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Sample records for cerebral ischemia induces

  1. Aqueous extract of Cordyceps alleviates cerebral ischemia-induced short-term memory impairment in gerbils

    Science.gov (United States)

    Lee, Sang-Hak; Ko, Il-Gyu; Kim, Sung-Eun; Hwang, Lakkyong; Jin, Jun-Jang; Choi, Hyun-Hee; Kim, Chang-Ju

    2016-01-01

    Cerebral ischemia is caused by reduced cerebral blood flow due to a transient or permanent cerebral artery occlusion. Ischemic injury in the brain leads to neuronal cell death, and eventually causes neurological impairments. Cordyceps, the name given to the fungi on insects, has abundant useful natural products with various biological activities. Cordyceps is known to have nephroprotective, hepatoprotective, anti-inflammatory, antioxidative, and antiapoptotic effects. We investigated the effects of Cordyceps on short-term memory, neuronal apoptosis, and cell proliferation in the hippocampal dentate gyrus following transient global ischemia in gerbils. For this study, a step-down avoidance test, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, immunohistochemistry for caspase-3 and 5-bromo-2′-de-oxyuridine, and western blot for Bax, Bcl-2, brain-derived neurotrophic factor (BDNF), and tyrosin kinase B were performed. In the present study, Cordyceps alleviated cerebral ischemia-induced short-term memory impairment. Cordyceps showed therapeutic effects through inhibiting cerebral ischemia-induced apoptosis in the hippocampus. Cordyceps suppressed cerebral ischemia-induced cell proliferation in the hippocampal dentate gyrus due to the reduced apoptotic neuronal cell death. Cordyceps treatment also enhanced BDNF and TrkB expressions in the hippocampus of ischemic gerbils. It can be suggested that Cordyceps overcomes cerebral ischemia-induced neuronal apoptosis, thus facilitates recovery following cerebral ischemia injury. PMID:27162767

  2. Aqueous extract of Cordyceps alleviates cerebral ischemia-induced short-term memory impairment in gerbils.

    Science.gov (United States)

    Lee, Sang-Hak; Ko, Il-Gyu; Kim, Sung-Eun; Hwang, Lakkyong; Jin, Jun-Jang; Choi, Hyun-Hee; Kim, Chang-Ju

    2016-04-01

    Cerebral ischemia is caused by reduced cerebral blood flow due to a transient or permanent cerebral artery occlusion. Ischemic injury in the brain leads to neuronal cell death, and eventually causes neurological impairments. Cordyceps, the name given to the fungi on insects, has abundant useful natural products with various biological activities. Cordyceps is known to have nephroprotective, hepatoprotective, anti-inflammatory, antioxidative, and antiapoptotic effects. We investigated the effects of Cordyceps on short-term memory, neuronal apoptosis, and cell proliferation in the hippocampal dentate gyrus following transient global ischemia in gerbils. For this study, a step-down avoidance test, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, immunohistochemistry for caspase-3 and 5-bromo-2'-de-oxyuridine, and western blot for Bax, Bcl-2, brain-derived neurotrophic factor (BDNF), and tyrosin kinase B were performed. In the present study, Cordyceps alleviated cerebral ischemia-induced short-term memory impairment. Cordyceps showed therapeutic effects through inhibiting cerebral ischemia-induced apoptosis in the hippocampus. Cordyceps suppressed cerebral ischemia-induced cell proliferation in the hippocampal dentate gyrus due to the reduced apoptotic neuronal cell death. Cordyceps treatment also enhanced BDNF and TrkB expressions in the hippocampus of ischemic gerbils. It can be suggested that Cordyceps overcomes cerebral ischemia-induced neuronal apoptosis, thus facilitates recovery following cerebral ischemia injury. PMID:27162767

  3. Experimental Focal Cerebral Ischemia

    DEFF Research Database (Denmark)

    Christensen, Thomas

    2007-01-01

    Focal cerebral ischemia due to occlusion of a major cerebral artery is the cause of ischemic stroke which is a major reason of mortality, morbidity and disability in the populations of the developed countries. In the seven studies summarized in the thesis focal ischemia in rats induced by occlusion...... of the middle cerebral artery (MCAO) was used as an experimental model of ischemic stroke. MCAO produces an acute lesion consisting of an ischemic core or focus with severely reduced blood flow surrounded by a borderzone or ischemic penumbra with less pronounced blood flow reduction. Cells in the...... radical scavenger α-PBN on the periinfarct depolarizations and infarct volume was investigated. In study number six, the activity of the mitochondrial electron transport complexes I, II and IV was evaluated histochemically during reperfusion after MCAO in order to assess the possible role of mitochondrial...

  4. Electroacupuncture pretreatment induces tolerance against focal cerebral ischemia through activation of canonical Notch pathway

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    Zhao Yu

    2012-09-01

    Full Text Available Abstract Background Electroacupuncture (EA pretreatment can induce the tolerance against focal cerebral ischemia. However, the underlying mechanisms have not been fully understood. Emerging evidences suggest that canonical Notch signaling may be involved in ischemic brain injury. In the present study, we tested the hypothesis that EA pretreatment-induced tolerance against focal cerebral ischemia is mediated by Notch signaling. Results EA pretreatment significantly enhanced Notch1, Notch4 and Jag1 gene transcriptions in the striatum, except Notch1 intracellular domain level, which could be increased evidently by ischemia. After ischemia and reperfusion, Hes1 mRNA and Notch1 intracellular domain level in ischemic striatum in EA pretreatment group were increased and reached the peak at 2 h and 24 h, respectively, which were both earlier than the peak achieved in control group. Intraventricular injection with the γ-secretase inhibitor MW167 attenuated the neuroprotective effect of EA pretreatment. Conclusions EA pretreatment induces the tolerance against focal cerebral ischemia through activation of canonical Notch pathway.

  5. Changes of hypoxia-inducible factor-1 signaling and the effect of cilostazol in chronic cerebral ischemia*

    Institute of Scientific and Technical Information of China (English)

    Han Chen; Aixuan Wei; Jinting He; Ming Yu; Jing Mang; Zhongxin Xu

    2013-01-01

    Hypoxia-inducible factor-1 and its specific target gene heme oxygenase-1, are involved in acute cerebral ischemia. However, very few studies have examined in detail the changes in the hypox-ia-inducible factor-1/heme oxygenase-1 signaling pathway in chronic cerebral ischemia. In this study, a rat model of chronic cerebral ischemia was established by permanent bilateral common carotid artery occlusion, and these rats were treated with intragastric cilostazol (30 mg/kg) for 9 weeks. Morris water maze results showed that cognitive impairment gradual y worsened as the cerebral ischemia proceeded. Immunohistochemistry, semi-quantitative PCR and western blot analysis showed that hypoxia-inducible factor-1α and heme oxygenase-1 expression levels in-creased after chronic cerebral ischemia, with hypoxia-inducible factor-1α expression peaking at 3 weeks and heme oxygenase-1 expression peaking at 6 weeks. These results suggest that the elevated levels of hypoxia-inducible factor-1α may upregulate heme oxygenase-1 expression fol-lowing chronic cerebral ischemia and that the hypoxia-inducible factor-1/heme oxygenase-1 sig-naling pathway is involved in the development of cognitive impairment induced by chronic cerebral ischemia. Cilostazol treatment al eviated the cognitive impairment in rats with chronic cerebral is-chemia, decreased hypoxia-inducible factor-1α and heme oxygenase-1 expression levels, and re-duced apoptosis in the frontal cortex. These findings demonstrate that cilostazol can protect against cognitive impairment induced by chronic cerebral ischemic injury through an anti-apoptotic mecha-nism.

  6. Inhibition of Sevoflurane Postconditioning Against Cerebral Ischemia Reperfusion-Induced Oxidative Injury in Rats

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    Shi-Dong Zhang

    2011-12-01

    Full Text Available The volatile anesthetic sevoflurane is capable of inducing preconditioning and postconditioning effects in the brain. In this study, we investigated the effects of sevoflurane postconditioning on antioxidant and immunity indexes in cerebral ischemia reperfusion (CIR rats. Rats were randomly assigned to five separate experimental groups I–V. In the sham group (I, rats were subjected to the same surgery procedures except for occlusion of the middle cerebral artery and exposed to 1.0 MAC sevoflurane 90 min after surgery for 30 min. IR control rats (group II were subjected to middle cerebral artery occlusion (MCAO for 90 min and exposed to O2 for 30 min at the beginning of reperfusion. Sevoflurane 0.5, 1.0 and 1.5 groups (III, IV, V were all subjected to MCAO for 90 min, but at the beginning of reperfusion exposed to 0.5 MAC, 1.0 MAC or 1.5 MAC sevoflurane for 30 min, respectively. Results showed that sevoflurane postconditioning can decrease serum tumor necrosis factor-alpha (TNF-α, interleukin-1 beta (IL-1β, nitric oxide (NO, nitric oxide synthase (NOS and increase serum interleukin-10 (IL-10 levels in cerebral ischemia reperfusion rats. In addition, sevoflurane postconditioning can still decrease blood lipid, malondialdehyde (MDA levels, infarct volume and increase antioxidant enzymes activities, normal pyramidal neurons density in cerebral ischemia reperfusion rats. It can be concluded that sevoflurane postconditioning may decrease blood and brain oxidative injury and enhance immunity indexes in cerebral ischemia reperfusion rats.

  7. Delayed ischemic electrocortical suppression during rapid repeated cerebral ischemia and kainate-induced seizures in rat

    DEFF Research Database (Denmark)

    Ilie, Andrei; Spulber, Stefan; Avramescu, Sinziana; Nita, Dragos Alexandru; Zagrean, Ana-Maria; Zagrean, Leon; Moldovan, Mihai

    2006-01-01

    Global cerebral ischemia induces, within seconds, suppression of spontaneous electrocortical activity, partly due to alterations in synaptic transmission. In vitro studies have found that repeated brief hypoxic episodes prolong the persistence of synaptic transmission due to weakened adenosine...... release. The aim of this study was to investigate in vivo whether the time to ischemic electrocortical suppression (T(ES)) could be altered during energy stress conditions such as rapid repeated global cerebral ischemia and kainate-induced seizures. Experiments were carried out in adult rats under chloral...... distinguish the alterations in spontaneous electrocortical activity we compared T(ES) with the ischemic suppression of visual evoked potentials (VEP). During the first ischemic episode, T(ES) was approximately 15 s and remained unchanged when five ischemic episodes were separated by 10-min reperfusion...

  8. Early immature neuronal death is partially involved in memory impairment induced by cerebral ischemia.

    Science.gov (United States)

    Yi, Jee Hyun; Cho, So Yeon; Jeon, Se Jin; Jung, Ji Wook; Park, Man Seok; Kim, Dong Hyun; Ryu, Jong Hoon

    2016-07-15

    Memory impairment is a common after an ischemic stroke. While delayed neuronal death in the CA1 region is usually linked to cerebral ischemia-induced memory impairment, the role of early immature neuronal death within the DG region in the memory state of an ischemic stroke model has rarely been studied. Here, we show a partial role of immature neuronal death in memory impairment in a global ischemia model. We found early immature neuronal death, which was determined by DCX and NeuN-double-staining. Injection of z-DEVD-fmk, a caspase-3 inhibitor, into the DG region rescued cells from immature neuronal death in the DG region without affecting delayed neuronal death in the CA1 region of an ischemic brain. Moreover, z-DEVD-fmk treatment partially rescued ischemia-induced spatial memory impairment. We also found that ischemia-induced LTP impairment in the perforant pathway was restored by z-DEVD-fmk treatment. These results suggest that early immature neuronal death is partially involved in ischemia-induced spatial memory impairment. PMID:27085588

  9. Mesenchymal stem cells transplantation suppresses inflammatory responses in global cerebral ischemia:contribution of TNF-α-induced protein 6

    Institute of Scientific and Technical Information of China (English)

    Qing-ming LIN; Shen ZHAO; Li-li ZHOU; Xiang-shao FANG; Yue FU; Zi-tong HUANG

    2013-01-01

    Aim:To investigate the effects of mesenchymal stem cells (MSCs) transplantation on rat global cerebral ischemia and the underlying mechanisms.Methods:Adult male SD rats underwent asphxial cardiac arrest to induce global cerebral ischemia,then received intravenous injection of 5x106 cultured MSCs of SD rats at 2 h after resuscitation.In another group of cardiac arrest rats,tumor necrosis factor-α-induced protein 6 (TSG-6,6 μg) was injected into the right lateral ventricle.Functional outcome was assessed at 1,3,and 7 d after resuscitation.Donor MSCs in the brains were detected at 3 d after resuscitation.The level of serum S-1OOB and proinflammatory cytokines in cerebral cortex were assayed using ELISA.The expression of TSG-6 and proinflammatory cytokines in cerebral cortex was assayed using RT-PCR.Western blot was performed to determine the levels of TSG-6 and neutrophil elastase in cerebral cortex.Results:MSCs transplantation significantly reduced serum S-1OOB level,and improved neurological function after global cerebral ischemia compared to the PBS-treated group.The MSCs injected migrated into the ischemic brains,and were observed mainly in the cerebral cortex.Furthermore,MSCs transplantation significantly increased the expression of TSG-6,and reduced the expression of neutrophil elastase and proinflammatory cytokines in the cerebral cortex.Intracerebroventricular injection of TSG-6 reproduced the beneficial effects of MSCs transplantation in rats with global cerebral ischemia.Conclusion:MSCs transplantation improves functional recovery and reduces inflammatory responses in rats with global cerebral ischemia,maybe via upregulation of TSG-6 expression.

  10. Protective Effects of Memantine Induced by Cerebral Ischemia and Reperfusion Injury in Rats

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    Hasan Hüseyin Özdemir

    2013-09-01

    Full Text Available OBJECTIVE: The severity of apoptosis developing after hypoxia-ischemia and reperfusion is an indicator of cerebral injury. In cerebral ischemia, there are many factors initiating the events progressing to cell death. The most common leading cause is excessive increase in intracellular calcium concentration. Ion channels in NMDA receptors cause cell death by increasing Ca+2 entries into the cell. Memantine is non-competitive excitatory amino acid blocker of NMDA receptor. Studies suggesting administration of memantine before and after ischemia decreasing the neural injury have been published. In this study we aimed to examine the memantine could have decreasing effect on neuronal injury resulting with apoptosis especially in penumbra region after ischemia and its effects on antioxidants and oxidants in brain tissues. METHODS: Experimental study was performed in three groups each of them including 7 rats. No procedure was performed in control group and it was used for evaluation of the normal brain tissue. Transient focal cerebral ischemia was performed by clipping the right common carotid arteries of the rats in ischemia and ischemia-drug groups. Ten mg/kg intraperitoneal memantine was administered in ischemia-drug group 30 minutes after ischemia and for 5 days. All of the rats were sacrificed after the experiment. Antioxidant and oxidant levels of the cerebral tissues were measured. Apoptotic cells were determined by immunohistochemically with TUNEL method. RESULTS: When the group administered memantine was compared with ischemia group, it was observed that memantine decreased apoptotic cells in the brain tissue and provided improvement in oxidant levels (p<0.05. CONCLUSION: In conclusion, memantine may be effective in prevention of apopitozis and neuronal injury in cerebral ischemic tissue via decreasing cerebral oxidant formations.

  11. Protective effect of extract of Cordyceps sinensis in middle cerebral artery occlusion-induced focal cerebral ischemia in rats

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    Tang Huiling

    2010-10-01

    Full Text Available Abstract Background Ischemic hypoxic brain injury often causes irreversible brain damage. The lack of effective and widely applicable pharmacological treatments for ischemic stroke patients may explain a growing interest in traditional medicines. From the point of view of "self-medication" or "preventive medicine," Cordyceps sinensis was used in the prevention of cerebral ischemia in this paper. Methods The right middle cerebral artery occlusion model was used in the study. The effects of Cordyceps sinensis (Caterpillar fungus extract on mortality rate, neurobehavior, grip strength, lactate dehydrogenase, glutathione content, Lipid Peroxidation, glutathione peroxidase activity, glutathione reductase activity, catalase activity, Na+K+ATPase activity and glutathione S transferase activity in a rat model were studied respectively. Results Cordyceps sinensis extract significantly improved the outcome in rats after cerebral ischemia and reperfusion in terms of neurobehavioral function. At the same time, supplementation of Cordyceps sinensis extract significantly boosted the defense mechanism against cerebral ischemia by increasing antioxidants activity related to lesion pathogenesis. Restoration of the antioxidant homeostasis in the brain after reperfusion may have helped the brain recover from ischemic injury. Conclusions These experimental results suggest that complement Cordyceps sinensis extract is protective after cerebral ischemia in specific way. The administration of Cordyceps sinensis extract significantly reduced focal cerebral ischemic/reperfusion injury. The defense mechanism against cerebral ischemia was by increasing antioxidants activity related to lesion pathogenesis.

  12. Protective Effects of Memantine Induced by Cerebral Ischemia and Reperfusion Injury in Rats

    OpenAIRE

    Hasan Hüseyin Özdemir; Demir, Caner F.; M. Said Berilgen; Bekir Akgün; Tuncay Kuloğlu; Oktay Kapan; Selçuk İlhan; Metin Balduz

    2013-01-01

    OBJECTIVE: The severity of apoptosis developing after hypoxia-ischemia and reperfusion is an indicator of cerebral injury. In cerebral ischemia, there are many factors initiating the events progressing to cell death. The most common leading cause is excessive increase in intracellular calcium concentration. Ion channels in NMDA receptors cause cell death by increasing Ca+2 entries into the cell. Memantine is non-competitive excitatory amino acid blocker of NMDA receptor. Studies suggesting ad...

  13. Endogenous IFN-β signaling exerts anti-inflammatory actions in experimentally induced focal cerebral ischemia

    DEFF Research Database (Denmark)

    Inácio, Ana R; Liu, Yawei; Clausen, Bettina H;

    2015-01-01

    grip strength tests, and cerebral infarct volumes were given by lack of neuronal nuclei immunoreactivity. RESULTS: Here, we report alterations in local and systemic inflammation in IFN-β knockout (IFN-βKO) mice over 8 days after induction of focal cerebral ischemia. Notably, IFN-βKO mice showed a...

  14. Angiotensin II type-2 receptor stimulation induces neuronal VEGF synthesis after cerebral ischemia.

    Science.gov (United States)

    Mateos, Laura; Perez-Alvarez, Maria Jose; Wandosell, Francisco

    2016-07-01

    Intense efforts are being undertaken to understand the pathobiology of ischemia and to develop novel and effective treatments. Angiotensin II type 2 receptor (AT2R) is related with a beneficial role in neurodegenerative disorders, including ischemia. However, the underlying molecular mechanism remains elusive. In this study, we have established that AT2R stimulation by C21 compound, a specific AT2R agonist, caused a VEGF upregulation. Using mouse primary cortical neurons exposed to oxygen-glucose deprivation (OGD), we established that this effect was mediated by a mechanism dependent of mTORC1 signaling since mTOR inhibition abolished the C21-induced VEGF upregulation. Also, we have temporally characterized the changes on VEGF levels after ischemia induction in rats using two different approaches: transient and permanent middle cerebral artery occlusion (tMCAO and pMCAO). VEGF levels were permanently augmented after reperfusion (tMCAO) whereas lower levels of VEGF were found after pMCAO, remarkably at 21days. Therefore, C21 compound accelerated the recovery of the neurological status of pMCAO rats, reduced the ischemic damage area and abolished pMCAO-induced VEGF downregulation at 21days. This effect of C21 compound was mainly observed in neurons of the peri-infarct area. Our results suggest that a C21-induced VEGF upregulation may be crucial after an ischemic neuronal insult in both of our experimental approaches. This upregulation was mediated by a mechanism dependent of Akt/mTOR signaling pathway, since mTOR inhibition abolished the VEGF upregulation induced by C21. Considering that VEGF is involved in regenerative processes, we propose that AT2R activation could be used as a potential pharmacological strategy after ischemic stroke. PMID:27045356

  15. Clinical Neuroimaging of cerebral ischemia

    International Nuclear Information System (INIS)

    Notice points in clinical imaging of cerebral ischemia are reviewed. When cerebral blood flow is determined in acute stage of cerebral embolism (cerebral blood flow SPECT), it is important to find area of ischemic core and ischemic penumbra. When large cortex area is assigned to ischemic penumbra, thrombolytic therapy is positively adapted, but cautious correspondence is necessary when ischemic core is recognized. DWI is superior in the detection of area equivalent to ischemic core of early stage, but, in imaging of area equivalent to ischemic penumbra, perfusion image or distribution image of cerebral blood volume (CBV) by MRI need to be combined. Luxury perfusion detected by cerebral blood flow SPECT in the cases of acute cerebral embolism suggests vascular recanalization, but a comparison with CT/MRI and continuous assessment of cerebral circulation dynamics were necessary in order to predict brain tissue disease (metabolic abnormality). In hemodynamic cerebral ischemia, it is important to find stage 2 equivalent to misery perfusion by quantification of cerebral blood flow SPECT. Degree of diaschisis can indicate seriousness of brain dysfunction for lacuna infarct. Because cerebral circulation reserve ability (perfusion pressure) is normal in all areas of the low cerebral blood flow by diaschisis mechanism, their areas are easily distinguished from those of hemodynamic cerebral ischemia. (K.H.)

  16. Sirt1 in cerebral ischemia

    OpenAIRE

    Koronowski, Kevin B.; Perez-Pinzon, Miguel A.

    2015-01-01

    Cerebral ischemia is among the leading causes of death worldwide. It is characterized by a lack of blood flow to the brain that results in cell death and damage, ultimately causing motor, sensory, and cognitive impairments. Today, clinical treatment of cerebral ischemia, mostly stroke and cardiac arrest, is limited and new neuroprotective therapies are desperately needed. The Sirtuin family of oxidized nicotinamide adenine dinucleotide (NAD+)-dependent deacylases has been shown to govern seve...

  17. Protective effect of extract of Cordyceps sinensis in middle cerebral artery occlusion-induced focal cerebral ischemia in rats

    OpenAIRE

    Liu, Zhenquan; Li, Pengtao; ZHAO, Dan; Tang, Huiling; Guo, Jianyou

    2010-01-01

    Background Ischemic hypoxic brain injury often causes irreversible brain damage. The lack of effective and widely applicable pharmacological treatments for ischemic stroke patients may explain a growing interest in traditional medicines. From the point of view of "self-medication" or "preventive medicine," Cordyceps sinensis was used in the prevention of cerebral ischemia in this paper. Methods The right middle cerebral artery occlusion model was used in the study. The effects of Cordyceps si...

  18. PUFA-induced neuroprotection against cerebral or spinal cord ischemia via the TREK-1 channel

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    Heurteaux Catherine

    2007-05-01

    Full Text Available The nutritional interest of polyunsaturated fatty acids from omega-3, that are mainly present in vegetal and fish oils is now validated by the scientific community. Their beneficial effects have first been reported in coronary heart diseases. Many neurological and chronic diseases are often related to deficiencies in omega-3 and omega-6 and their derivatives. Polyunsaturated fatty acids from omega-3 family are essential to brain growth and cognitive functions. They are recently considered as factors of improvement in some mental diseases. Today, polyunsaturated fatty acids could play a key role in the prevention and/or or the treatment of cerebral diseases. With the development of in vitro and in vivo experimental models, it is now possible to demonstrate the PUFA-induced neuronal protection against major pathologies such as epileptic seizures, cerebral and spinal ischemia. The molecular mechanism of neuronal protection induced by polyunsaturated fatty acids and particularly alphalinolenic acid is now clarified. The alpha-linolenic target would be a potassium channel, TREK-1, which belongs to the new family of 2-P domain potassium channels (K-2P. The discovery of the physiopathological role of these K-2P channels can represent an important therapeutical challenge not only in cerebrovascular diseases and epilepsy, but also in psychiatry.

  19. Electroacupuncture-Induced Neuroprotection against Cerebral Ischemia in Rats: Role of the Dopamine D2 Receptor

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    Ming-Shu Xu

    2013-01-01

    Full Text Available Background. Cerebral ischemia is known to produce brain damage and related behavioural deficits, including memory deficits and motor disorders. Evidence shows that EA significantly promotes recovery of neurological function and thus improves quality of life. Objective. Evidence exists for the involvement of catecholamines in human neuroplasticity. A better understanding of dopaminergic (DAergic modulation in this process will be important. Methods. A total of 72 adult male Sprague-Dawley (SD rats were divided into 6 groups: normal, model, EA, spiperone group, EA + spiperone group, and pergolide. The middle cerebral artery occlusion (MCAO model was used in all 6 groups except the normal group. A behavioural assessment was conducted at 1, 3, 5, and 7 days after MCAO. The percent of brain infarct area was also determined 7 days after MCAO. Tyrosine hydroxylase (TH and growth-associated protein 43 (GAP-43 fluorescence double labeling was performed in the striatum. Results. In this study, we found that EA at Fengchi (GB20 acupoints resulted in marked improvements based on a behavioural assessment. Both TTC staining and GAP-43 immunofluorescence labeling results showed that EA treatment reduced ischemia injury and promoted neuroplasticity compared with the model group. The D2R-selective agonist, pergolide, showed similar results, but these results were reversed by the D2R-selective antagonist, spiperone. We also found that there were more colocalization and expression of GAP-43 and TH in the EA and pergolide groups than those in the other groups. Conclusion. These results suggest that the neuroplasticity induced by EA was mediated by D2 autoreceptors in DAergic neurons.

  20. Unique action mechanisms of tramadol in global cerebral ischemia-induced mechanical allodynia.

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    Matsuura, Wataru; Kageyama, Erika; Harada, Shinichi; Tokuyama, Shogo

    2016-06-15

    Central poststroke pain is associated with specific somatosensory abnormalities, such as neuropathic pain syndrome. Although central poststroke pain is a serious condition, details pertaining to underlying mechanisms are not well established, making current standard treatments only partially effective. Here, we assessed the effects of tramadol, an analgesic drug mediated by opioid receptors, using a mouse model of global cerebral ischemia. Ischemia was induced by bilateral carotid artery occlusion (30 min) in male ddY mice. Development of hind-paw mechanical allodynia was measured 3 days after bilateral carotid artery occlusion using the von Frey test. Mechanical allodynia was significantly and dose dependently suppressed by intraperitoneal tramadol (10 or 20 mg/kg). These effects, which peaked at 10 min and continued for at least 60 min, were inhibited by naloxone (nonselective opioid receptor antagonist, 1 mg/kg, intraperitoneal). Tramadol antinociception was significantly negated by β-funaltrexamine (selective μ-opioid receptor antagonist, 20 mg/kg, intraperitoneal), but not naltrindole (selective δ-opioid receptor antagonist, 5 mg/kg, intraperitoneal) or nor-binaltorphimine (selective κ-opioid receptor antagonist, 10 mg/kg, intraperitoneal) after 5 min, by β-funaltrexamine and nor-binaltorphimine but not naltrindole after 10 min, and by all selective opioid receptor antagonists at 15 and 30 min after tramadol treatment. These results suggested that antinociception induced by tramadol through various opioid receptors was time dependent. Furthermore, it is possible that the opioid receptors involved in tramadol-induced antinociception change over time with the metabolism of this drug. PMID:27171031

  1. Is longer sevoflurane preconditioning neuroprotective in permanent focal cerebral ischemia?

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    Qiu, Caiwei; Sheng, Bo; Wang, Shurong; Liu, Jin

    2013-08-15

    Sevoflurane preconditioning has neuroprotective effects in the cerebral ischemia/reperfusion model. However, its influence on permanent cerebral ischemia remains unclear. In the present study, the rats were exposed to sevoflurane for 15, 30, 60, and 120 minutes, followed by induction of permanent cerebral ischemia. Results demonstrated that 30- and 60-minute sevoflurane preconditioning significantly reduced the infarct volume at 24 hours after cerebral ischemia, and 60-minute lurane preconditioning additionally reduced the number of TUNEL- and caspase-3-positive cells in the ischemic penumbra. However, 120-minute sevoflurane preconditioning did not show evident neuroprotective effects. Moreover, 60-minute sevoflurane preconditioning significantly attenuated neurological deficits and infarct volume in rats at 4 days after cerebral ischemia. These findings indicated that 60-minute sevoflurane preconditioning can induce the best neuroprotective effects in rats with permanent cerebral ischemia through the inhibition of apoptosis. PMID:25206521

  2. [Cerebral ischemia in young adults].

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    Berlit, P; Endemann, B; Vetter, P

    1991-08-01

    An overview is given over etiology and prognosis of cerebral ischemias until the age of 40. In a time period of 19 years, 168 patients were diagnosed with cerebral ischemia until the age of 40 (91 females, 77 males). The most frequent etiology is premature atherosclerosis in patients with vascular risk factors (up to 50%). Cardiogenic embolism is responsible for 1 to 34% of the cases: cardiac valve diseases and endocarditis being the most frequent sources. In 2 to 19% a vasculitis is diagnosed. While infectious arteritis is especially frequent in countries of the third world, immunovasculitides are common in Europe and the USA. Noninflammatory vasculopathies include spontaneous or traumatic dissection, fibromuscular dysplasia and vascular malformations. A migrainous stroke is especially frequent in female smokers with intake of oral contraceptives. During pregnancy both sinus thrombosis and arterial ischemia occur. Hematologic causes for ischemia are polycythemia, thrombocytosis and genetic diseases (sickle cell anemia, AT3-deficiency). Cerebral ischemia may occur in connection with the ingestion of ergot-derivates. The prognosis of cerebral ischemia in young adults is better than in older stroke-patients. PMID:1937340

  3. CART attenuates endoplasmic reticulum stress response induced by cerebral ischemia and reperfusion through upregulating BDNF synthesis and secretion.

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    Qiu, Bin; Hu, Shengdi; Liu, Libing; Chen, Man; Wang, Lai; Zeng, Xianwei; Zhu, Shigong

    2013-07-12

    Cocaine and amphetamine regulated transcript (CART), a neuropeptide, has shown strong neuroprotective effects against cerebral ischemia and reperfusion (I/R) injury in vivo and in vitro. Here, we report a new effect of CART on ER stress which is induced by cerebral I/R in a rat model of middle cerebral artery occlusion (MCAO) or by oxygen and glucose deprivation (OGD) in cultured cortical neurons, as well as a new functionality of BDNF in the neuroprotection by CART against the ER stress in cerebral I/R. The results showed that CART was effective in reducing the neuronal apoptosis and expression of ER stress markers (GRP78, CHOP and cleaved caspase12), and increasing the BDNF expression in I/R injury rat cortex both in vivo and in vitro. In addition, the effects of CART on ischemia-induced neuronal apoptosis and ER stress were suppressed by tyrosine receptor kinase B (TrkB) IgG, whereas the effects of CART on BDNF transcription, synthesis and secretion were abolished by CREB siRNA. This work suggests that CART is functional in inhibiting the cerebral I/R-induced ER stress and neuronal apoptosis by facilitating the transcription, synthesis and secretion of BDNF in a CREB-dependent way. PMID:23770418

  4. Brain edema and tumor necrosis factor-like weak inducer of apoptosis in rats with cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Renlan Zhou; Peng Xie

    2008-01-01

    BACKGROUND: Recent studies have demonstrated that tumor necrosis factor-like weak inducer of apoptosis (TWEAK) participates in brain edema. However, it is unclear whether blood-brain barrier (BBB) disruption is associated with TWEAK during the process of brain edema OBJECTIVE: To investigate the effects of TWEAK on BBB permeability in brain edema.DESIGN, TIME AND SETTING: An immunohistochemical observation, randomized, controlled animal experiment was pertbrmed at the Laboratory of Neurosurgical Anatomy, Xiangya Medical College, Central South University & Central Laboratory, Third Xiangya Hospital, Central South University between January 2006 and December 2007.MATERIALS: A total of 48 adult Wistar rats were randomly divided into three groups: normal control (n =8), sham-operated (n = 8), and ischemia/reperfusion (n = 32). Rats from the ischemia/reperfusion group were randomly assigned to four subgroups according to different time points, i.e., 2 hours of ischemia followed by 6 hours (n = 8), 12 hours {n = 8), 1 day (n = 8), or 12 days (n = 8) of reperfusion.METHODS: Focal cerebral ischemia/reperfusion injury was induced by middle cerebral artery occlusion (MCAO) using the suture method in rats from the ischemia/reperfusion group. Thread was introduced at a depth of 17-19 mm. Rats in the sham-operated group were subjected to experimental procedures similar to the ischemia/reperfusion group; however, the introducing depth of thread was 10 mm. The normal control group was not given any intervention.MAIN OUTCOME MEASURES: TWEAK expression was examined by immunohistochemistry; brain water content on the ischemic side was calculated as the ratio of dry to wet tissue weight; BBB permeability was measured by Evans blue extravasation.RESULTS: A total of eight rats died prior to and after surgery and an additional eight rats were randomly entered into the study. Thus 48 rats were included in the final analysis. In the ischemia/reperfusion group,TWEAK-positive cells were

  5. Vascular endothelial growth factor induced angiogenesis following focal cerebral ischemia/reperfusion injury in rabbits

    Institute of Scientific and Technical Information of China (English)

    Huaijun Liu; Jiping Yang; Fenghai Liu; Qiang Zhang; Hui Li

    2006-01-01

    BACKGROUND: Therapeutic angiogenesis has opened up new pathway for the treatment of ischemic cerebrovascular disease in recent years. The exploration of the effect of vascular endothelial growth factor (VEGF) on inducing angiogenesis following ischemia/reperfusion injury can provide better help for the long-term treatment of cerebrovascular disease in clinic.OBJECTIVE: To observe the effect of VEGF on inducing angiogenesis following focal cerebral ischemia/reperfusion injury in rabbits through the angiogenesis of microvessels reflected by the expression of the factors of vascular pseudohemophilia.DESIGN: A randomized controlled animal trial.SETTING: Department of Medical Imaging, Second Hospital of Hebei Medical University.MATERIALS: Sixty-five healthy male New Zealand rabbits of clean degree, weighing (2.6±0.2) kg, aged4.5-5 months, were used. The polyclonal antibody against vascular pseudohemophilia (Beijing Zhongshan Company), recombinant VEGF165 (Peprotech Company, USA), biotinylated second antibody and ABC compound (Wuhan Boster Company) were applied.METHODS: The experiments were carried out in the Laboratory of Neuromolecular Imaging and Neuropathy,Second Hospital of Hebei Medical University from May to August in 2005. ① The rabbits were randomly divided into three groups: sham-operated group (n=15), control group (n=25) and VEGF-treated group(n=25). In the control group and VEGF-treated group, models were established by middle cerebral artery occlusion (MCAO) induced focal cerebral ischemia/reperfusion. In the VEGF-treated group, VEGF165(2.5 mg/L) was stereotactically injected into the surrounding regions of the infarcted sites immediately after the 2-hour ischemia/reperfusion; Saline of the same dosage was injected in the control group. But the rabobserved on the 3rd, 7th, 14th, 28th and 70th days of the experiment respectively, 3 rabbits in the sham-operated group and 5 in the control group and VEGF-treated group were observed at each time point. The

  6. Centrophenoxine improves chronic cerebral ischemia induced cognitive deficit and neuronal degeneration in rats

    Institute of Scientific and Technical Information of China (English)

    Yun LIAO; Rui WANG; Xi-can TANG

    2004-01-01

    AIM: To study the effects of centrophenoxine (CPH, meclofenoxate) on chronic cerebral hypoperfusion induced deficits in rats. METHODS: Chronic hypoperfusion in rats was performed by permanent bilateral ligation of the common carotid arteries. Morris water maze was used to measure spatial memory performance. Spectrophotometrical techniques were used to assay SOD, GPx activities, MDA content, TXB2, and 6-keto-PGF1α levels. Morphological change was examined by HE staining. The expression of Bax and p53 protein were assayed by immunohistochemistry analysis. RESULTS: Chronic hypoperfusion in rats resulted in spatial memory impairments shown by longer escape latency and shorter time spent in the target quadrant. These behavioral dysfunction were accompanied by increase in SOD and GPx activities, the content of MDA, the levels of pro-inflammatory mediators (TXB2, 6-keto-PGF1α), overexpression of Bax and P53 protein, and delayed degeneration of neurons in cortex and hippocampus. Oral administration of CPH (100 mg/kg, once per day for 37 d) markedly improved the memory impairment, reduced the increase in antioxidant enzyme activities, MDA content and the levels of pro-inflammatory mediators to their normal levels, and attenuated neuronal damage. CONCLUSION: The abilities of CPH to attenuate memory deficits and neuronal damage after ischemia may be beneficial in cerebrovascular type dementia.

  7. Cervical sympathetic trunk transection affects inducible nitric oxide synthase expression in rat hippocampus following focal cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Liangzhi Xiong; Yan Wang; Qingxiu Wang; Qingshan Zhou

    2008-01-01

    BACKGROUND: The stellate ganglion block (SGB) plays a protective role in focal cerebral ischemia/reperfusion injury. The human SGB can be simulated by transection of the cervical sympathetic trunk (TCST) in rats.OBJECTIVE: To observe the effects of TCST on inducible nitric oxide synthase (iNOS) levels and cerebral infarct wolume in the hippocampus of rats with cerebral ischemia/reperfusion injury, and to analyze the mechanism of action.DESIGN, TIME AND SETTING: A completely randomized, controlled, neuropathological experiment was performed at the Institute of Neurological Disease, Taihe Hospital, Yunyang Medical College between March and September 2006.MATERIALS: A total of 93 Wistar rats, aged 17-18 weeks, of either gender, were used for this study. 2, 3, 5-triphenyl tetrazolium chloride was purchased from Changsha Hongyuan Biological Reagent Company, China. Rabbit iNOS antibody and goat anti-rabbit lgG antibody were the products of Wuhan Boster Biological Reagent Co., Ltd., China.METHODS: Ten rats were randomly selected for the sham-operated group. Cerebral ischemia/reperfusion injury was induced by middle cerebral artery occlusion (MCAO) using the suture method in the remaining rats. Forty successful rat models were randomly and equally divided into the following two groups: (1) TCST group: subsequent to TCST, MCAO was performed for 2 hours, followed by 24 hours reperfusion; (2) model group: rats underwent experimental procedures similar to the TCST group, with the exception of TCST. Rats in the sham-operated group were subjected to experimental procedures similar to the model group; however, the thread was only introduced to a depth of 10 mm.MAIN OUTCOME MEASURES: Following 24 hours of reperfusion, functional neurological deficits were scored. Brain tissue sections from ten rats of each group were used to measure cerebral infarct volume by TTC staining. Hippocampal tissue sections of an additional ten rats from each group were used to detect iNOS levels using

  8. Effect of pre-ischemia on hypoxia-inducible factor expression in the brain tissue of rats with cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: Hypoxia-inducible factor 1 (HIF-1) can lead to the adaptative reaction of body for hypoxia and ischemia. HIF-1 plays an important role in the response of ischemia-hypoxia. At present, there has been no overall report on the significance for the expression of HIF-1 following experimental cerebral ischemia.OBJECTIVE: To observe the expression of HIF-1 after middle cerebral artery occlusion (MCAO) by immunohistochemical method.DESIGN: Completely randomly grouped controlled animal experiment.SETTING: Second Hospital, Xi'an Jiaotong University.MATERIALS: Thirty-six Sprague-Dawley healthy male rats, with body mass of 250 - 330 g, were used in this study. Thirty-six rats were randomized into 3 groups: pre-ischemia group, sham-operation group and control group, with 12 rats in each.METHODS: This study was carried out in the clinical laboratory, People's Hospital of Ningjin County of Shandong Province from March 2006 to January 2007. Rats in the pre-ischemia group were created into pre-ischemia models by two embolisms twice. Three days after ischemic preconditioning, middle cerebral artery (MCA) was occluded for 2 hours with the same method. After being perfused for 22 hours, the rats were euthanized. In the sham-operation group, rats were not given the treatment of pre-ischemia. In the first operation, only common carotid artery (CCA) and its crotch were exposed in the first operation, and MCA was not blocked by inserting embolism. At postoperative 3 days, rats were euthanized after being subjected to MCAO for 2 hours and reperfusion 22 hours by the same procedure as that in the pre-ischemia group. As for each rat in the control group, only CCA and its crotch were exposed, and no any other treatment was carried out on them.MAIN OUTCOME MEASURES: Brain tissue of each rat was performed immunohistochemical staining at reperfusion 22 hours after pre-ischemia, HIF-1 expression and brain infarct volume were detected.RESULTS: Thirty-six Sprague-Dawley rats were

  9. Animal models of cerebral ischemia

    Science.gov (United States)

    Khodanovich, M. Yu.; Kisel, A. A.

    2015-11-01

    Cerebral ischemia remains one of the most frequent causes of death and disability worldwide. Animal models are necessary to understand complex molecular mechanisms of brain damage as well as for the development of new therapies for stroke. This review considers a certain range of animal models of cerebral ischemia, including several types of focal and global ischemia. Since animal models vary in specificity for the human disease which they reproduce, the complexity of surgery, infarct size, reliability of reproduction for statistical analysis, and adequate models need to be chosen according to the aim of a study. The reproduction of a particular animal model needs to be evaluated using appropriate tools, including the behavioral assessment of injury and non-invasive and post-mortem control of brain damage. These problems also have been summarized in the review.

  10. Mannosylated liposomal cytidine 5' diphosphocholine prevent age related global moderate cerebral ischemia reperfusion induced mitochondrial cytochrome c release in aged rat brain.

    Science.gov (United States)

    Ghosh, S; Das, N; Mandal, A K; Dungdung, S R; Sarkar, S

    2010-12-29

    Mitochondrial dysfunctions generating from cerebral ischemia-reperfusion exert a potential threat on neuronal cell survival and hence, accelerate the aging process and age dependent neuropathology. Thirty min moderate cerebral ischemia induced by bilateral common carotid artery occlusion (BCCAO) followed by 30 min reperfusion caused an increased diene production, depleted glutathione (GSH) content, reduced superoxide dismutase (SOD) and catalase activities and pyramidal neuronal loss in young (2 months old) and aged (20 months old) rat brain compared to sham operated controls. Cytidine 5' diphosphocholine (CDP-Choline) is a known neuroprotective drug. CDP-Choline after metabolism in the liver suffers hydrolysis and splits into cytidine and choline before entering systemic circulation and hardly circumvents blood brain barrier (BBB) as such. Previous reports show CDP-Choline liposomes significantly increased in vivo uptake compared to "free drug" administration in cerebral ischemia. To enhance the therapeutic concentration build up in brain we sought to formulate mannosylated liposomal CDP-Choline (MLCDP) utilizing the mannose receptors. We tested the therapeutic supremacy of MLCDP over liposomal CDP-Choline (LCDP) in global moderate cerebral ischemia reperfusion induced neuronal damage. CDP-Choline in MLCDP delivery system was found potent to exert substantial protection against global moderate cerebral ischemia reperfusion induced mitochondrial damage in aged rat brain. Membrane lipid peroxidation, GSSG/GSH ratio and reactive oxygen species (ROS) generation in cerebral tissue were found to be higher in aged, compared to young rat. Further decline of those parameters was observed in aged rat brain by the induction of global moderate cerebral ischemia and reperfusion. MLCDP treatment when compared to free or LCDP treatment prevented global moderate cerebral ischemia-reperfusion induced mitochondrial damage as evident ultra structurally and release of cytochrome c

  11. TLR4 signaling induced TLR2 expression in the process of mimic cerebral ischemia/reperfusion in vitro

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Both TLR4 and TLR2 participated in the mediation of the inflammatory injury in the process of partial cerebral ischemia/reperfusion.However,it still remains unclear whether a crosstalk exists between TLR2 and TLR4 in ischemic cerebral damage.In the present study,we investigated the effect of TLR4 signaling on TLR2 expression during mimic cerebral I/R in vitro.BV-2 cells were cultured and treated with ischemia/reperfusion,then transfected with the plasmid pEGFP-H1/TLR4-siRNA,the plasmid pEGFP-H1/control sequence-siRNA and the blank plasmid,respectively.Interestingly,the expression of TLR2 and TLR4 mRNA and protein,NF-κB p65 mRNA and supernatant TNF-α level were significantly higher in ischemia/reperfusion treated cells than those lack of ischemia/reperfusion treatment,and as compared with those in ischemia/reperfusion treated cells without transfection,no significant differences about the above mentioned gene and protein expression were found in the blank plasmid tranfected cells and the plasmid pEGFP-H1/control sequence-siRNA transfected cells respectively,while the expression levels in the plasmid pEGFP-H1/TLR4-siRNA transfected cells were significantly lower.Additionally,in order to determine the effects of pyrrolidinediethyldithiocarbamate (PDTC),an NF-κB inhibitor,on the TLR4-induced TLR2 expression in BV-2 cells treated with ischemia/reperfusion,it was found that TLR4 and TLR2 mRNA expressions in PDTC pretreated cells were significantly lower in comparison with normal saline pretreated cells and non-pretreated cells.The data suggested that TLR2 activation,signaled by TLR4 and regulated by NF-κB,might be directly involved play an important role in ischemia/reperfusion induced brain damage.

  12. Effect of certain antioxidants on cerebral ischemia induced in irradiated rats

    International Nuclear Information System (INIS)

    The present study was performed to investigate the possible roles of vitamin E, coenzyme-Q10 and rutin in ameliorating the biochemical changes in the brain and serum induced by cerebral ischemia/reperfusion (I/R) in rats exposed to whole body gamma radiation. Induction of I/R increased the brain oxidative stress as manifested by a marked increase in its content of MDA accompanied by depletion of its GSH content, and a compensatory elevation in the cytosolic activities of GPx and GR enzymes. In addition, it caused a significant rise in brain cytosolic activity of LDH and cytosolic Ca2+ level. Furthermore, I/R provoked a remarkable inflammatory response reflected by the observed significant increment in serum levels of the pro inflammatory cytokines TNF-α and IL-Iβ. Moreover, induction of I/R in fractionally or single irradiated rats resulted in a further increase in brain oxidative stress and cytosolic LDH activity, disturbed brain Ca2+ homeostasis, as well as an exaggerated inflammatory reaction. Concomitant to radiation, daily administration of each of vitamin E, coenzyme-Q10 and rutin to irradiated rats before induction of I/R, was effective in alleviating the brain oxidative stress (represented by a decrease in the increment of brain MDA concentration and the restoration of its GSH level). Moreover, each of these antioxidants caused a significant attenuation of the compensatory rise of the cytosolic activities of GPx and GR enzymes. Antioxidants were, also; able to partially correct the metabolic disturbances induced in brain by I/R and radiation, that correction was reflected by lowering of the cytosolic LDH activity and Ca2+ level. Administration of each of vitamin E and rutin revealed a potent ant inflammatory action of these antioxidants, while coenzyme-Q10 had no significant effect on serum levels of TNF-α and IL-Iβ. Finally, the present study justifies the use of antioxidants in hope to alleviate or minimize the various deleterious effects of either

  13. Exercise preconditioning reduces ischemia reperfusion-induced focal cerebral infarct volume through up-regulating the expression of HIF-1α.

    Science.gov (United States)

    Wang, Lu; Deng, Wenqian; Yuan, Qiongjia; Yang, Huijun

    2015-03-01

    To study the effect and mechanism of exercise preconditioning on focal cerebral ischemia reperfusion induced cerebral infarction via rat model; Sixty Sprague Dawley rats were divided into three groups at random: ischemia reperfusion group (IR, n=24), sham group (sham, n=12) and exercise preconditioning group (EP, n=24). Group EP carried out moderate exercise preconditioning for 4 weeks (swimming with non-weight bearing, 60 minutes/day, 6 days/week), Rats in Group EP and IR were established cerebral ischemia reperfusion injury model by Zea Longa's thread method. The cerebral infarct volume in rat of different group was evaluated after 2%TTC staining, expression of HIF-1α in rats' brain was detected by real-time RT-PCR, immunohistochmeistry method and western blot. No cerebral infarction and significant expression of HIF-1α in Group sham. Compared with Group IR, there was smaller infarct volume and stronger HIF-1α expression in Group EP (Pexercise preconditioning reduces ischemia reperfusion induced focal cerebral infarct volume through up-regulating the expression of HIF-1α. PMID:25796156

  14. Effect of policosanol on cerebral ischemia in Mongolian gerbils

    OpenAIRE

    Molina V; Arruzazabala M.L.; Carbajal D.; Valdés S.; Noa M.; Más R.; Fraga V.; Menéndez R.

    1999-01-01

    Policosanol is a mixture of higher aliphatic primary alcohols isolated from sugar cane wax, whose main component is octacosanol. An inhibitory effect of policosanol on platelet aggregation and cerebral ischemia in animal models has been reported. Thus, the objective of the present study was to evaluate the effect of policosanol on cerebral ischemia induced by unilateral carotid ligation and bilateral clamping and recirculation in Mongolian gerbils. Policosanol (200 mg/kg) administered immedia...

  15. Multiple molecular penumbras after focal cerebral ischemia.

    Science.gov (United States)

    Sharp, F R; Lu, A; Tang, Y; Millhorn, D E

    2000-07-01

    Though the ischemic penumbra has been classically described on the basis of blood flow and physiologic parameters, a variety of ischemic penumbras can be described in molecular terms. Apoptosis-related genes induced after focal ischemia may contribute to cell death in the core and the selective cell death adjacent to an infarct. The HSP70 heat shock protein is induced in glia at the edges of an infarct and in neurons often at some distance from the infarct. HSP70 proteins are induced in cells in response to denatured proteins that occur as a result of temporary energy failure. Hypoxia-inducible factor (HIF) is also induced after focal ischemia in regions that can extend beyond the HSP70 induction. The region of HIF induction is proposed to represent the areas of decreased cerebral blood flow and decreased oxygen delivery. Immediate early genes are induced in cortex, hippocampus, thalamus, and other brain regions. These distant changes in gene expression occur because of ischemia-induced spreading depression or depolarization and could contribute to plastic changes in brain after stroke. PMID:10908035

  16. EFFECT OF ELECTROACUPUNCTURE OF DUMAI-ACUPOINTS ON CEREBRAL NO AND BLOOD ENDOTHELIN CONTENTS IN RATS WITH ACUTE CEREBRAL ISCHEMIA

    Institute of Scientific and Technical Information of China (English)

    MaYang; XuNenggui; XuGuansun; ZhongPing; WangLianfa; ZhuShunli; ChenQuanzhu

    2000-01-01

    Thirty Wistar rats were randomly and evenly divided into control group, cerebral ischemia group and ischemia + electroacupuncture (EA) group. The bilateral common carotid arteries were occluded to induce acute cerebral ischemia. Nitric oxide (NO) and endothelin (ET)contents in the cerebral tissues and blood were measured under normal condition, immediately after ischemia and following EA. Results showed that after acute cerebral ischemia NO and ET contents in the cerebral tissues increased significantly (P<0.01) while serum ET increased and serum NO lowered obviously (P<0.05). Following EA of Baihui (GV 20) and Dazhui (GV 14), both NO and ET in cerebral tissues and serum turned to normal basically. It showed that EA could protect the cerebral tissues from injury induced by ischemia, NO and ET might participate in the modulation process of EA.

  17. EFFECT OF ELECTROACUPUNCTURE OF DUMAI-ACUPOINTS ON CEREBRAL NO AND BLOOD ENDOTHELIN CONTENTS IN RATS WITH ACUTE CEREBRAL ISCHEMIA

    Institute of Scientific and Technical Information of China (English)

    马杨; 许能贵; 许冠荪; 钟平; 王联发; 朱舜丽; 陈全珠

    2000-01-01

    Thirty Wistar rats were randomly and evenly divided into control group, cerebral ischemia group and ischemia + electroacupuncture (EA) group. The bilateral common carotid arteries were occluded to induce acute cerebral ischemia. Nitric oxide (NO) and endothelin (ET) contents in the cerebral tissues and blood were measured under normal condition, immediately after ischemia and following EA. Results showed that after acute cerebral ischemia NO and ET contents in the cerebral tissues increased significantly (P < 0.01) while serum ET increased and serum NO lowered obviously (P<0.05). Following EA of Baihui (GV 20) and Dazhui (GV 14), both NO and ET in cerebral tissues and serum turned to normal basically. It showed that EA could protect the cerebral tissues from injury induced bv ischemia. NO and ET might oarticioate in the modulation orocess of EA.

  18. Protective effect of aqueous extract of Embelia ribes Burm fruits in middle cerebral artery occlusion-induced focal cerebral ischemia in rats

    Directory of Open Access Journals (Sweden)

    Bhandari Uma

    2008-01-01

    Full Text Available Objective: The present study was carried out to evaluate the neuroprotective effect of the aqueous extract of Embelia ribes , in focal ischemic brain. Materials and Methods: Adult male Wistar albino rats were fed with the aqueous extract of Embelia ribes (100 and 200 mg/kg, p.o. for 30 days. After 30 days of feeding, all the animals were anaesthetized with chloral hydrate (400 mg/kg, i.p.. The right middle cerebral artery was occluded with a 4-0 suture for 2 h. The suture was removed after 2 h, to allow reperfusion injury. The animals were used for grip strength measurement, biochemical estimation in serum and brain tissue (hippocampus and frontal cortex and cerebral infarct size measurement. Results: In the ischemic group, a significant (P < 0.01 alteration in the markers of oxidative damage (thiobarbituric acid reactive substances (TBARS; reduced glutathione (GSH; glutathione peroxidase (GPx; glutathione reductase (GR; and, glutathione-S-transferase (GST was observed in the hippocampus and frontal cortex, as compared to sham operated rats. We observed that the animals treated with the aqueous extract of Embelia ribes had a significant (P < 0.01 increase in the poststroke grip strength activity. Further, supplementation with aqueous extract of Embelia ribes reversed the levels/activities of the above mentioned biochemical parameters significantly (P< 0.01 and also resulted in decreased cerebral infarct area, as compared to the ischemic group. Conclusion: The results of our study, for the first time, provide clear evidence that aqueous extract of Embelia ribes pretreatment ameliorates cerebral ischemia/reperfusion injury and enhances the antioxidant defense against middle cerebral artery occlusion-induced cerebral infarction in rats; it exhibits neuroprotective property.

  19. Porcine Brain Extract Attenuates Memory Impairments Induced by Focal Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    Jinatta Jittiwat

    2009-01-01

    Full Text Available Problem statement: Stroke or cerebral ischemia has been recognized as one important problem worldwide. To date, the effectiveness of protective and therapeutic strategies against stroke is still very limited. Therefore, the development of novel strategy is required. Porcine brain is traditional believed to improve brain functions. Recent studies showed that the extract of porcine brain could protect against brain damage related to the oxidative stress, therefore, we hypothesized that it could protect against brain damage in stroke. Approach: To test the potential of porcine brain extract as the novel protective supplement against stroke, various doses of porcine brain extract at doses of 0.5 and 2.5 mg kg-1 b.w. were orally given to male Wistar rats, weighing 300-350 g, at the period of 14 days before and 21 days after the occlusion of right middle cerebral artery. Then, all rats were determined the neurological score, motor performance, cognitive function and brain infarct volume. Moreover, the possible neuroprotective mechanisms of the extract were also determined via the alteration of Malondialdehyde (MDA or lipid peroxidation product and via the activities of scavenger enzymes including Superoxide Dismutase (SOD, Catalase (CAT and Glutathione Peroxides (GPx. Results: The results showed that the low dose of porcine extract decreased the infarct volume and improved brain functions including neurological score, motor performance and memory deficit. In addition, it also decreased MDA but increased the activities of SOD, CAT and GPx. Conclusion: Our results suggested the potential role of porcine brain extract as neuroprotectant. The possible underlying mechanism appeared to be related to the enhanced activities of SOD, CAT and GPx which in turn resulted in the decrease MDA. Moreover, our findings may shed light on the pharmacologic basis for the clinical application of traditional Chinese medicine to protect against stroke.

  20. Neuroprotective effects of rutaecarpine on cerebral ischemia reperfusion injury**

    Institute of Scientific and Technical Information of China (English)

    Chunlin Yan; Ji Zhang; Shu Wang; Guiping Xue; Yong Hou

    2013-01-01

    Rutaecarpine, an active component of the traditional Chinese medicine Tetradium ruticarpum, has been shown to improve myocardial ischemia reperfusion injury. Because both cardiovascular and cerebrovascular diseases are forms of ischemic vascular disease, they are closely related. We hypothesized that rutaecarpine also has neuroprotective effects on cerebral ischemia reperfusion injury. A cerebral ischemia reperfusion model was established after 84, 252 and 504 µg/kg carpine were given to mice via intraperitoneal injection, daily for 7 days. Results of the step through test, 2,3,5-triphenyl tetrazolium chloride dyeing and oxidative stress indicators showed that rutae-carpine could improve learning and memory ability, neurological symptoms and reduce infarction volume and cerebral water content in mice with cerebral ischemia reperfusion injury. Rutaecarpine could significantly decrease the malondialdehyde content and increase the activities of superoxide dismutase and glutathione peroxidase in mouse brain. Therefore, rutaecarpine could improve neu-rological function fol owing injury induced by cerebral ischemia reperfusion, and the mechanism of this improvement may be associated with oxidative stress. These results verify that rutaecarpine has neuroprotective effects on cerebral ischemia reperfusion in mice.

  1. Brazilein inhibits neuronal inflammation induced by cerebral ischemia and oxygen-glucose deprivation through targeting NOD2 expression.

    Science.gov (United States)

    Yan, Xiao-Jin; Chai, Yu-Shuang; Yuan, Zhi-Yi; Wang, Xin-Pei; Jiang, Jing-Fei; Lei, Fan; Xing, Dong-Ming; DU, Li-Jun

    2016-05-01

    Brazilein is reported to have immunosuppressive effect on cardiovascular and cerebral-vascular diseases. The essential roles of innate immunity in cerebral ischemia are increasingly identified, but no studies concerning the influence of brazilein on the innate immunity receptors have been reported. The present study was designed to investigate the regulation of NOD2 (Nucleotide-binding oligomerization domain-containing protein 2) by brazilein for its protection of neuron in cerebral ischemia in vivo and oxygen-glucose deprivation in vitro. The results showed that brazilein could reverse the elevated expression of NOD2 and TNFα (tumor necrosis factor alpha) elicited by cerebral ischemia and reperfusion. This reduction could also be detected in normal mice and C17.2 cells, indicating that this suppressive effect of brazilein was correlated with NOD2. The results from GFP reporter plasmid assay suggested brazilein inhibited NOD2 gene transcription. In conclusion, brazilein could attenuate NOD2 and TNFα expression in cerebral ischemia and NOD2 may be one possible target of brazilein for its immune suppressive effect in neuro-inflammation. PMID:27478098

  2. Ischemia-induced stimulation of Na-K-Cl cotransport in cerebral microvascular endothelial cells involves AMP kinase.

    Science.gov (United States)

    Wallace, Breanna K; Foroutan, Shahin; O'Donnell, Martha E

    2011-08-01

    Increased blood-brain barrier (BBB) Na-K-Cl cotransporter activity appears to contribute to cerebral edema formation during ischemic stroke. We have shown previously that inhibition of BBB Na-K-Cl cotransporter activity reduces edema and infarct in the rat middle cerebral artery occlusion (MCAO) model of ischemic stroke. We have also shown that the BBB cotransporter is stimulated by the ischemic factors hypoxia, aglycemia, and arginine vasopressin (AVP), although the mechanisms responsible are not well understood. AMP-activated protein kinase (AMPK), a key mediator of cell responses to stress, can be activated by a variety of stresses, including ischemia, hypoxia, and aglycemia. Previous studies have shown that the AMPK inhibitor Compound C significantly reduces infarct in mouse MCAO. The present study was conducted to evaluate the possibility that AMPK participates in ischemic factor-induced stimulation of the BBB Na-K-Cl cotransporter. Cerebral microvascular endothelial cells (CMEC) were assessed for Na-K-Cl cotransporter activity as bumetanide-sensitive (86)Rb influx. AMPK activity was assessed by Western blot analysis and immunofluorescence methods using antibodies that detect total versus phosphorylated (activated) AMPK. We found that hypoxia (7% and 2% O(2)), aglycemia, AVP, and oxygen-glucose deprivation (5- to 120-min exposures) increase activation of AMPK. We also found that Compound C inhibition of AMPK reduces hypoxia-, aglycemia-, and AVP-induced stimulation of CMEC Na-K-Cl cotransporter activity. Confocal immunofluorescence of perfusion-fixed rat brain slices revealed the presence of AMPK, both total and phosphorylated kinase, in BBB in situ of both control and ischemic brain. These findings suggest that ischemic factor stimulation of the BBB Na-K-Cl cotransporter involves activation of AMPK. PMID:21562306

  3. Protective effect of extract of Cordyceps sinensis in middle cerebral artery occlusion-induced focal cerebral ischemia in rats

    OpenAIRE

    Tang Huiling; Zhao Dan; Li Pengtao; Liu Zhenquan; Guo Jianyou

    2010-01-01

    Abstract Background Ischemic hypoxic brain injury often causes irreversible brain damage. The lack of effective and widely applicable pharmacological treatments for ischemic stroke patients may explain a growing interest in traditional medicines. From the point of view of "self-medication" or "preventive medicine," Cordyceps sinensis was used in the prevention of cerebral ischemia in this paper. Methods The right middle cerebral artery occlusion model was used in the study. The effects of Cor...

  4. Effects of Semelil (ANGIPARS™) on focal cerebral ischemia in male rats

    OpenAIRE

    Asadi-Shekaari, M; H Eftekhar Vaghefi; Talakoub, A; HR Khorram Khorshid

    2010-01-01

    "n  Background and the purpose of the study: Cerebral ischemia is one of the main causes of long term disability and death in aged populations. Many herbal drugs and extracts have been used for the treatment of cerebral ischemia induced insults. This study was designed to investigate the protective effect of Semelil (ANGIPARSTM), a new herbal drug, on focal cerebral ischemia in male rats. Material and methods: Male rats were divided into five groups: sham-operated, ischemic anim...

  5. Curcumin alters expression of glial fibrillary acidic protein and nestin following chronic cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Peng Zhang; Tianping Yu; Xiong Zhang; Yu Li

    2011-01-01

    Astrocytes can alter their appearance and become reactive following chronic cerebral ischemia. In the present study, a rat model of chronic cerebral ischemia was treated with 50 and 100 mg/kg curcumin. Results showed that pathological changes of neuronal injury in hippocampal CA1 area of rats induced by chronic cerebral ischemia were attenuated, as well as upregulated expression of glial fibrillary acidic protein and nestin, in a dose-dependent manner.

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

    Directory of Open Access Journals (Sweden)

    Nabi Shamsaei

    2015-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    Nabi Shamsaei; Mehdi Khaksari; Sohaila Erfani; Hamid Rajabi; Nahid Aboutaleb

    2015-01-01

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

  8. [Platelets, atherothrombosis, antiplatelet drugs and cerebral ischemia].

    Science.gov (United States)

    Bousser, Marie-Germaine

    2013-02-01

    Platelets play a much more important role in myocardial ischemia than in cerebral ischemia, because atherothrombosis - the underlying cause of the vast majority of myocardial infarcts - is responsible for only 25-30% of cerebral infarcts. Aspirin is the only effective antiplatelet drug for primary prevention of ischemic events, especially those affecting the heart. For secondary prevention of cerebral infarction, clopidogrel and the combination of aspirin with extended-release dipyridamole are both marginally better than aspirin alone, but aspirin remains the gold standard worldwide because of its remarkable cost/benefit/tolerability ratio. The clopidogrel-aspirin combination is to be avoided because of the risk of hemorrhage, particularly in the brain and gastrointestinal tract. Revascularization strategies and the choice of antiplatelet drugs for the acute phase of myocardial and cerebral ischemia are very different, consisting of endovascular treatment and aggressive platelet inhibition for coronary infarcts, versus intravenous thrombolysis and / or aspirin for cerebral infarcts. None of the new antiplatelet drugs used in acute coronary syndromes has so far been studied in acute cerebral ischemia. PMID:24919368

  9. Intravenous Administration of Cilostazol Nanoparticles Ameliorates Acute Ischemic Stroke in a Cerebral Ischemia/Reperfusion-Induced Injury Model

    Directory of Open Access Journals (Sweden)

    Noriaki Nagai

    2015-12-01

    Full Text Available It was reported that cilostazol (CLZ suppressed disruption of the microvasculature in ischemic areas. In this study, we have designed novel injection formulations containing CLZ nanoparticles using 0.5% methylcellulose, 0.2% docusate sodium salt, and mill methods (CLZnano dispersion; particle size 81 ± 59 nm, mean ± S.D., and investigated their toxicity and usefulness in a cerebral ischemia/reperfusion-induced injury model (MCAO/reperfusion mice. The pharmacokinetics of injections of CLZnano dispersions is similar to that of CLZ solutions prepared with 2-hydroxypropyl-β-cyclodextrin, and no changes in the rate of hemolysis of rabbit red blood cells, a model of cell injury, were observed with CLZnano dispersions. In addition, the intravenous injection of 0.6 mg/kg CLZnano dispersions does not affect the blood pressure and blood flow, and the 0.6 mg/kg CLZnano dispersions ameliorate neurological deficits and ischemic stroke in MCAO/reperfusion mice. It is possible that the CLZnano dispersions will provide effective therapy for ischemic stroke patients, and that injection preparations of lipophilic drugs containing drug nanoparticles expand their therapeutic usage.

  10. Magnetic resonance spectroscopy and imaging in cerebral ischemia

    International Nuclear Information System (INIS)

    In-vivo proton and phosphorus magnetic resonance spectroscopy was used to detect changes in cerebral metabolism during ischemia and other types of metabolic stress. Magnetic resonance imaging was performed in an animal model to observe morphological alterations during focal cerebral ischemia. Spectroscopy was performed in animal models with global ischemia, in volunteers during hyperventilation and pharmaco-logically altered cerebral perfusion, and in patients with acute and prolonged focal cerebral ischemia. (author). 396 refs.; 44 figs.; 14 tabs

  11. MiRNA-124 induces neuroprotection and functional improvement after focal cerebral ischemia.

    Science.gov (United States)

    Hamzei Taj, Somayyeh; Kho, Widuri; Riou, Adrien; Wiedermann, Dirk; Hoehn, Mathias

    2016-06-01

    microRNA-124 (miR-124), the most abundant miRNA of the CNS, was recently shown to modulate the polarization of activated microglia and infiltrating macrophages towards the anti-inflammatory M2 phenotype and protect neurons in various ways after brain disease. In ischemic stroke, microglia and macrophages of a detrimental and persistent pro-inflammatory M1 phenotype have been shown to aggravate the secondary injury. Thus, shifting the polarization of microglia/macrophages into the beneficial, anti-inflammatory M2-like phenotype is considered neuroprotective after stroke onset. Here, we have induced 30 min transient occlusion of the right middle cerebral artery (MCAO) in 34 male, C57BL/6 mice. Lesion development was monitored with T2-weighted MRI. Liposomated miR-124 was injected in 11 animals at 48 h and in 5 animals at 10 days after MCAO. Arg-1, a marker for M2 phenotype, was co-stained with Iba-1, NeuN or GFAP. The distribution of astrocytes, neurons and microglia/macrophages and their expression of Arg-1 were quantified. Early miR-124 injection resulted in a significantly increased neuronal survival and a significantly increased number of M2-like polarized microglia/macrophages. Moreover, the lesion core, delineated by reactive astrocytes, was significantly reduced over time upon early miR-124 injection. These neuroprotective and anti-inflammatory effects of the early miR-124 treatment were pronounced during the first week with Arg-1. Number of Arg-1+ microglia/macrophages correlated with neuronal protection and with functional improvement during the first week. Thus, our present results demonstrate that miR-124 may serve as a novel therapeutic strategy for neuroprotection and functional recovery upon stroke onset. PMID:27031810

  12. Neuroprotective Effect against Cerebral Ischemia of Passiflora foetida

    Directory of Open Access Journals (Sweden)

    Jintanaporn Wattanathorn

    2012-01-01

    Full Text Available Problem statement: Although cerebral ischemia induced by stroke has been regarded as the important problem worldwide, the therapeutic efficacy is still inadequate. Since the free radicals are implicated in the pathophysiology of cerebral ischemia, the prophylactic protection against stroke with neuroprotective agent possessing antioxidant effect has gained much attention. Therefore, this study was designed to determine whether the alcoholic extract of Passiflora foeida, a plant possessing antioxidant activity, could protect against brain damage and impairment in the cerebral ischemia induced by the occlusion of Middle Cerebral Artery Occlusion (MCAO. Approach: Male Wistar rats, weighing 300-350 g, were orally given the extract once daily at doses of 25, 100 and 400 mg kg-1 BW at a period of 2 weeks before and 3 weeks after the occlusion of right Middle Cerebral Artery (MCAO. The animals were assessed the cerebral infarction volume at 24 h after occlusion while the neurological score and % of foot withdrawal reflex in respond to mechanical stimuli were performed after single dose and every 7 days throughout the experimental period. Results: Rats subjected to P.foetida at dose of 25 mg kg-1 BW significantly decreased brain infarct volume both in cortical and sub cortical structures. The increasing doses further to 100 and 400 mg kg-1 BW could produce the significant reduction only in cerebral cortex. In addition, it was found that the plant extract could enhance neurological score and improved sensory response to both mechanical and temperature stimuli. Conclusion: The current study clearly demonstrates the neuroprotective effect of P.foetida. Therefore P.foetida may provide the advantage as functional food to protect against cerebral ischemia induced by stroke. However, further researches about possible active ingredient and the precise underlying mechanism are still necessary.

  13. Hyperbaric oxygen treatment induces dynamic ATPase activity changes in the rat brain following transient global cerebral ischemia-reperfusion

    Institute of Scientific and Technical Information of China (English)

    Shiming Xu; Hongjuan Wang; Tongnan Gu; Xiuyan Zhou; Rui Chen

    2008-01-01

    BACKGROUND: Energy depletion, induced by ischemia or hypoxia, is one of the first events in neuronal injury. OBJECTIVE: To investigate the dynamic changes of Na+-K+-ATPase and Ca2+-ATPase activity in the rat brain following transient global cerebral ischemia-reperfusion (IR), as well as the effects of hyperbaric oxygen (HBO) treatment. DESIGN, TIME AND SETTING: A randomized and controlled animal study was performed in the Department of Biochemistry and Molecular Biology, Capital Medical University between February and December 2006. MATERIALS: Clean-grade, female, Sprague Dawley rats were provided by the Animal Research Department of Capital Medical University (License number: SYXK11-00-0047). Na+-K+-ATPase and Ca2+-ATPase kits were provided by Nanjing Jiancheng Bioengineering Institute (Nanjing, China). A hyperbaric oxygen chamber (DWC150-300) was supplied by Shanghai 701 Medical Oxygen Chamber Factory (Shanghai, China). METHODS: Sixty-three rats were randomly divided into nine groups: sham operated group (sham-O) as control, groups of IR, and groups treated with hyperbaric oxygen (HBO) after IR. Animal from the IR and HBO groups were sacrificed after four different survival intervals of 6, 24, 48 and 96 hours, respectively. Each group consisted of seven rats. The rats of HBO groups were placed into the hyperbaric chamber. The HBO chamber was flushed with pure oxygen for 5 minutes, followed by a gradual rise in pressure over 5 minutes and stabilization at 0.2 MPa. Then, pure oxygen was supplied for 45 minutes in stabilized pressure, followed by gradually reduced pressure over 15 minutes. The rats of the 6-h HBO group were placed into the HBO chamber following reperfusion for 3 hours on the first day, which was repeated on three consecutive days, always at the same time. Rats in the sham-O group and IR group remained under normal atmospheric pressure. MAIN OUTCOME MEASURES: The Na+-K+-ATPase and Ca2+-ATPase activity in rat brain homogenate was detected by the

  14. Drug-Induced Hypothermia as Beneficial Treatment before and after Cerebral Ischemia

    DEFF Research Database (Denmark)

    Johansen, Flemming F; Hasseldam, Henrik; Rasmussen, Rune Skovgaard; Bisgård, Anne Sofie; Bonfils, Peter Kramshøj; Poulsen, Steen Seier; Hansen-Schwartz, Jacob

    2014-01-01

    Objectives: Hypothermia is still unproven as beneficial treatment in human stroke, although in animal models, conditioning the brain with hypothermia has induced tolerance to insults. Here, we delineate the feasibility of drug-induced mild hypothermia in reducing ischemic brain damage when...

  15. Forced Exercise Enhances Functional Recovery after Focal Cerebral Ischemia in Spontaneously Hypertensive Rats

    OpenAIRE

    Yonggeun Hong; Kyu-Tae Chang; Sunmi Kim; Seunghoon Lee; Sang-Rae Lee; Kanghui Park; Tserentogtokh Lkhagvasuren; Jinhee Shin; Sookyoung Park; Yunkyung Hong

    2012-01-01

    Caveolin is the principal protein of caveolae and has been implicated in the pathogenesis of cerebral ischemia. To investigate whether changed expression of caveolins has a pivotal role in focal cerebral ischemia, we induced middle cerebral artery occlusion (MCAo)-reperfusion and examined expression of caveolins, inflammatory activation markers, and mediators of autophagic cell death. We also treated MCAo rats with forced exercise to determine its effects on neurological outcome. Particularly...

  16. Montelukast, a cysteinyl leukotriene receptor-1 antagonist protects against hippocampal injury induced by transient global cerebral ischemia and reperfusion in rats.

    Science.gov (United States)

    Saad, M A; Abdelsalam, R M; Kenawy, S A; Attia, A S

    2015-01-01

    Cysteinyl leukotrienes (CysLTs) are potent pro-inflammatory and immune modulating lipid mediators involved in inflammatory diseases and were boosted in human brain after acute phase of cerebral ischemia. The antagonism of CysLTs receptors may offer protection against ischemic damage. Therefore it seemed interesting to study the possible neuroprotective effect of Montelukast, a CysLTR1 antagonist in global cerebral ischemia/reperfusion (IR) injury in rats. Global cerebral ischemia-reperfusion was induced by bilateral carotid artery occlusion for 15 min followed by 60 min reperfusion period. Animals were randomly allocated into three groups (n = 30 per group): Sham operated, I/R control and rats treated with montelukast (0.5 mg/kg, po) daily for 7 days then I/R was induced 1 h after the last dose of montelukast. After reperfusion rats were killed by decapitation, brains were removed and both hippocampi separated and the following biochemical parameters were estimated; lactate dehydrogenase activity, oxidative stress markers (lipid peroxides, nitric oxide and reduced glutathione), inflammatory markers (myeloperoxidase, tumor necrosis factor-alpha, nuclear factor kappa-B, interleukin-6 and interleukin-10), apoptotic biomarkers (caspase 3 and cytochrome C), neurotransmitters (glutamate, gamma aminobutyric acid), Cys-LTs contents and CysLT1 receptor expression; as well as total brain infarct size and histopathological examination of the hippocampus were assessed. Montelukast protected hippocampal tissue by reducing oxidative stress, inflammatory and apoptotic markers. Furthermore, it reduced glutamate and lactate dehydrogenase activity as well as infarct size elevated by I/R. These results were consistent with the histopathological findings. Montelukast showed a neuroprotective effects through antioxidant, anti-inflammatory and antiapoptotic mechanisms. PMID:25403620

  17. Protective effects of allicin on acute cerebral ischemia-reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    ZHENGYan-hua; CHENChong-hong

    2004-01-01

    AIM To study the protective effects of allicin on acute focal cerebral ischemia reperfusioninjury. METHODS: The model of cerebral ishemia-3 h/reperfusion - 24h was induced by middle cerebral artery occlusion (MCAO) in SD rats. Allicin (10,20mg·kg-1) was administered once daily in rats: at 0 h of reperfusion. After 24h reperfusion, the content of

  18. Effects of Semelil (ANGIPARS™ on focal cerebral ischemia in male rats

    Directory of Open Access Journals (Sweden)

    M Asadi-Shekaari

    2010-12-01

    Full Text Available "n  Background and the purpose of the study: Cerebral ischemia is one of the main causes of long term disability and death in aged populations. Many herbal drugs and extracts have been used for the treatment of cerebral ischemia induced insults. This study was designed to investigate the protective effect of Semelil (ANGIPARSTM, a new herbal drug, on focal cerebral ischemia in male rats. Material and methods: Male rats were divided into five groups: sham-operated, ischemic animals treated with distilled water as vehicle, ischemic animals treated with 1, 10 and 100 mg/kg of Semilil respectively. Middle cerebral artery occlusion (MCAO model was used in NMRI rats and neuronal injury analyzed in hippocampal CA1 sector after 48 hrs of Middle Cerebral Artery (MCAO. Results: Results of this study showed that treatment with semelil attenuated ischemic damages and has positive effects on focal cerebral ischemia.

  19. 3-N-butylphthalide improves neuronal morphology after chronic cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Wanhong Zhao; Chao Luo; Jue Wang; Jian Gong; Bin Li; Yingxia Gong; Jun Wang; Hanqin Wang

    2014-01-01

    3-N-butylphthalide is an effective drug for acute ischemic stroke. However, its effects on chronic cerebral ischemia-induced neuronal injury remain poorly understood. Therefore, this study li-gated bilateral carotid arteries in 15-month-old rats to simulate chronic cerebral ischemia in aged humans. Aged rats were then intragastrically administered 3-n-butylphthalide. 3-N-butylphtha-lide administration improved the neuronal morphology in the cerebral cortex and hippocampus of rats with chronic cerebral ischemia, increased choline acetyltransferase activity, and decreased malondialdehyde and amyloid beta levels, and greatly improved cognitive function. These findings suggest that 3-n-butylphthalide alleviates oxidative stress caused by chronic cerebral ischemia, improves cholinergic function, and inhibits amyloid beta accumulation, thereby im-proving cerebral neuronal injury and cognitive deifcits.

  20. 1H-magnetic resonance spectroscopy of vascular endothelial growth factor-induced neuroprotection following acute cerebral ischemia and reperfusion

    Institute of Scientific and Technical Information of China (English)

    Li Yi; Haiou Zhang; Hao Lei; Li Wei

    2008-01-01

    BACKGROUND: It has become generally accepted that measuring N-acetyI-L-aspartic acid through the use of 1H-magnetic resonance spectroscopy (1H-MRS) could be used to evaluate neuronal injury. OBJECTIVE: To study metabolic changes of N-acetyl-L-aspanic acid surrounding the acute cerebral ischcmia area following vascular endothelial growth factor (VEGF) treatment using 1H-MRS imaging, and to evaluate the neuroprotective effects of VEGE.DESIGN, TIME AND SETTING: Randomly controlled animal study, according to one-factor analysis of variance, was performed at the Shenzhen Hospital of Peking University and State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences from August 2003 to December 2005.MATERIALS: Twelve healthy, adult, Sprague Dawley rats were used to establish an ischemia/reperfusion model through the use of middle cerebral artery occlusion. The 4.7T superconducting nuclear magnetic resonance meter was provided by Brucker Company. VEGF164 was purchased from Shenzhen Jingmei Bioengineering Co., Ltd. Titus ancsthesia machine was purchased from Draeger Medical AG & Co. KG.METHODS: The rats were randomly divided into model control (n = 6) and VEGF-injected (n = 6) groups. All animals received 60-minute middle cerebral artery occlusion and 24-hour repcrfusion. Lateral cerebral ventricle injection was performed by stereotaxic technique at respective time points. The VEGF group received 0. 1 μ g/μ L VEGF (5 μL), and the model group received the same amount of normal saline, once daily for 3 days.MAIN OUTCOME MEASURES: Metabolic changes of N-acetyl-L-aspartic acid and lactic acid following cerebral ischemia and reperfusion were detected using 1H-MRS, and the ischemic volume was measured.RESULTS: Twelve rats were included in the final analysis. =H-MRS results revealed that the ischemic volume increased in the control group compared with prior to injection (P < 0.01). In the

  1. Infrared laser hemotherapy in cerebral ischemia modeling

    Science.gov (United States)

    Musienko, Julia I.; Nechipurenko, Natalia I.

