 10 mg/kg by oral gavage) for 30 days. On the 30th day of treatment, groups were randomized and DZP was administered (0.5 or 1.0 mg/kg by intraperitoneal injection). Control groups received saline. Results showed that DZP enhanced TBARS levels and protein carbonyl content and altered enzymatic activity in the brain of rats. Simvastatin prevented most of the alterations caused by DZP on the oxidative stress parameters. Data indicate that DZP administration causes an oxidative imbalance in the brain areas studied; however, in the presence of simvastatin, some of these alterations in oxidative stress were prevented. © 2016 Wiley Periodicals, Inc.

  4. How to minimize ischemic complication related to swollen temporalis muscle following indirect revascularization surgery in moyamoya disease: a technical report.

    Science.gov (United States)

    Joo, Sung Pil; Kim, Tae Sun; Moon, Hyung Sik

    2014-05-01

    There are several reports in the literature of postoperative ischemic events due to swelling of the temporalis muscle after indirect revascularization surgery. Here, we report our surgical technique for preventing ischemic events during the acute postoperative recovery period in moyamoya patients. We used various types of titanium mesh to cover the bony defect area in 8 patients (10 operations) with moyamoya disease. The mesh was cut and manipulated according to the shape of the bony defect. Surgical results were favorable, with no newly developed ischemic event or infarction in the acute recovery period. The mesh formed an outer table of skull, so there was no compressive effect on the temporalis muscle and no cosmetic defects. The titanium mesh appears to be effective and useful for prevention of ischemic insult in the treatment of moyamoya disease. The choice of this procedure depends on both the operative findings of temporalis muscle thickness and the status of ischemic vulnerability of moyamoya brain. Georg Thieme Verlag KG Stuttgart · New York.

  5. Modafinil treatment prevents REM sleep deprivation-induced brain function impairment by increasing MMP-9 expression.

    Science.gov (United States)

    He, Bin; Peng, Hua; Zhao, Ying; Zhou, Hui; Zhao, Zhongxin

    2011-12-02

    Previous work showed that sleep deprivation (SD) impairs hippocampal-dependent cognitive function and synaptic plasticity, and a novel wake-promoting agent modafinil prevents SD-induced memory impairment in rat. However, the mechanisms by which modafinil prevented REM-SD-induced impairment of brain function remain poorly understood. In the present study, rats were sleep-deprived by using the modified multiple platform method and brain function was detected. The results showed that modafinil treatment prevented REM-SD-induced impairment of cognitive function. Modafinil significantly reduced the number of errors compared to placebo and upregulated synapsin I expression in the dorsal hippocampal CA3 region. A synaptic plasticity-related gene, MMP-9 expression was also upregulated in modafinil-treated rats. Importantly, downregulation of MMP-9 expression by special siRNA decreased synapsin I protein levels and synapse numbers. Therefore, we demonstrated that modafinil increased cognition function and synaptic plasticity, at least in part by increasing MMP-9 expression in REM-SD rats. 2011. Published by Elsevier B.V.

  6. Feasibility of a skills-based substance abuse prevention program following traumatic brain injury.

    Science.gov (United States)

    Vungkhanching, Martha; Heinemann, Allen W; Langley, Mervin J; Ridgely, Mary; Kramer, Karen M

    2007-01-01

    To demonstrate the feasibility of a skills-based substance abuse prevention counseling program in a community setting for adults who sustained traumatic brain injury. Convenience sample of 117 participants (mean age=35 years) with preinjury history of alcohol or other drug use. Intervention group participants (n=36) from 3 vocational rehabilitation programs; a no-intervention comparison group (n=81) from an outpatient rehabilitation service. 12 individual counseling sessions featuring skills-based intervention. Changes in self-reported alcohol and other drug use, coping skillfulness, affect, and employment status from baseline to 9 months postintervention. Significant differences were noted at baseline for the intervention and comparison groups on ethnicity, time postinjury, marital status, and employment (Pcoping skillfulness (Pskills-based intervention provides a promising approach to promoting abstinence from all substances and increasing readiness for employment for adults with traumatic brain injuries in outpatient settings.

  7. Transient Ischemic Attack

    Medline Plus

    Full Text Available ... Ischemic Attack TIA , or transient ischemic attack, is a "mini stroke" that occurs when a blood clot blocks an artery for a short time. The only difference between a stroke ...

  8. Cardiovascular risk factors cause premature rarefaction of the collateral circulation and greater ischemic tissue injury.

    Science.gov (United States)

    Moore, Scott M; Zhang, Hua; Maeda, Nobuyo; Doerschuk, Claire M; Faber, James E

    2015-07-01

    Collaterals lessen tissue injury in occlusive disease. However, aging causes progressive decline in their number and smaller diameters in those that remain (collateral rarefaction), beginning at 16 months of age in mice (i.e., middle age), and worse ischemic injury-effects that are accelerated in even 3-month-old eNOS(-/-) mice. These findings have found indirect support in recent human studies. We sought to determine whether other cardiovascular risk factors (CVRFs) associated with endothelial dysfunction cause collateral rarefaction, investigate possible mechanisms, and test strategies for prevention. Mice with nine different models of CVRFs of 4-12 months of age were assessed for number and diameter of native collaterals in skeletal muscle and brain and for collateral-dependent perfusion and ischemic injury after arterial occlusion. Hypertension caused collateral rarefaction whose severity increased with duration and level of hypertension, accompanied by greater hindlimb ischemia and cerebral infarct volume. Chronic treatment of wild-type mice with L-N (G)-nitro-arginine methylester caused similar rarefaction and worse ischemic injury which were not prevented by lowering arterial pressure with hydralazine. Metabolic syndrome, hypercholesterolemia, diabetes mellitus, and obesity also caused collateral rarefaction. Neither chronic statin treatment nor exercise training lessened hypertension-induced rarefaction. Chronic CVRF presence caused collateral rarefaction and worse ischemic injury, even at relatively young ages. Rarefaction was associated with increased proliferation rate of collateral endothelial cells, effects that may promote accelerated endothelial cell senescence.

  9. Neurotherapeutic effect of mangiferin against hypoxic–ischemic ...

    African Journals Online (AJOL)

    Background: Hypoxic–ischemic encephalopathy (HIE) in perinatal condition is highly associated with mortality and several neurological disabilities. The present experiment was blueprinted to ascertain the protective efficacy of mangiferin (MF) against hypoxic–ischemic brain injury in neonatal rats. Materials and Methods: ...

  10. Complications of hemorrhagic and ischemic stroke : a CT perfusion evaluation

    NARCIS (Netherlands)

    Dankbaar, J.W.

    2010-01-01

    In this thesis the use of CT-perfusion (CTP) imaging in the evaluation of the most severe complications of subarachnoid hemorrhage (SAH)) and ischemic stroke was explored. These complications are delayed cerebral ischemia (DCI) after SAH and damage to the blood-brain barrier (BBB) after ischemic

  11. Paraneoplastic Ischemic Stroke: Case Report and Review

    Directory of Open Access Journals (Sweden)

    Murat Sumer

    2008-10-01

    Full Text Available OBJECTIVE: Paraneoplastic etiology is not frequent among cerebrovascular disorders. This rare disorder is interesting with different mechanisms, clinical manifestations and treatment options. Diagnosis may be overlooked for its rarity. We present a paraneoplastic ischemic stroke patient with its clinical and imaging characteristics for recalling this rare disease. CASE: A sixty years old woman with a history of ovarian and colon cancer and liver metastasis admitted with acute left sided hemiplegia. Brain magnetic resonance imaging showed multiple ischemic lesions at the same age. Laboratory findings were compatible with chronic disseminated intravascular coagulopathy. She was anticoagulated but the clinical findings were not changed. She died one month after her discharge from the hospital. CONCLUSIONS: Paraneoplastic ischemic stroke is rare and it should be recognized by the clinician to differentiate from other ischemic strokes by its different mechanisms, imaging characteristics and treatment modalities. Prognosis depends on the characteristics of the primary tumor

  12. Poverty, Stress, and Brain Development: New Directions for Prevention and Intervention.

    Science.gov (United States)

    Blair, Clancy; Raver, C Cybele

    2016-04-01

    We review some of the growing evidence of the costs of poverty to children's neuroendocrine function, early brain development, and cognitive ability. We underscore the importance of addressing the negative consequences of poverty-related adversity early in children's lives, given evidence supporting the plasticity of executive functions and associated physiologic processes in response to early intervention and the importance of higher order cognitive functions for success in school and in life. Finally, we highlight some new directions for prevention and intervention that are rapidly emerging at the intersection of developmental science, pediatrics, child psychology and psychiatry, and public policy. Copyright © 2016 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

  13. Iron supplement prevents lead-induced disruption of the blood-brain barrier during rat development

    International Nuclear Information System (INIS)

    Wang Qiang; Luo Wenjing; Zheng Wei; Liu Yiping; Xu Hui; Zheng Gang; Dai Zhongming; Zhang Wenbin; Chen Yaoming; Chen Jingyuan

    2007-01-01

    Children are known to be venerable to lead (Pb) toxicity. The blood-brain barrier (BBB) in immature brain is particularly vulnerable to Pb insults. This study was designed to test the hypothesis that Pb exposure damaged the integrity of the BBB in young animals and iron (Fe) supplement may prevent against Pb-induced BBB disruption. Male weanling Sprague-Dawley rats were divided into four groups. Three groups of rats were exposed to Pb in drinking water containing 342 μg Pb/mL as Pb acetate, among which two groups were concurrently administered by oral gavage once every other day with 7 mg Fe/kg and 14 mg Fe/kg as FeSO 4 solution as the low and high Fe treatment group, respectively, for 6 weeks. The control group received sodium acetate in drinking water. Pb exposure significantly increased Pb concentrations in blood by 6.6-folds (p < 0.05) and brain tissues by 1.5-2.0-folds (p < 0.05) as compared to controls. Under the electron microscope, Pb exposure in young animals caused an extensive extravascular staining of lanthanum nitrate in brain parenchyma, suggesting a leakage of cerebral vasculature. Western blot showed that Pb treatment led to 29-68% reduction (p < 0.05) in the expression of occludin as compared to the controls. Fe supplement among Pb-exposed rats maintained the normal ultra-structure of the BBB and restored the expression of occludin to normal levels. Moreover, the low dose Fe supplement significantly reduced Pb levels in blood and brain tissues. These data suggest that Pb exposure disrupts the structure of the BBB in young animals. The increased BBB permeability may facilitate the accumulation of Pb. Fe supplement appears to protect the integrity of the BBB against Pb insults, a beneficial effect that may have significant clinical implications

  14. Prevention and treatment of traumatic brain injury due to rapid-onset natural disasters

    Directory of Open Access Journals (Sweden)

    James L. Regens

    2014-04-01

    Full Text Available The prevention and treatment of traumatic brain injury (TBI attributable to rapid-onset natural disasters is a major challenge confronting disaster preparedness planners and emergency medical personnel responding to those incidents. The kinetic energy released by rapid-onset natural disasters such as earthquakes, hurricanes or typhoons, and tornadoes can cause mild, moderate or severe TBIs. As a result, neurotrauma is a major risk factor for mortality and morbidity outcomes within the spatial domain impacted by a rapid-onset natural disaster. This review article elucidates major challenges associated with immediate emergency medical response, long-term care, and prevention of post-event increases in pediatric TBIs because of child abuse when rapid-onset natural disasters occur.

  15. Prospective of ischemic stroke biomarkers

    Directory of Open Access Journals (Sweden)

    Szewczak Krzysztof

    2017-06-01

    Full Text Available Methods currently used in brain vascular disorder diagnostics are neither fast enough nor clear-out; thus, there exists a necessity of finding new types of testing which could enlarge and complete the actual panel of diagnostics or be an alternative to current methods. The discovery of sensitive and specific biomarkers of ischemic brain stroke will improve the effects of treatment and will help to assess the progress or complications of the disease. The relevant diagnosis of ischemic stroke (IS within the first 4.5 hours after the initial symptoms allows for the initiation of treatment with recombinant tissue plasminogen activators which limits the magnitude of negative changes in the brain and which enhance the final effectiveness of therapy. The potential biomarkers which are under investigation are substances involved in the processes of coagulation and fibrinolysis, and are of molecules released from damaged vascular endothelial cells and from nerves and cardiac tissue. The analyzed substances are typical of oxidative stress, apoptosis, excitotoxicity and damage of the blood brain barrier.

  16. Maternal pravastatin prevents altered fetal brain development in a preeclamptic CD-1 mouse model.

    Directory of Open Access Journals (Sweden)

    Alissa R Carver

    Full Text Available Using an animal model, we have previously shown that preeclampsia results in long-term adverse neuromotor outcomes in the offspring, and this phenotype was prevented by antenatal treatment with pravastatin. This study aims to localize the altered neuromotor programming in this animal model and to evaluate the role of pravastatin in its prevention.For the preeclampsia model, pregnant CD-1 mice were randomly allocated to injection of adenovirus carrying sFlt-1 or its control virus carrying mFc into the tail vein. Thereafter they received pravastatin (sFlt-1-pra "experimental group" or water (sFlt-1 "positive control" until weaning. The mFc group ("negative control" received water. Offspring at 6 months of age were sacrificed, and whole brains underwent magnetic resonance imaging (MRI. MRIs were performed using an 11.7 Tesla vertical bore MRI scanner. T2 weighted images were acquired to evaluate the volumes of 28 regions of interest, including areas involved in adaptation and motor, spatial and sensory function. Cytochemistry and cell quantification was performed using neuron-specific Nissl stain. One-way ANOVA with multiple comparison testing was used for statistical analysis.Compared with control offspring, male sFlt-1 offspring have decreased volumes in the fimbria, periaquaductal gray, stria medullaris, and ventricles and increased volumes in the lateral globus pallidus and neocortex; however, female sFlt-1 offspring showed increased volumes in the ventricles, stria medullaris, and fasciculus retroflexus and decreased volumes in the inferior colliculus, thalamus, and lateral globus pallidus. Neuronal quantification via Nissl staining exhibited decreased cell counts in sFlt-1 offspring neocortex, more pronounced in males. Prenatal pravastatin treatment prevented these changes.Preeclampsia alters brain development in sex-specific patterns, and prenatal pravastatin therapy prevents altered neuroanatomic programming in this animal model.

  17. Imaging of cerebral ischemic edema and neuronal death

    Energy Technology Data Exchange (ETDEWEB)

    Kummer, Ruediger von [Universitaetsklinikum Carl Gustav Carus, Institut fuer Diagnostische und Interventionelle Neuroradiologie, Dresden (Germany); Dzialowski, Imanuel [Elblandklinikum Meissen, Neurologische Rehabilitationsklinik Grossenhain, Meissen (Germany)

    2017-06-15

    In acute cerebral ischemia, the assessment of irreversible injury is crucial for treatment decisions and the patient's prognosis. There is still uncertainty how imaging can safely differentiate reversible from irreversible ischemic brain tissue in the acute phase of stroke. We have searched PubMed and Google Scholar for experimental and clinical papers describing the pathology and pathophysiology of cerebral ischemia under controlled conditions. Within the first 6 h of stroke onset, ischemic cell injury is subtle and hard to recognize under the microscope. Functional impairment is obvious, but can be induced by ischemic blood flow allowing recovery with flow restoration. The critical cerebral blood flow (CBF) threshold for irreversible injury is ∝15 ml/100 g x min. Below this threshold, ischemic brain tissue takes up water in case of any residual capillary flow (ionic edema). Because tissue water content is linearly related to X-ray attenuation, computed tomography (CT) can detect and measure ionic edema and, thus, determine ischemic brain infarction. In contrast, diffusion-weighted magnetic resonance imaging (DWI) detects cytotoxic edema that develops at higher thresholds of ischemic CBF and is thus highly sensitive for milder levels of brain ischemia, but not specific for irreversible brain tissue injury. CT and MRI are complimentary in the detection of ischemic stroke pathology and are valuable for treatment decisions. (orig.)

  18. Imaging of cerebral ischemic edema and neuronal death

    International Nuclear Information System (INIS)

    Kummer, Ruediger von; Dzialowski, Imanuel

    2017-01-01

    In acute cerebral ischemia, the assessment of irreversible injury is crucial for treatment decisions and the patient's prognosis. There is still uncertainty how imaging can safely differentiate reversible from irreversible ischemic brain tissue in the acute phase of stroke. We have searched PubMed and Google Scholar for experimental and clinical papers describing the pathology and pathophysiology of cerebral ischemia under controlled conditions. Within the first 6 h of stroke onset, ischemic cell injury is subtle and hard to recognize under the microscope. Functional impairment is obvious, but can be induced by ischemic blood flow allowing recovery with flow restoration. The critical cerebral blood flow (CBF) threshold for irreversible injury is ∝15 ml/100 g x min. Below this threshold, ischemic brain tissue takes up water in case of any residual capillary flow (ionic edema). Because tissue water content is linearly related to X-ray attenuation, computed tomography (CT) can detect and measure ionic edema and, thus, determine ischemic brain infarction. In contrast, diffusion-weighted magnetic resonance imaging (DWI) detects cytotoxic edema that develops at higher thresholds of ischemic CBF and is thus highly sensitive for milder levels of brain ischemia, but not specific for irreversible brain tissue injury. CT and MRI are complimentary in the detection of ischemic stroke pathology and are valuable for treatment decisions. (orig.)

  19. Substance Use and Mild Traumatic Brain Injury Risk Reduction and Prevention: A Novel Model for Treatment

    Directory of Open Access Journals (Sweden)

    Jennifer H. Olson-Madden

    2012-01-01

    Full Text Available Traumatic brain injury (TBI and substance use disorders (SUDs frequently co-occur. Individuals with histories of alcohol or other drug use are at greater risk for sustaining TBI, and individuals with TBI frequently misuse substances before and after injury. Further, a growing body of literature supports the relationship between comorbid histories of mild TBI (mTBI and SUDs and negative outcomes. Alcohol and other drug use are strongly associated with risk taking. Disinhibition, impaired executive function, and/or impulsivity as a result of mTBI also contribute to an individual’s proclivity towards risk-taking. Risk-taking behavior may therefore, be a direct result of SUD and/or history of mTBI, and risky behaviors may predispose individuals for subsequent injury or continued use of substances. Based on these findings, evaluation of risk-taking behavior associated with the co-occurrence of SUD and mTBI should be a standard clinical practice. Interventions aimed at reducing risky behavior among members of this population may assist in decreasing negative outcomes. A novel intervention (Substance Use and Traumatic Brain Injury Risk Reduction and Prevention (STRRP for reducing and preventing risky behaviors among individuals with co-occurring mTBI and SUD is presented. Areas for further research are discussed.

  20. Functional reconstruction of ischemic contracture in the

    Directory of Open Access Journals (Sweden)

    TANG Hao

    2011-04-01

    Full Text Available 【Abstract】Objective: To discuss the method of functional reconstruction of ischemic contracture in the lower limb and propose a classification protocol for ischemic contracture in the lower limb based on its severity and prognosis. Methods: A total of 42 patients with ischemic contracture in the lower limb were included in this study. According to different types of disturbance and degrees of severity, surgical reconstructions consisting of nerve decompression, tendon lengthening or transfer, intrinsic foot muscle release and sural-tibial nerve anastomosis were performed in every patient. Results: Postoperatively, all patients were able to walk on flat ground. Drop foot was corrected in 10 patients, and 5 patients still felt some difficulty during stair activity. Split Achilles tendon transfer to flexor hallucis longus tendon was performed in 12 patients, and their walking stability was improved. Seven patients accepted ipsilateral suraltibial nerve anastomosis, and sensitivity recovery reached to S2 in 2 patients and S3 in 5 patients. Conclusions: Ischemic contracture in the lower limb is a devastating complication after lower limb trauma. The prevention of contracture is much more important than the treatment of an established contracture. Split Achilles tendon transfer to flexor hallucis longus tendon and sural-tibial nerve anastomosis, which was initially implemented by us, could improve the functional recovery of ischemic contracture in lower limbs, and thus provides a new alternative for functional reconstruction of ischemic contracture in the lower limb. Key words: Ischemic contracture; Classification; Recovery of function

  1. Protection of retinal function by sulforaphane following retinal ischemic injury.

    Science.gov (United States)

    Ambrecht, Lindsay A; Perlman, Jay I; McDonnell, James F; Zhai, Yougang; Qiao, Liang; Bu, Ping

    2015-09-01

    Sulforaphane, a precursor of glucosinolate in cruciferous vegetables such as broccoli and cauliflower, has been shown to protect brain ischemic injury. In this study, we examined the effect of systemic administration of sulforaphane on retinal ischemic reperfusion injury. Intraocular pressure was elevated in two groups of C57BL/6 mice (n = 8 per group) for 45 min to induce retinal ischemic reperfusion injury. Following retinal ischemic reperfusion injury, vehicle (1% DMSO saline) or sulforaphane (25 mg/kg/day) was administered intraperitoneally daily for 5 days. Scotopic electroretinography (ERG) was used to quantify retinal function prior to and one-week after retinal ischemic insult. Retinal morphology was examined one week after ischemic insult. Following ischemic reperfusion injury, ERG a- and b-wave amplitudes were significantly reduced in the control mice. Sulforaphane treatment significantly attenuated ischemic-induced loss of retinal function as compared to vehicle treated mice. In vehicle treated mice, ischemic reperfusion injury produced marked thinning of the inner retinal layers, but the thinning of the inner retinal layers appeared significantly less with sulforaphane treatment. Thus, sulforaphane may be beneficial in the treatment of retinal disorders with ischemic reperfusion injury. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Contemporary management of transient ischemic attack: role of the pharmacist.

    Science.gov (United States)

    Rhoney, Denise H

    2011-02-01

    Transient ischemic attacks (TIAs) have been redefined recently. The new tissue-based definition of TIA abandons the 24-hour restriction on symptom duration previously used to differentiate TIA from acute ischemic stroke and requires neuroimaging studies to identify the cause of the ischemia and to determine the presence and extent of brain injury. This new definition brings to light the need for urgent diagnostic testing and timely initiation of treatment, as well as secondary prevention measures to reduce the increased risk of stroke, cardiovascular complications, and death in the days and weeks after a TIA. Pharmacists play a key role in identifying patients at risk for a first or recurrent TIA or stroke, educating high-risk patients on the signs and symptoms of TIA or stroke and the need for urgent evaluation and treatment, overcoming barriers to timely diagnosis and treatment, and ensuring that appropriate primary or secondary prevention strategies are in place. Furthermore, studies have shown that pharmacist-led interventions can lead to significant improvements in modifiable risk factors, such as blood pressure and cholesterol levels, as well as drug adherence, and may reduce the occurrence of strokes. These interventions may also help maintain patients' health-related quality of life and improve patients' satisfaction with care.