    2003-10-01

    Use of intravenous laser irradiation of blood (ILIB) is considered to be the most effective method of laser therapy and its application is expedient pathogenetically in the ischemic disturbances. The aim of this study is to investigate ILIB influence with infrared laser (IL) with 860 nm wavelength on hemostasis, acid-base status (ABS) of blood in normal rabbits and after modeling of local ischemia of brain (LIB). Experimental cerebral ischemia is characterized by development of hypercoagulation syndrom and metabolic acidosis. ILIB with infrared radiation of 2.0 mW power provokes hypocoagulation in intact animals. Application of ILIB in rabbits after LIB contributes for hemostasis and acid-base status normalizing compared to operated animals. IL radiation with 8,5 mW power results in marked hemostatic activation in all animals. Therefore, beneficial effect of low power laser radiation (LPLR) manifests in narrow power diapason in experimental brain ischemia.

  2. Effect of minocycline on cerebral ischemia- reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Yuanyin Zheng; Lijuan Xu; Jinbao Yin; Zhichao Zhong; Hongling Fan; Xi Li; Quanzhong Chang

    2013-01-01

    Minocylcine, a tetracycline derivate, has been shown to cross the blood-brain barrier and enter the central nervous system. In this study, cerebral ischemia-reperfusion injury models were established using the suture method, and minocycline was immediately injected intraperitoneally after cerebral ischemia-reperfusion (22.5 mg/kg, initially 45 mg/kg) at a 12-hour interval. Results showed that after minocycline treatment, the volume of cerebral infarction was significantly reduced, the number of surviving cell in the hippocampal CA1 region increased, the number of apoptotic cells decreased, the expression of caspase-3 and poly(adenosine diphosphate-ribose) polymerase-1 protein was down-regulated, and the escape latency in the water maze test was significantly shortened compared with the ischemia-reperfusion group. Our experimental findings indicate that minocycline can protect against neuronal injury induced by focal ischemia-reperfusion, which may be mediated by the inhibition of caspase-3 and poly(adenosine diphosphate-ribose) polymerase-1 protein expression.

  3. Relationship between cerebral sodium-glucose transporter and hyperglycemia in cerebral ischemia.

    Science.gov (United States)

    Yamazaki, Yui; Harada, Shinichi; Tokuyama, Shogo

    2015-09-14

    Post-ischemic hyperglycemia exacerbates the development of cerebral ischemia. To elucidate this exacerbation mechanism, we focused on sodium-glucose transporter (SGLT) as a mediator that lead hyperglycemia to cerebral ischemia. SGLT transport glucose into the cell, together with sodium ion, using the sodium concentration gradient. We have previously reported that suppression of cerebral SGLT ameliorates cerebral ischemic neuronal damage. However, detail relationship cerebral between SGLT and post-ischemic hyperglycemia remain incompletely defined. Therefore, we examined the involvement of cerebral SGLT on cerebral ischemic neuronal damage with or without hyperglycemic condition. Cell survival rate of primary cultured neurons was assessed by biochemical assay. A mouse model of focal ischemia was generated using a middle cerebral artery occlusion (MCAO). Neuronal damage was assessed with histological and behavioral analyses. Concomitant hydrogen peroxide/glucose treatment exacerbated hydrogen peroxide alone-induced cell death. Although a SGLT family-specific inhibitor, phlorizin had no effect on developed hydrogen peroxide alone-induced cell death, it suppressed cell death induced by concomitant hydrogen peroxide/glucose treatment. α-MG induced a concentration-dependent and significant decrease in neuronal survival. PHZ administered on immediately after reperfusion had no effect, but PHZ given at 6h after reperfusion had an effect. Our in vitro study indicates that SGLT is not involved in neuronal cell death in non-hyperglycemic condition. We have already reported that post-ischemic hyperglycemia begins to develop at 6h after MCAO. Therefore, current our in vivo study show post-ischemic hyperglycemic condition may be necessary for the SGLT-mediated exacerbation of cerebral ischemic neuronal damage. PMID:26254165

  4. Animal Models of Ischemic Stroke. Part Two: Modeling Cerebral Ischemia

    OpenAIRE

    Bacigaluppi, Marco; Comi, Giancarlo; Dirk M Hermann

    2010-01-01

    Animal models of stroke provide an essential tool for the understanding of the complex cellular and molecular pathophysiology of stroke and for testing novel recanalyzing, neuroprotective, neuroregenerative or anti- inflammatory drugs in pre- clinical setting. Since the first description of the distal occlusion of the middle cerebral artery (MCA) in rats, different techniques and methods to induce focal and global ischemia of the brains have been developed and optimized. The different models,...

  5. Post-Traumatic Late Onset Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    Gencer Genc

    2014-03-01

    Full Text Available Artery-to-artery emboli or occlusion of craniocervical arteries mostly due to dissection are the most common causes of ischemia after trauma. A 29 year-old male had been admitted to another hospital with loss of consciousness lasting for about 45 minutes after a hard parachute landing without head trauma three days ago. As his neurological examination and brain CT were normal, he had been discharged after 24 hours of observation. Two days after his discharge, he was admitted to our department with epileptic seizure. His neurological examination revealed left hemianopia. After observing occipital subacute ischemia at right side in brain magnetic resonance imaging (MRI, we performed cerebral angiography and no dissection was observed. Excluding the rheumatologic, cardiologic and vascular events, our final diagnosis was late onset cerebral ischemia. Anti-edema and antiepileptic treatment was initiated. He was discharged with left hemianopia and mild cognitive deficit. We suggest that it will be wise to hospitalize patients for at least 72 hours who has a history of unconsciousness following trauma.

  6. Ameliorating effects of traditional Chinese medicine preparation, Chinese materia medica and active compounds on ischemia/reperfusion-induced cerebral microcirculatory disturbances and neuron damage.

    Science.gov (United States)

    Sun, Kai; Fan, Jingyu; Han, Jingyan

    2015-01-01

    Ischemic stroke and ischemia/reperfusion (I/R) injury induced by thrombolytic therapy are conditions with high mortality and serious long-term physical and cognitive disabilities. They have a major impact on global public health. These disorders are associated with multiple insults to the cerebral microcirculation, including reactive oxygen species (ROS) overproduction, leukocyte adhesion and infiltration, brain blood barrier (BBB) disruption, and capillary hypoperfusion, ultimately resulting in tissue edema, hemorrhage, brain injury and delayed neuron damage. Traditional Chinese medicine (TCM) has been used in China, Korea, Japan and other Asian countries for treatment of a wide range of diseases. In China, the usage of compound TCM preparation to treat cerebrovascular diseases dates back to the Han Dynasty. Even thousands of years earlier, the medical formulary recorded many classical prescriptions for treating cerebral I/R-related diseases. This review summarizes current information and underlying mechanisms regarding the ameliorating effects of compound TCM preparation, Chinese materia medica, and active components on I/R-induced cerebral microcirculatory disturbances, brain injury and neuron damage. PMID:26579420

  7. Ameliorating effects of traditional Chinese medicine preparation, Chinese materia medica and active compounds on ischemia/reperfusion-induced cerebral microcirculatory disturbances and neuron damage

    Directory of Open Access Journals (Sweden)

    Kai Sun

    2015-01-01

    Full Text Available Ischemic stroke and ischemia/reperfusion (I/R injury induced by thrombolytic therapy are conditions with high mortality and serious long-term physical and cognitive disabilities. They have a major impact on global public health. These disorders are associated with multiple insults to the cerebral microcirculation, including reactive oxygen species (ROS overproduction, leukocyte adhesion and infiltration, brain blood barrier (BBB disruption, and capillary hypoperfusion, ultimately resulting in tissue edema, hemorrhage, brain injury and delayed neuron damage. Traditional Chinese medicine (TCM has been used in China, Korea, Japan and other Asian countries for treatment of a wide range of diseases. In China, the usage of compound TCM preparation to treat cerebrovascular diseases dates back to the Han Dynasty. Even thousands of years earlier, the medical formulary recorded many classical prescriptions for treating cerebral I/R-related diseases. This review summarizes current information and underlying mechanisms regarding the ameliorating effects of compound TCM preparation, Chinese materia medica, and active components on I/R-induced cerebral microcirculatory disturbances, brain injury and neuron damage.

  8. The role of Rho/Rho-kinase pathway and the neuroprotective effects of fasudil in chronic cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Ya-yun Yan; Xiao-ming Wang; Yan Jiang; Han Chen; Jin-ting He; Jing Mang; Yan-kun Shao; Zhong-xin Xu

    2015-01-01

    The Rho/Rho-kinase signaling pathway plays an important role in cerebral ischemia/reperfusion injury. However, very few studies have examined in detail the changes in the Rho/Rho-kinase signaling pathway in chronic cerebral ischemia. In this study, rat models of chronic cerebral ischemia were established by permanent bilateral common carotid artery occlusion and intra-gastrically administered 9 mg/kg fasudil, a powerful ROCK inhibitor, for 9 weeks. Morris water maze results showed that cognitive impairment progressively worsened as the cerebral ischemia proceeded. Immunohistochemistry, semi-quantitative RT-PCR and western blot analysis showed that the expression levels of Rho-kinase, its substrate myosin-binding subunit, and its relat-ed protein alpha smooth muscle actin, significantly increased after chronic cerebral ischemia. TUNEL staining showed that chronic cerebral ischemia could lead to an increase in neuronal apoptosis, as well as the expression level of caspase-3 in the frontal cortex of rats subjected to chronic cerebral ischemia. Fasudil treatment alleviated the cognitive impairment in rats with chronic cerebral ischemia, and decreased the expression level of Rho-kinase, myosin-binding subunit and alpha smooth muscle actin. Furthermore, fasudil could regulate cerebral injury by reducing cell apoptosis and decreasing caspase-3 expression in the frontal cortex. These ifndings demonstrate that fasudil can protect against cognitive impairment induced by chronic cerebral ischemiavia the Rho/Rho-kinase signaling pathway and anti-apoptosis mechanism.

  9. Induction of Nerve Injury-Induced Protein 1 (Ninjurin 1) in Myeloid Cells in Rat Brain after Transient Focal Cerebral Ischemia.

    Science.gov (United States)

    Lee, Hye-Kyung; Lee, Hahnbie; Luo, Lidan; Lee, Ja-Kyeong

    2016-04-01

    Nerve injury-induced protein-1 (Ninjurin-1, Ninj1) was initially identified as a novel adhesion molecule in rat sciatic nerve and to be up-regulated in neurons and Schwann cells of distal nerve segments after nerve transection or crush injury. Recently, Ninj1 was found to act as a modulator of cell migration, angiogenesis, and apoptosis. Accumulating evidence indicates that innate immune response plays beneficial and deleterious roles in brain ischemia, and the trans-endothelial migration of blood-derived immune cells is key initiator of this response. In the present study, we examined the expression profile and cellular distribution of Ninj1 in rat brain after transient focal cerebral ischemia. Ninj1 expression was found to be significantly induced in cortical penumbras 1 day after 60 min of middle cerebral artery occlusion (MCAO) and to increase gradually for 8 days and then declined. In infarction cores of cortices, patterns of Ninj1 expression were similar to those observed in cortical penumbras, except induction was maintained for 10 days. At 1 day post-MCAO, Ninj1 inductions were detected mainly in neutrophils and endothelial cells in both infarction cores and penumbras, but reactive macrophages were the major cellular expressers of Ninj1 at 4 days post-MCAO. Expressional induction in reactive macrophages was maintained in infarction cores after 12 days post-MCAO but not in penumbras. These dynamic expressions of Ninj1 in different immune cells at different times suggest that this protein performs various, critical roles in the modulation of acute and delayed immune responses in the postischemic brain. PMID:27122992

  10. Effect of minocycline on cerebral ischemia-reperfusion injury★

    OpenAIRE

    Zheng, Yuanyin; Xu, Lijuan; Yin, Jinbao; Zhong, Zhichao; Fan, Hongling; LI, XI; Chang, Quanzhong

    2013-01-01

    Minocylcine, a tetracycline derivate, has been shown to cross the blood-brain barrier and enter the central nervous system. In this study, cerebral ischemia-reperfusion injury models were established using the suture method, and minocycline was immediately injected intraperitoneally after cerebral ischemia-reperfusion (22.5 mg/kg, initially 45 mg/kg) at a 12-hour interval. Results showed that after minocycline treatment, the volume of cerebral infarction was significantly reduced, the number ...

  11. The morphologic changes of remote-organs after acute cerebral ischemia-reperfusion injury in rats and the protective effects of rofecoxib

    Institute of Scientific and Technical Information of China (English)

    YUJuan; QIULi-Ying; ZHOUYu; CHENChong-Hong

    2004-01-01

    AIM: To observe the pathomorphologic changes of major organs in thoracic-abdominal cavity induced by acute cerebral ischemia-reperfusion injury (CIRI and explore the protective effects of rofecoxib. METHODS: The model of local cerebral ischemia-2h/reperfusion -24h was induced by reversible middle cerebral artery occlusion (MCAO in SD rats.

  12. An Evidence-Based Review of Related Metabolites and Metabolic Network Research on Cerebral Ischemia

    Science.gov (United States)

    Liu, Mengting; Tang, Liying; Liu, Xin; Fang, Jing; Zhan, Hao; Wu, Hongwei; Yang, Hongjun

    2016-01-01

    In recent years, metabolomics analyses have been widely applied to cerebral ischemia research. This paper introduces the latest proceedings of metabolomics research on cerebral ischemia. The main techniques, models, animals, and biomarkers of cerebral ischemia will be discussed. With analysis help from the MBRole website and the KEGG database, the altered metabolites in rat cerebral ischemia were used for metabolic pathway enrichment analyses. Our results identify the main metabolic pathways that are related to cerebral ischemia and further construct a metabolic network. These results will provide useful information for elucidating the pathogenesis of cerebral ischemia, as well as the discovery of cerebral ischemia biomarkers. PMID:27274780

  13. 4(α-L-RHAMNOSYLOXY)-BENZYL ISOTHIOCYANATE, A BIOACTIVE PHYTOCHEMICAL THAT DEFENDS CEREBRAL TISSUE AND PREVENTS SEVERE DAMAGE INDUCED BY FOCAL ISCHEMIA/REPERFUSION.

    Science.gov (United States)

    Galuppo, M; Giacoppo, S; Iori, R; De Nicola, G R; Milardi, D; Bramanti, P; Mazzon, E

    2015-01-01

    Natural compounds are a promising source to treat several pathologies. The present study shows the in vivo pharmacological beneficial effect of 4(α-L-rhamnosyloxy)-benzyl isothiocyanate (glucomoringin isothiocyanate; GMG-ITC) obtained from glucomoringin (GMG; 4(α;-L-rhamnosyloxy)- benzyl glucosinolate), purified from Moringa oleifera seeds and hydrolyzed by myrosinase enzyme (β-thioglucoside glucohydrolase; E.C. 3.2.1.147). Cerebral ischemia/reperfusion (CIR) was induced in rats according to a classic model of carotid artery occlusion for a time period of 1 h and the reperfusion time was prolonged for seven days. GMG-ITC (3.5 mg GMG/ml plus 30 μl enzyme/rat; one ml i.p./rat) was administered 15 min after the beginning of ischemia and daily. The results clearly show that GMG-ITC possesses the capability to counteract the CIR-induced damage reducing TNF-alpha release, IκB-alpha cytosolic degradation/NFκBp65 nuclear translocation, as well as several other direct or indirect markers of inflammation (phospho-ERK p42/44, p-selectin) and oxidative stress (inducible Nitric Oxide Synthase (iNOS), MMP-9). GMG-ITC was shown to exert neuroprotective properties in preventing CIR-induced damage and the related cascade of inflammatory and oxidative mediators that exacerbate the progression of this disease in an experimental rat model. Our results clearly show that the tested phytochemical GMG-ITC possesses the capability to counteract CIR-induced damage. PMID:26122222

  14. Alpha-MSH decreases core and brain temperature during global cerebral ischemia in rats

    DEFF Research Database (Denmark)

    Spulber, S.; Moldovan, Mihai; Oprica, M.; Aronsson, A.F.; Post, C.; Winblad, B.; Schultzberg, M.

    2005-01-01

    A key pathological event during cerebral ischemia is the excitotoxic release of glutamate. We have shown previously that alpha-melanocyte-stimulating hormone (alpha-MSH) enhances the hypothermia induced by kainic acid. We have investigated the effects of systemic administration of alpha-MSH on four......-vessel occlusion forebrain ischemia on core temperature (CT) and brain temperature (BT), respectively. After 10 min cerebral ischemia, BT was lower in alpha-MSH- than in saline-injected animals. After 10 min reperfusion, both CT and BT were lower than the corresponding pre-ischemic levels after injection of alpha......-MSH. alpha-MSH did not influence CT or BT in sham-operated rats. The alpha-MSH-induced hypothermia and its potentiation of reduction in BT during global cerebral ischemia, may contribute to neuroprotective effects of alpha-MSH....

  15. Electro-acupuncture could be an effective pretreatment for cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Feng Zhang

    2010-10-01

    Full Text Available "nElectroacupuncture, the integration of traditional Chinese acupuncture and modern electrotherapy, has been used for clinical treatment of cerebral ischemic disease in both eastern and western countries; however, the mechanism underlying its effects is still unknown. It is well known that excessive glutamate results in neuronal excitotoxicity after ischemic stroke. Previous studies have indicated that electro-acupuncture may downregulate the overactivation of glutamate after ischemia, and a recent study implied that electro-acupuncture prior to ischemia could induce brain ischemic tolerance. Based on the present information, we hypothesize that electro-acupuncture could be an effective pretreatment for cerebral ischemia by regulating the glutamatergic system.

  16. Ulinastatin attenuates cerebral ischemia-reperfusion injury in rats

    OpenAIRE

    Chen, Hai-Ming; Huang, Huan-Sen; Ruan, Lin; He, Yan-Bing; Li, Xiong-Juan

    2014-01-01

    To investigate the effects of Ulinastatin (UTI) in cerebral ischemia-reperfusion (IR) injury in rats and whether this effect might be related to Aquaporin 4 (AQP4), one hundred and eighty adult male Sprague Dawley (SD) rats, weighing 230-280 g, were randomly divided into 3 groups: sham (S) group, IR group and UTI (U) group. Every group was further divided into 3 sub-groups: 6 h group, 24 h group and 48 h group. The transient focal IR injury was induced by inserting a silicone-coater monofilam...

  17. Neuroprotective effects of tadalafil on gerbil dopaminergic neurons following cerebral ischemia.

    Science.gov (United States)

    Kim, Kwang Taek; Chung, Kyung Jin; Lee, Han Sae; Ko, Il Gyu; Kim, Chang Ju; Na, Yong Gil; Kim, Khae Hawn

    2013-03-15

    Impairment of dopamine function, which is known to have major effects on behaviors and cognition, is one of the main problems associated with cerebral ischemia. Tadalafil, a long-acting phosphodiesterase type-5 inhibitor, is known to ameliorate neurologic impairment induced by brain injury, but not in dopaminergic regions. We investigated the neuroprotective effects of treatment with tadalafil on cyclic guanosine monophosphate level and dopamine function following cerebral ischemia. Forty adult Mongolian gerbils were randomly and evenly divided into five groups (n = 8 in each group): Sham-operation group, cerebral ischemia-induced and 0, 0.1, 1, and 10 mg/kg tadalafil-treated groups, respectively. Tadalafil dissolved in distilled water was administered orally for 7 consecutive days, starting 1 day after surgery. Cyclic guanosine monophosphate assay and immunohistochemistry were performed for thyrosine hydroxylase expression and western blot analysis for dopamine D2 receptor expression. A decrease in cyclic guanosine monophosphate level following cerebral ischemia was found with an increase in thyrosine hydroxylase activity and a decrease in dopamine D2 receptor expression in the striatum and substantia nigra region. However, treatment with tadalafil increased cyclic guanosine monophosphate expression, suppressed thyrosine hydroxylase expression and increased dopamine D2 receptor expression in the striatum and substantia nigra region in a dose-dependent manner. Tadalafil might ameliorate cerebral ischemia-induced dopaminergic neuron injury. Therefore, tadalafil has the potential as a new neuroprotective treatment strategy for cerebral ischemic injury. PMID:25206715

  18. [Neuroprotective activity of the proline-containing dipeptide noopept on the model of brain ischemia induced by the middle cerebral artery occlusion].

    Science.gov (United States)

    Gavrilova, S A; Us, K S; Ostrovskaia, R U; Koshelev, V B

    2006-01-01

    The influence of noopept (N-phenylacetyl-L-prolylglycine ethyl ester, GVS-111) on the extent of ischemic cortical stroke was investigated in experiments on white mongrel male rats with ischemia induced by a combination of the middle cerebral artery occlusion with ipsilateral common carotid artery ligation. Animals were treated with noopept (0.5 mg/kg, i.p.) according to the following schedule: 15 min and 2, 24, and 48 h after the occlusion. Test rats were decapitated 72 h after occlusion, brains were extracted and frozen, and thin brain slices were stained with 2,3,5-triphenyltetrazolium chloride. The slices were scanned and processed using Auc 1 computer program, which estimates the percentage of damaged area relative to that of the whole ipsilateral hemisphere. The conditions of coagulation the distal segment of middle cerebral artery were selected, which caused necrosis localized in the fronto-parietal and dorso-lateral regions of the brain cortex without any damage of subcortical structures. The extent of the brain damage in control group (treated by saline) was 18.6%, while that in the group treated with noopept was 12.2%, thus demonstrating a decrease in the infarction area by 34.5% (p noopept efficacy on the model of the extensive ischemic injury of brain cortex show that this drug has good prospects for use in the neuroprotective treatment of stroke. PMID:16995431

  19. Cerebral hypoxia and ischemia in preterm infants

    Directory of Open Access Journals (Sweden)

    Alberto Ravarino

    2014-06-01

    Full Text Available Premature birth is a major public health issue internationally affecting 13 million babies worldwide. Hypoxia and ischemia is probably the commonest type of acquired brain damage in preterm infants. The clinical manifestations of hypoxic-ischemic injury in survivors of premature birth include a spectrum of cerebral palsy and intellectual disabilities. Until recently, the extensive brain abnormalities in preterm neonates appeared to be related mostly to destructive processes that lead to substantial deletion of neurons, axons, and glia from necrotic lesions in the developing brain. Advances in neonatal care coincide with a growing body of evidence that the preterm gray and white matter frequently sustain less severe insults, where tissue destruction is the minor component. Periventricular leukomalacia (PVL is the major form of white matter injury and consists classically of focal necrotic lesions, with subsequent cyst formation, and a less severe but more diffuse injury to cerebral white mater, with prominent astrogliosis and microgliosis but without overt necrosis. With PVL a concomitant injury occurs to subplate neurons, located in the subcortical white matter. Severe hypoxic-ischemic insults that trigger significant white matter necrosis are accompanied by neuronal degeneration in cerebral gray and white matter. This review aims to illustrate signs of cerebral embryology of the second half of fetal life and correlate hypoxic-ischemic brain injury in the premature infant. This should help us better understand the symptoms early and late and facilitate new therapeutic strategies. Proceedings of the International Course on Perinatal Pathology (part of the 10th International Workshop on Neonatology · October 22nd-25th, 2014 · Cagliari (Italy · October 25th, 2014 · The role of the clinical pathological dialogue in problem solving Guest Editors: Gavino Faa, Vassilios Fanos, Peter Van Eyken

  20. Triptolide for cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Dengming Wei; Yiping Liao; Lin Wang; Guangzhao Huang; Yigu Zhang; Guangxun Rao

    2007-01-01

    BACKGROUND: Studies have demonstrated that triptolide has good anti-inflammatory and immunosuppressive effects. However, the effect of triptolide on cerebral ischemia/reperfusion injury is still unclear.OBJECTIVE: To observe the effects of triptolide on neurologic function, infarct volume, water content of brain tissue, neutrophil number in microvascular wall and intedeukin-1β (IL-1β ) expression in rat models of local ischemia/reperfusion, and analyze the mechanism of triptolide for protecting brain.DESIGN: Randomized controlled experiment.SETTING: Department of Pathology, Medical School of Ningbo University; Department of Forensic Medicine, Tongji Medical College of Huazhong University of Science and Technology.MATERIALS: Sixty Wistar rats of either gender, aged 4 months old, weighing from 200 to 250 g, were provided by the Experimental Animal Center, Tongji Medical College, Huazhong University of Science and Technology. Triptolide was purchased from Fujian Institute for Medical Science (purity 99.98%; Batch No.2000215). It was dissolved in 20 g/L propanediol, and filtered with 200-mesh filter for later use.METHODS: This experiment was carried out in the laboratory of Forensic Medicine, Tongji Medical College of Huazhong University of Science and Technology, Department of Pathology, Medical School of Ningbo University between January 2001 and September 2004. ① Sixty Wistar rats were randomized into 4 groups: sham-operation group, model group, low-dose triptolide group and high-dose triptolide group. Rats in each group, except for sham-operation group, were developed into rat models of cerebral ischemia/reperfusion according to the method of Longa et al. In the first 3 days of modeling, rats in the low-and high-dose triptolide groups were intraperitoneaily injected with 0.2 and 0.4 mg/kg triptolide respectively,once a day, 3 days in total. ② At ischemia 1 hour and reperfusion 24 hours, infarct volume, neurologic deficit (five-point scale, higher scores

  1. Cerebral Ischemia Due to Traumatic Carotid Artery Dissection: Case Report

    Directory of Open Access Journals (Sweden)

    Deniz Kamacı Şener

    2012-12-01

    Full Text Available Blunt injury to the neck region may lead to carotid artery dissection and cerebral ischemia. Blunt injury to carotid artery is not frequent but determination of the presence of trauma in the history of stroke patients will provide early diagnosis and treatment of them. In this article, a case with cerebral ischemia resulting from traumatic carotid artery dissection is presented and clinical findings, diagnostic procedures and choice of treatment are discussed in the light of the literature.

  2. mRNA redistribution during permanent focal cerebral ischemia.

    Science.gov (United States)

    Lewis, Monique K; Jamison, Jill T; Dunbar, Joseph C; DeGracia, Donald J

    2013-12-01

    Translation arrest occurs in neurons following focal cerebral ischemia and is irreversible in penumbral neurons destined to die. Following global cerebral ischemia, mRNA is sequestered away from 40S ribosomal subunits as mRNA granules, precluding translation. Here, we investigated mRNA granule formation using fluorescence in situ histochemistry out to 8 h permanent focal cerebral ischemia using middle cerebral artery occlusion in Long Evans rats with and without diabetes. Neuronal mRNA granules colocalized with PABP, HuR, and NeuN, but not 40S or 60S ribosomal subunits, or organelle markers. The volume of brain with mRNA granule-containing neurons decreased exponentially with ischemia duration, and was zero after 8 h permanent focal cerebral ischemia or any duration of ischemia in diabetic rats. These results show that neuronal mRNA granule response has a limited range of insult intensity over which it is expressed. Identifying the limits of effective neuronal stress response to ischemia will be important for developing effective stroke therapies. PMID:24323415

  3. Neuroprotective effect of morroniside on focal cerebral ischemia in rats.

    Science.gov (United States)

    Wang, Wen; Xu, Jingdong; Li, Lei; Wang, Peichang; Ji, Xunming; Ai, Houxi; Zhang, Li; Li, Lin

    2010-10-30

    Cornus officinalis Sieb. et Zucc., known as Shan-zhu-yu in Chinese, has been used to treat cerebrovascular disease and diabetes in Traditional Chinese Medicine for a long time and morroniside is the main component of Shan-zhu-yu. In this study, we examined whether morroniside could protect ischemia/reperfusion-induced brain injury by minimizing oxidative stress and anti-apoptosis. Morroniside was intragastrically administered to rats in doses of 30, 90 and 270mg/kg/day, starting 3h after the onset of middle cerebral artery occlusion. The behavioral test was performed by using the Zea-Longa scores, Prehensile Traction score and Ludmila Belayer score. Rats were sacrificed 3 days after ischemia occurred. The infarction volume of brain was assessed in the brain slices stained with 2,3,5-triphenyl tetrazolium chloride. Cortex tissues were also used for determination of malondialdehyde levels, glutathione levels and superoxide dismutase. The treatment with morroniside significantly improved Zea-Longa scores and Prehensile Traction score at the doses of 30, 90 and 270mg/kg, increased Ludmila Belayer score and reduced the infarction volume at the doses of 90 and 270mg/kg. Morroniside (30, 90 and 270mg/kg) treatment significantly decreased the level of malondialdehyde and caspase-3 activity by colorimetric analysis in ischemic cortex tissues. Morroniside (270mg/kg) treatment significantly increased the content of glutathione, enhanced the activity of superoxide dismutase, but decreased the caspase-3 expression by Western-blot analysis in ischemic cortex tissues. These findings demonstrated that morroniside could notably protect the brain from damage induced by focal cerebral ischemia which might be related to morroniside antioxidant and anti-apoptotic properties in the brain. PMID:20637265

  4. 12 hours after cerebral ischemia is the optimal time for bone marrow mesenchymal stem cell transplantation

    OpenAIRE

    Seyed Mojtaba Hosseini; Mohammad Farahmandnia; Zahra Razi; Somayeh Delavarifar; Benafsheh Shakibajahromi

    2015-01-01

    Cell therapy using stem cell transplantation against cerebral ischemia has been reported. However, it remains controversial regarding the optimal time for cell transplantation and the transplantation route. Rat models of cerebral ischemia were established by occlusion of the middle cerebral artery. At 1, 12 hours, 1, 3, 5 and 7 days after cerebral ischemia, bone marrow mesenchymal stem cells were injected via the tail vein. At 28 days after cerebral ischemia, rat neurological function was eva...

  5. Effect of policosanol on cerebral ischemia in Mongolian gerbils

    Directory of Open Access Journals (Sweden)

    V. Molina

    1999-10-01

    Full Text Available Policosanol is a mixture of higher aliphatic primary alcohols isolated from sugar cane wax, whose main component is octacosanol. An inhibitory effect of policosanol on platelet aggregation and cerebral ischemia in animal models has been reported. Thus, the objective of the present study was to evaluate the effect of policosanol on cerebral ischemia induced by unilateral carotid ligation and bilateral clamping and recirculation in Mongolian gerbils. Policosanol (200 mg/kg administered immediately after unilateral carotid ligation and at 12- or 24-h intervals for 48 h significantly inhibited mortality and clinical symptoms when compared with controls, whereas lower doses (100 mg/kg were not effective. Control animals showed swelling (tissue vacuolization and necrosis of neurons in all areas of the brain studied (frontal cortex, hippocampus, striatum and olfactory tubercle, showing a similar injury profile. In the group treated with 200 mg/kg policosanol swelling and necrosis were significantly reduced when compared with the control group. In another experimental model, comparison between groups showed that the brain water content of control gerbils (N = 15 was significantly higher after 15 min of clamping and 4 h of recirculation than in sham-operated animals (N = 13, whereas policosanol (200 mg/kg (N = 19 significantly reduced the edema compared with the control group, with a cerebral water content identical to that of the sham-operated animals. cAMP levels in the brain of control-ligated Mongolian gerbils (N = 8 were significantly lower than those of sham-operated animals (N = 10. The policosanol-treated group (N = 10 showed significantly higher cAMP levels (2.68 pmol/g of tissue than the positive control (1.91 pmol/g of tissue and similar to those of non-ligated gerbils (2.97 pmol/g of tissue. In conclusion, our results show an anti-ischemic effect of policosanol administered after induction of cerebral ischemia, in two different experimental

  6. Hippocampal neurogenesis in the new model of global cerebral ischemia

    Science.gov (United States)

    Kisel, A. A.; Chernysheva, G. A.; Smol'yakova, V. I.; Savchenko, R. R.; Plotnikov, M. B.; Khodanovich, M. Yu.

    2015-11-01

    The study aimed to evaluate the changes of hippocampal neurogenesis in a new model of global transient cerebral ischemia which was performed by the occlusion of the three main vessels (tr. brachiocephalicus, a. subclavia sinistra, and a. carotis communis sinistra) branching from the aortic arch and supplying the brain. Global transitory cerebral ischemia was modeled on male rats (weight = 250-300 g) under chloral hydrate with artificial lung ventilation. Animals after the same surgical operation without vessel occlusion served as sham-operated controls. The number of DCX-positive (doublecortin, the marker of immature neurons) cells in dentate gyrus (DG) and CA1-CA3 fields of hippocampus was counted at the 31st day after ischemia modeling. It was revealed that global cerebral ischemia decreased neurogenesis in dentate gyrus in comparison with the sham-operated group (P<0.05) while neurogenesis in CA1-CA3 fields was increased as compared to the control (P<0.05).

  7. Magnetic resonance imaging of experimental cerebral ischemia

    International Nuclear Information System (INIS)

    In the spectroscopic experiment on excised rat brain (cortex, white matter, hippocampus and thalamus for normal and ischemia-laden brain), T1 and T2 relaxation times and water content were determined. The ischemic insult was induced for 60 min by the method of Pulsinelli followed by 60 min of reperfusion. All of the T1, T2, and water content significantly increased in the ischemic tissue. Gray-white difference was evident in T1 and T1 was linearly correlated with the water content of the tissue. T2 way by far prolonged in the ischemic tissue compared with the increase in the water content, showing greater sensitivity of T2 for detection of ischemia. In the imaging experiment, coronal NMR imaging at 0.5 tesla was performed employing proton density-weighted saturation recovery (TR = 1.6 s, TE = 14 ms), T1-weighted inversion recovery (TR = 1.6 s, TI = 300 ms, TE = 14 ms) and T2-weighted spin echo (TR = 1.6 s, TE = 106 ms) pulse sequences. Spatial resolution of the images was excellent (0.3 - 0.5 mm) and the imaging of a gerbil brain clearly delineated anatomy separating cortex, white matter, hippocampus and thalamus. Hemispheric ischemia of a gerbil brain was detected as early as 30 min after occlusion of the carotid artery in T2-weighted images and the evolution of the lesion was clearly picturized in T1- and T2-weighted images. On the other hand. SR images were far less sensitive. Caluculated T1 and T2 relaxation times by the pixel-to-pixel computation indicated progress of the lesion and excellently correlated with the water content of the tissue (r = 0.892 and 0.744 for T1 and T2, respectively). (J.P.N.)

  8. The effect of herbs on cerebral energy metabolism in cerebral ischemia-reperfusion mice

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@Vascular dementia is one of the most familiar types of senile dementia. Over the past few years, the research on the damage of cerebral tissues after ischemia has become a focus. The factors and mechanism of cerebral tissue damage after ischemia are very complex. The handicap of energy metabolism is regarded as the beginning factor which leads to the damage of neurons, but its dynamic changes in ischemic area and its role during the process of neuronal damage are not very clear. There are few civil reports on using 31 P nuclear magnetic resonance instrument to explore the changes of cerebral energy metabolism in intravital animals. After exploring the influence of herbs on cerebral energy metabolism in ischemia-reperfusion mice, we came to the conclusion that herbs can improve the cerebral energy metabolism in ischemia-reperfusion mice.

  9. THE EFFECT OF ANISODAMINE ON CEREBRAL RESUSCITATION OF RATS IN ACUTE CEREBRAL ISCHEMIA FROM CARDIAC ARREST

    Institute of Scientific and Technical Information of China (English)

    彭新琦; 曹苏谊; 可君

    1995-01-01

    In order to investigate the mechanisms of acute cerebral ischemia,and to look for effective drugs on cerebral resuscitation,we made a model of acute complete global brain ischemia,reperfusion and resuscita-tion on rats according to Garavilla's method.Our results showed that the event of cerebral ischemia and reperfusion injury could result in the in-crease of total brain calcium content,and anisodamine has the same reducing brain calcium contents as dil-tiazem's,while improving neurological outcome and alleviating injury to neurons.

  10. Protective Effect of Extract of Folium Ginkgo on Repeated Cerebral Ischemia-Reperfusion Injury

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To study the protective effect of extract of Folium Ginkgo (FGE) on repeated cerebral ischemia-reperfusion injury. Methods: The model in waking mice induced by repeated cerebral ischemia-reperfusion were used in the experiment to observe the effect of FGE on behavior, oxygen free radical metabolism and prostaglandin E2 (PGE2) content by step-through experiment, diving stand and colorimetric method. Results: FGE could obviously improve the learning ability and memory of model animals, and could lower obviously the content of malonyldialdehyde, nitric oxide and PGE2, restore the lowered activity of superoxide dismutase and catalase in cerebral tissue. Conclusion: FGE has highly protective effect against repeated ischemia-reperfusion injury, the mechanism might be related with its action on anti-lipid oxidatin, improve the activity of antioxidase and inhibit the producing of PGE2.

  11. Doxycycline inhibits MMPs via modulation of plasminogen activators in focal cerebral ischemia.

    Science.gov (United States)

    Burggraf, Dorothe; Trinkl, Andreas; Dichgans, Martin; Hamann, Gerhard F

    2007-03-01

    Tetracyclines inhibit matrix metalloproteinases (MMPs) and reduce infarction volume following cerebral ischemia. In this thesis an involvement of urokinase could be proven. Cerebral ischemia in rats was induced for 3 h followed by 24 h reperfusion (suture model). Each 6 animals received orally either doxycycline or water. Doxycycline treatment began 10 days before ischemia. MMP-2 and MMP-9 were substantially decreased. The possibility of involvement of the endogenous MMP inhibitors in the MMP inhibiting mechanisms was excluded. The plasminogen activator uPA was significantly decreased by doxycycline indicating an MMP inhibiting mechanism including the plasminogen/plasmin system. In the doxycycline group, this resulted in a decreased damage to the cerebral microvessels and less loss of the basal lamina antigen collagen type IV. Hemoglobin extravasation was also significantly reduced. Our results suggest that doxycycline may have a potential use as an anti-ischemic compound since it provides microvascular protection by inhibiting the plasminogen system. PMID:17166729

  12. Hippophae salicifolia D.Don berries attenuate cerebral ischemia reperfusion injury in a rat model of middle cerebral artery occlusion

    Institute of Scientific and Technical Information of China (English)

    Santhrani Thakur; Pradeepthi Chilikuri; Bindu Pulugurtha; Lavanya Yaidikar

    2015-01-01

    Objective: To investigate the protective effect of Hippophae salicifolia D.Don (H. salicifolia) berries extract against cerebral reperfusion injury induced neurobehavioral and neurochemical changes in a rat model of middle cerebral artery occlusion (MCAO). Methods: Rats were pretreated with alcoholic extract of H. salicifolia (250 and 500 mg/kg) for 14 d and focal cerebral ischemia was induced by MCAO. After 60 min of MCAO, reperfused for 24 h, a battery of behavioral tests were assessed the extent of neurological deficits. Infarct volume and brain edema were measured in 2,3,5-triphenyltetrazolium chloride stained brain sections. TNF-α, oxidative stress parameters like reduced glutathione, calcium, glutamate, malondialdehyde and apoptotic parameters like caspase-3, and caspase-9 were estimated in the brain homogenates. Results:Pretreatment with alcoholic extract of H. salicifolia at doses of 250 and 500 mg/kg significantly improved the neurobehavioral alterations and reduced the infarct volume, edema induced by ischemia reperfusion injury. H. salicifolia significantly prevented ischemia induced increase in malondialdehyde, glutamate, calcium, caspase-3, caspase-9 and TNF-αlevels as compared to ischemic animals. Conclusions: Our results indicate that H. salicifolia mitigated the ischemia reperfusion induced neuronal damage.

  13. The effect of hyperglycemia on lipid peroxidation in the global cerebral ischemia of the rat.

    OpenAIRE

    Roh, J. K.; Hong, S B; Yoon, B. W.; Kim, M.S.; Myung, H.

    1992-01-01

    To investigate the influence of hyperglycemia on ischemic brain damage, we measured brain ATP, lactate and malondialdehyde (MDA) levels in global cerebral ischemic models of Wistar rats. We induced global cerebral ischemia by the 4-vessel occlusion method. After 30 or 60 min of occlusion, and after 30 min of reperfusion, we measured brain ATP, lactate and MDA levels. During the ischemic period, brain ATP levels decreased to 30-70% of sham groups both in normoglycemic and hyperglycemic groups....

  14. Moringa Oleifera Lam Mitigates Oxidative Damage and Brain Infarct Volume in Focal Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    Woranan Kirisattayakul

    2012-01-01

    Full Text Available Problem statement: At present, the therapeutic outcome of cerebral ischemia is still not in the satisfaction level. Therefore, the preventive strategy is considered. Based on the protective effect against oxidative damage of Moringa oleifera Lam. Leaves extract, we hypothesized that this plant extract might protect against cerebral ischemia, one of the challenge problems nowadays. In order to test this hypothesis, we aimed to determine the protective effect of M.oleifera leaves extract in animal model of focal cerebral ischemia induced by permanent occlusion of right middle cerebral artery. Approach: Male Wistar rats, weighing 300-350 g, were orally given the extract once daily at doses of 100, 200 and 400 mg kg-1 BW at a period of 2 weeks, then, they were permanently occluded the right Middle Cerebral Artery (MCAO. The animals were assessed the cerebral infarction volume and oxidative damage markers including MDA level and the activities of SOD, CAT and GSHPx enzymes at 24 h after occlusion. Results: Rats subjected to M.oleifera extract at all doses used in this study significantly decreased brain infarct volume both at cortical and subcortical structures in accompany with the elevation of SOD activity in both hippocampus and striatum while only the rats exposed to the extract at doses of 100 and 400 mg kg-1 BW showed the increased GSHPx activity in hippocampus. No the changes were observed. Therefore, our results demonstrates the potential benefit of M.oleifera leaves to decrease oxidative stress damage and brain infarct volume. Conclusion: This study is the first study to demonstrate the neuroprotective effect against focal cerebral ischemia of M.oleifera leaves. It suggests that M.oleifera may be served as natural resource for developing neuroprotectant against focal cerebral ischemia. However, the precise underlying mechanism and possible active ingredient are still required further study.

  15. Effects of buprenorphine and meloxicam analgesia on induced cerebral ischemia in C57BL/6 male mice

    DEFF Research Database (Denmark)

    Jacobsen, Kirsten R; Fauerby, Natasha; Raida, Zindy;

    2013-01-01

    Laboratory mice constitute an extensively used model to study the pathologic and functional outcomes of cerebral ischemic stroke. The middle cerebral artery occlusion (MCAO) model requires surgical intervention, which potentially can result in postsurgical pain and stress. In the present study, we...... investigated whether buprenorphine and meloxicam, at clinically relevant doses provided pain relief without altering infarct volume in male C57BL/6 mice. Common known side-effects of buprenorphine, including decreased food consumption, were noted after surgery in buprenorphine-treated mice, but these effects...... were brief and seen only during the treatment period. Fecal corticosterone metabolites did not differ significantly between the groups. In the present study, buprenorphine treatment did not alter infarction volume when compared with that of mice that did not receive analgesia. In contrast, meloxicam...

  16. Effect of curcumin on diabetic rat model of cerebral ischemia.

    Science.gov (United States)

    Miao, Mingsan; Cheng, Bolin; Li, Min

    2015-01-01

    To investigate the effect of curcumin on cerebral ischemia in diabetic rats the effects and features. intravenous injection alloxan diabetes model, to give alloxan first seven days the tail measured blood glucose value, the election successful model rats were fed with large, medium and small doses of curcumin suspension, Shenqijiangtang suspension and the same volume of saline, administered once daily. The first 10 days after administration 2h (fasting 12h) rat tail vein blood glucose values measured in the first 20 days after administration of 2h (fasting 12h), do cerebral ischemia surgery; rapid carotid artery blood after 30min rats were decapitated, blood serum, blood glucose and glycated serum protein levels; take part of the brain homogenates plus nine times the amount of normal saline, made 10 percent of brain homogenates. Another part of the brain tissue, in the light microscope observation of pathological tissue. Compared with model group, large, medium and small doses of curcumin can significantly lower blood sugar and glycated serum protein levels, significantly reduced brain homogenates lactic acid content and lactate dehydrogenase activity; large, medium-dose curcumin can significantly increase brain homogenates Na(+)-K(+)-ATP activity, dose curcumin can significantly improve brain homogenates Ca(+)-Mg(+)- ATP activity. Curcumin can reduce blood sugar in diabetic rat model of cerebral ischemia and improve brain energy metabolism, improve their brain tissue resistance to ischemia and hypoxia, cerebral ischemia in diabetic rats have a good drop the role of sugar and protect brain tissue. PMID:25631517

  17. Synthesis and Protective Effect of Scutellarein on Focal Cerebral Ischemia/Reperfusion in Rats

    Directory of Open Access Journals (Sweden)

    Nian-Guang Li

    2012-09-01

    Full Text Available Scutellarein, the main metabolite of scutellarin in vivo, has relatively better solubility, bioavailability and bio-activity than scutellarin. However, compared with scutellarin, it is very difficult to obtain scutellarein from Nature. Therefore, the present study focused on establishing an efficient route for the synthesis of scutellarein by hydrolyzing scutellarin. Neurological deficit score and cerebral infarction volume with the administration of scutellarein were then used to compare its neuroprotective effects on focal cerebral ischemia/reperfusion in rats induced by middle cerebral artery occlusion (MCAO with those of scutellarin. The results showed that scutellarein had better protective effect on focal cerebral ischemia/reperfusion than scutellarin, which laid the foundation for further research and development of scutellarein as a promising candidate for ischemic cerebro-vascular disease.

  18. Chronic oleoylethanolamide treatment improves spatial cognitive deficits through enhancing hippocampal neurogenesis after transient focal cerebral ischemia.

    Science.gov (United States)

    Yang, Li-Chao; Guo, Han; Zhou, Hao; Suo, Da-Qin; Li, Wen-Jun; Zhou, Yu; Zhao, Yun; Yang, Wu-Shuang; Jin, Xin

    2015-04-15

    Oleoylethanolamide (OEA) has been shown to have neuroprotective effects after acute cerebral ischemic injury. The aim of this study was to investigate the effects of chronic OEA treatment on ischemia-induced spatial cognitive impairments, electrophysiology behavior and hippocampal neurogenesis. Daily treatments of 30 mg/kg OEA significantly ameliorated spatial cognitive deficits and attenuated the inhibition of long-term potentiation (LTP) in the middle cerebral artery occlusion (MCAO) rat model. Moreover, OEA administration improved cognitive function in a manner associated with enhanced neurogenesis in the hippocampus. Further study demonstrated that treatment with OEA markedly increased the expressions of brain-derived neurotrophic factor (BDNF) and peroxisome proliferator-activated receptors α (PPARα). Our data suggest that chronic OEA treatment can exert functional recovery of cognitive impairments and neuroprotective effects against cerebral ischemic insult in rats via triggering of neurogenesis in the hippocampus, which supports the therapeutic use of OEA for cerebral ischemia. PMID:25748831

  19. Progesterone is neuroprotective by inhibiting cerebral edema after ischemia

    Institute of Scientific and Technical Information of China (English)

    Yuan-zheng Zhao; Min Zhang; Heng-fang Liu; Jian-ping Wang

    2015-01-01

    Ischemic edema can alter the structure and permeability of the blood-brain barrier. Recent stud-ies have reported that progesterone reduces cerebral edema after cerebral ischemia. However, the underlying mechanism of this effect has not yet been elucidated. In the present study, pro-gesterone effectively reduced Evans blue extravasation in the ischemic penumbra, but not in the ischemic core, 48 hours after cerebral ischemia in rats. Progesterone also inhibited the down-reg-ulation of gene and protein levels of occludin and zonula occludens-1 in the penumbra. These results indicate that progesterone may effectively inhibit the down-regulation of tight junctions, thereby maintaining the integrity of the blood-brain barrier and reducing cerebral edema.

  20. Synergistic effects of prostaglandin E1 and lithium in a rat model of cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Rong RAN; Bo GAO; Rui SHENG; Li-sha ZHANG; Hui-lin ZHANG; Zhen-lun GU; Zheng-hong QIN

    2008-01-01

    Aim:Heat shock proteins (HSPs) are important regulators of cellular survival and exert neuroprotective effects against cerebral ischemia.Both prostaglandin El (PGEI) and lithium have been reported to protect neurons against ischemic injury.The present study was undertaken to examine if lithium could potentiate the neuroprotection of PGE 1 against cerebral ischemia,and if the synergetic effects take place at the level of HSPs.Methods:Brain ischemia was induced by a permanent middle cerebral artery occlusion (pMCAO) in rats.Rats were pretreated with subcutaneous injection of lithium for 2 d and a single intravenous administration of PGEI immediately after ischemic insult.Cerebrocortical blood flow of each group was closely monitored prior to onset of ischemia,5 min,15 rain,30 min and 60 min after surgical operation.Body temperature was measured before,5 min,2 h and 24 h after the onset of pMCAO.The infarct volume,brain edema and motor behavior deficits were analyzed 24 h after ischemic insult.Cytoprotective HSP70 and heme oxygenase-1 (HO-1) in the striatum of the ipsilateral hemisphere were detected by immunoblotting.Brain sections from the striatum of the ipsilateral hemisphere were double-labeled with the anti-HSP70 antibody and 4,6-diamidino-2-phenylindole (DAPI).Results:Treatment with PGEI (8 and 16 ~tg/kg,iv) or lithium (0.5 mEq/kg,sc) alone reduced infarct volume,neurological deficits and brain edema induced by focal cerebral ischemia in rats.Moreover,a greater neuroprotection was observed when PGEI and lithium were given together.Co-administration of PGE1 and lithium significantly upregulated cytoprotective HSP70 and HO-1 protein levels.Conclusion:Lithium and PGEI may exert synergistic effects in treatment of cerebral ischemia and thus may have potential clinical value for the treatment of stroke.

  1. A simple and sensitive method to assess ischemia occurrence in the setting of focal cerebral ischemia in rat:A comparative study

    Institute of Scientific and Technical Information of China (English)

    张蓬勃; 刘勇; 李捷; 王莹

    2003-01-01

    Objective:Neurological evaluation is commonly applied to identify ischemia in focal cerebral ischemia model though it might not be sensitive.In present study,we hired sleeping time to assess ischemia occurrence.Methods:Permanent middle cerebral artery occlusion was induced in Sprague-Dawley rats under pentobarbital and ketamine anesthesia respectively.Sleeping time was recorded.Neurological evaluation was conducted by modified Bederson's scoring system at 4 h and histopathological evaluation was performed at 3 d after middle cerebral artery occlusion.Results:Slices of brain stained by TFC,H&E and hoechst 33258 revealed extensive lesion in the two ischemic groups.The sensitivity to identify ischemia by neurological evaluation was 62.5%,but it was 81.3% and 80% respectively when evaluating by sleeping time(pentobarbital:≥90.7 min,ketamine:≥36.1 min).The sensitivity to identify ischemia by sleeping time was significantly higher than that by neurological evaluation(P < 0.05).Conclusion:Our resuits suggested that to identify ischemia by sleeping time is a simple and sensitive method in the setting of focal cerebral ischemia in rat.

  2. Diffusion and Perfusion MRI in Acute Cerebral Ischemia

    Institute of Scientific and Technical Information of China (English)

    Tchoyoson CC Lim; Chong-Tin Tan

    2001-01-01

    Reeent advances in magnetic resonance imaging (MRI), in particular diffusion weighted imaging (DWI) and perfusion weighted imaging (PWI), have allowed clinicians to have the ability to differentiate between irreversible cerebral infarction and the potentially reversible ischemic penumbra. This article examines the principles and practice of DWI and PWI. With continued advances in thrombolysis and other therapy for acute cerebral ischemia, neuroimaging is poised to play an increasingly important role in decisionmaking in aeute stroke.

  3. Focal cerebral ischemia induces increased myelin basic protein and growth-associated protein-43 gene transcription in peri-infarct areas in the rat brain

    DEFF Research Database (Denmark)

    Gregersen, R; Christensen, Thomas; Lehrmann, E;

    2001-01-01

    Although oligodendrocytes are vulnerable to focal cerebral ischemia, remyelination of denuded or regenerating axons in the peri-infarct area has been observed in the central nervous system. We studied the expression of myelin basic protein (MBP), a major component of central nervous system myelin......, in peri-infarct areas in adult rat brain after transient middle cerebral artery occlusion (MCAO) and correlated it to the expression of the growth-associated protein-43 (GAP-43), a marker for axonal regeneration and sprouting, using non-radioactive in situ hybridization techniques. Within the infarct......, MBP messenger RNA (mRNA) had disappeared by 24 h, whereas myelin protein, identified by MBP and myelin oligodendrocyte glycoprotein (MOG) immunohistochemistry, appeared structurally intact until day 3. Peri-infarct oligodendrocytes increased their expression of MBP mRNA from 24 h to maximal levels at...

  4. Behavioral effects and neural changes induced by continuous and not continuous treadmill training, post bilateral cerebral ischemia in gerbils.

    Science.gov (United States)

    Kitabatake, Takae Tamy; Marini, Luana de Castro; Gonçalves, Renata Batagini; Bertolino, Guilherme; de Souza, Hugo Celso Dutra; de Araujo, João Eduardo

    2015-09-15

    This study aims to investigate the effects of treadmill training and the possible influences of the start, regularity, and duration after experimental ischemic stroke. We performed bilateral occlusion of both the carotid arteries for 5 min in Mongolian gerbils. The training groups were: continuous training for 5 consecutive days or not continuous training for 3 non-consecutive days. The groups remained in the treadmill for 15 min, and the training started 12 or 24h after the stroke. In the activity cage (AC), behaviors of crossing and distance traveled were registered. The forced motor behavior was analyzed by a Rota Rod test. After the experiments, the brains were perfused, and coronal sections of the striatum, motor cortex M1, and CA1 area of the hippocampus were cut and stained with hematoxylin and eosin. Behavioral and morphological data analysis was performed by an ANOVA and MANCOVA. Results showed an increased density of neurons in the CA1 area of the hippocampus, motor cortex M1, and the striatum in ischemic training groups compared to the not training ischemic groups. Animals subjected to continuous training that started 24h after ischemia showed a satisfactory behavior in the AC and a higher number of striatal neurons when compared to ischemic animals. The animals in the not continuous training started 12h after the stroke showed an unsatisfactory performance in the AC and Rota Rod. These findings suggest that early training and not continuous training are inadequate for motor behavior improvement after stroke. PMID:25975174

  5. Modulation of NADPH oxidase activation in cerebral ischemia/reperfusion injury in rats.

    Science.gov (United States)

    Genovese, Tiziana; Mazzon, Emanuela; Paterniti, Irene; Esposito, Emanuela; Bramanti, Placido; Cuzzocrea, Salvatore

    2011-02-01

    NADPH oxidase is a major complex that produces reactive oxygen species (ROSs) during the ischemic period and aggravates brain damage and cell death after ischemic injury. Although many approaches have been tested for preventing production of ROSs by NADPH oxidase in ischemic brain injury, the regulatory mechanisms of NADPH oxidase activity after cerebral ischemia are still unclear. The aim of this study is identifying apocynin as a critical modulator of NADPH oxidase and elucidating its role as a neuroprotectant in an experimental model of brain ischemia in rat. Treatment of apocynin 5min before of reperfusion attenuated cerebral ischemia in rats. Administration of apocynin showed marked reduction in infarct size compared with that of control rats. Medial carotid artery occlusion (MCAo)-induced cerebral ischemia was also associated with an increase in, nitrotyrosine formation, as well as IL-1β expression, IκB degradation and ICAM expression in ischemic regions. These expressions were markedly inhibited by the treatment of apocynin. We also demonstrated that apocynin reduces levels of apoptosis (TUNEL, Bax and Bcl-2 expression) resulting in a reduction in the infarct volume in ischemia-reperfusion brain injury. This new understanding of apocynin induced adaptation to ischemic stress and inflammation could suggest novel avenues for clinical intervention during ischemic and inflammatory diseases. PMID:21138737

  6. Attenuation of circulatory shock and cerebral ischemia injury in heat stroke by combination treatment with dexamethasone and hydroxyethyl starch

    Directory of Open Access Journals (Sweden)

    Yang Tsai-Hsiu

    2010-10-01

    Full Text Available Abstract Background Increased systemic cytokines and elevated brain levels of monoamines, and hydroxyl radical productions are thought to aggravate the conditions of cerebral ischemia and neuronal damage during heat stroke. Dexamethasone (DXM is a known immunosuppressive drug used in controlling inflammation, and hydroxyethyl starch (HES is used as a volume-expanding drug in cerebral ischemia and/or cerebral injury. Acute treatment with a combined therapeutic approach has been repeatedly advocated in cerebral ischemia experiments. The aim of this study is to investigate whether the combined agent (HES and DXM has beneficial efficacy to improve the survival time (ST and heat stroke-induced cerebral ischemia and neuronal damage in experimental heat stroke. Methods Urethane-anesthetized rats underwent instrumentation for the measurement of colonic temperature, mean arterial pressure (MAP, local striatal cerebral blood flow (CBF, heart rate, and neuronal damage score. The rats were exposed to an ambient temperature (43 degrees centigrade to induce heat stroke. Concentrations of the ischemic and damage markers, dopamine, serotonin, and hydroxyl radical productions in corpus striatum, and the serum levels of interleukin-1 beta, tumor necrosis factor-alpha and malondialdehyde (MDA were observed during heat stroke. Results After heat stroke, the rats displayed circulatory shock (arterial hypotension, decreased CBF, increased the serum levels of cytokines and MDA, increased cerebral striatal monoamines and hydroxyl radical productions release, and severe cerebral ischemia and neuronal damage compared with those of normothermic control rats. However, immediate treatment with the combined agent at the onset of heat stroke confers significant protection against heat stroke-induced circulatory shock, systemic inflammation; cerebral ischemia, cerebral monoamines and hydroxyl radical production overload, and improves neuronal damage and the ST in rats

  7. Cerebrovascular angiotensin AT1 receptor regulation in cerebral ischemia

    DEFF Research Database (Denmark)

    Edvinsson, Lars

    2008-01-01

    The mechanism behind the positive response to the inhibition of the angiotensin II receptor AT(1) in conjunction with stroke is elusive. Here we demonstrate that cerebrovascular AT(1) receptors show increased expression (upregulation) after cerebral ischemia via enhanced translation. This enhanced...

  8. Ligustrazine monomer against cerebral ischemia-reperfusion injury

    Directory of Open Access Journals (Sweden)

    Hai-jun Gao

    2015-01-01

    Full Text Available Ligustrazine (2,3,5,6-tetramethylpyrazine is a major active ingredient of the Szechwan lovage rhizome and is extensively used in treatment of ischemic cerebrovascular disease. The mechanism of action of ligustrazine use against ischemic cerebrovascular diseases remains unclear at present. This study summarizes its protective effect, the optimum time window of administration, and the most effective mode of administration for clinical treatment of cerebral ischemia/reperfusion injury. We examine the effects of ligustrazine on suppressing excitatory amino acid release, promoting migration, differentiation and proliferation of endogenous neural stem cells. We also looked at its effects on angiogenesis and how it inhibits thrombosis, the inflammatory response, and apoptosis after cerebral ischemia. We consider that ligustrazine gives noticeable protection from cerebral ischemia/reperfusion injury. The time window of ligustrazine administration is limited. The protective effect and time window of a series of derivative monomers of ligustrazine such as 2-[(1,1-dimethylethyloxidoimino]methyl]-3,5,6-trimethylpyrazine, CXC137 and CXC195 after cerebral ischemia were better than ligustrazine.

  9. The neuroprotection of Aspirin on Cerebral Ischemia-Reperfusion rats

    Institute of Scientific and Technical Information of China (English)

    QiuLi-ying; YuJuan; ChenChong-hong; ZhouYu

    2004-01-01

    AIM: Aspirin (aeetylsalicylic acid, ASA as a nonsteroidal anti-inflammatory drug not only has well-established efficacy in anti-thromboxane, but also has direct neuroprotective effect. In this study, we design to investigate its neuroprotective effect on focal cerebral ischemia-reperfusion injury (CIRI rats, and its effect on ATP level from occluded brain tis-

  10. Effect of Batroxobin on Neuronal Apoptosis During Focal Cerebral Ischemia and Reperfusion in Rats

    Institute of Scientific and Technical Information of China (English)

    吴卫平; 匡培根; 李振洲

    2001-01-01

    We have found that Batroxobin plays a protactive role in ischemic brain injury, which attracted us to investigate the effect of Batroxobin on apoptosis of neurons during cerebral ischemia and reperfusion. The apoptotic cells in ischemic rat brains at different reperfusion intervals were tested with method of TdT-mediated dUTP-DIG nick end labeling (TUNEL) and the effect of Batroxobin on the apoptosis of neurons was studied in left middle cerebral artery (LMCA) occlusion and reperfusion in rat models (n=18). The results showed that few scattered apoptosis cells were observed in right cerebral hemispheres after LMCA occlusion and reperfusion, and that a lot of apoptosis cells were found in left ischemic cortex and caudoputamen at 12h reperfusion, and they reached peak at 24h~48h reperfusion. However, in the rats pretreated with Batroxobin, the number of apoptosis cells in left cerebral cortex and caudoputamen reduced significantly and the neuronal damage was much milder at 24h reperfusion than that of saline-treated rats. The results indicate that administration of Batroxobin may reduce the apoptosis of neurons induced by cerebral ischemia and reperfusion and afford significant cerebroprotection in the model of focal cerebral ischemia and reperfusion.

  11. Early Exercise Affects Mitochondrial Transcription Factors Expression after Cerebral Ischemia in Rats

    Directory of Open Access Journals (Sweden)

    Yongshan Hu

    2012-02-01

    Full Text Available Increasing evidence shows that exercise training is neuroprotective after stroke, but the underlying mechanisms are unknown. To clarify this critical issue, the current study investigated the effects of early treadmill exercise on the expression of mitochondrial biogenesis factors. Adult rats were subjected to ischemia induced by middle cerebral artery occlusion followed by reperfusion. Expression of two genes critical for transcriptional regulation of mitochondrial biogenesis, peroxisome proliferator-activated receptor coactivator-1 (PGC-1 and nuclear respiratory factor-1 (NRF-1, were examined by RT-PCR after five days of exercise starting at 24 h after ischemia. Mitochondrial protein cytochrome C oxidase subunit IV (COX IV was detected by Western blot. Neurological status and cerebral infarct volume were evaluated as indices of brain damage. Treadmill training increased levels of PGC-1 and NRF-1 mRNA, indicating that exercise promotes rehabilitation after ischemia via regulation of mitochondrial biogenesis.

  12. Neuroprotective Effects of Pregabalin on Cerebral Ischemia and Reperfusion

    Science.gov (United States)

    Aşcı, Sanem; Demirci, Serpil; Aşcı, Halil; Doğuç, Duygu Kumbul; Onaran, İbrahim

    2016-01-01

    Background: Stroke is one of the most common causes of death and the leading cause of disability in adults. Cerebral ischemia/reperfusion injury causes cerebral edema, hemorrhage, and neuronal death. Aims: In post-ischemic reperfusion, free radical production causes brain tissue damage by oxidative stress. Pregabalin, an antiepileptic agent was shown to have antioxidant effects. The aim of this study was to evaluate the neuroprotective and antioxidant effects of pregabalin on ischemia and reperfusion in rat brain injury. Study Design: Animal experimentation. Methods: Male Wistar rats weighing (250–300 g) were randomly divided into six groups, each consisting of 6 rats: control (C), pregabalin (P), ischemia (I), pregabalin + ischemia (PI), ischemia + reperfusion (IR) and ischemia + reperfusion + pregabalin (PIR). Rats were initially pre-treated with 50 mg/kg/d pregabalin orally for two days. Then, animals that applied ischemia in I, PI, IR and PIR groups were exposed to carotid clamping for 30 minutes and 20 minutes reperfusion was performed in the relevant reperfusion groups. Results: NR2B receptor levels were significantly lower in the PIR group in comparison to the IR group. In the PIR group, Thiobarbituric acid reactive substance (TBARS) level had statistically significant decrease compared with IR group. Glutathione peroxidase (GSH-PX) levels were also significantly increased in the PIR group compared with I, IR and control groups. In the PI and PIR groups, catalase (CAT) levels were also significantly increased compared with I and IR groups (p=0.03 and p=0.07, respectively). Conclusion: Pregabalin may protect the damage of oxidative stress after ischemia + reperfusion. This result would illuminate clinical studies in the future.

  13. Cerebral ischemia upregulates vascular endothelin ET(B) receptors in rat

    DEFF Research Database (Denmark)

    Stenman, Emelie; Malmsjö, Malin; Uddman, Erik; Gidö, Gunilla; Wieloch, Tadeuz; Edvinsson, Lars

    2002-01-01

    BACKGROUND AND PURPOSE: Elevated levels of endothelin-1 (ET-1) have been reported in cerebral ischemia. A role for ET may prove more important if the vascular receptors were changed. We addressed whether there is any change in ET receptor expression in cerebral ischemia. METHODS: The right middle......, calculated as percentage of the contractile capacity of 63.5 mmol/L K+]=68+/-68%; P<0.0001), while there was no difference in the responses to ET-1 after cerebral ischemia. Real-time polymerase chain reaction revealed a significant upregulation of both the ET(A) and ET(B) receptors (both P<0.05) in the...... occluded MCA compared with the nonoccluded MCA from the same rats. CONCLUSIONS: Focal cerebral ischemia in rat induces increased transcription of both ET(A) and ET(B) receptors, which results in the appearance of a contractile response to the ET(B) receptor agonist S6c. These results suggest a role for ET...

  14. Effects of progesterone on neurite growth inhibitors in the hippocampus following global cerebral ischemia.

    Science.gov (United States)

    Espinosa-García, Claudia; Aguilar-Hernández, Alejandra; Cervantes, Miguel; Moralí, Gabriela

    2014-01-30

    In this study, the effects of progesterone (P4) on the immunoreactivity to the neurite growth inhibitor Nogo-A, its receptor (Ng-R), and its effector Rho-A in the rat hippocampus, in association with parameters of spatial learning and memory following global cerebral ischemia, were assessed. Adult male rats were subjected to global cerebral ischemia (15 min), and treated with P4 or its vehicle at 15 min, 2, 6, 24, 48 and 72 h of reperfusion. Immunoreactivity to Nogo-A, Ng-R, and Rho-A was evaluated at 24 h, 72 h or 7 d, or at 14 d of reperfusion after rats were tested in the Morris Water Maze (MWM). Global cerebral ischemia induced an increase in Nogo-A, Ng-R, and Rho-A immunoreactivities in the cell bodies of CA1 pyramidal neurons at 24h after global cerebral ischemia, peaking at 72 h, and persisting 14 d later. In addition, at 72 h, a strong immunoreactivity was observed in the hippocampal layers where dendritic arborizations of CA1 pyramidal neurons are located. Treatment with P4 reduced Nogo-A, Ng-R, and Rho-A immunoreactivities in CA1, particularly at 72 h of reperfusion. These effects of P4 were consistent with the parameters of a more efficient spatial learning and memory in the MWM, as compared to vehicle-treated rats. Overall results suggest the reduction of neurite growth inhibitory molecules Nogo-A, Ng-R, and Rho-A, as a part of the restorative effects of progesterone possibly allowing the plastic phenomena to occur, able to support the functional preservation of the hippocampus following global cerebral ischemia. PMID:24316245

  15. Fish oil prevents oxidative stress and exerts sustained antiamnesic effect after global cerebral ischemia.

    Science.gov (United States)

    Bacarin, Cristiano Correia; de Sá-Nakanishi, Anacharis Babeto; Bracht, Adelar; Matsushita, Makoto; Santos Previdelli, Isolde; Mori, Marco Aurélio; de Oliveira, Rúbia Maria Weffort; Milani, Humberto

    2015-01-01

    Transient, global cerebral ischemia (TGCI) causes hippocampal/cortical damage and the persistent loss of welltrained, long-term memory (retrograde amnesia). Fish oil (FO), a rich source of omega-3 polyunsaturated fatty acids, abolishes such amnesia in the absence of neurohistological protection. The present study investigated whether FO prevents ischemia-induced oxidative stress and whether such an action contributes to the lasting effect of FO on memory recovery. In a first experiment, FO was administered for 4 days prior to ischemia, and antioxidant status was subsequently measured after 24 h of reperfusion. In another experiment, naive rats were trained in an eight-arm radial maze until they achieved asymptotic performance and then subjected to TGCI. One group of rats received FO as in the first experiment (i.e., 4 days prior to ischemia), whereas another group received FO for 4 days prior to ischemia plus 6 days postischemia. Retrograde memory performance was assessed 2-5 weeks after ischemia. TGCI depleted the level of antioxidant enzymes and increased the amount of protein carbonylation, indicating oxidative damage. Fish oil reversed oxidative damage to control levels. The same treatment that attenuated oxidative stress after 24 h of reperfusion also prevented retrograde amnesia assessed several weeks later. This antiamnesic effect afforded by short preischemia treatment was comparable to 10 days of treatment but not as consistent. These data indicate that an antioxidant action in the hyperacute phase of ischemia/reperfusion may contribute to the long-term, antiamnesic effect of FO. PMID:25714977

  16. Gene expression profiling in the human middle cerebral artery after cerebral ischemia

    DEFF Research Database (Denmark)

    Vikman, P; Edvinsson, L

    2006-01-01

    We have investigated the gene expression in human middle cerebral artery (MCA) after ischemia. Ischemic stroke affects the perfusion in the affected area and experimental cerebral ischemia results in upregulation of vasopressor receptors in the MCA leading to the ischemic area. We obtained human...... MCA samples distributing to the ischemic area, 7-10 days post-stroke. The gene expression was examined with real-time polymerase chain reaction (PCR) and microarray, proteins were studied with immunohistochemistry. We investigated genes previously shown to be upregulated in animal models of cerebral...... ischemia (e.g. ET(A), ET(B), AT1, AT2, and 5-HT(2A/1B/1D)). Their mRNA expression was increased compared with controls, consistent with findings in experimental stroke. Immunohistochemistry showed upregulation of the receptors localized on the smooth muscle cells. The gene expression was profiled with...

  17. Evaluation of hyperacute cerebral ischemia in rats using micro SPECT/CT

    International Nuclear Information System (INIS)

    Objective: To assess the diagnostic value of 99Tcm-ECD SPECT for hyperacute cerebral ischemia using rats models. Methods: A stable and permanent acute cerebral ischemia model using unilateral middle cerebral occlusion was tested in 24 healthy SD rats. The rats were randomly divided into 6 groups according to the time duration between imaging and induced-ischemia (1, 2, 3, 4, 5 and 6 h, respectively). The rats were sacrificed immediately after 99Tcm-ECD SPECT/CT imaging and then the brain tissue was dissected for triphenyl tetrazolium chloride (TTC) and HE staining. The count ratio of affected cortex to the contralateral cortex of <50% was defined as ischemia on micro SPECT/CT. The volume of the ischemic area was calculated on both SPECT/CT and TTC images. Paired t test was used to determine the statistical difference between the volumes on SPECT/CT and TTC staining. Results: The ischemia volume evaluated by TTC staining at 1, 2, 3, 4, 5 and 6 h after occlusion was (73.98 ± 27.76), (90.75 ±29.00), (135.00±40.83), (136.25±22.51), (158.50±32.72) and (168.00±32.75) mm3, respectively. The corresponding ischemia volume evaluated by micro SPECT/CT was (98.50 ± 27.77), (110.40±26.80), (157.00±36.82), (165.50±26.54), (175.75±31.16) and (177.25 ±34.33) mm3, respectively, which was concordant with that by TTC staining at each time point (t: -1.681 to -0.390, all P>0.05). The ischemic area on micro SPECT/CT imaging was consistent with the pink area by TTC staining. The volume evaluated by micro SPECT/CT tended to be constant 3 h after the occlusion. The ischemia volume showed no significant difference among 3, 4, 5 and 6 h (all P>0.05). Conclusions: Micro SPECT/CT may have an haemodynamic value for evaluating in vivo cerebral ischemia applied in a rat model. It might have clinical value for the evaluation and decision-making of ultra acute cerebral infarctions. (authors)

  18. Selenium preserves mitochondrial function, stimulates mitochondrial biogenesis, and reduces infarct volume after focal cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Mehta Suresh L

    2012-07-01

    Full Text Available Abstract Background Mitochondrial dysfunction is one of the major events responsible for activation of neuronal cell death pathways during cerebral ischemia. Trace element selenium has been shown to protect neurons in various diseases conditions. Present study is conducted to demonstrate that selenium preserves mitochondrial functional performance, activates mitochondrial biogenesis and prevents hypoxic/ischemic cell damage. Results The study conducted on HT22 cells exposed to glutamate or hypoxia and mice subjected to 60-min focal cerebral ischemia revealed that selenium (100 nM pretreatment (24 h significantly attenuated cell death induced by either glutamate toxicity or hypoxia. The protective effects were associated with reduction of glutamate and hypoxia-induced ROS production and alleviation of hypoxia-induced suppression of mitochondrial respiratory complex activities. The animal studies demonstrated that selenite pretreatment (0.2 mg/kg i.p. once a day for 7 days ameliorated cerebral infarct volume and reduced DNA oxidation. Furthermore, selenite increased protein levels of peroxisome proliferator-activated receptor-γ coactivator 1alpha (PGC-1α and nuclear respiratory factor 1 (NRF1, two key nuclear factors that regulate mitochondrial biogenesis. Finally, selenite normalized the ischemia-induced activation of Beclin 1 and microtubule-associated protein 1 light chain 3-II (LC3-II, markers for autophagy. Conclusions These results suggest that selenium protects neurons against hypoxic/ischemic damage by reducing oxidative stress, restoring mitochondrial functional activities and stimulating mitochondrial biogenesis.

  19. Ketamine inhibits c-Jun protein expression in mouse hippocampus following cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Feng Xiao; Liangzhi Xiong; Qingxiu Wang; Long Zhou; Qingshan Zhou

    2012-01-01

    A model of cerebral ischemia and reperfusion was established in mice. Mice were treated with ketamine via intraperitoneal injection immediately following ischemia or ischemia/reperfusion. Ketamine did not remarkably change infarct volume in mice immediately following ischemia, but injection immediately following ischemia/reperfusion significantly decreased infarct volume. Ketamine injection immediately after ischemia or ischemia/reperfusion inhibited c-Jun protein expression in mouse hippocampus, but nuclear factor kappa B expression was unaltered. In addition, the Longa scale score for neural impairment was not reduced in mice following cerebral ischemia/reperfusion. These results indicate that ketamine can protect mice against cerebral ischemia and reperfusion injury by modulating c-Jun protein expression in mouse hippocampus.

  20. Cerebrovascular endothelin receptor upregulation in cerebral ischemia

    DEFF Research Database (Denmark)

    Edvinsson, Lars

    2009-01-01

    Stroke is a serious neurological disease and the third leading cause of death in the western world. In roughly 15 % of the cases, the cause is due to an intracranial haemorrhage, and the remaining 85 % represent ischemic strokes. Ischemic stroke is caused by the occlusion of a cerebral artery eit...

  1. Cerebrovascular endothelin receptor upregulation in cerebral ischemia

    DEFF Research Database (Denmark)

    Edvinsson, Lars

    2009-01-01

    Stroke is a serious neurological disease and the third leading cause of death in the western world. In roughly 15 % of the cases, the cause is due to an intracranial haemorrhage, and the remaining 85 % represent ischemic strokes. Ischemic stroke is caused by the occlusion of a cerebral artery...

  2. Activation of cerebral sodium-glucose transporter type 1 function mediated by post-ischemic hyperglycemia exacerbates the development of cerebral ischemia.

    Science.gov (United States)

    Yamazaki, Y; Ogihara, S; Harada, S; Tokuyama, S

    2015-12-01

    The regulation of post-ischemic hyperglycemia plays an important role in suppressing neuronal damage in therapeutic strategies for cerebral ischemia. We previously reported that the cerebral sodium-glucose transporter (SGLT) was involved in the post-ischemic hyperglycemia-induced exacerbation of cerebral ischemic neuronal damage. Cortical SGLT-1, one of the cerebral SGLT isoforms, is dramatically increased by focal cerebral ischemia. In this study, we focused on the involvement of cerebral SGLT-1 in the development of cerebral ischemic neuronal damage. It was previously reported that activation of 5'-adenosine monophosphate-activated protein kinase (AMPK) increases SGLT-1 expression. Moreover, ischemic stress-induced activation of AMPK exacerbates cerebral ischemic neuronal damage. Therefore, we directly confirmed the relationship between cerebral SGLT-1 and cerebral AMPK activation using in vitro primary culture of mouse cortical neurons. An in vivo mouse model of focal cerebral ischemia was generated using a middle cerebral artery occlusion (MCAO). The development of infarct volume and behavioral abnormalities on day 3 after MCAO were ameliorated in cerebral SGLT-1 knock down mice. Cortical and striatal SGLT-1 expression levels were significantly increased at 12h after MCAO. Immunofluorescence revealed that SGLT-1 and the neuronal nuclear antigen (NeuN) were co-localized in the cortex and striatum of MCAO mice. In the in vitro study, primary cortical neurons were cultured for five days before each treatment with reagents. Concomitant treatment with hydrogen peroxide and glucose induced the elevation of SGLT-1 and phosphorylated AMPK/AMPK ratio, and this elevation was suppressed by compound C, an AMPK inhibitor in primary cortical neurons. Moreover, compound C suppressed neuronal cell death induced by concomitant hydrogen peroxide/glucose treatment in primary cortical neurons. Therefore, we concluded that enhanced cerebral SGLT-1 function mediated by post

  3. Early Exercise Affects Mitochondrial Transcription Factors Expression after Cerebral Ischemia in Rats

    OpenAIRE

    Yongshan Hu; Jianhong Zhu; Pengyue Zhang; Jie Jia; Hongying Sha; Yi Wu; Qi Zhang

    2012-01-01

    Increasing evidence shows that exercise training is neuroprotective after stroke, but the underlying mechanisms are unknown. To clarify this critical issue, the current study investigated the effects of early treadmill exercise on the expression of mitochondrial biogenesis factors. Adult rats were subjected to ischemia induced by middle cerebral artery occlusion followed by reperfusion. Expression of two genes critical for transcriptional regulation of mitochondrial biogenesis, peroxisome pro...