  3. Mechanisms of team-sport-related brain injuries in children 5 to 19 years old: opportunities for prevention.

    Science.gov (United States)

    Cusimano, Michael D; Cho, Newton; Amin, Khizer; Shirazi, Mariam; McFaull, Steven R; Do, Minh T; Wong, Matthew C; Russell, Kelly

    2013-01-01

    There is a gap in knowledge about the mechanisms of sports-related brain injuries. The objective of this study was to determine the mechanisms of brain injuries among children and youth participating in team sports. We conducted a retrospective case series of brain injuries suffered by children participating in team sports. The Canadian Hospitals Injury Reporting and Prevention Program (CHIRPP) database was searched for brain injury cases among 5-19 year-olds playing ice hockey, soccer, American football (football), basketball, baseball, or rugby between 1990 and 2009. Mechanisms of injury were classified as "struck by player," "struck by object," "struck by sport implement," "struck surface," and "other." A descriptive analysis was performed. There were 12,799 brain injuries related to six team sports (16.2% of all brain injuries registered in CHIRPP). Males represented 81% of injuries and the mean age was 13.2 years. Ice hockey accounted for the greatest number of brain injuries (44.3%), followed by soccer (19.0%) and football (12.9%). In ice hockey, rugby, and basketball, striking another player was the most common injury mechanism. Football, basketball, and soccer also demonstrated high proportions of injuries due to contact with an object (e.g., post) among younger players. In baseball, a common mechanism in the 5-9 year-old group was being hit with a bat as a result of standing too close to the batter (26.1% males, 28.3% females). Many sports-related brain injury mechanisms are preventable. The results suggest that further efforts aimed at universal rule changes, safer playing environments, and the education of coaches, players, and parents should be targeted in maximizing prevention of sport-related brain injury using a multifaceted approach.

  4. Mechanisms of team-sport-related brain injuries in children 5 to 19 years old: opportunities for prevention.

    Directory of Open Access Journals (Sweden)

    Michael D Cusimano

    Full Text Available There is a gap in knowledge about the mechanisms of sports-related brain injuries. The objective of this study was to determine the mechanisms of brain injuries among children and youth participating in team sports.We conducted a retrospective case series of brain injuries suffered by children participating in team sports. The Canadian Hospitals Injury Reporting and Prevention Program (CHIRPP database was searched for brain injury cases among 5-19 year-olds playing ice hockey, soccer, American football (football, basketball, baseball, or rugby between 1990 and 2009. Mechanisms of injury were classified as "struck by player," "struck by object," "struck by sport implement," "struck surface," and "other." A descriptive analysis was performed.There were 12,799 brain injuries related to six team sports (16.2% of all brain injuries registered in CHIRPP. Males represented 81% of injuries and the mean age was 13.2 years. Ice hockey accounted for the greatest number of brain injuries (44.3%, followed by soccer (19.0% and football (12.9%. In ice hockey, rugby, and basketball, striking another player was the most common injury mechanism. Football, basketball, and soccer also demonstrated high proportions of injuries due to contact with an object (e.g., post among younger players. In baseball, a common mechanism in the 5-9 year-old group was being hit with a bat as a result of standing too close to the batter (26.1% males, 28.3% females.Many sports-related brain injury mechanisms are preventable. The results suggest that further efforts aimed at universal rule changes, safer playing environments, and the education of coaches, players, and parents should be targeted in maximizing prevention of sport-related brain injury using a multifaceted approach.

  5. Fingolimod prevents blood-brain barrier disruption induced by the sera from patients with multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Hideaki Nishihara

    Full Text Available OBJECTIVE: Effect of fingolimod in multiple sclerosis (MS is thought to involve the prevention of lymphocyte egress from lymphoid tissues, thereby reducing autoaggressive lymphocyte infiltration into the central nervous system across blood-brain barrier (BBB. However, brain microvascular endothelial cells (BMECs represent a possible additional target for fingolimod in MS patients by directly repairing the function of BBB, as S1P receptors are also expressed by BMECs. In this study, we evaluated the effects of fingolimod on BMECs and clarified whether fingolimod-phosphate restores the BBB function after exposure to MS sera. METHODS: Changes in tight junction proteins, adhesion molecules and transendothelial electrical resistance (TEER in BMECs were evaluated following incubation in conditioned medium with or without fingolimod/fingolimod-phosphate. In addition, the effects of sera derived from MS patients, including those in the relapse phase of relapse-remitting (RR MS, stable phase of RRMS and secondary progressive MS (SPMS, on the function of BBB in the presence of fingolimod-phosphate were assessed. RESULTS: Incubation with fingolimod-phosphate increased the claudin-5 protein levels and TEER values in BMECs, although it did not change the amount of occludin, ICAM-1 or MelCAM proteins. Pretreatment with fingolimod-phosphate restored the changes in the claudin-5 and VCAM-1 protein/mRNA levels and TEER values in BMECs after exposure to MS sera. CONCLUSIONS: Pretreatment with fingolimod-phosphate prevents BBB disruption caused by both RRMS and SPMS sera via the upregulation of claudin-5 and downregulation of VCAM-1 in BMECs, suggesting that fingolimod-phosphate is capable of directly modifying the BBB. BMECs represent a possible therapeutic target for fingolimod in MS patients.

  6. Retraining the addicted brain: a review of hypothesized neurobiological mechanisms of mindfulness-based relapse prevention.

    Science.gov (United States)

    Witkiewitz, Katie; Lustyk, M Kathleen B; Bowen, Sarah

    2013-06-01

    Addiction has generally been characterized as a chronic relapsing condition (Leshner, 1999). Several laboratory, preclinical, and clinical studies have provided evidence that craving and negative affect are strong predictors of the relapse process. These states, as well as the desire to avoid them, have been described as primary motives for substance use. A recently developed behavioral treatment, mindfulness-based relapse prevention (MBRP), was designed to target experiences of craving and negative affect and their roles in the relapse process. MBRP offers skills in cognitive-behavioral relapse prevention integrated with mindfulness meditation. The mindfulness practices in MBRP are intended to increase discriminative awareness, with a specific focus on acceptance of uncomfortable states or challenging situations without reacting "automatically." A recent efficacy trial found that those randomized to MBRP, as compared with those in a control group, demonstrated significantly lower rates of substance use and greater decreases in craving following treatment. Furthermore, individuals in MBRP did not report increased craving or substance use in response to negative affect. It is important to note, areas of the brain that have been associated with craving, negative affect, and relapse have also been shown to be affected by mindfulness training. Drawing from the neuroimaging literature, we review several plausible mechanisms by which MBRP might be changing neural responses to the experiences of craving and negative affect, which subsequently may reduce risk for relapse. We hypothesize that MBRP may affect numerous brain systems and may reverse, repair, or compensate for the neuroadaptive changes associated with addiction and addictive-behavior relapse. 2013 APA, all rights reserved

  7. Smoking Cessation Intervention After Ischemic Stroke or Transient Ischemic Attack. A Randomized Controlled Pilot Trial

    DEFF Research Database (Denmark)

    Brunner Frandsen, Nicole; Sørensen, Margit; Hyldahl, Tanja Kirstine

    2012-01-01

    BACKGROUND: Smoking cessation is widely recommended for secondary stroke prevention. However, little is known about the efficacy of smoking cessation intervention after stroke or transient ischemic attack (TIA). METHODS: Ninety-four smokers under age 76, admitted with ischemic stroke or TIA were...... to the results from other studies. Intensive smoking cessation intervention was not superior to short smoking cessation intervention. Thus, other factors than intensity of smoking cessation intervention might influence the smoking cessation rates after stroke or TIA....

  8. Silent stroke in patients with transient ischemic attack or minor ischemic stroke. The Dutch TIA Trial Study Group

    NARCIS (Netherlands)

    Herderscheê, D.; Hijdra, A.; Algra, A.; Koudstaal, P. J.; Kappelle, L. J.; van Gijn, J.

    1992-01-01

    BACKGROUND AND PURPOSE: We studied silent stroke (i.e., infarcts on computed tomographic scan not related to later symptoms) in patients after transient ischemic attack or minor ischemic stroke. METHODS: Ours is a cross-sectional study of 2,329 patients who were randomized in a secondary prevention

  9. Omega-3 prevents behavior response and brain oxidative damage in the ketamine model of schizophrenia.

    Science.gov (United States)

    Zugno, A I; Chipindo, H L; Volpato, A M; Budni, J; Steckert, A V; de Oliveira, M B; Heylmann, A S; da Rosa Silveira, F; Mastella, G A; Maravai, S G; Wessler, P G; Binatti, A R; Panizzutti, B; Schuck, P F; Quevedo, J; Gama, C S

    2014-02-14

    Supplementation with omega-3 has been identified as an adjunctive alternative for the treatment of psychiatric disorders, in order to minimize symptoms. Considering the lack of understanding concerning the pathophysiology of schizophrenia, the present study hypothesized that omega 3 prevents the onset of symptoms similar to schizophrenia in young Wistar rats submitted to ketamine treatment. Moreover, the role of oxidative stress in this model was assessed. Omega-3 (0.8g/kg) or vehicle was given by orogastric gavage once daily. Both treatments were performed during 21days, starting at the 30th day of life in young rats. After 14days of treatment with omega-3 or vehicle, a concomitant treatment with saline or ketamine (25mg/kg ip daily) was started and maintained until the last day of the experiment. We evaluated the pre-pulse inhibition of the startle reflex, activity of antioxidant systems and damage to proteins and lipids. Our results demonstrate that supplementation of omega-3 prevented: decreased inhibition of startle reflex, damage to lipids in the hippocampus and striatum and damage to proteins in the prefrontal cortex. Furthermore, these changes are associated with decreased GPx in brain tissues evaluated. Together, our results suggest the prophylactic role of omega-3 against the outcome of symptoms associated with schizophrenia. Copyright © 2014. Published by Elsevier Ltd.

  10. Preventive Effects of Safety Helmets on Traumatic Brain Injury after Work-Related Falls

    Directory of Open Access Journals (Sweden)

    Sang Chul Kim

    2016-10-01

    Full Text Available Introduction: Work-related traumatic brain injury (TBI caused by falls is a catastrophic event that leads to disabilities and high socio-medical costs. This study aimed to measure the magnitude of the preventive effect of safety helmets on clinical outcomes and to compare the effect across different heights of fall. Methods: We collected a nationwide, prospective database of work-related injury patients who visited the 10 emergency departments between July 2010 and October 2012. All of the adult patients who experienced work-related fall injuries were eligible, excluding cases with unknown safety helmet use and height of fall. Primary and secondary endpoints were intracranial injury and in-hospital mortality. We calculated adjusted odds ratios (AORs of safety helmet use and height of fall for study outcomes, and adjusted for any potential confounders. Results: A total of 1298 patients who suffered from work-related fall injuries were enrolled. The industrial or construction area was the most common place of fall injury occurrence, and 45.0% were wearing safety helmets at the time of fall injuries. The safety helmet group was less likely to have intracranial injury comparing with the no safety helmet group (the adjusted odds ratios (ORs (95% confidence interval (CI: 0.42 (0.24–0.73, however, there was no statistical difference of in-hospital mortality between two groups (the adjusted ORs (95% CI: 0.83 (0.34–2.03. In the interaction analysis, preventive effects of safety helmet on intracranial injury were significant within 4 m height of fall. Conclusions: A safety helmet is associated with prevention of intracranial injury resulting from work-related fall and the effect is preserved within 4 m height of fall. Therefore, wearing a safety helmet can be an intervention for protecting fall-related intracranial injury in the workplace.

  11. Preventive Effects of Safety Helmets on Traumatic Brain Injury after Work-Related Falls.

    Science.gov (United States)

    Kim, Sang Chul; Ro, Young Sun; Shin, Sang Do; Kim, Joo Yeong

    2016-10-29

    Work-related traumatic brain injury (TBI) caused by falls is a catastrophic event that leads to disabilities and high socio-medical costs. This study aimed to measure the magnitude of the preventive effect of safety helmets on clinical outcomes and to compare the effect across different heights of fall. We collected a nationwide, prospective database of work-related injury patients who visited the 10 emergency departments between July 2010 and October 2012. All of the adult patients who experienced work-related fall injuries were eligible, excluding cases with unknown safety helmet use and height of fall. Primary and secondary endpoints were intracranial injury and in-hospital mortality. We calculated adjusted odds ratios (AORs) of safety helmet use and height of fall for study outcomes, and adjusted for any potential confounders. A total of 1298 patients who suffered from work-related fall injuries were enrolled. The industrial or construction area was the most common place of fall injury occurrence, and 45.0% were wearing safety helmets at the time of fall injuries. The safety helmet group was less likely to have intracranial injury comparing with the no safety helmet group (the adjusted odds ratios (ORs) (95% confidence interval (CI)): 0.42 (0.24-0.73)), however, there was no statistical difference of in-hospital mortality between two groups (the adjusted ORs (95% CI): 0.83 (0.34-2.03). In the interaction analysis, preventive effects of safety helmet on intracranial injury were significant within 4 m height of fall. A safety helmet is associated with prevention of intracranial injury resulting from work-related fall and the effect is preserved within 4 m height of fall. Therefore, wearing a safety helmet can be an intervention for protecting fall-related intracranial injury in the workplace.

  12. Mild hypoxemia during initial reperfusion alleviates the severity of secondary energy failure and protects brain in neonatal mice with hypoxic-ischemic injury.

    Science.gov (United States)

    Niatsetskaya, Zoya V; Charlagorla, Pradeep; Matsukevich, Dzmitry A; Sosunov, Sergey A; Mayurasakorn, Korapat; Ratner, Veniamin I; Polin, Richard A; Starkov, Anatoly A; Ten, Vadim S

    2012-02-01

    Reperfusion triggers an oxidative stress. We hypothesized that mild hypoxemia in reperfusion attenuates oxidative brain injury following hypoxia-ischemia (HI). In neonatal HI-mice, the reperfusion was initiated by reoxygenation with room air (RA) followed by the exposure to 100%, 21%, 18%, 15% oxygen for 60 minutes. Systemic oxygen saturation (SaO(2)), cerebral blood flow (CBF), brain mitochondrial respiration and permeability transition pore (mPTP) opening, markers of oxidative injury, and cerebral infarcts were assessed. Compared with RA-littermates, HI-mice exposed to 18% oxygen exhibited significantly decreased infarct volume, oxidative injury in the brain mitochondria and tissue. This was coupled with improved mitochondrial tolerance to mPTP opening. Oxygen saturation maintained during reperfusion at 85% to 95% was associated (r=0.57) with the best neurologic outcome. Exposure to 100% or 15% oxygen significantly exacerbated brain injury and oxidative stress. Compared with RA-mice, hyperoxia dramatically increased reperfusion CBF, but exposure to 15% oxygen significantly reduced CBF to values observed during the HI-insult. Mild hypoxemia during initial reperfusion alleviates the severity of HI-brain injury by limiting the reperfusion-driven oxidative stress to the mitochondria and mPTP opening. This suggests that at the initial stage of reperfusion, a slightly decreased systemic oxygenation (SaO(2) 85% to 95%) may be beneficial for infants with birth asphyxia.

  13. NEUROGENETIC ASPECTS OF PERINATAL HYPOXIC-ISCHEMIC AFFECTIONS OF THE CENTRAL NERVOUS SYSTEM

    Directory of Open Access Journals (Sweden)

    George A. Karkashadze

    2016-01-01

    Full Text Available Neurogenetics is a thriving young science greatly contributing to the generally accepted concept of the brain development in health and disease. Thereby; scientists are not only able to highlight new key points in traditional ideas about the origin of diseases; but also to completely rethink their view on the problem of pathology development. In particular; new data on neurogenetics of perinatal affections of the central nervous system (CNS has appeared. Genetic factors in varying degrees affect perinatal hypoxic-ischemic CNS affections. Prematurity determination stays the most studied among them. Nevertheless; there is increasing evidence of significant epigenetic regulations of neuro-expression caused by hypoxia; malnutrition of a pregnant woman; stress; smoking; alcohol; drugs that either directly pathologically affect the developing brain; or form a brain phenotype sensitive to a perinatal CNS affection. New data obliges to change the approaches to prevention of perinatal CNS affections.

  14. Constraint-induced movement therapy promotes motor function recovery and downregulates phosphorylated extracellular regulated protein kinase expression in ischemic brain tissue of rats

    Directory of Open Access Journals (Sweden)

    Bei Zhang

    2015-01-01

    Full Text Available Motor function impairment is a common outcome of stroke. Constraint-induced movement therapy (CIMT involving intensive use of the impaired limb while restraining the unaffected limb is widely used to overcome the effects of ′learned non-use′ and improve limb function after stroke. However, the underlying mechanism of CIMT remains unclear. In the present study, rats were randomly divided into a middle cerebral artery occlusion (model group, a CIMT + model (CIMT group, or a sham group. Restriction of the affected limb by plaster cast was performed in the CIMT and sham groups. Compared with the model group, CIMT significantly improved the forelimb functional performance in rats. By western blot assay, the expression of phosphorylated extracellular regulated protein kinase in the bilateral cortex and hippocampi of cerebral ischemic rats in the CIMT group was significantly lower than that in the model group, and was similar to sham group levels. These data suggest that functional recovery after CIMT may be related to decreased expression of phosphorylated extracellular regulated protein kinase in the bilateral cortex and hippocampi.

  15. Insulin prevents mitochondrial generation of H₂O₂ in rat brain.

    Science.gov (United States)

    Muller, Alexandre Pastoris; Haas, Clarissa Branco; Camacho-Pereira, Juliana; Brochier, Andressa Wigner; Gnoatto, Jussânia; Zimmer, Eduardo Rigon; de Souza, Diogo Onofre; Galina, Antonio; Portela, Luis Valmor

    2013-09-01

    The mitochondrial electron transport system (ETS) is a main source of cellular ROS, including hydrogen peroxide (H₂O₂). The production of H₂O₂ also involves the mitochondrial membrane potential (ΔΨm) and oxygen consumption. Impaired insulin signaling causes oxidative neuronal damage and places the brain at risk of neurodegeneration. We evaluated whether insulin signaling cross-talks with ETS components (complexes I and F₀F₁ATP synthase) and ΔΨm to regulate mitochondrial H₂O₂ production, in tissue preparations from rat brain. Insulin (50 to 100 ng/mL) decreased H₂O₂ production in synaptosomal preparations in high Na(+) buffer (polarized state), stimulated by glucose and pyruvate, without affecting the oxygen consumption. In addition, insulin (10 to 100 ng/mL) decreased H₂O₂ production induced by succinate in synaptosomes in high K(+) (depolarized state), whereas wortmannin and LY290042, inhibitors of the PI3K pathway, reversed this effect; heated insulin had no effect. Insulin decreased H₂O₂ production when complexes I and F₀F₁ATP synthase were inhibited by rotenone and oligomycin respectively suggesting a target effect on complex III. Also, insulin prevented the generation of maximum level of ∆Ψm induced by succinate. The PI3K inhibitors and heated insulin maintained the maximum level of ∆Ψm induced by succinate in synaptosomes in a depolarized state. Similarly, insulin decreased ROS production in neuronal cultures. In mitochondrial preparations, insulin neither modulated H2O2 production or oxygen consumption. In conclusion, the normal downstream insulin receptor signaling is necessary to regulate complex III of ETS avoiding the generation of maximal ∆Ψm and increased mitochondrial H2O2 production. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Mineralocorticoid receptor blockade prevents stress-induced modulation of multiple memory systems in the human brain.

    Science.gov (United States)

    Schwabe, Lars; Tegenthoff, Martin; Höffken, Oliver; Wolf, Oliver T

    2013-12-01

    Accumulating evidence suggests that stress may orchestrate the engagement of multiple memory systems in the brain. In particular, stress is thought to favor dorsal striatum-dependent procedural over hippocampus-dependent declarative memory. However, the neuroendocrine mechanisms underlying these modulatory effects of stress remain elusive, especially in humans. Here, we targeted the role of the mineralocorticoid receptor (MR) in the stress-induced modulation of dorsal striatal and hippocampal memory systems in the human brain using a combination of event-related functional magnetic resonance imaging and pharmacologic blockade of the MR. Eighty healthy participants received the MR antagonist spironolactone (300 mg) or a placebo and underwent a stressor or control manipulation before they performed, in the scanner, a classification task that can be supported by the hippocampus and the dorsal striatum. Stress after placebo did not affect learning performance but reduced explicit task knowledge and led to a relative increase in the use of more procedural learning strategies. At the neural level, stress promoted striatum-based learning at the expense of hippocampus-based learning. Functional connectivity analyses showed that this shift was associated with altered coupling of the amygdala with the hippocampus and dorsal striatum. Mineralocorticoid receptor blockade before stress prevented the stress-induced shift toward dorsal striatal procedural learning, same as the stress-induced alterations of amygdala connectivity with hippocampus and dorsal striatum, but resulted in significantly impaired performance. Our findings indicate that the stress-induced shift from hippocampal to dorsal striatal memory systems is mediated by the amygdala, required to preserve performance after stress, and dependent on the MR. © 2013 Society of Biological Psychiatry.

  17. Post-ischemic inflammation regulates neural damage and protection

    Directory of Open Access Journals (Sweden)

    Takashi eShichita

    2014-10-01

    Full Text Available Post-ischemic inflammation is important in ischemic stroke pathology. However, details of the inflammation process, its resolution after stroke and its effect on pathology and neural damage have not been clarified. Brain swelling, which is often fatal in ischemic stroke patients, occurs at an early stage of stroke due to endothelial cell injury and severe inflammation by infiltrated mononuclear cells including macrophages, neutrophils, and lymphocytes. At early stage of inflammation, macrophages are activated by molecules released from necrotic cells (danger-associated molecular patterns (DAMPs, and inflammatory cytokines and mediators that increase ischemic brain damage by disruption of the blood-brain barrier are released. After post-ischemic inflammation, macrophages function as scavengers of necrotic cell and brain tissue debris. Such macrophages are also involved in tissue repair and neural cell regeneration by producing tropic factors. The mechanisms of inflammation resolution and conversion of inflammation to neuroprotection are largely unknown. In this review, we summarize information accumulated recently about DAMP-induced inflammation and the neuroprotective effects of inflammatory cells, and discuss next generation strategies to treat ischemic stroke.

  18. Involvement of the JNK/FOXO3a/Bim Pathway in Neuronal Apoptosis after Hypoxic-Ischemic Brain Damage in Neonatal Rats.

    Directory of Open Access Journals (Sweden)

    Deyuan Li

    Full Text Available c-Jun N-terminal kinase (JNK plays a key role in the regulation of neuronal apoptosis. Previous studies have revealed that forkhead transcription factor (FOXO3a is a critical effector of JNK-mediated tumor suppression. However, it is not clear whether the JNK/FOXO3a pathway is involved in neuronal apoptosis in the developing rat brain after hypoxia-ischemia (HI. In this study, we generated an HI model using postnatal day 7 rats. Fluorescence immunolabeling and Western blot assays were used to detect the distribution and expression of total and phosphorylated JNK and FOXO3a and the pro-apoptotic proteins Bim and CC3. We found that JNK phosphorylation was accompanied by FOXO3a dephosphorylation, which induced FOXO3a translocation into the nucleus, resulting in the upregulation of levels of Bim and CC3 proteins. Furthermore, we found that JNK inhibition by AS601245, a specific JNK inhibitor, significantly increased FOXO3a phosphorylation, which attenuated FOXO3a translocation into the nucleus after HI. Moreover, JNK inhibition downregulated levels of Bim and CC3 proteins, attenuated neuronal apoptosis and reduced brain infarct volume in the developing rat brain. Our findings suggest that the JNK/FOXO3a/Bim pathway is involved in neuronal apoptosis in the developing rat brain after HI. Agents targeting JNK may offer promise for rescuing neurons from HI-induced damage.

  19. Nonfasting triglycerides, cholesterol, and ischemic stroke in the general population

    DEFF Research Database (Denmark)

    Varbo, Anette; Nordestgaard, Børge G; Tybjaerg-Hansen, Anne

    2011-01-01

    Current guidelines on stroke prevention have recommendations on desirable cholesterol levels, but not on nonfasting triglycerides. We compared stepwise increasing levels of nonfasting triglycerides and cholesterol for their association with risk of ischemic stroke in the general population....

  20. Stroke subtypes and factors associated with ischemic stroke in ...

    African Journals Online (AJOL)

    . Better understanding and controlling factors associated will improve the prevention of the disease. This study reviews records of patients with ischemic stroke in Central Africa. Material and methods: Patients of Bantu ethnicity with clinical ...

  1. Efficacy and Safety of Vorapaxar With and Without a Thienopyridine for Secondary Prevention in Patients With Previous Myocardial Infarction and No History of Stroke or Transient Ischemic Attack: Results from TRA 2°P-TIMI 50.

    Science.gov (United States)

    Bohula, Erin A; Aylward, Philip E; Bonaca, Marc P; Corbalan, Ramon L; Kiss, Robert G; Murphy, Sabina A; Scirica, Benjamin M; White, Harvey; Braunwald, Eugene; Morrow, David A

    2015-11-17

    Vorapaxar antagonizes protease-activated receptor 1, the primary receptor for thrombin on human platelets, and reduces recurrent thrombotic events in stable patients with a previous myocardial infarction (MI). We wished to determine whether the efficacy and safety of antiplatelet therapy with vorapaxar was modified by concurrent thienopyridine use. The Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-Thrombolysis in Myocardial Infarction 50 (TRA 2°P-TIMI 50) was a randomized, double-blind, placebo-controlled trial of vorapaxar in 26,449 patients with previous atherothrombosis. This prespecified analysis included 16,897 patients who qualified with a MI in the preceding 2 weeks to 12 months and was restricted to patients without a history of stroke or transient ischemic attack given its contraindication in that population. Randomization was stratified on the basis of planned thienopyridine use. Thienopyridine was planned at randomization in 12,410 (73%). Vorapaxar significantly reduced the composite of cardiovascular death, MI, and stroke in comparison with placebo regardless of planned thienopyridine therapy (planned thienopyridine, hazard ratio, 0.80, 0.70-0.91, PGlobal Use of Strategies to Open Occluded Coronary Arteries (GUSTO) moderate or severe bleeding risk was increased with vorapaxar and was not significantly altered by planned thienopyridine (planned, hazard ratio, 1.50; 1.18-1.89, Phistory of previous MI, whether treated concomitantly with a thienopyridine or not. The relative risk of moderate or severe bleeding was similarly increased irrespective of thienopyridine use. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00526474. © 2015 American Heart Association, Inc.

  2. 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.

  3. Dronedarone administration prevents body weight gain and increases tolerance of the heart to ischemic stress: a possible involvement of thyroid hormone receptor alpha1.

    Science.gov (United States)

    Pantos, Constantinos; Mourouzis, Iordanis; Malliopoulou, Vassiliki; Paizis, Ioannis; Tzeis, Stylianos; Moraitis, Panagiotis; Sfakianoudis, Konstantinos; Varonos, Dennis D; Cokkinos, Dennis V

    2005-01-01

    Hypothyroid heart displays a phenotype of cardioprotection against ischemia and this study investigated whether administration of dronedarone, an amiodarone-like compound that has been shown to preferentially antagonize thyroid hormone binding to thyroid hormone receptor alpha1 (TRalpha1), results in a similar effect. Dronedarone was given in Wistar rats (90 mg/kg, once daily (od) for 2 weeks) (DRON), while untreated animals served as controls (CONT). Hypothyroidism (HYPO) was induced by propylthiouracil administration. Isolated rat hearts were perfused in Langendorff mode and subjected to 20 minutes of zero-flow global ischemia (I) followed by 45 minutes of reperfusion (R). 3,5,3' Triiodothyronine remained unchanged while body weight and food intake were reduced. alpha-Myosin heavy chain (alpha-MHC) decreased in DRON while beta-myosin heavy chain (beta-MHC) and sarcoplasmic reticulum Ca2+ adenosine triphosphatase (ATPase) expression (SERCA) was similar to CONT. In HYPO, alpha-MHC and SERCA were decreased while beta-MHC was increased. Myocardial glycogen content was increased in both DRON and HYPO. In DRON, resting heart rate and contractility were reduced and ischemic contracture was significantly suppressed while postischemic left ventricular end-diastolic pressure and lactate dehydrogenase release (IU/L min) after I/R were significantly decreased. In conclusion, dronedarone treatment results in cardioprotection by selectively mimicking hypothyroidism. This is accompanied by a reduction in body weight because of the suppression of food intake. TRs might prove novel pharmacologic targets for the treatment of cardiovascular illnesses.

  4. PAI-1 4G/5G polymorphism is associated with brain vessel reocclusion after successful fibrinolytic therapy in ischemic stroke patients.

    Science.gov (United States)

    Fernandez-Cadenas, I; Del Rio-Espinola, A; Rubiera, M; Mendioroz, M; Domingues-Montanari, S; Cuadrado, E; Hernandez-Guillamon, M; Rosell, A; Ribo, M; Alvarez-Sabin, J; Molina, C A; Montaner, J

    2010-04-01

    Despite t-PA proven benefits related to vessel reopening, up to 13% of stroke patients suffer reocclusions after t-PA. We aimed to analyze whether a functional polymorphism in a fibrinolysis inhibitor gene [plasminogen activator inhibitor-1 (PAI-1)] might be associated with reocclusion rates after stroke thrombolytic therapy. 165 patients with ischemic stroke who received t-PA 4G/5G polymorphism determination was performed by sequencing. PAI-1 mRNA was studied by real-time PCR analysis. National institutes of health stroke scale (NIHSS) was serially measured since patients arrival to assess the neurological outcome, and modified ranking scale (mRS) at 3rd month was used to evaluate functional outcome following stroke. PAI-1 4G/4G patients had higher reocclusion rates (4G/4G = 12.5% versus other genotypes = 2.7%, p = 0.025). . In a logistic regression, the 4G/4G genotype was the only factor associated with reocclusion (OR = 15.16 95%, CI = 1.4-163.4, p = 0.025). 4G/4G genotype was also associated with poor functional outcome at 3rd month (4G/4G = 4 versus others genotypes = 3, p = 0.017) and with mRNA levels at 12 h post stroke symptoms onset (4G/4G patients = 2.01% versus other genotypes = 0.68%, p = 0.034). PAI-1 4G/4G genotype is associated with reocclusion rates and poor functional outcome among stroke patients treated with t-PA.

  5. Brain Temperature Is Increased During the First Days of Life in Asphyxiated Newborns: Developing Brain Injury Despite Hypothermia Treatment.

    Science.gov (United States)

    Owji, Z P; Gilbert, G; Saint-Martin, C; Wintermark, P

    2017-11-01

    .34°C, and white matter, 33.07°C ± 1.71°C). Also, brain temperatures tended to remain slightly higher in the neonates who developed brain injury around day 10 of life and around 1 month of age. Therapeutic hypothermia using current guidelines decreased the brain temperature of neonates with hypoxic-ischemic encephalopathy during the first days of life but did not prevent an early increase of brain temperature in neonates with hypoxic-ischemic encephalopathy who developed brain injury despite this treatment. © 2017 by American Journal of Neuroradiology.

  6. Human Umbilical Cord-Derived Mesenchymal Stem Cells Improve Learning and Memory Function in Hypoxic-Ischemic Brain-Damaged Rats via an IL-8-Mediated Secretion Mechanism Rather than Differentiation Pattern Induction.

    Science.gov (United States)

    Zhou, Xiaoqin; Gu, Jialu; Gu, Yan; He, Mulan; Bi, Yang; Chen, Jie; Li, Tingyu

    2015-01-01

    MSCs are a promising therapeutic resource. Paracrine effects and the induction of differentiation patterns are thought to represent the two primary mechanisms underlying the therapeutic effects of mesenchymal stem cell (MSC) transplantation in vivo. However, it is unclear which mechanism is involved in the therapeutic effects of human umbilical cord-derived MSC (hUC-MSC) transplantation. Based on flow cytometry analysis, hUC-MSCs exhibited the morphological characteristics and surface markers of MSCs. Following directed neural induction, these cells displayed a neuron-like morphology and expressed high levels of neural markers. All types of hUC-MSCs, including differentiated and redifferentiated cells, promoted learning and memory function recovery in hypoxic-ischemic brain damaged (HIBD) rats. The hUC-MSCs secreted IL-8, which enhanced angiogenesis in the hippocampus via the JNK pathway. However, the differentiated and redifferentiated cells did not exert significantly greater therapeutic effects than the undifferentiated hUC-MSCs. hUC-MSCs display the biological properties and neural differentiation potential of MSCs and provide therapeutic advantages by secreting IL-8, which participates in angiogenesis in the rat HIBD model. These data suggest that hUC-MSC transplantation improves the recovery of neuronal function via an IL-8-mediated secretion mechanism, whereas differentiation pattern induction was limited. © 2015 S. Karger AG, Basel.

  7. [A clinical case of young, oral combined contraceptive using women, heterozygous carrier of the Factor V (Leiden) which revealed thrombosis of the left internal jugular vein and brain ischemia with cerebral infarction and ischemic stroke].

    Science.gov (United States)

    Kovachev, S; Ramshev, K; Ramsheva, Z; Ivanov, A; Ganovska, A

    2013-01-01

    Thrombophilia is associated with increased risks of venous thrombosis in women taking oral contraceptive preparations. Universal thrombophilia screening in women prior to prescribing oral contraceptive preparations is not supported by current evidence. The case is presented of a 23 year-old women with a personal history of interruption and on the same day started with oral contraceptive (0.03 microg ethynil estradiol - 0.075 microg gestodene), which due on a 18 pill/day to acute headache, increasing vomiting and speaking defects. Physical/neurologic/gynecologic examinations observed a normal status. The MRI and CT revealed thrombosis of the left internal jugular vein and brain ischemia with cerebral infarction and ischemic stroke. The acute therapy of thrombotic findings was accompanied with many tests. The thrombophilia PCR-Real time - test finds heterozygous carrier of the Factor V (Leiden). This case shows the need of large prospective studies that should be undertaken to refine the risks and establish the associations of thrombophilias with venous thrombosis among contraceptive users. The key to a prompt diagnosis is to know the risk factors. The relative value of a thrombophilia screening programme before contraceptive using needs to be established.

  8. MicroRNA-195 prevents dendritic degeneration and neuron death in rats following chronic brain hypoperfusion.

    Science.gov (United States)

    Chen, Xin; Jiang, Xue-Mei; Zhao, Lin-Jing; Sun, Lin-Lin; Yan, Mei-Ling; Tian, You; Zhang, Shuai; Duan, Ming-Jing; Zhao, Hong-Mei; Li, Wen-Rui; Hao, Yang-Yang; Wang, Li-Bo; Xiong, Qiao-Jie; Ai, Jing

    2017-06-01

    Impaired synaptic plasticity and neuron loss are hallmarks of Alzheimer's disease and vascular dementia. Here, we found that chronic brain hypoperfusion (CBH) by bilateral common carotid artery occlusion (2VO) decreased the total length, numbers and crossings of dendrites and caused neuron death in rat hippocampi and cortices. It also led to increase in N-terminal β-amyloid precursor protein (N-APP) and death receptor-6 (DR6) protein levels and in the activation of caspase-3 and caspase-6. Further study showed that DR6 protein was downregulated by miR-195 overexpression, upregulated by miR-195 inhibition, and unchanged by binding-site mutation and miR-masks. Knockdown of endogenous miR-195 by lentiviral vector-mediated overexpression of its antisense molecule (lenti-pre-AMO-miR-195) decreased the total length, numbers and crossings of dendrites and neuron death, upregulated N-APP and DR6 levels, and elevated cleaved caspase-3 and caspase-6 levels. Overexpression of miR-195 using lenti-pre-miR-195 prevented these changes triggered by 2VO. We conclude that miR-195 is involved in CBH-induced dendritic degeneration and neuron death through activation of the N-APP/DR6/caspase pathway.

  9. Combination of Constraint-Induced Movement Therapy with Electroacupuncture Improves Functional Recovery following Neonatal Hypoxic-Ischemic Brain Injury in Rats

    Directory of Open Access Journals (Sweden)

    Hyunha Kim

    2018-01-01

    Full Text Available Aim. Neonatal hypoxic-ischemia (HI due to insufficient oxygen supply and blood flow during the prenatal and postnatal periods can cause cerebral palsy, a serious developmental condition. The purpose of this study was to investigate the efficacy of combining constraint-induced movement therapy (CIMT and electroacupuncture to treat rat neonatal HI brain injury. Methods. The left common carotid arteries of postnatal day 7 rats were ligated to induce HI brain injury, and the neonates were kept in a hypoxia chamber containing 8% oxygen for 2 hrs. Electroacupuncture at Baihui (GV 20 and Zusanli (ST 36 was performed concurrently with CIMT 3 weeks after HI induction for 4 weeks. Results. Motor asymmetry after HI was significantly improved in the CIMT and electroacupuncture combination group, but HI lesion size was not improved. The combination of CIMT and electroacupuncture after HI injury increases NeuN and decreases GFAP levels in the cerebral cortex, suggesting that this combination treatment inversely regulates neurons and astrocytes. In addition, the combination treatment group reduced the level of cleaved caspase-3, a crucial mediator of apoptosis, in the cortex. Conclusions. Our findings indicate that a combination of CIMT and electroacupuncture is an effective method to treat hemiplegia due to neonatal HI brain injury.

  10. Effects of Ischemic Preconditioning of Different Intraoperative Ischemic Times of Vascularized Bone Graft Rabbit Models

    Directory of Open Access Journals (Sweden)

    Ahmad Sukari Halim

    2013-11-01

    Full Text Available BackgroundIschemic preconditioning has been shown to improve the outcomes of hypoxic tolerance of the heart, brain, lung, liver, jejunum, skin, and muscle tissues. However, to date, no report of ischemic preconditioning on vascularized bone grafts has been published.MethodsSixteen rabbits were divided into four groups with ischemic times of 2, 6, 14, and 18 hours. Half of the rabbits in each group underwent ischemic preconditioning. The osteomyocutaneous flaps consisted of the tibia bone, from which the overlying muscle and skin were raised. The technique of ischemic preconditioning involved applying a vascular clamp to the pedicle for 3 cycles of 10 minutes each. The rabbits then underwent serial plain radiography and computed tomography imaging on the first, second, fourth, and sixth postoperative weeks. Following this, all of the rabbits were sacrificed and histological examinations were performed.ResultsThe results showed that for clinical analysis of the skin flaps and bone grafts, the preconditioned groups showed better survivability. In the plain radiographs, except for two non-preconditioned rabbits with intraoperative ischemic times of 6 hours, all began to show early callus formation at the fourth week. The computed tomography findings showed more callus formation in the preconditioned groups for all of the ischemic times except for the 18-hour group. The histological findings correlated with the radiological findings. There was no statistical significance in the difference between the two groups.ConclusionsIn conclusion, ischemic preconditioning improved the survivability of skin flaps and increased callus formation during the healing process of vascularized bone grafts.

  11. Systematic Review of Traumatic Brain Injuries in Baseball and Softball: A Framework for Prevention

    Directory of Open Access Journals (Sweden)

    Michael D. Cusimano

    2017-10-01

    Full Text Available BackgroundTraumatic brain injuries (TBIs are an important public health challenge. The classification of baseball and softball as low contact sports and their association with extremity injuries cause individuals to overlook the risk of TBI in baseball and softball.PurposeTo summarize our knowledge of the epidemiology and risk factors of TBIs associated with baseball and softball with an aim to better design and implement preventive strategies.MethodsA search algorithm containing keywords that were synonymous to the terms “TBI,” “baseball” was applied to the following nine databases: MEDLINE, Scopus, PubMed, EMBASE, CINAHL, Healthstar, PsychINFO, AMED, Cochrane library. Cited reference lists of identified articles were also consulted yielding a total of eighty-eight articles for full review. The search was concluded on November 14, 2016. The level of evidence was evaluated according to the guidelines from Strengthening the Reporting of Observational Studies in Epidemiology statement.ResultsTwenty-nine articles published between 2000 and 2016 met the criteria for analysis. Collectively, they examined the years 1982–2015 and identified 242,731 baseball-and softball-related TBIs. The most explored outcome of TBI was concussion. The average injury rate per 1,000 athletic exposures was 0.13 (range 0.03–0.46. The most common mechanism of injury was being struck by bat for younger players and being struck by ball for older athletes (adolescent and beyond. Rates of TBI were on average 4.17 times greater in games compared to practices. Females were on average 2.04 times more likely to sustain a TBI than males. Severity of TBIs varied considerably from mild and returning to the field on the same day, to immediate death. Generally, there is poor compliance with helmet use and return-to-play post-concussion guidelines. An increase TBI rates was observed over time. Multifaceted preventive strategies must be implemented to reduce the frequency and

  12. Systematic Review of Traumatic Brain Injuries in Baseball and Softball: A Framework for Prevention.

    Science.gov (United States)

    Cusimano, Michael D; Zhu, Alice

    2017-01-01

    Traumatic brain injuries (TBIs) are an important public health challenge. The classification of baseball and softball as low contact sports and their association with extremity injuries cause individuals to overlook the risk of TBI in baseball and softball. To summarize our knowledge of the epidemiology and risk factors of TBIs associated with baseball and softball with an aim to better design and implement preventive strategies. A search algorithm containing keywords that were synonymous to the terms "TBI," "baseball" was applied to the following nine databases: MEDLINE, Scopus, PubMed, EMBASE, CINAHL, Healthstar, PsychINFO, AMED, Cochrane library. Cited reference lists of identified articles were also consulted yielding a total of eighty-eight articles for full review. The search was concluded on November 14, 2016. The level of evidence was evaluated according to the guidelines from Strengthening the Reporting of Observational Studies in Epidemiology statement. Twenty-nine articles published between 2000 and 2016 met the criteria for analysis. Collectively, they examined the years 1982-2015 and identified 242,731 baseball-and softball-related TBIs. The most explored outcome of TBI was concussion. The average injury rate per 1,000 athletic exposures was 0.13 (range 0.03-0.46). The most common mechanism of injury was being struck by bat for younger players and being struck by ball for older athletes (adolescent and beyond). Rates of TBI were on average 4.17 times greater in games compared to practices. Females were on average 2.04 times more likely to sustain a TBI than males. Severity of TBIs varied considerably from mild and returning to the field on the same day, to immediate death. Generally, there is poor compliance with helmet use and return-to-play post-concussion guidelines. An increase TBI rates was observed over time. Multifaceted preventive strategies must be implemented to reduce the frequency and burden of these injuries. It is difficult to compare the

  13. Brain Basics

    Medline Plus

    Full Text Available ... can lead to mental disorders, such as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits ... tailored treatments, and possibly prevention of such illnesses. The Working Brain Neurotransmitters Everything we do relies on ...

  14. Transient Ischemic Attack

    Medline Plus

    Full Text Available ... TIA , or transient ischemic attack, is a "mini stroke" that occurs when a blood clot blocks an ... a short time. The only difference between a stroke and TIA is that with TIA the blockage ...

  15. The role of monocytes in ischemic stroke pathobiology: New avenues to explore

    Directory of Open Access Journals (Sweden)

    Ayman eElAli

    2016-02-01

    Full Text Available Ischemic stroke accounts for the majority of stroke cases and constitutes a major cause of death and disability in the industrialized world. Inflammation has been reported to constitute a major component of ischemic stroke pathobiology. In the acute phase of ischemic stroke, microglia, the resident macrophages of the brain, are activated, followed by several infiltration waves of different circulating immune cells into the brain. Among these circulating immune cells, monocytes have been shown to play a particularly important role. Following their infiltration, monocytes differentiate into potent phagocytic cells, monocyte-derived macrophages (MDMs in the ischemic brain. Initially, the presence of these cells was considered as marker of an exacerbated inflammatory response that contributes to brain damage. However, the recent reports are suggesting a more complex and multiphasic roles of these cells in ischemic stroke pathobiology. Monocytes constitute a heterogeneous group of cells, which comprises two major subsets in rodent and three major subsets in human. In both species, two equivalent subsets exist, the pro-inflammatory subset and the anti-inflammatory subset. Recent data have demonstrated that ischemic stroke differentially regulate monocyte subsets, which directly affect ischemic stroke pathobiology and may have direct implications in ischemic stroke therapies. Here we review the recent findings that addressed the role of different monocyte subsets in ischemic stroke pathobiology, and the implications on therapies.