  4. Gender-specific response to isoflurane preconditioning in focal cerebral ischemia

    OpenAIRE

    Kitano, Hideto; Young, Jennifer M.; Cheng, Jian; Wang, Lan; Hurn, Patricia D.; Murphy, Stephanie J.

    2007-01-01

    Inhalation anesthetics are effective chemical preconditioning agents in experimental cerebral ischemia. However, previous work has been performed exclusively in male animals. We determined if there is a gender difference in ischemic outcome after isoflurane preconditioning (IsoPC), and if this sex-specific response is linked to differences in Akt phosphorylation or expression of neuronal inducible cell-death putative kinase (NIPK), a negative modulator of Akt activation. Young and middle-aged...

  5. Atorvastatin protects against cerebral ischemia/reperfusion injury through anti-inflammatory and antioxidant effects

    OpenAIRE

    Tu, Qiuyun; Cao, Hui; Zhong, Wei; Ding, Binrong; Tang, Xiangqi

    2014-01-01

    In addition to its lipid-lowering effect, atorvastatin exerts anti-inflammatory and antioxidant effects as well. In this study, we hypothesized that atorvastatin could protect against cerebral ischemia/reperfusion injury. The middle cerebral artery ischemia/reperfusion model was established, and atorvastatin, 6.5 mg/kg, was administered by gavage. We found that, after cerebral ischemia/reperfusion injury, levels of the inflammation-related factors E-selectin and myeloperoxidase were upregulat...

  6. Early CT findings in acute middle cerebral artery ischemia

    International Nuclear Information System (INIS)

    Stroke is characterized by a sudden onset of focal central neurological deficit, with symptoms lasting more than 24 hours, that can be fatal. The introduction of anti-coagulation treatments, together with continuous advances inneuroimaging techniques, have a positive impact, both on morbidity and mortality in stroke patients. It must be stressed, that 'therapeutic window' for fibrolytic treatment is up to 3 hours. The group consisted of 50 patients with clinical diagnosis of stroke, who met the following criteria: first ever, non-hemorrhagic stroke, middle cerebral artery territory involvement, first CT performed within 12 hours from the onset of symptoms, control CT, performed within 7 days, confirming signs of infarction in the distribution of middle cerebral artery. All CT were performed without contrast administration. First CT examinations were retrospectively studied for early evidence of ischemic changes, subsequently depicted as infarction in the control CT. Hyperdencemiddle cerebral artery sign (HMCAS), hypoattenuation of lentiform nucleus (ALN), loss of insular ribbon (LIR), hemispheric sulcus effacement (HES) were found as early abnormalities CT examinations continue to play a dominant role in the initial diagnosis of acute cerebral ischemia. Signs of early ischemia can be often detected within the first three hours from the onset, in the hyper acute phase. CT is used in evaluation of recent symptoms in acute phase and proper selection of patients for thrombolysis with significant therapeutic results. [author

  7. Changes of evoked potential and expression of nestin in subventricular zones in rats after focal cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    GAO Jie; WANG Yong-tang; WANG Li-li; ZENG Ling; WU Ya-min; SHAO Yang

    2007-01-01

    Objective:To study the characteristics of latency of somatosensory evoked potential (SEP)and motor evoked potential (MEP) and the expression of nestin in subventricular zones (SVZ) after persistent focal cerebral ischemia in rats. Methods: The model of cerebral ischemia in rats was made by middle cerebral artery occlusion (MCAO). All animals of ischemia were sacrificed after 12 h, 1 d, 3 d, 7 d,and 14 d to observe the changes of latency of SEP and MEP and to detect the expression of nestin, with an immunohistochemical approach. Results: The latencies of P1 (positive wave 1), N1 (negative wave 1) and P2 (positive wave 2) in SEP were significantly prolonged after MCAO. The latencies of N1 and N2 waves in MEP were postponed gradually and no statistical difference of latency of N1 wave was found in rats at 7d and 14 d after MCAO. The expression of nestin increased at 12 h, and showed a significant augmentation at 3 d and peaked at 7 d, then declined slightly at 14 d after MCAO. Conclusion: The cerebral ischemia prolonged the latency of EP waves and the expression of nestin was up-regulated and reached the peak at 7d, showing the ischemia induced the proliferation of nervous stem cells. The SEP and MEP may evaluate the proliferation in SVZ after brain ischemia.

  8. Ultrastructural Study of Neuronal Death in Rat Hippocampus after Transient and Permanent Focal Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    Majid Asadi-Shekaari

    2009-01-01

    Full Text Available Objective: Morphological changes of CA1 neurons in rat hippocampus after transientand permanent focal cerebral ischemia were studied to clarify the nature of postischemiccell death in the subfield.Materials and Methods: Male adult rats were divided into 3 groups: Control (Shamoperated,transient ischemic group (30 minutes of MCAO followed by 48 hours ofreperfusion, and permanent ischemic group (48 hours of MCAO. After the mentionedtimes, deep anesthesia was induced in the rats and their brains were removed andprocessed for transmission electron microscopy (TEM and evaluation.Results: Electron-microscopic examination on day 2 showed key morphological signsof apoptosis in the permanent ischemic group, while morphological signs of necrosiswere observed in the transient ischemic group.Conclusion: These results suggest necrosis (as dominant mechanism of neuronaldeath after transient ischemia and apoptosis (after permanent ischemia to be involvedin neuronal death.

  9. 12 hours after cerebral ischemia is the optimal time for bone marrow mesenchymal stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    Seyed Mojtaba Hosseini; Mohammad Farahmandnia; Zahra Razi; Somayeh Delavarifar; Benafsheh Shakibajahromi

    2015-01-01

    Cell therapy using stem cell transplantation against cerebral ischemia has been reported. However, it remains controversial regarding the optimal time for cell transplantation and the transplantation route. Rat models of cerebral ischemia were established by occlusion of the middle cerebral artery. At 1, 12 hours, 1, 3, 5 and 7 days after cerebral ischemia, bone marrow mesenchymal stem cells were injected via the tail vein. At 28 days after cerebral ischemia, rat neurological function was evaluated using a 6-point grading scale and the pathological change of ischemic cerebral tissue was observed by hematoxylin-eosin staining. Under the lfuorescence microscope, the migration of bone marrow mesenchymal stem cells was examined by PKH labeling. Caspase-3 activity was measured using spectrophotometry. The optimal neurological function recovery, lowest degree of ischemic cerebral damage, greatest number of bone marrow mesenchymal stem cells migrating to peri-ischemic area, and lowest caspase-3 activity in the ischemic cerebral tissue were observed in rats that underwent bone marrow mesenchymal stem cell transplantation at 12 hours after cerebral ischemia. These ifndings suggest that 12 hours after cerebral ischemia is the optimal time for tail vein injection of bone marrow mesenchymal stem cell transplantation against cerebral ischemia, and the strongest neuroprotective effect of this cell therapy appears at this time.

  10. Activation and subcellular distribution of ERK1/2 following cerebral ischemia/reperfusion in rat hippocampus

    Institute of Scientific and Technical Information of China (English)

    WANG Rui-min; ZHANG Guang-yi; ZHANG Quan-guang; YANG Fang; MA Wen-dong; LI Qi-jia

    2006-01-01

    Objective:To investigate the activation (phosphorylation) and subcellular localization of extracellular signal-regulated kinase(ERK1/2), as well as the possible mechanism, following cerebral ischemia and ischemia/reperfusion in rat hippocampus. Methods: Transient brain ischemia was induced by the four-vessel occlusion method in Sprague-Dawley rats. Western blot analysis. Results: During cerebral ischemia without reperfusion ERK1/2 activation immediately increased with a peak at 5 min and then decreased in the cytosol fraction, which was paralleled by the increase of ERK1/2 activation in the nucleus fraction. During reperfusion, ERK1/2 was activated with peaks occurring at 10 min in the cytosol and at 30 min in the nucleus, respectively. Under those conditions, the protein expressions had no significant change. In order to clarify the possible mechanism of ERK1/2 activation, the rats were intraperitoneally administrated with N-methyl D aspartate (NMDA) receptor antagonist dextromethorphan(DM), L-type voltage-gated Ca2+ channel (L-VGCC) antagonist nifedipine (ND) 20 min before ischemia, finding that DM and ND markedly prevented ERK1/2 activation of nucleus fraction induced by reperfusion, not by ischemia. Conclusion: These results suggested that the nuclear translocation mainly occurred during is chemia, while ischemia-reperfusion induced ERK1/2 activation both in the cytosol and the nucleus. Two type calcium channels contributed, at least partially, to the activation of ERK1/2.

  11. Animal models of cerebral ischemia for evaluation of drugs.

    Science.gov (United States)

    Gupta, Y K; Briyal, Seema

    2004-10-01

    Stroke is a major cause of death and disability worldwide. The resulting burden on the society continues to grow, with increase in the incidence of stroke. Brain attack is a term introduced to describe the acute presentation of stroke, which emphasizes the need for urgent action to remedy the situation. Though a large number of therapeutic agents like thrombolytics, NMDA receptor antagonists, calcium channel blockers and antioxidants, have been used or being evaluated, there remains a large gap between the benefits by these agents and properties an ideal drug for stroke should offer. In recent years much attention is being paid towards the exploration of herbal preparation, antioxidant agents and combination therapies including COX-2 inhibitors in experimental model of stroke. For better evaluation of the drugs and enhancement of their predictability from animal experimentation to clinical settings, it has been realized that the selection of animal models, the parameters to be evaluated should be critically assessed. Focal and global cerebral ischemia represents diseases that are common in the human population. Understanding the mechanisms of injury and neuroprotection in these diseases is important to learn new target sites to treat ischemia. There are many animal models available to investigate injury mechanisms and neuroprotective strategies. In this article we attempted to summarize commonly explored animal models of focal and global cerebral ischemia and evaluate their advantages and limitations. PMID:15907047

  12. Thrombolysis and neuroprotection in cerebral ischemia.

    Science.gov (United States)

    Gutiérrez, M; Díez Tejedor, E; Alonso de Leciñana, M; Fuentes, B; Carceller, F; Roda, J M

    2006-01-01

    Stroke is a major cause of death and disability worldwide. The resulting burden on society grows with the increase in the incidence of stroke. The term brain attack was introduced to describe the acute presentation of stroke and emphasize the need for urgent action to remedy the situation. Though a large number of therapeutic agents, like thrombolytics, NMDA receptor antagonists, calcium channel blockers and antioxidants, have been used or are being evaluated, there is still a large gap between the benefits of these agents and the properties of an ideal drug for stroke. So far, only thrombolysis with rtPA within a 3-hour time window has been shown to improve the outcome of patients with ischemic stroke. Understanding the mechanisms of injury and neuroprotection in these diseases is important to target news sites for treating ischemia. Better evaluation of the drugs and increased similarity between the results of animal experimentation and in the clinical setting requires critical assessment of the selection of animal models and the parameters to be evaluated. Our laboratory has employed a rat embolic stroke model to investigate the combination of rtPA with citicoline as compared to monotherapy alone and investigated whether neuroprotection should be provided before or after thrombolysis in order to achieve a greater reduction of ischemic brain damage. PMID:16651822

  13. Protective effect of delta opioid receptor agonist (D-Ala2, D-Leu5) enkephalin on permanent focal cerebral ischemia in rats.

    Science.gov (United States)

    Fu, Danyun; Liu, Haitong; Zhu, Hui; Li, Shitong; Yao, Junyan

    2016-07-01

    To investigate the effect of delta opioid receptor agonist (D-Ala, D-Leu) enkephalin (DADLE) on the permanent focal cerebral ischemia in rats. Thirty four male Sprague-Dawley rats were assigned randomly into three groups: sham group (group Sham, n=10), artificial cerebrospinal fluid group (group ACSF, n=12), and DADLE group (group DADLE, n=12). Permanent middle cerebral artery occlusion was performed to induce permanent focal cerebral ischemia in rats. Then, the animals in group DADLE and group ACSF were treated with DADLE or ACSF by an intracerebroventricular injection at 45 min after ischemia. Neurologic deficit scores were assessed according to the Garcia criterion at 24 h after ischemia. Infarct volume was determined using the 2,3,5-triphenyltetrazolium chloride staining method. The histological analysis was used to evaluate the extent of cerebral injury. Compared with the control group, the Garcia scores were significantly higher (P=0.000) and the infarct volumes (P=0.018) were significantly smaller in the DADLE treatment group at 24 h after ischemia. These neurologic changes were closely correlated with the outcome of the infarct volumes. In addition, the histological examination showed more intact neurons in rats treated with DADLE than those treated with ACSF at 24 h after ischemia (P=0.000). DADLE by intracerebroventricular administration at 45 min after ischemia can improve neurologic outcome and mitigate cortical neuronal injury induced by permanent focal cerebral ischemia in rats. PMID:27232517

  14. Characteristics of global cerebral ischemia models constructed by modified four-vessel occlusion in rats

    Institute of Scientific and Technical Information of China (English)

    Jinbao Li; Lai Jiang; Hua Xu; Yuanchang Xiong; Xiaoming Deng

    2006-01-01

    BACKGROUND: Pulsinelli et al developed a kind of rat models with four-vessel occlusion-induced global cerebral ischemia. Because the histo-pathological changes and severe cerebral ischemia reproducibility of this model are good and the stability of this model in circulation respiration is superior to that of other models, so four-vessel occlusion method has become a classic modeling method for global cerebral ischemia model. This model has been improved in some laboratories to meet different requirements in different studies. OBJECTIVE: To establish a highly reproducible rat model of reversible forebrain ischemia by modifying four-vessel occlusion model introduced by Pulsinelli et al, and to investigate its neurophysiological and pathological changes and the characteristics of modified operation. DESIGN: Completely randomized grouping, controlled trial. SETTING: Department of Anesthesiology,Changhai Hospital, Second Military Medical University of Chinese PLA. MATERIALS: A total of 65 male healthy SD rats, weighing 250-300 g, were provided by the Experimental Animal Center of Second Military Medical University of Chinese PLA. VSM hemodynamic monitor and temperature monitor (Thermal ert TH-5, U.S.A) were used.METHODS: The trial was conducted in the Department of Anesthesiology, Changhai Hospital, Second Military Medical University of Chinese PLA from January 2005 to March 2006. ① Experimental grouping: Sixty-five rats were randomly divided into the following 7 groups: sham-operation group (n =9): given the same operation, without occlusion of vessels; 5 minutes ischemia group (n =9): ischemia 5 minutes and reperfusion 72 hours; 10 minutes ischemia group (n =8): ischemia 10 minutes and reperfusion 72 hours; 15 minutes ischemia group (n =9): ischemia 15 minutes and reperfusion 72 hours; 20 minutes ischemia group (n =8): ischemia 20 minutes and reperfusion 72 hours; 30 minutes ischemia group (n =7); ischemia 30 minutes and reperfusion 72 hours; ischemia control group

  15. Resveratrol inhibits matrix metalloproteinases to attenuate neuronal damage in cerebral ischemia: a molecular docking study exploring possible neuroprotection

    Directory of Open Access Journals (Sweden)

    Anand Kumar Pandey

    2015-01-01

    Full Text Available The main pathophysiology of cerebral ischemia is the structural alteration in the neurovascular unit, coinciding with neurovascular matrix degradation. Resveratrol has been reported to be one of the most potent chemopreventive agents that can inhibit cellular processes associated with ischemic stroke. Matrix metalloproteinases (MMPs has been considered as a potential drug target for the treatment of cerebral ischemia. To explore this, we tried to investigate the interaction of resveratrol with MMPs through molecular docking studies. At 30 minutes before and 2 hours after cerebral ischemia/reperfusion induced by occlusion of the middle cerebral artery, 40 mg/kg resveratrol was intraperitoneally administered. After resveratrol administration, neurological function and brain edema were significantly alleviated, cerebral infarct volume was significantly reduced, and nitrite and malondialdehyde levels in the cortical and striatal regions were significantly decreased. The molecular docking study of resveratrol and MMPs revealed that resveratrol occupied the active site of MMP-2 and MMP-9. The binding energy of the complexes was -37.848672 kJ/mol and -36.6345 kJ/mol for MMP-2 and MMP-9, respectively. In case of MMP-2, Leu 164, Ala 165 and Thr 227 were engaged in H-Bonding with resveratrol and in case of MMP-9, H-bonding was found with Glu 402, Ala 417 and Arg 424 residues. These findings collectively reveal that resveratrol exhibits neuroprotective effects on cerebral ischemia through inhibiting MMP-2 and MMP-9 activity.

  16. Imaging of rat cerebral ischemia-reperfusion injury using99mTc-labeled duramycin

    International Nuclear Information System (INIS)

    Objectives: Prompt identification of necrosis and apoptosis in the infarct core and penumbra region is critical in acute stroke for delineating the underlying ischemic/reperfusion molecular pathologic events and defining therapeutic alternatives. The objective of this study was to investigate the capability of 99mTc-labeled duramycin in detecting ischemia-reperfusion injury in rat brain after middle cerebral artery (MCA) occlusion. Methods: Ischemic cerebral injury was induced in ten rats by vascular insertion of a nylon suture in the left MCA for 3 hr followed by 21–24 hr reperfusion. After i.v. injection of 99mTc-duramycin (1.0-3.5 mCi), dynamic cerebral images were acquired for 1 hr in six rats using a small-animal SPECT imager. Four other rats were imaged at 2 hr post-injection. Ex vivo images were obtained by autoradiography after sacrifice. Histologic analyses were performed to assess cerebral infarction and apoptosis. Results: SPECT images showed that 99mTc-duramycin uptake in the left cerebral hemisphere was significantly higher than that in the right at 1 and 2 hr post-injection. The level of radioactive uptake in the ischemic brain varied based on ischemic severity. The average ratio of left cerebral hot-spot uptake to right hemisphere radioactivity, as determined by computerized ROI analysis, was 4.92 ± 0.79. Fractional washout at 1 hr was 38.2 ± 4.5% of peak activity for left cerebral hot-spot areas and 80.9 ± 2.0% for remote control areas (P 99mTc-duramycin SPECT imaging may be useful for detecting and quantifying ongoing apoptotic neuronal cell loss induced by ischemia-reperfusion injury.

  17. CT perfusion during delayed cerebral ischemia after subarachnoid hemorrhage: distinction between reversible ischemia and ischemia progressing to infarction

    International Nuclear Information System (INIS)

    Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) can be reversible or progress to cerebral infarction. In patients with a deterioration clinically diagnosed as DCI, we investigated whether CT perfusion (CTP) can distinguish between reversible ischemia and ischemia progressing to cerebral infarction. From a prospectively collected series of aSAH patients, we included those with DCI, CTP on the day of clinical deterioration, and follow-up imaging. In qualitative CTP analyses (visual assessment), we calculated positive and negative predictive value (PPV and NPV) with 95 % confidence intervals (95%CI) of a perfusion deficit for infarction on follow-up imaging. In quantitative analyses, we compared perfusion values of the least perfused brain tissue between patients with and without infarction by using receiver-operator characteristic curves and calculated a threshold value with PPV and NPV for the perfusion parameter with the highest area under the curve. In qualitative analyses of 33 included patients, 15 of 17 patients (88 %) with and 6 of 16 patients (38 %) without infarction on follow-up imaging had a perfusion deficit during clinical deterioration (p = 0.002). Presence of a perfusion deficit had a PPV of 71 % (95%CI: 48-89 %) and NPV of 83 % (95%CI: 52-98 %) for infarction on follow-up. Quantitative analyses showed that an absolute minimal cerebral blood flow (CBF) threshold of 17.7 mL/100 g/min had a PPV of 63 % (95%CI: 41-81 %) and a NPV of 78 % (95%CI: 40-97 %) for infarction. CTP may differ between patients with DCI who develop infarction and those who do not. For this purpose, qualitative evaluation may perform marginally better than quantitative evaluation. (orig.)

  18. CT perfusion during delayed cerebral ischemia after subarachnoid hemorrhage: distinction between reversible ischemia and ischemia progressing to infarction

    Energy Technology Data Exchange (ETDEWEB)

    Cremers, Charlotte H.P. [University Medical Center Utrecht, Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, PO Box 85500, Utrecht, Utrecht (Netherlands); University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Vos, Pieter C. [University Medical Center Utrecht, Image Sciences Institute, Utrecht (Netherlands); Schaaf, Irene C. van der; Velthuis, Birgitta K.; Dankbaar, Jan Willem [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Vergouwen, Mervyn D.I.; Rinkel, Gabriel J.E. [University Medical Center Utrecht, Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, PO Box 85500, Utrecht, Utrecht (Netherlands)

    2015-09-15

    Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) can be reversible or progress to cerebral infarction. In patients with a deterioration clinically diagnosed as DCI, we investigated whether CT perfusion (CTP) can distinguish between reversible ischemia and ischemia progressing to cerebral infarction. From a prospectively collected series of aSAH patients, we included those with DCI, CTP on the day of clinical deterioration, and follow-up imaging. In qualitative CTP analyses (visual assessment), we calculated positive and negative predictive value (PPV and NPV) with 95 % confidence intervals (95%CI) of a perfusion deficit for infarction on follow-up imaging. In quantitative analyses, we compared perfusion values of the least perfused brain tissue between patients with and without infarction by using receiver-operator characteristic curves and calculated a threshold value with PPV and NPV for the perfusion parameter with the highest area under the curve. In qualitative analyses of 33 included patients, 15 of 17 patients (88 %) with and 6 of 16 patients (38 %) without infarction on follow-up imaging had a perfusion deficit during clinical deterioration (p = 0.002). Presence of a perfusion deficit had a PPV of 71 % (95%CI: 48-89 %) and NPV of 83 % (95%CI: 52-98 %) for infarction on follow-up. Quantitative analyses showed that an absolute minimal cerebral blood flow (CBF) threshold of 17.7 mL/100 g/min had a PPV of 63 % (95%CI: 41-81 %) and a NPV of 78 % (95%CI: 40-97 %) for infarction. CTP may differ between patients with DCI who develop infarction and those who do not. For this purpose, qualitative evaluation may perform marginally better than quantitative evaluation. (orig.)

  19. Attenuation of Brain Inflammatory Response after Focal Cerebral Ischemia/Reperfusion with Xuesaitong Injection(血塞通注射液) in Rats

    Institute of Scientific and Technical Information of China (English)

    HE Wei; XU Xiao-jun

    2006-01-01

    Objective: To investigate the neuro-protective effect of Xuesaitong Injection ( 血塞通注射液 ,XST) on brain inflammatory response after transient focal cerebral ischemia/reperfusion in rats. Methods:Focal cerebral ischemia/reperfusion models of male rats were induced by transient occlusion for 2 h of middle cerebral artery (MCA) which was followed by 24 h reperfusion. XST was administered through intraperitoneal injection of 25 mg/kg or 50 mg/kg at 4 h after the onset of ischemia. After reperfusion for 24 h, the neurological function score was evaluated, the brain edema was detected with dry-wet weight method, the myeloperoxidase (MPO) activity and the expression of intercellular adhesion molecule-1 (ICAM-1) of ischemic cerebral cortex and caudate putamen was determined by spectrophotometry and immunohistochemistry respectively. Results: XST not only lowered neurological function score at the dose of 50 mg/kg, but reduced brain edema and inhibited MPO activity and ICAM-1 expression as compared with the ischemia/reperfusion model group ( P<0.01 ). Conclusion: XST has a definite effect on inhibiting the expression of ICAM-1 and neutrophil infiltration in rats with cerebral ischemia/reperfusion when treatment started at 4 h after ischemia onset, and also attenuates inflammation in the infarcted cerebral area.neutrophil, intercellular adhesion molecule-1 of ischemic cerebral cortex and caudate putamen was determined by spectrophotometry and immunohistochemistry respectively. Results: XST not only lowered neurological function score at the dose of 50 mg/kg, but reduced brain edema and inhibited MPO activity and ICAM-1 expression as compared with the ischemia/reperfusion model group ( P<0.01 ). Conclusion: XST has a definite effect on inhibiting the expression of ICAM-1 and neutrophil infiltration in rats with cerebral ischemia/reperfusion when treatment started at 4 h after ischemia onset, and also attenuates inflammation in the infarcted cerebral area.

  20. Ellagic acid improves electrocardiogram waves and blood pressure against global cerebral ischemia rat experimental models

    OpenAIRE

    Nejad, Khojasteh Hoseiny; Dianat, Mahin; Sarkaki, Alireza; Naseri, Mohammad Kazem Gharib; Badavi, Mohammad; Farbood, Yaghoub

    2015-01-01

    Background: Global cerebral ischemia (GCIR) arises in patients that are shown a variety of clinical difficulty including cardiac arrest, asphyxia, and shock. In spite of advances in understanding of the brain, ischemia and protective effects to improve ischemic injury still remain unknown. The aim of our study was to investigate the effect of ellagic acid (EA) pretreatment in the rat models of global cerebral ischemia reperfusion. Methods: This experimental study was conducted in 2014 at the ...

  1. MicroRNA responses to focal cerebral ischemia in male and female mouse brain

    OpenAIRE

    Lusardi, Theresa A; Murphy, Stephanie J.; Phillips, Jay I.; Chen, Yingxin; Catherine M Davis; Young, Jennifer M.; Thompson, Simon J.; Saugstad, Julie A

    2014-01-01

    Stroke occurs with greater frequency in men than in women across diverse ethnic backgrounds and nationalities. Work from our lab and others have revealed a sex-specific sensitivity to cerebral ischemia whereby males exhibit a larger extent of brain damage resulting from an ischemic event compared to females. Previous studies revealed that microRNA (miRNA) expression is regulated by cerebral ischemia in males; however, no studies to date have examined the effect of ischemia on miRNA responses ...

  2. A comparison study of PET, NMR, and CT imaging in cerebral ischemia

    International Nuclear Information System (INIS)

    Whether ischemia without infarction produces recognizable changes in relaxation times of ischemic but viable brain is an important, unresolved issue. Therefore, a study was initiated of patients with cerebral ischemia, using positron emission tomography (PET), NMR, and computed tomography (CT) to compare and contrast the pathophysiologic information provided by each and to study the issue of whether cerebral ischemia without infarction can be appreciated by proton NMR imaging. Here the initial results are reported. 4 refs.; 2 figs.; 1 table

  3. Evaluation of the PBR/TSPO radioligand [18F]DPA-714 in a rat model of focal cerebral ischemia

    International Nuclear Information System (INIS)

    Focal cerebral ischemia leads to an inflammatory reaction involving an overexpression of the peripheral benzodiazepine receptor (PBR)/18-kDa translocator protein (TSPO) in the cerebral monocytic lineage (micro-glia and monocyte) and in astrocytes. Imaging of PBR/TSPO by positron emission tomography (PET) using radiolabeled ligands can document inflammatory processes induced by cerebral ischemia. We performed in vivo PET imaging with [18F]DPA-714 to determine the time course of PBR/TSPO expression over several days after induction of cerebral ischemia in rats. In vivo PET imaging showed significant increase in DPA (N, N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)- 5, 7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl)acetamide) uptake on the injured side compared with that in the contralateral area on days 7, 11, 15, and 21 after ischemia; the maximal binding value was reached 11 days after ischemia. In vitro autoradiography confirmed these in vivo results. In vivo and in vitro [18F]DPA-714 binding was displaced from the lesion by PK11195 and DPA-714. Immunohistochemistry showed increased PBR/TSPO expression, peaking at day 11 in cells expressing micro-glia/macrophage antigens in the ischemic area. At later times, a centripetal migration of astrocytes toward the lesion was observed, promoting the formation of an astrocytic scar. These results show that [18F]DPA-714 provides accurate quantitative information of the time course of PBR/TSPO expression in experimental stroke. (authors)

  4. Time course of motor and cognitive functions after chronic cerebral ischemia in rats.

    Science.gov (United States)

    Damodaran, Thenmoly; Hassan, Zurina; Navaratnam, Visweswaran; Muzaimi, Mustapha; Ng, Gandi; Müller, Christian P; Liao, Ping; Dringenberg, Hans C

    2014-12-15

    Cerebral ischemia is one of the leading causes of death and long-term disability in aging populations, due to the frequent occurrence of irreversible brain damage and subsequent loss of neuronal function which lead to cognitive impairment and some motor dysfunction. In the present study, the real time course of motor and cognitive functions were evaluated following the chronic cerebral ischemia induced by permanent, bilateral occlusion of the common carotid arteries (PBOCCA). Male Sprague Dawley rats (200-300g) were subjected to PBOCCA or sham-operated surgery and tested 1, 2, 3 and 4 weeks following the ischemic insult. The results showed that PBOCCA significantly reduced step-through latency in a passive avoidance task at all time points when compared to the sham-operated group. PBOCCA rats also showed significant increase in escape latencies during training in the Morris water maze, as well as a reduction of the percentage of times spend in target quadrant of the maze at all time points following the occlusion. Importantly, there were no significant changes in locomotor activity between PBOCCA and sham-operated groups. The BDNF expression in the hippocampus was 29.3±3.1% and 40.1±2.6% on day 14 and 28 post PBOCCA, respectively compared to sham-operated group. Present data suggest that the PBOCCA procedure effectively induces behavioral, cognitive symptoms associated with cerebral ischemia and, consequently, provides a valuable model to study ischemia and related neurodegenerative disorder such as Alzheimer's disease and vascular dementia. PMID:25239606

  5. Enhancement of an outwardly rectifying chloride channel in hippocampal pyramidal neurons after cerebral ischemia.

    Science.gov (United States)

    Li, Jianguo; Chang, Quanzhong; Li, Xiaoming; Li, Xiawen; Qiao, Jiantian; Gao, Tianming

    2016-08-01

    Cerebral ischemia induces delayed, selective neuronal death in the CA1 region of the hippocampus. The underlying molecular mechanisms remain unclear, but it is known that apoptosis is involved in this process. Chloride efflux has been implicated in the progression of apoptosis in various cell types. Using both the inside-out and whole-cell configurations of the patch-clamp technique, the present study characterized an outwardly rectifying chloride channel (ORCC) in acutely dissociated pyramid neurons in the hippocampus of adult rats. The channel had a nonlinear current-voltage relationship with a conductance of 42.26±1.2pS in the positive voltage range and 18.23±0.96pS in the negative voltage range, indicating an outward rectification pattern. The channel is Cl(-) selective, and the open probability is voltage-dependent. It can be blocked by the classical Cl(-) channel blockers DIDS, SITS, NPPB and glibenclamide. We examined the different changes in ORCC activity in CA1 and CA3 pyramidal neurons at 6, 24 and 48h after transient forebrain ischemia. In the vulnerable CA1 neurons, ORCC activity was persistently enhanced after ischemic insult, whereas in the invulnerable CA3 neurons, no significant changes occurred. Further analysis of channel kinetics suggested that multiple openings are a major contributor to the increase in channel activity after ischemia. Pharmacological blockade of the ORCC partly attenuated cell death in the hippocampal neurons. We propose that the enhanced activity of ORCC might contribute to selective neuronal damage in the CA1 region after cerebral ischemia, and that ORCC may be a therapeutic target against ischemia-induced cell death. PMID:27181516

  6. Regulatory mechanism of endothelin receptor B in the cerebral arteries after focal cerebral ischemia

    DEFF Research Database (Denmark)

    Grell, Anne-Sofie; Thigarajah, Rushani; Edvinsson, Lars;

    2014-01-01

    BACKGROUND AND PURPOSE: Increased expression of endothelin receptor type B (ETBR), a vasoactive receptor, has recently been implied in the reduced cerebral blood flow and exacerbated neuronal damage after ischemia-reperfusion (I/R). The study explores the regulatory mechanisms of ETBR to identify...... drug targets to restore normal cerebral artery contractile function as part of successful neuroprotective therapy. METHODS: We have employed in vitro methods on human and rat cerebral arteries to study the regulatory mechanisms and the efficacy of target selective inhibitor, Mithramycin A (MitA), to...... arteries. RESULTS: Increased expression of specificity protein (Sp1) was observed in human and rat cerebral arteries after organ culture, strongly correlating with the ETBR upregulation. Similar observations were made in MCAO rats. Treatment with MitA, a Sp1 specific inhibitor, significantly downregulated...

  7. Diagnosis of hemodynamic compromise in patients with chronic cerebral ischemia

    International Nuclear Information System (INIS)

    Tests using 133Xe inhalation method and single photon emission computed tomography (SPECT) with acetazolamide (Diamox) were performed in 23 patients with chronic cerebral ischemia, before and after extracranial-intracranial bypass surgery or carotid-endarterectomy. All patients complained of TIA, RIND, or minor completed stroke. Cerebral angiography demonstrated severe stenosis or occlusion in the ipsilateral internal carotid artery or middle cerebral artery. Cerebral blood flow (CBF) was measured with 133Xe SPECT, and was measured 15 minutes after intravenous administration of 10-12 mg/kg Diamox, which is known as a cerebral vasodilatory agent (Diamox test). Our results revealed that all patients could be divided into four types according to their resting rCBF and Diamox reactivity. The patients who had normal resting rCBF and normal Diamox reactivity (type 1) were considered to have well-developed collateral circulation and normal cerebral perfusion pressure (CPP) in spite of severe occlusive lesions in the carotid system. Moderate vasodilation due to reduced CPP was considered to occur in patients who had normal resting rCBF and decreased Diamox reactivity (type 2). The resting rCBF remained unchanged, but Diamox reactivity improved to normal after surgery in the patients of type 2, which indicated the improvement of CPP and the resolution of the autoregulatory vasodilation. Maximum vasodilation or dysautoregulation was considered to occur due to the inadequate collateral flow and the severely reduced CPP in patients whose findings revealed decrease in the resting rCBF and impaired Diamox reactivity (type 3). Remarkable improvement was seen in both resting rCBF and Diamox reactivity after surgery in the patients of type 3. In the patients who had decreased resting rCBF and normal Diamox reactivity (type 4), the decreased resting rCBF was considered to result from the reduction in metabolic demand because of irreversible ischemic neuronal damage. (J.P.N.)

  8. The TRIF-dependent signaling pathway is not required for acute cerebral ischemia/reperfusion injury in mice

    International Nuclear Information System (INIS)

    TIR domain-containing adaptor protein (TRIF) is an adaptor protein in Toll-like receptor (TLR) signaling pathways. Activation of TRIF leads to the activation of interferon regulatory factor 3 (IRF3) and nuclear factor kappa B (NF-κB). While studies have shown that TLRs are implicated in cerebral ischemia/reperfusion (I/R) injury and in neuroprotection against ischemia afforded by preconditioning, little is known about TRIF's role in the pathological process following cerebral I/R. The present study investigated the role that TRIF may play in acute cerebral I/R injury. In a mouse model of cerebral I/R induced by transient middle cerebral artery occlusion, we examined the activation of NF-κB and IRF3 signaling in ischemic cerebral tissue using ELISA and Western blots. Neurological function and cerebral infarct size were also evaluated 24 h after cerebral I/R. NF-κB activity and phosphorylation of the inhibitor of kappa B (IκBα) increased in ischemic brains, but IRF3, inhibitor of κB kinase complex-ε (IKKε), and TANK-binding kinase1 (TBK1) were not activated after cerebral I/R in wild-type (WT) mice. Interestingly, TRIF deficit did not inhibit NF-κB activity or p-IκBα induced by cerebral I/R. Moreover, although cerebral I/R induced neurological and functional impairments and brain infarction in WT mice, the deficits were not improved and brain infarct size was not reduced in TRIF knockout mice compared to WT mice. Our results demonstrate that the TRIF-dependent signaling pathway is not required for the activation of NF-κB signaling and brain injury after acute cerebral I/R.

  9. The TRIF-dependent signaling pathway is not required for acute cerebral ischemia/reperfusion injury in mice

    Energy Technology Data Exchange (ETDEWEB)

    Hua, Fang, E-mail: fhua2@emory.edu [Department of Emergency Medicine, Brain Research Laboratory, Emory University School of Medicine, 1365B Clifton Road, Suite 5100, Atlanta, GA 30322 (United States); Wang, Jun; Sayeed, Iqbal; Ishrat, Tauheed; Atif, Fahim; Stein, Donald G. [Department of Emergency Medicine, Brain Research Laboratory, Emory University School of Medicine, 1365B Clifton Road, Suite 5100, Atlanta, GA 30322 (United States)

    2009-12-18

    TIR domain-containing adaptor protein (TRIF) is an adaptor protein in Toll-like receptor (TLR) signaling pathways. Activation of TRIF leads to the activation of interferon regulatory factor 3 (IRF3) and nuclear factor kappa B (NF-{kappa}B). While studies have shown that TLRs are implicated in cerebral ischemia/reperfusion (I/R) injury and in neuroprotection against ischemia afforded by preconditioning, little is known about TRIF's role in the pathological process following cerebral I/R. The present study investigated the role that TRIF may play in acute cerebral I/R injury. In a mouse model of cerebral I/R induced by transient middle cerebral artery occlusion, we examined the activation of NF-{kappa}B and IRF3 signaling in ischemic cerebral tissue using ELISA and Western blots. Neurological function and cerebral infarct size were also evaluated 24 h after cerebral I/R. NF-{kappa}B activity and phosphorylation of the inhibitor of kappa B (I{kappa}B{alpha}) increased in ischemic brains, but IRF3, inhibitor of {kappa}B kinase complex-{epsilon} (IKK{epsilon}), and TANK-binding kinase1 (TBK1) were not activated after cerebral I/R in wild-type (WT) mice. Interestingly, TRIF deficit did not inhibit NF-{kappa}B activity or p-I{kappa}B{alpha} induced by cerebral I/R. Moreover, although cerebral I/R induced neurological and functional impairments and brain infarction in WT mice, the deficits were not improved and brain infarct size was not reduced in TRIF knockout mice compared to WT mice. Our results demonstrate that the TRIF-dependent signaling pathway is not required for the activation of NF-{kappa}B signaling and brain injury after acute cerebral I/R.

  10. Houshiheisan compound prescription protects neurovascular units after cerebral ischemia.

    Science.gov (United States)

    Wang, Haizheng; Wang, Lei; Zhang, Nan; Zhang, Qi; Zhao, Hui; Zhang, Qiuxia

    2014-04-01

    Houshiheisan is composed of wind-dispelling (chrysanthemun flower, divaricate saposhnikovia root, Manchurian wild ginger, cassia twig, Szechwan lovage rhizome, and platycodon root) and deficiency-nourishing (ginseng, Chinese angelica, large-head atractylodes rhizome, Indian bread, and zingiber) drugs. In this study, we assumed these drugs have protective effects against cerebral ischemia, on neurovascular units. Houshiheisan was intragastrically administered in a rat model of focal cerebral ischemia. Hematoxylin-eosin staining, transmission electron microscopy, immunofluorescence staining, and western blot assays showed that Houshiheisan reduced pathological injury to the ischemic penumbra, protected neurovascular units, visibly up-regulated neuronal nuclear antigen expression, and down-regulated amyloid precursor protein and amyloid-β 42 expression. Wind-dispelling and deficiency-nourishing drugs maintained NeuN expression to varying degrees, but did not affect amyloid precursor protein or amyloid-β 42 expression in the ischemic penumbra. Our results suggest that the compound prescription Houshiheisan effectively suppresses abnormal amyloid precursor protein accumulation, reduces amyloid substance deposition, maintains stabilization of the internal environment of neurovascular units, and minimizes injury to neurovascular units in the ischemic penumbra. PMID:25206882

  11. Reparative neurogenesis after cerebral ischemia: Clinical application prospects

    Science.gov (United States)

    Khodanovich, M. Yu.

    2015-11-01

    At the present time two main approaches are in the focus of neurobiological studies of brain recovery after a stroke. One of them is concerned with the infusion of stem cells in damaged brain. The second approach is directed at the stimulation of endogenous reparative processes, in particular, adult neurogenesis. This review considers alterations of adult neurogenesis caused by cerebral ischemia and possible pathways of its regulation. Multiple studies on animal models have shown that adult neurogenesis is mostly increased by cerebral ischemia. In spite of increasing proliferation and moving neural progenitors to infarct zone, most newborn neurons die before reaching maturity. Besides, an increase of neurogenesis in pathological conditions is mainly due to recruitment of new stem cells, but not due to an additional precursor-cells division that results in an overall decline of the regeneration capacity. Thus, the endogenous reparative mechanisms are not sufficient, and the search for new targets to promote proliferation, survival, and maturation of new neurons after a stroke is needed. Neurotransmitter systems and anti-inflammatory drugs are considered as potential regulators of post-ischemic neurogenesis growth factors.

  12. Reparative neurogenesis after cerebral ischemia: Clinical application prospects

    Energy Technology Data Exchange (ETDEWEB)

    Khodanovich, M. Yu., E-mail: khodanovich@mail.tsu.ru [Tomsk State University, Research Institute of Biology and Biophysics, Laboratory of Neurobiology (Russian Federation)

    2015-11-17

    At the present time two main approaches are in the focus of neurobiological studies of brain recovery after a stroke. One of them is concerned with the infusion of stem cells in damaged brain. The second approach is directed at the stimulation of endogenous reparative processes, in particular, adult neurogenesis. This review considers alterations of adult neurogenesis caused by cerebral ischemia and possible pathways of its regulation. Multiple studies on animal models have shown that adult neurogenesis is mostly increased by cerebral ischemia. In spite of increasing proliferation and moving neural progenitors to infarct zone, most newborn neurons die before reaching maturity. Besides, an increase of neurogenesis in pathological conditions is mainly due to recruitment of new stem cells, but not due to an additional precursor-cells division that results in an overall decline of the regeneration capacity. Thus, the endogenous reparative mechanisms are not sufficient, and the search for new targets to promote proliferation, survival, and maturation of new neurons after a stroke is needed. Neurotransmitter systems and anti-inflammatory drugs are considered as potential regulators of post-ischemic neurogenesis growth factors.

  13. Blood biomarkers in the early stage of cerebral ischemia.

    Science.gov (United States)

    Maestrini, I; Ducroquet, A; Moulin, S; Leys, D; Cordonnier, C; Bordet, R

    2016-03-01

    In ischemic stroke patients, blood-based biomarkers may be applied for the diagnosis of ischemic origin and subtype, prediction of outcomes and targeted treatment in selected patients. Knowledge of the pathophysiology of cerebral ischemia has led to the evaluation of proteins, neurotransmitters, nucleic acids and lipids as potential biomarkers. The present report focuses on the role of blood-based biomarkers in the early stage of ischemic stroke-within 72h of its onset-as gleaned from studies published in English in such patients. Despite growing interest in their potential role in clinical practice, the application of biomarkers for the management of cerebral ischemia is not currently recommended by guidelines. However, there are some promising clinical biomarkers, as well as the N-methyl-d-aspartate (NMDA) peptide and NMDA-receptor (R) autoantibodies that appear to identify the ischemic nature of stroke, and the glial fibrillary acidic protein (GFAP) that might be able to discriminate between acute ischemic and hemorrhagic strokes. Moreover, genomics and proteomics allow the characterization of differences in gene expression, and protein and metabolite production, in ischemic stroke patients compared with controls and, thus, may help to identify novel markers with sufficient sensitivity and specificity. Additional studies to validate promising biomarkers and to identify novel biomarkers are needed. PMID:26988891

  14. Reparative neurogenesis after cerebral ischemia: Clinical application prospects

    International Nuclear Information System (INIS)

    At the present time two main approaches are in the focus of neurobiological studies of brain recovery after a stroke. One of them is concerned with the infusion of stem cells in damaged brain. The second approach is directed at the stimulation of endogenous reparative processes, in particular, adult neurogenesis. This review considers alterations of adult neurogenesis caused by cerebral ischemia and possible pathways of its regulation. Multiple studies on animal models have shown that adult neurogenesis is mostly increased by cerebral ischemia. In spite of increasing proliferation and moving neural progenitors to infarct zone, most newborn neurons die before reaching maturity. Besides, an increase of neurogenesis in pathological conditions is mainly due to recruitment of new stem cells, but not due to an additional precursor-cells division that results in an overall decline of the regeneration capacity. Thus, the endogenous reparative mechanisms are not sufficient, and the search for new targets to promote proliferation, survival, and maturation of new neurons after a stroke is needed. Neurotransmitter systems and anti-inflammatory drugs are considered as potential regulators of post-ischemic neurogenesis growth factors

  15. Neuroprotective Activity of Lavender Oil on Transient Focal Cerebral Ischemia in Mice

    Directory of Open Access Journals (Sweden)

    Qiusheng Zheng

    2012-08-01

    Full Text Available The air-dried aerial parts of Lavandula angustifolia Mill, a traditional Uygur herbal drug, is used as resuscitation-inducing therapy to treat neurodisfunctions, such as stroke. This study was designed to assess the neuroprotective effects of lavender oil against ischemia/reperfusion (IR injury in mice. Focal cerebral ischemia was induced by the intraluminal occlusion method with a nylon string. The neurodysfuntion was evaluated by neurological deficit and the infarct area was showed by 2,3,5-triphenyltetrazolium chloride (TTC staining. The histopathological changes were observed by hematoxylin and eosin staining. The levels of mitochondria-generated reactive oxygen species (ROS, malondialdehyde (MDA and carbonyl, the ratio of reduced glutathione (GSH/glutathione disulfide (GSSG, the activities of superoxide dismutase (SOD, catalase (CAT and glutathion peroxidase (GSH-Px in brain tissue were measured to estimate the oxidative stress state. Neurological deficit, infarct size, histopathology changes and oxidative stress markers were evaluated after 22 h of reperfusion. In comparison with the model group, treatment with lavender oil significantly decreased neurological deficit scores, infarct size, the levels of MDA, carbonyl and ROS, and attenuated neuronal damage, upregulated SOD, CAT, GSH-Px activities and GSH/GSSG ratio. These results suggested that the neuroprotective effects of lavender oil against cerebral ischemia/reperfusion injury may be attributed to its antioxidant effects.

  16. Ultrastructural and Temporal Changes of the Microvascular Basement Membrane and Astrocyte Interface Following Focal Cerebral Ischemia

    OpenAIRE

    Kwon, Il; Kim, Eun Hee; del Zoppo, Gregory J.; Heo, Ji Hoe

    2009-01-01

    Microvascular integrity is lost during cerebral ischemia. Detachment of the microvascular basement membrane (BM) from the astrocyte, as well as degradation of the BM, is responsible for the loss of microvascular integrity. However, their ultrastructural and temporal changes during cerebral ischemia are not well known. Male Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAO) for 1, 4, 8, 12, 16, 20, and 48 hr. By using transmission electron microscopy, the p...

  17. Gene expression profiling in the human middle cerebral artery after cerebral ischemia.

    Science.gov (United States)

    Vikman, P; Edvinsson, L

    2006-12-01

    We have investigated the gene expression in human middle cerebral artery (MCA) after ischemia. Ischemic stroke affects the perfusion in the affected area and experimental cerebral ischemia results in upregulation of vasopressor receptors in the MCA leading to the ischemic area. We obtained human MCA samples distributing to the ischemic area, 7-10 days post-stroke. The gene expression was examined with real-time polymerase chain reaction (PCR) and microarray, proteins were studied with immunohistochemistry. We investigated genes previously shown to be upregulated in animal models of cerebral ischemia (e.g. ET(A), ET(B), AT1, AT2, and 5-HT(2A/1B/1D)). Their mRNA expression was increased compared with controls, consistent with findings in experimental stroke. Immunohistochemistry showed upregulation of the receptors localized on the smooth muscle cells. The gene expression was profiled with microarray and seven genes chosen for further investigation with real-time PCR; ELK3, LY64, Metallothionin IG, POU3F4, Actin alpha2, RhoA and smoothelin. Six of these were regulated the same way when confirming array expression with real-time PCR. Gene expression studies in the human MCA leading to the ischemic region is similar to that seen after MCA occlusion in rats. We found new genes that support the dynamic changes that occur in the MCA distributing to the ischemic region. PMID:17116215

  18. Serine racemase expression in mouse cerebral cortex after permanent focal cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Li-zhen WANG; Xing-zu ZHU

    2004-01-01

    AIM: To study the alterations of the expressions of serine racemase in C57BL/6 mouse brain after permanent focal cerebral ischemia. METHODS: The mRNA level and the protein level of serine racemase were assayed by semiquantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blot, respectively. The amount of D-serine and L-serine were measured by HPLC. RESULTS: High levels of serine racemase were constitutively expressed in the normal cortex of mouse. At early stage after middle cerebral artery occlusion (MCAO), no significant change in expression of serine racemase was observed in temporoparietal cortex in ipsilateral hemisphere. However,delayed transient decreases of serine racemase in both mRNA and protein levels were detected from d 6 to d 10 after ischemia. Correspondingly, D-serine concentration also declined in the ipsilateral cortex during this period when compared with the D-serine level in the contralateral cortex. CONCLUSION:Delayed decreases in serine racemase expression and D-serine level occurred in the temporoparietal cortex at the late stage after focal cerebral ischemia.

  19. Validation of enhanced and dynamic computed tomography for cerebral ischemia

    International Nuclear Information System (INIS)

    This paper shows the usefulness of enhanced and dynamic CT for ischemic stroke patients. Sixteen patients with disturbance of consciousness or neurological sign who did not have low-density area on plain CT were selected for this study. We performed enhanced CT sequentially. Enhanced CT image, time-density curve and functional image were compared with final infarcted area and occlusion level of cerebral artery. Three patients whose enhanced CT images showed obvious laterality had occlusion of internal carotid (IC) or horizontal portion of middle cerebral artery (M1). Four of five patients whose functional image and time density curve revealed abnormal region had ischemia because of more peripheral vessel occlusion or IC stenosis. Others with no abnormality on all images had lacunar infarction or did not have infarction finally. Occlusion of cerebral artery proximal portion could be diagnosed only with enhanced CT images. If selected slice was fit to the lesion, more distant level of ischemic area could be determined 100% by time-density curve and functional image. This examination takes only about ten minutes without transferring the patient. Enhanced CT and dynamic scan is useful tool to determine the diagnosis and management for ischemic stroke patients. (author)

  20. CDK5 knockdown prevents hippocampal degeneration and cognitive dysfunction produced by cerebral ischemia.

    Science.gov (United States)

    Gutiérrez-Vargas, Johana A; Múnera, Alejandro; Cardona-Gómez, Gloria P

    2015-12-01

    Acute ischemic stroke is a cerebrovascular accident and it is the most common cause of physical disabilities around the globe. Patients may present with repeated ictuses, experiencing mental consequences, such as depression and cognitive disorders. Cyclin-dependent kinase 5 (CDK5) is a kinase that is involved in neurotransmission and plasticity, but its dysregulation contributes to cognitive disorders and dementia. Gene therapy targeting CDK5 was administered to the right hippocampus of ischemic rats during transient cerebral middle artery occlusion. Physiologic parameters (blood pressure, pH, pO2, and pCO2) were measured. The CDK5 downregulation resulted in neurologic and motor improvement during the first week after ischemia. Cyclin-dependent kinase 5 RNA interference (RNAi) prevented dysfunctions in learning, memory, and reversal learning at 1 month after ischemia. These observations were supported by the prevention of neuronal loss, the reduction of microtubule-associated protein 2 (MAP2) immunoreactivity, and a decrease in astroglial and microglia hyperreactivities and tauopathy. Additionally, CDK5 silencing led to an increase in the expression of brain-derived neurotrophic factor (BDNF), its Tropomyosin Receptor kinase B (TRKB) receptor, and activation of cyclic AMP response element-binding protein (CREB) and extracellular signal-regulated kinase (ERK), which are important targets in neuronal plasticity. Together, our findings suggest that gene therapy based on CDK5 silencing prevents cerebral ischemia-induced neurodegeneration and motor and cognitive deficits. PMID:26104286

  1. Evaluation of Aged Garlic Extract Neuroprotective Effect in a Focal Model of Cerebral Ischemia

    Science.gov (United States)

    Aguilera, Penélope; Maldonado, Perla D.; Ortiz-Plata, Alma; Barrera, Diana; Chánez-Cárdenas, María Elena

    2008-02-01

    The oxidant species generated in cerebral ischemia have been implicated as important mediators of neuronal injury through damage to lipids, DNA, and proteins. Since ischemia as well as reperfusion insults generate oxidative stress, the administration of antioxidants may limit oxidative damage and ameliorate disease progression. The present work shows the transitory neuroprotective effect of the aged garlic extract (AGE) administration (a proposed antioxidant compound) in a middle cerebral artery occlusion (MCAO) model in rats and established its therapeutic window. To determine the optimal time of administration, animal received AGE (1.2 mL/kg) intraperitoneally 30 min before onset of reperfusion (-0.5 R), at the beginning of reperfusion (0R), or 1 h after onset of reperfusion (1R). Additional doses were administrated after 1, 2, or 3 h after onset of reperfusion. To establish the therapeutic window of AGE, the infarct area was determined for each treatment after different times of reperfusion. Results show that the administration of AGE at the onset of reperfusion reduced the infarct area by 70% (evaluated after 2 h reperfusion). The therapeutic window of AGE was determined. Repeated doses did not extend the temporal window of protection. A significant reduction in the nitrotyrosine level was observed in the brain tissue subjected to MCAO after AGE treatment at the onset of reperfusion. Data in the present work show that AGE exerts a transitory neuroprotective effect in response to ischemia/reperfusion-induced neuronal injury.

  2. Delayed Cerebral Ischemia following to Repair of Penetrating Trauma to External Carotid artery Introduction

    Directory of Open Access Journals (Sweden)

    M. Eskandarlou

    2016-01-01

    Full Text Available Introduction: Penetrating trauma to anterior neck can induce cerebral ischemia due to carotid artery injury. Brain ischemia also can present after surgical carotid repairs. Early diagnosis and suitable treatment modality prevent from permanent neurologic deficit post operatively. Case Report: A 30 years old man with stab wound to zone two left side of neck underwent exploration and penrose insertion. Due to excessive bleeding through drain tube, patient was transferred to Besat Hospital of Hamadan. Surgical repair of external carotid artery successfully was done. Four days later patient developed right hemiparesis suddenly. According to MRI and color Doppler sonography finding of thrombosis of left common and internal carotid artery, reoperation was done. After thrombectomy cerebral ischemia and hemi-paralysis improved. Conclusions: Surgical approach to symptomatic penetrating neck trauma is oblique cervical incision, control of bleeding, repair of internal carotid, repair or ligature of external carotid artery base on some factors and preferential repair of internal jugular vein. Meticulous and fine surgical technique for both vascular repair and protection of adjacent normal vessels for avoiding to blunt trauma or compression with retractors is noticeable. Exact postoperative care as repeated clinical examination with goal of early diagnosis of internal carotid artery thrombosis and rapid diagnostic and treatment planning of this complication are important factors for taking of good result in treatment of penetrating trauma to carotid. Sci J Hamadan Univ Med Sci . 2016; 22 (4 :353-357

  3. Effects of the mitochondrial calcium uniporter on cerebral edema in a rat model of cerebral ischemia reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Linlin Li; Shilei Wang; Haihong Luan

    2011-01-01

    The present study investigated the effects of the mitochondrial calcium uniporter inhibitor ruthenium red and the agonist spermine on cerebral edema in rats with cerebral ischemia reperfusion injury.Left middle cerebral artery occlusion (MCAO) was induced in rats using the suture method.Following 24 hours of ischemic reperfusion, neurological function scores of rats with MCAO, and rats pretreated with ruthenium red and spermine were significantly lower, however, water content of brain tissue, aquaporin 4 expression and immunoglobulin G (IgG) exudation were significantly higher than those of sham-operated rats.Compared with MCAO rats and spermine-treated rats, neurological function scores were considerably higher, and brain tissue water content, aquaporin 4 expression and IgG exudation decreased in ruthenium red-treated rats.These findings suggest that preventive application of the mitochondrial calcium uniporter inhibitor ruthenium red can significantly decrease aquaporin 4 and IgG expression, influence the permeability of the blood brain barrier, and thereby decrease the extent of cerebral edema.

  4. Effect of glutamate on inflammatory responses of intestine and brain after focal cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Lei Xu; Jie Sun; Ran Lu; Qing Ji; Jian-Guo Xu

    2005-01-01

    AIM: To study the modulation of glutamate on post-ischemic intestinal and cerebral inflammatory responses in a ischemic and excitotoxic rat model.METHODS: Adult male rats were subjected to bilateral carotid artery occlusion for 15 min and injection of monosodium glutamate intraperitoneally, to decapitate them at selected time points. Tumor necrosis factor alpha (TNF-α) level and nuclear factor kappa B (NF-κB) activity were determined by enzyme-linked immunosorbant assay (ELISA) and electrophoretic mobility shift assay (EMSA), respectively.Hemodynamic parameters were monitored continuously during the whole process of cerebral ischemia and reperfusion.RESULTS: Monosodium glutamate (MSG) treated rats displayed statistically significant high levels of TNF-α in cerebral and intestinal tissuess within the first 6 h of ischemia. The rats with cerebral ischemia showed a minor decrease of TNF-α production in cerebral and intestinal tissuess. The rats with cerebral ischemia and treated with MSG displayed statistically significant low levels of TNF-α in cerebral and intestinal tissues. These results correlated significantly with NF-κB production calculated at the same intervals. During experiment, the mean blood pressure and heart rates in all groups were stable.CONCLUSION: Glutamate is involved in the mechanism of intestinal and cerebral inflammation responses. The effects of glutamate on cerebral and intestinal inflammatory responses after ischemia are up-regulated at the transcriptional level,through the NF-κB signal transduction pathway.

  5. Short-term fasting induced tolerance against focal cerebral ischemia by autophagy activation in rats%短期禁食诱导自噬对大鼠脑缺血损伤的保护作用

    Institute of Scientific and Technical Information of China (English)

    丁培炎; 王冬; 赫曼; 阎文军

    2013-01-01

    evaluate cerebral ischemic injury.Activation of autophagy was assessed by the level of microtubule-associated protein 1 light chain 3-Ⅱ (LC3-Ⅱ) protein with immunoblotting.Results Short-term fasting markedly imrproved the neurobehavioral score and reduced the infarct volume compared with that of I/R group.The expression of LC3-II protein was significantly increased 72 h after reperfusion in fasting group compared with the sham and I/R groups.The pretreatment with 3-MA attenuated the neuroprotective effect of short-term fasting against cerebral ischemia-reperfusion,and the neurobehavioral score and infarct volume of 3-MA group were not significantly different from that of I/R group,suggesting that inhibition of autophagy which induced by short-term fasting can reserve neuroprotection of short-term fasting.Conclusion Short-term fasting elicits the neuroprotective effect against transient focal cerebral ischemia through up-regulation of autophngy.

  6. Microparticles generated during chronic cerebral ischemia deliver proapoptotic signals to cultured endothelial cells

    International Nuclear Information System (INIS)

    Highlights: • Microparticles are elevated in the plasma in a rodent model of chronic cerebral ischemia. • These microparticles initiate apoptosis in cultured cells. • Microparticles contain caspase 3 and they activate receptors for TNF-α and TRAIL. - Abstract: Circulating microparticles (MPs) are involved in many physiological processes and numbers are increased in a variety of cardiovascular disorders. The present aims were to characterize levels of MPs in a rodent model of chronic cerebral hypoperfusion (CCH) and to determine their signaling properties. MPs were isolated from the plasma of rats exposed to CCH and quantified by flow cytometry. When MPs were added to cultured endothelial cells or normal rat kidney cells they induced cell death in a time and dose dependent manner. Analysis of pellets by electron microscopy indicates that cell death signals are carried by particles in the range of 400 nm in diameter or less. Cell death involved the activation of caspase 3 and was not a consequence of oxidative stress. Inhibition of the Fas/FasL signaling pathway also did not improve cell survival. MPs were found to contain caspase 3 and treating the MPs with a caspase 3 inhibitor significantly reduced cell death. A TNF-α receptor blocker and a TRAIL neutralizing antibody also significantly reduced cell death. Levels of circulating MPs are elevated in a rodent model of chronic cerebral ischemia. MPs with a diameter of 400 nm or less activate the TNF-α and TRAIL signaling pathways and may deliver caspase 3 to cultured cells

  7. Microparticles generated during chronic cerebral ischemia deliver proapoptotic signals to cultured endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Schock, Sarah C. [Ottawa Hospital Research Institute, Neuroscience, 451 Smyth Road, Ottawa, ON K1H 8M5 (Canada); Edrissi, Hamidreza [University of Ottawa, Neuroscience Graduate Program, 451 Smyth Road, Ottawa, ON K1H 8M5 (Canada); Burger, Dylan [Ottawa Hospital Research Institute, Kidney Centre, 451 Smyth Road, Ottawa, ON K1H 8M5 (Canada); Cadonic, Robert; Hakim, Antoine [Ottawa Hospital Research Institute, Neuroscience, 451 Smyth Road, Ottawa, ON K1H 8M5 (Canada); Thompson, Charlie, E-mail: charliet@uottawa.ca [Ottawa Hospital Research Institute, Neuroscience, 451 Smyth Road, Ottawa, ON K1H 8M5 (Canada)

    2014-07-18

    Highlights: • Microparticles are elevated in the plasma in a rodent model of chronic cerebral ischemia. • These microparticles initiate apoptosis in cultured cells. • Microparticles contain caspase 3 and they activate receptors for TNF-α and TRAIL. - Abstract: Circulating microparticles (MPs) are involved in many physiological processes and numbers are increased in a variety of cardiovascular disorders. The present aims were to characterize levels of MPs in a rodent model of chronic cerebral hypoperfusion (CCH) and to determine their signaling properties. MPs were isolated from the plasma of rats exposed to CCH and quantified by flow cytometry. When MPs were added to cultured endothelial cells or normal rat kidney cells they induced cell death in a time and dose dependent manner. Analysis of pellets by electron microscopy indicates that cell death signals are carried by particles in the range of 400 nm in diameter or less. Cell death involved the activation of caspase 3 and was not a consequence of oxidative stress. Inhibition of the Fas/FasL signaling pathway also did not improve cell survival. MPs were found to contain caspase 3 and treating the MPs with a caspase 3 inhibitor significantly reduced cell death. A TNF-α receptor blocker and a TRAIL neutralizing antibody also significantly reduced cell death. Levels of circulating MPs are elevated in a rodent model of chronic cerebral ischemia. MPs with a diameter of 400 nm or less activate the TNF-α and TRAIL signaling pathways and may deliver caspase 3 to cultured cells.

  8. Hydrogen sulfide intervention in focal cerebral ischemia/reperfusion injury in rats

    Directory of Open Access Journals (Sweden)

    Xin-juan Li

    2015-01-01

    Full Text Available The present study aimed to explore the mechanism underlying the protective effects of hydrogen sulfide against neuronal damage caused by cerebral ischemia/reperfusion. We established the middle cerebral artery occlusion model in rats via the suture method. Ten minutes after middle cerebral artery occlusion, the animals were intraperitoneally injected with hydrogen sulfide donor compound sodium hydrosulfide. Immunofluorescence revealed that the immunoreactivity of P2X 7 in the cerebral cortex and hippocampal CA1 region in rats with cerebral ischemia/reperfusion injury decreased with hydrogen sulfide treatment. Furthermore, treatment of these rats with hydrogen sulfide significantly lowered mortality, the Longa neurological deficit scores, and infarct volume. These results indicate that hydrogen sulfide may be protective in rats with local cerebral ischemia/reperfusion injury by down-regulating the expression of P2X 7 receptors.

  9. Transesophageal echocardiography in patients with cryptogenic cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Dreger Henryk

    2009-03-01

    Full Text Available Abstract Background In about one third of all patients with cerebral ischemia, no definite cause can be identified (cryptogenic stroke. In many patients with initially suspected cryptogenic stroke, however, a cardiogenic etiology can eventually be determined. Hence, the aim of this study was to describe the prevalence of abnormal echocardiographic findings in a large number of these patients. Method Patients with cryptogenic cerebral ischemia (ischemic stroke, IS, and transient ischemic attack, TIA were included. The initial work-up included a neurological examination, EEG, cCT, cMRT, 12-lead ECG, Holter-ECG, Doppler ultrasound of the extracranial arteries, and transthoracic echocardiography. A multiplane transeophageal echocardiography (TEE, including i.v. contrast medium application [Echovist], Valsalva maneuver was performed in all patients Results 702 consecutive patients (380 male, 383 IS, 319 TIA, age 18–90 years were included. In 52.6% of all patients, TEE examination revealed relevant findings. Overall, the most common findings in all patients were: patent foramen ovale (21.7%, previously undiagnosed valvular disease (15.8%, aortic plaques, aortic valve sclerosis, atrial septal aneurysms, regional myocardial dyskinesia, dilated left atrium and atrial septal defects. Older patients (> 55 years, n = 291 and patients with IS had more relevant echocardiographic findings than younger patients or patients with TIA, respectively (p = 0.002, p = 0.003. The prevalence rates of PFO or ASD were higher in younger patients (PFO: 26.8% vs. 18.0%, p = 0.005, ASD: 9.6% vs. 4.9%, p = 0.014. Conclusion A TEE examination in cryptogenic stroke reveals contributing cardiogenic factors in about half of all patients. Younger patients had a higher prevalence of PFO, whereas older patients had more frequently atherosclerotic findings. Therefore, TEE examinations seem indicated in all patients with cryptogenic stroke – irrespective of age – because of

  10. Effect of Panax notoginseng saponins on the content of IL-8 in serum after cerebral ischemia-reperfusion in rat

    International Nuclear Information System (INIS)

    Objective: To investigate the effect of Panax notoginseng saponins (Pns) against cerebral ischemia-reperfusion injury. Methods: Focal cerebral ischemia-reperal ischemia-reperfusion model in rat was established by occlusion the middle cerebral artery for 2 h, after 3 h reperfusion. The serum concentration of IL-8 was detected with radioimmunoassay (RIA). Results: Png 50 mg·kg-1 ip, qd x 7d before MCAO decreased the serum content of IL-8 after ischemia-reperfusion. Conclusion: Pns has protective effect against cerebral ischemia-reperfusion injury by decreased the serum content of IL-8

  11. Categorical course in neuroradiology cerebral ischemia, hemorrhage, and vascular lesions

    International Nuclear Information System (INIS)

    The diagnostic imaging of acute stroke is primarily directed toward identifying the lesion, characterizing it as either intracranial hemorrhage or ischemia, and assessing the anatomic extent of the lesion. The acute medical or surgical management decisions are best aided by a combination of CT and cerebral angiography, the latter used acutely mostly for intracranial hemorrhage, especially subarachnoid hemorrhage. More complex presentations benefit from MR imaging evaluation as well. After the acute phase, the main goal of treatment, especially for patients who have had reasonable recovery from the acute stroke, is the prevention of recurrent, and perhaps more severe, stroke. Treatments such as aneurysm clipping or arteriovenous malformation removal for hemorrhagic lesions, or anticoagulation or carotid endarterectomy for ischemic lesions, require brain and vascular imaging studies for appropriate treatment planning. Angiography to show the anatomic vascular cause for the bleed or ischemia is therefore usually a requirement. The enlarging experience with MR imaging has contributed greatly to the identification of occult vascular lesions of the brain that may be prone to bleeding and to recognizing blood in the brain accurately. For this purpose MR imaging is sometimes more specific than CT

  12. Neurochemical Mechanism of Electroacupuncture: Anti-injury Effect on Cerebral Function after Focal Cerebral Ischemia in Rats †

    OpenAIRE

    Bo-Ying Chen; Lianjin Huan; Shubo Zhong; Zhongren Li

    2007-01-01

    We explored the neurochemical mechanism of electroacupuncture's (EA) protective effect on brain function in focal cerebral ischemia rats, using cerebral ischemia/reperfusion rats established by the middle cerebral artery occlusion (MCAO) method. Adult male Sprague–Dawley rats were randomly divided into four groups: Sham, Sham+EA, MCAO and MCAO+EA. The rats in Sham+EA and MCAO+EA were accepted EA treatment at ‘GV26’ and ‘GV20’ acupoints for 30 min. Electric stimulation was produced by a G-6805...

  13. Neuroprotective effects of salidroside on focal cerebral ischemia/reperfusion injury involves the nuclear erythroid 2-related factor 2 pathway

    Directory of Open Access Journals (Sweden)

    Jing Han

    2015-01-01

    Full Text Available Salidroside, the main active ingredient extracted from Rhodiola crenulata, has been shown to be neuroprotective in ischemic cerebral injury, but the underlying mechanism for this neuroprotection is poorly understood. In the current study, the neuroprotective effect of salidroside on cerebral ischemia-induced oxidative stress and the role of the nuclear factor erythroid 2-related factor 2 (Nrf2 pathway was investigated in a rat model of middle cerebral artery occlusion. Salidroside (30 mg/kg reduced infarct size, improved neurological function and histological changes, increased activity of superoxide dismutase and glutathione-S-transferase, and reduced malon-dialdehyde levels after cerebral ischemia and reperfusion. Furthermore, salidroside apparently increased Nrf2 and heme oxygenase-1 expression. These results suggest that salidroside exerts its neuroprotective effect against cerebral ischemia through anti-oxidant mechanisms and that activation of the Nrf2 pathway is involved. The Nrf2/antioxidant response element pathway may become a new therapeutic target for the treatment of ischemic stroke.

  14. The enzymatic histochemistry study in diaschisis area after focal cerebral ischemia

    International Nuclear Information System (INIS)

    Objective: To study the changes in activities of acetylcholine esterase (AChE), acid phosphatase (ACP) and succinic dehydrogenase (SDH) in diaschisis area after focal cerebral ischemia. Methods: The activities of AChE, ACP and SDH in diaschisis areas which were defined by cerebral blood flow autoradiography in a rat model of right middle cerebral artery occlusion (MCAO) were observed using enzymatic histochemistry. Results: With focal cerebral ischemia, there were no changes in AChE and ACP activities in the diaschisis areas, but SDH activity decreased. Conclusion: In the diaschisis areas the function of cholinergic system and lysosome was not affected, but metabolic activity of mitochondria decreased

  15. EFFECTS OF RAPAMYCIN ON CEREBRAL OXYGEN SUPPLY AND CONSUMPTION DURING REPERFUSION AFTER CEREBRAL ISCHEMIA

    Science.gov (United States)

    CHI, O. Z.; BARSOUM, S.; VEGA-COTTO, N. M.; JACINTO, E.; LIU, X.; MELLENDER, S. J.; WEISS, H. R.

    2016-01-01

    Abstract—Activation of the mammalian target of rapamycin (mTOR) leads to cell growth and survival. We tested the hypothesis that inhibition of mTOR would increase infarct size and decrease microregional O2 supply/consumption balance after cerebral ischemia–reperfusion. This was tested in isoflurane-anesthetized rats with middle cerebral artery blockade for 1 h and reperfusion for 2 h with and without rapamycin (20 mg/kg once daily for two days prior to ischemia). Regional cerebral blood flow was determined using a C14-iodoantipyrine autoradiographic technique. Regional small-vessel arterial and venous oxygen saturations were determined microspectrophotometrically. The control ischemic-reperfused cortex had a similar blood flow and O2 consumption to the contralateral cortex. However, microregional O2 supply/consumption balance was significantly reduced in the ischemic-reperfused cortex. Rapamycin significantly increased cerebral O2 consumption and further reduced O2 supply/consumption balance in the reperfused area. This was associated with an increased cortical infarct size (13.5 ± 0.8% control vs. 21.5 ± 0.9% rapamycin). We also found that ischemia–reperfusion increased AKT and S6K1 phosphorylation, while rapamycin decreased this phosphorylation in both the control and ischemic-reperfused cortex. This suggests that mTOR is important for not only cell survival, but also for the control of oxygen balance after cerebral ischemia–reperfusion. PMID:26742793

  16. Reactive changes in astrocytes, and delayed neuronal death, in the rat hippocampal CA1 region following cerebral ischemia/reperfusion

    Institute of Scientific and Technical Information of China (English)

    Guiqing Zhang; Xiang Luo; Zhiyuan Yu; Chao Ma; Shabei Xu; Wei Wang

    2009-01-01

    BACKGROUND: Blood supply to the hippocampus is not provided by the middle cerebral artery. However, previous studies have shown that delayed neuronal death in the hippocampus may occur following focal cerebral ischemia induced by middle cerebral artery occlusion. OBJECTIVE: To observe the relationship between reactive changes in hippocampal astrocytes and delayed neuronal death in the hippocampal CA1 region following middle cerebral artery occlusion. DESIGN, TIME AND SETTING: The immunohistochemical, randomized, controlled animal study was performed at the Laboratory of Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, from July to November 2007. MATERIALS: Rabbit anti-glial fibrillary acidic protein (GFAP) (Neomarkers, USA), goat anti-rabbit IgG (Sigma, USA) and ApoAlert apoptosis detection kit (Biosciences Clontech, USA) were used in this study. METHODS: A total of 42 healthy adult male Wistar rats, aged 3-5 months, were randomly divided into a sham operation group (n = 6) and a cerebral ischemia/reperfusion group (n = 36). In the cerebral ischemia/reperfusion group, cerebral ischemia/reperfusion models were created by middle cerebral artery occlusion. In the sham operation group, the thread was only inserted into the initial region of the internal carotid artery, and middle cerebral artery occlusion was not induced. Rats in the cerebral ischemia/reperfusion group were assigned to a delayed neuronal death (+) subgroup and a delayed neuronal death (-) subgroup, according to the occurrence of delayed neuronal death in the ischemic side of the hippocampal CA1 region following cerebral ischemia. MAIN OUTCOME MEASURES: Delayed neuronal death in the hippocampal CA1 region was measured by Nissl staining. GFAP expression and delayed neuronal death changes were measured in the rat hippocampal CA1 region at the ischemic hemisphere by double staining for GFAP and TUNEL. RESULTS: After 3 days of ischemia

  17. Melatonin combined with exercise cannot alleviate cerebral injury in a rat model of focal cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Seunghoon Lee; Kyu-Tae Chang; Yonggeun Hong; Jinhee Shin; Minkyung Lee; Yunkyung Hong; Sang-Kil Lee; Youngjeon Lee; Tserentogtokh Lkhagvasuren; Dong-Wook Kim; Young-Ae Yang

    2012-01-01

    Previous studies have demonstrated that melatonin combined with exercise can alleviate secondary damage after spinal cord injury in rats. Therefore, it is hypothesized that melatonin combined with exercise can also alleviate ischemic brain damage. In this study, adult rats were subjected to right middle cerebral artery occlusion after receiving 10 mg/kg melatonin or vehicle subcutaneously twice daily for 14 days. Forced exercise using an animal treadmill was performed at 20 m/min for 30 minutes per day for 6 days prior to middle cerebral artery occlusion. After middle cerebral artery occlusion, each rat received melatonin combined with exercise, melatonin or exercise alone equally for 7 days until sacrifice. Interestingly, rats receiving melatonin combined with exercise exhibited more severe neurological deficits than those receiving melatonin or exercise alone. Hypoxia-inducible factor 1α mRNA in the brain tissue was upregulated in rats receiving melatonin combined with exercise. Similarly, microtubule associated protein-2 mRNA expression was significantly upregulated in rats receiving melatonin alone. Chondroitin sulfate proteoglycan 4 (NG2) mRNA expression was significantly decreased in rats receiving melatonin combined with exercise as well as in rats receiving exercise alone. Furthermore, neural cell loss in the primary motor cortex was significantly reduced in rats receiving melatonin or exercise alone, but the change was not observed in rats receiving melatonin combined with exercise. These findings suggest that excessive intervention with melatonin, exercise or their combination may lead to negative effects on ischemia/reperfusion-induced brain damage.

  18. Inhibitory effect of acupuncture on neuronal apoptosis in rats after cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Bangyu Ju; Jing Zhang; Guohua Jiang

    2007-01-01

    BACKGROUND: Delayed neuronal death after total cerebral ischemia may accompany with apoptosis, but acupuncture may play a certain role in protecting nerve through inhibiting ischemic neuronal apoptosis.OBJECTIVE: To observe the effect of acupuncture on neuronal apoptosis in rats after cerebral ischemia and analyze its cerebral protective mechanism.DESIGN: Contrast observation among groups.SETTING: Heilongjiang University of Traditional Chinese Medicine.MATERIALS: A total of 30 male healthy Wistar rats of general grade and weighing (250±20) g were randomly divided into three groups, including sham operation group, cerebral ischemia group and acupuncture group with 10 rats in each group. Apoptosis in situ kit was provided by Baolingman Company,Germany.METHODS: The experiment was carried out in the Laboratory Center, Heilongjiang University of Traditional Chinese Medicine from May to November 2004. ① Rats in the cerebral ischemia group and the acupuncture group were used to establish total cerebral ischemic models with four vessels occlusion; in addition, models in the sham operation group were established with the same method as mentioned above.However, four vessels of rats in the sham operation were exposured and cerebral ischemia did not occur. Rats in the acupuncture group were given acupuncture treatment after operation. Needle of 40 mm in length was used to acupuncture bilateral Zusanli (St 36) and Quchi (LI 11) with the depth of 3 mm, and then bilateral acupoints were connected with KWD-808Ⅱ omnipotenc impulse electro-therapeutic apparatus (frequency: 1 Hz;thin waves; voltage: 2 V) once a day for totally 30 minutes. Meanwhile, needle of 25 mm in length was used to acupuncture Baihui (Du 20) with the depth of 3 mm, and then the needle was twirled once every 5 minutes for 30 minutes in total. The course was 7 days. ② Neuronal injuries in hippocampal CA1 area after cerebral ischemia were observed with Nissl body staining method at 7 days after treatment

  19. Effects of ketamine, midazolam, thiopental, and propofol on brain ischemia injury in rat cerebral cortical slices

    Institute of Scientific and Technical Information of China (English)

    Qing-shengXUE; Bu-weiYU; Ze-jianWANG; Hong-zhuanCHEN

    2004-01-01

    AIM: To compare the effects of ketamine, midazolam, thiopental, and propofol on brain ischemia by the model of oxygen-glucose deprivation (OGD) in rat cerebral cortical slices. METHODS: Cerebral cortical slices were incu-bated in 2 % 2,3,5-triphenyltetrazolium chloride (TTC) solution after OGD, the damages and effects of ketamine,midazolam, thiopental, and propofol were quantitativlye evaluated by ELISA reader of absorbance (A) at 490 nm,which indicated the red formazan extracted from slices, lactic dehydrogenase (LDH) releases in the incubated supernate were also measured. RESULTS: Progressive prolongation of OGD resulted in decreases of TTC staining.The percentage of tissue injury had a positive correlation with LDH releases, r=0.9609, P<0.01. Two hours of reincubation aggravated the decrease of TTC staining compared with those slices stained immediately after OGD(P<0.01). These four anesthetics had no effects on the TTC staining of slices. Ketamine completely inhibited thedecrease of A value induced by 10 min of OGD injury. High concentrations of midazolam (10 μmol/L) and thiopental (400μmol/L) partly attenuated this decrease. Propofol at high concentration (100 μmol/L) enhanced the decrease of A value induced by 10 min of OGD injury (P<0.01). CONCLUSION; Ketamine, high concentration of midazolam and thiopental have neuroprotective effects against OGD injury in rat cerebral cortical slices, while high concentration of propofol augments OGD injury in rat cerebral cortical slices.

  20. Neuroprotective activity of gossypin from Hibiscus vitifolius against global cerebral ischemia model in rats

    Directory of Open Access Journals (Sweden)

    V M Chandrashekhar

    2013-01-01

    Full Text Available Objectives: The objective of this study is to evaluate the neuroprotective effect of gossypin (isolated from Hibiscus vitifolius against global cerebral ischemia/reperfusion (I/R injury-induced oxidative stress in rats. Materials and Methods: Sprague Dawlet rats of wither gender were used in the study. Evaluation of cerbroprotective activity of bioflavonoid gossypin (in 5, 10 and 20 mg/kg oral doses isolated from H. vitifolius was carried out by using the global cerebral I/R model by bilateral carotid artery occlusion for 30 min, followed by 24 h reperfusion. The antioxidant enzymatic and non-enzymatic levels were estimated along with histopathological studies. Result: Gossypin showed dose-dependent neuroprotective activity by significant decrease in lipid peroxidation (P < 0.001 and increase in the superoxide dismutase, catalase, glutathione and total thiol levels in gossypin treated groups when compared to control group. Cerebral infarction area was markedly reduced in gossypin treated groups when compared to control group. Conclusion: Gossypin showed potent neuroprotective activity against global cerebral I/R injury-induced oxidative stress in rats.

  1. Electro-cortical signs of early neuronal damage following transient global cerebral ischemia in rat

    DEFF Research Database (Denmark)

    Moldovan, M; Zagrean, Ana-Maria; Avramescu, S; Savaran, V; Zagrean, L

    2004-01-01

    During recovery after a transient global cerebral ischemia (TGCI), rat electrocorticogram (ECoG) shows epochs of synchronized activity (SA) alternating with epochs of low amplitude background activity (BA). The aim of this study was to compare the changes in these electrical activities during a 30...... did not change during reperfusion. Our data indicate that following cerebral ischemia the recovery of SA can take place independently of BA. The lack of recovery in BA may indicate early subcortical neuronal damage....

  2. Histidine provides long-term neuroprotection after cerebral ischemia through promoting astrocyte migration

    OpenAIRE

    Ru-jia Liao; Lei Jiang; Rong-rong Wang; Hua-wei Zhao; Ying Chen; Ya Li; Lu Wang; Li-Yong Jie; Yu-dong Zhou; Xiang-nan Zhang; Zhong Chen; Wei-wei Hu

    2015-01-01

    The formation of glial scar impedes the neurogenesis and neural functional recovery following cerebral ischemia. Histamine showed neuroprotection at early stage after cerebral ischemia, however, its long-term effect, especially on glial scar formation, hasn’t been characterized. With various administration regimens constructed for histidine, a precursor of histamine, we found that histidine treatment at a high dose at early stage and a low dose at late stage demonstrated the most remarkable l...

  3. Carvacrol, a Food-Additive, Provides Neuroprotection on Focal Cerebral Ischemia/Reperfusion Injury in Mice

    OpenAIRE

    Yu, Hailong; Zhang, Zeng-Li; Chen, Jing; Pei, Aijie; Hua, Fang; Qian, Xuanchen; He, Jinjiang; Liu, Chun-Feng; Xu, Xingshun

    2012-01-01

    Carvacrol (CAR), a naturally occurring monoterpenic phenol and food additive, has been shown to have antimicrobials, antitumor, and antidepressant-like activities. A previous study demonstrated that CAR has the ability to protect liver against ischemia/reperfusion injury in rats. In this study, we investigated the protective effects of CAR on cerebral ischemia/reperfusion injury in a middle cerebral artery occlusion mouse model. We found that CAR (50 mg/kg) significantly reduced infarct volum...

  4. Targeting reactive nitrogen species: a promising therapeutic strategy for cerebral ischemia-reperfusion injury

    OpenAIRE

    Chen, Xing-miao; Chen, Han-sen; Xu, Ming-jing; Shen, Jian-gang

    2012-01-01

    Ischemic stroke accounts for nearly 80% of stroke cases. Recanalization with thrombolysis is a currently crucial therapeutic strategy for re-building blood supply, but the thrombolytic therapy often companies with cerebral ischemia-reperfusion injury, which are mediated by free radicals. As an important component of free radicals, reactive nitrogen species (RNS), including nitric oxide (NO) and peroxynitrite (ONOO(-)), play important roles in the process of cerebral ischemia-reperfusion injur...

  5. Effects of apoptosis-related proteins caspase-3, Bax and Bcl-2 on cerebral ischemia rats

    OpenAIRE

    Liu, Guangyi; Tao WANG; WANG, TINGING; Song, Jinming; Zhou, Zhen

    2013-01-01

    Neuron apoptosis is known to mediate a change of ethology following cerebral ischemia-reperfusion injury in rats. Additionally, Bcl-2, Bax and caspase-3 proteins may exert a significant effect on neuron injury. The aim of this study was to investigate the role, mechanism of action and clinical significance of these proteins in neuron apoptosis and functional impairment following cerebral ischemia-reperfusion injury in rats. Sixty male healthy adult Wistar rats were randomly assigned into cont...

  6. Valeriana officinalis Extracts Ameliorate Neuronal Damage by Suppressing Lipid Peroxidation in the Gerbil Hippocampus Following Transient Cerebral Ischemia.

    Science.gov (United States)

    Yoo, Dae Young; Jung, Hyo Young; Nam, Sung Min; Kim, Jong Whi; Choi, Jung Hoon; Kwak, Youn-Gil; Yoo, Miyoung; Lee, Sanghee; Yoon, Yeo Sung; Hwang, In Koo

    2015-06-01

    As a medicinal plant, the roots of Valeriana officinalis have been used as a sedative and tranquilizer. In the present study, we evaluated the neuroprotective effects of valerian root extracts (VE) on the hippocampal CA1 region of gerbils after 5 min of transient cerebral ischemia. Gerbils were administered VE orally once a day for 3 weeks, subjected to ischemia/reperfusion injury, and continued on VE for 3 weeks. The administration of 100 mg/kg VE (VE100 group) significantly reduced the ischemia-induced spontaneous motor hyperactivity 1 day after ischemia/reperfusion. Four days after ischemia/reperfusion, animals treated with VE showed abundant cresyl violet-positive neurons in the hippocampal CA1 region when compared to the vehicle or 25 mg/kg VE-treated groups. In addition, the VE treatment markedly decreased microglial activation in the hippocampal CA1 region 4 days after ischemia. Compared to the other groups, the VE100 group showed the lowest level of lipid peroxidation during the first 24 h after ischemia/reperfusion. In summary, the findings in this study suggest that pretreatment with VE has protective effects against ischemic injury in the hippocampal pyramidal neurons by decreasing microglial activation and lipid peroxidation. PMID:25785762

  7. Dietary and plant polyphenols exert neuroprotective effects and improve cognitive function in cerebral ischemia

    Science.gov (United States)

    Cerebral ischemia is caused by an interruption of blood flow to the brain which generally leads to irreversible brain damage. Ischemic injury is associated with vascular leakage, inflammation, tissue injury, and cell death. Cellular changes associated with ischemia include impairment of metabolism, ...

  8. Ablation of neurogenesis attenuates recovery of motor function after focal cerebral ischemia in middle-aged mice.

    Directory of Open Access Journals (Sweden)

    Fen Sun

    Full Text Available Depletion of neurogenesis worsens functional outcome in young-adult mice after focal cerebral ischemia, but whether a similar effect occurs in older mice is unknown. Using middle-aged (12-month-old transgenic (DCX-TK((+ mice that express herpes simplex virus thymidine kinase (HSV-TK under control of the doublecortin (DCX promoter, we conditionally depleted DCX-positive cells in the subventricular zone (SVZ and hippocampus by treatment with ganciclovir (GCV for 14 days. Focal cerebral ischemia was induced by permanent occlusion of the middle cerebral artery (MCAO or occlusion of the distal segment of middle cerebral artery (dMCAO on day 14 of vehicle or GCV treatment and mice were killed 24 hr or 12 weeks later. Increased infarct volume or brain atrophy was found in GCV- compared to vehicle-treated middle-aged DCX-TK((+ mice, both 24 hr after MCAO and 12 weeks after dMCAO. More severe motor deficits were also observed in GCV-treated, middle-aged DCX-TK((+ transgenic mice at both time points. Our results indicate that ischemia-induced newborn neurons contribute to anatomical and functional outcome after experimental stroke in middle-aged mice.

  9. Poly-IC preconditioning protects against cerebral and renal ischemia-reperfusion injury

    OpenAIRE

    Packard, Amy E. B.; Hedges, Jason C; Bahjat, Frances R; Stevens, Susan L; Michael J. Conlin; Salazar, Andres M.; Stenzel-Poore, Mary P

    2011-01-01

    Preconditioning induces ischemic tolerance, which confers robust protection against ischemic damage. We show marked protection with polyinosinic polycytidylic acid (poly-IC) preconditioning in three models of murine ischemia-reperfusion injury. Poly-IC preconditioning induced protection against ischemia modeled in vitro in brain cortical cells and in vivo in models of brain ischemia and renal ischemia. Further, unlike other Toll-like receptor (TLR) ligands, which generally induce significant ...

  10. Dopaminergic neurotransmission triggers ischemia-induced hyperactivity in Mongolian gerbils.

    Directory of Open Access Journals (Sweden)

    Yamamoto T

    2001-10-01

    Full Text Available It is recognized that sustained ischemia-induced hyperactivity is related to abnormalities in dopamine function. However, it is unclear that dopaminergic neurotransmission triggers such ischemia-induced hyperactivity. Therefore, the relationship between dopaminergic neurotransmission and ischemia-induced hyperactivity was investigated in an animal model using Mongolian gerbils. When haloperidol 2 mg/kg was administered i.p. 30 min after ischemia, the ischemia-induced hyperactivity at 24 h after ischemia was blocked. General behavior was similar to that of sham-operated animals. Haloperidol at doses of 0.1 and 0.2 mg/kg had no effect on locomotor activity in sham-operated animals and decreased ischemia-induced hyperactivity when the drug was administered 24 h after ischemia; these doses did not have any effect on ischemia-induced hyperactivity when the drug was administered 30 min after ischemia. On the other hand, when the animal was confined to a small, restrictive cage for the 24 h period immediately following ischemic injury, locomotor activity at 24 h after ischemia increased. Such behavior also increased in animals when they were returned to their original more permissive cages immediately after ischemia. It is conceivable that the decrease in the level of activity was not related to ischemia-induced hyperactivity. These data suggested that the inhibition of ischemia-induced hyperactivity can be induced by complete blockage of dopaminergic receptors immediately after ischemia.

  11. Buyanghuanwu decoction promotes angiogenesis after cerebral ischemia/reperfusion injury: mechanisms of brain tissue repair.

    Science.gov (United States)

    Zhang, Zhen-Qiang; Song, Jun-Ying; Jia, Ya-Quan; Zhang, Yun-Ke

    2016-03-01

    Buyanghuanwu decoction has been shown to protect against cerebral ischemia/reperfusion injury, but the underlying mechanisms remain unclear. In this study, rats were intragastrically given Buyanghuanwu decoction, 15 mL/kg, for 3 days. A rat model of cerebral ischemia/reperfusion injury was established by middle cerebral artery occlusion. In rats administered Buyanghuanwu decoction, infarct volume was reduced, serum vascular endothelial growth factor and integrin αvβ3 levels were increased, and brain tissue vascular endothelial growth factor and CD34 expression levels were increased compared with untreated animals. These effects of Buyanghuanwu decoction were partially suppressed by an angiogenesis inhibitor (administered through the lateral ventricle for 7 consecutive days). These data suggest that Buyanghuanwu decoction promotes angiogenesis, improves cerebral circulation, and enhances brain tissue repair after cerebral ischemia/reperfusion injury. PMID:27127482

  12. Buyanghuanwu decoction promotes angiogenesis after cerebral ischemia/reperfusion injury:mechanisms of brain tissue repair

    Institute of Scientific and Technical Information of China (English)

    Zhen-qiang Zhang; Jun-ying Song; Ya-quan Jia; Yun-ke Zhang

    2016-01-01

    Buyanghuanwu decoction has been shown to protect against cerebral ischemia/reperfusion injury, but the underlying mechanisms remain unclear. In this study, rats were intragastrically givenBuyanghuanwu decoction, 15 mL/kg, for 3 days. A rat model of cerebral ischemia/reper-fusion injury was established by middle cerebral artery occlusion. In rats administeredBuyanghuanwu decoction, infarct volume was reduced, serum vascular endothelial growth factor and integrinαvβ3 levels were increased, and brain tissue vascular endothelial growth factor and CD34 expression levels were increased compared with untreated animals. These effects ofBuyanghuanwu decoction were partially suppressed by an angiogenesis inhibitor (administered through the lateral ventricle for 7 consecutive days). These data suggest thatBuyanghuanwu de-coction promotes angiogenesis, improves cerebral circulation, and enhances brain tissue repair after cerebral ischemia/reperfusion injury.

  13. Buyanghuanwu decoction promotes angiogenesis after cerebral ischemia/reperfusion injury: mechanisms of brain tissue repair

    Directory of Open Access Journals (Sweden)

    Zhen-qiang Zhang

    2016-01-01

    Full Text Available Buyanghuanwu decoction has been shown to protect against cerebral ischemia/reperfusion injury, but the underlying mechanisms remain unclear. In this study, rats were intragastrically given Buyanghuanwu decoction, 15 mL/kg, for 3 days. A rat model of cerebral ischemia/reperfusion injury was established by middle cerebral artery occlusion. In rats administered Buyanghuanwu decoction, infarct volume was reduced, serum vascular endothelial growth factor and integrin αvβ3 levels were increased, and brain tissue vascular endothelial growth factor and CD34 expression levels were increased compared with untreated animals. These effects of Buyanghuanwu decoction were partially suppressed by an angiogenesis inhibitor (administered through the lateral ventricle for 7 consecutive days. These data suggest that Buyanghuanwu decoction promotes angiogenesis, improves cerebral circulation, and enhances brain tissue repair after cerebral ischemia/reperfusion injury.

  14. Role of nitric oxide synthases in early blood-brain barrier disruption following transient focal cerebral ischemia.

    Directory of Open Access Journals (Sweden)

    Zheng Jiang

    Full Text Available The role of nitric oxide synthases (NOSs in early blood-brain barrier (BBB disruption was determined using a new mouse model of transient focal cerebral ischemia. Ischemia was induced by ligating the middle cerebral artery (MCA at its M2 segment and reperfusion was induced by releasing the ligation. The diameter alteration of the MCA, arterial anastomoses and collateral arteries were imaged and measured in real time. BBB disruption was assessed by Evans Blue (EB and sodium fluorescein (Na-F extravasation at 3 hours of reperfusion. The reperfusion produced an extensive vasodilation and a sustained hyperemia. Although expression of NOSs was not altered at 3 hours of reperfusion, L-NAME (a non-specific NOS inhibitor abolished reperfusion-induced vasodilation/hyperemia and significantly reduced EB and Na-F extravasation. L-NIO (an endothelial NOS (eNOS inhibitor significantly attenuated cerebral vasodilation but not BBB disruption, whereas L-NPA and 7-NI (neuronal NOS (nNOS inhibitors significantly reduced BBB disruption but not cerebral vasodilation. In contrast, aminoguanidine (AG (an inducible NOS (iNOS inhibitor had less effect on either cerebral vasodilation or BBB disruption. On the other hand, papaverine (PV not only increased the vasodilation/hyperemia but also significantly reduced BBB disruption. Combined treatment with L-NAME and PV preserved the vasodilation/hyperemia and significantly reduced BBB disruption. Our findings suggest that nNOS may play a major role in early BBB disruption following transient focal cerebral ischemia via a hyperemia-independent mechanism.

  15. Osthole, a natural coumarin, improves neurobehavioral functions and reduces infarct volume and matrix metalloproteinase-9 activity after transient focal cerebral ischemia in rats.

    Science.gov (United States)

    Mao, Xuexuan; Yin, Wei; Liu, Mengfei; Ye, Minzhong; Liu, Peiqing; Liu, Jianxin; Lian, Qishen; Xu, Suowen; Pi, Rongbiao

    2011-04-18

    Previously we demonstrated that Osthole, a natural coumarin, protects against focal cerebral ischemia/reperfusion-induced injury in rats. In the present study, the effects of Osthole on neurobehavioral functions, infarct volume and matrix metalloproteinase-9 (MMP-9) in a rat 2h focal cerebral ischemia model were investigated. Osthole (100mg/kg per dose) was administrated intraperitoneally 30min before ischemic insult and immediately after reperfusion. Osthole treatment significantly reduced neurological deficit score and infarct volume by 38.5% and 33.8%, respectively, as compared with the untreated animals. Osthole reversed ischemia-reperfusion-induced increase in MMP-9 protein level/activity as evidenced by Western blotting and gelatin zymography. Taken together, these results for the first time demonstrate that Osthole reduces infarct volume, restores neurobehavioral functions and downregulates MMP-9 protein level/activity in ischemia/reperfused brain. PMID:21316348

  16. Discussion on the treatment of cerebral ischemia-reperfusion injuries following intra-arterial thrombolysis

    International Nuclear Information System (INIS)

    Objective: To investigate the therapeutic method of cerebral ischemia-reperfusion injuries occurred after arterial thrombolytic therapy for acute cerebral infarction. Methods: Thirty-five patients, encountered in authors' Department since Oct. 2005, with cerebral ischemia-reperfusion injuries, which occurred after thrombolytic therapy by using arterial perfusion of urokinase for acute cerebral infarction, were enrolled in this study. The clinical data were retrospectively analyzed. Results: After the thrombolytic therapy, completer or partial recanalization of the occluded cerebral arteries was obtained in 33 cases, while secondary cerebral hemorrhage occurred in 13 cases, of whom cerebral parenchyma bleeding was seen in 2 and hemorrhagic infarction in 11. Different degrees of cerebral edema were found in all 33 cases. Among them significant shift of the midline structures was detected in 18 (54.5%), which was manifested clinically as the worsening of disturbance of consciousness. Strict control of blood pressure, prompt adjustment of dehydration medication, strengthening the cerebral protection measures, cerebral decompression by fenestration, etc. were carried out. All the patients took a turn for the better and were out of danger with remarkable improvement of neurological functions except one patient who died from massive intracerebral hemorrhage. Conclusion: Usually, different degrees of reperfusion injuries will develop after thrombolytic therapy for cerebral arterial infarction. Strictly controlling blood pressure, promptly adjusting dehydration medication and strengthening cerebral protection are the keys to reduce the severity of cerebral reperfusion injuries. (authors)

  17. MicroRNA responses to focal cerebral ischemia in male and female mouse brain

    Directory of Open Access Journals (Sweden)

    Theresa Ann Lusardi

    2014-02-01

    Full Text Available Stroke occurs with greater frequency in men than in women across diverse ethnic backgrounds and nationalities. Work from our lab and others have revealed a sex-specific sensitivity to cerebral ischemia whereby males exhibit a larger extent of brain damage resulting from an ischemic event compared to females. Previous studies revealed that microRNA (miRNA expression is regulated by cerebral ischemia in males; however, no studies to date have examined the effect of ischemia on miRNA responses in females. Thus, we examined miRNA responses in male and female brain in response to cerebral ischemia using miRNA arrays. These studies revealed that in male and female brains, ischemia leads to both a universal miRNA response as well as a sexually distinct response to challenge. Target prediction analysis of the miRNAs increased in male or female ischemic brain reveal sex-specific differences in gene targets and protein pathways. These data support that the mechanisms underlying sexually dimorphic responses to cerebral ischemia includes distinct changes in miRNAs in male and female brain, in addition to a miRNA signature response to ischemia that is common to both.

  18. Anti-apoptosis effect of taurine on cerebral ischemia in rat

    Institute of Scientific and Technical Information of China (English)

    LuoCan; LiuJie; WuQin; ShiJing-Shan; GuoLian-Jun

    2004-01-01

    Aim To study anti -apoptosis effect of taurine on cerebral ischemia in rat. Methods 1. in vivo: taurine (250mg/Kg.d) was administrated by i. p. for one week in treated group. A nylon suture was inserted into fight internal carotid artery to occlude the beginning of middle cerebral artery (MCAO). After 3 hours'permanent occlusion, neurology deficit score

  19. Are bone marrow regenerative cells ideal seed cells for the treatment of cerebral ischemia?

    Institute of Scientific and Technical Information of China (English)

    Yi Li; Xuming Hua; Fang Hua; Wenwei Mao; Liang Wan; Shiting Li

    2013-01-01

    Bone marrow cells for the treatment of ischemic brain injury may depend on the secretion of a large number of neurotrophic factors. Bone marrow regenerative cells are capable of increasing the secretion of neurotrophic factors. In this study, after tail vein injection of 5-fluorouracil for 7 days, bone marrow cells and bone marrow regenerative cells were isolated from the tibias and femurs of rats, and then administered intravenously via the tail vein after focal cerebral ischemia. Immunohistological staining and reverse transcription-PCR detection showed that transplanted bone marrow cells and bone marrow regenerative cells could migrate and survive in the ischemic regions, such as the cortical and striatal infarction zone. These cells promote vascular endothelial cell growth factor mRNA expression in the ischemic marginal zone surrounding the ischemic penumbra of the cortical and striatal infarction zone, and have great advantages in promoting the recovery of neurological function, reducing infarct size and promoting angiogenesis. Bone marrow regenerative cells exhibited stronger neuroprotective effects than bone marrow cells. Our experimental findings indicate that bone marrow regenerative cells are preferable over bone marrow cells for cell therapy for neural regeneration after cerebral ischemia. Their neuroprotective effect is largely due to their ability to induce the secretion of factors that promote vascular regeneration, such as vascular endothelial growth factor.

  20. Protective Effects of Dihydrocaffeic Acid, a Coffee Component Metabolite, on a Focal Cerebral Ischemia Rat Model

    Directory of Open Access Journals (Sweden)

    Kyungjin Lee

    2015-06-01

    Full Text Available We recently reported the protective effects of chlorogenic acid (CGA in a transient middle cerebral artery occlusion (tMCAo rat model. The current study further investigated the protective effects of the metabolites of CGA and dihydrocaffeic acid (DHCA was selected for further study after screening using the same tMCAo rat model. In the current study, tMCAo rats (2 h of MCAo followed by 22 h of reperfusion were injected with various doses of DHCA at 0 and 2 h after onset of ischemia. We assessed brain damage, functional deficits, brain edema, and blood-brain barrier damage at 24 h after ischemia. For investigating the mechanism, in vitro zymography and western blotting analysis were performed to determine the expression and activation of matrix metalloproteinase (MMP-2 and -9. DHCA (3, 10, and 30 mg/kg, i.p. dose-dependently reduced brain infarct volume, behavioral deficits, brain water content, and Evans Blue (EB leakage. DHCA inhibited expression and activation of MMP-2 and MMP-9. Therefore, DHCA might be one of the important metabolites of CGA and of natural products, including coffee, with protective effects on ischemia-induced neuronal damage and brain edema.

  1. Visualization of cell death in mice with focal cerebral ischemia using fluorescent annexin A5, propidium iodide, and TUNEL staining

    OpenAIRE

    Bahmani, Peyman; Schellenberger, Eyk; Klohs, Jan; Steinbrink, Jens; Cordell, Ryan; Zille, Marietta; Müller, Jochen; Harhausen, Denise; Hofstra, Leo; Reutelingsperger, Chris; Farr, Tracy Deanne; Dirnagl, Ulrich; Wunder, Andreas

    2011-01-01

    To monitor stroke-induced brain damage and assess neuroprotective therapies, specific imaging of cell death after cerebral ischemia in a noninvasive manner is highly desirable. Annexin A5 has been suggested as a marker for imaging cell death under various disease conditions including stroke. In this study, C57BL6/N mice received middle cerebral artery occlusion (MCAO) and were injected intravenously with either active or inactive Cy5.5-annexin A5 48 hours after reperfusion. Some mice also rec...

  2. Dynamic changes of excitatory amino acid receptors in the rat hippocampus following transient cerebral ischemia

    International Nuclear Information System (INIS)

    The changes in excitatory amino acid receptor ligand binding induced by transient cerebral ischemia were studied in the rat hippocampal subfields. Ten minutes of ischemia was induced by common carotid artery occlusion combined with hypotension, and the animals were allowed variable periods of recovery ranging from 1 day to 4 weeks. The binding of 3H-AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) to quisqualate receptors, 3H-kainic acid (KA) to kainate receptors, and 3H-glutamate to N-methyl-D-aspartate (NMDA) receptors as determined by quantitative autoradiography. One week following ischemia the CA1 region of the hippocampus displayed a severe (90%) dendrosomatic lesion with preservation of presynaptic terminals. This was associated with a 60% decrease in AMPA binding and a 25% decrease in glutamate binding to NMDA receptors. At 4 weeks postischemia, both AMPA and NMDA sites were greatly reduced. Although the dentate gyrus granule cells are resistant to an ischemic insult of this magnitude, this region showed marked changes in receptor binding. One week following ischemia, the AMPA and NMDA binding decreased by approximately 40 and 20%, respectively. Following 2 weeks of recovery, the NMDA binding was not significantly different from control level, while the AMPA binding remained depressed up to 4 weeks postischemia. The high density of KA binding sites in the inner molecular layer of the dentate gyrus was unaffected by the ischemic insult, despite an extensive degeneration of cells in the hilus of dentate gyrus which projects glutamatergic afferents to this area

  3. Ursolic acid reduces the metalloprotease/anti-metalloprotease imbalance in cerebral ischemia and reperfusion injury

    Directory of Open Access Journals (Sweden)

    Wang Y

    2016-05-01

    Full Text Available Yanzhe Wang, Zhiyi He, Shumin Deng Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China Background: Activators of PPARs, particularly PPARγ, may be effective neuroprotective drugs against inflammatory responses in cerebral ischemia and reperfusion injury. Ursolic acid (UA may act as a PPARγ agonist and serve as an anti-inflammatory agent. In this study, we used a rat middle cerebral artery occlusion and reperfusion model to examine how UA acts as a neuroprotective agent to modulate the metalloprotease/anti-metalloprotease balance. Methods: The middle cerebral artery occlusion and reperfusion model (occlusion for 2 hours followed by reperfusion for 48 hours was induced in male Sprague Dawley rats. UA was administered intragastrically 0.5, 24, and 47 hours after reperfusion. Bisphenol A diglycidyl ether (a PPARγ antagonist was intraperitoneally administered 1, 24.5, and 47.5 hours after reperfusion. Forty-eight hours after reperfusion, neurological deficits and infarct volume were estimated. The PPARγ level and the metalloprotease/anti-metalloprotease balance were examined by Western blotting and immunohistochemistry. The activation of MAPK signaling pathways was also assessed. Results: UA-treated (5, 10, or 20 mg/kg rats showed significant improvement in neurological deficit score, infarct volume, and the number of intact neurons compared with control rats (P<0.01. Both the PPARγ protein level and the percentage of PPARγ-positive cells were increased in the UA-treated groups (P<0.01. Compared with the control group, the UA-treated groups exhibited reduced protein levels of MMP2, MMP9, and activated MAPKs (P<0.01 but an increased level of TIMP1 (P<0.01. UA exerted its protective effects in a dose-dependent manner. Co-treatment with UA and bisphenol A diglycidyl ether completely abolished the UA-induced changes in PPARγ expression; however UA continued to exert a

  4. Lateral intracerebroventricular injection of Apelin-13 inhibits apoptosis after cerebral ischemia/reperfusion injury

    Directory of Open Access Journals (Sweden)

    Xiao-ge Yan

    2015-01-01

    Full Text Available Apelin-13 inhibits neuronal apoptosis caused by hydrogen peroxide, yet apoptosis following cerebral ischemia-reperfusion injury has rarely been studied. In this study, Apelin-13 (0.1 µg/g was injected into the lateral ventricle of middle cerebral artery occlusion model rats. TTC, TUNEL, and immunohistochemical staining showed that compared with the cerebral ischemia/reperfusion group, infarct volume and apoptotic cell number at the ischemic penumbra region were decreased in the Apelin-13 treatment group. Additionally, Apelin-13 treatment increased Bcl-2 immunoreactivity and decreased caspase-3 immunoreactivity. Our findings suggest that Apelin-13 is neuroprotective against cerebral ischemia/reperfusion injury through inhibition of neuronal apoptosis.

  5. Puerarin partly counteracts the inflammatory response after cerebral ischemia/reperfusion via activating the cholinergic anti-inflammatory pathway

    Institute of Scientific and Technical Information of China (English)

    Xiaojie Liu; Zhigang Mei; Jingping Qian; Yongbao Zeng; Mingzhi Wang

    2013-01-01

    Puerarin, a major isoflavonoid derived from the Chinese medical herb radix puerariae (Gegen), has been reported to inhibit neuronal apoptosis and play an anti-inflammatory role in focal cerebral ischemia model rats. Recent findings regarding stroke pathophysiology have recognized that an-ti-inflammation is an important target for the treatment of ischemic stroke. The cholinergic an-ti-inflammatory pathway is a highly robust neural-immune mechanism for inflammation control. This study was to investigate whether activating the cholinergic anti-inflammatory pathway can be in-volved in the mechanism of inhibiting the inflammatory response during puerarin-induced cerebral ischemia/reperfusion in rats. Results showed that puerarin pretreatment (intravenous injection) re-duced the ischemic infarct volume, improved neurological deficit after cerebral ischemia/reperfusion and decreased the levels of interleukin-1β, interleukin-6 and tumor necrosis factor-αin brain tissue. Pretreatment with puerarin (intravenous injection) attenuated the inflammatory response in rats, which was accompanied by janus-activated kinase 2 (JAK2) and signal transducers and activators of transcription 3 (STAT3) activation and nuclear factor kappa B (NF-κB) inhibition. These observa-tions were inhibited by the alpha7 nicotinic acetylcholine receptor (α7nAchR) antagonistα-bungarotoxin (α-BGT). In addition, puerarin pretreatment increased the expression of α7nAchR mRNA in ischemic cerebral tissue. These data demonstrate that puerarin pretreatment strongly protects the brain against cerebral ischemia/reperfusion injury and inhibits the inflammatory re-sponse. Our results also indicated that the anti-inflammatory effect of puerarin may partly be me-diated through the activation of the cholinergic anti-inflammatory pathway.

  6. Human Microglia Transplanted in Rat Focal Ischemia Brain Induce Neuroprotection and Behavioral Improvement

    OpenAIRE

    Narantuya, Dashdemberel; NAGAI, Atsushi; Sheikh, Abdullah Md.; Masuda, Junichi; Kobayashi, Shotai; Yamaguchi, Shuhei; Seung U Kim

    2010-01-01

    Background and Purpose Microglia are resident immunocompenent and phagocytic cells of central nervous system (CNS), which produce various cytokines and growth factors in response to injury and thereby regulate disease pathology. The purpose of this study is to investigate the effects of microglial transplantation on focal cerebral ischemia model in rat. Methods Transient middle cerebral artery occlusion (MCAO) in rats was induced by the intraluminal filament technique. HMO6 cells, human micro...

  7. Non-traumatic neurological emergencies: imaging of cerebral ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Grunwald, Iris; Reith, Wolfgang [Department of Neuroradiology, Saarland University Clinic, Homburg/Saar (Germany)

    2002-07-01

    Cardiovascular disease is the leading cause of death worldwide with almost one-third of all cardiovascular deaths ascribed to stroke. Imaging modalities, such as CT, MRI, positron emission tomography (PET), and single photon emission CT (SPECT) provide tremendous insight into the pathophysiology of acute stroke. Computed tomography is considered the most important initial diagnostic study in patients with acute stroke, because underlying structural lesions, such as tumor, vascular malformation, or subdural hematoma, can mimic stroke clinically. Diffusion-weighted imaging (DWI) has the ability to visualize changes in diffusion within minutes after the onset of ischemia and has become a powerful tool in the evaluation of patients with stroke syndrome. Territories with diffusion and perfusion mismatch may define tissues at risk, but with potential recovery. An alternative strategy with CT technology uses rapid CT for dynamic perfusion imaging, with similar goals in mind. Angiography can be performed in the hyperacute stage if thrombolytic therapy is being considered. Indications for diagnostic angiography include transient ischemic attacks in a carotid distribution, amaurosis fugax, prior stroke in a carotid distribution, a high-grade stenotic lesion in a carotid artery, acquiring an angiographic correlation of magnetic resonance angiography (MRA) or computed tomographic angiography (CTA) concerning stenotic findings. In 50% of all angiograms performed in the hyperacute stage, occlusion of a vessel is observed; however, the need for angiography has been made less necessary due to the improvements of MRA, duplex ultrasound, and CTA. Numerous etiologies can lead to infarction. In children, pediatric stroke is very uncommon. The most common cause is an embolus from congenital heart disease with right-to-left shunts. Also a dissection of large extracranial vessels may result in cerebral infarction, and although the brain is equipped with numerous venous drainage routes

  8. Non-traumatic neurological emergencies: imaging of cerebral ischemia

    International Nuclear Information System (INIS)

    Cardiovascular disease is the leading cause of death worldwide with almost one-third of all cardiovascular deaths ascribed to stroke. Imaging modalities, such as CT, MRI, positron emission tomography (PET), and single photon emission CT (SPECT) provide tremendous insight into the pathophysiology of acute stroke. Computed tomography is considered the most important initial diagnostic study in patients with acute stroke, because underlying structural lesions, such as tumor, vascular malformation, or subdural hematoma, can mimic stroke clinically. Diffusion-weighted imaging (DWI) has the ability to visualize changes in diffusion within minutes after the onset of ischemia and has become a powerful tool in the evaluation of patients with stroke syndrome. Territories with diffusion and perfusion mismatch may define tissues at risk, but with potential recovery. An alternative strategy with CT technology uses rapid CT for dynamic perfusion imaging, with similar goals in mind. Angiography can be performed in the hyperacute stage if thrombolytic therapy is being considered. Indications for diagnostic angiography include transient ischemic attacks in a carotid distribution, amaurosis fugax, prior stroke in a carotid distribution, a high-grade stenotic lesion in a carotid artery, acquiring an angiographic correlation of magnetic resonance angiography (MRA) or computed tomographic angiography (CTA) concerning stenotic findings. In 50% of all angiograms performed in the hyperacute stage, occlusion of a vessel is observed; however, the need for angiography has been made less necessary due to the improvements of MRA, duplex ultrasound, and CTA. Numerous etiologies can lead to infarction. In children, pediatric stroke is very uncommon. The most common cause is an embolus from congenital heart disease with right-to-left shunts. Also a dissection of large extracranial vessels may result in cerebral infarction, and although the brain is equipped with numerous venous drainage routes

  9. Metabolism of biogenic amines in acute cerebral ischemia: Influence of systemic hyperglycemia

    Directory of Open Access Journals (Sweden)

    Milovanović Aleksandar

    2012-01-01

    Full Text Available Dopamine, norepinephrine and serotonin are biogenic amines which are transmitters of the central nervous system. The effects of ischemia on the brain parenchyma depends on many factors, such is the mechanism of blood flow interruption, velocity of the occurring blood flow interruption, duration of an ischemic episode, organization of anatomical structures of the brain blood vessels etc., which all influence the final outcome. During interruption of the brain circulation in experimental or clinical conditions, neurotransmitter metabolism, primarily of biogenic amines, is disturbed. Many researches with various experimental models of complete ischemia reported a decrease in the content of norepinephrine, dopamine and serotonin in the CNS tissue. It was proven that hyperglycemia can drastically increase cerebral injury followed by short-term cerebral ischemia. Considering the fact that biogenic amines (dopamine, norepinephrine and serotonin influence the size of neurologic damage, as well as the fact that in hyperglycemic conditions infarct size (from the morphological aspect is larger relative to normoglycemic status, the intention was to evaluate the role of biogenic amines in occurrence of damage in conditions of hyperglycemia, i.e. in the case of brain apoplexia in diabetics. Analysis of biogenic amines metabolism in states of acute hyperglycemia, as well as analysis of the effects of reversible and irreversible brain ischemia on metabolism of serotonin, dopamine and norepinephrine, showed that acute hyperglycemia slows down serotonin, dopamine and norepinephrine metabolism in the cerebral cortex and n. caudatus. Brain ischemia in normoglycemic animals by itself has no influence on biogenic amines metabolism, but the effect of ischemia becomes apparent during reperfusion. In recirculation, which corresponds to the occurrences in penumbra, release of biogenic amines is uncontrolled and increased. Brain ischemia in acute hyperglycemic animals

  10. Quantification and evaluation of thymoquinone loaded mucoadhesive nanoemulsion for treatment of cerebral ischemia.

    Science.gov (United States)

    Ahmad, Niyaz; Ahmad, Rizwan; Alam, Md Aftab; Samim, Mohd; Iqbal, Zeenat; Ahmad, Farhan Jalees

    2016-07-01

    Stroke is an important cause of deaths worldwide, resulting in an irreversible deterioration of the central nervous system. Finally, production of more free radicals. Therefore, Thymoquinone is having antioxidant property and reported to have a potential role in the amelioration of cerebral ischemia but due to low solubility and poor absorption; they exhibit low serum and tissue levels. Present work aims to prepare nanoemulsions in order enhance the bioavailability of drug and hence evaluate the drug targeting in brain via non-invasive nasal route administration. Thymoquinone Mucoadhesive Nanoemulsion (TMNE) was prepared by ionic gelation method; characterized for particles size, entrapment efficiency, zeta potential, and ex vivo permeation study. Optimized TMNE ended up with a mean globule size 94.8±6.61nm; zeta potential -13.5±1.01mV; drug content 99.86±0.35% and viscosity 110±12cp. Ultra Performance Liquid Chromatography-Photodiode Array (UPLC-PDA) based bioanalytical method was developed and validated for pharmacokinetics, biodistribution, brain-targeting efficiency (628.5786±44.79%) and brain drug-targeting potential (89.97±2.94%) studies via post intranasal administration which revealed enhanced bioavailability of TQ in brain as compared to intravenous administration. Improved neurobehavioural activity (locomotor and grip strength) was observed in middle cerebral artery occlusion induced cerebral ischemic rats after i.n. administration of TMNE. PMID:26976069

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

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    Shuai Hou

    2016-07-01

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

  12. Cerebral ischemia in rabbit: a new experimental model with immunohistochemical investigation.

    Science.gov (United States)

    Yamamoto, K; Yoshimine, T; Yanagihara, T

    1985-12-01

    Regional cerebral ischemia was produced in the rabbit by unilateral transorbital occlusion of the middle cerebral artery (procedure I); the middle cerebral and azygos anterior cerebral or anterior communicating artery (procedure II); or the middle cerebral, azygos anterior cerebral or anterior communicating, and internal carotid artery (procedure III). Evolution of ischemic lesions was examined with the immunohistochemical reaction for tubulin. With procedure I, ischemic lesions did not become constantly visible for 6 h in the basal ganglia and for 8 h in the frontoparietal region of the cerebral cortex. With procedure II, it was shortened to 3 h in the basal ganglia and to 6 h in the cerebral cortex. With procedure III, the ischemic lesions were observed in 1 h both in the basal ganglia and in the cerebral cortex as loss of the reaction for tubulin in the neuropil, nerve cell bodies, and dendrites. The evidence of neuronal damage became apparent in the same areas later by staining with hematoxylin-eosin. The experimental model presented here may be suitable for investigation of the mechanism that shifts reversible ischemia to cerebral infarction and for evaluation of the effectiveness of pharmacological intervention. PMID:3932374

  13. Improved assessment of outcomes following transient global cerebral ischemia in mice.

    Science.gov (United States)

    Spray, Stine; Edvinsson, Lars

    2016-07-01

    Mouse models of global cerebral ischemia (GCI) allow experimental examination of cerebral pathophysiology in genetically modified mice and fast screening of new treatment strategies. Various surgical protocols of GCI-induction in mice have been published; however, many of these studies are hindered by limited neurological assessment protocols and present insufficient reporting of the cumulative survival rate. Therefore, we aim at developing a reproducible and easily implementable model of transient GCI in mice with minimal impact on normal mouse behavior. GCI was induced in male C57BL/6 mice by bilateral occlusion of the common carotid arteries for 10 min combined with isoflurane-induced hypotension which resulted in severe reduction in the cerebral blood flow of the forebrain. Sham operation served as a control. Exploratory behavior was evaluated in a home-cage environment the day before and again daily for up to 7 days after GCI or sham operation and was found to be significantly decreased 1-7 days after GCI compared to sham. Furthermore, we found delayed neuronal cell death in the frontal cortex and hippocampus 5 and 7 days after GCI but not at day 3 or after sham operation. The survival rate at day 7 was 100 % after sham operation and 42 % after GCI. The model of GCI in mice presented in this study compromises the exploratory behavior and resembles the cerebral damage and mortality rate seen after cardiac arrest and/or GCI in man, and is therefore a good model to use for studies of GCI pathophysiology. PMID:26914479

  14. Matrix metalloproteinase-13 participates in neuroprotection and neurorepair after cerebral ischemia in mice.

    Science.gov (United States)

    Ma, Feifei; Martínez-San Segundo, Pablo; Barceló, Verónica; Morancho, Anna; Gabriel-Salazar, Marina; Giralt, Dolors; Montaner, Joan; Rosell, Anna

    2016-07-01

    New neuroreparative and neuroprotective therapies are being sought to treat stroke patients. One approach is the remodeling of extracellular matrix, which participates in both brain injury and neurovascular repair when matrix metalloproteinases (MMPs) are thought to be key players. Our aim was to investigate the role of MMP-13 (collagenase-3) in the acute (24h and 3days) and delayed (2weeks) phases of stroke. Permanent and transient cerebral ischemia models involving the cortex were induced in MMP-13 knock-out (KO) and wild-type (WT) mice. In the transient model, MMP-13 deficiency reduced the amount of TTC-stained infarct tissue, reduced hemorrhagic events and improved functional outcomes (pstroke peri-infarct vessel density increased in the WT mice (pstroke neurorepair, which is critical for optimal angiogenic and neurogenic responses. PMID:27001146

  15. Delayed hippocampal neuronal death in young gerbil following transient global cerebral ischemia is related to higher and longer-term expression of p63 in the ischemic hippocampus

    Directory of Open Access Journals (Sweden)

    Eun Joo Bae

    2015-01-01

    Full Text Available The tumor suppressor p63 is one of p53 family members and plays a vital role as a regulator of neuronal apoptosis in the development of the nervous system. However, the role of p63 in mature neuronal death has not been addressed yet. In this study, we first compared ischemia-induced effects on p63 expression in the hippocampal regions (CA1- 3 between the young and adult gerbils subjected to 5 minutes of transient global cerebral ischemia. Neuronal death in the hippocampal CA1 region of young gerbils was significantly slow compared with that in the adult gerbils after transient global cerebral ischemia. p63 immunoreactivity in the hippocampal CA1 pyramidal neurons in the sham-operated young group was significantly low compared with that in the sham-operated adult group. p63 immunoreactivity was apparently changed in ischemic hippocampal CA1 pyramidal neurons in both ischemia-operated young and adult groups. In the ischemia-operated adult groups, p63 immunoreactivity in the hippocampal CA1 pyramidal neurons was significantly decreased at 4 days post-ischemia; however, p63 immunoreactivity in the ischemia-operated young group was significantly higher than that in the ischemia-operated adult group. At 7 days post-ischemia, p63 immunoreactivity was decreased in the hippocampal CA1 pyramidal neurons in both ischemia-operated young and adult groups. Change patterns of p63 level in the hippocampal CA1 region of adult and young gerbils after ischemic damage were similar to those observed in the immunohistochemical results. These findings indicate that higher and longer-term expression of p63 in the hippocampal CA1 region of the young gerbils after ischemia/reperfusion may be related to more delayed neuronal death compared to that in the adults.

  16. Cerebral ischemia as initial neurological manifestation of atrial myxoma: case report

    Directory of Open Access Journals (Sweden)

    Almeida Leila Azevedo de

    2006-01-01

    Full Text Available Cerebral infarctions of cardiac etiology are observed in around 20% of patients with ischemic stroke. Cerebral ischemia is the first clinical manifestation in 1/3 of cases of atrial myxomas. Although almost half of patients with atrial myxoma show changes at neurological exam, non-hemorrhagic cerebral infarction is seen in computed tomography in practically all cases. We present the case of a 40 year-old woman whose first clinical manifestation of atrial myxoma was an ischemic stroke. We point out to the possibility of silent cerebral infarction in atrial myxoma patients.

  17. Regulation of extracellular signal-regulated kinase 1/2 inlfuences hippocampal neuronal survival in a rat model of diabetic cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Yaning Zhao; Jianmin Li; Qiqun Tang; Pan Zhang; Liwei Jing; Changxiang Chen; Shuxing Li

    2014-01-01

    Activation of extracellular signal-regulated kinase 1/2 has been demonstrated in acute brain ischemia. We hypothesized that activated extracellular signal-regulated kinase 1/2 can protect hippocampal neurons from injury in a diabetic model after cerebral ischemia/reperfusion. In this study, transient whole-brain ischemia was induced by four-vessel occlusion in normal and diabetic rats, and extracellular signal-regulated kinase 1/2 inhibitor (U0126) was administered into diabetic rats 30 minutes before ischemia as a pretreatment. Results showed that the number of surviving neurons in the hippocampal CA1 region was reduced, extracellular signal-regulated kinase 1/2 phosphorylation and Ku70 activity were decreased, and pro-apoptotic Bax expression was upregulated after intervention using U0126. These ifndings demonstrate that inhibition of extracellular signal-regulated kinase 1/2 activity aggravated neuronal loss in the hippocampus in a diabetic rat after cerebral ischemia/reperfusion, further decreased DNA repairing ability and ac-celerated apoptosis in hippocampal neurons. Extracellular signal-regulated kinase 1/2 activation plays a neuroprotective role in hippocampal neurons in a diabetic rat after cerebral ischemia/reperfusion.

  18. Curcumin reduces inflammatory reactions following transient cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Jing Zhao; Shanshan Yu; Lan Li; Xuemei Lin; Yong Zhao

    2011-01-01

    Inflammatory reactions are important pathophysiological mechanisms of ischemic brain injury. The present study analyzed the anti-inflammatory characteristics of curcumin via myeloperoxidase activity and nitric oxide content after 2-hour ischemia/24-hour reperfusion in Sprague Dawley rats. In addition, expressions of nuclear factor kappa B, tumor necrosis factor-α and interleukin-1β protein were measured. Curcumin significantly reduced myeloperoxidase and nitric oxide synthase activities and suppressed expressions of nuclear factor kappa B, tumor necrosis factor-a, and interleukin-1β in ischemia/reperfusion brain tissue. Results suggested that the neuroprotective effect of curcumin following cerebral ischemia/reperfusion injury could be associated with inhibition of inflammatory reactions.

  19. Protective effects of iptakalim, a novel ATP-sensitive potassium channel opener, on global cerebral ischemia-evoked insult in gerbils

    Institute of Scientific and Technical Information of China (English)

    Hua CHEN; Yong YANG; Hong-hong YAO; Xing-chun TANG; Jian-hua DING; Hai WANG; Gang HU

    2006-01-01

    Aim: To investigate the protective role of iptakalim, a novel ATP sensitive potassium channel opener, on global cerebral ischemia-evoked insult in gerbils and glutamate-induced PC 12 cell injury. Methods: Global cerebral ischemia was induced by occluding the bilateral common carotid arteries in gerbils for 5 min. The open field maze and T-maze were employed to investigate the experimental therapeutic value of iptakalim on ischemic brain insult (n=8). The pyramidal cells in the hippocampal CA1 regions were counted to assess the protective effects of iptakalim. Glutamate released from the gerbil hippocampus and PC 12 cells were determined by HPLC. Intracellular calcium was measured by Fluo-3 AM with A Bio-Rad Radiance 2100TM confocal system in conjunction with a Nikon TE300 microscope. Astrocyte glutamate uptake measurements were determined by liquid scintillation counting. Results: Iptakalim (0.5-4.0 mg/kg per day, ip) could reduce the high locomotor activity evoked by ischemia and improve global cerebral ischemia-induced working memory impairments. Histological studies revealed that iptakalim could increase the survival neuron in the hippocampus CA1 zone in a dose-dependent manner. Moreover, iptakalim could reverse ischemia-evoked increases of glutamate in the hippocampus of gerbils. In an in vitro study, iptakalim protected PC 12 cells against glutamate-induced excitotoxicity, reduced the [Ca2+]; increases, and enhanced the glutamate uptake activity of primary cultured astrocytes. Conclusions: Iptakalim plays a key role in preventing global cerebral ischemia-evoked insults in gerbils and glutamate-induced PC12 cell injury by anti-excitotoxicity. Iptakalim might be a promising novel candidate for the prevention and/or treatment of stroke.

  20. Targeting reactive nitrogen species: a promising therapeutic strategy for cerebral ischemia-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Xing-miao CHEN; Han-sen CHEN; Ming-jing XU; Jian-gang SHEN

    2013-01-01

    Ischemic stroke accounts for nearly 80% of stroke cases.Recanalization with thrombolysis is a currently crucial therapeutic strategy for re-building blood supply,but the thrombolytic therapy often companies with cerebral ischemia-reperfusion injury,which are mediated by free radicals.As an important component of free radicals,reactive nitrogen species (RNS),including nitric oxide (NO) and peroxynitrite (ONO0ˉ),play important roles in the process of cerebral ischemia-reperfusion injury.Ischemia-reperfusion results in the production of nitric oxide (NO) and peroxynitrite (ONOOˉ) in ischemic brain,which trigger numerous molecular cascades and lead to disruption of the blood brain barrier and exacerbate brain damage.There are few therapeutic strategies available for saving ischemic brains and preventing the subsequent brain damage.Recent evidence suggests that RNS could be a therapeutic target for the treatment of cerebral ischemia-reperfusion injury.Herein,we reviewed the recent progress regarding the roles of RNS in the process of cerebral ischemic-reperfusion injury and discussed the potentials of drug development that target NO and ONO0ˉ to treat ischemic stroke.We conclude that modulation for RNS level could be an important therapeutic strategy for preventing cerebral ischemiareperfusion injury.

  1. Expression profiles of microRNAs after focal cerebral ischemia/reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    Fengguo Zhai; Xiuping Zhang; Yue Guan; Xudong Yang; Yang Li; Gaochen Song; Lixin Guan

    2012-01-01

    Rat models of focal cerebral ischemia/reperfusion injury were established by occlusion of the middle cerebral artery. Microarray analysis showed that 24 hours after cerebral ischemia, there were nine up-regulated and 27 down-regulated microRNA genes in cortical tissue. Bioinformatic analysis showed that bcl-2 was the target gene of microRNA-384-5p and microRNA-494, and caspase-3 was the target gene of microRNA-129, microRNA-320 and microRNA-326. Real-time PCR and western blot analyses showed that 24 hours after cerebral ischemia, bcl-2 mRNA and protein levels in brain tissue were significantly decreased, while caspase-3 mRNA and protein levels were significantly increased. This suggests that following cerebral ischemia, differentially expressed microRNA-384-5p, microRNA-494, microRNA-320, microRNA-129 and microRNA-326 can regulate bcl-2 and caspase-3 expression in brain tissue.

  2. STUDY ON THE EFFECT OF ACUPUNCTURE ON CEREBRAL ISCHEMIA IN MICE

    Institute of Scientific and Technical Information of China (English)

    马瑞玲; 袁青

    2003-01-01

    Objective: To explore the possible mechanisms of "JIN San Zhen" (JIN's 3-acupoints-groups) intreatment of mental retardation. Methods: A total of 38 female mice were randomly divided into normal control (n=10), sham-operation (n= 10), model (n=8) and acupuncture (n= 10) groups. "Si Shen Zhen" [4 points around"Baihui" (GV 20): 0.3 cm anterior, posterior, left and right to GV-20 respectively], and "Zhi San Zhen" ["Shenting"(GV 24) and bilateral "Benshen" (GB 13)] of "JIN San Zhen" series are used. The memory ability, AChE positivefiber density and mono-amines transmitters of the brain are used as the indexes. Resultss: After 8 days' treatment,cerebral ischemia induced mental retardation (decline of learning-memory ability) was improved significantly shown byY-maze-test (P< 0.05- 0.01 ), simultaneously, AChE-positive fiber density of the frontal cerebral cortex and hip-pocampus, serotonie (5-HT), noradrenaline (NA) and dopamine (DA) contents of the brain increased significantly(P< 0.05). Conclusion: Acupuncture induced increase of AChE, 5-HT, NA and DA in the brain may contribute to theeffect of acupuncture in improving the memory capability of the RD mice.

  3. Anti-Inflammatory Effects of Total Isoflavones from Pueraria lobata on Cerebral Ischemia in Rats

    Directory of Open Access Journals (Sweden)

    In-Ho Kim

    2013-08-01

    Full Text Available Puerariae radix, the dried root of Pueraria lobata Ohwi, is one of earliest and most important edible crude herbs used for various medical purposes in Oriental medicine. The aim of the present study was to determine the anti-inflammatory effects of Total Isoflavones from P. lobata (TIPL, which contains the unique isoflavone puerarin, in ischemia in vivo models. Oral administration of TIPL (100 mg/kg reduced the brain infarct volume and attenuated ischemia-induced cyclooxygenase-2 (COX-2 up-regulation at 2 days after middle cerebral artery occlusion (MCAo in rats. Moreover, TIPL reduced activation of glial fibrillary acid protein (GFAP and CD11b antibody (OX-42 at 7 days after MCAo in hippocampal CA1 region. These results show that TIPL can protect the brain from ischemic damage after MCAo. Regarding the immunohistochemical study, the effects of TIPL may be attributable to its anti-inflammatory properties by the inhibition of COX-2 expression, astrocyte expression, and microglia.

  4. Pretreatment with scutellaria baicalensis stem-leaf total lfavonoid protects against cerebral ischemia/reperfusion injur y in hippocampal neurons

    Institute of Scientific and Technical Information of China (English)

    Xiangyu Kong; Wei Kong; Guangxin Miao; Shumin Zhao; Meng Chen; Xiaoying Zheng; Jiangtao Bai

    2014-01-01

    Previous experimental studies have shown that cerebral infarction can be effectively reduced following treatment with scutellaria baicalensis stem-leaf total lfavonoid (SSTF). However, the mechanism of action of SSTF as a preventive drug to treat cerebral infarction remains unclear. In this study, Sprague-Dawley rats were pretreated with 50, 100, 200 mg/kg SSTF via intragastric ad-ministration for 1 week prior to the establishment of focal cerebral ischemia/reperfusion injury. The results showed that pretreatment with SSTF effectively improved neurological function, re-duced brain water content and the permeability of blood vessels, ameliorated ischemia-induced morphology changes in hippocampal microvessels, down-regulated Fas and FasL protein expres-sion, elevated the activity of superoxide dismutase and glutathione peroxidase, and decreased malondialdehyde content. In contrast to low-dose SSTF pretreatment, the above changes were most obvious after pretreatment with moderate-and high-doses of SSTF. Experimental ifndings indicate that SSTF pretreatment can exert protective effects on the brain against cerebral isch-emia/reperfusion injury. The underlying mechanisms may involve reducing brain water content, increasing microvascular recanalization, inhibiting the apoptosis of hippocampal neurons, and attenuating free radical damage.

  5. Repeated short-term daily exercise ameliorates oxidative cerebral damage and the resultant motor dysfunction after transient ischemia in rats.

    Science.gov (United States)

    Hamakawa, Michiru; Ishida, Akimasa; Tamakoshi, Keigo; Shimada, Haruka; Nakashima, Hiroki; Noguchi, Taiji; Toyokuni, Shinya; Ishida, Kazuto

    2013-07-01

    Long-term exercise prior to brain ischemia enhances the activities of antioxidant enzymes and leads to a significant reduction in brain damage and neurological deficits in rats subjected to transient middle cerebral artery occlusion. However, it has not been established whether relatively short-term exercise generates similar results following middle cerebral artery occlusion. We aimed to determine whether short-term exercise could reduce oxidative damage and prevent sensori-motor dysfunction. Male Wistar rats were subjected to perform daily exercise on a treadmill for 30 min at a speed of 15 m/min for 3 weeks, followed by a 90-min middle cerebral artery occlusion. Animals were assessed after middle cerebral artery occlusion for neurological deficits and sensori-motor function. Brain tissues were processed to evaluate infarct volume and oxidative damage. Oxidative stress was assessed using immunohistochemistry for 4-hydroxy-2-nonenal-modified proteins and 8-hydroxy-2'-deoxyguanosine. Antioxidant enzymes were evaluated using immunohistochemistry for thioredoxin and activity assay for superoxide dismutase. Exercise for 3 weeks decreased the severity of paralysis and impairment in forelimb motor coordination. Furthermore, exercise had effect on superoxide dismutase and reduced the infarct volume and the number of cells immunopositive for 4-hydroxy-2-nonenal-modified proteins and 8-hydroxy-2'-deoxyguanosine. Our results suggest that pre-conditioning treadmill exercise for 3 weeks is useful for ameliorating ischemia-induced brain injury. PMID:23874064

  6. Acute embolic cerebral ischemia as an initial presentation of polycythemia vera: a case report

    OpenAIRE

    Zoraster, Richard M; Rison, Richard A

    2013-01-01

    Introduction Patients with polycythemia vera are at high risk for vaso-occlusive events including cerebral ischemia. Although unusual, acute ischemic stroke may be an initial presentation of polycythemia vera. It had been previously assumed that cerebral ischemic events were due to increased blood viscosity and platelet activation within the central nervous system arterial vessels. However, there are now a few isolated case reports of probable micro-embolic events originating from outside of ...

  7. Electroencephalographic response to sodium nitrite may predict delayed cerebral ischemia after severe subarachnoid hemorrhage

    OpenAIRE

    Garry, Payashi S.; Rowland, Matthew J.; Ezra, Martyn; Herigstad, Mari; Hayen, Anja; Sleigh, Jamie W.; Westbrook, Jon; Warnaby, Catherine E; Pattinson, Kyle T.

    2016-01-01

    OBJECTIVES: Aneurysmal subarachnoid hemorrhage often leads to death and poor clinical outcome. Injury occurring during the first 72 hours is termed "early brain injury," with disruption of the nitric oxide pathway playing an important pathophysiologic role in its development. Quantitative electroencephalographic variables, such as α/δ frequency ratio, are surrogate markers of cerebral ischemia. This study assessed the quantitative electroencephalographic response to a cerebral nitric oxide...

  8. Autophagy Upregulation and Apoptosis Downregulation in DAHP and Triptolide Treated Cerebral Ischemia

    OpenAIRE

    Yang Yang; Keqiang Gao; Zhiying Hu; Weiyun Li; Henry Davies; Shucai Ling; Rudd, John A.; Marong Fang

    2015-01-01

    It has previously been demonstrated that ischemic stroke activates autophagy pathways; however, the mechanism remains unclear. The aim of this study is to further investigate the role that autophagy plays in cerebral ischemia. 2, 4-diamino-6-hydroxy-pyrimidine (DAHP), for its nitric oxide synthase (NOS) inhibiting neuroprotective effect, and triptolide (TP), for its anti-inflammatory property, were selected to administer pre middle cerebral artery occlusion (MCAO). The drugs were administered...

  9. Severe instead of mild hyperglycemia inhibits neurogenesis in the subventricular zone of adult rats after transient focal cerebral ischemia.

    Science.gov (United States)

    Tan, S; Zhi, P K; Luo, Z K; Shi, J

    2015-09-10

    Accumulated evidence suggests that enhanced neurogenesis stimulated by ischemic injury contributes to stroke outcome. However, it is unclear whether hyperglycemia, which is frequently tested positive in patients with acute ischemic stroke, influences stroke-induced neurogenesis. The aim of the present study is to examine the effect of hyperglycemia on stroke-induced neurogenesis in a rat model of transient focal cerebral ischemia. For this purpose, adult male Sprague-Dawley rats (220-250 g) were subjected to 90 min of middle cerebral artery occlusion (MCAO). Glucose was administered during ischemia to produce target blood levels ranging from 4.83 ± 0.94 mM (normoglycemia) to 20.76 ± 1.56 mM. To label proliferating cells in ischemic ipsilateral subventricular zone (SVZ) of lateral ventricles, 5'-bromo-2'-deoxyuridine (BrdU) was injected 24h after MCAO. Brains were harvested 2h post-BrdU to evaluate the effects of hyperglycemia on infarct volume and SVZ cell proliferation. Rats that were severely hyperglycemic (19.26 ± 1.48 mM to 20.76 ± 1.56 mM) during ischemia had 24.26% increase in infarct volume (Pneurogenesis by a mechanism involving suppression of CREB and BDNF signaling. PMID:26126927

  10. Protective effects of mangiferin on cerebral ischemia-reperfusion injury and its mechanisms.

    Science.gov (United States)

    Yang, Zhang; Weian, Chen; Susu, Huang; Hanmin, Wang

    2016-01-15

    The aim of our study was to investigate the protective properties of mangiferin, a natural glucosyl xanthone found in both mango and papaya on the cerebral ischemia-reperfusion injury and the underlying mechanism. Wistar male rats were subjected to middle cerebral artery occlusion for 2h followed by 24h of reperfusion. Mangiferin (25, 50, and 100mg/kg, ig) or 0.5% carboxymethyl cellulose sodium was administered three times before ischemia and once at 2h after the onset of ischemia. Neurological score, infarct volume, and brain water content, some oxidative stress markers and inflammatory cytokines were evaluated after 24h of reperfusion. Treatment with mangiferin significantly ameliorated neurologic deficit, infarct volume and brain water content after cerebral ischemia reperfusion. Mangiferin also reduced the content of malondialdehyde (MDA), IL-1β and TNF-α, and up-regulated the activities of superoxide dismutase (SOD), glutathione (GSH) and IL-10 levels in the brain tissue of rats with the cerebral ischemia-reperfusion injury. Moreover, mangiferin up-regulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream anti-oxidant protein heme oxygenase-1 (HO-1). The results indicate that mangiferin can play a certain protective role in the cerebral ischemia-reperfusion injury, and the protective effect of mangiferin may be related to the improvement on the antioxidant capacity of brain tissue and the inhibition of overproduction of inflammatory cytokines. The mechanisms are associated with enhancing the oxidant defense systems via the activation of Nrf2/HO-1 pathway. PMID:26656757

  11. Blood gases and energy metabolites in mouse blood before and after cerebral ischemia: the effects of anesthetics.

    Science.gov (United States)

    Schwarzkopf, Tina M; Horn, Tobias; Lang, Dorothee; Klein, Jochen

    2013-01-01

    The levels of blood gases and energy metabolites strongly influence the outcome of animal experiments, for example in experimental stroke research. While mice have become prominent animal models for cerebral ischemia, little information is available on the effects of anesthetic drugs on blood parameters such as blood gases, glucose and lactate in this species. In this work, we collected arterial and venous blood samples from female CD-1 mice before and after cerebral ischemia induced by middle cerebral artery occlusion (MCAO), and we tested the influence of different anesthetic drugs. We found that all of the injectable anesthetics tested (ketamine/xylazine, chloral hydrate, propofol and pentobarbital) caused a decrease in blood pH and partial pressure of oxygen (pO2) and an increase of partial pressure of carbon dioxide (pCO2), indicating respiratory depression. This was not observed with inhalable anesthetics such as isoflurane, sevoflurane and halothane. Significant and up to two-fold increases of blood glucose concentration were observed under isoflurane, halothane, ketamine/xylazine, chloral hydrate, and propofol anesthesia. Lactate concentration rose significantly by 2-3-fold during inhalation of isoflurane and halothane treatment, but decreased by more than 50% after administration of pentobarbital. Permanent cerebral ischemia induced respiratory acidosis (low pH and pO2, high pCO2) which was most prominent after 24 h. Postsurgical treatment with Ringer-lactate solution (1 mL, intraperitoneal) caused a recovery of blood gases to basal levels after 24 h. Use of isoflurane for surgery caused a minor increase of blood glucose concentrations after one hour, but a strong increase of blood lactate. In contrast, anesthesia with pentobarbital did not affect glucose concentration but strongly reduced blood lactate concentrations one hour after surgery. All values recovered at three hours after MCAO. In conclusion, anesthetic drugs have a strong influence on murine

  12. Exercise induces mitochondrial biogenesis after brain ischemia in rats.

    Science.gov (United States)

    Zhang, Q; Wu, Y; Zhang, P; Sha, H; Jia, J; Hu, Y; Zhu, J

    2012-03-15

    Stroke is a major cause of death worldwide. Previous studies have suggested both exercise and mitochondrial biogenesis contribute to improved post-ischemic recovery of brain function. However, the exact mechanism underlying this effect is unclear. On the other hand, the benefit of exercise-induced mitochondrial biogenesis in brain has been confirmed. In this study, we attempted to determine whether treadmill exercise induces functional improvement through regulation of mitochondrial biogenesis after brain ischemia. We subjected adult male rats to ischemia, followed by either treadmill exercise or non-exercise and analyzed the effect of exercise on the amount of mitochondrial DNA (mtDNA), expression of mitochondrial biogenesis factors, and mitochondrial protein. In the ischemia-exercise group, only peroxisome proliferator activated receptor coactivator-1 (PGC-1) expression was increased significantly after 3 days of treadmill training. However, after 7 days of training, the levels of mtDNA, nuclear respiratory factor 1, NRF-1, mitochondrial transcription factor A, TFAM, and the mitochondrial protein cytochrome C oxidase subunit IV (COXIV) and heat shock protein-60 (HSP60) also increased above levels observed in non-exercised ischemic animals. These changes followed with significant changes in behavioral scores and cerebral infarct volume. The results indicate that exercise can promote mitochondrial biogenesis after ischemic injury, which may serve as a novel component of exercise-induced repair mechanisms of the brain. Understanding the molecular basis for exercise-induced neuroprotection may be beneficial in the development of therapeutic approaches for brain recovery from the ischemic injury. Based upon our findings, stimulation or enhancement of mitochondrial biogenesis may prove a novel neuroprotective strategy in the future. PMID:22266265

  13. Effects of acupoint versus non-acupoint electroacupuncture on cerebral cortical neuronal Bcl-2,Bax and caspase-3 expression in a rat model of focal cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Jun Wang; Junming Fan; Yongshu Dong; Xia Huang; Hongxia Zhang

    2008-01-01

    BACKGROUND: Several studies have demonstrated that electroacupuncture by acupoint selection can inhibit cerebral cortical neuronal apoptosis following cerebral ischemia/reperfusion.OBJECTIVE: To validate the effects of electroacupuncture by acupoint selection on the expression level of cortical neuronal anti-apoptotic Bcl-2 protein and the apoptotic executive protein, caspase-3, in rat models of focal cerebral ischemia/reperfusion.DESIGN, TIME AND SETTING: This randomized grouping, neural cell and molecular biology animal experiment was performed at the Laboratory of Pharmacology of Traditional Chinese Medicine and the Laboratory Animal Center of Henan Institute of Traditional Chinese Medicine between November 2006 and May 2007.MATERIALS: Atotal of 40 healthy male adult Sprague-Dawley rats were randomly and evenly divided into four groups: sham-operated, model, electroacupuncture and non-acupoint control. G6895 electro-acupuncture instruments were purchased from Shanghai Huayi Instrument Factory, China. Caspase-3, Bcl-2 and Bax kits were provided by Wuhan Boster Bioengineering Co., Ltd., China.METHODS: Middle cerebral artery occlusion was induced in the model, electroacupuncture and non-acupoint groups. In the electroacupuncture group, the acupoints Jianyu (LI15), Waiguan (SJ5), Biguan (ST31), and Zusanli (ST36) were given electroacupuncture. In the non-acupoint control group, at each time point (immediately after ischemia and after reperfusion, or 2 hours after reperfusion), electroacupuncture was performed at the midpoints of Tianquan (PC2)-Quze (PC 3) line, Quze (PC 3)-Ximen (PC4) line, Zuwuli (LRlO)-Yinbao (LRg) line, and Xiguan (LR7)-Zhongdu (LR6) line. Electroacupuncture parameters were set with a continuous wave with a frequency of 10 Hz, wave width 0.6 ms, voltage 1.5-3.0 V, and a duration of 10 minutes. The sham-operated and model groups received only animal fixation without electroacupuncture procedure.MAIN OUTCOME MEASURES: Five rats were selected from

  14. Diet Induced Obesity Causes Cerebral Vessel Remodeling and Increases the Damage Caused by Ischemic Stroke

    OpenAIRE

    Deutsch, Christian; Portik-Dobos, Vera; Smith, Anita D; Ergul, Adviye; Dorrance, Anne M.

    2009-01-01

    Hypertension, elevated fasting blood glucose and plasma insulin develop in rats fed a high fat (HF) diet. Our goal was to assess the effects of obesity, beginning in childhood, on the adult cardiovascular system. We hypothesized that rats fed a HF diet would have larger ischemic cerebral infarcts and middle cerebral artery (MCA) remodeling. Three-week-old male Sprague Dawley rats were fed a HF (Obese) or control diet for 10 weeks. Cerebral ischemia was induced by MCA occlusion (MCAO). MCA str...

  15. Hypoxic ischemia encephalopathy leading to external hydrocephalus and the cerebral atrophy: mechanism and differential diagnosis

    International Nuclear Information System (INIS)

    Objective: It is a study of the mechanism and differential diagnosis of the infant external hydrocephalus and cerebral atrophy. Methods: In total 84 cases of neonatal hypoxic ischemia encephalopathy followed by infant external hydrocephalus were investigated, among which 26 patients gradually were found having developed cerebral atrophy in follow up. Results: Characteristic dilation of the frontal-parietal subarachnoid space and the adjacent cistern was noted on the CT images of the external hydrocephalus. CT revealed the enlarged ventricle besides the dilated subarachnoid space in the cases of cerebral atrophy, while these two entities were indistinguishable on CT in the early stage. Conclusion: Clinical manifestations make a major differential diagnosis of the external hydrocephalus and cerebral atrophy: tic and mild delayed development of locomotion over major presentation of external hydrocephalus, while cerebral atrophy is featured by remarkable dysnoesia and severe delayed development of locomotion. In addition, hemiplegia and increased muscular tension are presented in a few cases of cerebral atrophy

  16. Focal Cerebral Ischemia Model by Endovascular Suture Occlusion of the Middle Cerebral Artery in the Rat

    OpenAIRE

    Uluç, Kutluay; Miranpuri, Amrendra; Kujoth, Gregory C.; Aktüre, Erinç; Başkaya, Mustafa K.

    2011-01-01

    Stroke is the leading cause of disability and the third leading cause of death in adults worldwide1. In human stroke, there exists a highly variable clinical state; in the development of animal models of focal ischemia, however, achieving reproducibility of experimentally induced infarct volume is essential. The rat is a widely used animal model for stroke due to its relatively low animal husbandry costs and to the similarity of its cranial circulation to that of humans2,3. In humans, the mid...

  17. Pretreatment with scutellaria baicalensis stem-leaf total flavonoid prevents cerebral ischemia-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Shumin Zhao; Wei Kong; Shufeng Zhang; Meng Chen; Xiaoying Zheng; Xiangyu Kong

    2013-01-01

    Pretreatment with scutel aria baicalensis stem-leaf total flavonoid has protective effects against ischemia and attenuates myocardial ischemia-reperfusion injury. In this study, rats were given scu-tel aria baicalensis stem-leaf total flavonoid intragastrical y at 50, 100, and 200 mg/kg per day for 7 days before focal cerebral ischemia-reperfusion injury models were established using the suture method. We then determined the protective effects of scutel aria baicalensis stem-leaf total flavo-noid pretreatment on focal cerebral ischemia-reperfusion injury. Results showed that neurological deficit scores increased, infarct volumes enlarged, apoptosis increased and Bcl-2 and Bax protein expression were upregulated at 24 hours after reperfusion. Pretreatment with scutel aria baicalensis stem-leaf total flavonoid at any dose lowered the neurological deficit scores, reduced the infarct volume, prevented apoptosis in hippocampal cells, attenuated neuronal and blood-brain barrier damage and upregulated Bcl-2 protein expression but inhibited Bax protein expression. Doses of 100 and 200 mg/kg were the most efficacious. Our findings indicate that pretreatment with scutel a-ria baicalensis stem-leaf total flavonoid at 100 and 200 mg/kg can improve the neurological func-tions and have preventive and protective roles after focal cerebral ischemia-reperfusion injury.

  18. CSF and Serum Biomarkers Focusing on Cerebral Vasospasm and Ischemia after Subarachnoid Hemorrhage

    Directory of Open Access Journals (Sweden)

    Carla S. Jung

    2013-01-01

    Full Text Available Delayed cerebral vasospasm (CVS and delayed cerebral ischemia (DCI remain severe complications after subarachnoid hemorrhage (SAH. Although focal changes in cerebral metabolism indicating ischemia are detectable by microdialysis, routinely used biomarkers are missing. We therefore sought to evaluate a panel of possible global markers in serum and cerebrospinal fluid (CSF of patients after SAH. CSF and serum of SAH patients were analyzed retrospectively. In CSF, levels of inhibitory, excitatory, and structural amino acids were detected by high-performance liquid chromatography (HPLC. In serum, neuron-specific enolase (NSE and S100B level were measured and examined in conjunction with CVS and DCI. CVS was detected by arteriography, and ischemic lesions were assessed by computed tomography (CT scans. All CSF amino acids were altered after SAH. CSF glutamate, glutamine, glycine, and histidine were significantly correlated with arteriographic CVS. CSF glutamate and serum S100B were significantly correlated with ischemic events after SAH; however, NSE did not correlate neither with ischemia nor with vasospasm. Glutamate, glutamine, glycine, and histidine might be used in CSF as markers for CVS. Glutamate also indicates ischemia. Serum S100B, but not NSE, is a suitable marker for ischemia. These results need to be validated in larger prospective cohorts.

  19. CSF and Serum Biomarkers Focusing on Cerebral Vasospasm and Ischemia after Subarachnoid Hemorrhage

    Science.gov (United States)

    Jung, Carla S.; Lange, Bettina; Zimmermann, Michael; Seifert, Volker

    2013-01-01

    Delayed cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI) remain severe complications after subarachnoid hemorrhage (SAH). Although focal changes in cerebral metabolism indicating ischemia are detectable by microdialysis, routinely used biomarkers are missing. We therefore sought to evaluate a panel of possible global markers in serum and cerebrospinal fluid (CSF) of patients after SAH. CSF and serum of SAH patients were analyzed retrospectively. In CSF, levels of inhibitory, excitatory, and structural amino acids were detected by high-performance liquid chromatography (HPLC). In serum, neuron-specific enolase (NSE) and S100B level were measured and examined in conjunction with CVS and DCI. CVS was detected by arteriography, and ischemic lesions were assessed by computed tomography (CT) scans. All CSF amino acids were altered after SAH. CSF glutamate, glutamine, glycine, and histidine were significantly correlated with arteriographic CVS. CSF glutamate and serum S100B were significantly correlated with ischemic events after SAH; however, NSE did not correlate neither with ischemia nor with vasospasm. Glutamate, glutamine, glycine, and histidine might be used in CSF as markers for CVS. Glutamate also indicates ischemia. Serum S100B, but not NSE, is a suitable marker for ischemia. These results need to be validated in larger prospective cohorts. PMID:23509668

  20. Spreading Depolarizations: A Therapeutic Target Against Delayed Cerebral Ischemia After Subarachnoid Hemorrhage.

    Science.gov (United States)

    Chung, David Y; Oka, Fumiaki; Ayata, Cenk

    2016-06-01

    Delayed cerebral ischemia is the most feared cause of secondary injury progression after subarachnoid hemorrhage. Initially thought to be a direct consequence of large artery spasm and territorial ischemia, recent data suggests that delayed cerebral ischemia represents multiple concurrent and synergistic mechanisms, including microcirculatory dysfunction, inflammation, and microthrombosis. Among these mechanisms, spreading depolarizations (SDs) are arguably the most elusive and underappreciated in the clinical setting. Although SDs have been experimentally detected and examined since the late 1970s, their widespread occurrence in human brain was not unequivocally demonstrated until relatively recently. We now know that SDs occur with very high incidence in human brain after ischemic or hemorrhagic stroke and trauma, and worsen outcomes by increasing metabolic demand, decreasing blood supply, predisposing to seizure activity, and possibly worsening brain edema. In this review, we discuss the causes and consequences of SDs in injured brain. Although much of our mechanistic knowledge comes from experimental models of focal cerebral ischemia, clinical data suggest that the same principles apply regardless of the mode of injury (i.e., ischemia, hemorrhage, or trauma). The hope is that a better fundamental understanding of SDs will lead to novel therapeutic interventions to prevent SD occurrence and its adverse consequences contributing to injury progression in subarachnoid hemorrhage and other forms of acute brain injury. PMID:27258442

  1. Enhanced autophagy signaling in diabetic rats with ischemia-induced seizures.

    Science.gov (United States)

    Xia, Luoxing; Lei, Zhigang; Shi, Zhongshan; Guo, Dave; Su, Henry; Ruan, Yiwen; Xu, Zao C

    2016-07-15

    Seizures are among the most common neurological sequelae of stroke, and ischemic insult in diabetes notably increases the incidence of seizures. Recent studies indicated that autophagy influences the outcome of stroke and involved in epileptogenesis. However, the association of autophagy and post-ischemic seizures in diabetes remains unclear. The present study aimed to reveal the involvement of autophagy in the seizures following cerebral ischemia in diabetes. Diabetes was induced in adult male Wistar rats by intraperitoneal injection of streptozotocin (STZ). The diabetic rats were subjected to transient forebrain ischemia. The neuronal damage was assessed using hematoxylin-eosin staining. Western blotting and immunohistochemistry were performed to investigate the alteration of autophagy marker microtubule-associated protein light chain 1B (LC3B). The results showed that all diabetic animals developed seizures after ischemia. However, no apparent cell death was observed in the hippocampus of seizure rats 12h after the insult. The expression of LC3B was significantly enhanced in naïve animals after ischemia and was further increased in diabetic animals after ischemia. Immunofluorescence double-labeling study indicated that LC3B was mainly increased in neurons. Our study demonstrated, for the first time, that autophagy activity is significantly increased in diabetic animals with ischemia-induced seizures. Further studies are needed to explore the role of autophagy in seizure generation after ischemia in diabetic conditions. PMID:27125597

  2. Protective effect of rhMG53 protein on a focal cerebral ischemia/reperfusion in a rat model

    Directory of Open Access Journals (Sweden)

    Yong-gang YAO

    2014-08-01

    Full Text Available Objective To identify the protective effect of rhMG53 (exogenous recombinant human MG53 protein on focal cerebral ischemia/reperfusion injury in a rat model. Methods The cerebral ischemia reperfusion model was reproduced in SD rats using middle cerebral artery occlusion (MCAO method, and the rats were then randomly divided into sham operation group, ischemia reperfusion group, and ischemia reperfusion+rhMG53 group (n=7. The Zea-Longa score of nervous system, brain tissue TTC staining and pathological sections were observed. Result Compared with the ischemia reperfusion group, nerve dysfunction was improved obviously in ischemia reperfusion+rhMG53 group. The area of cerebral infarction was reduced, and the extent of brain tissue necrosis was alleviated. Furthermore, the protective effect showed a relation with the treatment time. The time-window of effective protection of exogenous rhMG53 on cerebral ischemia reperfusion injury was within 4 hours. Conclusion The exogenous rhMG53 may have an effective protective effect on focal cerebral ischemia reperfusion injury. DOI: 10.11855/j.issn.0577-7402.2014.06.03

  3. Minocycline inhibits 5-lipoxygenase activation and brain inflammation after focal cerebral ischemia in rats

    Institute of Scientific and Technical Information of China (English)

    Li-sheng CHU; San-hua FANG; Yu ZHOU; Guo-hang YU; Meng-ling WANG; Wei-ping ZHANG; Er-qing WEI

    2007-01-01

    Aim: To determine whether the anti-inflanunatory effect of minocycline on postis-chemic brain injury is mediated by the inhibition of 5-lipoxygenase (5-LOX) expression and enzymatic activation in rats.Methods: Focal cerebral ischemia was induced for 30 min with middle cerebral artery occlusion, followed by reperfusion. The ischemic injuries, endogenous IgG exudation, the accumulation of neutrophils and macrophage/microglia, and 5-LOX mRNA expression were determined 72 h after reperfusion. 5-LOX metabolites (leukotriene B4 and cysteinyl leukotrienes) were measured 3 h after reperfusion.Results: Minocycline (22.5 and 45 mg/kg, ip, for 3 d) attenuated ischemic injuries, IgG exudation, and the accumulation of neutrophils and macrophage/microglia 72 h after reperfusion. It also inhibited 5-LOX expression 72 h after reperfusion and the production of leukotrienes 3 h after reperfusion.Conclusion: Minocycline inhibited postis-chemic brain inflammation, which might be partly mediated by the inhibition of 5-LOX expression and enzymatic activation.