  16. Molecular chaperones and hypoxic-ischemic encephalopathy

    Directory of Open Access Journals (Sweden)

    Cong Hua

    2017-01-01

    Full Text Available Hypoxic-ischemic encephalopathy (HIE is a disease that occurs when the brain is subjected to hypoxia, resulting in neuronal death and neurological deficits, with a poor prognosis. The mechanisms underlying hypoxic-ischemic brain injury include excitatory amino acid release, cellular proteolysis, reactive oxygen species generation, nitric oxide synthesis, and inflammation. The molecular and cellular changes in HIE include protein misfolding, aggregation, and destruction of organelles. The apoptotic pathways activated by ischemia and hypoxia include the mitochondrial pathway, the extrinsic Fas receptor pathway, and the endoplasmic reticulum stress-induced pathway. Numerous treatments for hypoxic-ischemic brain injury caused by HIE have been developed over the last half century. Hypothermia, xenon gas treatment, the use of melatonin and erythropoietin, and hypoxic-ischemic preconditioning have proven effective in HIE patients. Molecular chaperones are proteins ubiquitously present in both prokaryotes and eukaryotes. A large number of molecular chaperones are induced after brain ischemia and hypoxia, among which the heat shock proteins are the most important. Heat shock proteins not only maintain protein homeostasis; they also exert anti-apoptotic effects. Heat shock proteins maintain protein homeostasis by helping to transport proteins to their target destinations, assisting in the proper folding of newly synthesized polypeptides, regulating the degradation of misfolded proteins, inhibiting the aggregation of proteins, and by controlling the refolding of misfolded proteins. In addition, heat shock proteins exert anti-apoptotic effects by interacting with various signaling pathways to block the activation of downstream effectors in numerous apoptotic pathways, including the intrinsic pathway, the endoplasmic reticulum-stress mediated pathway and the extrinsic Fas receptor pathway. Molecular chaperones play a key role in neuroprotection in HIE. In

  17. Acute ischemic cerebral attack

    OpenAIRE

    Franco-Garcia Samir; Barreiro-Pinto Belis

    2010-01-01

    The decrease of the cerebral blood flow below the threshold of autoregulation led to changes of cerebral ischemia and necrosis that traduce in signs and symtoms of focal neurologic dysfunction called acute cerebrovascular symdrome (ACS) or stroke. Two big groups according to its etiology are included in this category the hemorragic that constitue a 20% and the ischemic a 80% of cases. Great interest has wom the ischemic ACS because of its high social burden, being the third cause of no violen...

  18. Mesenchymal Stromal Cell-Derived Extracellular Vesicles Protect the Fetal Brain After Hypoxia-Ischemia.

    Science.gov (United States)

    Ophelders, Daan R M G; Wolfs, Tim G A M; Jellema, Reint K; Zwanenburg, Alex; Andriessen, Peter; Delhaas, Tammo; Ludwig, Anna-Kristin; Radtke, Stefan; Peters, Vera; Janssen, Leon; Giebel, Bernd; Kramer, Boris W

    2016-06-01

    Preterm neonates are susceptible to perinatal hypoxic-ischemic brain injury, for which no treatment is available. In a preclinical animal model of hypoxic-ischemic brain injury in ovine fetuses, we have demonstrated the neuroprotective potential of systemically administered mesenchymal stromal cells (MSCs). The mechanism of MSC treatment is unclear but suggested to be paracrine, through secretion of extracellular vesicles (EVs). Therefore, we investigated in this study the protective effects of mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) in a preclinical model of preterm hypoxic-ischemic brain injury. Ovine fetuses were subjected to global hypoxia-ischemia by transient umbilical cord occlusion, followed by in utero intravenous administration of MSC-EVs. The therapeutic effects of MSC-EV administration were assessed by analysis of electrophysiological parameters and histology of the brain. Systemic administration of MSC-EVs improved brain function by reducing the total number and duration of seizures, and by preserving baroreceptor reflex sensitivity. These functional protections were accompanied by a tendency to prevent hypomyelination. Cerebral inflammation remained unaffected by the MSC-EV treatment. Our data demonstrate that MSC-EV treatment might provide a novel strategy to reduce the neurological sequelae following hypoxic-ischemic injury of the preterm brain. Our study results suggest that a cell-free preparation comprising neuroprotective MSC-EVs could substitute MSCs in the treatment of preterm neonates with hypoxic-ischemic brain injury, thereby circumventing the potential risks of systemic administration of living cells. Bone marrow-derived mesenchymal stromal cells (MSCs) show promise in treating hypoxic-ischemic injury of the preterm brain. Study results suggest administration of extracellular vesicles, rather than intact MSCs, is sufficient to exert therapeutic effects and avoids potential concerns associated with administration

  19. Pioglitazone after Ischemic Stroke or Transient Ischemic Attack.

    Science.gov (United States)

    Kernan, Walter N; Viscoli, Catherine M; Furie, Karen L; Young, Lawrence H; Inzucchi, Silvio E; Gorman, Mark; Guarino, Peter D; Lovejoy, Anne M; Peduzzi, Peter N; Conwit, Robin; Brass, Lawrence M; Schwartz, Gregory G; Adams, Harold P; Berger, Leo; Carolei, Antonio; Clark, Wayne; Coull, Bruce; Ford, Gary A; Kleindorfer, Dawn; O'Leary, John R; Parsons, Mark W; Ringleb, Peter; Sen, Souvik; Spence, J David; Tanne, David; Wang, David; Winder, Toni R

    2016-04-07

    Patients with ischemic stroke or transient ischemic attack (TIA) are at increased risk for future cardiovascular events despite current preventive therapies. The identification of insulin resistance as a risk factor for stroke and myocardial infarction raised the possibility that pioglitazone, which improves insulin sensitivity, might benefit patients with cerebrovascular disease. In this multicenter, double-blind trial, we randomly assigned 3876 patients who had had a recent ischemic stroke or TIA to receive either pioglitazone (target dose, 45 mg daily) or placebo. Eligible patients did not have diabetes but were found to have insulin resistance on the basis of a score of more than 3.0 on the homeostasis model assessment of insulin resistance (HOMA-IR) index. The primary outcome was fatal or nonfatal stroke or myocardial infarction. By 4.8 years, a primary outcome had occurred in 175 of 1939 patients (9.0%) in the pioglitazone group and in 228 of 1937 (11.8%) in the placebo group (hazard ratio in the pioglitazone group, 0.76; 95% confidence interval [CI], 0.62 to 0.93; P=0.007). Diabetes developed in 73 patients (3.8%) and 149 patients (7.7%), respectively (hazard ratio, 0.48; 95% CI, 0.33 to 0.69; Pischemic stroke or TIA, the risk of stroke or myocardial infarction was lower among patients who received pioglitazone than among those who received placebo. Pioglitazone was also associated with a lower risk of diabetes but with higher risks of weight gain, edema, and fracture. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT00091949.).

  20. Voluntary exercise prevents oxidative stress in the brain of phenylketonuria mice

    NARCIS (Netherlands)

    Mazzola, Priscila Nicolao; Bruinenberg, Vibeke; Anjema, Karen; van Vliet, Danique; Dutra-Filho, Carlos Severo; van Spronsen, Francjan J; van der Zee, Eddy A; Zschocke, Johannes; Baumgartner, Matthias; Patterson, Marc; Rahman, Shamima

    2015-01-01

    BACKGROUND: High phenylalanine levels in phenylketonuria (PKU) have been associated with brain oxidative stress and amino acid imbalance. Exercise has been shown to improve brain function in hyperphenylalaninemia and neurodegenerative diseases. This study aimed to verify the effects of exercise on

  1. Association of Osteopontin, Neopterin, and Myeloperoxidase With Stroke Risk in Patients With Prior Stroke or Transient Ischemic Attacks: Results of an Analysis of 13 Biomarkers From the Stroke Prevention by Aggressive Reduction in Cholesterol Levels Trial.

    Science.gov (United States)

    Ganz, Peter; Amarenco, Pierre; Goldstein, Larry B; Sillesen, Henrik; Bao, Weihang; Preston, Gregory M; Welch, K Michael A

    2017-12-01

    Established risk factors do not fully identify patients at risk for recurrent stroke. The SPARCL trial (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) evaluated the effect of atorvastatin on stroke risk in patients with a recent stroke or transient ischemic attack and no known coronary heart disease. This analysis explored the relationships between 13 plasma biomarkers assessed at trial enrollment and the occurrence of outcome strokes. We conducted a case-cohort study of 2176 participants; 562 had outcome strokes and 1614 were selected randomly from those without outcome strokes. Time to stroke was evaluated by Cox proportional hazards models. There was no association between time to stroke and lipoprotein-associated phospholipase A 2 , monocyte chemoattractant protein-1, resistin, matrix metalloproteinase-9, N-terminal fragment of pro-B-type natriuretic peptide, soluble vascular cell adhesion molecule-1, soluble intercellular adhesion molecule-1, or soluble CD40 ligand. In adjusted analyses, osteopontin (hazard ratio per SD change, 1.362; P strokes. After adjustment for the Stroke Prognostic Instrument-II and treatment, osteopontin, neopterin, and myeloperoxidase remained independently associated with outcome strokes. The addition of these 3 biomarkers to Stroke Prognostic Instrument-II increased the area under the receiver operating characteristic curve by 0.023 ( P =0.015) and yielded a continuous net reclassification improvement (29.1%; P stroke and improved risk classification when added to a clinical risk algorithm. URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00147602. © 2017 American Heart Association, Inc.

  2. Clinical usefulness of a biomarker-based diagnostic test for acute stroke: the Biomarker Rapid Assessment in Ischemic Injury (BRAIN) study.

    Science.gov (United States)

    Laskowitz, Daniel T; Kasner, Scott E; Saver, Jeffrey; Remmel, Kerri S; Jauch, Edward C

    2009-01-01

    One of the significant limitations in the evaluation and management of patients with suspected acute cerebral ischemia is the absence of a widely available, rapid, and sensitive diagnostic test. The objective of the current study was to assess whether a test using a panel of biomarkers might provide useful diagnostic information in the early evaluation of stroke by differentiating patients with cerebral ischemia from other causes of acute neurological deficit. A total of 1146 patients presenting with neurological symptoms consistent with possible stroke were prospectively enrolled at 17 different sites. Timed blood samples were assayed for matrix metalloproteinase 9, brain natriuretic factor, d-dimer, and protein S100beta. A separate cohort of 343 patients was independently enrolled to validate the multiple biomarker model approach. A diagnostic tool incorporating the values of matrix metalloproteinase 9, brain natriuretic factor, d-dimer, and S-100beta into a composite score was sensitive for acute cerebral ischemia. The multivariate model demonstrated modest discriminative capabilities with an area under the receiver operating characteristic curve of 0.76 for hemorrhagic stroke and 0.69 for all stroke (likelihood test P<0.001). When the threshold for the logistic model was set at the first quartile, this resulted in a sensitivity of 86% for detecting all stroke and a sensitivity of 94% for detecting hemorrhagic stroke. Moreover, results were reproducible in a separate cohort tested on a point-of-care platform. These results suggest that a biomarker panel may add valuable and time-sensitive diagnostic information in the early evaluation of stroke. Such an approach is feasible on a point-of-care platform. The rapid identification of patients with suspected stroke would expand the availability of time-limited treatment strategies. Although the diagnostic accuracy of the current panel is clearly imperfect, this study demonstrates the feasibility of incorporating a

  3. Randomized controlled trial of a coordinated care intervention to improve risk factor control after stroke or transient ischemic attack in the safety net: Secondary stroke prevention by Uniting Community and Chronic care model teams Early to End Disparities (SUCCEED).

    Science.gov (United States)

    Towfighi, Amytis; Cheng, Eric M; Ayala-Rivera, Monica; McCreath, Heather; Sanossian, Nerses; Dutta, Tara; Mehta, Bijal; Bryg, Robert; Rao, Neal; Song, Shlee; Razmara, Ali; Ramirez, Magaly; Sivers-Teixeira, Theresa; Tran, Jamie; Mojarro-Huang, Elizabeth; Montoya, Ana; Corrales, Marilyn; Martinez, Beatrice; Willis, Phyllis; Macias, Mireya; Ibrahim, Nancy; Wu, Shinyi; Wacksman, Jeremy; Haber, Hilary; Richards, Adam; Barry, Frances; Hill, Valerie; Mittman, Brian; Cunningham, William; Liu, Honghu; Ganz, David A; Factor, Diane; Vickrey, Barbara G

    2017-02-06

    Recurrent strokes are preventable through awareness and control of risk factors such as hypertension, and through lifestyle changes such as healthier diets, greater physical activity, and smoking cessation. However, vascular risk factor control is frequently poor among stroke survivors, particularly among socio-economically disadvantaged blacks, Latinos and other people of color. The Chronic Care Model (CCM) is an effective framework for multi-component interventions aimed at improving care processes and outcomes for individuals with chronic disease. In addition, community health workers (CHWs) have played an integral role in reducing health disparities; however, their effectiveness in reducing vascular risk among stroke survivors remains unknown. Our objectives are to develop, test, and assess the economic value of a CCM-based intervention using an Advanced Practice Clinician (APC)-CHW team to improve risk factor control after stroke in an under-resourced, racially/ethnically diverse population. In this single-blind randomized controlled trial, 516 adults (≥40 years) with an ischemic stroke, transient ischemic attack or intracerebral hemorrhage within the prior 90 days are being enrolled at five sites within the Los Angeles County safety-net setting and randomized 1:1 to intervention vs usual care. Participants are excluded if they do not speak English, Spanish, Cantonese, Mandarin, or Korean or if they are unable to consent. The intervention includes a minimum of three clinic visits in the healthcare setting, three home visits, and Chronic Disease Self-Management Program group workshops in community venues. The primary outcome is blood pressure (BP) control (systolic BP control of other vascular risk factors including lipids and hemoglobin A1c, (3) inflammation (C reactive protein [CRP]), (4) medication adherence, (5) lifestyle factors (smoking, diet, and physical activity), (6) estimated relative reduction in risk for recurrent stroke or myocardial

  4. Neural Responses to Injury: Prevention, Protection and Repair; Volume 7: Role Growth Factors and Cell Signaling in the Response of Brain and Retina to Injury

    National Research Council Canada - National Science Library

    Bazan, Nicolas

    1996-01-01

    ...: Prevention, Protection, and Repair, Subproject: Role of Growth Factors and Cell Signaling in the Response of Brain and Retina to Injury, are as follows: Species Rat(Albino Wistar), Number Allowed...

  5. Relationship between vascular dysfunction in peripheral arteries and ischemic episodes during daily life in patients with ischemic heart disease and hypercholesterolemia

    DEFF Research Database (Denmark)

    Søndergaard, Eva; Møller, Jacob E; Egstrup, Kenneth

    2002-01-01

    BACKGROUND: It is well established that endothelial dysfunction is present in patients with ischemic heart disease and hypercholesterolemia. Some of these patients will have signs of transient myocardial ischemia during Holter monitoring. We sought to describe the correlation between daily life...... cardiovascular risk factors. CONCLUSIONS: These results indicate a significant relationship between ischemic episodes and vascular dysfunction in patients with ischemic heart disease and hypercholesterolemia and may justify an aggressive preventive therapy targeted directly at the endothelium....

  6. Pharmacokinetic Study of Piracetam in Focal Cerebral Ischemic Rats.

    Science.gov (United States)

    Paliwal, Pankaj; Dash, Debabrata; Krishnamurthy, Sairam

    2018-04-01

    Cerebral ischemia affects hepatic enzymes and brain permeability extensively. Piracetam was investigated up to phase III of clinical trials and there is lack of data on brain penetration in cerebral ischemic condition. Thus, knowledge of the pharmacokinetics and brain penetration of piracetam during ischemic condition would aid to improve pharmacotherapeutics in ischemic stroke. Focal cerebral ischemia was induced by middle cerebral artery occlusion for 2 h in male Wistar rats followed by reperfusion. After 24 h of middle cerebral artery occlusion or 22 h of reperfusion, piracetam was administered for pharmacokinetic, brain penetration, and pharmacological experiments. In pharmacokinetic study, blood samples were collected at different time points after 200-mg/kg (oral) and 75-mg/kg (intravenous) administration of piracetam through right external jugular vein cannulation. In brain penetration study, the cerebrospinal fluid, systemic blood, portal blood, and brain samples were collected at pre-designated time points after 200-mg/kg oral administration of piracetam. In a separate experiment, the pharmacological effect of the single oral dose of piracetam in middle cerebral artery occlusion was assessed at a dose of 200 mg/kg. All the pharmacokinetic parameters of piracetam including area under curve (AUC 0-24 ), maximum plasma concentration (C max ), time to reach the maximum plasma concentration (t max ), elimination half-life (t 1/2 ), volume of distribution (V z ), total body clearance, mean residence time, and bioavailability were found to be similar in ischemic stroke condition except for brain penetration. Piracetam exposure (AUC 0-2 ) in brain and CSF were found to be 2.4- and 3.1-fold higher, respectively, in ischemic stroke compared to control rats. Piracetam significantly reduced infarct volume by 35.77% caused by middle cerebral artery occlusion. There was no change in the pharmacokinetic parameters of piracetam in the ischemic stroke model except for

  7. Molecular mechanisms of ischemic preconditioning in the kidney

    Science.gov (United States)

    Haase, Volker H.

    2015-01-01

    More effective therapeutic strategies for the prevention and treatment of acute kidney injury (AKI) are needed to improve the high morbidity and mortality associated with this frequently encountered clinical condition. Ischemic and/or hypoxic preconditioning attenuates susceptibility to ischemic injury, which results from both oxygen and nutrient deprivation and accounts for most cases of AKI. While multiple signaling pathways have been implicated in renoprotection, this review will focus on oxygen-regulated cellular and molecular responses that enhance the kidney's tolerance to ischemia and promote renal repair. Central mediators of cellular adaptation to hypoxia are hypoxia-inducible factors (HIFs). HIFs play a crucial role in ischemic/hypoxic preconditioning through the reprogramming of cellular energy metabolism, and by coordinating adenosine and nitric oxide signaling with antiapoptotic, oxidative stress, and immune responses. The therapeutic potential of HIF activation for the treatment and prevention of ischemic injuries will be critically examined in this review. PMID:26311114

  8. Absent collateral function of the circle of Willis as risk factor for ischemic stroke

    NARCIS (Netherlands)

    Hoksbergen, A. W. J.; Legemate, D. A.; Csiba, L.; Csáti, G.; Síró, P.; Fülesdi, B.

    2003-01-01

    Background. Autopsy studies show a higher prevalence of circle of Willis anomalies in brains with signs of ischemic infarction. Our goal was to examine the collateral function of the circle of Willis in ischemic stroke patients and to assess in a case-control study if a collateral deficient circle

  9. Increased serum neuron specific enolase concentrations in patients with hyperglycemic cortical ischemic stroke

    NARCIS (Netherlands)

    Elting, JW; De Keyser, J; Sulter, G.

    1998-01-01

    A detrimental effect of hyperglycemia in ischemic brain has been demonstrated in laboratory experiments and it has been found that hyperglycemia in ischemic stroke is a predictor of poor outcome. We determined serum neuron specific enolase (NSE) concentrations in 41 consecutive patients with a

  10. Prevention and management of brain edema in patients with acute liver failure

    DEFF Research Database (Denmark)

    Wendon, J.; Larsen, Finn Stolze

    2008-01-01

    1. Intracranial pressure is the pressure exerted by the cranial contents on the dural envelope and consists of the partial pressures of the brain, blood, and cerebrospinal fluid. 2. Severe cases of acute liver failure are frequently complicated by brain edema (due to cytotoxic edema) and an incre......1. Intracranial pressure is the pressure exerted by the cranial contents on the dural envelope and consists of the partial pressures of the brain, blood, and cerebrospinal fluid. 2. Severe cases of acute liver failure are frequently complicated by brain edema (due to cytotoxic edema......) and an increase in cerebral blood flow while the cerebrospinal fluid volume remains constant. 3. The development of intracranial hypertension in patients with acute liver failure may be controlled by manipulation of the position, body temperature, plasma tonicity, arterial carbon dioxide tension, and arterial...

  11. Sex differences in behavioral outcome following neonatal hypoxia ischemia: insights from a clinical meta-analysis and a rodent model of induced hypoxic ischemic brain injury.

    Science.gov (United States)

    Smith, Amanda L; Alexander, Michelle; Rosenkrantz, Ted S; Sadek, Mona Lisa; Fitch, R Holly

    2014-04-01

    Hypoxia ischemia (HI; reduced oxygen and/or blood flow to the brain) is one of the most common injuries among preterm infants and term infants with birth complications. Both populations show cognitive/behavioral deficits, including impairments in sensory, learning/memory, and attention domains. Clinical data suggests a sex difference in HI outcomes, with males exhibiting more severe cognitive/behavioral deficits relative to matched females. Our laboratory has also reported more severe behavioral deficits among male rats with induced HI relative to females with comparable injury (Hill et al., 2011a,b). The current study initially examined published clinical studies from the past 20years where long-term IQ outcome scores for matched groups of male and female premature infants were reported separately (IQ being the most common outcome measure). A meta-analysis revealed a female "advantage," as indicated by significantly better scores on performance and full scale IQ (but not verbal IQ) for premature females. We then utilized a rodent model of neonatal HI injury to assess sham and postnatal day 7 (P7) HI male and female rats on a battery of behavioral tasks. Results showed expected deficits in HI male rats, but also showed task-dependent sex differences, with HI males having significantly larger deficits than HI females on some tasks but equivalent deficits on other tasks. In contrast to behavioral results, post mortem neuropathology associated with HI was comparable across sex. These findings suggest: 1) neonatal female "protection" in some behavioral domains, as indexed by superior outcome following early injury relative to males; and 2) female protection may entail sex-specific plasticity or compensation, rather than a reduction in gross neuropathology. Further exploration of the mechanisms underlying this sex effect could aid in neuroprotection efforts for at-risk neonates in general, and males in particular. Moreover, our current report of comparable anatomical

  12. Neuroprotective effects of the antioxidant action of 2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride against ischemic neuronal damage in the brain

    Directory of Open Access Journals (Sweden)

    Soo Young Choi

    2013-07-01

    Full Text Available Ischemia is characterized by oxidative stress and changes in theantioxidant defense system. Our recent in vitro study showedthat 2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochlorideprotects cortical astrocytes against oxidative stress. In the currentstudy, we examined the effects of 2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride on ischemia-induced neuronaldamage in a gerbil ischemia/reperfusion models. Extensive neuronaldeath in the hippocampal CA1 area was observed 4 daysafter ischemia/reperfusion. Intraperitoneal injection of 2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride (0.3 mg/kgbody weight significantly prevented neuronal death in the CA1region of the hippocampus in response to transient forebrainischemia. 2-Cyclopropylimino-3-methyl-1,3-thiazoline hydrochlorideadministration reduced ischemia-induced increases inreactive oxygen species levels and malondialdehyde content. Italso attenuated the associated reductions in glutathione level andsuperoxide dismutase, catalase, and glutathione peroxidaseactivities. Taken together, our results suggest that 2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride protects againstischemia-induced neuronal damage by reducing oxidative stressthrough its antioxidant actions. [BMB Reports 2013; 46(7:370-375

  13. Long-Term Prognosis of Ischemic Stroke in Young Adults

    OpenAIRE

    Varona, Jose F.

    2010-01-01

    There is limited information about long-term prognosis of ischemic stroke in young adults. Giving the potentially negative impact in physical, social, and emotional aspects of an ischemic stroke in young people, providing early accurate long-term prognostic information is very important in this clinical setting. Moreover, detection of factors associated with bad outcomes (death, recurrence, moderate-to-severe disability) help physicians in optimizing secondary prevention strategies. The prese...

  14. Pumping the Brakes: Neurotrophic Factors for the Prevention of Cognitive Impairment and Dementia after Traumatic Brain Injury.