  4. Combination of HBO and Memantine in Focal Cerebral Ischemia: Is There a Synergistic Effect?

    Science.gov (United States)

    Wang, Feng; Liang, Wei; Lei, Chong; Kinden, Renee; Sang, Hanfei; Xie, Yaning; Huang, Yi; Qu, Yan; Xiong, Lize

    2015-12-01

    Hyperbaric oxygen (HBO) therapy and memantine, a non-competitive NMDA antagonist, are both promising treatment strategies for improving stroke prognosis. However, HBO's narrow therapeutic time window (HBO treatment. Transient focal cerebral ischemia was induced in male Sprague-Dawley rats by middle cerebral artery occlusion (MCAO) for 120 min. MCAO produced neurobehavioral deficits, increased infarction volume, increased Evans blue (EB) content and levels of pro-inflammatory factors, as well as depleted glutathione (GSH), and reduced catalase (CAT) and superoxide dismutase (SOD) activity in the ischemic ipsilateral hemisphere. The combination of 5 mg/kg MEM treatment 15 min after the onset of ischemic event and HBO therapy 12 h post-reperfusion significantly restored neurologic scores, EB concentration and IL-10 levels, as well as significantly decreased infarct volume and increased antioxidant activity. These results imply that the combination of MEM and HBO therapy not only prolongs the therapeutic window of HBO treatment, but also lowers the dosage requirement of MEM. The mechanism underlying the neuroprotective effects of the combined treatment may lie in alleviated blood-brain barrier (BBB) permeability, inhibited inflammatory response, and up-regulation of the antioxidant enzyme activity. PMID:25352446

  5. Reactive Hippocampal Astrocytes Display an Increased Expression of Trpv4 Channels After Cerebral Hypoxia/Ischemia

    Czech Academy of Sciences Publication Activity Database

    Butenko, Olena; Džamba, Dávid; Prajerová, Iva; Benešová, Jana; Honsa, Pavel; Benfenati, V.; Ferroni, S.; Anděrová, Miroslava

    2011-01-01

    Roč. 59, Supplement 1 (2011), S126-S127. ISSN 0894-1491. [European meeting on Glial Cells in Health and Disease /10./. 13.09.2011-17.09.2011, Prague] Institutional research plan: CEZ:AV0Z50390703; CEZ:AV0Z50520701 Keywords : TRPV4 * astrocytes * cerebral hypoxia/ ischemia Subject RIV: FH - Neurology

  6. Mild focal cerebral ischemia in the rat. The effect of local temperature on infarct size

    DEFF Research Database (Denmark)

    Hildebrandt-Eriksen, Elisabeth S; Christensen, Thomas; Diemer, Nils Henrik

    2002-01-01

    We aimed at investigating a new model of mild focal cerebral ischemia in rats with repeated, noninvasive magnetic resonance scanning combined with histology. Magnetic resonance imaging yielded information about infarct development enabling us to test the putative growth of the infarct over time. ...

  7. Baicalin and jasminoidin effects on gene expression and compatibility in the hippocampus following focal cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Lin Guo; Fanyun Meng; Guodong Zhang; Jing Zhao; Zhanjun Zhang; Caixiu Zhou; Zhong Wang

    2011-01-01

    The compound traditional Chinese medicine Qingkailing, which is an ingredient used to treat cerebral ischemia, has been limited to studies concerning single genes or single pathways.Interactions and pharmacological mechanisms of the compound ingredients (baicalin and jasminoidin) remain poody understood.In the present study, baicalin and jasminoidin, as well as the combination, were used to separately treat mouse models of cerebral ischemia, cDNA microarray analyses of 374 cerebral ischemia-related genes were utilized to determine changes in gene-expression profiles.Arraytrack 3.40 and Ingenuity Pathway Analysis (IPA) databases were utilized to analyze changes in gene molecular functions and network path functions.Baicalin or jasminoidin alone effectively reduced infarct area, and the combination resulted in significantly better outcomes.IPA showed inhibited cell apoptosis in the baicalin group and Ca2+ channel regulation in the jasminoidin group.The combination of baicalin and jasminoidin activated HTR3A and F5 expression, regulated Ca2+ channels, activated kappa light polypeptide gene enhancer inhibitor IKBKG in B cells to control IkB kinase/nuclear factor-kB cascade, suppressed activation of inflammatory cytokine interleukin-6 receptors and activated transduction of guanine-nucleotide-binding protein (G protein) signal.Results suggested that the combination of baicalin and jasminoidin resulted in similar molecular mechanisms to baicalin and jasminoidin alone.However,novel pharmacological actions of compatibility were detected, demonstrating significant protection against cerebral ischemia.

  8. The VASOGRADE: A Simple Grading Scale for Prediction of Delayed Cerebral Ischemia After Subarachnoid Hemorrhage

    NARCIS (Netherlands)

    Oliveira Manoel, A.L. de; Jaja, B.N.; Germans, M.R.; Yan, H.; Qian, W.; Kouzmina, E.; Marotta, T.R.; Turkel-Parrella, D.; Schweizer, T.A.; Macdonald, R.L.

    2015-01-01

    BACKGROUND AND PURPOSE: Patients are classically at risk of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage. We validated a grading scale-the VASOGRADE-for prediction of DCI. METHODS: We used data of 3 phase II randomized clinical trials and a single hospital series to asses

  9. Point application with Angong Niuhuang sticker protects hippocampal and cortical neurons in rats with cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Dong-shu Zhang

    2015-01-01

    Full Text Available Angong Niuhuang pill, a Chinese materia medica preparation, can improve neurological functions after acute ischemic stroke. Because of its inconvenient application and toxic components (Cinnabaris and Realgar, we used transdermal enhancers to deliver Angong Niuhuang pill by modern technology, which expanded the safe dose range and clinical indications. In this study, Angong Niuhuang stickers administered at different point application doses (1.35, 2.7, and 5.4 g/kg were administered to the Dazhui (DU14, Qihai (RN6 and Mingmen (DU4 of rats with chronic cerebral ischemia, for 4 weeks. The Morris water maze was used to determine the learning and memory ability of rats. Hematoxylin-eosin staining and Nissl staining were used to observe neuronal damage of the cortex and hippocampal CA1 region in rats with chronic cerebral ischemia. The middle- and high-dose point application of Angong Niuhuang stickers attenuated neuronal damage in the cortex and hippocampal CA1 region, and improved the memory of rats with chronic cerebral ischemia with an efficacy similar to interventions by electroacupuncture at Dazhui (DU14, Qihai (RN6 and Mingmen (DU4. Our experimental findings indicate that point application with Angong Niuhuang stickers can improve cognitive function after chronic cerebral ischemia in rats and is neuroprotective with an equivalent efficacy to acupuncture.

  10. Caffeine reduces dipyridamole-induced myocardial ischemia

    International Nuclear Information System (INIS)

    The mechanism of action of coronary vasodilation after dipyridamole may be based on inhibition of cellular uptake of circulating endogenous adenosine. Since caffeine has been reported to be a competitive antagonist of adenosine we studied the effect of caffeine on the outcome of dipiridamole-201Tl cardiac imaging in one patient. During caffeine abstinence dipyridamole induced myocardial ischemia with down-slope ST depressions on the ECG, and reversible perfusion defects on the scintigrams. When the test was repeated 1 wk later on similar conditions, but now shortly after infusion of caffeine (4 mg/kg), the ECG showed nodepressions, and the scintigrams only slight signs of ischemia. We conclude that when caffeine abstinence is not sufficient, the widespread use of coffee and related products may be responsible for false-negative findings in dipyridamole-201Tl cardiac imaging

  11. THE EFFECT OF LIGUSTRAZINE ON NEUROGENESIS IN CORTEX AFTER FOCAL CEREBRAL ISCHEMIA IN RATS

    Institute of Scientific and Technical Information of China (English)

    邱芬; 刘勇; 张蓬勃; 康前雁; 田英芳; 陈新林; 赵建军; 祁存芳

    2006-01-01

    It has been demonstrated that there are neuralstemcells that can self-renewand differentiate intomultiple cell types[1-3]in central nervous system ofadult mammals.After cerebral ischemia,these cellscan proliferate,migrate,differentiate and partici-pate in the repair of ischemic cerebral injuries[4-6].Neural stemcells play a very i mportant role in alle-viating ischemic cerebral injuries and promotingfunctional recovery.Ligustrazine,an active ingre-dient of Ligustici,can help dilate blood vessels,i m-prove m...

  12. Mechanisms of angiogenesis in a Curculigoside A-treated rat model of cerebral ischemia and reperfusion injury.

    Science.gov (United States)

    Zhu, Haibo; He, Jie; Ye, Liang; Lin, Fei; Hou, Jian; Zhong, Yan; Jiang, Wanglin

    2015-11-01

    Curculigoside A has shown protective effects against rat cortical neuron damage in vivo. However, the molecular mechanisms through which Curculigoside A affords this protection are unclear. In the present study, we sought to elucidate the mechanisms of angiogenesis in rat aortic endothelial cells (RAEC), rat aortic smooth muscle cells (RASMC) as well as a rat model of cerebral ischemia and reperfusion injury following treatment with Curculigoside A. We examined the role of Curculigoside A on RAEC and RASMC proliferation, migration, and tube formation in vitro and in a cerebral ischemia and reperfusion injury rat model. We used the recombinant Dickkopf (DKK)-1 protein, a Wnt/β-catenin inhibitor, and the recombinant WIF-1 protein, a Wnt5a antagonist to determine mechanisms. In addition, we measured leakage of the blood-brain barrier (BBB) and tested for angiogenesis associated proteins. Our data suggest that Curculigoside A induces angiogenesis in vitro by increasing proliferation, migration and tube formation in RAEC and RASMC. The increase in Curculigoside A-induced proliferation and tube formation was counteracted by DKK-1 and WIF-1. Curculigoside A increased expression of VEGF, p-VEGFR, p-CREB, Egr-3, VCAM-1, Ang1 and Tie2 while prohibiting BBB leakage in cerebral ischemia and reperfusion injured rats. However, Cyclosporine A, a CREB inhibitor, reduced the expression of p-CREB, Egr-3, VCAM-1, Ang1 and Tie2. These data suggest that Curculigoside A induces cell proliferation and angiogenesis through the Wnt5a/β-catenin and VEGF/CREB/Egr-3/VCAM-1 signaling axis and promotes maturation and stability of new blood vessels via increasing Ang1 and Tie-2 expression. PMID:26283324

  13. EFFECT OF ELECTROACUPUNCTURE ON SERUM IL-1β AND TNF-α CONTENTS IN CEREBRAL ISCHEMIA-REPERFUSION RATS

    Institute of Scientific and Technical Information of China (English)

    陈玲; 骆明军; 明建扩; 陈邦国

    2003-01-01

    Purpose: To study the mechanism of early acupuncture treatment in resisting inflammatory injury in cerebral ischemia-reperfusion (IR) rats. Methods: A total of 120 Wistar rats were randomly divided into normal control, sham-operation, model and EA groups, and each of them were further divided into IR-12 hr, IR-24 hr and IR-48 hr subgroups, with 10 cases being in each subgroup. Cerebral ischemia was produced by occlusion of the middle cerebral artery for 0.5 hr. Shuigou (GV 26) and Baihui (GV 20) were punctured and stimulated electrically with an EA therapeutic apparatus. Serum IL-1β and tumor necrosis factor (TNF)-α contents were assayed by using radioimmunoassay.Results: Results showed that serum IL-1β and TNF-c contents of model group were significantly higher than those of normal control and sham-operation groups at IR 12 hr, 24 hr and 48 hr ( P < 0.05), meaning that following IR, the production and release of these two cytokines in the blood increased obviously; comparison between EA and model groups displayed that serum IL-1β and TNF-α levels of EA group were strikingly lower than those of model group (P<0.01),suggesting that EA stimulation can suppress IR induced increase of production and release of these two cytokines. Conclusion: EA can suppress cerebral IR induced increase of serum IL-1β and TNF-α, which may contribute to the effect of acupuncture in resisting cerebral IR injury in the treatment of stroke.

  14. Changes of cerebral blood flow in rats with acute cerebral ischemia and the effect of nitric oxide donor S-nitroso-N-acetyl-penicillamine

    Institute of Scientific and Technical Information of China (English)

    Feng Gao; Zhiqiang Yi; Guijun Lin

    2006-01-01

    BACKGROUND: Previous studies show that nitric oxide donor can increase cerebral blood flow and improve the function of neurons in cerebral ischemia, but the change does not happen in all the models of cerebral ischemia. OBJECTIVE: To observe the effects of nitric oxide donor S-nitroso-N-acetyl-penicillamine (SNAP) on the cerebral blood flow, cyclic guanosine monophosphate (cGMP) content in cerebral cortex, infarct volume and blood pressure in acute ischemic rat brain.DESIGN: A randomized and control animal experiment. SETTING: Department of Neurosurgery, Aerospace Central Hospital, Peking University. MATERIALS: Twenty-eight male Wistar rats of SPF grade, weighing 250-300 g, aged 10-12 weeks were randomly divided into control group (n =14) and SNAP-treated group (n =14). SNAP (5 mg/bottle) was provided by Beijing Chemical Reagent Company. Laser Doppler Flowmeter (FLO C1; Omegawave Inc., Tokyo, Japan) and immunoassay kit (Amersham Pharmacia Biotech, UK) were applied.METHODS: ① Model establishment: In the control group, models of cerebral ischemia were induced by ligating right common, internal and external carotid arteries; In the SNAP-treated group, models of cerebral ischemia were induced by ligating right common and external carotid arteries, followed by occluding middle cerebral artery and ligating internal carotid artery. ② Administration: In the SNAP-treated group, SNAP (100 μg/kg) was intravenously infused within 2 minutes, whereas in the control group, phosphate buffered saline (PBS, 1 mL) was intravenously infused (0.5 mL per minute). Six rats were used to measure the volume of cerebral infarction, and the other 8 rats were used to determine other indexes in each group respectively. ③ Determination of indexes: Regional cerebral blood flow (rCBF) was continuously measured by laser-Doppler flowmetry in the ischemic penumbra and contralateral cortex under the continuous monitoring of blood pressure, cGMP concentrations in brain tissue were determined

  15. The effect of Scutellaria baicalensis stem-leaf flavonoids on spatial learning and memory in chronic cerebral ischemia-induced vascular dementia of rats.

    Science.gov (United States)

    Cao, Yanjing; Liang, Lizhen; Xu, Jian; Wu, Jiali; Yan, Yongxing; Lin, Ping; Chen, Qiang; Zheng, Fengming; Wang, Qin; Ren, Qian; Gou, Zengmei; Du, Yifeng

    2016-05-01

    Flavonoids have been shown to improve cognitive function and delay the dementia progression. However, the underlying mechanisms remain elusive. In the present study, we examined the effect of Scutellaria baicalensis stem-leaf total flavonoids (SSTFs) extracted from S. baicalensis Georgi on spatial learning and memory in a vascular dementia (VaD) rat model and explored its molecular mechanisms. The VaD rats were developed by permanent bilateral occlusion of the common carotid artery. Seven days after recovery, the VaD rats were treated with either 50 or 100 mg/kg of SSTF for 60 days. The spatial learning and memory was evaluated in the Morris water maze (MWM) test. The tau hyperphosphorylation and the levels of the related protein kinases or phosphatases were examined by western blot analysis. In VaD rats, SSTF treatment at 100 mg/kg significantly reduced the escape latency in training trial in MWM test. In the probe trial, SSTF treatment increased the searching time and travel distance in the target quadrant. SSTF treatment inhibited the tau phosphorylation in both cortex and hippocampus in VaD rats. Meanwhile, SSTF reduced the activity of glycogen synthase kinase 3β and cyclin-dependent kinase 5 in VaD rats. In contrast, SSTF treatment increased the level of the protein phosphatase 2A subunit B in VaD rats. SSTF treatment significantly improved the spatial cognition in VaD rats. Our results suggest that SSTF may alleviate tau-hyperphosphorylation-induced neurotoxicity through coordinating the activity of kinases and phosphatase after a stroke. SSTF may be developed into promising novel therapeutics for VaD. PMID:27118553

  16. Correlation between lipid profile & carotid intima media thickness in cerebral ischemia.

    Science.gov (United States)

    Sengupta, Debalina; Bardhan, Jayati; Baran, Anil; Mahapatra, Singha; Banerjee, Joyshree; Rout, Jayanta Kumar

    2014-01-01

    Cerebrovascular accident or stroke is defined by an abrupt onset of neurological deficit that is attributable to a focal vascular cause. Stroke is a major cause of morbidity and mortality worldwide. This may result from brain infarction or hemorrhage. Carotid atherosclerosis is a reasonable risk factor for cerebral ischemic stroke. Deranged lipid metabolism due to various modifiable and non-modifiable risk factors leads to the pathogenesis of atherosclerosis. This study is intended to find out any association between altered lipid metabolism (Cholesterol, Triglycerides, LDL : HDL ratio) and development of cerebral ischemia. An observational case control study was conducted with 50 cases of cerebral ischemia and 50 age & sex matched healthy controls within age group 50-70 years. After inclusion of cases and controls and taking informed consent they underwent history taking, proper clinical examination & biochemical investigations (lipid profile). Then data were collected and results were statistically analyzed using Chi-square test & Independent Sample "T-test". The study showed altered lipid profile is associated with cerebral ischemia by increasing carotid intima media thickness (IMT). There was significant (p cerebral ischemic stroke thereby reducing morbidity and mortality. PMID:26215001

  17. The Hypothermic Influence on CHOP and Ero1-α in an Endoplasmic Reticulum Stress Model of Cerebral Ischemia

    DEFF Research Database (Denmark)

    Poone, Gagandip K.; Hasseldam, Henrik; Munkholm, Nina;

    2015-01-01

    ischemic stroke, we investigated whether hypothermia regulates the unfolded protein response of CHOP and Endoplas micreticulum oxidoreductin-α (Ero1-α), because Ero1-α is suggested to be a downstream CHOP target. The gene expression of CHOP and Ero1-α was measured using Quantitative-PCR (Q-PCR) in rat...... hippocampi following global cerebral ischemia, and inhypoxic pheochromocytoma cells during normothermic (37 °C) and hypothermic (31 °C)conditions. As a result of ischemia, a significant increase in expression of CHOP andEro1-α was observed after three, six and twelve hours of reperfusion following...... globalischemia. A stable increase in CHOP expression was observed throughout the time course (p < 0.01, p < 0.0001), whereas Ero1-α expression peaked at three to six hours (p < 0.0001). Induced hypothermia in hypoxia stressed PC12 cells resulted in a decreased expression of CHOP after three, six and twelve hours...

  18. Region-specific effects on brain metabolites of hypoxia and hyperoxia overlaid on cerebral ischemia in young and old rats: a quantitative proton magnetic resonance spectroscopy study

    Directory of Open Access Journals (Sweden)

    Giuliani Patricia

    2010-02-01

    Full Text Available Abstract Background Both hypoxia and hyperoxia, deregulating the oxidative balance, may play a role in the pathology of neurodegenerative disorders underlain by cerebral ischemia. In the present study, quantitative proton magnetic resonance spectroscopy was used to evaluate regional metabolic alterations, following a 24-hour hypoxic or hyperoxic exposure on the background of ischemic brain insult, in two contrasting age-groups of rats: young - 3 months old and aged - 24 months old. Methods Cerebral ischemia was induced by ligation of the right common carotid artery. Concentrations of eight metabolites (alanine, choline-containing compounds, total creatine, γ-aminobutyric acid, glutamate, lactate, myo-inositol and N-acetylaspartate were quantified from extracts in three different brain regions (fronto-parietal and occipital cortices and the hippocampus from both hemispheres. Results In the control normoxic condition, there were significant increases in lactate and myo-inositol concentrations in the hippocampus of the aged rats, compared with the respective values in the young ones. In the ischemia-hypoxia condition, the most prevalent changes in the brain metabolites were found in the hippocampal regions of both young and aged rats; but the effects were more evident in the aged animals. The ischemia-hyperoxia procedure caused less dedicated changes in the brain metabolites, which may reflect more limited tissue damage. Conclusions We conclude that the hippocampus turns out to be particularly susceptible to hypoxia overlaid on cerebral ischemia and that old age further increases this susceptibility.

  19. Middle cerebral artery flow velocity and blood flow during exercise and muscle ischemia in humans

    DEFF Research Database (Denmark)

    Jørgensen, L G; Perko, M; Hanel, B; Schroeder, T V; Secher, N H

    1992-01-01

    Changes in middle cerebral artery flow velocity (Vmean), measured by transcranial Doppler ultrasound, were used to determine whether increases in mean arterial pressure (MAP) or brain activation enhance cerebral perfusion during exercise. We also evaluated the role of "central command......," mechanoreceptors, and/or muscle "metaboreceptors" on cerebral perfusion. Ten healthy subjects performed two levels of dynamic exercise corresponding to a heart rate of 110 (range 89-134) and 148 (129-170) beats/min, respectively, and exhaustive one-legged static knee extension. Measurements were continued during 2......-2.5 min of muscle ischemia. MAP increased similarly during static [114 (102-133) mmHg] and heavy dynamic exercise [121 (104-136) mmHg] and increased during muscle ischemia after dynamic exercise. During heavy dynamic exercise, Vmean increased 24% (10-47%; P less than 0.01) over approximately 3 min despite...

  20. Impairment of neuropsychological function in patients with hemodynamic cerebral ischemia and efficacy of bypass surgery

    International Nuclear Information System (INIS)

    In order to evaluate the relation between neuropsychological functions and hemodynamic cerebral ischemia, the author analyzed neuropsychological examination and the cerebral blood flow and metabolism of patients before and after bypass surgery. Twenty-five patients were defined by clinical and laboratory criteria as suffering from hemodynamic cerebral ischemia. All patients had one or more episodes of focal cerebral ischemia due to unilateral internal carotid or middle cerebral artery occlusion. Computerized tomography scans either were normal or showed evidence of watershed infarction. Based on these criteria, superficial temporal artery-proximal middle cerebral artery anastomosis was performed. The baseline cerebral blood flow (CBF), oxygen extraction fraction (OEF), cerebral metabolic rate of oxygen (CMRO2) and cerebrovascular reserve capacity (CVRC) were studied using positron emission computerized tomography (PET) and the acetazolamide test. Neuropsychological evaluations including Hasegawa Dementia Scale-Revised, Mini-Mental State and Wechsler Adult Intelligence Scale-Revised (WAIS-R), and PET study were completed one month after the last ischemic event and 3-6 months after the operation. A significant negative correlation was observed between OEF and neuropsychological functions. Postoperative neuropsychological functions showed significant improvement. Significant correlations were observed for ΔWAIS-R (preoperative WAIS-R postoperative WAIS-R) versus preoperative CMRO2 (r=0.52), for ΔWAIS-R versus preoperative OEF (r=0.47). In view of these findings, the author concludes that elevation of OEF impairs neuropsychological functions and bypass surgery improves neuropsychological functions in patients with normal CMRO2 and elevated OEF. (author)

  1. Impairment of neuropsychological function in patients with hemodynamic cerebral ischemia and efficacy of bypass surgery

    Energy Technology Data Exchange (ETDEWEB)

    Sasoh, Masayuki [Iwate Medical Univ., Morioka (Japan). School of Medicine

    1999-08-01

    In order to evaluate the relation between neuropsychological functions and hemodynamic cerebral ischemia, the author analyzed neuropsychological examination and the cerebral blood flow and metabolism of patients before and after bypass surgery. Twenty-five patients were defined by clinical and laboratory criteria as suffering from hemodynamic cerebral ischemia. All patients had one or more episodes of focal cerebral ischemia due to unilateral internal carotid or middle cerebral artery occlusion. Computerized tomography scans either were normal or showed evidence of watershed infarction. Based on these criteria, superficial temporal artery-proximal middle cerebral artery anastomosis was performed. The baseline cerebral blood flow (CBF), oxygen extraction fraction (OEF), cerebral metabolic rate of oxygen (CMRO{sub 2}) and cerebrovascular reserve capacity (CVRC) were studied using positron emission computerized tomography (PET) and the acetazolamide test. Neuropsychological evaluations including Hasegawa Dementia Scale-Revised, Mini-Mental State and Wechsler Adult Intelligence Scale-Revised (WAIS-R), and PET study were completed one month after the last ischemic event and 3-6 months after the operation. A significant negative correlation was observed between OEF and neuropsychological functions. Postoperative neuropsychological functions showed significant improvement. Significant correlations were observed for {delta}WAIS-R (preoperative WAIS-R postoperative WAIS-R) versus preoperative CMRO{sub 2} (r=0.52), for {delta}WAIS-R versus preoperative OEF (r=0.47). In view of these findings, the author concludes that elevation of OEF impairs neuropsychological functions and bypass surgery improves neuropsychological functions in patients with normal CMRO{sub 2} and elevated OEF. (author)

  2. Bumetanide promotes neural precursor cell regeneration and dendritic development in the hippocampal dentate gyrus in the chronic stage of cerebral ischemia

    OpenAIRE

    Wang-shu Xu; Xuan Sun; Cheng-guang Song; Xiao-peng Mu; Wen-ping Ma; Xing-hu Zhang; Chuan-sheng Zhao

    2016-01-01

    Bumetanide has been shown to lessen cerebral edema and reduce the infarct area in the acute stage of cerebral ischemia. Few studies focus on the effects of bumetanide on neuroprotection and neurogenesis in the chronic stage of cerebral ischemia. We established a rat model of cerebral ischemia by injecting endothelin-1 in the left cortical motor area and left corpus striatum. Seven days later, bumetanide 200 µg/kg/day was injected into the lateral ventricle for 21 consecutive days with a mini-...

  3. Inhibition of retinoblastoma mRNA degradation through Poly (A involved in the neuroprotective effect of berberine against cerebral ischemia.

    Directory of Open Access Journals (Sweden)

    Yu-Shuang Chai

    Full Text Available Berberine is one kind of isoquinoline alkaloid with anti-apoptotic effects on the neurons suffering ischemia. To address the explanation for these activities, the berberine-induced cell cycle arrest during neurons suffering ischemia/reperfusion had been studied in the present study. According to the in vitro neurons with oxygen-glucose deprivation and in vivo ICR mice with cerebral ischemia/reperfusion, it was found that berberine could protect the mRNA of retinoblastoma (Rb from degradation through its function on the poly(A tail. The prolonged half-life of retinoblastoma 1 (gene of Rb, RB1 mRNA level secures the protein level of retinoblastoma, which facilitates cell cycle arrest of neurons in the process of ischemia/reperfusion and subsequently avoids cells entering in the apoptotic process. The poly(A tail of RB1 mRNA, as a newly identified target of berberine, could help people focus on the interaction between berberine and mRNA to further understand the biological activities and functions of berberine.

  4. Mechanism of Mitochondrial Connexin43's Protection of the Neurovascular Unit under Acute Cerebral Ischemia-Reperfusion Injury.

    Science.gov (United States)

    Hou, Shuai; Shen, Ping-Ping; Zhao, Ming-Ming; Liu, Xiu-Ping; Xie, Hong-Yan; Deng, Fang; Feng, Jia-Chun

    2016-01-01

    We observed mitochondrial connexin43 (mtCx43) expression under cerebral ischemia-reperfusion (I/R) injury, analyzed its regulation, and explored its protective mechanisms. Wistar rats were divided into groups based on injections received before middle cerebral artery occlusion (MCAO). Cerebral infarction volume was detected by 2,3,5-triphenyltetrazolim chloride staining, and cell apoptosis was observed by transferase dUTP nick end labeling. We used transmission electron microscopy to observe mitochondrial morphology and determined superoxide dismutase (SOD) activity and malondialdehyde (MDA) content. MtCx43, p-mtCx43, protein kinase C (PKC), and p-PKC expression were detected by Western blot. Compared with those in the IR group, cerebral infarction volumes in the carbenoxolone (CBX) and diazoxide (DZX) groups were obviously smaller, and the apoptosis indices were down-regulated. Mitochondrial morphology was damaged after I/R, especially in the IR and 5-hydroxydecanoic acid (5-HD) groups. Similarly, decreased SOD activity and increased MDA were observed after MCAO; CBX, DZX, and phorbol-12-myristate-13-acetate (PMA) reduced mitochondrial functional injury. Expression of mtCx43 and p-mtCx43 and the p-Cx43/Cx43 ratio were significantly lower in the IR group than in the sham group. These abnormalities were ameliorated by CBX, DZX, and PMA. MtCx43 may protect the neurovascular unit from acute cerebral IR injury via PKC activation induced by mitoKATP channel agonists. PMID:27164087

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

    Directory of Open Access Journals (Sweden)

    Fang-fang Liu

    2015-01-01

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

  6. Neuroprotective effects of SMAds in a rat model of cerebral ischemia/reperfusion

    Institute of Scientific and Technical Information of China (English)

    Fang-fang Liu; Chao-ying Liu; Xiao-ping Li; Sheng-zhe Zheng; Qing-quan Li; Qun Liu; Lei Song

    2015-01-01

    Previous studies have shown that up-regulation of transforming growth factorβ1 results in neuroprotective effects. However, the role of the transforming growth factorβ1 downstream molecule, SMAD2/3, following ischemia/reperfusion remains unclear. Here, we investigated the neuroprotective effects of SMAD2/3 by analyzing the relationships between SMAD2/3 expression and cell apoptosis and inlfammation in the brain of a rat model of cerebral ischemia/reperfusion. Levels of SMAD2/3 mRNA were up-regulated in the ischemic penumbra 6 hours after cerebral ischemia/reperfusion, reached a peak after 72 hours and were then decreased at 7 days. Phos-phorylated SMAD2/3 protein levels at the aforementioned time points were consistent with the mRNA levels. Over-expression of SMAD3 in the brains of the ischemia/reperfusion model rats viadelivery of an adeno-associated virus containing the SMAD3 gene could reduce tumor ne-crosis factor-α and interleukin-1β mRNA levels, down-regulate expression of the pro-apoptotic gene, capase-3, and up-regulate expression of the anti-apoptotic protein, Bcl-2. The SMAD3 protein level was negatively correlated with cell apoptosis. These ifndings indicate that SMAD3 exhibits neuroprotective effects on the brain after ischemia/reperfusion through anti-inlfamma-tory and anti-apoptotic pathways.

  7. An Experimental Proton Magnetic Resonance Spectroscopy Analysis on Early Stage of Acute Focal Cerebral Ischemia

    Institute of Scientific and Technical Information of China (English)

    易黎; 张苏明; 张新江

    2002-01-01

    Summary: Using different models of focal cerebral ischemia, the temporal and spatial rules ofmetabolism and energy changes in the post-ischemia brain tissue were measured by proton magnet-ic resonance spectroscopy(1HMRS) to provide valuable information for judging the prognosis of a-cute focal cerebral ischemia and carrying out effective therapy. Nine healthy Sprague-Dawly rats(both sexes) were randomly divided into two groups: The rats in the group A (n=4) were occlud-ed with self-thrombus for 1 h; The rats in the group B (n=5) were occluded with thread-embolifor 1 h. The 1H MRS at 30, 40, 50, 60 min respectively was examined and the metabolicchanges of NAA, Cho and Lac in the regions of interest were semiquantitatively analyzed. Thespectrum intregral calculus area ratio of NAA, Cho, Lac to Pcr+Ct was set as the criterion. Thevalues of NAA ~ Cho in the regions of interest were declined gradually within 1 h after ischemia,especially, the ratio of Cho/(Pcr+Cr), NAA/(Pcr+Cr) at 60 min had significant difference withthat at 50 min (P<0. 05). The ratio of Lac/(Pcr+Cr) began to decrease at 40 min from initial in-crease of Lac in both A and B groups. MR proton spectrum analysis was a non-invasive, direct andcomprehensive tool for the study of cellular metabolism and the status of the biochemical energy inacute ischemia stroke.

  8. Energy metabolism variation in experimental cerebral ischemia in mongolian gerbils examined by using in vivo 31P-NMR

    International Nuclear Information System (INIS)

    The mongolian gerbil is a characteristic animal in which cerebral ischemia is similar to that of the human being in that it can be induced by the ligation of the unilateral caortid artery. Howerver, although ischemia is induced in only 40 to 60 percent of the examined gerbils, there is no appropriate method to assess the development of ischemia in the living state. Recently, it has become possible to investigate the energy metabolism in sequence in a living animal by using the in vivo 31P-NMR method. In this study, the energy metabolism in the brain of living gerbils was investigated by measuring the in vivo 31P-NMR with the surface coil method, and consequently, variations in the development of ischemia in this model was detected. A unilateral carotid artery was ligated in 33 gerbils. Ishemic changes in 31P-NMR spectra, which consisted of a decrease in the peaks of ATP and phosphocreatine (PCr), and a concommitant increase in inorganic phosphate (Pi) associated with a decline of tissue pH, were observed on the ligated-side hemisphere in 9 of the 33 gerbils. The time required for developing these ischemic change varied from immediately after ligation to several hours after ligation. In two cases, the changes in the spectrum were transient and recovered spontaneously within 1 hour. In other gerbils, the recovery of energy metabolism was observed when circulation was restored to the ischemic brain. No ischemic changes in the spectrum were observed in 18 of the 33 gerbils. In all cases, no ischemic changes were observed in spectra obtained from the opposite-side hemisphere. However, the ischemic changes appeared immediately after ligation in all gerbils in which the bilateral carotid artery was ligated. Thus, it was apparent that in this model, there was a wide variation not only in the uncertainty of developing ischemia, but also in the time course of developing the ischemic change. (J.P.N.)

  9. [The pathogenetic prerequisites for the application of the general magnetic therapy in the children presenting with cerebral ischemia].

    Science.gov (United States)

    Denisova, O I; Davydkin, N F; Kulikov, A G

    2014-01-01

    This article presents the analysis of the current literature and the original data of the authors providing the rationale for the use of magnetic therapy for the treatment of the children presenting with cerebral ischemia taking into consideration pathogenesis of this disease. It is demonstrated that the application of the general magnetic field decreases the tone of the cerebral vessels and improves blood flow to the brain which increases resistance to cerebral hypoxia. The results of investigations into the microcirculatory changes and liquor dynamics in conjunction with the ventriculometric measurements give evidence of the effectiveness of the combined treatment of cerebral ischemia making use of general magnetic therapy. PMID:25536760

  10. Interleukin-1 exacerbates focal cerebral ischemia and reduces ischemic brain temperature in the rat.

    Science.gov (United States)

    Parry-Jones, Adrian R; Liimatainen, Timo; Kauppinen, Risto A; Gröhn, Olli H J; Rothwell, Nancy J

    2008-06-01

    The proinflammatory cytokine interleukin-1 (IL-1) is a key mediator of inflammation in cerebral ischemia, but its precise mechanisms of action remain elusive. Temperature is critical to outcome in brain injury and given the importance of IL-1 in pyrogenesis this has clear mechanistic implications. IL-1 exacerbates ischemia independently of core (rectal) temperature. However, it is temperature in the ischemic brain that influences outcome and rectal temperature is likely to be a poor surrogate marker. This study tested the hypothesis that IL-1 exacerbates cerebral ischemia by increasing ischemic brain temperature. Wistar rats undergoing transient middle cerebral artery occlusion received either 4 microg/kg IL-1 (n=9) or vehicle (n=10) intraperitoneally. NMR-generated maps of brain temperature, tissue perfusion, and the trace of the diffusion tensor were collected during occlusion, early reperfusion, and at 24 hr. IL-1 significantly increased ischemic damage at 24 hr by 35% but rectal temperature did not vary significantly between groups. However, ischemic brain was 1.7 degrees C cooler on reperfusion in IL-1-treated animals (vs. vehicle) and a corresponding reduction in cerebral blood flow was identified in the ischemic striatum. Contrary to the stated hypothesis, IL-1 reduced ischemic brain temperature during reperfusion and this may be due to a reduction in tissue perfusion. PMID:18421691

  11. Protective effects of inhibition of adenosine monophosphate activated protein kinase activity against cerebral ischemia-reperfusion injury in mice

    Institute of Scientific and Technical Information of China (English)

    补娟

    2013-01-01

    Objective To observe the effect of inhibition of adenosine monophosphate activated protein kinase (AMPK) on shape,function and inflammatory factor of microglia for mice after cerebral ischemia-reperfusion

  12. Reduced PBR/TSPO Expression After Minocycline Treatment in a Rat Model of Focal Cerebral Ischemia: A PET Study Using [18F]DPA-714

    International Nuclear Information System (INIS)

    Background: Many new candidate pharmaceuticals designed to improve recovery after stroke have been proposed recently, but there are still too few molecular imaging methods capable to assess their efficacy. A hallmark of the inflammatory reaction that follows focal cerebral ischemia is overexpression of the mitochondrial peripheral benzodiazepine receptor/18 kDa translocator protein (PBR/TSPO) in the monocytic lineage and astrocytes. This overexpression can be imaged with positron emission tomography (PET) using PBR/TSPO-selective radioligands such as [18F]DPA-714. Purpose: Here, we tested whether PET with [18F]DPA-714 would evidence the effect of minocycline, a broad spectrum antibiotic presently tested as neuro-protective agent after stroke, on the inflammatory reaction induced in an experimental model of stroke. Procedures: Ten rats were subjected to a 2-h transient middle cerebral artery occlusion with reperfusion. Minocycline or saline was intravenously administrated 1 h after reperfusion and daily during the following 6 days. PET studies were performed using [18F]DPA-714 at 7 days after cerebral ischemia. Results: In vivo PET imaging showed a significant decrease in [18F]DPA-714 uptake at 7 days after cerebral ischemia in rats treated with minocycline with respect to saline-treated animals. Minocycline treatment had no effect on the size of the infarcted area. Conclusion: Minocycline administered daily during 7 days after ischemia decreases [18F]DPA- 714 binding, suggesting that the drug exerts an anti-inflammatory activity. [18F]DPA-714 PET is a useful bio-marker to study novel anti-inflammatory strategies in experimental cerebral ischemia. (authors)

  13. Long lasting local and systemic inflammation after cerebral hypoxic ischemia in newborn mice.

    Directory of Open Access Journals (Sweden)

    Max Winerdal

    Full Text Available BACKGROUND: Hypoxic ischemia (HI is an important cause of neonatal brain injury and subsequent inflammation affects neurological outcome. In this study we performed investigations of systemic and local activation states of inflammatory cells from innate and adaptive immunity at different time points after neonatal HI brain injury in mice. METHODOLOGY/PRINCIPAL FINDINGS: We developed a multiplex flow cytometry based method combined with immunohistochemistry to investigate cellular immune responses in the brain 24 h to 7 months after HI brain injury. In addition, functional studies of ex vivo splenocytes after cerebral hypoxic ischemia were performed. Both central and peripheral activation of CD11b(+ and CD11c(+ antigen presenting cells were seen with expression of the costimulatory molecule CD86 and MHC-II, indicating active antigen presentation in the damaged hemisphere and in the spleen. After one week, naïve CD45rb(+ T-lymphocytes were demonstrated in the damaged brain hemisphere. In a second phase after three months, pronounced activation of CD45rb(- T-lymphocytes expressing CD69 and CD25 was seen in the damaged hemisphere. Brain homogenate induced proliferation in splenocytes after HI but not in controls. CONCLUSIONS/SIGNIFICANCE: Our findings demonstrate activation of both local and systemic immune responses months after hypoxic ischemic neonatal brain injury. The long term immune activation observed is of general importance for future studies of the inflammatory response after brain injury as most previous studies have focused on the first few weeks after damage, while the effects of the late inflammation phase may be missed. Furthermore, the self-reactive component raises the question if there is a correlation with development of autoimmune brain disease later in life.

  14. [Comparative evaluation of the neuroprotective activity of phenibut and piracetam under experimental cerebral ischemia conditions in rats].

    Science.gov (United States)

    Tiurenkov, I N; Bagmetov, M N; Epishina, V V; Borodkina, L E; Voronkov, A V

    2006-01-01

    The neuroprotective properties of phenibut and piracetam were studied in rats with cerebral ischemia caused by bilateral irreversible simultaneous occlusion of carotid arteries and gravitational overload in craniocaudal vector. In addition, the effects of both drugs on microcirculation in brain cortex under ischemic injury conditions were studied. Phenibut and (to a lower extent) piracetam reduced a neuralgic deficiency, amnesia, and the degree of cerebral circulation drop, and improved the spontaneous movement and research activity deteriorated by brain ischemia. PMID:16878492

  15. In vivo cellular uptake of glutamate is impaired in the rat hippocampus during and after transient cerebral ischemia

    DEFF Research Database (Denmark)

    Bruhn, T; Christensen, Thomas; Diemer, Nils Henrik

    2001-01-01

    Using microdialysis in CA1 of the rat hippocampus, we studied the effect of transient cerebral ischemia on in vivo uptake and on extracellular levels of glutamate during, and at different time points after ischemia. (3)H-D-aspartate (test substance), and (14)C-mannitol (reference substance), were...

  16. Pictorial essay: Susceptibility-weighted imaging in cerebral ischemia

    International Nuclear Information System (INIS)

    The susceptiblity effect in magnetic resonance imaging (MRI) has been recognized for long and often has been considered undesirable, producing unnecessary noise. Susceptibility-weighted imaging (SWI) aims at exploiting this effect to provide a different type of contrast that is suited for vascular imaging. We describe five different cases in which SWI was found useful to delineate the underlying ischemia or to arrive at the corect diagnosis

  17. Minocycline inhibits neuroinflammation and enhances vascular endothelial growth factor expression in a cerebral ischemia/reperfusion rat model

    Institute of Scientific and Technical Information of China (English)

    Zhiyou Cai; Yong Yan; Changyin Yu; Jun Zhang

    2008-01-01

    BACKGROUND: Brain ischemia involves secondary inflammation, which significantly contributes to the outcome of ischemic insults. Vascular endothelial growth factor (VEGF) may play an important role in the vascular response to cerebral ischemia, because ischemia stimulates VEGF expression in the brain, and VEGF promotes formation of new cerebral blood vessels. Minocyclinc, a tetracycline derivative, protects against cerebral ischemia and reduces inflammation, oxidative stress, and apoptosis.OBJECTIVE: To observe the influence of minocycline on VEGE interleukin-1 beta (IL-1β), and tumor necrosis factor alpha (TNF-α) expression in Wistar rats with focal cerebral ischemia/rcperfusion injury, and to study the neuroproteetion mechanism of minocycline against focal cerebral ischemia/rcpeffusion injury.DESIGN, TIME AND SETTING: Randomized, controlled experiment, which was performed in the Chongqing Key Laboratory of Neurology between March 2007 and March 2008.MATERIALS: A total of 36 female, Wistar rats underwent surgery to insert a thread into the left middle cerebral artery. Animals were randomly divided into sham-operation, minocyclinc treatment, and ischemia/reperfusion groups, with 12 rats in each group. Minocycline (Huishi Pharmaceutical Limited Company, China) was dissolved to 0.5 g/L in normal saline.METHODS: A 0.5- 1.0 cm thread was inserted into rats from the sham-operation group. Rats in the ischemia/reperfusion group underwent ischemia and reperfusion. The minocycline group received minocycline (50 mg/kg) 12 and 24 hours following ischemia and reperfusion, whereas the other groups received saline at the corresponding time points.MAIN OUTCOME MEASURES: mRNA and protein expression of IL-1β and TNF-α was measured by reverse transcriptase-polymerasc chain reaction (RT-PCR) and enzyme linked immunosorbent assay (ELISA), respectively. VEGF mRNA and protein expression was examined by RT-PCR, Western blot, and ELISA.RESULTS: Minocycline decreased the focal infarct

  18. 香青兰总黄酮对短暂性脑缺血诱导的炎症反应的影响%Effect of Total Flavones of Dracocephalum moldavica L.on Inflammation Induced by Transient Cerebral Ischemia

    Institute of Scientific and Technical Information of China (English)

    孙雅煊; 刘婷; 戴雪伶; 高兆兰; 郑秋生; 姜招峰

    2012-01-01

    In order to study the effect and possible mechanism of total flavones of Dracocephalum moldavica L. (TFDM) on transient cerebral ischemic injury in rats, male Wistar rats were randomly divided into five groups: the model group, the sham group, the high-dose TFDM group (50 mg/kg), the middle-dose TFDM group (25 mg/kg), and the iow-dose TFDM group (12.5 mg/kg). Middle cerebral artery occlusion (MCAO) model was established with the suture method. The infarction size, histopathology change, myeloperoxidase (MPO) activity and intercellular adhesion molecule-1 (ICAM-1) expression were measured at 22 h after reperfusion. The results showed that TFDM could significantly reduce the infarct size, alleviate histopathological injury, decrease the activity of MPO and extenuate ICAM-1 expression in the ischemic region. Among the three TFDM treated groups, the high-dose TFDM showed the best efficacy. The results suggested that TFDM was able to protect brains from transient cerebral ischemia by reducing the inflammatory reaction.%为了研究香青兰总黄酮在大鼠短暂性脑缺血损伤中的作用及可能机制,将雄性Wistar大鼠随机分为模型组、假手术组、香青兰总黄酮高剂量(50 mg/kg)组、香青兰总黄酮中剂量(25 mg/kg)组,以及香青兰总黄酮低剂量(12.5 mg/kg)组.采用线栓法建立大脑中动脉栓塞(middle cerebral artery occlusion,MCAO)模型.再灌后22h,测定脑梗死面积、组织病理学变化、髓过氧化物酶(myeloperoxidase,MPO)活性和细胞间黏附分子-1(intercellular adhesion molecule-1,ICAM-1)的表达.结果显示香青兰总黄酮可明显减少缺血区域梗死面积、改善组织病理学变化、降低MPO活性和ICAM-I的表达.在三个香青兰总黄酮处理组中,高剂量香青兰总黄酮作用最强.以上结果表明,香青兰总黄酮可以通过减轻炎症反应,对抗短暂性脑缺血,保护脑组织.

  19. Role of soluble epoxide hydrolase in the sex-specific vascular response to cerebral ischemia

    OpenAIRE

    Zhang, Wenri; Iliff, Jeffrey J.; Campbell, Caitlyn J; Wang, Ruikang K.; Hurn, Patricia D.; Alkayed, Nabil J.

    2009-01-01

    Soluble epoxide hydrolase (sEH), a key enzyme in the metabolism of vasodilator eicosanoids called epoxyeicosatrienoic acids (EETs), is sexually dimorphic and suppressed by estrogen. We determined if the sex difference in blood flow during focal cerebral ischemia is linked to sEH. Soluble epoxide hydrolase expression in brain, hydrolase activity in cerebral vessels, and plasma 14,15-dihydroxyeicosatrienoic acid (14,15-DHET) were determined in male and female wild-type (WT) and sEH knockout (sE...

  20. Effect of propofol pretreatment on apoptosis in rat brain cortex after focal cerebral ischemia and reperfusion

    Institute of Scientific and Technical Information of China (English)

    Haiyan Xu; Chengwei Zhang; Chunxiao Zhang

    2011-01-01

    The present study aimed to observe cortical expression of Bcl-2 and Bax, cysteine-dependent aspartate directed proteases-3 activity and apoptotic cell death in a rat model of middle cerebral artery occlusion pretreated with propofol. Results showed that, propofol pretreatment significantly reduced oxidative stress levels and attenuated neuronal apoptosis in the cortex of rats. Propofol pretreatment upregulated Bcl-2 expression, and downregulated Bax expression and cysteine-dependent aspartate directed proteases-3 activity. These findings indicate that propofol pretreatment inhibits cell apoptosis during focal cerebral ischemia/reperfusion injury. This neuroprotective effect is most likely achieved through the Bcl-2/Bax/cysteine-dependent aspartate directed proteases-3 pathway.

  1. The function of point injection in improving learning and memory dysfunction caused by cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Chen Hua-De

    2001-02-01

    Full Text Available This experiment has investigated the influence of Yamen (Du. 15 point injection on learning and memory dysfunction caused by cerebral ischemia and reprofusion in bilateral cervical general artery combined with bleeding on mouse tail to mimic vascular dementia in human beings. By dividing 40 mice into 4 groups (group1false operation group, group2model group, group3point injection with Cerebrolysin group4point injection with saline. According to random dividing principles, we observed the influence of Yamen(Du. 15 point injection on the time of swimming the whole course used by model mice which had received treatment for different days in different groups, and the influence of those mice on wrong times they entered blind end. The result showed that point injection with Cerebrolysin and saline could improve learning and memory dysfunction of the mice caused by cerebral ischemia.

  2. Systemically administered anti-TNF therapy ameliorates functional outcomes after focal cerebral ischemia

    DEFF Research Database (Denmark)

    Clausen, Bettina Hjelm; Degn, Matilda; Martin, Nellie Anne;

    2014-01-01

    BackgroundThe innate immune system contributes to the outcome after stroke, where neuroinflammation and post-stroke systemic immune depression are central features. Tumor necrosis factor (TNF), which exists in both a transmembrane (tm) and soluble (sol) form, is known to sustain complex...... inflammatory responses associated with stroke. We tested the effect of systemically blocking only solTNF versus blocking both tmTNF and solTNF on infarct volume, functional outcome and inflammation in focal cerebral ischemia.MethodsWe used XPro1595 (a dominant-negative inhibitor of solTNF) and etanercept...... (which blocks both solTNF and tmTNF) to test the effect of systemic administration on infarct volume, functional recovery and inflammation after focal cerebral ischemia in mice. Functional recovery was evaluated after one, three and five days, and infarct volumes at six hours, 24 hours and five days...

  3. Autophagy in cerebral ischemia and the effects of traditional Chinese medicine

    Institute of Scientific and Technical Information of China (English)

    Xiao-ping Huang; Huang Ding; Jin-dong Lu; Ying-hong Tang; Bing-xiang Deng; Chang-qing Deng

    2015-01-01

    Autophagy is a lysosome-mediated degradation process for non-essential or damaged celular constituents, playing an important homeostatic role in cel survival, differentiation and development to maintain homeostasis. Autophagy is involved in tumors as wel as neurodegenerative, cardiovascular and cerebrovascular diseases. Recently, active compounds from traditional Chinese medicine (TCM) have been found to modulate the levels of autophagy in tumor cels, nerve cels, myocardial cels and endothelial cels. Ischemic stroke is a major cause of neurological disability and places a heavy burden on family and society. Regaining function can signiifcantly reduce dependence and improve the quality of life of stroke survivors. In healthy cels, autophagy plays a key role in adapting to nutritional deprivation and eliminating aggregated proteins, however inappropriate activation of autophagy may lead to cel death in cerebral ischemia. This paper reviews the process and the molecular basis of autophagy, as wel as its roles in cerebral ischemia and the roles of TCM in modulating its activity.

  4. Preliminary EEG study of protective effects of Tebonin in transient global cerebral ischemia in rats

    DEFF Research Database (Denmark)

    Zagrean, L; Vatasescu, R; Munteanu, A M;

    2000-01-01

    metabolism. The objective of this study was to investigate the effects of preventive treatment with Ginkgo biloba extract (EGb 761--Tebonin) in cerebral global ischemia and reperfusion in rats using computerized EEG analysis. Ginkgo biloba extract, known to be, in vitro, a free radicals scavanger and a PAF......--antagonist, was administrated in dose of 100 mg/kg over 24 hours, for 5 days before and 5 days after cerebral ischemia--reperfusion. The apparition of isoelectric EEG (flat-line) following 4-vessel occlusion was observed after a mean time of 25 sec. in Ginkgo biloba treated rats and after 18 sec. in control rats...... (p < 0.0015). Computerized spectral analysis of EEG has shown that the percentage of slow waves at 10 minutes after reperfusion was 117% higher in control group than in Ginkgo biloba group (p < 0.015) and the percentage of slow waves after 15 minutes of reperfusion was 100% higher in the control...

  5. Sildenafil attenuates placental ischemia-induced hypertension.

    Science.gov (United States)

    George, Eric M; Palei, Ana C; Dent, Edward A; Granger, Joey P

    2013-08-15

    Preeclampsia is a complication of pregnancy that is marked by hypertension, proteinuria, and maternal endothelial dysfunction. A central factor in the etiology of the disease is the development of placental hypoxia/ischemia, which releases pathogenic soluble factors. There is currently no effective treatment for preeclampsia, but the phosphodiesterase-5 (PDE-5) inhibitor sildenafil has been suggested, as PDE-5 is enriched in the uterus, and its antagonism could improve uteroplacental function. Here, we report in the reduced uterine perfusion pressure (RUPP) rat model that administration of oral sildenafil is effective in attenuating placental ischemia-induced hypertension during gestation. RUPP animals have significantly elevated arterial pressure compared with control animals (132 ± 3 vs. 100 ± 2 mmHg; P PDE-5/β-actin ratio (1 ± 0.14 vs. 1.63 ± 0.18; P < 0.05) expression with a resulting reduction in renal medullary cGMP (1.5 ± 0.15 vs. 0.99 ± 0.1 pmol/μg protein, P < 0.05) compared with controls. Although sildenafil had no effect on renal medullary cGMP in control animals, it significantly increased cGMP in RUPP animals (1.3 ± 0.1 pmol/μg protein; P < 0.05). These data suggest that sildenafil might provide an effective therapeutic option for the management of hypertension during preeclampsia. PMID:23785075

  6. The protective effect of dl-3n-butylphthalide on local cerebral ischemia-reperfusion injury in experimental rats

    International Nuclear Information System (INIS)

    Objective: To observe the effect of dl-3n-butylphthalide (NBP) on the expression of vascular endothelial growth factor (VEGF) in the rat model with focal cerebral ischemia-reperfusion injury and to discuss its impact on the therapeutic time window for cerebral ischemia-reperfusion injury. Methods: Seventy-two SD rats were randomly and equally divided into three groups with 24 rats in each group: sham operation (SO) group, ischemia-reperfusion (I-R) group and NBP group; and each group was again randomly and equally subdivided into three subgroups: 2-hour, 3-hour and 4-hour reperfusion subgroup according to the reperfusion time after ischemia. By using modified suture embolus method the focal cerebral ischemia-reperfusion model was established. The experimental models were kept under close observation for the extent of cerebral infarction and the neurological deficit. The expressions of VEGF in the brain tissues were determined with immunohistochemical method. The results were statistically analyzed and compared among different groups. Results: As the ischemia time went on, the extent of cerebral infarction and the neurological deficit after reperfusion increased. The severity of cerebral infarction and the neurological deficit in NBP group was significantly lower than that in I-R group, the difference between the two groups was significant (P0.05). Along with the increased ischemia time the expressions of VEGF in brain tissues in both NBP group and I-R group were significantly decreased (P<0.01). The expression level of VEGF in NBP group was significantly higher than those in both I-R group and SO group (P<0.01). Conclusion: The dl-3n-butylphthalide has a protective effect on focal cerebral ischemia-reperfusion injury. Its mechanism may be associated with VEGF expression level. The use of dl-3n-butylphthalide can prolong the therapeutic time window of reperfusion. (authors)

  7. The function of point injection in improving learning and memory dysfunction caused by cerebral ischemia

    OpenAIRE

    Chen Hua-De

    2001-01-01

    This experiment has investigated the influence of Yamen (Du. 15) point injection on learning and memory dysfunction caused by cerebral ischemia and reprofusion in bilateral cervical general artery combined with bleeding on mouse tail to mimic vascular dementia in human beings. By dividing 40 mice into 4 groups (group1false operation group, group2model group, group3point injection with Cerebrolysin group4point injection with saline.) According to random dividing principles, we observed the inf...

  8. Nimodipine in Animal Model Experiments of Focal Cerebral Ischemia. A Systematic Review

    OpenAIRE

    Horn, J.; Haan, R.J. de; Luiten, P.G.M.; Limburg, M.

    2001-01-01

    Background and Purpose—Based on the results of animal experiments, clinical trials were performed with nimodipine, which did not demonstrate a beneficial effect on outcome after stroke. The aim of this study was to determine whether the evidence from animal experiments with nimodipine supported the use of nimodipine in clinical trials. Methods—We performed a systematic review of animal experiments with nimodipine in focal cerebral ischemia. Studies were identified by searching Medline and Emb...

  9. Epidemiology and Risk Factors of Cerebral Ischemia and Ischemic Heart Diseases: Similarities and Differences

    OpenAIRE

    Soler, Ernest Palomeras; Ruiz, Virgina Casado

    2010-01-01

    Cerebral ischemia and ischemic heart diseases, common entities nowadays, are the main manifestation of circulatory diseases. Cardiovascular diseases, followed by stroke, represent the leading cause of mortality worldwide. Both entities share risk factors, pathophisiology and etiologic aspects by means of a main common mechanism, atherosclerosis. However, each entity has its own particularities. Ischemic stroke shows a variety of pathogenic mechanisms not present in ischemic heart disease. An ...

  10. Studies on the contact-kinin system and macrophage activation in experimental focal cerebral ischemia

    OpenAIRE

    Heydenreich, Nadine

    2013-01-01

    Traditionally, ischemic stroke has been regarded as the mere consequence of cessation of cerebral blood flow, e.g. due to the thromboembolic occlusion of a major brain supplying vessel. However, the simple restoration of blood flow via thrombolysis and/or mechanical recanalization alone often does not guarantee a good functional outcome. It appears that secondary detrimental processes are triggered by hypoxia and reoxygenation, which are referred to as ischemia/reperfusion (I/R) injury. Durin...

  11. Transcription factor changes following long term cerebral ischemia/reperfusion injury★

    OpenAIRE

    Zhang, Hongbo; Gao, Weijuan; Qian, Tao; Tang, Jinglong; Li, Jun

    2013-01-01

    The present study established a rat model of cerebral ischemia/reperfusion injury using four-vessel occlusion and found that hippocampal CA1 neuronal morphology was damaged, and that there were reductions in hippocampal neuron number and DNA-binding activity of cAMP response element binding protein and CCAAT/enhancer binding protein, accompanied by decreased learning and memory ability. These findings indicate that decline of hippocampal cAMP response element binding protein and CCAAT/enhance...

  12. Can Gender Differences Be Evaluated in a Rhesus Macaque (Macaca mulatta) Model of Focal Cerebral Ischemia?

    OpenAIRE

    Murphy, Stephanie J.; Kirsch, Jeffrey R; Zhang, Wenri; Grafe, Marjorie R; West, G Alex; del Zoppo, Gregory J.; Traystman, Richard J.; Hurn, Patricia D.

    2008-01-01

    Gender differences, sex steroid effects, and sex-specific candidate therapeutics in ischemic stroke have been studied in rodents but not in nonhuman primates. In this feasibility study (n = 3 per group), we developed a model of transient focal cerebral ischemia in adult male and female rhesus macaques that consistently includes white matter injury. The animals also were used to determine whether gender-linked differences in histopathologic outcomes could be evaluated in this model in future, ...

  13. Neonatal Cerebral Ischemia: A Risk Factor for ADHD

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2004-03-01

    Full Text Available The effect of low neonatal cerebral blood flow (CBF on dopaminergic neurotransmission was studied in 6 genetically susceptible high-risk, preterm neonates followed with attention deficit hyperactivity disorder (ADHD at Aarhus University Hospital, Denmark, and tested at 12-14 years of age.

  14. Neuroprotective effect of Shenqi Fuzheng injection pretreatment in aged rats with cerebral ischemia/reperfusion injury

    Directory of Open Access Journals (Sweden)

    Ying-min Cai

    2016-01-01

    Full Text Available Shenqi Fuzheng injection is extracted from the Chinese herbs Radix Astragali and Radix Codonopsis. The aim of the present study was to investigate the neuroprotective effects of Shenqi Fuzheng injection in cerebral ischemia and reperfusion. Aged rats (20-22 months were divided into three groups: sham, model, and treatment. Shenqi Fuzheng injection or saline (40 mL/kg was injected into the tail vein daily for 1 week, after which a cerebral ischemia/reperfusion injury model was established. Compared with model rats that received saline, rats in the treatment group had smaller infarct volumes, lower brain water and malondialdehyde content, lower brain Ca 2+ levels, lower activities of serum lactate dehydrogenase and creatine kinase, and higher superoxide dismutase activity. In addition, the treatment group showed less damage to the brain tissue ultrastructure and better neurological function. Our findings indicate that Shenqi Fuzheng injection exerts neuroprotective effects in aged rats with cerebral ischemia/reperfusion injury, and that the underlying mechanism relies on oxygen free radical scavenging and inhibition of brain Ca 2+ accumulation.

  15. Increased expression of neurotrophin 4 following focal cerebral ischemia in adult rat brain with treadmill exercise.

    Directory of Open Access Journals (Sweden)

    Jin-Young Chung

    Full Text Available Neurotrophin 4 (NT-4 belongs to the family of neurotrophic factors, and it interacts with the tyrosine kinase B (trkB receptor. NT-4 has neuroprotective effects following cerebral ischemia. Its role might be similar to brain-derived neurotrophic factor (BDNF, because both interact with trkB. Exercise also improves neural function by increasing neurotrophic factors. However, expression profiles of NT-4 in the brain during exercise are unknown. Here, we assessed the expressions of NT-4 and its receptor, trkB, following cerebral ischemia and hypothesized that exercise changes the expressions of NT-4 and trkB. Results showed that in a permanent middle cerebral artery occlusion rat model, ischemia decreased NT-4 and trkB expression. Immunohistochemistry showed their immunoreactivities around the region of the ischemic area. Treadmill exercise changed the expression of NT-4, which increased in the contralateral hemisphere in rats with ischemic injury. TrkB also showed similar patterns to its neurotophins. The change in NT-4 suggested that exercise might have primed NT4 production so that further injury causes slightly greater increases in NT4 compared with non-exercise controls.

  16. The angiotensin type 2 receptor agonist Compound 21 elicits cerebroprotection in endothelin-1 induced ischemic stroke

    DEFF Research Database (Denmark)

    Joseph, Jason P; Mecca, Adam P; Regenhardt, Robert W; Bennion, Douglas M; Rodríguez, Vermali; Desland, Fiona; Patel, Neal A; Pioquinto, David J; Unger, Thomas; Katovich, Michael J; Steckelings, Ulrike Muscha; Sumners, Colin

    2014-01-01

    artery occlusion (MCAO), a model of cerebral ischemia. Rats infused centrally (intracerebroventricular) with C21 before endothelin-1 induced MCAO exhibited significant reductions in cerebral infarct size and the neurological deficits produced by cerebral ischemia. Similar cerebroprotection was obtained...

  17. Interleukin-10 inhibits the expression of nuclear factor kappa B in rats with cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Zhihua Wu; Nan Liu; Houwei Du; Ronghua Chen; An Zheng; Huapin Huang

    2006-01-01

    BACKGROUND: Plenty of studies have demonstrated that inflammatory reaction is involved in ischemic cerebral damage, and the expression of inflammatory cytokines can be observed at the initial sites of cerebral damage at early period, including interleukin-6, interleukin-8, etc., which are all the target gene products of nuclear factor kappa B (NF-кB). The process of ischemic damage can be affected by adjusting and controlling NF-кB activity via multi-links.OBJECTIVE: To investigate the inhibitory effect of interleukin-10 on the expression of NF-кB in the ischemic sites of rats with focal cerebral ischemia in rats and its molecular mechanisms.DESIGN: A randomized and controlled animal trial.SETTING: Department of Neurology, the Affiliated Union Hospital of Fujian Medical University.MATERIALS: Thirty-two adult male Sprague-Dawley rats weighing (250±30) g were used. NF-кB p65 (RelA)rabbit anti-rat monoclonal primary antibody was the product of Neomarkers Company; Immunohistochemical kit of the SP two-step method was purchased from Beijing Zhongshan Biotechnology Co., Ltd.METHODS: The experiment was carried out in the Affiliated Union Hospital of Fujian Medical University from August 2005 to April 2006. The rats were randomly assigned into sham-operated group, middle cerebral artery occlusion (MCAO) group, vehicle-treated group and interleukin-10 treated group, 8 rats in each group. Focal cerebral ischemia was induced by occlusion of the middle cerebral artery as previously described. Rats in the MCAO group were anesthetized intraperitoneally, thyroid was bluntly dissected. Right common, external and internal carotid arteries were isolated, the trunk of external carotid artery was ligated and freed, an artery clamp was placed at the internal carotid artery, then a "V" shape incision was made at the free section of external carotid artery, filament was inserted for a depth of (18.5±0.5) mm. The rats in the sham-operated group were given the same treatments with

  18. Expression of cyclin-dependent protein kinase 5 in the hippocampus of vascular dementia mice after cerebral ischemia and reperfusion

    Institute of Scientific and Technical Information of China (English)

    Tianjun Wang; Peiyuan Lü; Hezhen Zhang; Hebo Wang; Wei Jin; Zongcheng Guo; Changlin Liu

    2009-01-01

    BACKGROUND: The p25-activated cyclin-dependent protein kinase 5 (Cdk5) may induce neuronal cell death and cause the development of dementia following cerebral ischemia and reperfusion. OBJECTIVE: To observe changes in the expression of Cdk5 and p25 in hippocampal tissue of vascular dementia mice at different time points following cerebral ischemia and reperfusion. DESIGN, TIME AND SETTING: A randomized, controlled animal experiment was performed in the clinical trial center of Hebei Provincial People's Hospital between September 2007 and October 2008.MATERIALS: Cdk5 rabbit anti-mouse polyclonal antibody, p35 rabbit anti-mouse polyclonal antibody, and β-actin mouse monoclonal antibody were purchased from Santa Cruz Biotechnology, Inc., USA; horseradish peroxidase-labeled goat anti-rabbit IgG and horseradish peroxidase-labeled goat anti-mice IgG were offered by Beijing Zhongshan Goldenbridye Biotechnology Co.,Ltd., China; the protein quantitative kit was produced by Applygen Gene Technology Corp., Beijing, China; cDNA reverse transcription and PCR amplification reagents were products of TianGen&Biotech (Beijing) Co.,Ltd., China.METHODS: One hundred and sixty male Kunming mice were randomly divided into two groups: a sham-operated group (n=65) and a model group (n=95). Vascular dementia was induced with three periods of transient ischemia and reperfusion of the bilateral common carotid arteries. In the sham-operated group, the bilateral common carotid arteries were not blocked.MAIN OUTCOME MEASURES: Behavioral tests were done at four and six weeks post surgery. Pathological changes in the hippocampal CA1 region were observed with hematoxylin-eosin staining. Cdk5 mRNA expression was examined by RT-PCR, and Western blots were used to evaluate Cdk5 and p25 expression. Learning and memory performance were assayed using the Morris water maze. RESULTS: Vascular dementia reduced learning and memory performance at 4 and 6 weeks post surgery. Vascular dementia also caused

  19. Effects of nerve growth factor on the expression of caspase-12 of nerve cells in cerebral ischemia/reperfusion area

    Institute of Scientific and Technical Information of China (English)

    Jiping Yang; Huaijun Liu; Ying Li; Yan Liu; Haiqing Yang

    2006-01-01

    BACKGROUND: Researches suggest that cascade reaction of cysteine protease mediated by caspase-12 can cause apoptosis after cerebral ischemia/reperfusion injury;however, nerve growth factor (NGF) can reduce apoptosis through inhibiting activation of that reaction.OBJECTTVE: To observe the effect of NGF on the expression of caspase-12 in brain tissue of rabbits with cerebral ischemia/reperfusion injury, and elucidate the protective mechanism of NGF on neural apoptosis induced by cerebral ischemia/reperfusion injury.DESIGN: Randomized controlled animal study.SETTING: Department of Image, Second Hospital, Hebei Medical University.MATERIALS: A total of 26 healthy New Zealand rabbits, of clean grade, aged 4.5-5 months, weighing (2.6±0.2) kg, were selected in this study. Reagents: NGF (Xiamen Beida Zhilu Biotechnology Co., Ltd.);caspase-12 (Santa Cruz Biotechnology Company, USA, clone number: SC-12395); caspase-3 (Santa Cruz Biotechnology Company, USA, clone number: SC-7272); biotin-antibody Ⅱ and ABC compound (Wuhan Boster Company); in situ end-labeling (ISEL, Beijing Zhongshan Company).METHODS: The experiment was carried out in the Laboratories of Nerve Molecule Image Science and Neurology of the Second Hospital of Hebei Medical University from May to August 2005. ① All animals were randomly divided into three groups. Ischemia/reperfusion (I/R) group (n=10): Left middle cerebral artery (MCA) was blocked for 2 hours and then blooded for 2 hours in order to establish focal cerebral ischemia/reperfusion models. Sham operation group (n=6): Cork was inserted with 3 cm in depth, and then pulled to common carotid artery. Other procedures were as the same as those in ischemia/reperfusion group.Treatment group (n=10): After modeling, 400 AU (16 μg/L) NGF was inserted into cerebral infarction focus sham operation group and at 3 days after reperfusion in other two groups. In addition, contents of caspase-12 and caspase-3 were measured with immunohistochemical technique; mean

  20. Method of empirical dependences in estimation and prediction of activity of creatine kinase isoenzymes in cerebral ischemia

    Science.gov (United States)

    Sergeeva, Tatiana F.; Moshkova, Albina N.; Erlykina, Elena I.; Khvatova, Elena M.

    2016-04-01

    Creatine kinase is a key enzyme of energy metabolism in the brain. There are known cytoplasmic and mitochondrial creatine kinase isoenzymes. Mitochondrial creatine kinase exists as a mixture of two oligomeric forms - dimer and octamer. The aim of investigation was to study catalytic properties of cytoplasmic and mitochondrial creatine kinase and using of the method of empirical dependences for the possible prediction of the activity of these enzymes in cerebral ischemia. Ischemia was revealed to be accompanied with the changes of the activity of creatine kinase isoenzymes and oligomeric state of mitochondrial isoform. There were made the models of multiple regression that permit to study the activity of creatine kinase system in cerebral ischemia using a calculating method. Therefore, the mathematical method of empirical dependences can be applied for estimation and prediction of the functional state of the brain by the activity of creatine kinase isoenzymes in cerebral ischemia.

  1. Neuroprotective effect of TAT-14-3-3ε fusion protein against cerebral ischemia/reperfusion injury in rats.

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    Yuanjun Zhu

    Full Text Available Stroke is the major cause of death and disability worldwide, and the thrombolytic therapy currently available was unsatisfactory. 14-3-3ε is a well characterized member of 14-3-3 family, and has been reported to protect neurons against apoptosis in cerebral ischemia. However, it cannot transverse blood brain barrier (BBB due to its large size. A protein transduction domain (PTD of HIV TAT protein, is capable of delivering a large variety of proteins into the brain. In this study, we generated a fusion protein TAT-14-3-3ε, and evaluated its potential neuroprotective effect in rat focal ischemia/reperfusion (I/R model. Western blot analysis validated the efficient transduction of TAT-14-3-3ε fusion protein into brain via a route of intravenous injection. TAT-14-3-3ε pre-treatment 2 h before ischemia significantly reduced cerebral infarction volume and improved neurologic score, while post-treatment 2 h after ischemia was less effective. Importantly, pre- or post-ischemic treatment with TAT-14-3-3ε significantly increased the number of surviving neurons as determined by Nissl staining, and attenuated I/R-induced neuronal apoptosis as showed by the decrease in apoptotic cell numbers and the inhibition of caspase-3 activity. Moreover, the introduction of 14-3-3ε into brain by TAT-mediated delivering reduced the formation of autophagosome, attenuated LC3B-II upregulation and reversed p62 downregulation induced by ischemic injury. Such inhibition of autophagy was reversed by treatment with an autophagy inducer rapamycin (RAP, which also attenuated the neuroprotective effect of TAT-14-3-3ε. Conversely, autophagy inhibitor 3-methyladenine (3-MA inhibited I/R-induced the increase in autophagic activity, and attenuated I/R-induced brain infarct. These results suggest that TAT-14-3-3ε can be efficiently transduced into brain and exert significantly protective effect against brain ischemic injury through inhibiting neuronal apoptosis and autophagic

  2. Ergotamine-induced upper extremity ischemia: a case report

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    Kim, Man Deuk; Lee, Gun [Bundang CHA General Hospital, Pochon (China); Shin, Sung Wook [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2005-06-15

    Ergotamine-induced limb ischemia is an extremely rare case. We present a case of a 64-year-old man, who developed ischemia on the right upper extremity due to long-term use of Ergot for migraine headache. Angiography revealed diffused, smooth, and tapered narrowing of the brachial artery. The patient was successfully treated with intravenous nitroprusside.

  3. Ergotamine-induced upper extremity ischemia: a case report

    International Nuclear Information System (INIS)

    Ergotamine-induced limb ischemia is an extremely rare case. We present a case of a 64-year-old man, who developed ischemia on the right upper extremity due to long-term use of Ergot for migraine headache. Angiography revealed diffused, smooth, and tapered narrowing of the brachial artery. The patient was successfully treated with intravenous nitroprusside

  4. Ergotamine-Induced Upper Extremity Ischemia: A Case Report

    OpenAIRE

    Kim, Man Deuk; Lee, Gun; Shin, Sung Wook

    2005-01-01

    Ergotamine-induced limb ischemia is an extremely rare case. We present a case of a 64-year-old man, who developed ischemia on the right upper extremity due to long-term use of Ergot for migraine headache. Angiography revealed diffused, smooth, and tapered narrowing of the brachial artery. The patient was successfully treated with intravenous nitroprusside.

  5. Long-term existence of cerebral hypoxic tissue in a rat model of cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Yidong Wang; Jingrui Pan; Yu Qiu; Xiangpen Li; Mei Li; Ying Peng

    2009-01-01

    BACKGROUND: Hypoxic tissue surrounding the ischemic core may represent the ischemic penumbra following cerebral infarction. However, some studies have shown that the duration of ischemic tissue is longer than previously believed.OBJECTIVE: To clarify whether cerebral hypoxic tissue could survive long-term and whether it is altered in rats following cerebral infarction; to establish an ischemia/reperfusion model in which hypoxic tissue exists for extended periods of time.DESIGN, TIME AND SETTING: A completely randomized grouping and controlled experiment was performed at the Experimental Animal Center of Sun Yat-sen University and Medical Research Center, the Second Affiliated Hospital of Sun Yat-sen University between June and December 2008. MATERIALS: 4,9-diaza-3,3,10,10-tetramethyldodecan-2, 11-dione dioxime (BnAO) (HL91), used as the hypoxic marker for autoradiography, was supplied by the Beijing Syncor Star Medicinal, China, and the flesh eluent Na99TcmO4 to mark HL91 was supplied by Guangzhou Medical Isotope Center of the China Institute of Atomic Energy. 2-(2-nitro-1H-imidazole-1-yl)-N-(2,2,3,3,3-pentafluoropropyl) acetamide (EF5) and its antibody ELK3-51, used as a hypoxic marker for immunofluorescence, were supplied by the University of Pennsylvania, USA.METHODS: Male Sprague Dawley rats were randomly divided into four groups: 1.5-hour ischemia/reperfusion group (1.5 h IR), 2-hour ischemia/reperfusion group (2 h IR), 3-hour ischemia/reperfusion group (3 h IR), and permanent ischemia (PI) group, with 21 rats in each group. The middle cerebral artery occlusion model was established using the intraluminal suture method, while reperfusion was performed by removing the suture at each observation time point. However, in the PI group, the suture was left in the artery.MAIN OUTCOME MEASURES: Area and average absorbance of fluorescence, representing hypoxic tissue, were measured by image-analysis.RESULTS: Autoradiography revealed positive hypoxia at days 1 and 14

  6. Protective effects of icariin on neurons injured by cerebral ischemia/reperfusion

    Institute of Scientific and Technical Information of China (English)

    LI Li; ZHOU Qi-xin; SHI Jing-shan

    2005-01-01

    Background It is very important to search for novel anti-ischemia/reperfusion neuroprotective drugs for prevention or treatment of cerebrovascular diseases. Icariin, the major active component of traditional Chinese herb Yinyanghuo, may have a beneficial role for neurons in cerebral ischemia/reperfusion caused by accident. However, it was not clear yet. In this study, we observed the protective effects of icariin on neurons injured by ischemia/reperfusion in vitro and in vivo and investigated its protective mechanism.Methods Cerebral cortical neurons of Wistar rats in primary culture were studied during the different periods of oxygen-glucose deprivation and reperfusion with oxygen and glucose. Cell viability was determined by methyl thiazoleterazolium (MTT) assay. The activity of lactate dehydrogenase (LDH) leaked from neurons, cell apoptosis and the concentration of intracellular free calcium were measured respectively. On the other hand, the mice model of transient cerebral ischemia/reperfusion was made by bilateral occlusion of common carotid arteries and ischemic hypotension/reperfusion. The mice were divided into several groups at random: sham operated group, model group and icariin preventive treatment group. The changes of mice behavioral, activities of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) were measured, respectively. Results Treatment with icariin (final concentration 0.25, 0.5, and 1 mg/L) during ischemia/reperfusion-mimetic incubation in vitro concentration-dependently attenuated neuronal damage with characteristics of increasing injured neuronal absorbance of MTT, decreasing LDH release, decreasing cell apoptosis, and blunting elevation of intracellular calcium concentration. And in vivo the learning and memory abilities significantly decreased,activities of SOD were diminished and MDA level increased obviously in model group,compared with that in sham operated group. But pre-treatment of model mice with icariin (10, 30

  7. Inducing effect of total flavones in rhododendra on endothelium-derived hyperpolarizing factor responses in cerebral basilar artery of rats subjected to global cerebral ischemia reperfusion%映山红花总黄酮对全脑缺血再灌注大鼠脑基底动脉超极化反应的诱导作用

    Institute of Scientific and Technical Information of China (English)

    韩黎黎; 范一菲; 陈志武

    2011-01-01

    Objective To study the effect of endothelium-derived hyperpolarizing factor (EDHF)-mediated responses of relaxation and hyperpolarization of vascular smooth muscle cell (VSMC) of rat cerebral basilar artery (CBA) subjected to cerebral ischemia/reperfusion (I/R) to total flavones in rhododendra (TFR). Methods The model of global cerebral I/R in rats was made by 4-vessel occlusion (4-VO). The vasodilation and resting membrane potential (RMP) of VSMC of rat CBA were detected in vitro.Results In the presence of 3×10-5 mol/L Nω-nitro-L-arginine-methyl-ester (L-NAME, an inhibitor of nitric oxide synthase) and 1 × 10-5 mol/L Indomethacin (Indo, an inhibitor of PGI2 synthesis), the global cerebral I/R markedly enhanced 1 × 10-7-1 × 10-5 mol/L acetylcholine (Ach)-elicited relaxation and hyperpolarization of RMP of VSMC in rat CBA. In the presence of L-NAME and Indo, 11 -2 700 mg/L TFR induced significant and dose-dependent hyperpolarization of RMP of VSMC and relaxation of rat CBA subjected to global cerebral I/R. The hyperpolarization and relaxation were obviously inhibited by tetraethylammonium (an inhibitor of IKca at 1 mmol/L) and 1 ×10-4 mol/L dl-propargylglycine (PPG), an inhibitor of endogenous hydrogen sulfide (H2S) synthase. Conclusion Global cerebral I/R could enhance the non-NO-non-PGI2-mediated responses of hyperpolarization and vasorelaxation in rat CAB. In rat CAB subjected to global cerebral I/R, TFR could significantly induce this non-NO-non-PGl2 hyperpolarization and relaxation, the so-called EDHF response that might be mediated by endogenous H2S.%目的 探讨映山红花总黄酮(TFR)对内皮源性超极化因子(EDHF)介导的全脑缺血再灌注大鼠脑基底动脉(CBA)血管舒张和平滑肌细胞膜静息电位超极化反应的诱导作用.方法 采用四血管结扎法建立大鼠全脑缺血再灌注模型,测定离体大鼠CBA平滑肌细胞膜静息电位和血管舒张功能.结果 在3×10-5mol/L L-NAME和1×10-5mol/L吲哚美辛存

  8. Estrogen intervention in microvascular morphology and choline acetyltransferase expression in rat hippocampal neurons in chronic cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Zhenjun Yang; Hongwei Yan; Guomin Zhang; Zhihong Chen; Jingfeng Xue

    2011-01-01

    We observed dynamic changes in microvessels and a protective effect of estrogen on chronic cerebral ischemia ovariectomized rat models established through permanent occlusion of bilateral carotid arteries at 7, 14 and 21 days. The results revealed that estrogen improved microvasculature in the hippocampus of chronic cerebral ischemic rats, upregulated Bcl-2 protein expression, downregulated Bax protein expression, increased choline acetyltransferase expression in hippocampal cholinergic neurons, and suppressed hippocampal neuronal apoptosis. These findings indicate that estrogen can protect hippocampal neurons in rats with chronic cerebral ischemia.