    Science.gov (United States)

    Corrigan, Frances; Arulsamy, Alina; Teng, Jason; Collins-Praino, Lyndsey E

    2017-03-01

    Traumatic brain injury (TBI) is the leading cause of disability and death worldwide, affecting as many as 54,000,000-60,000,000 people annually. TBI is associated with significant impairments in brain function, impacting cognitive, emotional, behavioral, and physical functioning. Although much previous research has focused on the impairment immediately following injury, TBI may have much longer-lasting consequences, including neuropsychiatric disorders and cognitive impairment. TBI, even mild brain injury, has also been recognized as a significant risk factor for the later development of dementia and Alzheimer's disease. Although the link between TBI and dementia is currently unknown, several proposed mechanisms have been put forward, including alterations in glucose metabolism, excitotoxicity, calcium influx, mitochondrial dysfunction, oxidative stress, and neuroinflammation. A treatment for the devastating long-term consequences of TBI is desperately needed. Unfortunately, however, no such treatment is currently available, making this a major area of unmet medical need. Increasing the level of neurotrophic factor expression in key brain areas may be one potential therapeutic strategy. Of the neurotrophic factors, granulocyte-colony stimulating factor (G-CSF) may be particularly effective for preventing the emergence of long-term complications of TBI, including dementia, because of its ability to reduce apoptosis, stimulate neurogenesis, and increase neuroplasticity.

  15. Neuronal Rho GTPase Rac1 elimination confers neuroprotection in a mouse model of permanent ischemic stroke.

    Science.gov (United States)

    Karabiyik, Cansu; Fernandes, Rui; Figueiredo, Francisco Rosário; Socodato, Renato; Brakebusch, Cord; Lambertsen, Kate Lykke; Relvas, João Bettencourt; Santos, Sofia Duque

    2017-09-28

    The Rho GTPase Rac1 is a multifunctional protein involved in distinct pathways ranging from development to pathology. The aim of the present study was to unravel the contribution of neuronal Rac1 in regulating the response to brain injury induced by permanent focal cerebral ischemia (pMCAO). Our results show that pMCAO significantly increased total Rac1 levels in wild type mice, mainly through rising nuclear Rac1, while a reduction in Rac1 activation was observed. Such changes preceded cell death induced by excitotoxic stress. Pharmacological inhibition of Rac1 in primary neuronal cortical cells prevented the increase in oxidative stress induced after overactivation of glutamate receptors. However, this was not sufficient to prevent the associated neuronal cell death. In contrast, RNAi-mediated knock down of Rac1 in primary cortical neurons prevented cell death elicited by glutamate excitotoxicity and decreased the activity of NADPH oxidase. To test whether in vivo down regulation of neuronal Rac1 was neuroprotective after pMCAO, we used tamoxifen-inducible neuron-specific conditional Rac1-knockout mice. We observed a significant 50% decrease in brain infarct volume of knockout mice and a concomitant increase in HIF-1α expression compared to littermate control mice, demonstrating that ablation of Rac1 in neurons is neuroprotective. Transmission electron microscopy performed in the ischemic brain showed that lysosomes in the infarct of Rac1- knockout mice were preserved at similar levels to those of non-infarcted tissue, while littermate mice displayed a decrease in the number of lysosomes, further corroborating the notion that Rac1 ablation in neurons is neuroprotective. Our results demonstrate that Rac1 plays important roles in the ischemic pathological cascade and that modulation of its levels is of therapeutic interest. © 2017 International Society of Neuropathology.

  16. Overexpression of caveolin-1 attenuates brain edema by inhibiting tight junction degradation.

    Science.gov (United States)

    Choi, Kang-Ho; Kim, Hyung-Seok; Park, Man-Seok; Lee, Eun-Bin; Lee, Jung-Kil; Kim, Joon-Tae; Kim, Ja-Hae; Lee, Min-Cheol; Lee, Hong-Joon; Cho, Ki-Hyun

    2016-10-18

    Cerebral edema from the disruption of the blood-brain barrier (BBB) after cerebral ischemia is a major cause of morbidity and mortality as well as a common event in patients with stroke. Caveolins (Cavs) are thought to regulate BBB functions. Here, we report for the first time that Cav-1 overexpression (OE) decreased brain edema from BBB disruption following ischemic insult. Edema volumes and Cav-1 expression levels were measured following photothrombosis and middle cerebral artery occlusion (MCAO). Endothelial cells that were transduced with a Cav-1 lentiviral expression vector were transplanted into rats. BBB permeability was quantified with Evans blue extravasation. Edema volume was determined from measures of the extravasation area, brain water content, and average fluorescence intensity after Cy5.5 injections. Tight junction (TJ) protein expression was measured with immunoblotting. Cav-1 expression levels and vasogenic brain edema correlated strongly after ischemic insult. Cav-1 expression and BBB disruption peaked 3 d after the MCAO. In addition, intravenous administration of endothelial cells expressing Cav-1 effectively increased the Cav-1 levels 3 d after the MCAO ischemic insult. Importantly, Cav-1 OE ameliorated the vasogenic edema by inhibiting the degradation of TJ protein expression in the acute phase of ischemic stroke. These results suggested that Cav-1 OE protected the integrity of the BBB mainly by preventing the degradation of TJ proteins in rats. These findings need to be confirmed in a clinical setting in human subjects.

  17. Supplementation with different teas from Camellia sinensis prevents memory deficits and hippocampus oxidative stress in ischemia-reperfusion.

    Science.gov (United States)

    Martins, Alexandre; Schimidt, Helen L; Garcia, Alexandre; Colletta Altermann, Caroline Dalla; Santos, Francielli W; Carpes, Felipe P; da Silva, Weber Cláudio; Mello-Carpes, Pâmela B

    2017-09-01

    Memory and cognition impairments resultant of ischemic stroke could be minimized or avoided by antioxidant supplementation. In this regard, the neuroprotective potential of Green tea from Camellia sinensis has been investigated. However, there is a lack of information regarding the neuroprotective potential of others teas processed from the Camellia sinensis. Here we investigate the neuroprotective role of green, red, white and black tea on memory deficits and brain oxidative stress in a model of ischemic stroke in rats. Our findings show that green and red teas prevent deficits in object and social recognition memories, but only green tea protects against deficits in spatial memory and avoids hippocampal oxidative status and intense necrosis and others alterations in the brain tissue. In summary, green tea shows better neuroprotection in ischemic stroke than the others teas from Camellia sinensis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Prevention

    Science.gov (United States)

    ... Error processing SSI file About Heart Disease & Stroke Prevention Heart disease and stroke are an epidemic in ... secondhand smoke. Barriers to Effective Heart Disease & Stroke Prevention Many people with key risk factors for heart ...

  19. Biomarkers of Hypoxic Ischemic Encephalopathy in Newborns

    Directory of Open Access Journals (Sweden)

    Martha V. Douglas-Escobar

    2012-11-01

    Full Text Available As neonatal intensive care has evolved, the focus has shifted from improving mortality alone to an effort to improve both mortality and morbidity. The most frequent source of neonatal brain injury occurs as a result of hypoxic-ischemic injury. Hypoxic-ischemic injury occurs in about 2 of 1,000 full-term infants and severe injured infants will have lifetime disabilities and neurodevelopmental delays. Most recently, remarkable efforts toward neuroprotection have been started with the advent of therapeutic hypothermia and a key step in the evolution of neonatal neuroprotection is the discovery of biomarkers that enable the clinician-scientist to screen infants for brain injury, monitor progression of disease, identify injured brain regions, and assess efficacy of neuroprotective clinical trials. Lastly, biomarkers offer great hope identifying when an injury occurred shedding light on the potential pathophysiology and the most effective therapy. In this article, we will review biomarkers of HIE including S100b, neuron specific enolase, umbilical cord IL-6, CK-BB, GFAP, myelin basic protein, UCHL-1, and pNF-H. We hope to contribute to the awareness, validation and clinical use of established as well as novel neonatal brain injury biomarkers.

  20. Transient ischemic attack: diagnostic evaluation.

    Science.gov (United States)

    Messé, Steven R; Jauch, Edward C

    2008-08-01

    A transient ischemic attack portends significant risk of a stroke. Consequently, the diagnostic evaluation in the emergency department is focused on identifying high-risk causes so that preventive strategies can be implemented. The evaluation consists of a facilitated evaluation of the patient's metabolic, cardiac, and neurovascular systems. At a minimum, the following tests are recommended: fingerstick glucose level, electrolyte levels, CBC count, urinalysis, and coagulation studies; noncontrast computed tomography (CT) of the head; electrocardiography; and continuous telemetry monitoring. Vascular imaging studies, such as carotid ultrasonography, CT angiography, or magnetic resonance angiography, should be performed on an urgent basis and prioritized according to the patient's risk stratification for disease. Consideration should be given for echocardiography if no large vessel abnormality is identified.

  1. Genesis of the use of corticosteroids in the treatment and prevention of brain edema.

    Science.gov (United States)

    McClelland, Shearwood; Long, Donlin M

    2008-04-01

    Since the groundbreaking article from the University of Minnesota in 1961 by Drs. Galicich, French, and Melby describing the use of dexamethasone for peritumoral cerebral edema, the use of corticosteroids in patients with brain tumors has become routine. Unfortunately, little has been reported regarding the environment that fostered arguably the greatest translational research contribution in the history of neurosurgery. During a pilot study to assess corticosteroid uptake in brain tumors, Dr. Galicich observed that patients given a large dose of corticosteroids just before craniotomy had a relatively benign postoperative course. This led, in October 1959, to the administration of high-dose corticosteroids to a patient with a large recurrent glioblastoma who was semicomatose and severely hemiparetic. The results were dramatic, with almost complete resolution of neurological deficit during a period of several days and marked reduction of midline shift on repeat angiograms. This finding prompted the studies that confirmed the efficacy of high-dose corticosteroids in reducing peritumoral brain edema in humans reported in the 1961 article. After publication, a revolution in brain tumor management occurred because corticosteroid therapy markedly reduced the morbidity and mortality associated with brain tumors both in the United States and worldwide. The combination of astute clinical observation and follow up by rigorous clinical research at the University of Minnesota resulted in one of the greatest contributions in the history of neurosurgery, rivaled only by the operative microscope in its effect on morbidity, and unsurpassed in reduction of mortality.

  2. Brain magnetic resonance imaging of infants exposed prenatally to buprenorphine

    Energy Technology Data Exchange (ETDEWEB)

    Kahila, H.; Kivitie-Kallio, S.; Halmesmaki, E.; Valanne, L.; Autti, T. [Dept. of Obstetrics and Gynecology, Dept. of Pediatrics, and Helsinki Medical Imaging Center, Helsinki Univ. Central Hospital (Finland)

    2007-02-15

    Purpose: To evaluate the brains of newborns exposed to buprenorphine prenatally. Material and Methods: Seven neonates followed up antenatally in connection with their mothers' buprenorphine replacement therapy underwent 1.5T magnetic resonance imaging (MRI) of the brain before the age of 2 months. The infants were born to heavy drug abusers. Four mothers were hepatitis C positive, and all were HIV negative. All mothers smoked tobacco and used benzodiazepines. All pregnancies were full term, and no perinatal asphyxia occurred. All but one neonate had abstinence syndrome and needed morphine replacement therapy. Results: Neither structural abnormalities nor abnormalities in signal intensity were recorded. Conclusion: Buprenorphine replacement therapy does not seem to cause any major structural abnormalities of the brain, and it may prevent known hypoxic-ischemic brain changes resulting from uncontrolled drug abuse. Longitudinal studies are needed to assess possible abnormalities in the brain maturation process.

  3. Brain magnetic resonance imaging of infants exposed prenatally to buprenorphine

    International Nuclear Information System (INIS)

    Kahila, H.; Kivitie-Kallio, S.; Halmesmaki, E.; Valanne, L.; Autti, T.

    2007-01-01

    Purpose: To evaluate the brains of newborns exposed to buprenorphine prenatally. Material and Methods: Seven neonates followed up antenatally in connection with their mothers' buprenorphine replacement therapy underwent 1.5T magnetic resonance imaging (MRI) of the brain before the age of 2 months. The infants were born to heavy drug abusers. Four mothers were hepatitis C positive, and all were HIV negative. All mothers smoked tobacco and used benzodiazepines. All pregnancies were full term, and no perinatal asphyxia occurred. All but one neonate had abstinence syndrome and needed morphine replacement therapy. Results: Neither structural abnormalities nor abnormalities in signal intensity were recorded. Conclusion: Buprenorphine replacement therapy does not seem to cause any major structural abnormalities of the brain, and it may prevent known hypoxic-ischemic brain changes resulting from uncontrolled drug abuse. Longitudinal studies are needed to assess possible abnormalities in the brain maturation process

  4. Ischemic strokes and migraine

    International Nuclear Information System (INIS)

    Bousser, M.G.; Baron, J.C.; Chiras, J.

    1985-01-01

    Lasting neurological deficits, though most infrequent, do occur in migrainous subjects and are well documented by clinical angiographic computed tomographic (CT scan) and even pathological studies. However the mechanism of cerebral ischemia in migraine remains widely unknown and the precise role of migraine in the pathogenesis of ischemic strokes is still debated. (orig./MG)

  5. TIA (Transient Ischemic Attack)

    Science.gov (United States)

    ... Hemorrhagic | Cryptogenic | Understanding Stroke Risks Learn about the stroke risk factors you can control, teat and improve. Share the ... About Ischemic Strokes Let's Talk About Children and Stroke Let's Talk About Risk Factors for Stroke Let's Talk About Lifestyle Changes to ...

  6. The in vitro blood-brain barrier model under OGD condition

    DEFF Research Database (Denmark)

    Tornabene, Erica; Helms, Hans Christian Cederberg; Berndt, Philipp

    Introduction - The blood-brain barrier (BBB) is a physical, transport and metabolic barrier which plays a key role in preventing uncontrolled exchanges between blood and brain, ensuring an optimal environment for neurons activity. This extent interface is created by the endothelial cells forming...... the wall of brain capillaries. The restrictive nature of the BBB is due to the presence of tight junctions, which seal the paracellular space, a low number of endocytotic vesicles and the presence of efflux transporters, resulting in a very tight layer. Ischemic insult and the subsequent reperfusion...

  7. PARP Inhibition Prevents Ethanol-Induced Neuroinflammatory Signaling and Neurodegeneration in Rat Adult-Age Brain Slice Cultures

    Science.gov (United States)

    Tajuddin, Nuzhath; Kim, Hee-Yong

    2018-01-01

    Using rat adult-age hippocampal-entorhinal cortical (HEC) slice cultures, we examined the role of poly [ADP-ribose] polymerase (PARP) in binge ethanol’s brain inflammatory and neurodegenerative mechanisms. Activated by DNA strand breaks, PARP (principally PARP1 in the brain) promotes DNA repair via poly [ADP-ribose] (PAR) products, but PARP overactivation triggers regulated neuronal necrosis (e.g., parthanatos). Previously, we found that brain PARP1 levels were upregulated by neurotoxic ethanol binges in adult rats and HEC slices, and PARP inhibitor PJ34 abrogated slice neurodegeneration. Binged HEC slices also exhibited increased Ca+2-dependent phospholipase A2 (PLA2) isoenzymes (cPLA2 IVA and sPLA2 IIA) that mobilize proinflammatory ω6 arachidonic acid (ARA). We now find in 4-day–binged HEC slice cultures (100 mM ethanol) that PARP1 elevations after two overnight binges precede PAR, cPLA2, and sPLA2 enhancements by 1 day and high-mobility group box-1 (HMGB1), an ethanol-responsive alarmin that augments proinflammatory cytokines via toll-like receptor-4 (TLR4), by 2 days. After verifying that PJ34 effectively blocks PARP activity (↑PAR), we demonstrated that, like PJ34, three other PARP inhibitors—olaparib, veliparib, and 4-aminobenzamide—provided neuroprotection from ethanol. Importantly, PJ34 and olaparib also prevented ethanol’s amplification of the PLA2 isoenzymes, and two PLA2 inhibitors were neuroprotective—thus coupling PARP to PLA2, with PLA2 activity promoting neurodegeneration. Also, PJ34 and olaparib blocked ethanol-induced HMGB1 elevations, linking brain PARP induction to TLR4 activation. The results provide evidence in adult brains that induction of PARP1 may mediate dual neuroinflammatory pathways (PLA2→phospholipid→ARA and HMGB1→TLR4→proinflammatory cytokines) that are complicit in binge ethanol-induced neurodegeneration. PMID:29339456

  8. Prevention and management of brain edema in patients with acute liver failure

    DEFF Research Database (Denmark)

    Wendon, J.; Larsen, Finn Stolze

    2008-01-01

    1. Intracranial pressure is the pressure exerted by the cranial contents on the dural envelope and consists of the partial pressures of the brain, blood, and cerebrospinal fluid. 2. Severe cases of acute liver failure are frequently complicated by brain edema (due to cytotoxic edema......) and an increase in cerebral blood flow while the cerebrospinal fluid volume remains constant. 3. The development of intracranial hypertension in patients with acute liver failure may be controlled by manipulation of the position, body temperature, plasma tonicity, arterial carbon dioxide tension, and arterial...

  9. Intermittent fasting attenuates inflammasome activity in ischemic stroke.

    Science.gov (United States)

    Fann, David Yang-Wei; Santro, Tomislav; Manzanero, Silvia; Widiapradja, Alexander; Cheng, Yi-Lin; Lee, Seung-Yoon; Chunduri, Prasad; Jo, Dong-Gyu; Stranahan, Alexis M; Mattson, Mark P; Arumugam, Thiruma V

    2014-07-01

    Recent findings have revealed a novel inflammatory mechanism that contributes to tissue injury in cerebral ischemia mediated by multi-protein complexes termed inflammasomes. Intermittent fasting (IF) can decrease the levels of pro-inflammatory cytokines in the periphery and brain. Here we investigated the impact of IF (16h of food deprivation daily) for 4months on NLRP1 and NLRP3 inflammasome activities following cerebral ischemia. Ischemic stroke was induced in C57BL/6J mice by middle cerebral artery occlusion, followed by reperfusion (I/R). IF decreased the activation of NF-κB and MAPK signaling pathways, the expression of NLRP1 and NLRP3 inflammasome proteins, and both IL-1β and IL-18 in the ischemic brain tissue. These findings demonstrate that IF can attenuate the inflammatory response and tissue damage following ischemic stroke by a mechanism involving suppression of NLRP1 and NLRP3 inflammasome activity. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Remote ischemic preconditioning: a novel protective method from ischemia reperfusion injury--a review.

    Science.gov (United States)

    Tapuria, Niteen; Kumar, Yogesh; Habib, Meer Mohammad; Abu Amara, Mahmoud; Seifalian, Alexander M; Davidson, Brian R

    2008-12-01

    Restoration of blood supply to an organ after a critical period of ischemia results in parenchymal injury and dysfunction of the organ referred to as reperfusion injury. Ischemia reperfusion injury is often seen in organ transplants, major organ resections and in shock. Ischemic preconditioning (IPC) is an adaptational response of briefly ischemic tissues which serves to protect against subsequent prolonged ischemic insults and reperfusion injury. Ischemic preconditioning can be mechanical or pharmacological. Direct mechanical preconditioning in which the target organ is exposed to brief ischemia prior to prolonged ischemia has the benefit of reducing ischemia-reperfusion injury (IRI) but its main disadvantage is trauma to major vessels and stress to the target organ. Remote (inter organ) preconditioning is a recent observation in which brief ischemia of one organ has been shown to confer protection on distant organs without direct stress to the organ. To discuss the evidence for remote IPC (RIPC), underlying mechanisms and possible clinical applications of RIPC. METHODS OF SEARCH: A Pubmed search with the keywords "ischemic preconditioning," "remote preconditioning," "remote ischemic preconditioning," and "ischemia reperfusion" was done. All articles on remote preconditioning up to September 2006 have been reviewed. Relevant reference articles from within these have been selected for further discussion. Experimental studies have demonstrated that the heart, liver, lung, intestine, brain, kidney and limbs are capable of producing remote preconditioning when subjected to brief IR. Remote intra-organ preconditioning was first described in the heart where brief ischemia in one territory led to protection in other areas. Translation of RIPC to clinical application has been demonstrated by the use of brief forearm ischemia in preconditioning the heart prior to coronary bypass and in reducing endothelial dysfunction of the contra lateral limb. Recently protection of the

  11. Description of an early cognitive behavioral intervention (UPFRONT-intervention) following mild traumatic brain injury to prevent persistent complaints and facilitate return to work

    NARCIS (Netherlands)

    Scheenen, Myrthe E; Visser-Keizer, Annemarie C.; van der Naalt, Joukje; Spikman, Jacoba M

    2017-01-01

    Purpose: Many patients with mild traumatic brain injury do not fully return to work owing to persistent posttraumatic complaints. Research suggests that preventing chronic complaints might be prevented by giving cognitive behavioral therapy early after injury. Therefore, a new cognitive behavioral

  12. Novel Therapeutic Effects of Leonurine On Ischemic Stroke: New Mechanisms of BBB Integrity

    Directory of Open Access Journals (Sweden)

    Qiu-Yan Zhang

    2017-01-01

    Full Text Available Stroke is a leading cause of morbidity and mortality globally. Leonurine (also named SCM-198, a compound extracted from Herba leonuri, was effective on the prevention of various cardiovascular and brain diseases. The purpose of this study was to explore the possible therapeutic potential of SCM-198 against ischemia reperfusion injury and underlying mechanisms. In the in vivo transient middle cerebral artery occlusion (tMCAO rat model, we found that treatment with SCM-198 could decrease infarct volume and improve neurological deficit by protecting against blood-brain barrier (BBB breakdown. In the in vitro model of cell oxygen-glucose deprivation and reoxygenation (OGD/R, consistent results were obtained with decreased reactive oxygen species (ROS production and maintained the BBB integrity. Further study demonstrated that SCM-198 increased the expression of histone deacetylase- (HDAC- 4 which could inhibit NADPH oxidase- (NOX- 4 and matrix metalloproteinase- (MMP- 9 expression, resulting in the elevation of tight junction proteins, including claudin-5, occludin, and zonula occluden- (ZO- 1. These results indicated SCM-198 protected BBB integrity by regulating the HDAC4/NOX4/MMP-9 tight junction pathway. Our findings provided novel insights into the protective effects and mechanisms of SCM-198 on ischemic stroke, indicating SCM-198 as a new class of potential drug against acute onset of ischemic stroke.

  13. Elucidation of mechanism of blood-brain barrier damage for prevention and treatment of vascular dementia.

    Science.gov (United States)

    Ueno, Masaki

    2017-03-28

    It is well-known that the blood-brain barrier (BBB) plays significant roles in transporting intravascular substances into the brain. The BBB in cerebral capillaries essentially impedes the influx of intravascular compounds from the blood to the brain, while nutritive substances, such as glucose, can be selectively transported through several types of influx transporters in endothelial cells. In the choroid plexus, intravascular substances can invade the parenchyma as fenestrations exist in endothelial cells of capillaries. However, the substances cannot invade the ventricles easily as there are tight junctions between epithelial cells in the choroid plexus. This restricted movement of the substances across the cytoplasm of the epithelial cells constitutes a blood-cerebrospinal fluid barrier (BCSFB). In the brain, there are circumventricular organs, in which the barrier function is imperfect in capillaries. Accordingly, it is reasonable to consider that intravascular substances can move in and around the parenchyma of the organs. Actually, it was reported in mice that intravascular substances moved in the corpus callosum, medial portions of the hippocampus, and periventricular areas via the subfornical organs or the choroid plexus. Regarding pathways of intracerebral interstitial and cerebrospinal fluids to the outside of the brain, two representative drainage pathways, or perivascular drainage and glymphatic pathways, are being established. The first is the pathway in a retrograde direction to the blood flow through the basement membrane in walls of cerebral capillaries, the tunica media of arteries, and the vessels walls of the internal carotid artery. The second is in an anterograde direction to blood flow through the para-arterial routes, aquaporin 4-dependent transport through the astroglial cytoplasm, and para-venous routes, and then the fluids drain into the subarachnoid CSF. These fluids are finally considered to drain into the cervical lymph nodes or veins

  14. Chronic Exposure to Subtherapeutic Antibiotics Aggravates Ischemic Stroke Outcome in Mice

    Directory of Open Access Journals (Sweden)

    Xiao-Hui Dong

    2017-10-01

    Full Text Available Subtherapeutic antibiotics have been widely used in agriculture since the 1950s, which can be accumulated in human body through various approaches and may have long-term consequences. However, there is limited information about the link between chronic subtherapeutic antibiotic exposure and the outcome of ischemic brain injury. Here we showed that long-term treatment with subtherapeutic chlortetracycline, penicillin or vancomycin, which were widely used in agriculture approved by US Food and Drug Administration (FDA, could impair EPC functions, reduce ischemic brain angiogenesis and aggravate cerebral ischemic injury and long-term stroke outcomes in mice. In addition, transplantated EPCs from chronic antibiotic-treated mice showed a lower therapeutic effect on cerebral ischemic injury reduction and local angiogenesis promotion compared to those from control mice, and EPCs from the donor animals could integrate into the recipient ischemic brain in mice. Furthermore, transplanted EPCs might exert paracrine effects on cerebral ischemic injury reduction in mice, which could be impaired by chronic antibiotic exposure. In conclusion, chronic subtherapeutic antibiotic exposure aggravated cerebral ischemic injury in mice, which might be partly attributed to the impairment of both EPC-mediated angiogenesis and EPCs' paracrine effects. These findings reveal a previously unrecognized impact of chronic subtherapeutic antibiotic exposure on ischemic injury.

  15. Intravenous immunoglobulins prevent the breakdown of the blood-brain barrier in experimentally induced sepsis.

    Science.gov (United States)

    Esen, Figen; Senturk, Evren; Ozcan, Perihan E; Ahishali, Bulent; Arican, Nadir; Orhan, Nurcan; Ekizoglu, Oguzhan; Kucuk, Mutlu; Kaya, Mehmet

    2012-04-01

    The effects of immunoglobulin G and immunoglobulins enriched with immunoglobulin A and immunoglobulin M on blood-brain barrier integrity and survival rates in septic rats were comparatively investigated. Sepsis was induced by cecal ligation and perforation in Sprague-Dawley rats. The animals were divided into the following groups: Sham, cecal ligation and perforation, cecal ligation and perforation plus immunoglobulin G (250 mg/kg, intravenous), and cecal ligation and perforation plus immunoglobulins enriched with immunoglobulin A and immunoglobulin M (250 mg/kg, intravenous). Immunoglobulins were administered 5 mins before cecal ligation and perforation and the animals were observed for behavioral changes for 24 hrs following cecal ligation and perforation. Blood-brain barrier permeability was functionally and structurally evaluated by determining the extravasation of Evans Blue and horseradish peroxidase tracers, respectively. Immunohistochemistry and Western blotting for occludin were performed. The high mortality rate (34%) noted in the septic rats was decreased to 15% and 3% by immunoglobulin G and immunoglobulins enriched with immunoglobulin A and immunoglobulin M, respectively (p immunoglobulin G and immunoglobulins enriched with immunoglobulin A and immunoglobulin M alleviated the symptoms of sickness behavior in the septic rats, with the animals becoming healthy and active. Increased extravasation of Evans Blue into the brain tissue of the septic rats was markedly decreased with the administration of both immunoglobulin G and immunoglobulins enriched with immunoglobulin A and immunoglobulin M (p immunoglobulin G or immunoglobulins enriched with immunoglobulin A and immunoglobulin M treatment, no ultrastructural evidence of leaky capillaries in the brain was observed in the septic rats, indicating the blockade of the transcellular pathway by immunoglobulins administration. Our study suggests that immunoglobulin G and immunoglobulins enriched with

  16. Relation between reperfusion and hemorrhagic transformation in acute ischemic stroke

    NARCIS (Netherlands)

    Horsch, Alexander D; Dankbaar, Jan Willem; van der Graaf, Yolanda; Niesten, Joris M; van Seeters, Tom; van der Schaaf, Irene C; Kappelle, L Jaap; Velthuis, Birgitta K

    2015-01-01

    INTRODUCTION: Intravenous recombinant tissue plasminogen activator (IV-rtPA) is given in acute ischemic stroke patients to achieve reperfusion. Hemorrhagic transformation (HT) is a serious complication of IV-rtPA treatment and related to blood-brain barrier (BBB) injury. It is unclear whether HT

  17. Relation between reperfusion and hemorrhagic transformation in acute ischemic stroke

    NARCIS (Netherlands)

    Horsch, Alexander D.; Dankbaar, Jan Willem; van der Graaf, Yolanda; Niesten, Joris M.; van Seeters, Tom; van der Schaaf, Irene C.; Kappelle, L. Jaap; Velthuis, Birgitta K.; Majoie, C. B.; Roos, Y. B.; Duijm, L. E.; Keizer, K.; van der Lugt, A.; Dippel, D. W.; Droogh-deGreve, K. E.; van Walderveen, M. A.; Wermer, M. J.; Lycklama à Nijeholt, G. J.; Boiten, J.; Duyndam, D.; Kwa, V. I.; Meijer, F. J.; van Dijk, E. J.; Kesselring, F. O.; Hofmeijer, J.; Vos, J. A.; Schonewille, W. J.; van Rooij, W. J.; de Kort, P. L.; Pleiter, C. C.; Bakker, S. L.; Bot, J.; Visser, M. C.; Velthuis, B. K.; van der Schaaf, I. C.; Dankbaar, J. W.; Mali, W. P.; van Seeters, T.; Horsch, A. D.; Niesten, J. M.; Biessels, G. J.; Kappelle, L. J.; Luitse, M. J.; van der Graaf, Y.

    2015-01-01

    Intravenous recombinant tissue plasminogen activator (IV-rtPA) is given in acute ischemic stroke patients to achieve reperfusion. Hemorrhagic transformation (HT) is a serious complication of IV-rtPA treatment and related to blood-brain barrier (BBB) injury. It is unclear whether HT occurs secondary

  18. Early environmental enrichment affects neurobehavioral development and prevents brain damage in rats submitted to neonatal hypoxia-ischemia.

    Science.gov (United States)

    Schuch, Clarissa Pedrini; Diaz, Ramiro; Deckmann, Iohanna; Rojas, Joseane Jiménez; Deniz, Bruna Ferrary; Pereira, Lenir Orlandi

    2016-03-23

    Our previous results demonstrated improved cognition in adolescent rats housed in environmental enrichment (EE) that underwent neonatal hypoxia-ischemia (HI). The aim of this study was to investigate the effects of early EE on neurobehavioral development and brain damage in rats submitted to neonatal HI. Wistar rats were submitted to the HI procedure on the 7th postnatal day (PND) and housed in an enriched environment (8th-20th PND). The maturation of physical characteristics and the neurological reflexes were evaluated and the volume of striatum, corpus callosum and neocortex was measured. Data analysis demonstrated a clear effect of EE on neurobehavioral development; also, daily performance was improved in enriched rats on righting, negative geotaxis and cliff aversion reflex. HI caused a transient motor deficit on gait latency. Brain atrophy was found in HI animals and this damage was partially prevented by the EE. In conclusion, early EE stimulated neurobehavioral development in neonate rats and also protects the neocortex and the corpus callosum from atrophy following HI. These findings reinforce the potential of EE as a strategy for rehabilitation following neonatal HI and provide scientific support to the use of this therapeutic strategy in the treatment of neonatal brain injuries in humans. Copyright © 2016. Published by Elsevier Ireland Ltd.

  19. Standardized Environmental Enrichment Supports Enhanced Brain Plasticity in Healthy Rats and Prevents Cognitive Impairment in Epileptic Rats

    Science.gov (United States)

    Kouchi, Hayet Y.; Bodennec, Jacques; Morales, Anne; Georges, Béatrice; Bonnet, Chantal; Bouvard, Sandrine; Sloviter, Robert S.; Bezin, Laurent

    2013-01-01

    Environmental enrichment of laboratory animals influences brain plasticity, stimulates neurogenesis, increases neurotrophic factor expression, and protects against the effects of brain insult. However, these positive effects are not constantly observed, probably because standardized procedures of environmental enrichment are lacking. Therefore, we engineered an enriched cage (the Marlau™ cage), which offers: (1) minimally stressful social interactions; (2) increased voluntary exercise; (3) multiple entertaining activities; (4) cognitive stimulation (maze exploration), and (5) novelty (maze configuration changed three times a week). The maze, which separates food pellet and water bottle compartments, guarantees cognitive stimulation for all animals. Compared to rats raised in groups in conventional cages, rats housed in Marlau™ cages exhibited increased cortical thickness, hippocampal neurogenesis and hippocampal levels of transcripts encoding various genes involved in tissue plasticity and remodeling. In addition, rats housed in Marlau™ cages exhibited better performances in learning and memory, decreased anxiety-associated behaviors, and better recovery of basal plasma corticosterone level after acute restraint stress. Marlau™ cages also insure inter-experiment reproducibility in spatial learning and brain gene expression assays. Finally, housing rats in Marlau™ cages after severe status epilepticus at weaning prevents the cognitive impairment observed in rats subjected to the same insult and then housed in conventional cages. By providing a standardized enriched environment for rodents during housing, the Marlau™ cage should facilitate the uniformity of environmental enrichment across laboratories. PMID:23342033

  20. Standardized environmental enrichment supports enhanced brain plasticity in healthy rats and prevents cognitive impairment in epileptic rats.

    Directory of Open Access Journals (Sweden)

    Raafat P Fares

    Full Text Available Environmental enrichment of laboratory animals influences brain plasticity, stimulates neurogenesis, increases neurotrophic factor expression, and protects against the effects of brain insult. However, these positive effects are not constantly observed, probably because standardized procedures of environmental enrichment are lacking. Therefore, we engineered an enriched cage (the Marlau™ cage, which offers: (1 minimally stressful social interactions; (2 increased voluntary exercise; (3 multiple entertaining activities; (4 cognitive stimulation (maze exploration, and (5 novelty (maze configuration changed three times a week. The maze, which separates food pellet and water bottle compartments, guarantees cognitive stimulation for all animals. Compared to rats raised in groups in conventional cages, rats housed in Marlau™ cages exhibited increased cortical thickness, hippocampal neurogenesis and hippocampal levels of transcripts encoding various genes involved in tissue plasticity and remodeling. In addition, rats housed in Marlau™ cages exhibited better performances in learning and memory, decreased anxiety-associated behaviors, and better recovery of basal plasma corticosterone level after acute restraint stress. Marlau™ cages also insure inter-experiment reproducibility in spatial learning and brain gene expression assays. Finally, housing rats in Marlau™ cages after severe status epilepticus at weaning prevents the cognitive impairment observed in rats subjected to the same insult and then housed in conventional cages. By providing a standardized enriched environment for rodents during housing, the Marlau™ cage should facilitate the uniformity of environmental enrichment across laboratories.

  1. Effect of Nigella sativa seed administration on prevention of febrile neutropenia during chemotherapy among children with brain tumors.

    Science.gov (United States)

    Mousa, HebatAlla Fathi Mohamed; Abd-El-Fatah, Nesrin Kamal; Darwish, Olfat Abdel-Hamid; Shehata, Shehata Farag; Fadel, Shady Hassan

    2017-05-01

    Seeds of Nigella sativa (NS) are used to combat various disease conditions through their antibacterial effects. To evaluate the seeds' potential, we studied their effect on the prevention of febrile neutropenia (FN) in children with brain tumors. A randomized pretest-post-test control group study including 80 children (2-18 years) with brain tumors undergoing chemotherapy were equally allocated into two groups. Intervention group received 5 g of NS seeds daily throughout treatment while controls received nothing. CBC with differentials, incidence of FN, and LOS were noted on each follow-up. The majority of children 38/40 (95%), of the intervention group, took the seeds for 3-9 consecutive months. Eight out of 372 (2.2%) FN episodes were experienced by children of intervention group compared to controls 63/327 (19.3%) (p = 0.001) and a shorter LOS (median = 2.5 days) vs 5 days in the control group (p = 0.006). Children in both groups belonged to almost same geographical area with similar socio-economic background. Weights of children were almost equal at diagnosis. NS seeds showed a decrease in incidence of FN in children with brain tumors with shortening of subsequent LOS which may improve their outcome and thereby quality of life. Larger scale studies are needed to further evaluate the seeds' potential.

  2. Re-Training the Addicted Brain: A Review of Hypothesized Neurobiological Mechanisms of Mindfulness-Based Relapse Prevention

    Science.gov (United States)

    Witkiewitz, Katie; Lustyk, M. Kathleen B.; Bowen, Sarah

    2013-01-01

    Addiction has generally been characterized as a chronic relapsing condition. Several laboratory, preclinical, and clinical studies have provided evidence that craving and negative affect are strong predictors of the relapse process. These states, as well as the desire to avoid them, have been described as primary motives for substance use. A recently developed behavioral treatment, Mindfulness-Based Relapse Prevention (MBRP), was designed to target experiences of craving and negative affect and their roles in the relapse process. MBRP offers skills in cognitive behavioral relapse prevention integrated with mindfulness meditation. The mindfulness practices in MBRP are intended to increase discriminative awareness, with a specific focus on acceptance of uncomfortable states or challenging situations without reacting “automatically.” A recent efficacy trial found that those randomized to MBRP, as compared to those in a control group, demonstrated significantly lower rates of substance use and greater decreases in craving following treatment. Furthermore, individuals in MBRP did not report increased craving or substance use in response to negative affect. Importantly, areas of the brain that have been associated with craving, negative affect, and relapse have also been shown to be affected by mindfulness training. Drawing from the neuroimaging literature, we review several plausible mechanisms by which MBRP might be changing neural responses to the experiences of craving and negative affect, which subsequently may reduce risk for relapse. We hypothesize that MBRP may affect numerous brain systems and may reverse, repair, or compensate for the neuroadaptive changes associated with addiction and addictive behavior relapse. PMID:22775773

  3. Brain Basics

    Medline Plus

    Full Text Available ... The brain continues maturing well into a person's early 20s. Knowing how the brain is wired and ... for mental disorders. This could greatly help in early detection, more tailored treatments, and possibly prevention of ...

  4. Aging Brain: Prevention of Oxidative Stress by Vitamin E and Exercise

    Directory of Open Access Journals (Sweden)

    Sambe Asha Devi

    2009-01-01

    Full Text Available With aging, the brain undergoes neuronal loss in many areas. Although the loss of cells in the cerebral cortex, in particular the frontal cortex, has been recognized with aging, the influence of synaptic losses has a larger impact on cognitive decline. Much of the recent research on animals, as well as humans, has been aimed at slowing the cognitive decline through enrichment, and it has been found that the key factors are antioxidants and exercise. Several reports support the concept that regular supplementation of vitamin E and physical activity from as early as middle age can slow the cognitive decline observed during the later years. A few studies have also suggested that exercise is analogous to acetylcholine esterase inhibitors that are also used extensively to treat cognitive impairment and dementia in Alzheimer's disease. In addition, reports also support that vitamin E and exercise may act synergistically to overcome free radical injury and oxidative stress in the aging brain.

  5. Estratégias de prevenção do acidente vascular encefálico cardioembólico na doença de Chagas Prevention strategies of cardioembolic ischemic stroke in Chagas' disease

    Directory of Open Access Journals (Sweden)

    Andréa Silvestre de Sousa

    2008-11-01

    Full Text Available FUNDAMENTO: O acidente vascular encefálico isquêmico (AVEi cardioembólico é uma manifestação clínica importante da cardiopatia chagásica crônica, no entanto, ainda não foram definidos sua incidência e os fatores de risco associados a este evento. OBJETIVO: Definir estratégias de prevenção de uma complicação freqüente e incapacitante da doença de Chagas, o AVEi cardioembólico. MÉTODOS: No período de março de 1990 a março de 2002, 1.043 pacientes com doença de Chagas foram recrutados e acompanhados até março de 2003 em um estudo prospectivo e observacional de coorte. Por meio da regressão de Cox foi desenvolvido um escore de risco de AVEi, que se correlacionou com a incidência anual desse evento: 4-5 pontos, > 4%; 3 pontos, 2% a 4%; 2 pontos, 1% a 2 %; e 0-1 ponto, 48 anos sendo desenvolvido um escore de risco de AVEi, que se relacionou com a incidência anual desse evento. No grupo 2, não houve complicações hemorrágicas, e a incidência anual de AVEi foi de 3,2%, todos em pacientes com 4-5 pontos. CONCLUSÃO: Por meio da análise de risco-benefício, varfarina estaria indicada aos pacientes com 4-5 pontos, cuja incidência de evento supera a taxa de sangramento maior. No subgrupo de 3 pontos, as taxas de evento e sangramento com anticoagulante se equivalem, sendo indicados AAS ou varfarina, conforme o risco individual de sangramento ou embolização. Nos pacientes com 2 pontos, com baixa incidência de AVEi, seriam recomendados AAS ou nenhuma profilaxia. Os pacientes com 0-1 ponto, com incidência do evento próxima a zero, não necessitam de profilaxia.BACKGROUND: The cardioembolic (CE ischemic stroke is an important clinical manifestation of chronic chagasic cardiopathy; however, its incidence and the risk factors associated to this event have yet to be defined. OBJECTIVE: To determine prevention strategies for a common and devastating complication of Chagas' disease, the cardioembolic (CE ischemic stroke

  6. Exercise for the diabetic brain: how physical training may help prevent dementia and Alzheimer's disease in T2DM patients.

    Science.gov (United States)

    Bertram, Sebastian; Brixius, Klara; Brinkmann, Christian

    2016-08-01

    Epidemiological studies indicate that patients with type 2 diabetes mellitus (T2DM) are at increased risk of developing dementia/Alzheimer's disease (AD). This review, which is based on recent studies, presents a molecular framework that links the two diseases and explains how physical training could help counteract neurodegeneration in T2DM patients. Inflammatory, oxidative, and metabolic changes in T2DM patients cause cerebrovascular complications and can lead to blood-brain-barrier (BBB) breakdown. Peripherally increased pro-inflammatory molecules can then pass the BBB more easily and activate stress-activated pathways, thereby promoting key pathological features of dementia/AD such as brain insulin resistance, mitochondrial dysfunction, and accumulation of neurotoxic beta-amyloid (Aβ) oligomers, leading to synaptic loss, neuronal dysfunction, and cell death. Ceramides can also pass the BBB, induce pro-inflammatory reactions, and disturb brain insulin signaling. In a vicious circle, oxidative stress and the pro-inflammatory environment intensify, leading to further cognitive decline. Low testosterone levels might be a common risk factor in T2DM and AD. Regular physical exercise reinforces antioxidative capacity, reduces oxidative stress, and has anti-inflammatory effects. It improves endothelial function and might increase brain capillarization. Physical training can further counteract dyslipidemia and reduce increased ceramide levels. It might also improve Aβ clearance by up-regulating Aβ transporters and, in some cases, increase basal testosterone levels. In addition, regular physical activity can induce neurogenesis. Physical training should therefore be emphasized as a part of prevention programs developed for diabetic patients to minimize the risk of the onset of neurodegenerative diseases among this specific patient group.

  7. Piezosurgery prevents brain tissue damage: an experimental study on a new rat model

    Czech Academy of Sciences Publication Activity Database

    Pavlíková, G.; Foltán, R.; Burian, M.; Horká, E.; Adámek, S.; Hejčl, Aleš; Hanzelka, T.; Šedý, Jiří

    2011-01-01

    Roč. 40, č. 8 (2011), s. 840-844 ISSN 0901-5027 R&D Projects: GA MŠk(CZ) LC554; GA ČR GAP304/10/0320 Grant - others:GA MŠk(CZ) 1M0538 Program:1M Institutional research plan: CEZ:AV0Z50390703 Keywords : piezosurgery * brain * tissue damage Subject RIV: FJ - Surgery incl. Transplants; FH - Neurology (UEM-P) Impact factor: 1.506, year: 2011

  8. ischemic brain injury in neonatal rats

    African Journals Online (AJOL)

    Alpha-lipoic acid (ALA) is an endogenous antioxidant synthesized mainly by the mitochondria of the liver, heart, ... Chemicals. Alpha-lipoic acid, dimethyl sulfoxide, and bromophenol blue were purchased from Sigma- ..... have been due to free-radical generation. Both. ALA doses (50 and 100 mg/kg) substantially improved ...

  9. ischemic brain injury in neonatal rats

    African Journals Online (AJOL)

    Tropical Journal of Pharmaceutical Research. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 16, No 5 (2017) >. Log in or Register to get access to full text downloads.

  10. [Ischemic stroke in the young adult].

    Science.gov (United States)

    Calvet, D

    2016-01-01

    Ischemic stroke is not rare in young adults since one in ten stroke patients are less than 50 years old. This incidence increased over the past last years, mainly due to the rise in the prevalence of traditional vascular risk factors in this sub-group of age but also of illegal drug use. Even though both survival and functional outcome of young stroke patients are better than those observed in older patients, socio-economic and quality of life consequences make this disease a main objective in terms of primary and secondary prevention. Identifying the cause of ischemic stroke in young adults is of major importance to prevent stroke recurrence. However, given the wide variety of potential underlying causes, the etiologic work-up of stroke in young adults requires a different approach from that in the elderly. In this context, a sequential diagnostic work-up is needed in order to optimize the yield of diagnostic tests, to reduce their cost and risks for the patient. Arterial dissection is the most frequent cause of stroke in young adults but other less frequent causes are numerous. Despite a comprehensive work-up, about one third of cases remains unexplained leading to the diagnosis of cryptogenic ischemic stroke. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  11. [Genetics of ischemic stroke].