  9. Effects of fastigial nucleus electrical stimulation on lateral ventricle nestin expression after focal cerebral ischemia/reperfusion in adult rats

    Institute of Scientific and Technical Information of China (English)

    Yanjun Huang; Yong Luo

    2008-01-01

    BACKGROUND: Previous studies have confirmed that fastigial nucleus electrical stimulation can induce endogenous neuroprotective mechanisms and produce wide and long-lasting neuroprotective effects. Nevertheless, the precise mechanisms remain poorly understood. OBJECTIVE: This study was designed to observe the effects of fastigial nucleus electrical stimulation on nestin-positive cell expression in adult rat lateral ventricle after focal cerebral ischemia/reperfusion, as well as neurological functional changes as a function of time.DESIGN: A randomized controlled animal experiment. SETTING: Department of Neurology, First Affiliated Hospital of Chongqing Medical University; Chongqing Key Laboratory of Neurology.MATERIALS: This study was performed in the Department of Neurology, First Affiliated Hospital of Chongqing Medical University and Chongqing Key Laboratory of Neurology from September 2004 to February 2006. A total of 180 healthy, adult, male Wistar rats, aged 8 weeks old, were provided by the Laboratory Animal Center of Chongqing Medical University. The main reagents and equipments were as follows: rabbit anti-rat nestin monoclonal antibody (Wuhan Boster Company, China).MAIN OUTCOME MEASURES: Nestin-positive cells were detected by immunohistochemical staining in the rat ischemic lateral cerebral ventricle at 1, 3, 7, 14, 21, and 28 days post-reperfusion. RESULTS: Morphological changes of nestin-positive cells in the ischemic lateral ventricle: in the normal control group, very few nestin-positive cells were detected in the choroid plexus, ependyma, and subependymal region of the lateral ventricle. In the model group, the number of nestin-positive cells exhibited a tendency towards a single peak, i.e., cells increased at day 1, reached peak levels by day 7, and then decreased sharply. Fastigial nucleus electrical stimulation was administered following focal cerebral ischemia/reperfusion, and results revealed that nestin-positive cell morphology was similar to

  10. Flavonoids from Scutellaria baicalensis Georgi are effective to treat cerebral ischemia/reperfusion

    Institute of Scientific and Technical Information of China (English)

    Yazhen Shang; Hong Zhang; Jianjun Cheng; Hong Miao; Yongping Liu; Kai Cao; Hui Wang

    2013-01-01

    Based on previous studies that have shown flavonoids from the stems and leaves of Scutellaria baicalensis Georgi are neuroprotective agents in a naturally senile, D-galactose, aging in vivo model, as well as an in vitro model of oxidative/hypoxic injury, we established a cerebral ischemia/reperfusion model in rats by middle cerebral artery occlusion. The light/electron microscopic observations found significant neuropathological changes including neuron loss or swelling and rough endoplasmic reticulum injury. Moreover, the activities of lactate dehydrogenase, Na+-K+-ATPase, Ca2+-ATPase and superoxide dismutase were significantly lowered, and the levels of malonaldehyde increased. In addition, the memory of rats worsened. However, treatment with flavonoids from Scutellaria baicalensis Georgi (35, 70 and 140 mg/kg) for 13 days dramatically improved the above abnormal changes. These results suggest that the ability of flavonoids from Scutellaria baicalensis Georgi in attenuating cerebral functional and morphological consequences after cerebral ischemia/reperfusion may be beneficial for the treatment of ischemic brain disease.

  11. Dynamic Changes of the CT Perfusion Parameters in the Embolic Model of Cerebral Ischemia

    Institute of Scientific and Technical Information of China (English)

    陈唯唯; 漆剑频; 张进华; 黄文华; 宋金梅

    2004-01-01

    To study the dynamic changes of CT perfusion parameters during the first 12 h in the embolic cerebral ischemia models. Local cerebral ischemia model were established in 7 New Zealand white rabbits. All CT scans were performed with a GE Lightspeed 16 multislice CT. Following the baseline scan, further CT perfusion scans were performed at the same locations 20 min, 1-6 h and8, 10 and 12 h after the embolus delivery. Maps of all parameters were obtained by CT perfusion software at each time point. The brains, taken 12 h after the scan, were sliced corresponding to the positions of the CT slices and stained by 2,3,5-triphenyltetrazolium chloride (TTC). On the basis of the TTC results, the ischemicsides were divided into 3 regions: core, penumbra and the relatively normal region. The changes of all parameters were then divided into 3 stages. In the first two hours (the first stage), the CBV dropped more remarkably in the core than in the penumbra but rose slightly in the relatively normal region while the CBF decreased and MTT, TTP extended in all regions to varying degrees. In the 2nd-5th h (the second stage), all the parameters fluctuated slightly around a certain level. In the 5th-12th h (the third stage), the CBV and CBF dropped,and MTT and TTP were prolonged or shortened slightly in the core and penumbra though much notably in the former while the CBV, CBF roseand MTT, TTP were shortened remarkably in the relatively normal region. We experimentally demonstrated that the location and extent of cerebral ischemia could be accurately assessed by CT perfusion imaging. The pathophysiology of the ischemia could be reflected by the CT perfusion to varying degrees.

  12. An extended window of opportunity for G-CSF treatment in cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Schwab Stefan

    2006-10-01

    Full Text Available Abstract Background Granulocyte-colony stimulating factor (G-CSF is known as a powerful regulator of white blood cell proliferation and differentiation in mammals. We, and others, have shown that G-CSF is effective in treating cerebral ischemia in rodents, both relating to infarct size as well as functional recovery. G-CSF and its receptor are expressed by neurons, and G-CSF regulates apoptosis and neurogenesis, providing a rational basis for its beneficial short- and long-term actions in ischemia. In addition, G-CSF may contribute to re-endothelialisation and arteriogenesis in the vasculature of the ischemic penumbra. In addition to these trophic effects, G-CSF is a potent neuroprotective factor reliably reducing infarct size in different stroke models. Results Here, we have further delayed treatment and studied effects of G-CSF on infarct volume in the middle cerebral artery occlusion (MCAO model and functional outcome in the cortical photothrombotic model. In the MCAO model, we applied a single dose of 60 μg/kg bodyweight G-CSF in rats 4 h after onset of ischemia. Infarct volume was determined 24 h after onset of ischemia. In the rat photothrombotic model, we applied 10 μg/kg bodyweight G-CSF daily for a period of 10 days starting either 24 or 72 h after induction of ischemia. G-CSF both decreased acute infarct volume in the MCAO model, and improved recovery in the photothrombotic model at delayed timepoints. Conclusion These data further strengthen G-CSF's profile as a unique candidate stroke drug, and provide an experimental basis for application of G-CSF in the post-stroke recovery phase.

  13. Intravenous digital subtraction angiography investigation of reversible cerebral ischemia

    International Nuclear Information System (INIS)

    The brachio-cephalic, carotid, vertebral and intra-cranial vessels of 497 patients presenting reversible ischemic attacks (R.I.A) were evaluated with venous digital subtraction angiography (V.D.S.A.). Alterations of the vascular wall were observed in 289/497 (58.2%) patients, of whom 60% presented multiple locations (539 lesions): obstruction (12%), stenosis >50% (29%), stenosis 50%. The incidence of vascular lesions was higher (p<0.01) in patients with multiple R.I.A. (66.6%) than in those with one isolated R.I.A. (55.6%). Among the patients (207/497) studied also with cerebral computed tomography (C.T.) no relationship could be defined between the extra-cranial vascular lesions demonstrated by V.D.S.A. and the cerebral alterations shown by C.T. Among the patients (64/497) studied also with high frequence ultrasonography (U.S.), the lesion shown by V.D.S.A. could be also demonstrated by U.S. in 84.8% of cases. The personal flow-chart in the study of R.I.A. is described emphasizing the primary role played by V.D.S.A. as well as the complementary role of the other techniques, both non invasive (U.S.,C.T.) and invasive (conventional or digital subtraction angiography)

  14. Spatiotemporal expression of Nogo-66 receptor after focal cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Yue Cao; Ya-xian Dong; Jie Xu; Guo-liang Chu; Zhi-hua Yang; Yan-ming Liu

    2016-01-01

    NgR, the receptor for the neurite outgrowth inhibitor Nogo-66, plays a critical role in the plasticity and regeneration of the nervous system after injury such as ischemic stroke. In the present study, we used immunohistochemistry to investigate the regional expression of NgR in rat brain following middle cerebral artery occlusion (MCAO). NgR protein expression was not observed in the center of the lesion, but was elevated in the marginal zone compared with control and sham-operated rats. The cerebral cortex and hippocampus (CA1, CA2, and CA3) showed the greatest expression of NgR. Furthermore, NgR expression was higher in the ipsilesional hemisphere than on the control side in the same coronal section. Although time-dependent changes in NgR expression across brain regions had their own characteristics, the overall trend complied with the following rules: NgR expression changes with time showed two peaks and one trough; the ifrst peak in expression appeared between 1 and 3 days after MCAO; expression declined at 5 days; and the second peak occurred at 28 days.

  15. Effects of phycocyanin on apoptosis and expression of superoxide dismutase in cerebral ischemia reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Meizeng Zhang; Lihua Wang; Yunliang Guo

    2006-01-01

    BACKGROUND: The application of exogenous antioxidant is always the focus in the prevention and treatment of cerebral ischemia. Phycocyanin has the effects against oxidation and inflammation, but its role in the pathophysiological process of cerebral ischemia reperfusion injury still needs further investigation.OBJECTIVE: To observe the effects of phycocyanin on the expression of superoxide dismutase (SOD),apoptosis and form of the nerve cells in rats after cerebral ischemia reperfusion injury.DESIGN: A randomized control animal experiment.SETTING: Institute of Cerebrovascular Disease, Medical School Hospital of Qingdao University.MATERIALS: Fifty-two healthy adult male Wistar rats of clean degree, weighing 220-260 g, were used. Phycocyanin was provided by the Institute of Oceanology, Chinese Academy of Sciences.METHODS: The experiments were carried out in Shangdong Key Laboratory for Prevention and Treatment of Brain Diseases from May to December 2005. ① All the rats were divided into three groups according to the method of random number table: sham-operated group (n=4), control group (n=24) and treatment group (n=24). Models of middle cerebral artery occlusion/reperfusion (MCAO/R) were established by the introduction of thread through external and internal carotid arteries in the control group and treatment group. After 1-hour ischemia and 2-hour reperfusion, rats in the treatment group were administrated with gastric perfusion of phycocyanin suspension (0.1 mg/g), and those in the control group were given saline of the same volume, and no treatment was given to the rats in the sham-operated group. ②The samples were removed and observed at ischemia for 1 hour and reperfusion for 6 and 12 hours and 1, 3, 7 and 14 days respectively in the control group and treatment group, 4 rats for each time point, and those were removed at 1 day postoperatively in the sham-operated group. Forms of the nerve cells were observed with toluidine blue staining. Apoptosis after

  16. ARGININE VASOPRESSIN GENE EXPRESSION IN SUPRAOPTIC NUCLEUS AND PARAVENTRICULAR NUCLEUS OF HYPOTHALAMOUS FOLLOWING CEREBRAL ISCHEMIA AND REPERFUSION

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Background. Our previous studies indicated that the increased arginine vasopressin(AVP) in ischemic brain regions of gerbils could exacerbate the ischemic brain edema. This experiments is further clarify the relation between AVP and cerebral ischemia at the molecular level. Methods. The contents of AVP, AVP mRNA, AVP immunoreactive(ir) neurons in supraoptic nucleus(SON)and paraventricular nucleus(PVN) after cerebral ischemia and reperfusion were respectively determined by radioim-munoassay(RIA), immunocytochemistry( Ⅱ C), situ hybridization and computed image pattem analysis. Results. The contents of AVP in SON, PVN were increased, and the AVP ir positive neurons in SON and PVN were also significantly increased as compared with the controls after ischemia and reperfusion. And there were very light staining of AVP ir positive neurons in the other brain areas such as suprachiasmatic nucleus (SC) and periven-tricular hypothalamic nucleus (PE), but these have no significant changes as compared with the controls. During dif-ferent periods of cerebral ischemia (30~ 120 min) and reperfusion (30 min), AVP mRNA expression in SON and PVN were more markedly increased than the controls. Condusions. The transcription of AVP gene elevated, then promoting synthesis and release of AVP in SON,PVN. Under the specific condition of cerebral ischemia and repeffusion, the activity and contents of central AVP in-creased abnormally is one of the important factors which causes ischemia brain damage.

  17. EFFECT OF VASOPRESSIN ON DELAYED NEURONAL DAMAGE IN HIPPOCAMPUS FOLLOWING CEREBRAL ISCHEMIA AND REPERFUSION IN GERBILS

    Institute of Scientific and Technical Information of China (English)

    刘新峰; 金泳清; 陈光辉

    1996-01-01

    Mongolian gerbils were used as delayed neuronal damage (DND) animal models.At the end of 15 minute cerebral ischermia and at various reperfusion time ranging from 1 to 96 hours,the content of water and arginine vasopressin (AVP) in the CA1 sector of hippocampus were measured by the specific gravity method and radioimmunoassy.Furthermore,we also examined the effect of intracerebroventricular (ICV) injection of AVP,AVP antiserum on calcium,Na+,K+-ATP ase activity in the CA1 sector after ischemia and 96 hour reperfusion.The results showed that AVP Contents of CA1 sector of hippocampus during 6 to 96 hour recirculation,and the water content of CA1 sector during 24 to 96 hour were significantly and continuously increased.After ICV injection of AVP,the water content and calcium in CA1 sector of hippocampus at cerebral ischemia and 96 hour recirculation further increased,and the Na+,K+-AT-tion of AVP antiserum,the water contenr and calcium in CA1 sector were significantly decreased as compared with that of control.These suggested that AVP was involved in the pathopysiologic process of DND in hippocampus following cerbral ischemia and reprfusion.Its mechanism might be through the change of intracellular action mediated by specific AVP receptor to lead to Ca inos over-load of neuron and inhibit the Na+,K+-ATPase activity,thereby to exacerbate the DND in hippocampus.

  18. Panretinal photocoagulation for radiation-induced ocular ischemia

    International Nuclear Information System (INIS)

    We present preliminary findings on the effectiveness of panretinal photocoagulation in preventing neovascular glaucoma in eyes with radiation-induced ocular ischemia. Our study group consisted of 20 patients who developed radiation-induced ocular ischemia following cobalt-60 plaque radiotherapy for a choroidal or ciliary body melanoma. Eleven of the 20 patients were treated by panretinal photocoagulation shortly after the diagnosis of ocular ischemia, but nine patients were left untreated. In this non-randomized study, the rate of development of neovascular glaucoma was significantly lower (p = 0.024) for the 11 photocoagulated patients than for the nine who were left untreated

  19. U0126 PREVENTS ERK PATHWAY PHOSPHORYLATION AND INTERLEUKIN-1β mRNA PRODUCTION AFTER CEREBRAL ISCHEMIA

    Institute of Scientific and Technical Information of China (English)

    Zhi-qiu Wang; Xian-cheng Chen; Guo-yuan Yang; Liang-fu Zhou

    2004-01-01

    Objective To study the role of extracellular sigual-regulated kinase (ERK) in cerebral ischemia and the mechanism of protective effects of U0126 ( 1,4-diamino-2,3-dicyano- 1,4-bis[2-aminophenylthio] butadiene) on ischemic brain.Methods Mice underwent left middle cerebral artery occlusion (MCAO) by introducing a suture in the lumen. U0126 was injected intravenously through the internal jugular vein. The immuno-activity of phosphorylated ERK1/2 (pERK1/2), phosphorylated mitogen activated protein kinase kinase (pMEK), and phosphorylated Elk-1 (pElk-1) was assessed by Western blot analysis and immunohistochemistry. Interleukin (IL)-1β mRNA level was measured by ribonuclease protection assay.Results Phosphorylated ERK1/2 in 2 hours MCAO mice was down-regulated after intravenous injection of U0126. The inhibition was dose dependent and treatment time related. pMEK and pElk-1 were also reduced in a similar fashion after U0126treatment. IL-1β mRNA increased after 1 and 2 hours of MCAO. After injection of U0126, it was down-regulated during 1to 4 hours after MCAO.Conclusion Intravenous administration of the MEK inhibitor U0126 inhibits pMEK, pERK1/2, and pElk-1 up-regulation induced by cerebral ischemia. The protective effect of U0126 against ischemic injury is probably resulted from the reduction of IL-1 β mRNA via the inhibition of ERK pathway.

  20. Role of N-Nitro-L-Arginine-Methylester as anti-oxidant in transient cerebral ischemia and reperfusion in rats

    Directory of Open Access Journals (Sweden)

    Awooda Hiba A

    2013-01-01

    Full Text Available Abstract Background Previous reports assessing the neuroprotective role of nonselective Nitric Oxide synthase (NOS inhibitor N-nitro-L-arginine-methylester (L-NAME following cerebral ischemia/reperfusion are contradictory. The aim of this work was to examine the potential benefits of L-NAME on rats subjected to transient focal cerebral ischemia/reperfusion. Methods The study involved 30 adult male Wistar rats divided into three groups 10 rats in each: First group was sham-operated and served as a control, a ischemia/reperfusion (I/R group of rats infused with 0.9% normal saline intraperitoneally 15 minutes prior to 30 minutes of left common carotid artery (CCA occlusion and a test group infused with L-NAME intraperitoneally 15 minutes prior to ischemia. Neurobehavioral assessments were evaluated and quantitative assessment of malondialdehyde (MDA, Nitric oxide (NO metabolites and total antioxidant capacity (TAC in both serum and the affected cerebral hemisphere were achieved. Results Rats’ neurological deficit and TAC were significantly decreased while NO and MDA were significantly increased in the I/R compared with the control group (P Conclusions L-NAME pretreatment for rats undergoing cerebral ischemia/reperfusion significantly improves neurological deficit while reducing oxidative stress biomarkers in the affected cerebral hemisphere.

  1. Downstream Toll-like receptor signaling mediates adaptor-specific cytokine expression following focal cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Bolanle Famakin

    2012-07-01

    Full Text Available Abstract Background Deletion of some Toll-like receptors (TLRs affords protection against cerebral ischemia, but disruption of their known major downstream adaptors does not. To determine whether compensation in the production of downstream effectors by one pathway when the other is disrupted can explain these findings, we examined cytokine/chemokine expression and inflammatory infiltrates in wild-type (WT, MyD88−/− and TRIF-mutant mice following permanent middle cerebral artery occlusion (pMCAO. Methods Cytokine/chemokine expression was measured with a 25-plex bead array in the serum and brains of all three groups of mice at baseline (no surgery/naïve and at 3 hours and 24 hours following pMCAO. Brain inflammatory and neutrophil infiltrates were examined 24 hours following pMCAO. Results IL-6, keratinocyte chemoattractant (KC, granulocyte colony-stimulating factor (G-CSF and IL-10 were significantly decreased in MyD88−/− mice compared to WT mice following pMCAO. Significantly, decreased levels of the neutrophil chemoattractants KC and G-CSF corresponded with a trend toward fewer neutrophils in the brains of MyD88−/− mice. IP-10 was significantly decreased when either pathway was disrupted. MIP-1α was significantly decreased in TRIF-mutant mice, consistent with TRIF-dependent production. MyD88−/− mice showed elevations of a number of Th2 cytokines, such as IL-13, at baseline, which became significantly decreased following pMCAO. Conclusions Both MyD88 and TRIF mediate pathway-specific cytokine production following focal cerebral ischemia. Our results also suggest a compensatory Th2-type skew at baseline in MyD88−/− mice and a paradoxical switch to a Th1 phenotype following focal cerebral ischemia. The MyD88 pathway directs the expression of neutrophil chemoattractants following cerebral ischemia.

  2. Caffeine induced changes in cerebral circulation

    International Nuclear Information System (INIS)

    While the caffeine induced cerebral vasoconstriction is well documented, the effects of oral ingestion of the drug in a dose range comparable to the quantities in which it is usually consumed and the intensity and duration of the associated reduction in cerebral circulation are unknown. Cerebral blood flow was measured via the 133Xenon inhalation technique before and thirty and ninety minutes after the oral administration of 250 mg of caffeine or a placebo, under double-blind conditions. Caffeine ingestion was found to be associated with significant reductions in cerebral perfusion thirty and ninety minutes later. The placebo group showed no differences between the three sets of cerebral blood flow values

  3. Acute embolic cerebral ischemia as an initial presentation of Polycythemia Vera

    Directory of Open Access Journals (Sweden)

    Chhatwani Chirag M

    2016-06-01

    Full Text Available Introduction-Patients with Polycythemia vera (PV are at high risk for vaso-occlusive events including cerebral ischemia. Ischemic stroke may be the first presenting symptom of PV in 15% or more of those affected. It had been previously assumed that cerebral ischemic events were due to increased blood viscosity and platelet activation within the central nervous system arterial vessels. However, there are now a few isolated case reports of probable micro-embolic events originating from outside of the brain. Case report- A 45-year old man presented with left sided hemiperesis (recovered within 12 hours in our Medicine OPD. Hematologic investigation revealed a hyperviscous state (Hemoglobin 21.9gm% and PCV 66%. Acute infarction in right corona radiata and basal ganglia was found in magnetic resonance imaging(MRI of brain. Conclusion- Although unusual, acute embolic cerebral ischemia may be an initial presentation of PV. The etiology of stroke in polycythemic patients is likely to be multifactorial. All clinicians involved in the care of stroke patients should be aware of the association of PV and ischemic stroke. [Natl J Med Res 2016; 6(2.000: 210-211

  4. Comparison of cerebral blood flow and metabolism to flumazenil binding potential in patients with hemodynamic ischemia

    International Nuclear Information System (INIS)

    Because benzodiazepine receptors (BZR) are abundant in the cortex, an accumulation of 11C-flumazenil which selectively bind to BZR may be useful as markers of neuron density. The aims of this study were to clarify the relationship between neuron density and cerebral oxygen metabolism and to investigate the usefulness of 11C-flumazenil PET for detecting misery perfusion. The subjects were 16 patients with either internal carotid or middle cerebral arterial occlusive disease who underwent PET. Regional cerebral blood flow (CBF), regional cerebral oxygen extraction fraction (OEF), regional cerebral metabolic rate for oxygen (CMRO2) and regional cerebrovascular reserve capacity (CVRC) to acetazolamide were calculated. After CBF study, flumazenil binding potential was measured using the [11C] flumazenil bolus injection method. Forty-eight regions of interests (ROIs) were obtained in 16 patients. Flumazenil binding potential was correlated to CMRO2 (r=0.337, p=0.0069), but in 7 of 48 ROIs, CMRO2 decreased, whereas flumazenil binding potential did not change. Seventeen of 29 ROIs with decreased CVRC showed high OEF and the remaining 12 showed normal OEF. Flumazenil binding potential in ROIs with normal OEF was significantly lower than in those with high OEF (p=0.0003). This study demonstrated that 11C-flumazenil PET is useful for detecting misery perfusion in patients with hemodynamic ischemia. (author)

  5. Twin-twin transfusion syndrome: cerebral ischemia is not the only fetal MR imaging finding

    International Nuclear Information System (INIS)

    Twin-twin transfusion syndrome (TTTS) is a complication of monochorionic/diamniotic twin pregnancies. An imbalance of blood flow occurs through placental anastomoses, causing potentially significant morbidity and mortality in both twins. Although the sonographic findings of TTTS are well documented, we believe that MR imaging is a valuable adjunct. We describe the fetal MR imaging findings associated with TTTS. From 2003 to 2005, 37 consecutive MR imaging studies were performed on multiple-gestation pregnancies. Of the 37, 25 were consistent with TTTS, correlated and confirmed by sonographic criteria. MR fetal abnormalities were documented. Cerebral ischemia, which could not be demonstrated by sonography, was delineated well by MR imaging. New findings noted on fetal MR imaging were enlargement of cerebral venous sinuses in both twins, dilatation of the renal collecting system in the recipient, lung lesions in the recipient and cerebral malformations in the donor. MR imaging is an important adjunct in TTTS imaging. Its benefit over sonography is its clear definition of cerebral pathology, which is important for intervention and counseling. The new findings, particularly in the urinary tract and cerebral venous sinuses, also help support the diagnosis of TTTS and might reveal additional consequences of the altered hemodynamics that occur in TTTS. (orig.)

  6. Brain-derived neurotrophic factor inhibits glucose intolerance after cerebral ischemia

    Science.gov (United States)

    Shu, Xiaoliang; Zhang, Yongsheng; Xu, Han; Kang, Kai; Cai, Donglian

    2013-01-01

    Brain-derived neurotrophic factor is associated with the insulin signaling pathway and glucose tabolism. We hypothesized that expression of brain-derived neurotrophic factor and its receptor may be involved in glucose intolerance following ischemic stress. To verify this hypothesis, this study aimed to observe the changes in brain-derived neurotrophic factor and tyrosine kinase B receptor expression in glucose metabolism-associated regions following cerebral ischemic stress in mice. At day 1 after middle cerebral artery occlusion, the expression levels of brain-derived neurotrophic factor were significantly decreased in the ischemic cortex, hypothalamus, liver, skeletal muscle, and pancreas. The expression levels of tyrosine kinase B receptor were decreased in the hypothalamus and liver, and increased in the skeletal muscle and pancreas, but remained unchanged in the cortex. Intrahypothalamic administration of brain-derived neurotrophic factor (40 ng) suppressed the decrease in insulin receptor and tyrosine-phosphorylated insulin receptor expression in the liver and skeletal muscle, and inhibited the overexpression of gluconeogenesis-associated phosphoenolpyruvate carboxykinase and glucose-6-phosphatase in the liver of cerebral ischemic mice. However, serum insulin levels remained unchanged. Our experimental findings indicate that brain-derived neurotrophic factor can promote glucose metabolism, reduce gluconeogenesis, and decrease blood glucose levels after cerebral ischemic stress. The low expression of brain-derived neurotrophic factor following cerebral ischemia may be involved in the development of glucose intolerance. PMID:25206547

  7. Impact of Intra-Extracranial Hemodynamics on Cerebral Ischemia by Arterial Hypertension (Part 1

    Directory of Open Access Journals (Sweden)

    Alexander G. Kruglov, PhD, ScD

    2012-06-01

    Full Text Available The present study was conducted to examine the interaction of biochemical parameters within the blood flow, their effect on the cerebral blood flow, as well as the mechanisms of cerebral ischemia by stable arterial hypertension. The hemodynamics and biochemical indicators of cerebral blood flow without the additives of the extracranial blood were obtained by the catheterization method via a probe wedged at the level of the bulb of the superior jugular vein. Sampling of the arterial blood was done in the thoracic aorta. Correlation and factor analysis of the relationship of the biochemical substances within the blood flow, and of the hemodynamic indicators of the cerebral inflow and outflow of blood were conducted by stable arterial hypertension compared with similar data of the control group. The differences thus identified led to the conclusion that by stable arterial hypertension, there is a loss of the homeostatic control of the factors determining the rheological and thrombogenic properties of the blood involved in the formation of cerebral ischemic events.

  8. Brain-derived neurotrophic factor inhibits glucose intolerance after cerebral ischemia***

    Institute of Scientific and Technical Information of China (English)

    Xiaoliang Shu; Yongsheng Zhang; Han Xu; Kai Kang; Donglian Cai

    2013-01-01

    Brain-derived neurotrophic factor is associated with the insulin signaling pathway and glucose tabolism. We hypothesized that expression of brain-derived neurotrophic factor and its receptor may be involved in glucose intolerance fol owing ischemic stress. To verify this hypothesis, this study aimed to observe the changes in brain-derived neurotrophic factor and tyrosine kinase B receptor expression in glucose metabolism-associated regions fol owing cerebral ischemic stress in mice. At day 1 after middle cerebral artery occlusion, the expression levels of brain-derived neurotrophic factor were significantly decreased in the ischemic cortex, hypothalamus, liver, skeletal muscle, and pancreas. The expression levels of tyrosine kinase B receptor were decreased in the hypothalamus and liver, and increased in the skeletal muscle and pancreas, but remained unchanged in the cortex. Intrahypothalamic administration of brain-derived neurotrophic factor (40 ng) suppressed the de-crease in insulin receptor and tyrosine-phosphorylated insulin receptor expression in the liver and skeletal muscle, and inhibited the overexpression of gluconeogenesis-associated phosphoenolpy-ruvate carboxykinase and glucose-6-phosphatase in the liver of cerebral ischemic mice. However, serum insulin levels remained unchanged. Our experimental findings indicate that brain-derived neurotrophic factor can promote glucose metabolism, reduce gluconeogenesis, and decrease blood glucose levels after cerebral ischemic stress. The low expression of brain-derived neurotrophic factor fol owing cerebral ischemia may be involved in the development of glucose intolerance.

  9. Cerebral blood flow in cerebral ischemia. A review (with 1 color plate)

    DEFF Research Database (Denmark)

    Lassen, N A

    In the majority of apoplexy patients the absence of a primary haemorrhage points to acute vascular occclusion with regional ischemia as the initiating event. Yet, in many such cases in particular with transient symptoms, no occlusions can be found angiographically. This along with other evidences...

  10. Short-term sleep deprivation stimulates hippocampal neurogenesis in rats following global cerebral ischemia/reperfusion.

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    Oumei Cheng

    Full Text Available Sleep deprivation (SD plays a complex role in central nervous system (CNS diseases. Recent studies indicate that short-term SD can affect the extent of ischemic damage. The aim of this study was to investigate whether short-term SD could stimulate hippocampal neurogenesis in a rat model of global cerebral ischemia/reperfusion (GCIR.One hundred Sprague-Dawley rats were randomly divided into Sham, GCIR and short-term SD groups based on different durations of SD; the short-term SD group was randomly divided into three subgroups: the GCIR+6hSD*3d-treated, GCIR+12hSD-treated and GCIR+12hSD*3d-treated groups. The GCIR rat model was induced via the bilateral occlusion of the common carotid arteries and hemorrhagic hypotension. The rats were sleep-deprived starting at 48 h following GCIR. A Morris water maze test was used to assess learning and memory ability; cell proliferation and differentiation were analyzed via 5-bromodeoxyuridine (BrdU and neuron-specific enolase (NSE, respectively, at 14 and 28 d; the expression of hippocampal BDNF was measured after 7 d.The different durations of short-term SD designed in our experiment exhibited improvement in cognitive function as well as increased hippocampal BDNF expression. Additionally, the short-term SD groups also showed an increased number of BrdU- and BrdU/NSE-positive cells compared with the GCIR group. Of the three short-term SD groups, the GCIR+12hSD*3d-treated group experienced the most substantial beneficial effects.Short-term SD, especially the GCIR+12hSD*3d-treated method, stimulates neurogenesis in the hippocampal dentate gyrus (DG of rats that undergo GCIR, and BDNF may be an underlying mechanism in this process.

  11. Baicalin alleviates ischemia-induced memory impairment by inhibiting the phosphorylation of CaMKII in hippocampus.

    Science.gov (United States)

    Wang, Peng; Cao, Yonggang; Yu, Juan; Liu, Ruxia; Bai, Bing; Qi, Hanping; Zhang, Qianlong; Guo, Wenguang; Zhu, Hui; Qu, Lihui

    2016-07-01

    Baicalin has a significant neuroprotective effect in stroke. However, the mechanism remains unclear. This study was to reveal the mechanisms by which baicalin protected hippocampal neurons and improved learning and memory impairment after global cerebral ischemia/reperfusion in gerbil. In the present study, the Morris water maze test showed that baicalin significantly improved learning and memory impairment after global cerebral ischemia/reperfusion in gerbils. Laser scanning confocal fluorescence microscope examination showed that baicalin suppressed OGD-induced augmentation of intracellular calcium concentration. Western blotting analysis indicated that baicalin suppressed ischemia-caused elevated phosphorylation level of CaMKII in vivo, in hippocampal neurons in culture, and in SH-SY5Y cells in culture. Western blotting, TUNEL and RNA interference technology were applied to detect effects of baicalin on neuronal apoptosis. We found that baicalin, a CaMKII inhibitor and knocking down the CaMKII prevented OGD-induced apoptosis of hippocampal or SH-SY5Y cells in culture. Therefore, these results suggested that baicalin improves learning and memory impairment induced by global cerebral ischemia/reperfusion in gerbils via attenuating the phosphorylation level of CaMKII and further preventing hippocampal neuronal apoptosis. PMID:27016057

  12. Electrical stimulation upregulates angiopoietin-1/Tie-2 mRNA expression in a rat model of focal cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Shasha Li; Yonghong Yang; Qiang Gao; Jing He; Chengqi He

    2010-01-01

    Angiopoietin-1/tyrosine kinase with immunoglobulin and epidermal growth factor homology domains 2(Tie-2)is a newly discovered signaling pathway of angiogenesis.Angiogenesis benefits recovery of neurological functions such as swallowing.In the present study,a rat model of dysphagia following stroke was induced by middle cerebral artery occlusion to investigate the influence of low frequency electrical stimulus with bidirectional square waves and triangular waves on angiopoietin-1/Tie-2 mRNA expression.Reverse transcription-polymerase chain reaction results showed that low frequency electrical stimulus significantly improved the neurological scores of the model rats,and increased angiopoietin-1/Tie-2 mRNA expression.This demonstrates that low frequency electrical stimulation can ameliorate neurological function in rats with focal brain ischemia,potentially through regulation of angiopoietin-1/Tie-2 expression in the angiogenesis pathway.

  13. Radix Ilicis Pubescentis total flavonoids combined with mobilization of bone marrow stem cells to protect cerebral ischemia/reperfusion injury

    OpenAIRE

    Ming-san Miao; Lin Guo; Rui-qi Li; Xiao Ma

    2016-01-01

    Previous studies have shown that Radix Ilicis Pubescentis total flavonoids have a neuroprotective effect, but it remains unclear whether Radix Ilicis Pubescentis total flavonoids have a synergistic effect with the recombinant human granulocyte colony stimulating factor-mobilized bone marrow stem cell transplantation on cerebral ischemia/reperfusion injury. Rat ischemia models were administered 0.3, 0.15 and 0.075 g/kg Radix Ilicis Pubescentis total flavonoids from 3 days before modeling to 2 ...

  14. Cerebral Ischemia Mediates the Effect of Serum Uric Acid on Cognitive Function

    Science.gov (United States)

    Vannorsdall, Tracy D.; Jinnah, H.A.; Gordon, Barry; Kraut, Michael; Schretlen, David J.

    2016-01-01

    Background and Purpose High normal concentrations of serum uric acid (UA) are associated with mild cognitive dysfunction and increased cerebral ischemia as indexed by white matter hyperintensity volumes. We hypothesized that individual differences in white matter hyperintensities mediate the association between UA and mild cognitive dysfunction. Methods One hundred eighty community-dwelling adults aged 20 to 96 years completed neuropsychological testing, laboratory blood studies, and a brain MRI scan. Results Serum UA was associated (Pischemia might mediate the association between UA and cognitive dysfunction. Even mild elevations in UA appear to contribute to structural and functional brain changes. PMID:18772442

  15. Cerebral ischemia enhances vascular angiotensin AT1 receptor-mediated contraction in rats

    DEFF Research Database (Denmark)

    Stenman, Emelie; Edvinsson, Lars

    2004-01-01

    MCA occlusion (P<0.05). The angiotensin II type 1 (AT1) receptor antagonists candesartan and losartan abolished the enhanced responses to angiotensin II (P<0.05), whereas the AT2 receptor antagonist PD123319 had no effect. The amount of AT1 receptor mRNA was lower in the occluded MCAs compared with....... These results support a role for AT1 receptors in cerebral ischemia, and we think that AT1 receptors might be a future therapeutic target in ischemic stroke....

  16. Bumetanide promotes neural precursor cell regeneration and dendritic development in the hippocampal dentate gyrus in the chronic stage of cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Wang-shu Xu

    2016-01-01

    Full Text Available Bumetanide has been shown to lessen cerebral edema and reduce the infarct area in the acute stage of cerebral ischemia. Few studies focus on the effects of bumetanide on neuroprotection and neurogenesis in the chronic stage of cerebral ischemia. We established a rat model of cerebral ischemia by injecting endothelin-1 in the left cortical motor area and left corpus striatum. Seven days later, bumetanide 200 µg/kg/day was injected into the lateral ventricle for 21 consecutive days with a mini-osmotic pump. Results demonstrated that the number of neuroblasts cells and the total length of dendrites increased, escape latency reduced, and the number of platform crossings increased in the rat hippocampal dentate gyrus in the chronic stage of cerebral ischemia. These findings suggest that bumetanide promoted neural precursor cell regeneration, dendritic development and the recovery of cognitive function, and protected brain tissue in the chronic stage of ischemia.

  17. Bumetanide promotes neural precursor cell regeneration and dendritic development in the hippocampal dentate gyrus in the chronic stage of cerebral ischemia

    Science.gov (United States)

    Xu, Wang-shu; Sun, Xuan; Song, Cheng-guang; Mu, Xiao-peng; Ma, Wen-ping; Zhang, Xing-hu; Zhao, Chuan-sheng

    2016-01-01

    Bumetanide has been shown to lessen cerebral edema and reduce the infarct area in the acute stage of cerebral ischemia. Few studies focus on the effects of bumetanide on neuroprotection and neurogenesis in the chronic stage of cerebral ischemia. We established a rat model of cerebral ischemia by injecting endothelin-1 in the left cortical motor area and left corpus striatum. Seven days later, bumetanide 200 µg/kg/day was injected into the lateral ventricle for 21 consecutive days with a mini-osmotic pump. Results demonstrated that the number of neuroblasts cells and the total length of dendrites increased, escape latency reduced, and the number of platform crossings increased in the rat hippocampal dentate gyrus in the chronic stage of cerebral ischemia. These findings suggest that bumetanide promoted neural precursor cell regeneration, dendritic development and the recovery of cognitive function, and protected brain tissue in the chronic stage of ischemia.

  18. An Early Continuous Experimental Study on Magnetic Resonance Diffusion-weighted Image of Focal Cerebral Ischemia and Reperfusion in Rats

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    The chronological and spatial rules of changes during focal cerebral ischemia and reperfusion in different brain regions with magnetic resonance diffusion-weighted imaging (DWI) in a model of occlusion of middle cerebral artery (MCAO) and the development of cytotoxic edema in acute phase were explored. Fifteen healthy S-D rats with MCA occluded by thread-emboli were randomly divided into three groups. 15 min after the operation, the serial imaging was scanned on DWI for the three groups. The relative mean signal intensity (RMSI) of the frontal lobe, parietal lobe, lateral cauda-putamen, medial cauda-putamen and the volume of regions of hyperintense signal on DWI were calculated. After the last DWI scanning, T2 WI was performed for the three groups. After 15min ischemia, the rats was presented hyperintense signals on DWI. The regions of hyperintense signal were enlarged with prolonging ischemia time. The regions of hyperintense signal were back to normal after 60 min reperfusion with a small part remaining to show hyperintense signal. The RMSIs of parietal lobe and lateral cauda-putamen were higher than that of the frontal lobe and medial cauda-putamen both in ischemia phase and recanalization phase. The three groups werenormal on T2WI imaging. DWI had good sensitivity to acute cerebral ischemia, which was used to study the chronological and spatial rules of development of early cell edema in ischemia regions.

  19. Matrix metalloproteinase-9 expression and blood brain barrier permeability in the rat brain after cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Lifang Lei; Xiaohong Zi; Qiuyun Tu

    2008-01-01

    BACKGROUND: The integrity of the blood brain barrier (BBB) plays an important role in the patho-physiological process of cerebral ischemia/reperfusion injury. It has been recently observed that metalloproteinase-9 (MMP-9) is closely related to cerebral ischemia/reperfusion injuryOBJECTIVE: This study was designed to observe MMP-9 expression in the rat brain after cerebral ischemia/reperfusion injury and to investigate its correlation to BBB permeability.DESIGN, TIME AND SETTING: This study, a randomized controlled animal experiment, was performed at the Institute of Neurobiology, Central South University between September 2005 and March 2006.MATERIALS: Ninety healthy male SD rats, aged 3-4 months, weighing 200-280g, were used in the present study. Rabbit anti-rat MMP-9 polyclonal antibody (Boster, Wuhan, China) and Evans blue (Sigma, USA) were also used.METHODS: All rats were randomly divided into 9 groups with 10 rats in each group: normal control group, sham-operated group, and ischemia for 2 hours followed by reperfusion for 3,6,12 hours, 1,2,4 and 7 days groups. In the ischemia/reperfusion groups, rats were subjected to ischemia/reperfusion injury by suture occlusion of the right middle cerebral artery. In the sham-operated group, rats were merely subjected to vessel dissociation. In the normal control group, rats were not modeled.MAIN OUTCOME MEASURES: BBB permeability was assessed by determining the level of effusion of Evans blue. MMP-9 expression was detected by an immunohistochemical method.RESULTS: All 90 rats were included in the final analysis. BBB permeability alteration was closely correlated to ischemia/reperfusion time. BBB permeability began to increase at ischemia/reperfusion for 3 hours, then it gradually reached a peak level at ischemia/reperfusion for 1 day, and thereafter it gradually decreased. MMP-9 expression began to increase at ischemia/reperfusion for 3 hours, then gradually reached its peak level 2 days after perfusion, and thereafter

  20. Interventional effect of flunarizine on the expression of cyclooxygenase-2 and plasminogen activator inhibitor type-1 during experimental Cerebral ischemia/reperfusion in gerbils

    Institute of Scientific and Technical Information of China (English)

    Wensheng Zhou; Zhiping Hu; Yan Hong

    2006-01-01

    BACKGROUND:Some researches suggest that induced cyclooxygenase-2 (COX-2) can cause brain injury through a series of ways at the phase of cerebral ischemia/hypoxia.Plasminogen activator inhibitor type-1(PAI-1)is a kind of inhibitor of serine stretch protein enzyme and is able to protect cell surface and microvascular basement membrane from degradation of protease and also protect contact surface among cells so as to maintain integrality of tissue structure.However,correlation of protective effect of flunarizine on brain with COX-2 and PAI-1 should be studied further.OBJECTIVE:To observe the effect of flunadzine on expressions of COX-2 and PAI-1 protein in forebrain and degree of brain injury among gerbils after cerebral ischemia.DESIGN:A randomized controlled animal study.SEITING:Department of Neurology,the Second Xiangya Hospital of Central South University;Department of Neurology,Mawangdui Hospital of Hunan Province.MATERIALS:A total of 40 healthy gerbils,of both genders,aged 9 months,weighing(90±10)g,were selected in this study.Anti-COX-2 multi-antibody,anti-PAI-1 multi-antibody,SABC immunohistochemical kit and DAB kit were provided by Wuhan Boster Biological Engineering Co.,Ltd.;and flunarizine capsule was provided by Xi'an Yangsen Pharmaceutical Company(batch number:041018726,dosage:5 mg/pill).METHODS:The experiment was Carried out in Laboratory of Mental Disease,Hunan Provincial Gedatdcs Institute affiliated by Hunan Provincial Mawangdui Hospital from January 2004 to March 2005.① All gerbils were randomly divided into cerebral ischemia group,flunarizine intervention group,sham operation group and normal control group with 10 in each group.Gerbils in normal control group were only cut off their heads.Gerbils in sham operation group were only dissected their bilateral common carotid arteries and sacdficad 1 day later.Gerbils in cerebral ischemia group and flunanzine intervention group were anesthetized,centrally cut open skin of neck,bluntly dissected

  1. Repeated episodes of focal cerebral ischemia in a patient with mitral valve prolapse and migraine headache

    Directory of Open Access Journals (Sweden)

    Raičević Ranko

    2002-01-01

    Full Text Available Migraine is episodic, paroxysmal disorder where the headache represents the central symptom and is followed with different combinations of neurological gastrointestinal and vegetative changes. Not until the diagnostic procedures were developed, ischemic lesions were verified even in the patients with ordinary migraine. This is a report of a patient with migraine headache followed twice by verified episodes of temporary ischemic attacks and verified focal ischemic lesion of cerebral parenchyma. The mitral valve prolapse was also detected. This all imposed the administration of combined prophylactic antimigrainous and anticoagulant therapy as an imperative because of the risk of the development of repeated ischemia of cerebral tissue. This association also confirmed an opinion that migraine is a wider disorder with the dominant dysfunction of limbic system.

  2. Lettuce glycoside B ameliorates cerebral ischemia reperfusion injury by increasing nerve growth factor and neurotrophin-3 expression of cerebral cortex in rats

    Directory of Open Access Journals (Sweden)

    Heqin Zhan

    2014-01-01

    Full Text Available Aims: The aim of the study was to investigate the effects of LGB on cerebral ischemia-reperfusion (I/R injury in rats and the mechanisms of action of LGB. Materials and Methods: The study involved extracting LGB from P. laciniata, exploring affects of LGB on brain ischemia and action mechanism at the molecular level. The cerebral ischemia reperfusion injury of middle cerebral artery occlusion was established. We measured brain histopathology and brain infarct rate to evaluate the effects of LGB on brain ischemia injury. The expressions of nerve growth factor (NGF and neurotrophin-3 (NT-3 were also measured to investigate the mechanisms of action by the real-time polymerase chain reaction and immunohistochemistry. Statistical analysis: All results were mentioned as mean ± standard deviation. One-way analysis of variance was used to determine statistically significant differences among the groups. Values of P < 0.05 were considered to be statistically significant. Results: Intraperitoneal injection of LGB at the dose of 12, 24, and 48 mg/kg after brain ischemia injury remarkably ameliorated the morphology of neurons and brain infarct rate (P < 0.05 , P < 0.01. LGB significantly increased NGF and NT-3 mRNA (messenger RNA and both protein expression in cerebral cortex at the 24 and 72 h after drug administration (P < 0.05, P < 0.01. Conclusions: LGB has a neuroprotective effect in cerebral I/R injury and this effect might be attributed to its upregulation of NGF and NT-3 expression ability in the brain cortex during the latter phase of brain ischemia.

  3. Cerebral energy metabolism during induced mitochondrial dysfunction

    DEFF Research Database (Denmark)

    Nielsen, T H; Bindslev, TT; Pedersen, S M;

    2013-01-01

    In patients with traumatic brain injury as well as stroke, impaired cerebral oxidative energy metabolism may be an important factor contributing to the ultimate degree of tissue damage. We hypothesize that mitochondrial dysfunction can be diagnosed bedside by comparing the simultaneous changes in...... brain tissue oxygen tension (PbtO(2)) and cerebral cytoplasmatic redox state. The study describes cerebral energy metabolism during mitochondrial dysfunction induced by sevoflurane in piglets....

  4. Astrocytic effect of low molecular weight heparin-superoxide dismutase conjugate in interleukin-6 overexpressing mice following local cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Yizhao Li; Guixiang Cui; Qingde Wang; Hongxia Liu; Xiaoxia Zhang; Fengshan Wang; Keqin Xie

    2009-01-01

    BACKGROUND: Studies have shown that low molecular weight heparin-superoxide dismutase conjugate exhibits a remarkable neuroprotective effect.OBJECTIVE: To investigate the effect of low molecular weight heparin-superoxide dismutase conjugate on astrocytes in an interleukin-6 (IL-6) overexpressing mice following local cerebral ischemia.DESIGN, TIME AND SETTING: Randomized, cytological, controlled, animal study was performed in the Department of Physiology and Neuroscience, Neurology and Biochemistry and Molecular Biology, Medical University of South Carolina from January 2005 to March 2005.MATERIALS: Nine IL-6 transgenic mice, irrespective of gender, were randomly divided into three groups: sham-operated, model, and treatment, with three mice in each group. With exception of the sham-operated group, right middle cerebral artery occlusion was induced in the mice.Expression of glial fibrillary acidic protein, an astrocyte marker, was determined by immunohistochemistry. Low molecular weight heparin-superoxide dismutase conjugate was purchased from Biochemistry and Biotechnique Institute, Shandong University.METHODS: Two minutes prior to ischemia induction, 0.5 mL/kg saline or 20 000 U/kg low molecular weight heparin-superoxicle dismutase conjugate were administrated via the femoral artery in the model group and treatment group, respectively. The sham-operated group underwent the same protocols, with the exception of occlusion and treatment.MAIN OUTCOME MEASURES: The number of glial fibrillary acidic protein-positive cells was quantified under light microscopy (x200).RESULTS: In the sham-operated group, there were a large number of astrocytes in the IL-6 transgenic mice. However, the cell bodies were small, and the branches were few and thin. The number of astrocytes in the model group was remarkably less than the sham-operated group. Compared to the model and sham-operated groups, the number of astrocytes significantly increased, and the cell body became larger

  5. Hydrogen saline offers neuroprotection by reducing oxidative stress in a focal cerebral ischemia-reperfusion rat model

    OpenAIRE

    Liu Ying; Liu Wenwu; Sun Xuejun; Li Runping; Sun Qiang; Cai Jianmei; Kang Zhimin; Lv Shijun; Zhang John H; Zhang Wei

    2011-01-01

    Abstract Hydrogen gas is neuroprotective in cerebral ischemia animal models. In this study, we tested the neuroprotective effects of hydrogen saline, which is safe and easy to use clinically, in a rat model of middle cerebral artery occlusion (MCAO). Sprague-Dawley male rats weighting 250-280 g were divided into sham, MCAO plus hydrogen saline and MCAO groups, and subjected to 90-min ischemia followed by 24 h of reperfusion. Hydrogen saline was injected intraperitoneally at 1 ml/100 g body we...

  6. Electroacupuncture-attenuated ischemic brain injury increases insulin-like growth factor-1expression in a rat model of focal cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Huanmin Gao; Ling Wang; Yunliang Guo

    2010-01-01

    Acupuncture has recently gained popularity in many countries as an alternative and complementary therapeutic intervention.Previous studies have shown that changes in genes,proteins,and their metabolites were measureable during acupuncture for treatment of cerebral ischemia.Through the use of in situ hybridization and immunohistochemistry,the present study confirmed that electroacupuncture increased insulin-like growth factor-1 mRNA and protein expression in the corpus striatum following cerebral ischemia,reduced brain edema following middle cerebral artery occlusion repeffusion,and decreased infarct volume.Results suggested that electroacupuncture is effective in the relief of cerebral ischemia by increasing endogenous insulin-like growth factor-1 expression.

  7. Reversal of apparent diffusion coefficient (ADC) following transient focal cerebral ischemia in cats

    International Nuclear Information System (INIS)

    To determine the minimal threshold ADC ratio suggesting reversible ischemia in a temporary model of MCAO. Seven Korean cats weighing 3-3.5 kg were used as a temporary model of MCAO. The MCA was occluded for 1 hour, and diffusion-weighted images (DWI), and ADC and regional cerebral blood volume (rCBV) maps, were obtained at 1, 3, 6 and 24 hours after reperfusion using a 1.5T MR unit. The Cats were sacrificed 24 hours after imaging. Triphenyl tetrazolium chloride (TTC) staining of brain slices was performed, and DWI images and TTC-stained brain slices were compared with the naked eye. Reversible ischemia was defined as the area of high signal intensity at 1-hour DWI that normalized at follow-up DWI and in which TTC staining was normal. Using the ADC image obtained at 1 hour after reperfusion, 60 ADC ratios were obtained in the periphery of the infarct and reversible ischemia. Tissue survival showing normal TTC staining was used for final determination. The sensitivity and specificity of each ADC ratio was obtained and an ROC curve was plotted. Five of seven cats showed the reversible ischemia. An area of high signal intensity was seen on DWI images obtained 1 hours after reperfusion, and this improved at follow-up imaging. The distribution of the ADC ratio in the periphery of the infarct core was 0.71-0.81, and in the periphery of reversible ischemia it was 0.79-0.93. The ADC ratio of 0.80 obtained 1 hr after reperfusion predicted the survival of the ischemic tissure with 93% sensitivity and 90% specificity. The ADC ratio of the reversible ischemia was 0.82 ±0.03 at 1 hour after reperfusion, and this was higher than that of the infarct, which was 0.74±0.03. The minimal threshold ADC ratio suggesting reversible ischemia in this temporary model of MCAO was 0.80

  8. bcl-xl over-expression in transgenic mice reduces cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Furong Wang; Yongsheng Jiang; Yan Liu; Wenwu Xiao; Suming Zhang

    2008-01-01

    BACKGROUND: Basal cell lymphoma-extra large (bcl-xl) can inhibit neuronal apoptosis by stabilizing the mitochondrial membrane and suppressing cytochrome C release into the cytoplasm. OBJECTIVE: This study aimed to further investigate the cascade reaction pathway of cellular apoptosis. We established an ischemia/dreperfusion model by middle cerebral artery occlusion (MCAO) in transgenic and wild-type mice, and observed changes in the number and distribution of apoptotic neural cells, differences in cerebral infarct volume, in neurological function score, and in cytochrome C expression in the ischemic cerebral cortex, at different time points, DESIGN AND SETTING: The present gene engineering and cell biology experiment was performed at the Laboratory of Biology, Hubei Academy of Agricultural Sciences and at the Laboratory of Immunology, Tongji Medical College, Huazhong University of Science and Technology. MATERIALS: Male bcl-xl over-expression Kunming mice aged 8 weeks and age-matched male wild-type mice were used for this study. Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) kits were purchased from Boliman, France. Cytochrome C antibody and Bcl-x immunohistochemical kit were purchased from PharMingen, USA and Santa Cruz Biotechnology, USA, respectively. METHODS: Following MCAO and reperfusion, apoptosis in the ischemic cerebral cortex was detected by the TUNEL assay. Prior to MCAO and 3 hours after reperfusion, the Bcl-xl protein level in the ischemic cerebral cortex was measured by immunohistochemistry. At 3, 6, 12 and 24 hours after reperfusion, the level of cytochrome C in the ischemic cerebral cortex was examined by western blot analysis. Subsequent to MCAO, cerebral infarct volume measurement and neurological examination were performed. MAIN OUTCOME MEASURES: Neural cell apoptosis and cytochrome C expression in the ischemic cerebral cortex; cerebral infarct volume and neurological function score. RESULTS: Twenty-four hours after

  9. Effects of transection of cervical sympathetic trunk on cerebral infarct volume and oxygen free radical levels in rats with focal cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Liangzhi Xiong; Yongxia Shi; Feng Xiao; Qingxiu Wang

    2008-01-01

    BACKGROUND: Stellate ganglion block (SGB) plays a protective role on the brain, but the precise mechanism of action is not clear.OBJECTIVE: To simulate SGB by transection of the cervical sympathetic trunk (TCST) and to investigate the TCST effects on changes in cerebral infarct volume and oxygen free radical levels in rats with focal cerebral ischemia/reperfusion injury.DESIGN, TIME AND SETTING: A complete randomized control animal experiment was performed at the Institute of Neurological Diseases of Taihe Hospital, Yunyang Medical College from February to December 2005.MATERIALS: A total of 101 healthy Wistar rats, weighing 280-320g, of both genders, aged 17-18 weeks, were used in this study. 2,3,5-triphenyltetrazolium chloride (TTC) was purchased from Changsha Hongyuan Biological Company. Superoxide dismutase (SOD), malondialdehyde (MDA) and nitric oxide (NO) assay kits were provided by Nanjing Jiancheng Bioengineering Institute.METHODS: Rats were randomly divided into a TCST group, a model group and a sham operation group. Successful models were included in the final analysis, with at least 20 rats in each group. After TCST, rat models of focal cerebral ischemia/reperfusion injury were established in the TCST group by receiving middle cerebral artery occlusion (MCAO) by the intraluminal suture method for 2 hours, followed by 24 hours of reperfusion. Rat models of focal cerebral ischemia/reperfusion injury were made in the model group. Rats in the sham operation group underwent experimental procedures as for the model group, threading depth of 10mm, and middle cerebral artery was not ligated.MAIN OUTCOME MEASURES: Brain tissue sections of ten rats from each group were used to measure cerebral infarct volume by TTC staining. Brain tissue homogenate of another ten rats from each group was used to detect SOD activities, MDA contents and NO levels. Rat neurological function was assessed by neurobehavioral measures.RESULTS: Cerebral infarct volume was bigger in the

  10. A role for interferon-gamma in focal cerebral ischemia in mice

    DEFF Research Database (Denmark)

    Lambertsen, Kate Lykke; Gregersen, Rikke; Meldgaard, Michael;

    2004-01-01

    damage by mechanisms that appear to be independent of TNF or synergistic neurotoxic interactions of IFNgamma and TNF Irrespective of the mechanism(s) involved, this enhancing effect of IFNgamma on ischemia-induced neurotoxicity may need to be considered in diseases where immune IFNgamma is involved, such...

  11. Inhibitory Effects of Isoquinoline Alkaloid Berberine on Ischemia-Induced Apoptosis via Activation of Phosphoinositide 3-Kinase/Protein Kinase B Signaling Pathway

    OpenAIRE

    Kim, Mia; Shin, Mal Soon; Lee, Jae Min; Cho, Han Sam; Kim, Chang Ju; Kim, Young Joon; Choi, Hey Ran; Jeon, Jung Won

    2014-01-01

    Purpose Berberine is a type of isoquinoline alkaloid that has been used to treat various diseases. A neuroprotective effect of berberine against cerebral ischemia has been reported; however, the effects of berberine on apoptosis in relation to reactive astrogliosis and microglia activation under ischemic conditions have not yet been fully evaluated. In the present study, we investigated the effects of berberine on global ischemia-induced apoptosis, and focused on the phosphoinositide 3-kinase...

  12. Effect of tetramethylpyrazine on the spatial learning and memory function of rats after focal cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Jianjun Zhao; Yong Liu; Xinlin Chen; Jianxin Liu; Yingfang Tian; Pengbo Zhang; Qianyan Kang; Fen Qiu

    2006-01-01

    BACKGROUND: Tetramethylpyrazine (TMP) presents the effect of anti-platelet aggregation, reduces arterial resistance, increases cerebral blood flow, and improves microcirculation.OBJECTIVE: To observe the effects of TMP on the learning and memory abilities and the number of neurons in cortex and hippocampus after focal cerebral ischemia in rats DESIGN: A randomized controlled trial.SETTING: Department of Human Anatomy and Histological Embryology, School of Medicine, Xi'an Jiaotong University.MATERIALS: Fifty adult male Sprague-Dawley rats, weighing 250-300 g were supplied by the Experimental Animal Center, School of Medicine, Xi'an Jiaotong University. TMP was purchased from Wuxi Seventh Pharmaceutical Co. Ltd (Lot Number: 2004051106, Specification: 2 mL/piece).METHODS: The experiments were carried out in School of Medicine of Xi'an Jiaotong University from June 2004 to May 2005. The 50 rats were randomly divided into five groups according to the random number table method: sham-operated group, cerebral ischemia control group, Iow-dose TMP group, middle-dose TMP group and high-dose TMP group, 10 rats in each group. Rats in the TMP groups were immediately treated with intraperitoneal injection of TMP of 40, 80 and 120 mg/kg respectively, and those in the sham-operated group and cerebral ischemia control group were injected intraperitoneally by isovolume saline, once a day for 14 days successively. On the 15th day, the spatial learning and memory abilities of the rats were assessed with the Morris water maze test, and then the changes of neuron numbers in cortex and hippocampus were observed by Nissl staining of brain sections.MAIN OUTCOME MEASURES: The results of Morris water maze test and the changes of neuron numbers in cortex and hippocampus by Nissl staining of brain sections were observed,RESULTS : Finally 39 rats were involved in the analysis of results, and the other 11 died of excessive anesthesia or failure in model establishment. ① The rats in the

  13. Roles of Oxidative Stress, Apoptosis, PGC-1α and Mitochondrial Biogenesis in Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    Ding-I Yang

    2011-10-01

    Full Text Available The primary physiological function of mitochondria is to generate adenosine triphosphate through oxidative phosphorylation via the electron transport chain. Overproduction of reactive oxygen species (ROS as byproducts generated from mitochondria have been implicated in acute brain injuries such as stroke from cerebral ischemia. It was well-documented that mitochondria-dependent apoptotic pathway involves pro- and anti-apoptotic protein binding, release of cytochrome c, leading ultimately to neuronal death. On the other hand, mitochondria also play a role to counteract the detrimental effects elicited by excessive oxidative stress. Recent studies have revealed that oxidative stress and the redox state of ischemic neurons are also implicated in the signaling pathway that involves peroxisome proliferative activated receptor-γ (PPARγ co-activator 1α (PGC1-α. PGC1-α is a master regulator of ROS scavenging enzymes including manganese superoxide dismutase 2 and the uncoupling protein 2, both are mitochondrial proteins, and may contribute to neuronal survival. PGC1-α is also involved in mitochondrial biogenesis that is vital for cell survival. Experimental evidence supports the roles of mitochondrial dysfunction and oxidative stress as determinants of neuronal death as well as endogenous protective mechanisms after stroke. This review aims to summarize the current knowledge focusing on the molecular mechanisms underlying cerebral ischemia involving ROS, mitochondrial dysfunction, apoptosis, mitochondrial proteins capable of ROS scavenging, and mitochondrial biogenesis.

  14. Application of magnetic resonance imaging for monitoring stem cell transplantation for the treatment of cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Xianglin Zhang; Gang Wang; Furen Dong; Zhiming Wang

    2012-01-01

    OBJECTIVE: To identify global research trends in the application of MRI for monitoring stem cell transplantation using a bibliometric analysis of Web of Science. DATA RETRIEVAL: We performed a bibliometric analysis of studies relating to the application of MRI for detecting stem cell transplantation for the treatment of cerebral ischemia using papers in Web of Science published from 2002 to 2011. SELECTION CRITERIA: The inclusion criteria were: (a) peer-reviewed articles on the application of MRI for detecting transplanted stem cells published and indexed in Web of Science; (b) year of publication between 2002 and 2011. Exclusion criteria were: (a) articles that required manual searching or telephone access; (b) some corrected papers.MAIN OUTCOME MEASURES: (1) Annual publication output; (2) distribution according to journals; (3) distribution according to institution; (4) distribution according to country; (5) top cited authors over the last 10 years.RESULTS: A total of 1 498 studies related to the application of MRI for monitoring stem cell transplantation appeared in Web of Science from 2002 to 2011, almost half of which were derived from American authors and institutes. The number of studies on the application of MRI for detecting stem cell transplantation has gradually increased over the past 10 years. Most papers on this topic appeared in Magnetic Resonance in Medicine. CONCLUSION: This analysis suggests that few experimental studies have been investigated the use of MRI for tracking SPIO-labeled human umbilical cord blood-derived mesenchymal stem cells during the treatment of cerebral ischemia.

  15. Comparison between cerebral ischemia disease and multiple sclerosis by using MR diffusion tensor imaging

    International Nuclear Information System (INIS)

    Objective: To assess the value of MR diffusion tensor imaging (DTI) in the differentiation between the patients with cerebral ischemia disease and multiple sclerosis. Methods: MR diffusion tensor imaging was performed in thirty-two patients with internal carotid artery stenosis ≥70% and eighteen patients with clinical diagnosed multiple sclerosis. Fractional anisotropy (FA) value of the germ, splenium, body of the corpus callosum, and the white matter of the frontal and occipital lobe were measured respectively, and independent-sample t-test statistical analysis was performed. Results: The FA value was decreased obviously in the anterior and posterior body and splenium of the corpus callosumin the MS patients compared with the ICA severe stenosis patients (0.67 ± 0.12 vs. 0.75 ± 0.05, t=3.443, P0.05; 0.34 ± 0.08 vs. 0.34 ± 0.05, t=0.137, P> 0.05; 0.29 ± 0.06 vs. 0.40 ± 0.06, t=5.449, P>0.05). Conclusion: DTI can noninvasive detect the potential disorder of corpus callosum in vivo, thus providing useful information to differentiate the cerebral ischemia disease from multiple sclerosis. (authors)

  16. Loss of endoplasmic reticulum Ca homeostasis:contribution to neuronal cell death during cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Ankur BODALIA; Hongbin LI; Michael F JACKSON

    2013-01-01

    The loss of Ca2+ homeostasis during cerebral ischemia is a hallmark of impending neuronal demise.Accordingly,considerable cellular resources are expended in maintaining low resting cytosolic levels of Ca2+.These include contributions by a host of proteins involved in the sequestration and transport of Ca2+,many of which are expressed within intracellular organelles,including lysosomes,mitochondria as well as the endoplasmic reticulum (ER).Ca2+ sequestration by the ER contributes to cytosolic Ca2+ dynamics and homeostasis.Furthermore,within the ER Ca2+ plays a central role in regulating a host of physiological processes.Conversely,impaired ER Ca2+ homeostasis is an important trigger of pathological processes.Here we review a growing body of evidence suggesting that ER dysfunction is an important factor contributing to neuronal injury and loss post-ischemia.Specifically,the contribution of the ER to cytosolic Ca2+ elevations during ischemia will be considered,as will the signalling cascades recruited as a consequence of disrupting ER homeostasis and function.

  17. Repeated short-term daily exercise ameliorates oxidative cerebral damage and the resultant motor dysfunction after transient ischemia in rats

    OpenAIRE

    Hamakawa, Michiru; Ishida, Akimasa; Tamakoshi, Keigo; Shimada, Haruka; Nakashima, Hiroki; Noguchi, Taiji; Toyokuni, Shinya; Ishida, Kazuto

    2013-01-01

    Long-term exercise prior to brain ischemia enhances the activities of antioxidant enzymes and leads to a significant reduction in brain damage and neurological deficits in rats subjected to transient middle cerebral artery occlusion. However, it has not been established whether relatively short-term exercise generates similar results following middle cerebral artery occlusion. We aimed to determine whether short-term exercise could reduce oxidative damage and prevent sensori-motor dysfunction...

  18. The Effects of Antecedent Exercise on Motor Function Recovery and Brain-derived Neurotrophic Factor Expression after Focal Cerebral Ischemia in Rats

    OpenAIRE

    KIM, GYEYEOP; Kim, Eunjung

    2013-01-01

    [Purpose] In the present study, we investigated the effect of antecedent exercise on functional recovery and brain-derived neurotrophic factor (BDNF) expression following focal cerebral ischemia injury. [Subjects] The rat middle cerebral artery occlusion (MCAO) model was employed. Adult male Sprague-Dawley rats were randomly divided into 4 groups. Group I included untreated normal rats (n=10); Group II included untreated rats with focal cerebral ischemia (n=10); Group III included rats that p...

  19. Pretreatment of rats with increased bioavailable berberine attenuates cerebral ischemia-reperfusion injury via down regulation of adenosine-5'monophosphate kinase activity.

    Science.gov (United States)

    Chen, Weijia; Wei, Shengnan; Yu, Yang; Xue, Huan; Yao, Fan; Zhang, Ming; Xiao, Jun; Hatch, Grant M; Chen, Li

    2016-05-15

    Berberine (BBR) exhibits multiple beneficial biological effects. However, poor bioavailability of BBR has limited its clinical application. We previously demonstrated that solid dispersion of BBR with sodium caprate (HGSD) remarkably improves its bioavailability. We examined whether this increased bioavailability of BBR could protect the brain from ischemia-reperfusion (IR) induced injury. Rats treated with HGSD, SC and saline for 7 days then subjected to cerebral ischemia reperfusion by middle cerebral artery occlusion for 2h followed 12h reperfusion. Neurological deficit scores, infarct size, SOD, MDA and NO levels were examined. P-AMPK, Bax, cleaved-Caspase-3 in brain was determined. To further probe for the mechanism of beneficial effect of HGSD, PC12 cells were incubated with serum from control or HGSD pretreated animals, incubated with 300μM H2O2 to induce apoptosis. Caspase-3 activity and cell apoptosis was evaluated. HGSD pretreatment significantly attenuated neurological deficit scores, reduced infarct size, increased SOD and decreased MDA and NO after cerebral IR injury compared to controls. Meanwhile, HGSD pretreatment significantly reduced expression of p-AMPK, Bax, cleaved-Caspase-3 after cerebral IR injury. Sodium caprate (100mg/kg/d) pretreatment alone did not exhibit any of these beneficial effects. PC12 cell apoptosis was attenuated when cells were cultured with HGSD serum compared to control. The presence of AMPK activator (AICAR) attenuated whereas AMPK inhibitor (Compound C) augmented the protective effect of HGSD serum on PC12 cell apoptosis.The results indicate that HGSD-pretreatment of rats protects the brain from ischemia-reperfusion injury and the mechanism is due to its anti-apoptotic effect mediated by decreased activation of AMPK. PMID:26957053

  20. Expression of somatostatin mRNA and peptide in rat hippocampus after cerebral ischemia

    DEFF Research Database (Denmark)

    Bering, Robert; Johansen, Flemming Fryd

    Somatostatin, ischemia, hippocampus, rat, in situ hybridisation, immunocytochemistry, neuropathology......Somatostatin, ischemia, hippocampus, rat, in situ hybridisation, immunocytochemistry, neuropathology...

  1. Chinese herbal formula Tongluo Jiunao injection protects against cerebral ischemia by activating neurotrophin 3/tropomyosin-related kinase C pathway

    Directory of Open Access Journals (Sweden)

    Peiman Alesheikh

    2015-01-01

    Full Text Available The Chinese herbal formula Tongluo Jiunao, containing the active components Panax notoginseng and Gardenia jasminoides, has recently been patented and is in use clinically. It is known to be neuroprotective in cerebral ischemia, but the underlying pathway remains poorly understood. In the present study, we established a rat model of cerebral ischemia by occlusion of the middle cerebral artery, and administered Tongluo Jiunao, a positive control (Xuesai Tong, containing Panax notoginseng or saline intraperitoneally to investigate the pathway involved in the action of Tongluo Jiunao injection. 2,3,5-Triphenyltetrazolium chloride (TTC staining showed that the cerebral infarct area was significantly smaller in model rats that received Tongluo Jiunao than in those that received saline. Enzyme-linked immunosorbent assay revealed significantly greater expression of neurotrophin 3 and growth-associated protein 43 in ischemic cerebral tissue, and serum levels of neurotrophin 3, in the Tongluo Jiunao group than in the saline group. The reverse transcription polymerase chain reaction and immunohistochemical staining showed that after treatment with Tongluo Jiunao or Xuesai Tong, tropomyosin-related kinase C gene expression and immunoreactivity were significantly elevated compared with saline, with the greatest expression observed after Tongluo Jiunao treatment. These findings suggest that Tongluo Jiunao injection exerts a neuroprotective effect in rats with cerebral ischemia by activating the neurotrophin 3/tropomyosin-related kinase C pathway.

  2. MicroRNA and Cerebral Ischemia%微小RNA与缺血性脑损伤

    Institute of Scientific and Technical Information of China (English)

    张煜; 郭军

    2012-01-01

    微小RNA (miRNA)是一类高度保守的单链RNA,在机体发育代谢过程中发挥重要调节作用.中枢神经系统存在大量的miRNA,不仅与神经细胞的发育、分化和生理功能密切相关,在脑缺血后神经病变和功能失调中也发挥重要的调节作用.特定miRNA能通过自身水平变化影响缺血后其靶基因的表达,参与神经细胞保护机制以及凋亡再生机制的调控.充分了解脑内特异性miRNA的功能和调控机制,有助于从基因水平上为缺血性脑损伤的预防、诊断和治疗提供新的策略.%MicroRNAs (miRNAs) are a class of highly conserved single-stranded RNA molecules that modulate gene translation. By targeting the mRNA of protein- coding genes, miRNAs play a critical role in neuronal differentiation, cell proliferation, apoptosis and metabolism. There are a lot of miRNAs in central nervous system, which are not only closely linked to development, differentiation and function of nerve cells, also play an important role in nerve lesions and dysfunction after cerebral ischemia. Specific miRNA through their own changes affect their target gene expression levels after focal cerebral ischemia, involving in the protection against apoptosis in neurons and regeneration after cerebral ischemia. A full understanding of the specific microRNA function and its underlying mechanism in the brain can provide a new strategy for the prevention, diagnosis, and treatment of ischemic cerebral injury at gene level.

  3. Visualization of cell death in mice with focal cerebral ischemia using fluorescent annexin A5, propidium iodide, and TUNEL staining.

    Science.gov (United States)

    Bahmani, Peyman; Schellenberger, Eyk; Klohs, Jan; Steinbrink, Jens; Cordell, Ryan; Zille, Marietta; Müller, Jochen; Harhausen, Denise; Hofstra, Leo; Reutelingsperger, Chris; Farr, Tracy Deanne; Dirnagl, Ulrich; Wunder, Andreas

    2011-05-01

    To monitor stroke-induced brain damage and assess neuroprotective therapies, specific imaging of cell death after cerebral ischemia in a noninvasive manner is highly desirable. Annexin A5 has been suggested as a marker for imaging cell death under various disease conditions including stroke. In this study, C57BL6/N mice received middle cerebral artery occlusion (MCAO) and were injected intravenously with either active or inactive Cy5.5-annexin A5 48 hours after reperfusion. Some mice also received propidium iodide (PI), a cell integrity marker. Only in mice receiving active Cy5.5-annexin A5 were fluorescence intensities significantly higher over the hemisphere ipsilateral to MCAO than on the contralateral side. This was detected noninvasively and ex vivo 4 and 8 hours after injection. The majority of cells positive for fluorescent annexin A5 were also positive for PI and fragmented DNA as detected by terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling (TUNEL) staining. This study demonstrates the high specificity of annexin A5 for visualization of cell death in a mouse model of stroke. To our knowledge, this is the first study to compare the distribution of injected active and inactive annexin A5, PI, and TUNEL staining. It provides important information on the experimental and potential clinical applications of annexin A5-based imaging agents in stroke. PMID:21245871

  4. Protective Effect of Caffeic Acid Phenethyl Ester in Rat Cerebral Ischemia/Reperfusion Damage

    Directory of Open Access Journals (Sweden)

    Ertuğrul Uzar

    2011-09-01

    Full Text Available OBJECTIVE: Because oxidative stress is related to cerebral ischemia/reperfusion (I/R injury, modulation of oxygen free radical production may represent a new approach to the management of cerebral I/R. Caffeic acid phenethyl ester (CAPE has been determined to have neuroprotective, antioxidant, anti-inflammatory, and anti-apoptotic activities. The aim of this study was to investigate whether CAPE has a protective effect on cerebral I/R damage, and to determine the possible effects of CAPE on total antioxidant/oxidant status. METHODS: A total of 30 rats were randomly divided into three groups as control group, I/R group, and I/R + CAPE. Total oxidant status (TOS, total antioxidant status (TAS and oxidative stress index (OSI levels and histopathological cellular structures were evaluated in cerebral tissues obtained after the experiment procedure in all groups. RESULTS: In the brain tissue, TOS and OSI levels were found to be significantly increased in the I/R group compared to the controls (p= 0.023, p= 0.001, respectively. Significantly decreased TAS levels were found in the I/R group compared to the controls (p= 0.001. CAPE treatment prevented the increase in TOS and OSI that is produced by cerebral I/R (p= 0.041, p= 0.001, respectively. TAS was found to be increased in the CAPE + I/R group compared with the I/R group (p= 0.002. In the I/R group, the brain sections showed findings of cerebral I/R damage including inflammation, vascular congestion and necrosis (for both variables, p= 0.001. These histopathological cerebral damage findings were found to be significantly reduced in the CAPE + I/R group compared to the I/R group (for both parameters, p< 0.05. CONCLUSION: In this study, it was found that oxidative stress had an important role in the pathogenesis of cerebral I/R damage, and histopathological and biochemical evaluations showed significantly decreased I/R damage following CAPE treatment in rats.

  5. THE FATE OF MDACH1-EXPRESSING CELLS IN THE DORSAL PART OF THE LATERAL VENTRICLES FOLLOWING FOCAL CEREBRAL ISCHEMIA

    Czech Academy of Sciences Publication Activity Database

    Anděrová, Miroslava; Pivoňková, Helena; Honsa, Pavel

    2013-01-01

    Roč. 61, Supplement 1 (2013), S125-S126. ISSN 0894-1491. [European Meeting on Glial Cell Function in Health and Disease /11./. 03.07.2013-06.07.2013, Berlin] Institutional support: RVO:68378041 Keywords : cerebral ischemia * neuroscience * MDACH1 Subject RIV: FH - Neurology

  6. Focal cerebral ischemia measured by the intra-arterial 133xenon method. Limitations of 2-dimensional blood flow measurements

    DEFF Research Database (Denmark)

    Skyhøj Olsen, T; Larsen, B; Bech Skriver, E; Enevoldsen, E; Lassen, N A

    1981-01-01

    The limitations of 2-dimensional isotope techniques in the study of focal cerebral ischemia were investigated using the intra-carotid 133 xenon injection method and a 254 multidetector scintillation camera. To make sure that the detectors "look" directly on infarcted areas, only patients with inf...

  7. Inhibition of chemokine-like factor 1 improves blood-brain barrier dysfunction in rats following focal cerebral ischemia.

    Science.gov (United States)

    Kong, Ling-Lei; Wang, Zhi-Yuan; Hu, Jin-Feng; Yuan, Yu-He; Li, Hua; Chen, Nai-Hong

    2016-08-01

    Disruption of blood-brain barrier (BBB) and subsequent edema are major contributors to the pathogenesis of ischemic stroke, and the current clinical therapy remains unsatisfied. Chemokine-like factor 1 (CKLF1), as a novel C-C chemokine, plays important roles in immune response. The expression of CKLF1 increased after focal cerebral ischemia and inhibition of CKLF1 activity showed neuroprotective effect by alleviating infiltration of neutrophil and neuron apoptosis in cerebral ischemia. However, few studies have focused on the role of CKLF1 on BBB integrity. The objective of present study was to investigate the role of CKLF1 on BBB integrity by applying anti-CKLF1 antibodies in rat focal cerebral ischemia and reperfusion model. Brain water content, Evans blue leakage and the expression of aquaporin-4 (AQP-4), matrix metalloproteinase-9 (MMP-9), Zonula Occludens-1 (ZO-1) and Occludin were measured. After treatment with anti-CKLF1 antibody, brain water content and Evans blue leakage in ipsilateral hemisphere were decreased in a dose-dependent manner at 24h after reperfusion, but not changed in contralateral hemisphere. Anti-CKLF1 antibody reduced the expression of AQP-4 and MMP-9, and upregulated the expression of ZO-1 and Occludin. These results suggest that CKLF1 is involved in BBB disruption after reperfusion. Inhibition of CKLF1 protects against cerebral ischemia by maintaining BBB integrity, possibly via inhibiting the expression of AQP-4 and MMP-9, and increasing the expression of tight junction protein. PMID:27283776

  8. Protective effects of Echium amoenum Fisch. and C.A. Mey. against cerebral ischemia in the rats

    Directory of Open Access Journals (Sweden)

    Leila Safaeian

    2015-01-01

    Conclusion: The anthocyanin rich fraction from E. amoenum was found to have protective effects against some brain damages postischemic reperfusion . However, further researches are required for investigating the exact mechanisms of the effect of this plant in the prevention of cerebral ischemia in human.

  9. Effects of immediate and delayed mild hypothermia on endogenous antioxidant enzymes and energy metabolites following global cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hong; ZHANG Jun-jian; MEI Yuan-wu; SUN Sheng-gang; TONG E-tang

    2011-01-01

    Background The optimal time window for the administration of hypothermia following cerebral ischemia has been studied for decades,with disparity outcomes.In this study,the efficacy of mild brain hypothermia beginning at different time intervals on brain endogenous antioxidant enzyme and energy metabolites was investigated in a model of global cerebral ischemia.Methods Forty-eight male Sprague-Dawley rats were divided into a sham-operated group,a normothermia (37℃-38℃) ischemic group and a mild hypothermic (31℃-32℃) ischemia groups.Rats in the last group were subdivided into four groups:240 minutes of hypothermia,30 minutes of normothermia plus 210 minutes of hypothermia,60 minutes of normothermia plus 180 minutes of hypothermia and 90 minutes of normothermia plus 150 minutes of hypothermia (n=8).Global cerebral ischemia was established using the Pulsinelli four-vessel occlusion model for 20minutes and mild hypothermia was applied after 20 minutes of ischemia.Brain.tissue was collected following 20 minutes of cerebral ischemia and 240 minutes of reperfusion,and used to measure the levels of superoxide dismutase (SOD),glutathione peroxidase (GSH-Px),reduced glutathione (GSH) and adenosine triphosphate (ATP).Results Mild hypothermia that was started within 0 to 60 minutes delayed the consumption of SOD,GSH-Px,GSH,and ATP (P <0.05 or P <0.01) in ischemic tissue,as compared to a normothermic ischemia group.In contrast,mild hypothermia beginning at 90 minutes had little effect on the levels of SOD,GSH-Px,GSH,and ATP (P>0.05).Conclusions Postischemic mild brain hypothermia can significantly delay the consumption of endogenous antioxidant enzymes and energy metabolites,which are critical to the process of cerebral protection by mild hypothermia.These results show that mild hypothermia limits ischemic injury if started within 60 minutes,but loses its protective effects when delayed until 90 minutes following cerebral ischemia.

  10. Reconstruction of cerebral hemodynamics with dynamic contrast-enhanced time-resolved near-infrared measurements before and during ischemia

    Science.gov (United States)

    Elliott, Jonathan T.; Diop, Mamadou; Morrison, Laura B.; Lee, Ting-Yim; St. Lawrence, Keith

    2013-03-01

    We present a dynamic contrast-enhanced near-infrared (DCE-NIR) technique that is capable of non-invasive quantification of cerebral hemodynamics in adults. The challenge of removing extracerebral contamination is overcome through the use of multi-distance time-resolved DCE-NIR combined with the kinetic deconvolution optical reconstruction (KDOR) analytical method. As proof-of-principle, cerebral blood flow, cerebral blood volume and mean transit time recovered with DCE-NIR are compared with CT perfusion values in an adult pig during normocapnia, hypocapnia, and ischemia. Measurements of blood flow acquired with DCE-NIR were compared against concomitant measurements using CT Perfusion.

  11. Changes in the BDNF-immunopositive cell population of neocortical layers I and II/III after focal cerebral ischemia in rats.

    Science.gov (United States)

    Choi, Yongwon; Kang, Sung Goo; Kam, Kyung-Yoon

    2015-04-24

    Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family and is widely distributed in the central nervous system, including the cerebral cortex. BDNF plays an important role in normal neural development, survival of existing neurons, and activity-dependent neuroplasticity. BDNF can also be neuroprotective and evoke neurogenesis in certain pathological conditions, such as cerebral ischemia. Neocortical layer I is an important region that can integrate feedforward and feedback information from other cortical areas and subcortical regions. In addition, it has recently been proposed as a possible source of neuronal progenitor cells after ischemia. Therefore, we investigated changes in the BDNF-immunoreactive cell population of neocortical layers I and II/III after middle cerebral artery occlusion (MCAO)-induced cerebral ischemia in rats. In unaffected condition, the number of BDNF(+) cells in layer I was significantly less than in layer II/III in the cingulate cortex and in the motor and sensory areas. The increase in the number of BDNF(+) cells in layer I 8 days after MCAO was more remarkable than layer II/III, in all regions except the area of cingulate cortex farthest from the infarct core. Only BDNF(+)-Ox-42(+) cells showed a tendency to increase consistently toward the infarct core in both layers I and II/III, implying a major source of BDNF for response to ischemic injury. The present study suggests that some beneficial effects during recovery from ischemic injury, such as increased supportive microglia/macrophages, occur owing to a sensitive response of BDNF in layer I. PMID:25681548

  12. Neuroprotection against cerebral ischemia/reperfusion injury by intravenous administration of liposomal fasudil.

    Science.gov (United States)

    Fukuta, Tatsuya; Asai, Tomohiro; Sato, Akihiko; Namba, Mio; Yanagida, Yosuke; Kikuchi, Takashi; Koide, Hiroyuki; Shimizu, Kosuke; Oku, Naoto

    2016-06-15

    Fasudil, a Rho-kinase inhibitor, is a promising neuroprotectant against ischemic stroke; however, its low bioavailability is an obstacle to be overcome. Our previous study revealed that the liposomal drug delivery system is a hopeful strategy to increase the therapeutic efficacy of neuroprotectants. In the present study, the usefulness of intravenously administered liposomal fasudil for cerebral ischemia/reperfusion (I/R) injury treatment was examined in transient middle cerebral artery occlusion (t-MCAO) rats. The results showed that PEGylated liposomes of approximately 100nm in diameter accumulated more extensively in the I/R region compared with those of over 200nm. Confocal images showed that fluorescence-labeled liposomal fasudil was widely distributed in the I/R region, and was not noticeably taken up by microglia, which are well-known resident macrophages in the brain, and neuronal cells. These data indicated that liposomal fasudil mainly exerted its pharmacological activity by releasing fasudil from the liposomes in the I/R region. Moreover, liposomal fasudil effectively suppressed neutrophil invasion and brain cell damage in the t-MCAO rats, resulting in amelioration of their motor function deficits. These findings demonstrated both the importance of particle size for neuroprotectant delivery and the effectiveness of liposomal fasudil for the treatment of cerebral I/R injury. PMID:27107903

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    PNQX (9-methyl-amino-6-nitro-hexahydro-benzo(F)quinoxalinedione) is a selective AMPA antagonist with demonstrated neuroprotective effects in focal ischemia in rats. Here we report corresponding effects in mouse hippocampal slice cultures subjected to oxygen and glucose deprivation (OGD) and in....... For comparison, other cultures were exposed to the NMDA antagonist MK-801 using the same protocol. Both PNQX and MK-801 displayed significant neuroprotective effects in all hippocampal subfields when present during and after OGD. When added just after OGD, only PNQX retained some neuroprotective...... effect. When added 2 h after OGD neither PNQX nor MK-801 had an effect. Transient global cerebral ischemia was induced in Mongolian gerbils by occlusion of both common carotid arteries for 4.5 min, with PNQX (10 mg/kg) being injected i.p. 30, 60 and 90 min after the insult. Subsequent analysis of brain...

  14. Influence of rotating magnetic field on cerebral infarction volume, cerebral edema and free radicals metabolism after cerebral ischemia/reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    Xiaohong Liu; Zhiqiang Zhang; Lixin Zhang

    2006-01-01

    BACKGROUND: It has shown that magnetic field can improve blood circulation, decrease blood viscosity, inhibit free radicals, affect Ca2+ flow in nerve cells, control inflammatory and immunological reaction, and accelerate nerve cell regeneration. In addition, protective effect of magnetic field, which acts as an iatrophysics, on ischemic brain tissues has been understood gradually.OBJECTIVE: To investigate the effects of rotating magnetic field (RMF) on volume of cerebral infarction,cerebral edema and metabolism of free radicals in rats after cerebral ischemia/reperfusion injury.DESIGN: Randomized controlled animal study.SETTING: Rehabilitation Center of disabled children, Liaoniang; Department of Rehabilitation, the Second Affiliated Hospital, China Medical University; Department of Rehabilitation Physiotherapy, the First Affiliated Hospital, China Medical University.MATERIALS: A total of 70 healthy Wistar rats aged 18-20 weeks of both genders were selected and randomly divided into 3 groups: sham operation group with 12 rats, control group with 20 rats and treatment group with 38 rats. The treatment group included 4 time points: immediate reperfusion with 6 ones, 6-hour reperfusion with 20 ones, 12-hour reperfusion with 6 ones and 18-hour reperfusion with 6 rats. Main instruments were detailed as follows: magnetic head of rotating magnetic device was 6 cm in diameter; magnetic induction intensity at the surface of magnetic head was 0.25 T in silence; the maximal magnetic induction intensity was 0.09 T at the phase of rotation; the average rotating speed was 2500 r per minute.METHODS: The experiment was carried out in the China Medical University in March 2003. Focal cerebral ischemic animal models were established with modified Longa's method. Operation was the same in the sham operation, but the thread was inserted as 10 mm. Neurologic impairment was assessed with 5-rating method to screen out cases. Those survivals with grade 1 and grade 2 after ischemia for 2

  15. Cerebral ischemia—induced neuronal apoptosis mediated by nitric oxide

    Institute of Scientific and Technical Information of China (English)

    NomuY

    2002-01-01

    To elucidate the cellular and molecular mechanism of cerebral ischemia-induced neuronal apoptosis mediated by nitric oxide (NO) in the brain,we investigated:(1)cell death in hippocampal CA1 neurons of rats after a rransient four vessel occlusion (4VO)/reperfusion and (2) apoptosis induced by NOC18(NO releaser) using SHSY5Y cells,a human neuroblastoma cell line.We found that 4VO caused expression of inducible type of NO synthase (iNOS) in glial cells and neuronal apoptosis in CA1 region of rats.Next we examined in vitro apoptotic effects of NOC18 on SHSY5Y cells and suggest that NO decrease mitochondrial membrane potential,release cytochrome C from mitochondria,activates caspase-3,degrade inhibitor of caspase-activated DNase(Icad),and activated DNase translocate into nucleus and induce DNA fragmentation.Thus we conclude that the excess amount of NO produced by glial iNOS at cerebral ischemia could be involved in neuronal apoptosis in CA1 region.Regarding NO action on neurons,we further obtained that NO propects neuronal apoptosis in PC12 cells perhaps by nitrosylation of caspase,subsequent reduction of proteolytic activity.Taken together,we suggest that NO seem to exert dual effects(toxic and beneficial) on neuronal apoptosis,the one (toxic);apoptosis-induction throuth the decrease in mitochondrial membrane potentials and cytochrome C release and the othe (beneficial);protection against apoptosis through the inhibition of caspase activity.

  16. Reformulated meat products protect against ischemia-induced cardiac damage.

    Science.gov (United States)

    Asensio-Lopez, M C; Lax, A; Sanchez-Mas, J; Avellaneda, A; Planes, J; Pascual-Figal, D A

    2016-02-17

    The protective effects of the antioxidants present in food are of great relevance for cardiovascular health. This study evaluates whether the extracts from reformulated meat products with a reduction in fat and/or sodium content exert a cardioprotective effect against ischemia-induced oxidative stress in cardiomyocytes, compared with non-meat foods. Ischemic damage caused loss of cell viability, increased reactive oxygen species and lipid peroxidation and decreased the antioxidant activity. Pretreatment for 24 h with digested or non-digested extracts from reformulated meat products led to protection against ischemia-induced oxidative damage: increased cell viability, reduced oxidative stress and restored the antioxidant activity. Similar results were obtained using extracts from tuna fish, but not with the extracts of green peas, salad or white beans. These results suggest that reformulated meat products have a beneficial impact in protecting cardiac cells against ischemia, and they may represent a source of natural antioxidants with benefits for cardiovascular health. PMID:26751429

  17. Clostridium butyricum pretreatment attenuates cerebral ischemia/reperfusion injury in mice via anti-oxidation and anti-apoptosis.

    Science.gov (United States)

    Sun, Jing; Ling, Zongxin; Wang, Fangyan; Chen, Wenqian; Li, Haixiao; Jin, Jiangtao; Zhang, Huiqing; Pang, Mengqi; Yu, Junjie; Liu, Jiaming

    2016-02-01

    Probiotics participate actively in the neuropsychiatric disorders. However, their roles on ischemic stroke remain unclear. This study aims to determine whether Clostridium butyricum (C. butyricum) could attenuate cerebral ischemia/reperfusion (I/R) injury and its possible mechanisms. Male ICR mice were intragastrically pretreated with C. butyricum for 2 successive weeks, and then subjected to cerebral I/R injury induced by the bilateral common carotid artery occlusion (BCCAO) for 20min. After 24h of the reperfusion, neurological deficit scores were evaluated. Histopathological changes of the hippocampus neurons were observed using Hematoxylin and eosin (H&E) and TUNEL staining. Malondialdehyde (MDA) contents and superoxide dismutase (SOD) activities in the brain were detected. The expression of Caspase-3, Bax and Bcl-2 were investigated by Western blot and immunohistochemistry analysis. The butyrate contents in the brain were determined. Our results showed that cerebral I/R injury led to neurological deficit, increased levels of Caspase-3 and Bax and decreased Bcl-2/Bax ratio. C. butyricum significantly improved neurological deficit, relieved histopathologic change, decreased MDA contents and increased SOD activities in the I/R injury mice. After C. butyricum pretreatment, the expression of Caspase-3 and Bax were significantly decreased, the Bcl-2/Bax ratio was significantly increased, and butyrate contents in the brain were significantly increased. These findings suggested that C. butyricum is able to exert neuroprotective effects against I/R injury mice through anti-oxidant and anti-apoptotic mechanisms, and reversing decrease of butyrate contents in the brain might be involved in its neuroprotection. PMID:26733300

  18. The value of multi-slice computed tomography for early diagnosis of focal cerebral ischemia

    International Nuclear Information System (INIS)

    The aim of this survey is the characterization of the present value of multi-slice computed tomography (MSCT) for the assessment of hyperacute cerebral ischemia based on our experience and a review of the literature. MSCT is compared with single-slice CT (SSCT) as to the diagnostic value of standard cranial CT, CT angiography (CTA) and perfusion CT. CTA obtained with MSCT surpasses CTA obtained with SSCT. For perfusion CT, the value added by MSCT is small. With regard to standard cranial CT, MSCT and SSCT are considered equivalent. CTA and perfusion CT should be used in patients with acute stroke if the indication for thrombolysis is entertained but diffusion and perfusion weighted MRI cannot be carried out. This applies to both SSCT and MSCT. If advanced MRI and advanced CT are available, MRI continues to be the preferred imaging modality. (orig.)

  19. Cerebral Ischemia Reperfusion Exacerbates and Pueraria Flavonoids Attenuate Depressive Responses to Stress in Mice

    Institute of Scientific and Technical Information of China (English)

    LAN Jiaqi; YAN Bin; ZHAO Yu'nan; WANG Daoyi; HU Jun; XING Dongming; DU Lijun

    2008-01-01

    Previous studies have shown that mice experiencing cerebral ischemia reperfusion (CIR) and stress can serve as a model of post stroke depression (PSD).The present study verified the acute antide-pressant effects of radix puerariae extract (PE) on PSD mice through behavior and gene expression ex-periments.CIR was found to reduce the sucrose consumption and tyrosine hydroxylase (TH) gene expres-sion.PE administration after CIR surgery was observed to significantly enhance the mRNA expression of TH in the hippocampus compared with the PSD group on Day 0 and Day 3 postsurgery.These findings in-dicate that PE contributes to the amelioration of behavior response in PSD mice,which is closely related with the protective effects of catecholamine synthesize against CIR brain damage.

  20. Effects of cerebral ischemia on human neurovascular coupling, CO2 reactivity, and dynamic cerebral autoregulation.

    Science.gov (United States)

    Salinet, Angela S M; Robinson, Thompson G; Panerai, Ronney B

    2015-01-15

    Cerebral blood flow (CBF) regulation can be impaired in acute ischemic stroke but the combined effects of dynamic cerebral autoregulation (CA), CO2 cerebrovascular reactivity (CVR), and neurovascular coupling (NVC), obtained from simultaneous measurements, have not been described. CBF velocity in the middle cerebral artery (MCA) (CBFv, transcranial Doppler), blood pressure (BP, Finometer), and end-tidal Pco2 (PetCO2 , infrared capnography) were recorded during a 1-min passive movement of the arm in 27 healthy controls [mean age (SD) 61.4 (6.0) yr] and 27 acute stroke patients [age 63 (11.7) yr]. A multivariate autoregressive-moving average model was used to separate the contributions of BP, arterial Pco2 (PaCO2 ), and the neural activation to the CBFv responses. CBFv step responses for the BP, CO2, and stimulus inputs were also obtained. The contribution of the stimulus to the CBFv response was highly significant for the difference between the affected side [area under the curve (AUC) 104.5 (4.5)%] and controls [AUC 106.9 (4.3)%; P = 0.008]. CBFv step responses to CO2 [affected hemisphere 0.39 (0.7), unaffected 0.55 (0.8), controls 1.39 (0.9)%/mmHg; P = 0.01, affected vs. controls; P = 0.025, unaffected vs. controls] and motor stimulus inputs [affected hemisphere 0.20 (0.1), unaffected 0.22 (0.2), controls 0.37 (0.2) arbitrary units; P = 0.009, affected vs. controls; P = 0.02, unaffected vs. controls] were reduced in the stroke group compared with controls. The CBFv step responses to the BP input at baseline and during the paradigm were not different between groups (P = 0.07), but PetCO2 was lower in the stroke group (P < 0.05). These results provide new insights into the interaction of CA, CVR, and NVC in both health and disease states. PMID:25593216

  1. Different CT perfusion algorithms in the detection of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage

    Energy Technology Data Exchange (ETDEWEB)

    Cremers, Charlotte H.P. [University Medical Center Utrecht, Department of Neurology and Neurosurgery, Room G03.232, Brain Center Rudolf Magnus Department of Neurology and Neurosurgery, PO Box 85500, Utrecht (Netherlands); University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Dankbaar, Jan Willem; Bennink, Edwin; Velthuis, Birgitta K.; Schaaf, Irene C. van der [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Vergouwen, Mervyn D.I.; Rinkel, Gabriel J.E. [University Medical Center Utrecht, Department of Neurology and Neurosurgery, Room G03.232, Brain Center Rudolf Magnus Department of Neurology and Neurosurgery, PO Box 85500, Utrecht (Netherlands); Vos, Pieter C. [University Medical Center Utrecht, Image Sciences Institute, Utrecht (Netherlands)

    2015-05-01

    Tracer delay-sensitive perfusion algorithms in CT perfusion (CTP) result in an overestimation of the extent of ischemia in thromboembolic stroke. In diagnosing delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH), delayed arrival of contrast due to vasospasm may also overestimate the extent of ischemia. We investigated the diagnostic accuracy of tracer delay-sensitive and tracer delay-insensitive algorithms for detecting DCI. From a prospectively collected series of aSAH patients admitted between 2007-2011, we included patients with any clinical deterioration other than rebleeding within 21 days after SAH who underwent NCCT/CTP/CTA imaging. Causes of clinical deterioration were categorized into DCI and no DCI. CTP maps were calculated with tracer delay-sensitive and tracer delay-insensitive algorithms and were visually assessed for the presence of perfusion deficits by two independent observers with different levels of experience. The diagnostic value of both algorithms was calculated for both observers. Seventy-one patients were included. For the experienced observer, the positive predictive values (PPVs) were 0.67 for the delay-sensitive and 0.66 for the delay-insensitive algorithm, and the negative predictive values (NPVs) were 0.73 and 0.74. For the less experienced observer, PPVs were 0.60 for both algorithms, and NPVs were 0.66 for the delay-sensitive and 0.63 for the delay-insensitive algorithm. Test characteristics are comparable for tracer delay-sensitive and tracer delay-insensitive algorithms for the visual assessment of CTP in diagnosing DCI. This indicates that both algorithms can be used for this purpose. (orig.)

  2. Different CT perfusion algorithms in the detection of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage

    International Nuclear Information System (INIS)

    Tracer delay-sensitive perfusion algorithms in CT perfusion (CTP) result in an overestimation of the extent of ischemia in thromboembolic stroke. In diagnosing delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH), delayed arrival of contrast due to vasospasm may also overestimate the extent of ischemia. We investigated the diagnostic accuracy of tracer delay-sensitive and tracer delay-insensitive algorithms for detecting DCI. From a prospectively collected series of aSAH patients admitted between 2007-2011, we included patients with any clinical deterioration other than rebleeding within 21 days after SAH who underwent NCCT/CTP/CTA imaging. Causes of clinical deterioration were categorized into DCI and no DCI. CTP maps were calculated with tracer delay-sensitive and tracer delay-insensitive algorithms and were visually assessed for the presence of perfusion deficits by two independent observers with different levels of experience. The diagnostic value of both algorithms was calculated for both observers. Seventy-one patients were included. For the experienced observer, the positive predictive values (PPVs) were 0.67 for the delay-sensitive and 0.66 for the delay-insensitive algorithm, and the negative predictive values (NPVs) were 0.73 and 0.74. For the less experienced observer, PPVs were 0.60 for both algorithms, and NPVs were 0.66 for the delay-sensitive and 0.63 for the delay-insensitive algorithm. Test characteristics are comparable for tracer delay-sensitive and tracer delay-insensitive algorithms for the visual assessment of CTP in diagnosing DCI. This indicates that both algorithms can be used for this purpose. (orig.)

  3. Nitro-Oxidative Stress after Neuronal Ischemia Induces Protein Nitrotyrosination and Cell Death

    Directory of Open Access Journals (Sweden)

    Marta Tajes

    2013-01-01

    Full Text Available Ischemic stroke is an acute vascular event that obstructs blood supply to the brain, producing irreversible damage that affects neurons but also glial and brain vessel cells. Immediately after the stroke, the ischemic tissue produces nitric oxide (NO to recover blood perfusion but also produces superoxide anion. These compounds interact, producing peroxynitrite, which irreversibly nitrates protein tyrosines. The present study measured NO production in a human neuroblastoma (SH-SY5Y, a murine glial (BV2, a human endothelial cell line (HUVEC, and in primary cultures of human cerebral myocytes (HC-VSMCs after experimental ischemia in vitro. Neuronal, endothelial, and inducible NO synthase (NOS expression was also studied up to 24 h after ischemia, showing a different time course depending on the NOS type and the cells studied. Finally, we carried out cell viability experiments on SH-SY5Y cells with H2O2, a prooxidant agent, and with a NO donor to mimic ischemic conditions. We found that both compounds were highly toxic when they interacted, producing peroxynitrite. We obtained similar results when all cells were challenged with peroxynitrite. Our data suggest that peroxynitrite induces cell death and is a very harmful agent in brain ischemia.

  4. Pomegranate seed hydroalcoholic extract improves memory deficits in ovariectomized rats with permanent cerebral hypoperfusion /ischemia

    Directory of Open Access Journals (Sweden)

    Alireza Sarkaki

    2014-12-01

    Full Text Available Objective: Estrogen deficit following menopause results in cognitive behaviors impairment. Severity of these impairments in menopause women suffer with cerebral hypo perfusion/ischemia (HI cause the brain damage and neuronal death. This study aimed to evaluate the effects of pomegranate seed extract (PGSE on avoidance memories after permanent bilateral common carotid arteries occlusion (2CCAO in ovariectomized (OVX rats. Materials and Methods: Adult female Wistar rats were divided randomly into eight groups with 8 rats in each group: 1 Sham-operated for ovaries and 2CCAO (ShO; 2 OVX and sham operated for ischemia (OShI; 3-7 OVX with 2CCAO (OI received PGSE (100, 200, 400 and 800 mg/2ml/kg or normal saline, orally for 14 days (OI+E100, 200, 400, 800 or OI+Veh; 8 OShI received most effective dose of PGSE (200 and 400 mg/kg for passive and active avoidance memories respectively. Active and passive avoidance tasks were measured in Y-maze and two-way shuttle box respectively. Data were analyzed with one-way and RM-ANOVA followed by HSD post-hoc test. Results: Sensorimotor impaired in OShI+Veh and OI+Veh (P

  5. Batroxobin plus hypothermia for protection of cerebral ischemia/reperfusion injury models in gerbils

    Institute of Scientific and Technical Information of China (English)

    Lin Zhang; Pixing Zhang; Yinming Zeng; Qun Chen

    2006-01-01

    BACKGROUND: Hypothermia plays a protective role in cerebral ischemia/reperfusion injury. Dose combination with batroxobin, an active drug for treating cerebrovascular disease, will enhance its protection? OBJECTIVE: To explore the effects of hypothermia, batroxobin, hypothermia combined with batroxobin on complete cerebral ischemia/reperfusion injury in gerbils.DESIGN: A randomized block comparison observation. SETTING: Jiangsu Key Lab of Anesthesiology. MATERIALS: Experimental animal: Sixty Mongolia gerbils weighing 50-80 g, male or female, were provided by the Animals Center of Xuzhou Medical College. Drugs and agents: Batroxobin was provided by Dongling Phar maceutical Industry Organization (Japan). Superoxide dismutase (SOD) and malondiadehyde (MDA) kits were offered by Nanjing Jiancheng Bioengineering Institute. Other reagents were all import or national analytical pure grade. HITACHI R22A refrigerated high-speed centrifuge, and HARRIS ultra-hypothermia refrigerator were used.METHODS: The experiments were completed in Jiangsu Key Lab of Anesthesiology from May 2004 to January 2005. ① The animals were divided into 6 groups by random member table method: sham-operated group (n =6), ischemia control group (n =6), normothermia group (n =12), hypothermia group (n =12), batroxobin group (n =12) and hypothermia+batroxobin group (n =12). Gerbil rats were abdominally anesthetized with sodium pentobarbital. The neck skin was incised to separate bilateral common carotid arteries. Complete cerebral ischemia models were established by occluding bilateral common carotid arteries with artery clamp for 10 minutes, then the clamp was loosened to perfuse the arteries. Iso-electric level of brain electric wave showed the models were established successfully. The gerbils in the batroxobin group and hypothermia+batroxobin group were abdominally injected with batroxobin (8 BU/kg) while reperfusion, and isovolumetric saline was administered to the gerbils in the other groups

  6. Curcumin attenuates the middle cerebral artery occlusion-induced reduction in γ-enolase expression in an animal model.

    Science.gov (United States)

    Gim, Sang-Ah; Lee, So-Ra; Shah, Fawad-Ali; Koh, Phil-Ok

    2015-12-01

    Curcumin exerts a protective effect in cerebral ischemia through its anti-oxidant and anti-inflammatory activities. γ-enolase is a glycolytic enzyme expressed in neurons that is known to exerts a neuroprotective effect. We investigated whether curcumin regulates γ-enolase expression in focal cerebral ischemic injury in rats. Middle cerebral artery occlusion (MCAO) was performed to induce focal cerebral ischemia. Adult male rats were injected intraperitoneally with either vehicle or curcumin (50 mg/kg) 1 h after MCAO and cerebral cortex tissues were isolated 24 h after MCAO. We found that MCAO-induced injury resulted in a reduction in γ-enolase expression in vehicle-treated animals using a proteomics approach. However, this reduction was attenuated in animals with MCAO treated with curcumin. Reverse-transcription PCR and Western blot analyses also showed that curcumin treatment prevented the MCAO injury-induced reduction in γ-enolase expression. The results of this study suggest that curcumin exerts its neuroprotective function in focal cerebral ischemia by regulating the expression of γ-enolase. PMID:26755923

  7. Total Flavone of Hawthorn Leaf inhibits neuronal apoptosis in brain tissue of rat models of chronic cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Tan Rong-fang; Xia Ai-hua; Wu Xiao-guang; Cao Na-na; Li Meng-meng; Zhang Tian-ge; Wang Yi-ru; Yue Zhi-ling

    2014-01-01

    BACKGROUND: Cerebrovascular disease often causes dysfunction of the brain nerve, and nerve cel apoptosis is the important factor of cerebral nerve dysfunction. The excessive expression of c-fos can block the transduction of intracelular signal so that producing some apoptosis-promoting factors, which involve in nerve cel apoptosis process after ischemia injury of brain. Bcl-2 is an inhibited factor. It might to be the key to treat ischemic cerebrovascular disease by inhibiting or reducing the apoptosis of nerve cels after ischemia injury. OBJECTIVE: To investigate the therapeutic effect and mechanism of the Total Flavone of Hawthorn Leaf on chronic cerebral ischemia rats. METHODS: A total of 72 healthy male Sprague-Dawley rats were randomly divided into sham surgery group, model group, Total Flavone of Hawthorn Leaf group and ginkgo leaf group. Permanent bilateral carotid artery ligation was used to prepare chronic cerebral ischemia model in the model group, Total Flavone of Hawthorn Leaf group and ginkgo leaf group. Total Flavone of Hawthorn Leaf group and ginkgo leaf group respectively received 140 mg/kg Total Flavone of Hawthorn Leaf and 12.3 mg/kg ginkgo leaf intragastricaly for 36 days from 36 days after model induction. Model group and sham surgery group received 3.5 mL/kg physiological saline intragastricaly. RESULTS AND CONCLUSION: Compared with the model group, the expression of c-fos protein significantly deceased in the Total Flavone of Hawthorn Leaf group (P 0.05). These data indicated that the protective effect of Total Flavone of Hawthorn Leaf on chronic cerebral ischemia was associated with its inhibition of neuronal apoptosis. Its mechanism of anti-apoptosis might be associated with up-regulating expression of Bcl-2, down-regulating expression of c-fos and decreasing Ca2+ content in brain.

  8. Effect of Electroacupuncture on Expression of p53 Protein in Cerebral Cortex of Rats with Global Cerebral Ischemia/Reperfusion Injury

    Institute of Scientific and Technical Information of China (English)

    卜渊; 耿德勤; 葛巍; 徐兴顺; 曾因明

    2004-01-01

    Objective: To observe the effect of electroacupuncture (EA) on expression of p53 protein in cerebral cortex of senile rats with global cerebral ischemia/reperfusion (IR) injury and to explore its mechanism. Methods: The cerebral IR injury rat model was established referring to Pulsinelli 4-vessel occlusion method. Thirty-six SD rats were randomly and evenly divided into the control group, the IR group and the IR plus EA (IR-EA) group. The animals in the control group were subjected to electrocauterization of vertebral arteries in bilateral flank orifice alone with the general carotid arteries unoccluded.To rats in the IR-EA group, immediately and 24h, 48h, 72h after cerebral IR, EA treatment on bilateral acupoint "Zusanli"(ST36) was applied once a day, lasting for 60 minutes. After the final treatment, all the rats were sacrificed and their brains were taken to examine p53 protein expression by the immunohistochemical method. Results: Cells with positive p53 immunoreactivity in the cerebral cortex of rats in the IR group was significantly higher than that in the control group ( P<0.05), while that in the IR-EA group was significantly lower than that in the IR group (P<0.05). Conclusion: EA could remarkably reduce expression of p53 protein in the cerebral cortex of senile rats with global cerebral IR injury, which might be one of the means for EA to inhibit neuronal apoptosis after cerebral IR injury.

  9. Protective effect and its mechanism of curcumin on ischemia-reperfusion injury of cerebral cortex in rats

    OpenAIRE

    Liu, Li; Bo-tao TAN; Li, Yu; Yu, Gang

    2013-01-01

    Objective  To investigate the effect of curcumin pretreatment on the expression of uncoupling protein 2 (UCP2) and mitochondrial transcription factor A (MTFA) in rats' cerebral cortex against focal ischemia reperfusion injury. Methods  Eighty male SD rats weighed 220g–300g were randomly divided into 4 groups: sham-operated group, ischemia/reperfusion (I/R) group, curcumine 50mg/kg+I/R (low dose) group, and curcumine 100mg/kg+I/R (high dose) group. The common carotid artery, external carotid a...

  10. Changes in cerebral blood flow and psychometric indicators in veterans with early forms of chronic brain ischemia

    Directory of Open Access Journals (Sweden)

    Vasilenko Т.М.

    2015-09-01

    Full Text Available The goal is to study the cerebral blood flow and psychometric characteristics in veterans of Afghanistan with early forms of chronic brain ischemia. Material and Methods. The study included 74 veterans of the Afghan war aged from 45 to 55 years: group 1, 28 people with NPNKM; Group 2-28 patients with circulatory encephalopathy stage 1; group 3-18 healthy persons. Doppler examination of cerebral vessels was carried out on the unit «Smart-lite». Reactive and personal anxiety of patients was assessed using the scale of Spielberger, evaluation of the quality of life through the test SAN. Determining the level of neuroticism and psychoticism was conducted by the scale of neuroticism and psy-choticism. Results: The study of cerebral blood flow in the Afghan war veterans showed signs of insolvency of carotid and carotid-basilar anastomoses, hypoperfusion phenomenon with the depletion of autoregulation, violation of the outflow of venous blood at the level of the microvasculature, accompanied by cerebral arteries spasm. More than 40% of patients with early forms of chronic brain ischemia had high personal anxiety, low levels of well-being and activity, with maximum expression of dyscirculatory hypoxia. Conclusion. Readaptation of veterans of Afghanistan is accompanied by the changes in psychometric performance and the formation of the earliest forms of brain chronic ischemia associated with inadequate hemodynamics providing increased functional activity of the brain and the inefficiency of compensatory-adaptive reactions.

  11. 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

    Institute of Scientific and Technical Information of China (English)

    Zongjun Guo; Lumin Wang

    2012-01-01

    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.

  12. Differential Neuroprotective Effects of Carnosine, Anserine, and N-Acetyl Carnosine against Permanent Focal Ischemia

    OpenAIRE

    Min, Jiangyong; Senut, Marie-Claude; Rajanikant, Krishnamurthy; Greenberg, Eric; Bandagi, Ram; Zemke, Daniel; Mousa, Ahmad; Kassab, Mounzer; Farooq, Muhammad U.; Gupta, Rishi; Majid, Arshad

    2008-01-01

    Carnosine (β-alanyl-L-histidine) has been shown to exhibit neuroprotection in rodent models of cerebral ischemia. In the present study, we further characterized the effects of carnosine treatment in a mouse model of permanent focal cerebral ischemia and compared them with its related peptides anserine and N-acetylated carnosine. We also evaluated the efficacy of bestatin, a carnosinase inhibitor, in ameliorating ischemic brain damage. Permanent focal cerebral ischemia was induced by occlusion...

  13. Brain immune cell composition and functional outcome after cerebral ischemia: Comparison of two mouse strains

    Directory of Open Access Journals (Sweden)

    Hyun Ah eKim

    2014-11-01

    Full Text Available Inflammatory cells may contribute to secondary brain injury following cerebral ischemia. The C57Bl/6 mouse strain is known to exhibit a T helper 1-prone, pro-inflammatory type response to injury, whereas the FVB strain is relatively T helper 2-prone, or anti-inflammatory, in its immune response. We tested whether stroke outcome is more severe in C57Bl/6 than FVB mice. Male mice of each strain underwent sham surgery or 1 h occlusion of the middle cerebral artery followed by 23 h of reperfusion. Despite no difference in infarct size, C57Bl/6 mice displayed markedly greater functional deficits than FVB mice after stroke, as assessed by neurological scoring and hanging wire test. Total numbers of CD45+ leukocytes tended to be larger in the brains of C57Bl/6 than FVB mice after stroke, but there were marked differences in leukocyte composition between the two mouse strains. The inflammatory response in C57Bl/6 mice primarily involved T and B lymphocytes, whereas neutrophils, monocytes and macrophages were more prominent in FVB mice. Our data are consistent with the concept that functional outcome after stroke is dependent on the immune cell composition which develops following ischemic brain injury.

  14. Pre-stroke DNA immunization against neurite growth inhibitors is beneficial to the recovery from focal cerebral ischemia in rats

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: Inhibitory signals, I.e. Neurite growth inhibitors (NGIs), presenting on central nervous system (CNS) myelin have been shown to play a crucial role in inhibiting lesioned axonal sprouting and leading to less functional recovery. Vaccines targeting NGIs may provide multifactorial protection against brain insults by overcoming the inhibitory effects of these NGIs and boosting the immune repair mechanisms of body.OBJECTIVE: To evaluate the effect of pre-stroke DNA immunization against NGIs on the rehabilitation for sensorimotor function of rat models of focal cerebral ischemia.DESIGN: A completely randomized design, and controlled experiment.SETTING: Brain Injury Research Laboratory, Department of Neurosurgery, National Neuroscience Institute,Singapore.MATERIALS: Sixty adult male Sprague-Dawley rats ranging in age from 45 to 120 days and in body mass from 180 to 250 g were provided by the Animal Center of Department of Anatomy, Faculty of Medicine,National University of Singapore. pcDNA3.1(+)-neurite growth inhibitors (pcDNA-NGIs) a gift was provided by Dr. Xiao from the Department of Clinical Research, Singapore General Hospital, Singapore.METHODS: The experiment was carried out at Brain Injury Research Laboratory, Department of Neurosurgery, National Neuroscience Institute, Singapore from August 2003 to April 2005. ① The involved rats were randomized into 3 groups: model group (group A), pcDNA3.1 (+) group (group B) and pcDNA-NGIs group (group C), with 20 rats in each group. Left focal cerebral ischemia was permanently induced through middle cerebral artery occlusion with the assistance of an operating microscope.Successful middle cerebral artery occlusion was determined by a 20% decrease to baseline in the ipsilateral cerebral blood flow. 100 μ g of pcDNA-NGIs eluted in phosphate-buffered saline (PBS) was intramuscularly injected into the tibial muscle once a week before middle cerebral artery occlusion for 6 weeks in group C. As control, pcDNA3

  15. Tin chloride enhances parvalbumin-positive interneuron survival by modulating heme metabolism in a model of cerebral ischemia.

    Science.gov (United States)

    Li Volti, Giovanni; Zappalà, Agata; Leggio, Gian Marco; Mazzola, Carmen; Drago, Filippo; La Delia, Francesco; Serapide, Maria Francesca; Pellitteri, Rosalia; Giannone, Ignazio; Spatuzza, Michela; Cicirata, Valentina; Cicirata, Federico

    2011-03-29

    SnCl(2) has been reported to increase the expression of heme-oxygenase 1 (HO-1), a major antioxidant enzyme, and to decrease ischemic injury, in non-nervous tissues. This study examined the neuroprotective effect of SnCl(2) in the hippocampus of rats submitted to cerebral ischemia. SnCl(2) was administered 18 h before bilateral carotids obstruction. Changes in HO-1 expression and activity, heme content, inducible nitric oxide synthase (iNOS) expression and parvalbumin positive interneuron survival were studied. Thereafter both behavior and memory recovery were tested. The administration of SnCl(2) increased the expression of HO-1 protein and HO activity in the hippocampus and concomitantly decreased heme content at both mitochondrial and nuclear level. Furthermore, ischemized animals showed a strong increase in iNOS expression in the hippocampus, where a loss of parvalbumin positive interneurons also occurred. Pre-treatment with SnCl(2), decreased both iNOS expression in ischemized rats and increased cell survival. The beneficial effects of SnCl(2) were prevented by concomitant treatment with SnMP, a strong inhibitor of HO activity. SnCl(2) also caused an improvement in short term memory recovery. Our results showed that following SnCl(2) administration, HO-1 is strongly induced in the hippocampus and modulate iNOS expression, resulting in a strong neuroprotective effect. PMID:21276833

  16. The Effect of Treadmill Training Pre-Exercise on Glutamate Receptor Expression in Rats after Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    Yang Wang

    2010-07-01

    Full Text Available Physical exercise has been demonstrated to be neuroprotective in both clinical and laboratory settings. However, the exact mechanism underlying this effect is unclear. Our study aimed to investigate whether pre-ischemic treadmill training could serve as a form of ischemic preconditioning in a rat model undergoing middle cerebral artery occlusion (MCAO. Thirty-six rats were divided into three groups: a sham control group, a non-exercise with operation group and an exercise with operation group. After treadmill training, ischemia was induced by occluding the MCA for 2 h, followed by reperfusion. Half of the rats in each group were sacrificed for mRNA detection of mGluR5 and NR2B 80 min after occlusion. The remaining animals were evaluated for neurological deficits by behavioral scoring and then decapitated to assess the infarct volume. The mRNA expression of mGluR5 and NR2B was detected by real-time PCR. The results suggest that pre-ischemic treadmill training may induce brain ischemic tolerance by reducing the mRNA levels of mGluR5 and NR2B, and thus, the results indicate that physical exercise might be an effective method to establish ischemic preconditioning.

  17. The effects of erythropoietin on STAT1 and STAT3 levels following cerebral ischemia-reperfusion in rats

    International Nuclear Information System (INIS)

    Objective: To explore the effects of erythropoietin (EPO) on the expression of signal transducer and activator of transcription (STAT) 1, phosphorylated STAT1 (P-STAT1), STAT3, P-STAT3 and cell apoptosis in rat models of focal cerebral ischemia-reperfusion. Methods: Eighty male Sprague-Dawley rats were randomly and evenly divided into four groups by completely random design method: sham-operation (group A), cerebral ischemia-reperfusion (group B), cerebral ischemia-reperfusion ± saline (group C) and cerebral ischemia-reperfusion ± EPO (group D). The model of focal cerebral ischemia-reperfusion injury was established by blocking the left middle cerebral artery. All rats underwent MRI for the detection of the changes of infarct area between 2 h post ischemia and 24 h of reperfusion. Western blot was used to observe the expression of STAT1, P-STAT1, STAT3, P-STAT3. Terminal oxynucleotidyl transferase mediated dUTP biotin nick end labeling (TUNEL) was used to evaluate the cell apoptosis including the relative area (ROI area/whole brain area of the same layer × 100%) of abnormal signal region,relative optical density (rOD) and apoptotic index. One-way analysis of variance and q test were used to analyze the data. Results: On T2WI imaging, rats in group B and group C presented large hyperintense areas in the cortex and subcortex of left hemispheric ((28.00±4.60)% and (29.70±4.80)% respectively). Group D presented less hyperintense areas in the cortex and subcortex of left hemispheric compared with group B and group C ((21.10±2.40) %; F=11.285, P<0.01). The expression of STAT1 and STAT3 proteins was not significantly affected by ischemia-reperfusion and EPO intervention compared with normal brain tissue (F=0.806, 1.558, both P>0.05). However, the level of P-STAT1 was low in group A (rOD =0.75±0.13) but increased after cerebral ischemia-reperfusion. Compared with group B and group C, P-STAT1 expression was lower in group D (B-D: 2.08±0.15, 2.05±0.16, 1.92±0.05; F

  18. No Additional Prognostic Value of Genetic Information in the Prediction of Vascular Events after Cerebral Ischemia of Arterial Origin: The PROMISe Study

    OpenAIRE

    Achterberg, Sefanja; Kappelle, L. Jaap; de Bakker, Paul I.W.; Traylor, Matthew; Algra, Ale; ,

    2015-01-01

    Background Patients who have suffered from cerebral ischemia have a high risk of recurrent vascular events. Predictive models based on classical risk factors typically have limited prognostic value. Given that cerebral ischemia has a heritable component, genetic information might improve performance of these risk models. Our aim was to develop and compare two models: one containing traditional vascular risk factors, the other also including genetic information. Methods and Results We studied ...

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

    Directory of Open Access Journals (Sweden)

    Jing Sun

    2015-01-01

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

  20. Moderately delayed post-insult treatment with normobaric hyperoxia reduces excitotoxin-induced neuronal degeneration but increases ischemia-induced brain damage

    Directory of Open Access Journals (Sweden)

    Haelewyn Benoit

    2011-04-01

    Full Text Available Abstract Background The use and benefits of normobaric oxygen (NBO in patients suffering acute ischemic stroke is still controversial. Results Here we show for the first time to the best of our knowledge that NBO reduces both NMDA-induced calcium influxes in vitro and NMDA-induced neuronal degeneration in vivo, but increases oxygen and glucose deprivation-induced cell injury in vitro and ischemia-induced brain damage produced by middle cerebral artery occlusion in vivo. Conclusions Taken together, these results indicate that NBO reduces excitotoxin-induced calcium influx and subsequent neuronal degeneration but favors ischemia-induced brain damage and neuronal death. These findings highlight the complexity of the mechanisms involved by the use of NBO in patients suffering acute ischemic stroke.

  1. 乙醇对脑缺血再灌注大鼠海马凋亡诱导因子和胱天蛋白酶-3表达的影响%Effects of alcohol on hippocampal apoptosis-inducing factor and caspase-3 expression in cerebral ischemia/reperfusion in rats

    Institute of Scientific and Technical Information of China (English)

    李健; 刘志辉; 张培; 王彬

    2013-01-01

    Objective To investigate the effects of alcohol on hippocampal apoptosis-inducing factor (AIF) and caspase-3 expression in cercbral ischemia/reperfusion in rats.Methods Sixty-eight healthy adult male Wistar rats were randomly divided into a sham operation group (n =4) and a saline control group as well as low-dose (1.0 g/kg),medium-dose (1.5 g/kg) and high-dose (2.0 g/kg) ethanol groups.The saline control group and each dose alcohol group were redivided into ischemia/reperfusion 0,1,2 and 3 h subgroups according to the intervention time points (n =4 in each group).A model of middle cerebral artery ischemia/reperfusion in rats was induced by the suture method.The corresponding doses of ethanol or an equal volume of saline were injected intraperitoneally at ischemia for 2 h and reperfusion for 0,1,2 and 3 h in the alcohol groups and the saline control group.At ischemia for 2 hand reperfusion for 24 h,the neurological deficit in rats was evaluated by using behavioral score.Immunohistochemistry assay was used to detect the expressions of AIF and caspase3 in the hippocampus of ischemic sides at ischemia for 2 hand reperfusion for 24 h.Results The behavior evaluation showed that the neurological deficit score was 0 in the sham operation group.The neurological deficit scores in the different dose ethanol groups were significantly lower than those in the saline control group at the same intervention time points (all P=0.000),and there were significant differences between the same intervention time points in the different dose ethanol groups (all P =0.000).The high-dose ethanol group was the lowest.There were no significant differences between the different intervention time points in the same dose ethanol groups (all P>0.05).Immunohistochemistry revealed that the numbers of positive cells of AIF and caspase-3 in the sham operation group were 17.21 ±2.86 and 20.60 ±4.39,respectively,and they were significantly less than those in the saline control group and the each

  2. Nrf2/antioxidant defense pathway is involved in the neuroprotective effects of Sirt1 against focal cerebral ischemia in rats after hyperbaric oxygen preconditioning.

    Science.gov (United States)

    Xue, Fen; Huang, Jin-Wen; Ding, Pei-Yan; Zang, Hong-Gang; Kou, Zhi-Jian; Li, Ting; Fan, Juan; Peng, Zheng-Wu; Yan, Wen-Jun

    2016-08-01

    Sirtuin 1 (Sirt1) is a class III histone deacetylase involved in neuroprotection induced by hyperbaric oxygen preconditioning (HBO-PC) in animal models of ischemia. However, the underlying mechanisms remain to be illustrated. In the present study, rats exposed to middle cerebral artery occlusion (MCAO) were used to establish an ischemic stroke model. The infarct volume ratio, neurobehavioral score, and expressions of Sirt1, nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), and superoxide dismutase 1 (SOD1) were evaluated at 7 days after reperfusion, and the level of malondialdehyde (MDA) was used to assess oxidative stress. HBO-PC increased the expression of Sirt1 and reduced infarct volume ratio and neurobehavioral deficit in MCAO rats. Meanwhile, HBO-PC also increased expression of Nrf2, HO-1, and SOD1 and decreased MDA content. Furthermore, either Sirt1 or Nrf2 knockdown by short interfering RNA (siRNA) inhibited the expression of Nrf2, HO-1, and SOD1 and eliminated the neuroprotective effects of HBO-PC. Taken together, the results suggest that the Nrf2/antioxidant defense pathway is involved in the long lasting neuroprotective effects of Sirt1 induced by HBO-PC against transient focal cerebral ischemia. PMID:27131779

  3. Time-dependent changes of glial fibriliary acidic protein and cytosolic phospholipase A2 in hippocampal area of focal cerebral ischemia/reperfusion in rats

    Institute of Scientific and Technical Information of China (English)

    Qingzhou Cheng; Xingui Ming

    2006-01-01

    BACKGROUND: Interaction between astrocyte and neuron may two-dimensionally influence on ischemic injury; however, glial fibriliary acidic protein (GFAP) and cytosolic phospholipase A2 (cPLA2) are both important markers to reflect changes of astrocyte and neuron after cerebral ischemia, respectively.OBJECTIVE: To observe the changes of GFAP and positive cPLA2 cells in hippocampal area of model rats with focal cerebral ischemia in various phases of cerebral ischemia/reperfusion.DESIGN: Randomized contrast observation.SETTTNG: Department of Basic Medical Science, Medical College of Wuhan Polytechnic University; Faculty of Human Anatomy and Histology & Embryology, Medical College of Wuhan University.MATERIALS: The experiment was carried out in the Department of Basic Medical Science, Medical College of Wuhan Industry College from May to June 2004. A total of 28 healthy SD rats of either gender and weighing 200-250 g were provided by Animal Department of Medical College of Jianghan University.METHODS: All 28 rats were randomly divided into 7 groups, including sham operation group, 2-, 6-, 12-,24- and 48-reperfusion groups, and triphenyltetrazolium chloride (TTC) group, with 4 in each group. Two hours after ischemia, ischemia/reperfusion models were established in left middle cerebral artery (MCA);common carotid artery was ligated and line cork was inserted into it with the depth of (1.8±0.5) cm. Rats in sham operation group were inserted with the depth of 1.0 cm, and other operations were as the same as those in 2-hour ischemia/reperfusion groups. Models in TTC group were established as the same as those in 2-hour ischemia/24-hour reperfusion group, and they were used to evaluate the therapeutic effect.Changes of GFAP and cPLA2 in hippocampal area in various phases were detected with immunohistochemical method.MATN OUTCOME MEASURES: Changes of GFAP and positive cPLA2 cells in hippocampal area of rats with focai cerebral ischemia in various phases of ischemia

  4. Identification of exercise-induced ischemia using QRS slopes.

    Science.gov (United States)

    Firoozabadi, Reza; Gregg, Richard E; Babaeizadeh, Saeed

    2016-01-01

    In this work we studied a computer-aided approach using QRS slopes as unconventional ECG features to identify the exercise-induced ischemia during exercise stress testing and demonstrated that the performance is comparable to the experts' manual analysis using standard criteria involving ST-segment depression. We evaluated the performance of our algorithm using a database including 927 patients undergoing exercise stress tests and simultaneously collecting the ECG recordings and SPECT results. High resolution 12-lead ECG recordings were collected continuously throughout the rest, exercise, and recovery phases. Patients in the database were classified into three categories of moderate/severe ischemia, mild ischemia, and normal according to the differences in sum of the individual segment scores for the rest and stress SPECT images. Philips DXL 16-lead diagnostic algorithm was run on all 10-s segments of 12-lead ECG recordings for each patient to acquire the representative beats, ECG fiducial points from the representative beats, and other ECG parameters. The QRS slopes were extracted for each lead from the averaged representative beats and the leads with highest classification power were selected. We employed linear discriminant analysis and measured the performance using 10-fold cross-validation. Comparable performance of this method to the conventional ST-segment analysis exhibits the classification power of QRS slopes as unconventional ECG parameters contributing to improved identification of exercise-induced ischemia. PMID:26607407

  5. Placental Growth Factor Administration Abolishes Placental Ischemia-Induced Hypertension.

    Science.gov (United States)

    Spradley, Frank T; Tan, Adelene Y; Joo, Woo S; Daniels, Garrett; Kussie, Paul; Karumanchi, S Ananth; Granger, Joey P

    2016-04-01

    Preeclampsia is a pregnancy-specific disorder of new-onset hypertension. Unfortunately, the most effective treatment is early delivery of the fetus and placenta. Placental ischemia appears central to the pathogenesis of preeclampsia because placental ischemia/hypoxia induced in animals by reduced uterine perfusion pressure (RUPP) or in humans stimulates release of hypertensive placental factors into the maternal circulation. The anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1), which antagonizes and reduces bioavailable vascular endothelial growth factor and placental growth factor (PlGF), is elevated in RUPP rats and preeclampsia. Although PlGF and vascular endothelial growth factor are both natural ligands for sFlt-1, vascular endothelial growth factor also has high affinity to VEGFR2 (Flk-1) causing side effects like edema. PlGF is specific for sFlt-1. We tested the hypothesis that PlGF treatment reduces placental ischemia-induced hypertension by antagonizing sFlt-1 without adverse consequences to the mother or fetus. On gestational day 14, rats were randomized to 4 groups: normal pregnant or RUPP±infusion of recombinant human PlGF (180 μg/kg per day; AG31, a purified, recombinant human form of PlGF) for 5 days via intraperitoneal osmotic minipumps. On day 19, mean arterial blood pressure and plasma sFlt-1 were higher and glomerular filtration rate lower in RUPP than normal pregnant rats. Infusion of recombinant human PlGF abolished these changes seen with RUPP along with reducing oxidative stress. These data indicate that the increased sFlt-1 and reduced PlGF resulting from placental ischemia contribute to maternal hypertension. Our novel finding that recombinant human PlGF abolishes placental ischemia-induced hypertension, without major adverse consequences, suggests a strong therapeutic potential for this growth factor in preeclampsia. PMID:26831193

  6. Neuroprotective effect of pretreatment with ganoderma lucidum in cerebral ischemia/reperfusion injur y in rat hippocampus

    Institute of Scientific and Technical Information of China (English)

    Wangxin Zhang; Qiuling Zhang; Wen Deng; Yalu Li; Guoqing Xing; Xianjun Shi; Yifeng Du

    2014-01-01

    Ganoderma lucidum is a traditional Chinese medicine, which has been shown to have both an-ti-oxidative and anti-inlfammatory effects, and noticeably decreases both the infarct area and neuronal apoptosis of the ischemic cortex. This study aimed to investigate the protective effects and mechanisms of pretreatment with ganoderma lucidum (by intragastric administration) in cerebral ischemia/reperfusion injury in rats. Our results showed that pretreatment with ganoder-ma lucidum for 3 and 7 days reduced neuronal loss in the hippocampus, diminished the content of malondialdehyde in the hippocampus and serum, decreased the levels of tumor necrosis fac-tor-αand interleukin-8 in the hippocampus, and increased the activity of superoxide dismutase in the hippocampus and serum. hTese results suggest that pretreatment with ganoderma lucidum was protective against cerebral ischemia/reperfusion injury through its anti-oxidative and an-ti-inlfammatory actions.

  7. Feasibility of establishing cerebral ischemia models by using aerocyst-blocking bilateral ascending pharyngeal artery of piglets Imaging assessment

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: The cerebral ischemia and ischemia/reperfusion animal models are used to simulate the human cerebrovascular diseases is one of the popular topics of neurological science recently. To study the pathophysiology, pathogenesis, prophylaxis and treatment of ischemic cerebrovascular diseases and to establish the ideal animal model that is the most similar to the human cerebral ischemia, are the topics that the people generally cared about.OBJECTIVE: To evaluate the effects of aerocyst-blocking bilateral ascending pharyngeal artery on the establishment of cerebral ischemia models by using digital subtraction angiography (DSA), magnetic resonance diffusion-weighted imaging (DWI) and magnetic resonance perfusion-weighted imaging (PWI). DESIGN: Repetitive measure animal experiment.SETTING: Zhongshan Hospital Affiliated to Dalian University.MATERIALS: The experiment was carried out in the Animal Laboratory (Provincial Laboratory),Zhongshan Hospital of Dalian Univeristy from January to May 2006. A total of 14 domestic piglets, of 6 months old, weighing 12 - 15 kg, of either gender, were selected from Animal Experimental Center, Dalian University. Multistar T.O.P digital subtraction angiography machine was provided by Siemens Company,German.METHODS: Aerocyst-blocking bilateral ascending pharyngeal artery was used to establish cerebral ischemia models. And then, Multistar T.O.P. DSA was used for imaging of cerebral vessels before blocking, during blocking and at 0.5 and 2 hours after ischemia perfusion. GE Signa 1.5 T supraconduction magnetic resonance imaging was used for DWI examination; in addition, PWI was used based on focal sites and areas.Otherwise, magnetic resonance imaging (MRI) was used to detect signal changes of T1WI and T2WI in ischemic areas.MAIN OUTCOME MEASURES: Analytic results of DSA, DWI, PWI and MRI.RESULTS: All 14 experimental piglets were involved in the final analysis. ① DSA: The blood flow of bilateral ascending pharyngeal arteries and its

  8. Dose-dependent effects of procyanidin on nerve growth factor expression following cerebral ischemia/ reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    Feng Li; Hai Xie; Ying Gao; Tongxia Zhan

    2008-01-01

    BACKGROUND: Recently, grape seed procyanidin (GSP) has been shown to be exhibit antioxidant effects, effectively reducing ischemia/reperfusion injury and inhibiting brain cell apoptosis.OBJECTIVE: To study the effects of GSP on nerve growth factor (NGF) expression and neurological function following cerebral ischemia/reperfusion injury in rats.DESIGN: Randomized controlled study based on SD rats.SETTING: Weifang Municipal People's Hospital. MATERIALS: Forty-eight healthy adult SD rats weighing 280-330 g and irrespective of gender were provided by the Experimental Animal Center of Shandong University. GSP derived from grape seed was a new high-effective antioxidant provided by Tianjin Jianfeng Natural Product Researching Company (batch number: 20060107). Rabbit-anti-rat NGF monoclonal antibody was provided by Beijing Zhongshan Biotechnology Co., Ltd., and SABC immunohistochemical staining kit by Wuhan Boster Bioengineering Co., Ltd. METHODS: The present study was performed in the Functional Laboratory of Weifang Medical College from April 2006 to January 2007. Forty-eight SD rats were randomly divided into the sham operation group, ischemia/reperfusion group, high-dose GSP (40 mg/kg) group, or low-dose GSP (10 mg/kg) group (n = 12 per group). Ischemia/reperfusion injury was established using the threading embolism method of the middle cerebral artery. Rats in the ischemia/reperfusion model group were given saline injection (2 mL/kg i.p.) once daily for seven days pre-ischemia/reperfusion, and once more at 15 minutes before reperfusion. Rats in the high-dose and low-dose GSP groups were injected with GSP (20 or 5 mg/mL i.p., respectively, 2 mL/kg) with the same regime as the ischemia/reperfusion model group. The surgical procedures in the sham operation group were as the same as those in the ischemia/reperfusion model group, but the thread was approximately 10 mm long, thus, the middle cerebral artery was not blocked. MAIN OUTCOME MEASURES: NGF expression in the

  9. Neuroprotective effects of atorvastatin against cerebral ischemia/reperfusion injury through the inhibition of endoplasmic reticulum stress

    Institute of Scientific and Technical Information of China (English)

    Jian-wen Yang; Zhi-ping Hu

    2015-01-01

    Cerebral ischemia triggers secondary ischemia/reperfusion injury and endoplasmic reticulum stress initiates cell apoptosis. However, the regulatory mechanism of the signaling pathway remains unclear. We hypothesize that the regulatory mechanisms are mediated by the protein kinase-like endoplasmic reticulum kinase/eukaryotic initiation factor 2α in the endoplasmic reticulum stress signaling pathway. To verify this hypothesis, we occluded the middle cere-bral artery in rats to establish focal cerebral ischemia/reperfusion model. Results showed that the expression levels of protein kinase-like endoplasmic reticulum kinase and caspase-3, as well as the phosphorylation of eukaryotic initiation factor 2α, were increased after ischemia/reperfusion. Administration of atorvastatin decreased the expression of protein kinase-like endoplasmic reticulum kinase, caspase-3 and phosphorylated eukaryotic initiation factor 2α, reduced the infarct volume and improved ultrastructure in the rat brain. After salubrinal, the speciifc inhibitor of phosphorylated eukaryotic initiation factor 2α was given into the rats in-tragastrically, the expression levels of caspase-3 and phosphorylated eukaryotic initiation factor 2α in the were decreased, a reduction of the infarct volume and less ultrastructural damage were observed than the untreated, ischemic brain. However, salubrinal had no impact on the expression of protein kinase-like endoplasmic reticulum kinase. Experimental ifndings indi-cate that atorvastatin inhibits endoplasmic reticulum stress and exerts neuroprotective effects. The underlying mechanisms of attenuating ischemia/reperfusion injury are associated with the protein kinase-like endoplasmic reticulum kinase/eukaryotic initiation factor 2α/caspase-3 pathway.

  10. An effective solution to discover synergistic drugs for anti-cerebral ischemia from traditional Chinese medicinal formulae.

    Directory of Open Access Journals (Sweden)

    Shaojing Li

    Full Text Available Recently, the pharmaceutical industry has shifted to pursuing combination therapies that comprise more than one active ingredient. Interestingly, combination therapies have been used for more than 2500 years in traditional Chinese medicine (TCM. Understanding optimal proportions and synergistic mechanisms of multi-component drugs are critical for developing novel strategies to combat complex diseases. A new multi-objective optimization algorithm based on least angle regression-partial least squares was proposed to construct the predictive model to evaluate the synergistic effect of the three components of a novel combination drug Yi-qi-jie-du formula (YJ, which came from clinical TCM prescription for the treatment of encephalopathy. Optimal proportion of the three components, ginsenosides (G, berberine (B and jasminoidin (J was determined via particle swarm optimum. Furthermore, the combination mechanisms were interpreted using PLS VIP and principal components analysis. The results showed that YJ had optimal proportion 3(G: 2(B: 0.5(J, and it yielded synergy in the treatment of rats impaired by middle cerebral artery occlusion induced focal cerebral ischemia. YJ with optimal proportion had good pharmacological effects on acute ischemic stroke. The mechanisms study demonstrated that the combination of G, B and J could exhibit the strongest synergistic effect. J might play an indispensable role in the formula, especially when combined with B for the acute stage of stroke. All these data in this study suggested that in the treatment of acute ischemic stroke, besides restoring blood supply and protecting easily damaged cells in the area of the ischemic penumbra as early as possible, we should pay more attention to the removal of the toxic metabolites at the same time. Mathematical system modeling may be an essential tool for the analysis of the complex pharmacological effects of multi-component drug. The powerful mathematical analysis method could

  11. Exploratory Pharmacokinetics of Geniposide in Rat Model of Cerebral Ischemia Orally Administered with or without Baicalin and/or Berberine

    OpenAIRE

    Linmei Pan; Wenzhe Wang; Feiyan Shi; Jing Zhou; Meng Zhang; Huaxu Zhu; Mingfei Zeng

    2013-01-01

    Huang-Lian-Jie-Du-Tang (HLJDT), a classical Chinese prescription, has been clinically employed to treat cerebral ischemia for thousands of years. Geniposide is the major active ingredient in HLJDT. The aim is to investigate the comparative evaluations on pharmacokinetics of geniposide in MCAO rats in pure geniposide, geniposide : berberine, and geniposide : berberine : baicalin. Obviously, the proportions of geniposide : berberine, geniposide : baicalin, and geniposide : berberine : baicalin ...

  12. In vivo imaging of activated microglia in a mouse model of focal cerebral ischemia by two-photon microscopy

    OpenAIRE

    Bok, Seoyeon; Wang, Taejun; Lee, Chan-Ju; Jeon, Seong-Uk; Kim, Young-eun; Kim, Jeongwoo; Hong, Beom-Ju; Yoon, Calvin Jinse; Kim, Sungjee; Lee, Seung-Hoon; KIM, HAK JAE; Kim, Il Han; Kim, Ki Hean; Ahn, G-One

    2015-01-01

    Microglia are brain resident macrophages rapidly responding to various stimuli to exert appropriate inflammatory responses. Although they have recently been exploited as an attractive candidate for imaging neuroinflammation, it is still difficult to visualize them at the cellular and molecular levels. Here we imaged activated microglia by establishing intracranial window chamber (ICW) in a mouse model of focal cerebral ischemia by using two-photon microscopy (TPM), in vivo. Intravenous inject...

  13. A derivative of the CRMP2 binding compound lanthionine ketimine provides neuroprotection in a mouse model of cerebral ischemia

    OpenAIRE

    Nada, Shadia E.; Tulsulkar, Jatin; Raghavan, Aparna; Hensley, Kenneth; Shah, Zahoor A.

    2012-01-01

    Lanthionines are novel neurotrophic and neuroprotective small molecules that show promise for the treatment of neurodegenerative diseases. In particular, a recently developed, cell permeable lanthionine derivative known as LKE (lanthionine ketimine 5-ethyl ester) promotes neurite growth at low nanomolar concentrations. LKE also has neuroprotective, anti-apoptotic, and anti-inflammatory properties. Its therapeutic potential in cerebral ischemia and its mechanisms of neurotrophic action remain ...

  14. The Immune Response to Acute Focal Cerebral Ischemia and Associated Post-stroke Immunodepression: A Focused Review

    OpenAIRE

    Famakin, Bolanle M.

    2014-01-01

    It is currently well established that the immune system is activated in response to transient or focal cerebral ischemia. This acute immune activation occurs in response to damage, and injury, to components of the neurovascular unit and is mediated by the innate and adaptive arms of the immune response. The initial immune activation is rapid, occurs via the innate immune response and leads to inflammation. The inflammatory mediators produced during the innate immune response in turn lead to r...

  15. Pharmacologic preconditioning with berberine attenuating ischemia-induced apoptosis and promoting autophagy in neuron.

    Science.gov (United States)

    Zhang, Qichun; Bian, Huimin; Guo, Liwei; Zhu, Huaxu

    2016-01-01

    Pharmacologic preconditioning is an intriguing and emerging approach adopted to prevent injury of ischemia/reperfusion. Neuroprotection is the cardinal effect of these pleiotropic actions of berberine. Here we investigated that whether berberine could acts as a preconditioning stimuli contributing to attenuate hypoxia-induced neurons death as well. Male Sprague-Dawley rats of middle cerebral artery occlusion (MCAO) and rat primary cortical neurons undergoing oxygen and glucose deprivation (OGD) were preconditioned with berberine (40 mg/kg, for 24 h in vivo, and 10(-6) mol/L, for 2 h in vitro, respectively). The neurological deficits and cerebral water contents of MCAO rats were evaluated. The autophagy and apoptosis were further determined in primary neurons in vitro. Berberine preconditioning (BP) was then shown to ameliorate the neurological deficits, decrease cerebral water content and promote neurogenesis of MCAO rats. Decreased LDH release from OGD-treated neurons was observed via BP, which was blocked by LY294002 (20 µmol/L), GSK690693 (10 µmol/L), or YC-1 (25 µmol/L). Furthermore, BP stimulated autophagy and inhibited apoptosis via modulated the autophagy-associated proteins LC 3, Beclin-1 and p62, and apoptosis-modulating proteins caspase 3, caspase 8, caspase 9, PARP and BCL-2/Bax. In conclusion, berberine acts as a stimulus of preconditioning that exhibits neuroprotection via promoting autophagy and decreasing anoxia-induced apoptosis. PMID:27158406

  16. Effects of low molecular weight heparin-superoxide dismutase conjugate on serum levels of nitric oxide, glutathione peroxidase, and myeloperoxidase in a gerbil model of cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Qingde Wang; Guixiang Cui; Hongxia Liu; Yizhao Li; Fengshan Wang

    2008-01-01

    BACKGROUND: Several studies have demonstrated that low molecular weight heparin-superoxide dismutase (LMWH-SOD) conjugate may exhibit good neuroprotective effects on cerebral ischemia/reperfusion injury though anticoagulation, decreasing blood viscosity, having anti-inflammatory activity, and scavenging oxygen free radicals. OBJECTIVE: To investigate the intervention effects of LMWH-SOD conjugate on serum levels of nitric oxide (NO), glutathione peroxidase (GSH-Px), and myeloperoxidase (MPO) following cerebral ischemia/reperfusion injury. DESIGN, TIME AND SETTING: A randomized, controlled, and neurobiochemical experiment was performed at the Institute of Biochemical Pharmacy, School of Pharmaceutical Sciences, Shandong University between April and July 2004. MATERIALS: A total of 60 Mongolian gerbils of either gender were included in this study. Total cerebral ischemia/reperfusion injury was induced in 50 gerbils by occluding bilateral common carotid arteries. The remaining 10 gerbils received a sham-operation (sham-operated group). Kits of SOD, NO, and MPO were sourced from Nanjing Jiancheng Bioengineering Institute, China. LMWH, SOD, and LMWH-SOD conjugates were provided by Institute of Biochemistry and Biotechnique, Shandong University, China. METHODS: Fifty successful gerbil models of total cerebral ischemia/reperfusion injury were evenly randomized to five groups: physiological saline, LMWH-SOD, SOD, LMWH + SOD, and LMWH. At 2 minutes prior to ischemia, 0.5 mL/65 g physiological saline, 20 000 U/kg LMWH-SOD conjugate, 20 000 U/kg SOD, a mixture of SOD (20 000 U/kg) and LMWH (LMWH dose calculated according to weight ratio, LMWH: SOD = 23.6:51), and LMWH (dose as in the LMWH + SOD group) were administered through the femoral artery in each above-mentioned group, respectively. MAIN OUTCOME MEASURES: Serum levels of NO, MPO, and GSH-Px. RESULTS: Compared with 10 sham-operated gerbils, the cerebral ischemia/reperfusion injury gerbils exhibited decreased serum

  17. Erythropoietin Modulates Cerebral and Serum Degradation Products from Excess Calpain Activation following Prenatal Hypoxia-Ischemia.

    Science.gov (United States)

    Jantzie, Lauren L; Winer, Jesse L; Corbett, Christopher J; Robinson, Shenandoah

    2016-01-01

    Preterm infants suffer central nervous system (CNS) injury from hypoxia-ischemia and inflammation - termed encephalopathy of prematurity. Mature CNS injury activates caspase and calpain proteases. Erythropoietin (EPO) limits apoptosis mediated by activated caspases, but its role in modulating calpain activation has not yet been investigated extensively following injury to the developing CNS. We hypothesized that excess calpain activation degrades developmentally regulated molecules essential for CNS circuit formation, myelination and axon integrity, including neuronal potassium-chloride co-transporter (KCC2), myelin basic protein (MBP) and phosphorylated neurofilament (pNF), respectively. Further, we predicted that post-injury EPO treatment could mitigate CNS calpain-mediated degradation. Using prenatal transient systemic hypoxia-ischemia (TSHI) in rats to mimic CNS injury from extreme preterm birth, and postnatal EPO treatment with a clinically relevant dosing regimen, we found sustained postnatal excess cortical calpain activation following prenatal TSHI, as shown by the cleavage of alpha II-spectrin (αII-spectrin) into 145-kDa αII-spectrin degradation products (αII-SDPs) and p35 into p25. Postnatal expression of the endogenous calpain inhibitor calpastatin was also reduced following prenatal TSHI. Calpain substrate expression following TSHI, including cortical KCC2, MBP and NF, was modulated by postnatal EPO treatment. Calpain activation was reflected in serum levels of αII-SDPs and KCC2 fragments, and notably, EPO treatment also modulated KCC2 fragment levels. Together, these data indicate that excess calpain activity contributes to the pathogenesis of encephalopathy of prematurity. Serum biomarkers of calpain activation may detect ongoing cerebral injury and responsiveness to EPO or similar neuroprotective strategies. PMID:26551007

  18. Angiopoietin-1 mRNA expression in estradiol-treated ovariectomized rats with focal cerebral ischemia after reperfusion

    Institute of Scientific and Technical Information of China (English)

    Ling Tang; Jun Zuo; Yonghong Wang; Yuanda Zhou; Haixia He

    2008-01-01

    BACKGROUND: Epidemiologic studies have indicated that the incidence of stroke in premenopausal females is lower than in males at the same age, but it significantly rises in postmenopausal females. Estrogen is used clinically to alleviate injury caused by cerebral ischemia. It has been hypothesized that the neuroprotective role of estrogen relates to angiopoietin (Angpt), which plays an important role in vascularization, vascular remodeling and maturation.OBJECTIVE: To observe and validate the effect of estradiol on angiopoietin-1 (Angpt1) mRNA expression in ovariectomized rats with focal cerebral ischemia alter reperfusion, so as to explore the molecular mechanisms of estradiol-mediated protection from cerebral ischemic damage.DESIGN, TIME AND SETTING: Randomized, controlled, molecular biology, prospective animal study. The experiment was performed at the Central Laboratory of Chongqing Medical University from September to December 2005.MATERIALS: Fifty healthy female wild type (WT) rats aged 6 months and fifty female rats aged 6 months with knockout of the estrogen-alpha receptor gene (ERKO).METHODS: WT rats and ERKO rats were divided into estradiol and control groups (n = 25), and injected intramuscularly with estradiol benzoate (100 μg/kg per day) or corn oil (1 mL/kg per day) for 7 days, 30 days after bilateral ovariectomy. Rat models of cerebral ischemia/reperfusion were established with the middle cerebral artery occlusion method. After 30 minutes of middle cerebral artery occlusion, rats from the estradiol and control groups were injected intramuscularly with estradiol benzoate or corn oil at the above dose.MAIN OUTCOME MEASURES: We used radio-immunity analysis and laser-Doppler flowmetry to measure plasma estradiol levels and changes in cerebral blood flow. We used immunohistochemical staining of CD34 epitopes to measure changes in the capillary density in brain following cerebral ischemia/reperfusion, and quantitative RT-PCR analysis to assess m

  19. Neuroprotective effect ofShenqi Fuzheng injection pretreatment in aged rats with cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Ying-min Cai; Yong Zhang; Peng-bo Zhang; Lu-ming Zhen; Xiao-ju Sun; Zhi-ling Wang; Ren-yan Xu; Rong-liang Xue

    2016-01-01

    Shenqi Fuzheng injection is extracted from the Chinese herbsRadix Astragali andRadix Codonopsis. The aim of the present study was to investigate the neuroprotective effects of Shenqi Fuzheng injection in cerebral ischemia and reperfusion. Aged rats (20–22 months) were divided into three groups: sham, model, and treatment.Shenqi Fuzheng injection or saline (40 mL/kg) was injected into the tail vein daily for 1 week, after which a cerebral ischemia/reperfusion injury model was established. Compared with model rats that received saline, rats in the treatment group had smaller infarct volumes, lower brain water and malondialdehyde content, lower brain Ca2+levels, lower ac-tivities of serum lactate dehydrogenase and creatine kinase, and higher superoxide dismutase activity. In addition, the treatment group showed less damage to the brain tissue ultrastructure and better neurological function. Our ifndings indicate thatShenqi Fuzheng injec-tion exerts neuroprotective effects in aged rats with cerebral ischemia/reperfusion injury, and that the underlying mechanism relies on oxygen free radical scavenging and inhibition of brain Ca2+ accumulation.

  20. EAAC1 Gene Deletion Increases Neuronal Death and Blood Brain Barrier Disruption after Transient Cerebral Ischemia in Female Mice

    Directory of Open Access Journals (Sweden)

    Bo Young Choi

    2014-10-01

    Full Text Available EAAC1 is important in modulating brain ischemic tolerance. Mice lacking EAAC1 exhibit increased susceptibility to neuronal oxidative stress in mice after transient cerebral ischemia. EAAC1 was first described as a glutamate transporter but later recognized to also function as a cysteine transporter in neurons. EAAC1-mediated transport of cysteine into neurons contributes to neuronal antioxidant function by providing cysteine substrates for glutathione synthesis. Here we evaluated the effects of EAAC1 gene deletion on hippocampal blood vessel disorganization after transient cerebral ischemia. EAAC1−/− female mice subjected to transient cerebral ischemia by common carotid artery occlusion for 30 min exhibited twice as much hippocampal neuronal death compared to wild-type female mice as well as increased reduction of neuronal glutathione, blood–brain barrier (BBB disruption and vessel disorganization. Pre-treatment of N-acetyl cysteine, a membrane-permeant cysteine prodrug, increased basal glutathione levels in the EAAC1−/− female mice and reduced ischemic neuronal death, BBB disruption and vessel disorganization. These findings suggest that cysteine uptake by EAAC1 is important for neuronal antioxidant function under ischemic conditions.