    Science.gov (United States)

    Gschwendtner, A; Dichgans, M

    2013-02-01

    Stroke is one of the most widespread causes of mortality und disability worldwide. Around 80 % of strokes are ischemic and different forms of intracranial bleeding account for the remaining cases. Monogenic stroke disorders are rare but the diagnosis may lead to specific therapeutic consequences for the affected patients who are predominantly young. In common sporadic stroke, genetic factors play a role in the form of susceptibility genes. Their discovery may give rise to new therapeutic options in the future.

  12. Hypercholesterolemia in patients of ischemic stroke

    International Nuclear Information System (INIS)

    Saeed, E.; Ali, R.; Din, M.J.U.; Saeed, A.; Jadoon, R.J.

    2015-01-01

    Background: Stroke is a common neurological disease that results in significant mortality and morbidity globally. Several risk factors have been identified for stroke among which hyperlipidaemia is one of the modifiable risk factors. Recent clinical trials have shown a reduction in ischemic stroke for patients taking lipid lowering medications. Therefore, the aim of this study was to find out the frequency of hypercholesterolemia in patients of ischemic stroke in Hazara region. Method: This cross sectional study was carried out in the Medical Department of Ayub Teaching Hospital, Abbottabad. Ninety patients of stroke confirmed as ischemic by CT scan brain were enrolled in the study after informed consent. The frequency of hypercholesterolemia in patients was recorded. Results: There were 55 (61.1 percentage) males. The mean age of patients was 64.4±11.5 years. The mean serum cholesterol in all patients was 4.16±1.1 mmol/l. The mean serum cholesterol of male patients was 4.3±1.2 mmol/l and 4.0±10.9 mmol/l in the case of females. Conclusions: Hypercholesterolemia could not be established as a major risk factor for stroke in our setup through this study that allude to the fact that other risk factors might be contributing more to the incidence of cerebrovascular accident in our population. (author)

  13. Prevention

    Science.gov (United States)

    ... Contact Aging & Health A to Z Find a Geriatrics Healthcare Professional Medications & Older Adults Making Your Wishes ... Prevention Hearing Loss Heart Attack High Blood Pressure Nutrition Osteoporosis Shingles Skin Cancer Related News Quitting Smoking, ...

  14. Prevention of pressure ulcers in patients undergoing sub-acute rehabilitation after severe brain injury

    DEFF Research Database (Denmark)

    Sachs, Marianne Brostrup; Wolffbrandt, Mia Moth; Poulsen, Ingrid

    2018-01-01

    that patients' rehabilitation days be planned in such a manner that activities, mobilisation and training are conducted throughout the day and evening. We also recommend that professional staff are encouraged to seek information about the former life of patients with severe brain injury. This article...... knowledge about PU care and performing the activities. However, our observations revealed one important additional aspect; a very distinct impression that the healthcare professionals were committed to learning about the patients' former life and actively used this knowledge in their planning and provision...

  15. In Alzheimer's disease, 6-month treatment with GLP-1 analog prevents decline of brain glucose metabolism

    DEFF Research Database (Denmark)

    Gejl, Michael; Gjedde, Albert; Egefjord, Lærke

    2016-01-01

    with AD to treatment with the GLP-1 analog liraglutide (n = 18), or placebo (n = 20). We measured Aβ load in brain with tracer [11C]PIB (PIB), CMRglc with [18F]FDG (FDG), and cognition with the WMS-IV scale (ClinicalTrials.gov NCT01469351). The PIB binding increased significantly in temporal lobe...... in placebo and treatment patients (both P = 0.04), and in occipital lobe in treatment patients (P = 0.04). Regional and global increases of PIB retention did not differ between the groups (P ≥ 0.38). In placebo treated patients CMRglc declined in all regions, significantly so by the following means...

  16. Chlorogenic Acid Prevents Alcohol-induced Brain Damage in Neonatal Rat

    Science.gov (United States)

    Guo, Zikang; Li, Jiang

    2017-01-01

    Abstract The present investigation evaluates the neuroprotective effect of chlorogenic acid (CA) in alcohol-induced brain damage in neonatal rats. Ethanol (12 % v/v, 5 g/kg) was administered orally in the wistar rat pups on postnatal days (PD) 7-9. Chlorogenic acid (100 and 200 mg/kg, p.o.) was administered continuously from PD 6 to 28. Cognitive function was estimated by Morris water maze (MWM) test. However, activity of acetylcholinesterase, inflammatory mediators, parameters of oxidative stress and activity of caspase-3 enzyme was estimated in the tissue homogenate of cerebral cortex and hippocampus of ethanol-exposed pups. It has been observed that treatment with CA attenuates the altered cognitive function in ethanol-exposed pups. There was a significant decrease in the activity of acetylcholinesterase in the CA treated group compared to the negative control group. However, treatment with CA significantly ameliorates the increased oxidative stress and concentration of inflammatory mediators in the brain tissues of ethanol-exposed pups. Activity of caspase-3 enzyme was also found significantly decreased in the CA treated group compared to the negative control group. The present study concludes that CA attenuates the neuronal damage induced in alcohol exposed neonatal rat by decreasing the apoptosis of neuronal cells. PMID:29318034

  17. Report of ischemic stroke mimicking isolated ulnar nerve paralysis

    Directory of Open Access Journals (Sweden)

    Çetin Kürşad Akpınar

    2016-12-01

    Full Text Available The cortical motor hand area is the precentral gyrus. Small cortical infarcts of this area can caused isolated hand weakness. Weakness can consist of either all fingers or ulnar-sided fingers. A 71-year-old man admitted to the emergency department with sudden weakness of the right fourth and fifth fingers Diffusion-weighted brain imaging of a magnetic resonance imaging scan revealed acute infarction of right precentral gyrus. Cardioembolus is the determined ischemic stroke subtype. This report presented a case of ischemic stroke mimicking isolated ulnar nerve paralysis.

  18. Potential role of abciximab in ischemic cerebrovascular disease.

    Science.gov (United States)

    Winkley, J M; Adams, H P

    2000-04-27

    Abciximab is an intravenously administered antiplatelet agent that could be used alone or in conjunction with thrombolytic therapy to treat patients with acute ischemic stroke. However, experience with medication for treatment of patients with stroke is limited. Symptomatic intracranial bleeding is the most common serious complication of therapies that aim at restoring or improving blood flow to the brain after stroke and it is the most likely potential serious complication of the use of abciximab in this setting. Preliminary data suggest that abciximab is not associated with a prohibitively high rate of symptomatic intracranial hemorrhage. Further research is needed to determine the safety and potential efficacy of abciximab for treatment of ischemic stroke.

  19. Using Ferumoxytol-Enhanced MRI to Measure Inflammation in Patients With Brain Tumors or Other Conditions of the CNS

    Science.gov (United States)

    2017-08-30

    Brain Injury; Central Nervous System Degenerative Disorder; Central Nervous System Infectious Disorder; Central Nervous System Vascular Malformation; Hemorrhagic Cerebrovascular Accident; Ischemic Cerebrovascular Accident; Primary Brain Neoplasm; Brain Cancer; Brain Tumors

  20. Ischemic stroke and transient ischemic attack in young adults: risk factors, diagnostic yield, neuroimaging, and thrombolysis.

    Science.gov (United States)

    Ji, Ruijun; Schwamm, Lee H; Pervez, Muhammad A; Singhal, Aneesh B

    2013-01-01

    Approximately 10% to 14% of ischemic strokes occur in young adults. To investigate the yield of diagnostic tests, neuroimaging findings, and treatment of ischemic strokes in young adults. We retrospectively reviewed data from our Get with the Guidelines-Stroke database from 2005 through 2010. University hospital tertiary stroke center. A total of 215 consecutive inpatients aged 18 to 45 years with ischemic stroke/transient ischemic attack. The mean (SD) age was 37.5 (7) years; 51% were male. There were high incidence rates of hypertension (20%), diabetes mellitus (11%), dyslipidemia (38%), and smoking (34%). Relevant abnormalities were shown on cerebral angiography in 136 of 203 patients, on cardiac ultrasonography in 100 of 195, on Holter monitoring in 2 of 192; and on hypercoagulable panel in 30 of 189 patients. Multiple infarcts were observed in 31% and were more prevalent in individuals younger than age 35 years. Relevant arterial lesions were frequently detected in the middle cerebral artery (23%), internal carotid artery (13%), and vertebrobasilar arteries (13%). Cardioembolic stroke occurred in 47% (including 17% with isolated patent foramen ovale), and 11% had undetermined stroke etiology. The median National Institutes of Health Stroke Scale score was 3 (interquartile range, 0-9) and 81% had good outcome at hospital discharge. Of the 29 patients receiving thrombolysis (median National Institutes of Health Stroke Scale score, 14; interquartile range, 9-17), 55% had good outcome at hospital discharge and none developed symptomatic brain hemorrhage. This study shows the contemporary profile of ischemic stroke in young adults admitted to a tertiary stroke center. Stroke etiology can be determined in nearly 90% of patients with modern diagnostic tests. The causes are heterogeneous; however, young adults have a high rate of traditional vascular risk factors. Thrombolysis appears safe and short-term outcomes are favorable.

  1. Estradiol prevents ozone-induced increases in brain lipid peroxidation and impaired social recognition memory in female rats.

    Science.gov (United States)

    Guevara-Guzmán, R; Arriaga, V; Kendrick, K M; Bernal, C; Vega, X; Mercado-Gómez, O F; Rivas-Arancibia, S

    2009-03-31

    There is increasing concern about the neurodegenerative and behavioral consequences of ozone pollution in industrialized urban centers throughout the world and that women may be more susceptible to brain neurodegenerative disorders. In the present study we have investigated the effects of chronic (30 or 60 days) exposure to ozone on olfactory perception and memory and on levels of lipid peroxidation, alpha and beta estrogen receptors and dopamine beta-hydroxylase in the olfactory bulb in ovariectomized female rats. The ability of 17beta-estradiol to prevent these effects was then assessed. Results showed that ozone exposure for 30 or 60 days impaired formation/retention of a selective olfactory recognition memory 120 min after exposure to a juvenile stimulus animal with the effect at 60 days being significantly greater than at 30 days. They also showed impaired speed in locating a buried chocolate reward after 60 days of ozone exposure indicating some loss of olfactory perception. These functional impairments could all be prevented by coincident estradiol treatment. In the olfactory bulb, levels of lipid peroxidation were increased at both 30- and 60-day time-points and numbers of cells with immunohistochemical staining for alpha and beta estrogen receptors, and dopamine beta-hydroxylase were reduced as were alpha and beta estrogen receptor protein levels. These effects were prevented by estradiol treatment. Oxidative stress damage caused by chronic exposure to ozone does therefore impair olfactory perception and social recognition memory and may do so by reducing noradrenergic and estrogen receptor activity in the olfactory bulb. That these effects can be prevented by estradiol treatment suggests increased susceptibility to neurodegenerative disorders in aging women may be contributed to by reduced estrogen levels post-menopause.

  2. Prevention

    DEFF Research Database (Denmark)

    Halken, S; Høst, A

    2001-01-01

    , breastfeeding should be encouraged for 4-6 months. In high-risk infants a documented extensively hydrolysed formula is recommended if exclusive breastfeeding is not possible for the first 4 months of life. There is no evidence for preventive dietary intervention neither during pregnancy nor lactation...... populations. These theories remain to be documented in proper, controlled and prospective studies. Breastfeeding and the late introduction of solid foods (>4 months) is associated with a reduced risk of food allergy, atopic dermatitis, and recurrent wheezing and asthma in early childhood. In all infants....... Preventive dietary restrictions after the age of 4-6 months are not scientifically documented....

  3. L-carnitine Prevents Oxidative Stress in the Brains of Rats Subjected to a Chemically Induced Chronic Model of MSUD.

    Science.gov (United States)

    Mescka, Caroline Paula; Rosa, Andrea Pereira; Schirmbeck, Gabriel; da Rosa, Thales Hein; Catarino, Felipe; de Souza, Laila Oliveira; Guerreiro, Gilian; Sitta, Angela; Vargas, Carmen Regla; Dutra-Filho, Carlos Severo

    2016-11-01

    Maple syrup urine disease (MSUD), or branched-chain α-keto aciduria, is an inherited disorder that is caused by a deficiency in branched-chain α-keto acid dehydrogenase complex (BCKAD) activity. Blockade of this pathway leads to the accumulation of the branched-chain amino acids (BCAAs), leucine, isoleucine, and valine, and their respective ketoacids in tissues. The main clinical symptoms presented by MSUD patients include ketoacidosis, hypoglycemia, opisthotonos, poor feeding, apnea, ataxia, convulsions, coma, psychomotor delay, and mental retardation. Although increasing evidence indicates that oxidative stress is involved in the pathophysiology of this disease, the mechanisms of the brain damage caused by this disorder remain poorly understood. In the present study, we investigated the effect of BCAAs on some oxidative stress parameters and evaluated the efficacy of L-carnitine (L-car), an efficient antioxidant that may be involved in the reduction of oxidative damage observed in some inherited neurometabolic diseases, against these possible pro-oxidant effects of a chronic MSUD model in the cerebral cortex and cerebellum of rats. Our results showed that chronic BCAA administration was able to promote both lipid and protein oxidation, impair brain antioxidant defenses, and increase reactive species production, particularly in the cerebral cortex, and that L-car was able to prevent these effects. Taken together, the present data indicate that chronic BCAA administration significantly increased oxidative damage in the brains of rats subjected to a chronic model of MSUD and that L-car may be an efficient antioxidant in this disorder.

  4. Middle age onset short-term intermittent fasting dietary restriction prevents brain function impairments in male Wistar rats.

    Science.gov (United States)

    Singh, Rumani; Manchanda, Shaffi; Kaur, Taranjeet; Kumar, Sushil; Lakhanpal, Dinesh; Lakhman, Sukhwinder S; Kaur, Gurcharan

    2015-12-01

    Intermittent fasting dietary restriction (IF-DR) is recently reported to be an effective intervention to retard age associated disease load and to promote healthy aging. Since sustaining long term caloric restriction regimen is not practically feasible in humans, so use of alternate approach such as late onset short term IF-DR regimen which is reported to trigger similar biological pathways is gaining scientific interest. The current study was designed to investigate the effect of IF-DR regimen implemented for 12 weeks in middle age rats on their motor coordination skills and protein and DNA damage in different brain regions. Further, the effect of IF-DR regimen was also studied on expression of energy regulators, cell survival pathways and synaptic plasticity marker proteins. Our data demonstrate that there was an improvement in motor coordination and learning response with decline in protein oxidative damage and recovery in expression of energy regulating neuropeptides. We further observed significant downregulation in nuclear factor kappa B (NF-κB) and cytochrome c (Cyt c) levels and moderate upregulation of mortalin and synaptophysin expression. The present data may provide an insight on how a modest level of short term IF-DR, imposed in middle age, can slow down or prevent the age-associated impairment of brain functions and promote healthy aging by involving multiple regulatory pathways aimed at maintaining energy homeostasis.

  5. Physical training prevents depressive symptoms and a decrease in brain-derived neurotrophic factor in Parkinson's disease.

    Science.gov (United States)

    Tuon, T; Valvassori, S S; Dal Pont, G C; Paganini, C S; Pozzi, B G; Luciano, T F; Souza, P S; Quevedo, J; Souza, C T; Pinho, R A

    2014-09-01

    Depression is a neuropsychiatric disorder that is commonly found in patients with Parkinson's disease (PD). Many studies have suggested that physical exercise can have an antidepressant effect by increasing the levels of brain-derived neurotrophic factor (BDNF), and may also prevent neurodegenerative disease. However, different forms of training may promote different changes in the brain. The aim of this study was to investigate the effects of two types of physical training on depressive-like behavior, and on the levels of proBDNF, BDNF, and its receptor, TrkB, in a mouse model of PD. C57BL/6 mice were subjected to 60 days of exercise: either running on a treadmill or performing a strength exercise. PD was induced by striatal administration of 6-OHDA 24h after the last physical exercise session. Seven days after 6-OHDA injection, depressive-like behavior and apomorphine-induced rotational behavior were evaluated. The levels of proBDNF, BDNF, and TRKB were measured in the striatum and the hippocampus of mice by immunoblotting assay. The 6-OHDA-treated animals showed a significant increase in immobility time and rotational behavior compared with the control group. In addition, significant decreases in the levels of proBDNF, BDNF, and its receptor, TrkB were observed in the 6-OHDA group. Both types of physical exercise prevented depressive-like behavior and restored the levels of proBDNF, BDNF, and TrkB in the striatum and hippocampus of mice administered 6-OHDA. Our results demonstrate that exercise training was effective for neuroprotection in the striatum and the hippocampus in an experimental model of PD. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Ketogenic diet in a patient with congenital hyperinsulinism: a novel approach to prevent brain damage.

    Science.gov (United States)

    Maiorana, Arianna; Manganozzi, Lucilla; Barbetti, Fabrizio; Bernabei, Silvia; Gallo, Giorgia; Cusmai, Raffaella; Caviglia, Stefania; Dionisi-Vici, Carlo

    2015-09-24

    Congenital hyperinsulinism (CHI) is the most frequent cause of hypoglycemia in children. In addition to increased peripheral glucose utilization, dysregulated insulin secretion induces profound hypoglycemia and neuroglycopenia by inhibiting glycogenolysis, gluconeogenesis and lipolysis. This results in the shortage of all cerebral energy substrates (glucose, lactate and ketones), and can lead to severe neurological sequelae. Patients with CHI unresponsive to medical treatment can be subjected to near-total pancreatectomy with increased risk of secondary diabetes. Ketogenic diet (KD), by reproducing a fasting-like condition in which body fuel mainly derives from beta-oxidation, is intended to provide alternative cerebral substrates such ketone bodies. We took advantage of known protective effect of KD on neuronal damage associated with GLUT1 deficiency, a disorder of impaired glucose transport across the blood-brain barrier, and administered KD in a patient with drug-unresponsive CHI, with the aim of providing to neurons an energy source alternative to glucose. A child with drug-resistant, long-standing CHI caused by a spontaneous GCK activating mutation (p.Val455Met) suffered from epilepsy and showed neurodevelopmental abnormalities. After attempting various therapeutic regimes without success, near-total pancreatectomy was suggested to parents, who asked for other options. Therefore, we proposed KD in combination with insulin-suppressing drugs. We administered KD for 2 years. Soon after the first six months, the patient was free of epileptic crises, presented normalization of EEG, and showed a marked recover in psychological development and quality of life. KD could represent an effective treatment to support brain function in selected cases of CHI.

  7. Smoking and Risk of Ischemic Stroke in Young Men.

    Science.gov (United States)

    Markidan, Janina; Cole, John W; Cronin, Carolyn A; Merino, Jose G; Phipps, Michael S; Wozniak, Marcella A; Kittner, Steven J

    2018-05-01

    There is a strong dose-response relationship between smoking and risk of ischemic stroke in young women, but there are few data examining this association in young men. We examined the dose-response relationship between the quantity of cigarettes smoked and the odds of developing an ischemic stroke in men under age 50 years. The Stroke Prevention in Young Men Study is a population-based case-control study of risk factors for ischemic stroke in men ages 15 to 49 years. The χ 2 test was used to test categorical comparisons. Logistic regression models were used to calculate the odds ratio for ischemic stroke occurrence comparing current and former smokers to never smokers. In the first model, we adjusted solely for age. In the second model, we adjusted for potential confounding factors, including age, race, education, hypertension, myocardial infarction, angina, diabetes mellitus, and body mass index. The study population consisted of 615 cases and 530 controls. The odds ratio for the current smoking group compared with never smokers was 1.88. Furthermore, when the current smoking group was stratified by number of cigarettes smoked, there was a dose-response relationship for the odds ratio, ranging from 1.46 for those smoking ischemic stroke among young men. Although complete smoking cessation is the goal, even smoking fewer cigarettes may reduce the risk of ischemic stroke in young men. © 2018 American Heart Association, Inc.

  8. Obstructive sleep apnea in ischemic stroke patients

    Directory of Open Access Journals (Sweden)

    Aliye Tosun

    2008-01-01

    Full Text Available OBJECTIVE: To investigate the prevalence of obstructive sleep apnea in patients with ischemic stroke and to evaluate the effectiveness of nasal continuous positive airway pressure treatment. METHODS: Overnight polysomnography was performed by a computerized system in 19 subjects with ischemic stroke. Patients with an apnea-hypopnea index > 5 were considered to have obstructive sleep apnea. The appropriate level of continuous positive airway pressure for each patient was determined during an all-night continuous positive airway pressure determination study. Attended continuous positive airway pressure titration was performed with a continuous positive airway pressure auto-titrating device. RESULTS: Obstructive sleep apnea prevalence among patients with ischemic stroke was 73.7%. The minimum SaO2 was significantly lower, and the percent of total sleep time in the wake stage and stage 1 sleep was significantly longer in patients with obstructive sleep apnea. In two patients with severe obstructive sleep apnea, we observed a decrease in the apnea-hypopnea index, an increase in mean wake time, mean SaO2, and minimum SaO2, and alterations in sleep structures with continuous positive airway pressure treatment. CONCLUSION: As the diagnosis and treatment of obstructive sleep apnea is of particular importance in secondary stroke prevention, we suggest that the clinical assessment of obstructive sleep apnea be part of the evaluation of stroke patients in rehabilitation units, and early treatment should be started.

  9. TOWARD THE QUESTION OF ISCHEMIC MYOCARDIAL DYSFUNCTION

    Directory of Open Access Journals (Sweden)

    V. V. Kalyuzhin

    2014-01-01

    Full Text Available The authors of the review have analyzed papers published on the problem of ischemic myocardial dysfunction. They begin with a definition of the term “ischemia” (derived from two Greek words: ischō, meaning to hold back, and haima, meaning blood - a condition at which the arterial blood flow is insufficient to provide enough oxygen to prevent intracellular respiration from shifting from the aerobic to the anaerobic form. The poor rate of ATP generation from this process causes a decrease in cellular ATP, a concomitant rise in ADP, and ultimately, to depression inotropic (systolic and lusitropic (diastolic function of the affected segments of the myocardium. But with such simplicity of basic concepts, the consequences of ischemia so diverse. Influence of an ischemia on myocardial function so unequally at different patients, which is almost impossible to find two identical cases (as in the case of fingerprints. It depends on the infinite variety of lesions of coronary arteries, reperfusion (time and completeness of restoration of blood flow and reactions of a myocardium which, apparently, has considerable flexibility in its response. Ischemic myocardial dysfunction includes a number of discrete states, such as acute left ventricular failure in angina, acute myocardial infarction, ischemic cardiomyopathy, stunning, hibernation, pre- and postconditioning. There are widely differing underlying pathophysiologic states. The possibility exists that several of these states can coexist.