  1. Effects of ligustrazine on somatosensory evoked potential in normal rabbits and rabbits with cerebral ischemia-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Deshan Liu; Shuli Wang; Yuanyuan Hao

    2006-01-01

    BACKGROUND: Somatosensory evoked potential (SEP) has become a method with higher sensitivity and specificity than electroencephalogram in detecting the brain function and the region, range and degree of ischemia. However, the effects of ligustrazine on SEP is still not clear.OBJECTIVE: To study the protective effects of ligustrazini injection on cerebral ischemia-reperfusion injury.DESIGN: Auto-control study, random grouping.SETTING: Qilu Hospital of Shandong University.MATERIALS: The experiment was completed in the Cerebral Functional Room of Qilu Hospital Affiliated to Shandong University from March 2002 to June 2004. A totally of 24 healthy Harbin rabbits were randomly divided into blank control group (n=8), model control group (n=8) and ligustrazine treatment group (n=8).Hydrochloric ligustrazine injection, 40 mg/2 mL each ampoule, was provided by the Third Pharmaceutical Factory of Beijing (certification: 93035236273). The main component was hydrochloric ligustrazine and the chemical name was 2, 3, 5, 6-tetramethyl pyrazine hydrochloride.METHODS: ① Modeling method: The bilateral common carotid artery ligation was adopted to make the model. ② Index of cerebral functional lesion evaluated with SEP during ischemia-reperfusion: DISA 2000C neuromyoeletrometer provided by Dantec Electronics Ltd, Denmark was used to detect SEP. ③ Interventional process: Blank control group: The latencies and amplitudes of SEP were measured before injection with 1.5 mg/kg ligustrazine and at the points of 15 minutes, 20 minutes, 30 minutes, 60 minutes, 90 minutes and 120 minutes after injection. Ligustrazine treatment group: Rabbits were injected with 1.5 mg/kg ligustrazine, and those of model control group were injected the same volume of saline. Thirty minutes later, the bilateral common carotid artery of the rabbits all had been ligated for 30 minutes, and then reperfused for 120 minutes. The latencies and amplitudes of SEP were measured before injection, before ligation, at

  2. 电针对脑缺血再灌注损伤大鼠海马诱导型一氧化氮合酶mRNA表达的影响%Effect of electroacupuncture on inducible nitric oxide synthase mRNA expression in hippocampus of the rats with cerebral ischemia-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    周爽; 黄建华; 方邦江; 袁凌松

    2005-01-01

    注后大鼠海马诱导型一氧化氮合酶mRNA表达,从而减少一氧化氮的产生,有助于减轻脑缺血再灌注损伤.%BACKGROUND: Researches indicate that inducible nitric oxide synthase(iNOS) plays an important role in relieving destruction of blood brain barrier and protecting vascular endothelium and brain tissue in cerebral ischemia-reperfusion injury.OBJECTIVE: To observe the effect of Shuigou (DU26), Neiguan (PC6)and Zusanli (ST36) on the expression of inducible nitric oxide synthase messenger ribonucleic acid (iNOS mRNA) in hippocampus of the rats with cerebral ischemia-reperfusion.DESIGN: Randomized controlled study.SETTING: Shanghai University of Traditional Chinese Medicine, Shanghai Institute of Acupuncture and Meridian and Huashan Hospital Affiliated to Fudan University.METHODS: The experiment was completed at the Experimental Animal Center in Shanghai University of Traditional Chinese Medicine, Threegrade Acupuncture Immunological Laboratory of Shanghai Research Institute of Acupuncture and Meridian and Huashan Hospital Affiliated to Fudan University from December 2003 to December 2004. Totally 40 SD rats were randomly divided as normal group, sham operation group, model group and electroacupuncture group with 10 in each group. The hypertension model rats were induced with bi-kidney-bi-clip method, then the focal cerebral ischemia-reperfusion rat model was induced by reversible occlusion for a middle cerebral artery with a thread on the stroke prone renovascular hypertensive model rat. While the rats in sham operation group were operated without thread insertion. Shuigou (Du 26), bilateral Neiguan(PC 6) and bilateral Housanli (Zusanli, ST 36) were located according to"Atlas of Experimental Animal Acupoints" made by Hua's. Shuigou (Du26): 1 mm below nasal apex right on the Labium leporinum, be punctured 1 mm obliquely upward; Neiguan (PC 6): at the lateral palm of the forearm3 mm above wrist joint, between ulna and radius, be punctured 1 mm

  3. Inhibition of P2X7 receptor ameliorates transient global cerebral ischemia/reperfusion injury via modulating inflammatory responses in the rat hippocampus

    Directory of Open Access Journals (Sweden)

    Chu Ketan

    2012-04-01

    Full Text Available Abstract Background Neuroinflammation plays an important role in cerebral ischemia/reperfusion (I/R injury. The P2X7 receptor (P2X7R has been reported to be involved in the inflammatory response of many central nervous system diseases. However, the role of P2X7Rs in transient global cerebral I/R injury remains unclear. The purpose of this study is to determine the effects of inhibiting the P2X7R in a rat model of transient global cerebral I/R injury, and then to explore the association between the P2X7R and neuroinflammation after transient global cerebral I/R injury. Methods Immediately after infusion with the P2X7R antagonists Brilliant blue G (BBG, adenosine 5′-triphosphate-2′,3′-dialdehyde (OxATP or A-438079, 20 minutes of transient global cerebral I/R was induced using the four-vessel occlusion (4-VO method in rats. Survival rate was calculated, neuronal death in the hippocampal CA1 region was observed using H & E staining, and DNA cleavage was observed by deoxynucleotidyl transferase-mediated UTP nick end labeling TUNEL. In addition, behavioral deficits were measured using the Morris water maze, and RT-PCR and immunohistochemical staining were performed to measure the expression of IL-1β, TNF-α and IL-6, and to identify activated microglia and astrocytes. Results The P2X7R antagonists protected against transient global cerebral I/R injury in a dosage-dependent manner. A high dosage of BBG (10 μg and A-0438079 (3 μg, and a low dosage of OxATP (1 μg significantly increased survival rates, reduced I/R-induced learning memory deficit, and reduced I/R-induced neuronal death, DNA cleavage, and glial activation and inflammatory cytokine overexpression in the hippocampus. Conclusions Our study indicates that inhibiting P2X7Rs protects against transient global cerebral I/R injury by reducing the I/R-induced inflammatory response, which suggests inhibition of P2X7Rs may be a promising therapeutic strategy for clinical treatment of

  4. Poststroke DNA immunization against neurite growth inhibitors is beneficial to the recovery from local cerebral ischemia in rats

    Institute of Scientific and Technical Information of China (English)

    Xingbao Zhu; Jasmine Lee; Jill Wong; Wan Loo Tan; Zhongtang Feng; Tinghua Wang; Zhicheng Xiao; Ivan Ng

    2007-01-01

    BACKGROUND: Inhibitory signals, i.e. neurite growth inhibitors (NGIs), presenting on central nervous system (CNS) myelin have been shown to play a crucial role in inhibiting lesioned axonal sprouting and leading to less functional recovery. Vaccines targeting NGIs may provide multifactorial protection against brain insults by overcoming the inhibitory effects of these NGIs and boosting the body's immune repair mechanisms.OBJECTIVE: To evaluate the effect of poststroke DNA immunization against NGIs on the rehabilitation for sensorimotor function of rat models of local cerebral ischemia.DESIGN: Completely randomized grouping design, and controlled experiment.SETTING: Brain Injury Research Laboratory, Department of Neurosurgery, National Neuroscience Institute,Singapore.MATERIALS: Sixty adult male Sprague-Dawley rats ranging in age from 45 to 120 days and in weight from 180 to 250 grams were provided by Animal Center of Department of Anatomy, Faculty of Medicine,National University of Singapore. pcDNA3.1(+)-neurite growth inhibitors (pcDNA-NGls) a gift was provided by Dr. Xiao from Department of Clinical Research, Singapore General Hospital, Singapore.METHODS: The experiment was carried out at Brain Injury Research Laboratory, Department of rats were randomized into 3 groups: pcDNA-NGIs group (group A), pcDNA3.1 (+) group (group B) and model group (group C), with 20 rats in each group. Left focal cerebral ischemia (FCI) was permanently induced through middle cerebral artery occlusion (MCAO) with the assistance of an operating microscope.Successful MCAO was determined by a 20% decrease to baseline in the ipsilateral cerebral blood flow. 100 μg of pcDNA-NGIs eluted in phosphate-buffered saline (PBS) was intramuscularly injected into the tibial muscle once a week after MCAO for 6 weeks in group A. As control, pcDNA3.1 (+) was also administrated severity score (mNSS), a composite of motor, sensory, reflex and balance tests, was used to test the sensorimotor deficit. The

  5. Cold Ischemia Induces Isograft Arteriopathy, but Does Not Augment Allograft Arteriopathy in Non-Immunosuppressed Hosts

    OpenAIRE

    Furukawa, Yutaka; Libby, Peter; Stinn, Jennifer L.; Becker, Gerold; Mitchell, Richard N

    2002-01-01

    Prolonged cold ischemia has been suggested as a factor that will exacerbate later graft arterial disease (GAD), a major limiting factor for long-term transplant survival. We therefore examined the effects of cold ischemia on GAD as well as adhesion molecule and cytokine expression in murine cardiac grafts. Mild GAD developed in isografts undergoing 4-hour cold ischemia. Relative to control isografts, cold ischemia induced transiently enhanced endothelial expression of intercellular adhesion m...

  6. EFFECT OF ELECTROACUPUNCTURE ON SYNAPTIC PLASTICITY OF HPPOCAMPAL NEURONS IN CEREBRAL ISCHEMIA RATS

    Institute of Scientific and Technical Information of China (English)

    杨卓欣; 于海波; 王玲; 张家维

    2004-01-01

    Objective:To observe the effect of electroacupuncture (EA) on synaptic structure of hippocampal nerve felts and synaptophysin(SYN)expression in rats with cerebral ischemic injury. Methods: Sixty Wistar rats were randomized into sham-operation group, cerebral ischemia (CI) group and EA group, each of which was further divided into 1week (W) and 5W subgroups. CI injury model was established by occlusion of the bilateral common carotid arteries. "Baihui"(百会 GV 20), "Dazhui" (大椎 GV 14), "Renzhong"(人中 GV 26) and "Guanyuan"(关元 CV 4) were punctured and stimulated electrically. The brain tissue sections containing hippocampus region were stained with immunohistochemical technique and observed under light microscope and transmission electronic microscope. Results: After CI, the ischemic injury as degeneration of the presynapse compositions, decrease of the synaptic numeral density, and low expression of SYN were observed in hippocampal CA1 area. By the 5th week after CI, the neonatal synapses of CI and EA groups appeared, and SYN expression was upregulated. In EA group, the recovery of the numeral density of synapses was especially noticeable, being 93.8% of that of sham-operation group and significantly higher than that in CI group (P<0.01). Compared with sham-operation group, the calibrated optical density (COD) values of SYN increased to 70% in CI group, and 93.3% in EA group, and COD value in EA group was significantly higher than that in CI group (P<0.01). Conclusion: EA can function in promoting synaptic regeneration and enhancing and perfecting the actions of the reconstructed synapses in hippocampal CA1 area in CI rats.

  7. Serial magnetic resonance imaging of evolving focal cerebral ischemia in the CAT

    International Nuclear Information System (INIS)

    Magnetic resonance imaging (MRI) is recognized as a sensitive medium for detecting lesions within the central nervous system. Three cats were scanned under light pentobarbital anesthesia using various MRI techniques before and after right middle cerebral artery (MCA) occlusion. Scanning began as early as four minutes after MCA occlusion and continued 8 to 10 hours. The animals were subsequently perfused with a colloidal carbon and phosphate buffered formalin. Brains were removed and sliced for histopathologic examination. The sharpest images were produced with a single spin-echo, multi-slice technique using a 0.6 Tesla (T) FIELD, 0.4 cm slice thickness, and a surface coil. Changes were apparent within 1 hr after MCA occlusion with T2 weighting (TR 2000 msec, TE 120 msec). Increased signal with this technique correlated with areas of decreased colloidal carbon perfusion. One animal with a large cortical infarction showed increased cortical signal at the time of the first MRI scan completed in the first 20 min. An animal with only mild cortical changes and severe ischemic changes in the dorsal thalamus nuclei had similar MRI results. T1 weighted images (TR 500 msec, TE 30 msec) revealed changes in hemispheric contour possibly corresponding to edema at 4 hours post occlusion. One animal imaged with almost double the slice thickness (0.75 cm) and with a 1.5 T field showed poor image quality using the above techniques but without a surface coil. MRI is sensitive in detecting changes due to cerebral ischemia within 30 minutes of onset. Increased MRI signal correlated with areas of decreased colloidal carbon perfusion, demonstrated at later times

  8. Rodent Hypoxia–Ischemia Models for Cerebral Palsy Research: A Systematic Review

    Science.gov (United States)

    Rumajogee, Prakasham; Bregman, Tatiana; Miller, Steven P.; Yager, Jerome Y.; Fehlings, Michael G.

    2016-01-01

    Cerebral palsy (CP) is a complex multifactorial disorder, affecting approximately 2.5–3/1000 live term births, and up to 22/1000 prematurely born babies. CP results from injury to the developing brain incurred before, during, or after birth. The most common form of this condition, spastic CP, is primarily associated with injury to the cerebral cortex and subcortical white matter as well as the deep gray matter. The major etiological factors of spastic CP are hypoxia/ischemia (HI), occurring during the last third of pregnancy and around birth age. In addition, inflammation has been found to be an important factor contributing to brain injury, especially in term infants. Other factors, including genetics, are gaining importance. The classic Rice–Vannucci HI model (in which 7-day-old rat pups undergo unilateral ligation of the common carotid artery followed by exposure to 8% oxygen hypoxic air) is a model of neonatal stroke that has greatly contributed to CP research. In this model, brain damage resembles that observed in severe CP cases. This model, and its numerous adaptations, allows one to finely tune the injury parameters to mimic, and therefore study, many of the pathophysiological processes and conditions observed in human patients. Investigators can recreate the HI and inflammation, which cause brain damage and subsequent motor and cognitive deficits. This model further enables the examination of potential approaches to achieve neural repair and regeneration. In the present review, we compare and discuss the advantages, limitations, and the translational value for CP research of HI models of perinatal brain injury. PMID:27199883

  9. A rat pup model of cerebral palsy induced by prenatal inflammation and hypoxia

    Institute of Scientific and Technical Information of China (English)

    Yanrong Hu; Feng Gao; Jianxin Li; Lihui Zhao; Gang Chen; Hong Wan; Zhiyou Zhang; Hong Zhi; Wei Liu; Xinwei Qian; Mingzhao Chen; Linbao Wen

    2013-01-01

    Animal models of cerebral palsy established by simple infection or the hypoxia/ischemia method cannot effectively simulate the brain injury of a premature infant. Healthy 17-day-pregnant Wistar rats were intraperitoneally injected with lipopolysaccharide then subjected to hypoxia. The pups were used for this study at 4 weeks of age. Simultaneously, a hypoxia/ischemia group and a control group were used for comparison. The results of the footprint test, the balance beam test, the water maze test, neuroelectrophysiological examination and neuropathological examination demonstrated that, at 4 weeks after birth, footprint repeat space became larger between the forelimbs and hindlimbs of the rats, the latency period on the balance beam and in the Morris water maze was longer, place navigation and ability were poorer, and the stimulus intensity that induced the maximal wave amplitude of the compound muscle action potential was greater in the lipopolysaccharide/hypoxia and hypoxia/ischemia groups than in the control group. We observed irregular cells around the periventricular area, periventricular leukomalacia and breakage of the nuclear membrane in the lipopolysaccharide/hypoxia and hypoxia/ischemia groups. These results indicate that we successfully established a Wistar rat pup model of cerebral palsy by intraperitoneal injection of lipopolysaccharide and hypoxia.

  10. Effect of Hypoxic Preconditioning on Neural Cell Apoptosis and Expression of Bcl-2 and Bax in Cerebral Ischemia-Reperfusion in Rats

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In order to investigate the protective effect of hypoxic preconditioning on the cerebral ischemia-reperfusion injury, the expression of Bcl-2 and Bax was detected by using immunohistochemical staining after 3 h cerebral ischemia followed by 1, 6, 12, 24 and 48 h reperfusion respectively in rats treated with or without hypoxic preconditioning before cerebral ischemia. In addition,the apoptosis of neural cells and the behavioral scores for neurological functions recovery were evaluated by TUNEL staining and "crawvling method", respectively. Compared with control group (cerebral ischemia-reperfusion without hypoxic preconditioning), the expression of Bcl-2 was significantly increased, but that of Bax decreased in the hypoxic preconditioning group (cerebral ischemiareperfusion with hypoxic preconditioning), both P<0. 05. The pre-treatment with hypoxic preconditioning could reduce the apoptosis of neural cells and promote the neurological function recovery as compared to control group. It was suggested that hypoxic preconditioning may have protective effects on the cerebral ischemia-reperfusion injury by inhibiting the apoptosis of neural cells, increase the expression of Bcl-2 and decrease the expression of Bax.

  11. Correlation of aquaporin-4 expression to blood-brain barrier permeability in rats with focal cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Pengcheng Xu; Haorong Feng; Jinbu Xu; Yongping Wu

    2008-01-01

    BACKGROUND: Ischemic cerebrovascular disease causes injury to the blood-brain barrier. The occurrence of brain edema is associated with aquaporin expression following cerebral ischemia/reperfusion. OBJECTIVE: To analyze the correlation of aquaporin-4 expression to brain edema and blood-brain barrier permeability in brain tissues of rat models of ischemia/reperfusion. DESIGN, TIME AND SETTING: The randomized control experiment was performed at the Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, China from December 2006 to October 2007. MATERIALS: A total of 112 adult, male, Sprague-Dawley rats, weighing 220-250 g, were used to establish rat models of middle cerebral artery occlusion and reperfusion by the suture method. Rabbit anti-aquaporin-4 (Santa Cruz, USA) and Evans blue (Sigma, USA) were used to analyze the tissue. METHODS: The rats were randomized into sham-operated (n = 16) and ischemia/reperfusion (n = 96) groups. There were 6 time points in the ischemia/reperfusion group, comprising 4, 6, 12, 24, 48, and 72 hours after reperfusion, with 16 rats for each time point. Rat models in the sham-operated group at 4 hours after surgery and rat models in the ischemia/reperfusion group at different time points were equally and randomly assigned into 4 different subgroups. MAIN OUTCOME MEASURES: Brain water content on the ischemic side and the control side was measured using the dry-wet weight method. Blood-brain barrier function was determined by Evans Blue. Aquaporin-4 expression surrounding the ischemic focus, as well as the correlation of aquaporin-4 expression with brain water content and Evans blue staining, were measured using immunohistochemistry and Western blot analysis. RESULTS: Brain water content on the ischemic side significantly increased at 12 hours after reperfusion, reached a peak at 48 hours, and was still high at 72 hours. Brain water content was greater on the ischemic hemispheres, compared with the control hemispheres

  12. The effect of the excitatory amino acid receptor antagonist dizocilipine maleate (MK-801) on hemispheric cerebral blood flow and metabolism in dogs: modification by prior complete cerebral ischemia.

    Science.gov (United States)

    Perkins, W J; Lanier, W L; Karlsson, B R; Milde, J H; Michenfelder, J D

    1989-09-25

    The effect of the N-methyl-D-aspartate (NMDA) receptor antagonist dizociplipine maleate (MK-801) on cerebral blood flow (CBF), cerebral metabolic rate for oxygen (CMRO2), intracranial pressure and systemic variables was examined in 6 normal dogs (Group I). In 6 additional dogs (Group II), the effects of a prior 11 min episode of complete cerebral ischemia on the response to dizocilipine was studied. CBF was measured with a sagittal sinus outflow technique and CMRO2 was calculated as the product of CBF and the arterial to sagittal sinus O2 content difference. Dizocilipine was administered as a 150 micrograms/kg i.v. bolus followed by a 75 micrograms.kg-1.h-1 infusion for 90 min. Plasma dizocilipine levels were greater than 25 ng/ml for the duration of the infusion. The CSF levels were approximately half the plasma levels. Five minutes after initiation of dizocilipine treatment, Group I dogs experienced a 63% increase in heart rate (P less than 0.01) and an 8% decrease in the mean arterial blood pressure (P less than 0.05). Over the same time interval. CBF increased by 85% (P less than 0.01) and intracranial pressure nearly doubled (P less than 0.05). In addition, dizocilipine treatment in all Group I animals resulted in EEG quasiperiodic bursts of delta-waves and polyspikes on a background of beta-activity. With the exception of the intracranial pressure, the above changes in systemic and cerebral variables persisted for the duration of the drug infusion. Intracranial pressure was no longer significantly elevated after 80 min of drug infusion. Hemispheric CMRO2 was unchanged by dizocilipine in Group I dogs. There was a decrease in the cortical glucose level at the end of the study, but no significant change in phosphocreatine, ATP, lactate, or energy charge when compared with 6 laboratory normals. An identical dose of dizocilipine administered after an 11 min episode of complete cerebral ischemia resulted in no significant changes in either cerebral or systemic

  13. Recombinant human granulocyte-colony stimulating factor and differential expression of cerebral cortical proteins in the subacute stage of cerebral ischemia/reperfusion

    Institute of Scientific and Technical Information of China (English)

    Baohua Liu; Jing Dong; Lei Lu; Ying Sha; Lei Song; Qun Liu

    2011-01-01

    Recombinant human granulocyte-colony stimulating factor(hG-CSF)has been shown to protect the nervous system after brain ischemia.However,the neuroprotective mechanism of hG-CSF remains unclear.The present study established a rat model of cerebral ischemia/reperfusion and subcutaneously injected recombinant hG-CSF after reperfusion for 2 hours.Cerebral cortical protein was extracted following 14 days of reperfusion and subjected to two-dimensional electrophoresis.In brain ischemic rats,56 different protein spots were screened,including 17 that were upregulated and 17 that were downregulated,compared with the sham-surgery group.Matrix assisted laser desorption ionization/time of flight mass spectrometry was used to determine peptide mass fingerprinting.Following a National Center for Biotechnology Information database search and confirmation with the Swiss-Prot database,19 spots were identified as known proteins.Following hG-CSF treatment,35 different protein spots were found,including 16 that were downregulated and 19 that were upregulated.Six were known proteins,including dihydropyrimidinase-associated protein 2,glial fibrillary acidic protein,endomucin,Rho GDP dissociation inhibitor,Rab GDP dissociation inhibitor and guanine-nucleotide-binding protein.Results indicate that hG-CSF is involved in neuroprotection after brain ischemia,possibly by regulating the expression of various neural regeneration-associated proteins at the subacute stage.

  14. The impact of Ly6Clow monocytes after cerebral hypoxia-ischemia in adult mice

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    Michaud, Jean-Philippe; Pimentel-Coelho, Pedro Moreno; Tremblay, Yannick; Rivest, Serge

    2014-01-01

    After an ischemic stroke, mononuclear phagocytic cells such as microglia, macrophages, and monocytes migrate to the lesion site and coordinate an immune response. Monocytes, which are recruited from the bloodstream after ischemic brain injury, can be categorized into two subsets in mice: inflammatory and patrolling monocytes. Although inflammatory monocytes (Ly6Chi) seem to have a protective role in stroke progression, the impact of patrolling monocytes (Ly6Clow) is unknown. To address the role of Ly6Clow monocytes in stroke, we generated bone marrow chimeric mice in which their hematopoietic system was replaced by Nr4a1−/− cells, allowing the complete and permanent ablation of Ly6Clow monocytes without affecting the Ly6Chi subset. We then subjected adult mice to cerebral hypoxia-ischemia using the Levine/Vannucci model. Functional outcomes after stroke such as body weight change, neurologic score, motor functions and spatial learning were not affected. Moreover, depletion in Ly6Clow monocytes did not change significantly the total infarct size, cell loss, atrophy, the number, or the activation state of microglia/macrophages at the lesion site. These data suggest that Ly6Clow patrolling monocytes are redundant in the progression and recovery of ischemic stroke. PMID:24780898

  15. Tissue Kallikrein Alleviates Cerebral Ischemia-Reperfusion Injury by Activating the B2R-ERK1/2-CREB-Bcl-2 Signaling Pathway in Diabetic Rats

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    Yuan, Kunxiong; Hu, Bin; Sang, Hongfei; Xie, Yi; Xu, Lili; Cao, Qinqin; Chen, Xin; Zhao, Lingling; Liu, Xinfeng; Liu, Ling; Zhang, Renliang

    2016-01-01

    Diabetes mellitus (DM) substantially increases the risk of ischemic stroke and reduces the tolerance to ischemic insults. Tissue kallikrein (TK) has been demonstrated to protect neurons from ischemia/reperfusion (I/R) injury in orthoglycemic model by activating the bradykinin B2 receptor (B2R). Considering the differential effects of B2R or bradykinin B1 receptor (B1R) on cardioprotection and neuroprotection in I/R with or without diabetes, this study was designed to investigate the role of TK during cerebral I/R injury in streptozotocin-induced diabetic rats. Intravenous injection of TK inhibited apoptosis in neurons, alleviated edema and inflammatory reactions after focal cerebral I/R, significantly reduced the infarct volume, and improved functional recovery. These beneficial effects were accompanied by activation of the extracellular signal-regulated kinase 1/2 (ERK1/2), cAMP response element-binding (CREB), and Bcl-2 signal proteins. Inhibition of the B2R or ERK1/2 pathway abated the effects of TK, whereas an antagonist of B1R enhanced the effects. These findings reveal that the neuroprotective effect of TK against cerebral I/R injury in streptozotocin-induced diabetic rats mainly involves the enhancement of B2R and ERK1/2-CREB-Bcl-2 signaling pathway activity.

  16. Electroacupuncture Could Regulate the NF-κB Signaling Pathway to Ameliorate the Inflammatory Injury in Focal Cerebral Ischemia/Reperfusion Model Rats.

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    Qin, Wen-Yi; Luo, Yong; Chen, Ling; Tao, Tao; Li, Yang; Cai, Yan-Li; Li, Ya-Hui

    2013-01-01

    The activated nuclear factor-KappaB signaling pathway plays a critical role in inducing inflammatory injury. It has been reported that electroacupuncture could be an effective anti-inflammatory treatment. We aimed to explore the complex mechanism by which EA inhibits the activation of the NF- κ B signal pathway and ameliorate inflammatory injury in the short term; the effects of NEMO Binding Domain peptide for this purpose were compared. Focal cerebral I/R was induced by middle cerebral artery occlusion for 2 hrs. Total 380 male Sprague-Dawley rats are in the study. The neurobehavioral scores, infarction volumes, and the levels of IL-1 β and IL-13 were detected. NF- κ B p65, I κ B α , IKK α , and IKK β were analyzed and the ability of NF- κ B binding DNA was investigated. The EA treatment and the NBD peptide treatment both reduced infarct size, improved neurological scores, and regulated the levels of IL-1 β and IL-13. The treatment reduced the expression of IKK α and IKK β and altered the expression of NF- κ B p65 and I κ B α in the cytoplasm and nucleus; the activity of NF- κ B was effectively reduced. We conclude that EA treatment might interfere with the process of NF- κ B nuclear translocation. And it also could suppress the activity of NF- κ B signaling pathway to ameliorate the inflammatory injury after focal cerebral ischemia/reperfusion. PMID:23970940

  17. Electroacupuncture Could Regulate the NF-κB Signaling Pathway to Ameliorate the Inflammatory Injury in Focal Cerebral Ischemia/Reperfusion Model Rats

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    Wen-yi Qin

    2013-01-01

    Full Text Available The activated nuclear factor-KappaB signaling pathway plays a critical role in inducing inflammatory injury. It has been reported that electroacupuncture could be an effective anti-inflammatory treatment. We aimed to explore the complex mechanism by which EA inhibits the activation of the NF-κB signal pathway and ameliorate inflammatory injury in the short term; the effects of NEMO Binding Domain peptide for this purpose were compared. Focal cerebral I/R was induced by middle cerebral artery occlusion for 2 hrs. Total 380 male Sprague-Dawley rats are in the study. The neurobehavioral scores, infarction volumes, and the levels of IL-1β and IL-13 were detected. NF-κB p65, IκBα, IKKα, and IKKβ were analyzed and the ability of NF-κB binding DNA was investigated. The EA treatment and the NBD peptide treatment both reduced infarct size, improved neurological scores, and regulated the levels of IL-1β and IL-13. The treatment reduced the expression of IKKα and IKKβ and altered the expression of NF-κB p65 and IκBα in the cytoplasm and nucleus; the activity of NF-κB was effectively reduced. We conclude that EA treatment might interfere with the process of NF-κB nuclear translocation. And it also could suppress the activity of NF-κB signaling pathway to ameliorate the inflammatory injury after focal cerebral ischemia/reperfusion.

  18. Combined intra-arterial thrombolysis and neuprotectant agents reduce cerebral infarction in rabbits with experimental acute cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Pei Shi

    2006-01-01

    BACKGROUND:The intra-arterial thrombolytic therapy is one of main methods for more patients to obtain bene-fits.The percentage of arterial recanalization treated with intre-arterial therapy is higher than with intra-venous therapy.next,the dose of thrombolytic medicines is lower and the therapeutic time window may be possibly longer.Related researches are focus on intra-artedal thrombolysis combining with neuprotectant agents to treat acute ischemic stroke.The results show that combination of them can further prolong the therapeutic time window.improve the percentage of arterial recanalization and reduce cerebral infarction volume.OBJECTIVE:To observe the effect of single thmmbolitic therapy combined with neuroprotectant agents in the treatment of acute ischemic stroke.DESIGN:Randomized block design.SETTING:Xinhua Hospital of Xixiang City.Henan Province.MATERIALS:Thirty-six adult male white rabbits.weighing 1.5-2.0 kg.dean grade.were provided by Expedmental Animal Center of Xinxiang Medical College.All rabbits were randomly divided into three groups:intra-arterial thrombolysis control group.corenalin control group and combination group with 12 in each group.Urekinase was provided by Beijing Saisheng Pharmaceutical Co.,Ltd.(batch number:020923);corenalin by Sanjing Pharmaceutical Co.,Ltd.of Harbin Pharmacautical Group(batch number:021106):nimodipine by Shandong Xihua Pharmaceutical Co.,Ltd.(batch number:020611):contrast medium IOPAMlR0300 by Bracco s.P.a.Milano italian (batch number:0584);2,3,5-triphenyltetrazolium chloride(TTC)by Beijing Mashi Fine ChemicaL Product Co.,Ltd.(batch number:020926).METHODS: The experiment was camed out in the Department of Intervention. Second People's Hospital of Xinxiang from September 2002 to May 2003.①According to techniques of Benes et al and Zhu et al,animal models with acute ischemia were established.Two hours later.the therapy began.Intra-artedal thrombolysis control group:5 000 U/kg urokinase was dripped in Ieft common

  19. Rolipram improves cognition, reduces anxiety- and despair-like behaviors and impacts hippocampal neuroplasticity after transient global cerebral ischemia.

    Science.gov (United States)

    Soares, Lígia Mendes; De Vry, Jochen; Steinbusch, Harry W M; Milani, Humberto; Prickaerts, Jos; Weffort de Oliveira, Rúbia M

    2016-06-21

    Cognitive impairment, anxiety- and depressive-like symptoms are well recognized outcome of cerebral ischemia in clinical and preclinical settings. Rolipram, a phosphodiesterase-4 (PDE-4) inhibitor, improves cognition and produces anxiolytic- and antidepressant-like effects in rodents. Rolipram also exerts anti-inflammatory effects and enhances survival of newborn hippocampal neurons in mice subjected to transient global cerebral ischemia. Here, we evaluated the effects of chronic rolipram treatment in mice subjected to transient global brain ischemia. C56B6/7 mice were subjected to bilateral common carotid artery occlusion (BCCAO) and were then tested in a multi-tiered behavioral battery including the elevated zero maze (EZM), open field (OF), object location test (OLT), and forced swim test (FST). We also investigated the effects of rolipram on hippocampal neurodegeneration and the expression of the neuronal plasticity markers doublecortin (DCX) and microtubule-associated protein (MAP-2). Ischemic mice exhibited memory deficits OLT, higher levels of anxiety EZM and behavioral despair FST. BCCAO caused neuronal loss in the CA3 hippocampal subfield and basolateral amygdala (BLA). In the hippocampus of BCCAO mice, a disrupted neuronal plasticity was evidenced by decreased DCX expression. Chronic treatment with rolipram attenuated the behavioral effects of BCCAO. Rolipram also decreased neurodegeneration in the CA3 while it increased dendritic arborization of DCX-immunoreactive (DCX-IR) neurons and microtubule associate MAP-2 expression in the hippocampus of BCCAO mice. These data suggest that chronic inhibition of PDE-4 can be a useful therapeutic strategy to improve the emotional and cognitive outcomes of transient global cerebral ischemia. PMID:27058148

  20. Anti-apoptotic effects of aspirin following cerebral ischemia-reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    Liying Qiu; Bin Du; Ying Li; Hongbin Fan; Zhiyong Yang

    2008-01-01

    BACKGROUND: The pharmacological effects of aspirin on apoptosis are complex. The underlying mechanisms have not been properly defined. OBJECTIVE: To observe the effect of different doses of aspirin on brain cell apoptosis following focal cerebral ischemia-reperfusion injury (CIRI) in rats. DESING, TIME AND SETTING: A randomized, controlled, animal experiment, performed at the School of Medicine and Pharmaceutics, Jiangnan University between June and October 2006. MATERIALS: Twenty-six male, adult, Sprague Dawley rats (grade II), weighing 240-290 g, were obtained from Shanghai Experimental Animal Center, Chinese Academy of Sciences. Aspirin was provided by Sigma (USA). METHODS: The rats were randomly divided into four groups: sham-operation (SO), CIRI+ vehicle, CIRI+ aspirin (6 mg/kg), and CIRI + aspirin (60 mg/kg). Rats in the lesion groups were intragastrically administrated saline, aspirin (6 mg/kg), or aspirin (60 mg/kg), respectively. MAIN OUTCOME MEASURES: The number of pyramidal neurons with normal appearance in the cerebral cortex at 2-4 mm from the midline; apoptotic cell death as measured by TUNEL; Bcl-2 and Bax protein localization was determined by immunohistochemistry; maiondiaidehyde (MDA) and super oxidation (SOD) content were determined by biochemistry method; adenosine triphosphate (ATP) content measured by capillary electrophoresis. RESULTS: Following CIRI, the following parameters were altered compared with sham-operated animals: the number of neurons with normal appearance was significantly reduced in the cerebral cortex; the number of apoptotic cells increased; Bax protein expression was enhanced; and the ratio between Bcl-2 and Bax decreased. In addition, MDA content increased significantly, whereas ATP content decreased (P < 0.01 ). Aspirin ameliorated the loss of healthy pyramidal neurons. Both 6 and 60 mg/kg aspirin increased the ratio between Bcl-2 and Bax, with no significant difference between the treatment groups. In addition, 60 mg

  1. A new non-human primate model of photochemically induced cerebral infarction.

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    Satoshi Ikeda

    Full Text Available BACKGROUND AND PURPOSE: Rat models of photochemically induced cerebral infarction have been readily studied, but to date there are no reports of transcranial photochemically induced infarctions in the marmoset. In this report, we used this non-human primate as a model of cerebral thrombosis and observed the recovery process. METHODS: Five common marmosets were used. Cerebral ischemia was produced via intravascular thrombosis induced by an intravenous injection of Rose Bengal and irradiation with green light. After inducing cerebral infarction, we observed the behavior of marmosets via a continuous video recording. We evaluated maximum speed, mean speed, and distance traveled in 1 min. In addition, we evaluated scores for feeding behavior, upper limb grip, and lower limb grip. We confirmed the infarct area after cerebral infarction using 2,3,5-triphenyltetrazolium chloride staining in a separate marmoset. RESULTS: We found functional decreases 2 days after creating the cerebral infarction in all measurements. Total distance traveled, average speed, upper limb score, and feeding behavior score did not recover to pre-infarction levels within 28 days. Maximum speed in 1 min and lower limb score recovered 28 days after infarction as compared to pre-infarction levels. We confirmed the infarct area of 11.4 mm × 6.8 mm as stained with 2,3,5-triphenyltetrazolium chloride. CONCLUSION: We were able to create a primate photothrombosis-induced cerebral infarction model using marmosets and observe functional recovery. We suggest that this is a useful model for basic research of cerebral infarction.

  2. β-Dystroglycan cleavage by matrix metalloproteinase-2/-9 disturbs aquaporin-4 polarization and influences brain edema in acute cerebral ischemia.

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    Yan, W; Zhao, X; Chen, H; Zhong, D; Jin, J; Qin, Q; Zhang, H; Ma, S; Li, G

    2016-06-21

    Dystroglycan (DG) is widely expressed in various tissues, and throughout the cerebral microvasculature. It consists of two subunits, α-DG and β-DG, and the cleavage of the latter by matrix metalloproteinase (MMP)-2 and -9 underlies a number of physiological and pathological processes. However, the involvement of MMP-2/-9-mediated β-DG cleavage in cerebral ischemia remains uncertain. In astrocytes, DG is crucial for maintaining the polarization of aquaporin-4 (AQP4), which plays a role in the regulation of cytotoxic and vasogenic edema. The present study aimed to explore the effects of MMP-2/-9-mediated β-DG cleavage on AQP4 polarization and brain edema in acute cerebral ischemia. A model of cerebral ischemia was established via permanent middle cerebral artery occlusion (pMCAO) in male C57BL/6 mice. Western blotting, real-time polymerase chain reaction (PCR), immunohistochemical staining, immunofluorescent staining, electron microscopy, and light microscopy were used. Captopril was applied as a selective MMP-2/-9 inhibitor. Recombinant mouse MMP (rmMMP)-2 and -9 were used in an in vitro cleavage experiment. The present study demonstrated evidence of β-DG cleavage by MMP-2/-9 in pMCAO mouse brains; this cleavage was implicated in AQP4 redistribution and brain edema in cerebral ischemia. In addition, captopril exacerbated cytotoxic edema and ameliorated vasogenic edema at 24h after pMCAO, and alleviated brain edema and neurological deficit at 48h and 72h. In conclusion, this study provides novel insight into the effects of MMP-2/-9-mediated β-DG cleavage in acute cerebral ischemia. Such findings might facilitate the development of a therapeutic strategy for the optimization of MMP-2/-9 targeted treatment in cerebral ischemia. PMID:27038751

  3. Upregulation of mesencephalic astrocyte-derived neurotrophic factor in glial cells is associated with ischemia-induced glial activation

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    Shen Yujun

    2012-11-01

    Full Text Available Abstract Background Mesencephalic astrocyte-derived neurotrophic factor (MANF, a 20 kDa secreted protein, was originally derived from a rat mesencephalic type-1 astrocyte cell line. MANF belongs to a novel evolutionally conserved family of neurotrophic factors along with conserved dopamine neurotrophic factor. In recent years, ever-increasing evidence has shown that both of them play a remarkable protective role against various injuries to neurons in vivo or in vitro. However, the characteristics of MANF expression in the different types of glial cells, especially in astrocytes, remain unclear. Methods The model of focal cerebral ischemia was induced by rat middle cerebral artery occlusion. Double-labeled immunofluorescent staining was used to identify the types of neural cells expressing MANF. Primarily cultured glial cells were used to detect the response of glial cells to endoplasmic reticulum stress stimulation. Propidium iodide staining was used to determine dead cells. Reverse transcription PCR and western blotting were used to detect the levels of mRNA and proteins. Results We found that MANF was predominantly expressed in neurons in both normal and ischemic cortex. Despite its name, MANF was poorly expressed in glial cells, including astrocytes, in normal brain tissue. However, the expression of MANF was upregulated in the glial cells under focal cerebral ischemia, including the astrocytes. This expression was also induced by several endoplasmic reticulum stress inducers and nutrient deprivation in cultured primary glial cells. The most interesting phenomenon observed in this study was the pattern of MANF expression in the microglia. The expression of MANF was closely associated with the morphology and state of microglia, accompanied by the upregulation of BIP/Grp78. Conclusions These results indicate that MANF expression was upregulated in the activated glial cells, which may contribute to the mechanism of ischemia-induced neural injury.

  4. Neuroprotective mechanisms of puerarin in middle cerebral artery occlusion-induced brain infarction in rats

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    Chang Yi

    2009-01-01

    Full Text Available Abstract Puerarin, a major isoflavonoid derived from the Chinese medical herb Radix puerariae (kudzu root, has been reported to be useful in the treatment of various cardiovascular diseases. In the present study, we examined the detailed mechanisms underlying the inhibitory effects of puerarin on inflammatory and apoptotic responses induced by middle cerebral artery occlusion (MCAO in rats. Treatment of puerarin (25 and 50 mg/kg; intraperitoneally 10 min before MCAO dose-dependently attenuated focal cerebral ischemia in rats. Administration of puerarin at 50 mg/kg, showed marked reduction in infarct size compared with that of control rats. MCAO-induced focal cerebral ischemia was associated with increases in hypoxia-inducible factor-1α (HIF-1α, inducible nitric oxide synthase (iNOS, and active caspase-3 protein expressions as well as the mRNA expression of tumor necrosis factor-α (TNF-α in ischemic regions. These expressions were markedly inhibited by the treatment of puerarin (50 mg/kg. In addition, puerarin (10~50 μM concentration-dependently inhibited respiratory bursts in human neutrophils stimulated by formyl-Met-Leu-Phe. On the other hand, puerarin (20~500 μM did not significantly inhibit the thiobarbituric acid-reactive substance reaction in rat brain homogenates. An electron spin resonance (ESR method was conducted on the scavenging activity of puerarin on the free radicals formed. Puerarin (200 and 500 μM did not reduce the ESR signal intensity of hydroxyl radical formation. In conclusion, we demonstrate that puerarin is a potent neuroprotective agent on MCAO-induced focal cerebral ischemia in vivo. This effect may be mediated, at least in part, by the inhibition of both HIF-1α and TNF-α activation, followed by the inhibition of inflammatory responses (i.e., iNOS expression, apoptosis formation (active caspase-3, and neutrophil activation, resulting in a reduction in the infarct volume in ischemia-reperfusion brain injury. Thus

  5. Combined intra-arterial thrombolysis and neuprotectant agents reduce cerebral infarction in rabbits with experimental acute cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Pei Shi

    2006-01-01

    BACKGROUND:The intra-arterial thrombolytic therapy is one of main methods for more patients to obtain bene-fits.The percentage of arterial recanalization treated with intre-arterial therapy is higher than with intra-venous therapy.next,the dose of thrombolytic medicines is lower and the therapeutic time window may be possibly longer.Related researches are focus on intra-artedal thrombolysis combining with neuprotectant agents to treat acute ischemic stroke.The results show that combination of them can further prolong the therapeutic time window.improve the percentage of arterial recanalization and reduce cerebral infarction volume.OBJECTIVE:To observe the effect of single thmmbolitic therapy combined with neuroprotectant agents in the treatment of acute ischemic stroke.DESIGN:Randomized block design.SETTING:Xinhua Hospital of Xixiang City.Henan Province.MATERIALS:Thirty-six adult male white rabbits.weighing 1.5-2.0 kg.dean grade.were provided by Expedmental Animal Center of Xinxiang Medical College.All rabbits were randomly divided into three groups:intra-arterial thrombolysis control group.corenalin control group and combination group with 12 in each group.Urekinase was provided by Beijing Saisheng Pharmaceutical Co.,Ltd.(batch number:020923);corenalin by Sanjing Pharmaceutical Co.,Ltd.of Harbin Pharmacautical Group(batch number:021106):nimodipine by Shandong Xihua Pharmaceutical Co.,Ltd.(batch number:020611):contrast medium IOPAMlR0300 by Bracco s.P.a.Milano italian (batch number:0584);2,3,5-triphenyltetrazolium chloride(TTC)by Beijing Mashi Fine ChemicaL Product Co.,Ltd.(batch number:020926).METHODS: The experiment was camed out in the Department of Intervention. Second People's Hospital of Xinxiang from September 2002 to May 2003.①According to techniques of Benes et al and Zhu et al,animal models with acute ischemia were established.Two hours later.the therapy began.Intra-artedal thrombolysis control group:5 000 U/kg urokinase was dripped in Ieft common

  6. Secretory pathway Ca(2+)-ATPase isoform 1 knockdown promotes Golgi apparatus stress injury in a mouse model of focal cerebral ischemia-reperfusion: In vivo and in vitro study.

    Science.gov (United States)

    Fan, Yongmei; Zhang, Changjie; Peng, Wenna; Li, Ting; Yin, Jing; Kong, Ying; Lan, Chunna; Li, Xiaofang; Wang, Rumi; Hu, Zhiping

    2016-07-01

    The present study was designed to investigate the potential role of secretory pathway Ca(2+)-ATPase isoform 1(SPCA1) in experimental focal cerebral ischemia-reperfusion injury. Cerebral ischemia-reperfusion was induced by transient middle cerebral artery occlusion (MCAO) for 2h s in Sprague-Dawley rats, and then the expression levels of SPAC1 mRNA and protein were determined. Results showed that SPCA1 level was transiently increased 1 day after reperfusion in peri-infarction area, while markedly increased in infarction core on 3day and 7 day after reperfusion. Then a SPCA1 lentivirus was used to achieve knockdown of SPCA1 gene: Ca(2+) transporting type 2C, member 1 (ATP2C1) gene. It has been observed that SPCA1 knockdown by lentivirus markedly increased cerebral infarction volume in vivo. Meanwhile, SPCA1 knockdown also facilitated per-oxidative production, including nitric oxide (NO) and 3-nitrotyrosine (3-NT) and decreased the expression of total superoxide dismutase (SOD) and manganese superoxide dismutase (MnSOD). Moreover, in vitro study showed that SPCA1 knockdown increased hydrogen peroxide (H2O2)-induced lactate dehydrogenase (LDH) leakage dose-dependently, and elevated caspase3 level in neuro-2a (N2a) cells. In addition, SPCA1 knockdown increased H2O2-induced production of nitric oxide and 3-NT dose-dependently, and reversed the increased activity of total SOD and MnSOD in neuro-2a cells. In conclusion, the present study indicated that SPCA1 could suppress over active Golgi apparatus (GA) stress thus attenuate cerebral ischemia-reperfusion injury. PMID:27038757

  7. Neuroprotective effects of DAHP and Triptolide in Focal Cerebral Ischemia via Apoptosis Inhibition and PI3K/Akt/mTOR pathway Activation

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    Zhiying Hu

    2015-04-01

    Full Text Available Triptolide (TP, one of the major active components of the traditional Chinese herb Tripterygium wilfordii Hook F, and 2, 4-diamino-6-hydroxypyrimidine (DAHP, an inhibitor of tetrahydrobiopterin (BH4 synthesis, have been reported to have potent anti-inflammatory and immunosuppressive properties. However, the protective effects of TP and DAHP on cerebral ischemia have not been reported yet. In this study, we investigated the neuroprotective effects of TP and DAHP in a middle cerebral artery occlusion (MCAO rat model. Furthermore, we examined whether the neuroprotective effects of TP and DAHP were associated with the inhibition of apoptosis through suppressing BH4 and inducible NOS (iNOS synthesis or the activation of the phosphoinositide-3-kinase/serine-threonine kinase Akt/ mammalian target of rapamycin (PI3K/Akt/mTOR pathway. Our results showed that pretreatments with Triptolide (0.2 mg/kg and DAHP (0.5g/kg significantly reduced ischemic lesion volume, water content and neuronal cell death compared with the vehicle MCAO rats. In addition, compared with the MCAO group, TP and DAHP pretreatment groups significantly reduced astrocyte numbers, caspase-3, cleaved caspase-3 and NF-κB up-regulation, while increased Bcl-2 expression. Moreover, protein expressions of PI3K, Akt and mTOR increased, while extracellular signal-regulated protein kinases 1 and 2 (ERK1and 2 phosphorylation decreased in both the TP-treated rats and DAHP-treated rats. These results demonstrate that TP and DAHP can decrease cell apoptosis in focal cerebral ischemia rat brains and that the mechanism may be related to the activation of the PI3K/Akt/mTOR pathway and inactivation of the ERK1/2 pathway. Thus our hypothesis was reached PI3K/Akt/mTOR and ERK1/2 pathways may provide distinct cellular targets for a new generation of therapeutic agents for the treatment of stroke, and TP and DAHP may be potential neuroprotective agents for cerebral ischemia/reperfusion injury.

  8. Hydrogen saline offers neuroprotection by reducing oxidative stress in a focal cerebral ischemia-reperfusion rat model

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    Liu Ying

    2011-07-01

    Full Text Available Abstract Hydrogen gas is neuroprotective in cerebral ischemia animal models. In this study, we tested the neuroprotective effects of hydrogen saline, which is safe and easy to use clinically, in a rat model of middle cerebral artery occlusion (MCAO. Sprague-Dawley male rats weighting 250-280 g were divided into sham, MCAO plus hydrogen saline and MCAO groups, and subjected to 90-min ischemia followed by 24 h of reperfusion. Hydrogen saline was injected intraperitoneally at 1 ml/100 g body weight. Infarct volume and brain water content were evaluated at different time points after reperfusion. Oxidative stress, inflammation, and apoptotic cell death markers were measured. Hydrogen saline significantly reduced the infarct volume and edema and improved the neurological function, when it was administered at 0, 3 and 6 h after reperfusion. Hydrogen saline decreased 8-hydroxyl-2'-deoxyguanosine (8-OHdG, reduced malondidehyde, interleukin-1β, tumor necrosis factor-α, and suppressed caspase 3 activity in the ischemic brain. These findings demonstrated hydrogen saline is neuroprotective when administered within 6 h after ischemia. Because hydrogen saline is safe and easy to use, it has clinical potentials to reduce neurological injuries.

  9. Studies on the active constituents in radix salviae miltiorrhizae and their protective effects on cerebral ischemia reperfusion injury and its mechanism

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    Yan-hui Li

    2015-01-01

    Full Text Available Background: To extract, purify and identify the active constituents in ethanol extract of Radix Salviae Miltiorrhizae, and to analyze the protective effects of tanshinone IIA on cerebral ischemia-reperfusion injury in rats. Materials and Methods: Radix Salviae Miltiorrhizae was extracted by ultrasonic extraction, effective parts were extracted by extraction method, compounds were isolated by preparative TLC and preparative HPLC, and structures of compounds were identified by 1 H NMR and 13 C NMR; the effects of tanshinone IIA on cerebral ischemia-reperfusion injury in rats were determined by establishing rat model of middle cerebral artery occlusion (MCAO. Results: The experimental data show four compounds were isolated, namely tanshinone IIB, hydroxymethylene tanshinone, salvianolic acid B and 9"′-methyl lithospermate B. Tanshinone IIA could alleviate the symptoms of neurological deficit in rats, the neurological deficit alleviating effect became more obvious with the increase of dose; tanshinone IIA experimental groups could reduce the cerebral infarction size and brain water content in rats, different concentrations of tanshinone IIA could decrease the SOD content and increase the MDA content in the frontal and parietal cortices of ischemic hemisphere in the ischemia reperfusion group, the differences were statistically significant compared with the ischemia reperfusion group. Conclusion: Radix Salviae Miltiorrhizae has the protective effects on cerebral ischemia reperfusion injury in rats.

  10. Protective effect and its mechanism of curcumin on ischemia-reperfusion injury of cerebral cortex in rats

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    Li LIU

    2013-03-01

    Full Text Available Objective  To investigate the effect of curcumin pretreatment on the expression of uncoupling protein 2 (UCP2 and mitochondrial transcription factor A (MTFA in rats' cerebral cortex against focal ischemia reperfusion injury. Methods  Eighty male SD rats weighed 220g–300g were randomly divided into 4 groups: sham-operated group, ischemia/reperfusion (I/R group, curcumine 50mg/kg+I/R (low dose group, and curcumine 100mg/kg+I/R (high dose group. The common carotid artery, external carotid artery and internal carotid artery on the right side were exposed in the sham-operated group. Animals of the other groups were subjected to a 2-hour period of right middle cerebral artery occlusion, followed by 24 hours of reperfusion, and then they were sacrificed. Curcumin was administered (ip in a dose of 50mg/kg (low dose group or 100mg/kg (high dose group for 5 days, respectively, prior to arterial occlusion. The pathological changes in neurons and their mitochondria in the cerebral cortex supplied by middle cerebral artery were observed with Nissl staining and electron microscope, respectively. The expressions of UCP2 and MTFA in corresponding cotex were assessed by immunohistochemistry and RT-PCR. Results  Compared with sham-operated group, animals in I/R group presented edema of neurons in the corresponding cortex, reduction in the number of Nissl bodies, and swelling of mitochondria with broken, even lysis of cristae. Low dose and high dose of curcumin pretreatment before brain ischemia significantly alleviated the loss of neurons and the damage of mitochondria, accompanied with an increase in the expression of UCP2 and TFAM (P<0.05, and the changes appeared a dose-dependent manner (P<0.05. Conclusions  Curcumin may prevent neurons from focal cerebral ischemia reperfusion injury by up-regulating UCP2 and MTFA. Regulation of mitochondrial biogenesis may probably be a potential target of curcumin as a neuroprotective drug.

  11. Promoting neurogenesis via Wnt/β-catenin signaling pathway accounts for the neurorestorative effects of morroniside against cerebral ischemia injury.

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    Sun, Fang-Ling; Wang, Wen; Zuo, Wei; Xue, Jin-Long; Xu, Jing-dong; Ai, Hou-Xi; Zhang, Li; Wang, Xiao-Min; Ji, Xun-Ming

    2014-09-01

    Ischemic stroke is a leading cause of mortality and permanent disability in adults worldwide. Neurogenesis triggered by ischemia in the adult mammalian brain may provide insights into stroke treatment. Morroniside is an active component of sarcocarp of C. officinalis that have shown neuroprotective effects. The aim of the present study is to test whether morroniside promotes neurogenesis via Wnt/β-catenin signaling pathway for brain recovery in a rat model of focal cerebral ischemia. Morroniside was administered intragastrically once daily at the concentrations of 30, 90 and 270 mg/kg for 7 days post-ischemia. Neurological functions were detected by Ludmila Belayev score tests. Endogenous neural stem cells responses were investigated with immunofluorescence staining of Ki-67 and Nestin to identify the neurogenesis in the subventricular zone (SVZ). The expression of proteins involved in and related to Wnt/β-catenin signaling pathway was detected by western blotting analysis. Morroniside significantly promoted neurogenesis for brain recovery 7 days post-ischemia. Increased expression of Wnt 3a, β-catenin and T-cell transcription factor-4 (Tcf-4), along with activation of downstream transcription factors Pax6 and neurogenin2 (Ngn2), indicated that the neurorestorative effects of morroniside may be associated with Wnt/β-catenin signaling pathway. These data provide support for understanding the mechanisms of morroniside in neurorestorative effects and suggest a potential new strategy for ischemic stroke treatment. PMID:24876057

  12. Effects of the cyclooxygenase-2 inhibitor nimesulide on cerebral infarction and neurological deficits induced by permanent middle cerebral artery occlusion in the rat

    Directory of Open Access Journals (Sweden)

    Muñoz Eduardo

    2005-01-01

    Full Text Available Abstract Background Previous studies suggest that the cyclooxygenase-2 (COX-2 inhibitor nimesulide has a remarkable protective effect against different types of brain injury including ischemia. Since there are no reports on the effects of nimesulide on permanent ischemic stroke and because most cases of human stroke are caused by permanent occlusion of cerebral arteries, the present study was conducted to assess the neuroprotective efficacy of nimesulide on the cerebral infarction and neurological deficits induced by permanent middle cerebral artery occlusion (pMCAO in the rat. Methods Ischemia was induced by permanent occlusion of the middle cerebral artery in rats, via surgical insertion of a nylon filament into the internal carotid artery. Infarct volumes (cortical, subcortical and total and functional recovery, assessed by neurological score evaluation and rotarod performance test, were performed 24 h after pMCAO. In initial experiments, different doses of nimesulide (3, 6 and 12 mg/kg; i.p or vehicle were administered 30 min before pMCAO and again at 6, 12 and 18 h after stroke. In later experiments we investigated the therapeutic time window of protection of nimesulide by delaying its first administration 0.5–4 h after the ischemic insult. Results Repeated treatments with nimesulide dose-dependently reduced cortical, subcortical and total infarct volumes as well as the neurological deficits and motor impairment resulting from permanent ischemic stroke, but only the administration of the highest dose (12 mg/kg was able to significantly (P Conclusions These data show that nimesulide protects against permanent focal cerebral ischemia, even with a 2 h post-treatment delay. These findings have important implications for the therapeutic potential of using COX-2 inhibitors in the treatment of stroke.

  13. Information entropy-based fitting of the disease trajectory of brain ischemia-induced vascular cognitive impairment

    Institute of Scientific and Technical Information of China (English)

    Lin Liu; Ju Huo; Ying Zhao; Yu Tian

    2012-01-01

    The present study investigated the disease trajectory of vascular cognitive impairment using the entropy of information in a neural network mathematical simulation based on the free radical and excitatory amino acids theories.Glutamate, malondialdehyde, and inducible nitric oxide synthase content was significantly elevated, but acetylcholine, catalase, superoxide dismutase, glutathione peroxidase and constitutive nitric oxide synthase content was significantly decreased in our vascular cognitive impairment model.The fitting curves for each factor were obtained using Matlab software.Nineteen, 30 and 49 days post ischemia were the main output time frames of the influence of these seven factors.Our results demonstrated that vascular cognitive impairment involves multiple factors.These factors include excitatory amino acid toxicity and nitric oxide toxicity.These toxicities disrupt the dynamic equilibrium of the production and removal of oxygen free radicals after cerebral ischemia, reducing the ability to clear oxygen free radicals and worsening brain injury.

  14. Transplantation of mesenchymal stem cells promotes the functional recovery of the central nervous system following cerebral ischemia by inhibiting myelin-associated inhibitor expression and neural apoptosis

    Science.gov (United States)

    FENG, NIANPING; HAO, GUANG; YANG, FENGGANG; QU, FUJUN; ZHENG, HAIHONG; LIANG, SONGLAN; JIN, YONGHUA

    2016-01-01

    Cerebral ischemia, which may lead to cerebral hypoxia and damage of the brain tissue, is a leading cause of human mortality and adult disability. Mesenchymal stem cells (MSCs) are a class of adult progenitor cells with the ability to differentiate into multiple cell types. The transplantation of bone marrow-derived MSCs is a potential therapeutic strategy for cerebral ischemia. However, the underlying mechanism has yet to be elucidated. In the present study, primary MSCs were isolated from healthy rats, labeled and transplanted into the brains of middle cerebral artery occlusion rat models. The location of the labeled MSCs in the rat brains were determined by fluorescent microscopy, and the neurological functions of the rats were scored. Immunohistochemical analyses demonstrated that the protein expression levels of myelin-associated inhibitors of regeneration, including Nogo-A, oligodendrocyte myelin glycoprotein and myelin-associated glycoprotein, were decreased following transplantation of the bone marrow-derived MSCs. Furthermore, the mRNA expression levels of Capase-3 and B-cell lymphoma 2, as determined by reverse transcription-quantitative polymerase chain reactions, were downregulated and upregulated, respectively, in the MSC-transplanted rats; thus suggesting that neural apoptosis was inhibited. The results of the present study suggested that the transplantation of bone marrow-derived MSCs was able to promote the functional recovery of the central nervous system following cerebral ischemia. Accordingly, inhibitors targeting myelin-associated inhibitors and apoptosis may be of clinical significance for cerebral ischemia in the future.

  15. Unsupervised nonlinear dimensionality reduction machine learning methods applied to multiparametric MRI in cerebral ischemia: preliminary results

    Science.gov (United States)

    Parekh, Vishwa S.; Jacobs, Jeremy R.; Jacobs, Michael A.

    2014-03-01

    The evaluation and treatment of acute cerebral ischemia requires a technique that can determine the total area of tissue at risk for infarction using diagnostic magnetic resonance imaging (MRI) sequences. Typical MRI data sets consist of T1- and T2-weighted imaging (T1WI, T2WI) along with advanced MRI parameters of diffusion-weighted imaging (DWI) and perfusion weighted imaging (PWI) methods. Each of these parameters has distinct radiological-pathological meaning. For example, DWI interrogates the movement of water in the tissue and PWI gives an estimate of the blood flow, both are critical measures during the evolution of stroke. In order to integrate these data and give an estimate of the tissue at risk or damaged; we have developed advanced machine learning methods based on unsupervised non-linear dimensionality reduction (NLDR) techniques. NLDR methods are a class of algorithms that uses mathematically defined manifolds for statistical sampling of multidimensional classes to generate a discrimination rule of guaranteed statistical accuracy and they can generate a two- or three-dimensional map, which represents the prominent structures of the data and provides an embedded image of meaningful low-dimensional structures hidden in their high-dimensional observations. In this manuscript, we develop NLDR methods on high dimensional MRI data sets of preclinical animals and clinical patients with stroke. On analyzing the performance of these methods, we observed that there was a high of similarity between multiparametric embedded images from NLDR methods and the ADC map and perfusion map. It was also observed that embedded scattergram of abnormal (infarcted or at risk) tissue can be visualized and provides a mechanism for automatic methods to delineate potential stroke volumes and early tissue at risk.

  16. Taurine inhibits ischemia/reperfusion-induced compartment syndrome in rabbits

    Institute of Scientific and Technical Information of China (English)

    Ji-xian WANG; Yan LI; Li-ke ZHANG; Jing ZHAO; Yong-zheng PANG; Chao-shu TANG; Jing ZHANG

    2005-01-01

    Aim: To investigate effects of taurine on ischemia/reperfusion (I/R)-induced compartment syndrome in rabbit hind limbs.Methods: Rabbits underwent femoral artery occ lusion after ligation of branches from terminal aorta to femoral artery.After a 7-h ischemia, reperfusion was established with the use of heparinized by iv infusion 10 min before shunt placement.During reperfusion, anterior compartment pressure (ACP) was monitored continuously in the left lower extremity.Gastrocnemius muscle triphenyltetrazolium chloride (TTC) level, taurine content and myeloperoxidase activity were assayed.Oxidative stress was induced in the in vitro gastrocnemius muscle slices by free radical generating systems (FRGS),and the malondialdehyde content was measured in presence or absence of taurine.Results: After 7 h of ischemia, none of the parameters that we measured were different from those before ischemia, except that TTC reduction decreased by 80%.In the control group, after 2 h of reperfusion, ACP increased 4.5-fold, and gastrocnemius muscle taurine content was reduced by 33%.In taurine-treated animals, at 2 h reperfusion, the mean arterial blood pressure and heart rate were increased, by 6% and 10%.ACP decreased by 39%, muscle edema decreased by 16%, TTC reduction increased by 150%, and lactate dehydrogenase decreased by 36% compared to control group.Plasma and muscle taurine content increased by 70% and 88%, respectively.In the taurine-treated group, at 2 h reperfusion, plasma malondialdehyde and conjugated diene content were decreased by 38% and 23%,respectively, and muscle malondialdehyde and conjugated diene content decreased by 22% and 30%, respectively compared to the control group.At 2 h reperfusion,myeloperoxidase activity was increased 3.5-fold in control animals.In the in vitro study, taurine decreased malondialdehyde content in muscle slices incubated with hypochlorous acid in a dose-dependent manner, but there was no change when incubated with hydrogen peroxide and

  17. Preliminary evaluation of [1-11C]octanoate as a PET tracer for studying cerebral ischemia. A PET study in rat and canine models of focal cerebral ischemia

    International Nuclear Information System (INIS)

    Octanoate is taken up into the brain and is converted in astrocytes to glutamine through the tricarboxylic acid (TCA) cycle after β-oxidation. We speculate that [1-11C]octanoate may be used as a tracer for astroglial functions and/or fatty acid metabolism in the brain and may be useful for studying cerebral ischemia. In the present study we investigated brain distribution of [1-11C]octanoate and compared it with cerebral blood flow (CBF) by using rat and canine models of middle cerebral artery (MCA) occlusion and a high resolution PET. In rats brain distribution of [15O]H2O measured 1-2 h and 5-6 h after insult was compared with that of [1-11C]octanoate measured 3-4 h after insult. Radioactivity ratios of lesioned to normal hemispheres determined with [15O]H2O were lower than those determined with [1-11C]octanoate. These results were confirmed by a study on a canine model of MCA-occlusion. Twenty-four hours after insult, CBF decreased in the MCA-territory of the occluded hemisphere, whereas normal or higher accumulation of [1-11C]octanoate was observed in the ischemic regions. The uptake of [1-11C]octanoate-derived radioactivity therefore increased relative to CBF in the ischemic regions, indicating that [1-11C]octanoate provides functional information different from CBF. In conclusion, we found that [1-11C]octanoate is a potential radiopharmaceutical for studying the pathophysiology of cerebral ischemia. (author)

  18. A basic study on molecular hydrogen (H2) inhalation in acute cerebral ischemia patients for safety check with physiological parameters and measurement of blood H2 level

    OpenAIRE

    Ono Hirohisa; Nishijima Yoji; Adachi Naoto; Sakamoto Masaki; Kudo Yohei; Kaneko Kumi; Nakao Atsunori; Imaoka Takashi

    2012-01-01

    Abstract Background In animal experiments, use of molecular hydrogen ( H2) has been regarded as quite safe and effective, showing benefits in multiple pathological conditions such as ischemia-reperfusion injury of the brain, heart, kidney and transplanted tissues, traumatic and surgical injury of the brain and spinal cord, inflammation of intestine and lung , degenerative striatonigral tissue and also in many other situations. However, since cerebral ischemia patients are in old age group, th...

  19. Preventive administration of cromakalim reduces aquaporin-4 expression and blood-brain barrier permeability in a rat model of cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Shilei Wang; Yanting Wang; Yan Jiang; Qingxian Chang; Peng Wang; Shiduan Wang

    2011-01-01

    Cromakalim, an adenosine triphosphate-sensitive potassium channel opener, exhibits protective effects on cerebral ischemia/reperfusion injury. However, there is controversy as to whether this effect is associated with aquaporin-4 and blood-brain barrier permeability. Immunohistochemistry results show that preventive administration of cromakalim decreased aquaporin-4 and IgG protein expression in rats with ischemia/reperfusion injury; it also reduced blood-brain barrier permeability, and alleviated brain edema, ultimately providing neuroprotection.

  20. Stroke severity and incidence of acute large vessel occlusions in patients with hyper-acute cerebral ischemia

    DEFF Research Database (Denmark)

    Hansen, Christine Kraup; Christensen, Anders Fogh; Ovesen, C;

    2015-01-01

    vessel occlusions and describe the relations to the National Institutes of Health Stroke Scale (NIHSS), lesion site and time from symptom onset in unselected consecutive patients with hyper-acute cerebral ischemia. METHODS: A prospective single hospital registry was based on consecutive unselected...... occlusions and the effect of time after symptom onset was assessed. RESULTS: Six hundred thirty-seven patients, with admission NIHSS: 1-42, were included; 183 patients presented with acute vessel occlusions (28.7%) in 15 different combinations of occlusions. The best NIHSS-cut-off for detecting any occlusion...

  1. Awareness intervention for Beijing neurologists regarding secondary prevention of cerebral infarction/transient ischemia Cross-sectional investigation

    Institute of Scientific and Technical Information of China (English)

    Ruihua Ma; Mingjie Xu; Zhuo Zhang; Li Wang; Weiwei Zhang; Lang Lin; Jiping Tan; Yao Li; Ming Wei; Hongtao Li; Chunxue Wang; Xianwei Wang; Yuhui Zhang; Yongjun Wang; Yilong Wang; Xingquan Zhao; Jingjing Li; Ying Lü

    2008-01-01

    BACKGROUND: Stroke prevention guidelines should be made available to neurologists for clinical application to aid in uniformity, timing, preciseness, and acceptance of disease.OBJECTIVE: To investigate the awareness of neurologists in some Beijing hospitals of intervention in secondary prevention of cerebral infarction/transient ischemia.DESIGN: Cross-sectional study.SETTING: Beijing Tiantan Hospital, Beijing Anzhen Hospital, General Hospital of Beijing Military Area, Command of Chinese PLA, Beijing Chuiyangliu Hospital, Beijing 6th Hospital, Beijing Hepingli Hospital, and Beijing Daxing District Hospital.PARTICIPANTS: A total of 28 (associate) chief physicians, 58 attending physicians, and 54 resident physicians who engaged in clinical treatment of cerebrovascular diseases were selected from 8 hospitals in Beijing from March to April 2007. All physicians provided informed consent.METHODS: Self-made closed questionnaires were provided for data collection, consisting of 16 questions that were single choice or multiple choice. Specifically, questions 1-7 focused on awareness of blood pressure regulation in different patients and first choice of decompression drug; questions 8-12 focused on awareness of lipid regulation; and questions 13-16 focused on awareness of anti-blood platelet drugs applied in secondary prevention. The scores ranged from 0-100 points, and each question was worth 6.25 points. The scores positively correlated with the awareness rate. To test leveling real-time, the survey lasted for a maximum of 20 minutes. One questionnaire was independently finished by each subject in the survey. MAIN OUTCOME MEASURES: Awareness intervention among neurologists during secondary prevention of cerebral infarction/transient ischemia and questionnaire scores.RESULTS: 140 subjects were included in the final analysis. ① The awareness rate among neurologists for intervention during secondary prevention of cerebral infarction/transient ischemia ranged from 0

  2. Alpha-chloralose is a Suitable Anesthetic for Chronic Focal Cerebral Ischemia Studies in the Rat: A comparative study

    OpenAIRE

    Luckl, Janos; Keating, Jeffrey; Greenberg, Joel H

    2007-01-01

    α–chloralose is widely used as an anesthetic in studies of the cerebrovasculature because it provides robust metabolic and hemodynamic responses to functional stimulation. However, there have been no controlled studies of focal ischemia in the rat under α–chloralose anesthesia. Artificially ventilated rats were prepared using 1.2−1.5 % isoflurane anesthesia for filament occlusion of the right middle cerebral artery (MCA), and anesthesia was either switched to α–chloralose (60 mg/kg bolus, 30 ...

  3. Intestinal ischemia/reperfusion induces bronchial hyperreactivity and increases serum TNF-alpha in rats

    Directory of Open Access Journals (Sweden)

    Arruda Marcio Jose Cristiano de

    2006-01-01

    Full Text Available INTRODUCTION: Intestinal or hepatic ischemia/reperfusion induces acute lung injury in animal models of multiple organ failure. Tumor necrosis factor (TNF- alpha is involved in the underlying inflammatory mechanism of acute respiratory distress syndrome. Although the inflammatory cascade leading to acute respiratory distress syndrome has been extensively investigated, the mechanical components of acute respiratory distress syndrome are not fully understood. Our hypothesis is that splanchnic ischemia/reperfusion increases airway reactivity and serum TNF-alpha levels. OBJECTIVE: To assess bronchial smooth muscle reactivity under methacholine stimulation, and to measure serum TNF-alpha levels following intestinal and/or hepatic ischemia/reperfusion in rats. METHOD: Rats were subjected to 45 minutes of intestinal ischemia, or 20 minutes of hepatic ischemia, or to both (double ischemia, or sham procedures (control, followed by 120 minutes of reperfusion. The animals were then sacrificed, and the bronchial response to increasing methacholine molar concentrations (10-7 to 3 x 10-4 was evaluated in an ex-vivo bronchial muscle preparation. Serum TNF-alpha was determined by the L929-cell bioassay. RESULTS: Bronchial response (g/100 mg tissue showed increased reactivity to increasing methacholine concentrations in the intestinal ischemia and double ischemia groups, but not in the hepatic ischemia group. Similarly, serum TNF-alpha (pg/mL concentration was increased in the intestinal ischemia and double ischemia groups, but not in the hepatic ischemia group. CONCLUSION: Intestinal ischemia, either isolated or associated with hepatic ischemia, increased bronchial smooth muscle reactivity, suggesting a possible role for bronchial constriction in respiratory dysfunction following splanchnic ischemia/reperfusion. This increase occurred in concomitance with serum TNF-alpha increase, but whether the increase in TNF-alpha caused this bronchial contractility remains

  4. Enhanced expressions of microvascular smooth muscle receptors after focal cerebral ischemia occur via the MAPK MEK/ERK pathway

    DEFF Research Database (Denmark)

    Maddahi, Aida; Edvinsson, Lars

    2008-01-01

    quantitative Western blot. We demonstrate that there is an increase in the number of contractile smooth muscle receptors inthe MCA and in micro- vessels within the ischemic region. The enhanced expression occurs in the smooth muscle cells as verified by co-localization studies. This receptor upregulation is...... furthermore associated with enhanced expression of pERK1/2 and of transcription factor pElk-1 in the vascular smooth muscle cells. Blockade of transcription with the MEK1 inhibitor U0126, given at the onset of reperfusion or as late as 6 hours after the insult, reduced transcription (pERK1/2 and pElk-1), the......BACKGROUND: MEK1/2 is a serine/threonine protein that phosphorylates extracellular signal-regulated kinase (ERK1/2). Cerebral ischemia results in enhanced expression of cerebrovascular contractile receptors in the middle cerebral artery (MCA) leading to the ischemic region. Here we explored the...

  5. Effects of strain, body mass, and thread tip preparation on the establishment of focal cerebral ischemia mouse models

    Institute of Scientific and Technical Information of China (English)

    Xuemei Chen; Yun Xu

    2008-01-01

    BACKGROUND: What are the successful factors of the establishment of the thread-blocking method for focal cerebral ischemia/reperfusion mouse models?OBJECTIVE: To study the effects of strain, body mass, and thread tip preparation for the establishment of focal cerebral ischemia mouse models by using middle cerebral artery occlusion (MCAO).DESIGN: Observational contrast animal study.SETTING: Gulou Hospital, Medical College of Nanjing University.MATERIALS: ① The following experiment was performed at the Animal Experimental Center, Gulou Hospital Affiliated to Medical College of Nanjing University from December 2006 to April 2007. Sixty male white Kunming mice, whose body masses were 18–22 g (n =40), 25–29 g (n =10) and 30–33 g (n =10), as well as 10 male C57BL/6J mice, whose body mass was 18–22 g, were provided by the Animal Experimental Center, Gulou Hospital Affiliated to Medical College of Nanjing University. All mice were 10–12 weeks old. The project received confirmed consent from the local ethics committee. ②Experimental materials: tripheryltetrazolium hydrochloride (TTC) and 0.1% poly-L-lysine were provided by Sigma Company, USA; citromint was provided by Shanghai Lingfeng Chemical Company Limited. METHODS: ① Strain comparison: Ten white Kunming mice (weighing 18–22 g) and ten C57BL/6J mice (weighing 18–22 g) were selected. ② Comparison of body mass: Thirty white Kunming mice, whose body masses were 18–22 g (n =10), 25–30 g (n =10), and 30–35 g (n =10), were divided into groups. ③ Comparison of thread tip preparation: White Kunming mice weighing 18–22 g were divided into a poly-L-lysine line group and general line group, with 10 mice in each group. Mice in these two groups, which were respectively treated with poly-L-lysine or nothing, underwent MCAO. ④ All experimental mice received MCAO. Three hours after ischemia, and 24 hours after reperfusion, neurological deficit scores were measured and a success rate of model

  6. Enhanced cerebrovascular expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 via the MEK/ERK pathway during cerebral ischemia in the rat

    DEFF Research Database (Denmark)

    Maddahi, Aida; Chen, Qingwen; Edvinsson, Lars

    2009-01-01

    BACKGROUND: Cerebral ischemia is usually characterized by a reduction in local blood flow and metabolism and by disruption of the blood-brain barrier in the infarct region. The formation of oedema and opening of the blood-brain barrier in stroke is associated with enhanced expression of metallopr......BACKGROUND: Cerebral ischemia is usually characterized by a reduction in local blood flow and metabolism and by disruption of the blood-brain barrier in the infarct region. The formation of oedema and opening of the blood-brain barrier in stroke is associated with enhanced expression...

  7. Influence of mild hypothermia on vascular endothelial growth factor and infarct volume in brain tissues after cerebral ischemia in rats

    Institute of Scientific and Technical Information of China (English)

    Fei Ye; Gangming Xi; Biyong Qin; Shifeng Wang; Chengyan Li

    2006-01-01

    BACKGROUND: It has been demonstrated that mild hypothermia has obvious protective effect on both whole and local cerebral ischemia. However, the definite mechanism is still unclear for the brain protection of mild hypothermia on cerebral edema, inhibiting inflammatory reaction, stabilizing blood brain barrier, etc.OBJECTIVE: To investigate the effect of mild hypothermia on the expression of vascular endothelial growth factor and the infarct volume after cerebral ischemia in rats, and analyze the brain protective mechanism of mild hypothermia.DESIGN: A randomized grouping and controlled animal trial.SETTING: Department of Neurology, People's Hospital of Yunyang Medical College.MATERIALS: Twenty adult male SD rats of clean degree, weighing (250±30) g, were provided by the animal experimental center, School of Medicine, Wuhan University. The kits for SP immunohistochemistry were purchased from Beijing Zhongshan Golden Bridge Biotechnology Co., Ltd.METHODS: The experiments were carried out in the laboratory of Department of Neurology, Renmen Hospital of Wuhan University from May to July 2005. ① The 20 rats were divided randomly into normal temperature group (n =10) and mild hypothermia group (n =10). Models of permanent middle cerebral artery occlusion were established with modified nylon suture embolization. The rats were assessed with the Longa standards: O point for without nerve dysfunction; 1 for mild neurological deficit (fore claws could no extend completely); 2 for moderate neurological deficit (circling towards the affected side); 3 for severe neurological deficit (tilting towards the affected side); 4 for coma and unconscious; 1 -3 points represented that models were successfully established. The rats of the normal temperature group were fed at room temperature, and those in the mild hypothermia group were induced by hypothermia from 2 hours postoperatively, and the rectal temperature was kept at 34-35 ℃ for 72 hours. ② Measurement of infarct volume

  8. Ischemia-induced endothelial cell swelling and mitochondrial dysfunction are attenuated by dietary polyphenols in vitro

    Science.gov (United States)

    Polyphenols possess anti-oxidant and anti-inflammatory properties. Oxidative stress (OS) and inflammation have been implicated