  10. The effects of citicoline on acute ischemic stroke

    DEFF Research Database (Denmark)

    Overgaard, Karsten

    2014-01-01

    Early reopening of the occluded artery is, thus, important in ischemic stroke, and it has been calculated that 2 million neurons die every minute in an ischemic stroke if no effective therapy is given; therefore, "Time is Brain." In massive hemispheric infarction and edema, surgical decompression...... lowers the risk of death or severe disability defined as a modified Rankin Scale score greater than 4 in selected patients. The majority, around 80%-85% of all ischemic stroke victims, does not fulfill the criteria for revascularization therapy, and also for these patients, there is no effective acute...... therapy. Also there is no established effective acute treatment of spontaneous intracerebral bleeding. Therefore, an effective therapy applicable to all stroke victims is needed. The neuroprotective drug citicoline has been extensively studied in clinical trials with volunteers and more than 11...

  11. Ischemic tolerance modulates TRAIL expression and its receptors and generates a neuroprotected phenotype

    OpenAIRE

    Cantarella, G; Pignataro, G; Di Benedetto, G; Anzilotti, S; Vinciguerra, A; Cuomo, O; Di Renzo, G F; Parenti, C; Annunziato, L; Bernardini, R

    2014-01-01

    TNF-related apoptosis inducing ligand (TRAIL), a member of the TNF superfamily released by microglia, appears to be involved in the induction of apoptosis following focal brain ischemia. Indeed, brain ischemia is associated with progressive enlargement of damaged areas and prominent inflammation. As ischemic preconditioning reduces inflammatory response to brain ischemia and ameliorates brain damage, the purpose of the present study was to evaluate the role of TRAIL and its receptors in strok...

  12. Modelling Ischemic Stroke and Temperature Intervention Using Vascular Porous Method

    Science.gov (United States)

    Blowers, Stephen; Valluri, Prashant; Marshall, Ian; Andrews, Peter; Harris, Bridget; Thrippleton, Michael

    2017-11-01

    In the event of cerebral infarction, a region of tissue is supplied with insufficient blood flow to support normal metabolism. This can lead to an ischemic reaction which incurs cell death. Through a reduction of temperature, the metabolic demand can be reduced, which then offsets the onset of necrosis. This allows extra time for the patient to receive medical attention and could help prevent permanent brain damage from occurring. Here, we present a vascular-porous (VaPor) blood flow model that can simulate such an event. Cerebral blood flow is simulated using a combination of 1-Dimensional vessels embedded in 3-Dimensional porous media. This allows for simple manipulation of the structure and determining the effect of an obstructed vessel. Results show regional temperature increase of 1-1.5°C comparable with results from literature (in contrast to previous simpler models). Additionally, the application of scalp cooling in such an event dramatically reduces the temperature in the affected region to near hypothermic temperatures, which points to a potential rapid form of first intervention.

  13. Non-Selective Cannabinoid Receptor Antagonists, Hinokiresinols Reduce Infiltration of Microglia/Macrophages into Ischemic Brain Lesions in Rat via Modulating 2-Arachidonolyglycerol-Induced Migration and Mitochondrial Activity.

    Directory of Open Access Journals (Sweden)

    Angela M A Anthony Jalin

    Full Text Available Growing evidence suggests that therapeutic strategies to modulate the post-ischemic inflammatory responses are promising approaches to improve stroke outcome. Although the endocannabinoid system has been emerged as an endogenous therapeutic target to regulate inflammation after stroke insult, the downstream mechanisms and their potentials for therapeutic intervention remain controversial. Here we identified trans- and cis-hinokiresinols as novel non-selective antagonists for two G-protein-coupled cannabinoid receptors, cannabinoid receptor type 1 and type 2. The Electric Cell-substrate Impedance Sensing and Boyden chamber migration assays using primary microglial cultures revealed that both hinokiresinols significantly inhibited an endocannabinoid, 2-arachidonoylglycerol-induced migration. Hinokiresinols modulated 2-arachidonoylglycerol-induced mitochondrial bioenergetics in microglia as evidenced by inhibition of ATP turnover and reduction in respiratory capacity, thereby resulting in impaired migration activity. In rats subjected to transient middle cerebral artery occlusion (1.5-h followed by 24-h reperfusion, post-ischemic treatment with hinokiresinols (2 and 7-h after the onset of ischemia, 10 mg/kg significantly reduced cerebral infarct and infiltration of ED1-positive microglial/macrophage cells into cerebral ischemic lesions in vivo. Co-administration of exogenous 2-AG (1 mg/kg, i.v., single dose at 2 h after starting MCAO abolished the protective effect of trans-hinokiresionol. These results suggest that hinokiresinols may serve as stroke treatment by targeting the endocannabinoid system. Alteration of mitochondrial bioenergetics and consequent inhibition of inflammatory cells migration may be a novel mechanism underlying anti-ischemic effects conferred by cannabinoid receptor antagonists.

  14. Knowledge of ischemic stroke among a Mexico City population.

    Science.gov (United States)

    Góngora-Rivera, Fernando; Gutiérrez-Jiménez, Eugenio; Zenteno, Marco Antonio

    2009-01-01

    Knowledge of risk factors (RF) and warning signs of stroke by the general population is fundamental to implement efficient preventive measures and provide timely treatment. The objective of this study was to assess this knowledge in a sample population of Mexico City. Personal interview was conducted in a multifamily building complex in Mexico City. The questionnaire included sociodemographic and comorbidity factors. Knowledge was determinated according to the number of correct answers. Chi-square and Wilcoxon rank tests were performed and significant variables were included in a multivariate logistic regression model using level of knowledge as the dependent variable. A total of 330 subjects were interviewed. Of the respondents, 66.7% named one RF associated with ischemic stroke, whereas only 12.1% identified 3 or more; one warning sign was identified by 36.7% and only 2.1% identified 3 or more. The factors associated with knowledge of RF were history of hypertension, educational level, and family history of ischemic stroke. Educational level and a family history of stroke were also associated with knowledge of warning signs. A Family history of ischemic stroke was the most important way to receive information about RF and warning signs of ischemic stroke. The study shows the need for informing the public about prevention and early detection of ischemic stroke.

  15. Evidence That Ly6C(hi) Monocytes are Protective in Acute Ischemic Stroke by Promoting M2 Macrophage Polarization.

    Science.gov (United States)

    Chu, Hannah X; Broughton, Brad R S; Kim, Hyun Ah; Lee, Seyoung; Drummond, Grant R; Sobey, Christopher G

    2015-07-01

    Ly6C(hi) monocytes are generally thought to exert a proinflammatory role in acute tissue injury, although their impact after injuries to the central nervous system is poorly defined. CC chemokine receptor 2 is expressed on Ly6C(hi) monocytes and plays an essential role in their extravasation and transmigration into the brain after cerebral ischemia. We used a selective CC chemokine receptor 2 antagonist, INCB3344, to assess the effect of Ly6C(hi) monocytes recruited into the brain early after ischemic stroke. Male C57Bl/6J mice underwent occlusion of the middle cerebral artery for 1 hour followed by 23 hours of reperfusion. Mice were administered either vehicle (dimethyl sulfoxide/carboxymethylcellulose) or INCB3344 (10, 30 or 100 mg/kg IP) 1 hour before ischemia and at 2 and 6 hours after ischemia. At 24 hours, we assessed functional outcomes, infarct volume, and quantified the immune cells in blood and brain by flow cytometry or immunofluorescence. Gene expression of selected inflammatory markers was assessed by quantitative polymerase chain reaction. Ly6C(hi) monocytes were increased 3-fold in the blood and 10-fold in the brain after stroke, and these increases were selectively prevented by INCB3344 in a dose-dependent manner. Mice treated with INCB3344 exhibited markedly worse functional outcomes and larger infarct volumes, in association with reduced M2 polarization and increased peroxynitrite production in macrophages, compared with vehicle-treated mice. Our data suggest that Ly6C(hi) monocytes exert an acute protective effect after ischemic stroke to limit brain injury and functional deficit that involves promotion of M2 macrophage polarization. © 2015 American Heart Association, Inc.

  16. Development of the Young Brain

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    Full Text Available ... Health (2 items) Military Service Members (1 item) Prevention Suicide Prevention (8 items) Research BRAIN Initiative (5 ... Health (2 items) Military Service Members (1 item) Prevention Suicide Prevention (8 items) Research BRAIN Initiative (5 ...

  17. Development of the Young Brain

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  18. Development of the Young Brain

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  19. Development of the Young Brain

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  20. Development of the Young Brain

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  1. Development of the Young Brain

    Medline Plus

    Full Text Available ... item) Prevention Suicide Prevention (8 items) Research BRAIN Initiative (5 items) Basic Research (27 items) Clinical Research ... item) Prevention Suicide Prevention (8 items) Research BRAIN Initiative (5 items) Basic Research (27 items) Clinical Research ...

  2. VERBAL CHOICE IN ISCHEMIC STROKE PATIENTS WITH ANOMIC APHASIA.

    Directory of Open Access Journals (Sweden)

    Мaya P. Danovska

    2014-03-01

    Full Text Available Background and purposes: Anomic aphasia is common in patients with left hemispheric strokes. The purpose of this study was to explore the verbal production of ischemic stroke patients with anomic aphasia. Contingent and methods: Fifty ischemic stroke patients admitted to the Neurology Clinic of University Hospital Pleven were studied by neuropsychological battery and CT scan of the brain. Verbal productivity changes found were analyzed in relation to the speech recovery education. Results: All the patients showed lower scores at all nominative and reproductive speech subtests. Discussion: Among the ischemic stroke patients with mild anomic aphasia comparatively great was the percentage of low frequency word actualization and verbal fluency impairment. The usage of nominatives in speech expression of ischemic stroke patients is less as compared with that one of predicatives. Actualization of particles, unions, prepositions and interjections was comparatively high thus compensating the difficulty in choice of a definite lexical number. Conclusion: Future studies on testing of verbal choice in ischemic stroke patients should confirm its practical significance for the assessment of speech disorders concerning a special speech- recovery education.

  3. SONOlysis in prevention of Brain InfaRctions During Internal carotid Endarterectomy (SONOBIRDIE) trial - study protocol for a randomized controlled trial.

    Science.gov (United States)

    Hrbáč, Tomáš; Netuka, David; Beneš, Vladimír; Nosáľ, Vladimír; Kešnerová, Petra; Tomek, Aleš; Fadrná, Táňa; Beneš, Vladimír; Fiedler, Jiří; Přibáň, Vladimír; Brozman, Miroslav; Langová, Kateřina; Herzig, Roman; Školoudík, David

    2017-01-17

    Carotid endarterectomy (CEA) is a beneficial procedure for selected patients with an internal carotid artery (ICA) stenosis. Surgical risk of CEA varies from between 2 and 15%. The aim of the study is to demonstrate the safety and effectiveness of sonolysis (continual transcranial Doppler monitoring, TCD) using a 2-MHz diagnostic probe with maximal diagnostic energy on the reduction of the incidence of stroke, transient ischemic attack (TIA) and brain infarction detected using magnetic resonance imaging (MRI) by the activation of the endogenous fibrinolytic system during CEA. Design: a multicenter, randomized, double-blind, sham-controlled trial. international, multicenter trial for patients with at least 70% symptomatic or asymptomatic ICA stenosis undergoing CEA. patients with symptomatic or asymptomatic ICA stenosis of at least 70% are candidates for CEA; a sufficient temporal bone window for TCD; aged 40-85 years, functionally independent; provision of signed informed consent. Randomization: consecutive patients will be assigned to the sonolysis or control (sham procedure) group by computer-generated 1:1 randomization. Prestudy calculations showed that a minimum of 704 patients in each group is needed to reach a significant difference with an alpha value of 0.05 (two-tailed) and a beta value of 0.8 assuming that 10% would be lost to follow-up or refuse to participate in the study (estimated 39 endpoints). the primary endpoint is the incidence of stroke or TIA during 30 days after CEA and the incidence of new ischemic lesions on brain MRI performed 24 h after CEA in the sonolysis and control groups. Secondary endpoints are occurrence of death, any stroke, or myocardial infarction within 30 days, changes in cognitive functions 1 year post procedure related to pretreatment scores, and number of new lesions and occurrence of new lesions ≥0.5 mL on post-procedural brain MRI. descriptive statistics and linear/logistic multiple regression models will be

  4. Dual inhibitory roles of geldanamycin on the c-Jun NH2-terminal kinase 3 signal pathway through suppressing the expression of mixed-lineage kinase 3 and attenuating the activation of apoptosis signal-regulating kinase 1 via facilitating the activation of Akt in ischemic brain injury.

    Science.gov (United States)

    Wen, X-R; Li, C; Zong, Y-Y; Yu, C-Z; Xu, J; Han, D; Zhang, G-Y

    2008-10-15

    It is well documented that heat-shock protein (hsp90) plays an essential role in maintaining stability and activity of its clients. Recent studies have shown that geldanamycin (GA), an inhibitor of hsp90, could decrease the protein of mixed-lineage kinase (MLK) 3 and activate Akt; our previous research documented that MLK3 and Akt and subsequent c-Jun N-terminal kinase (JNK) were involved in neuronal cell death in ischemic brain injury. Here, we investigated whether GA could decrease the protein of MLK3 and activate Akt in rat four-vessel occlusion ischemic model. Our results showed that global cerebral ischemia followed by reperfusion could enhance the association of hsp90 with MLK3, the association of hsp90 with Src, and JNK3 activation. As a result, GA decreased the protein of MLK3 and down-regulated JNK activation. On the other hand, Src kinase was activated and phosphorylated Cbl, which then recruited the p85 subunit of phosphatidylinositol 3-kinase (PI-3K), resulting in PI-3K activation, and as a consequence increased Akt activation, which inhibited ASK1 activation and down-regulated JNK3 activation. In summary, our results indicated that GA showed a dual inhibitory role on JNK3 activation and exerted strong neuroprotection in vivo and in vitro, which provides a new possible approach for stroke therapy.

  5. It's All about Timing: The Involvement of Kir4.1 Channel Regulation in Acute Ischemic Stroke Pathology

    Science.gov (United States)

    Milton, Meagan; Smith, Patrice D.

    2018-01-01

    An acute ischemic stroke is characterized by the presence of a blood clot that limits blood flow to the brain resulting in subsequent neuronal loss. Acute stroke threatens neuronal survival, which relies heavily upon proper function of astrocytes. Neurons are more susceptible to cell death when an astrocyte is unable to carry out its normal functions in supporting the neuron in the area affected by the stroke (Rossi et al., 2007; Takano et al., 2009). For example, under normal conditions, astrocytes initially swell in response to changes in extracellular osmotic pressure and then reduce their regulatory volume in response to volume-activated potassium (K+) and chloride channels (Vella et al., 2015). This astroglial swelling may be overwhelmed, under ischemic conditions, due to the increased levels of glutamate and extracellular K+ (Lai et al., 2014; Vella et al., 2015). The increase in extracellular K+ contributes to neuronal damage and loss through the initiation of harmful secondary cascades (Nwaobi et al., 2016). Reducing the amount of extracellular K+ could, in theory, limit or prevent neuronal damage and loss resulting in an improved prognosis for individuals following ischemic stroke. Kir4.1, an inwardly rectifying K+ channel, has demonstrated an ability to regulate the rapid reuptake of this ion to return the cell to basal levels allowing it to fire again in rapid transmission (Sibille et al., 2015). Despite growing interest in this area, the underlying mechanism suggesting that neuroprotection could occur through modification of the Kir4.1 channel's activity has yet to be described. The purpose of this review is to examine the current literature and propose potential underlying mechanisms involving Kir4.1, specially the mammalian target of rapamycin (mTOR) and/or autophagic pathways, in the pathogenesis of ischemic stroke. The hope is that this review will instigate further investigation of Kir4.1 as a modulator of stroke pathology. PMID:29503609

  6. It's All about Timing: The Involvement of Kir4.1 Channel Regulation in Acute Ischemic Stroke Pathology

    Directory of Open Access Journals (Sweden)

    Meagan Milton

    2018-02-01

    Full Text Available An acute ischemic stroke is characterized by the presence of a blood clot that limits blood flow to the brain resulting in subsequent neuronal loss. Acute stroke threatens neuronal survival, which relies heavily upon proper function of astrocytes. Neurons are more susceptible to cell death when an astrocyte is unable to carry out its normal functions in supporting the neuron in the area affected by the stroke (Rossi et al., 2007; Takano et al., 2009. For example, under normal conditions, astrocytes initially swell in response to changes in extracellular osmotic pressure and then reduce their regulatory volume in response to volume-activated potassium (K+ and chloride channels (Vella et al., 2015. This astroglial swelling may be overwhelmed, under ischemic conditions, due to the increased levels of glutamate and extracellular K+ (Lai et al., 2014; Vella et al., 2015. The increase in extracellular K+ contributes to neuronal damage and loss through the initiation of harmful secondary cascades (Nwaobi et al., 2016. Reducing the amount of extracellular K+ could, in theory, limit or prevent neuronal damage and loss resulting in an improved prognosis for individuals following ischemic stroke. Kir4.1, an inwardly rectifying K+ channel, has demonstrated an ability to regulate the rapid reuptake of this ion to return the cell to basal levels allowing it to fire again in rapid transmission (Sibille et al., 2015. Despite growing interest in this area, the underlying mechanism suggesting that neuroprotection could occur through modification of the Kir4.1 channel's activity has yet to be described. The purpose of this review is to examine the current literature and propose potential underlying mechanisms involving Kir4.1, specially the mammalian target of rapamycin (mTOR and/or autophagic pathways, in the pathogenesis of ischemic stroke. The hope is that this review will instigate further investigation of Kir4.1 as a modulator of stroke pathology.

  7. Cellular and Molecular Mechanisms Underlying Non-Pharmaceutical Ischemic Stroke Therapy in Aged Subjects.

    Science.gov (United States)

    Sandu, Raluca Elena; Dumbrava, Danut; Surugiu, Roxana; Glavan, Daniela-Gabriela; Gresita, Andrei; Petcu, Eugen Bogdan

    2017-12-29

    The incidence of ischemic stroke in humans increases exponentially above 70 years both in men and women. Comorbidities like diabetes, arterial hypertension or co-morbidity factors such as hypercholesterolemia, obesity and body fat distribution as well as fat-rich diet and physical inactivity are common in elderly persons and are associated with higher risk of stroke, increased mortality and disability. Obesity could represent a state of chronic inflammation that can be prevented to some extent by non-pharmaceutical interventions such as calorie restriction and hypothermia. Indeed, recent results suggest that H₂S-induced hypothermia in aged, overweight rats could have a higher probability of success in treating stroke as compared to other monotherapies, by reducing post-stroke brain inflammation. Likewise, it was recently reported that weight reduction prior to stroke, in aged, overweight rats induced by caloric restriction, led to an early re-gain of weight and a significant improvement in recovery of complex sensorimotor skills, cutaneous sensitivity, or spatial memory. animal models of stroke done in young animals ignore age-associated comorbidities and may explain, at least in part, the unsuccessful bench-to-bedside translation of neuroprotective strategies for ischemic stroke in aged subjects.

  8. Cellular and Molecular Mechanisms Underlying Non-Pharmaceutical Ischemic Stroke Therapy in Aged Subjects

    Directory of Open Access Journals (Sweden)

    Raluca Elena Sandu

    2017-12-01

    Full Text Available The incidence of ischemic stroke in humans increases exponentially above 70 years both in men and women. Comorbidities like diabetes, arterial hypertension or co-morbidity factors such as hypercholesterolemia, obesity and body fat distribution as well as fat-rich diet and physical inactivity are common in elderly persons and are associated with higher risk of stroke, increased mortality and disability. Obesity could represent a state of chronic inflammation that can be prevented to some extent by non-pharmaceutical interventions such as calorie restriction and hypothermia. Indeed, recent results suggest that H2S-induced hypothermia in aged, overweight rats could have a higher probability of success in treating stroke as compared to other monotherapies, by reducing post-stroke brain inflammation. Likewise, it was recently reported that weight reduction prior to stroke, in aged, overweight rats induced by caloric restriction, led to an early re-gain of weight and a significant improvement in recovery of complex sensorimotor skills, cutaneous sensitivity, or spatial memory. Conclusion: animal models of stroke done in young animals ignore age-associated comorbidities and may explain, at least in part, the unsuccessful bench-to-bedside translation of neuroprotective strategies for ischemic stroke in aged subjects.

  9. Physics of the Brain. Prevention of the Epileptic Seizures by the Multi-photon Pulsed-operated Fiber Lasers in the Ultraviolet Range of Frequencies.

    Science.gov (United States)

    Stefan, V. Alexander; IAPS Team

    The novel study of the epileptogenesis mechanisms is proposed. It is based on the pulsed-operated (amplitude modulation) multi-photon (frequency modulation) fiber-laser interaction with the brain epilepsy-topion (the epilepsy onset area), so as to prevent the excessive electrical discharge (epileptic seizure) in the brain. The repetition frequency, Ω, matches the low frequency (epileptic) phonon waves in the brain. The laser repetition frequency (5-100 pulses per second) enables the resonance-scanning of the wide range of the phonon (possible epileptic-to-be) activity in the brain. The tunable fiber laser frequencies, Δω (multi photon operation), are in the ultraviolet frequency range, thus enabling monitoring of the electrical charge imbalance (within the 10s of milliseconds), and the DNA-corruption in the epilepsy-topion, as the possible cause of the disease. Supported by Nikola Tesla Labs., Stefan University.

  10. Intranasal Inhalations of Bioactive Factors Produced by M2 Macrophages in Patients With Organic Brain Syndrome

    Science.gov (United States)

    2017-11-06

    Organic Brain Syndrome, Nonpsychotic; Neurocognitive Disorders; Mental Disorder, Organic; Delirium, Dementia, Amnestic, Cognitive Disorders; Nonpsychotic Organic Brain Syndrome; Organic Mental Disorder; Encephalopathy, Post-Traumatic, Chronic; Encephalopathy, Ischemic; Brain Ischemia

  11. Admitting acute ischemic stroke patients to a stroke care monitoring unit versus a conventional stroke unit : a randomized pilot study

    NARCIS (Netherlands)

    Sulter, Geert; Elting, Jan Willem; Langedijk, Marc; Maurits, Natasha M; De Keyser, Jacques

    2003-01-01

    BACKGROUND AND PURPOSE: Pathophysiological considerations and observational studies indicate that elevated body temperature, hypoxia, hypotension, and cardiac arrhythmias in the acute phase of ischemic stroke may aggravate brain damage and worsen outcome. METHODS: Both units were organized with the