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Sample records for cerebral ischemic rats

  1. Effects of rhynchophylline on monoamine transmitters of striatum and hippocampus in cerebral ischemic rats

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    LUYuan-Fu; XIEXiao-Long; WUQin; WENGuo-Rong; YANGSu-Fen; SHIJing-Shan

    2004-01-01

    AIM To investigate the effects of rhynchophylline ( Rhy on monoamine transmitters and its metabolites in striatum and hippocampus of cerebral ischemic rats. METItODS The cerebral ischemic injury of rat was induced by middle cerebral artery occlusion (MCAO). The extracellular fluid of striatum and hippocampus in cerebral ischemic rats was collected by using

  2. Temperature modulation of cerebral depolarization during focal cerebral ischemia in rats: correlation with ischemic injury.

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    Chen, Q; Chopp, M; Bodzin, G; Chen, H

    1993-05-01

    The role of cerebral depolarizations in focal cerebral ischemia is unknown. We therefore measured the direct current (DC) electrical activity in the cortex of Wistar rats subjected to transient occlusion of the middle cerebral artery (MCA). Focal ischemia was induced for 90 min by insertion of an intraluminal filament to occlude the MCA. To modulate cell damage, we subjected the rats to hypothermic (30 degrees C, n = 4), normothermic (37 degrees C, n = 4), and hyperthermic (40 degrees C, n = 6) ischemia. Controlled temperatures were also maintained during 1 h of reperfusion. Continuous cortical DC potential changes were measured using two active Ag-AgCl electrodes placed in the cortical lesion. Animals were killed 1 week after ischemia. The brains were sectioned and stained with hematoxylin and eosin, for evaluation of neuronal damage, and calculation of infarct volume. All animals exhibited an initial depolarization within 30 min of ischemia, followed by a single depolarization event in hypothermic animals, and multiple periodic depolarization events in both normothermic and hyperthermic animals. Hyperthermic animals exhibited significantly more (p < 0.05) DC potential deflections (n = 6.17 +/- 0.67) than normothermic animals (n = 2.75 +/- 0.96). The ischemic infarct volume (% of hemisphere) was significantly different for the various groups; hypothermic animals exhibited no measurable infarct volume, while the ischemic infarct volume was 10.2 +/- 12.3% in normothermic animals and 36.5 +/- 3.4% in hyperthermic animals (p < 0.05). A significant correlation was detected between the volume of infarct and number of depolarization events (r = 0.90, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Apoptosis in rat transient focal cerebral ischemic stroke: clinical implications

    Institute of Scientific and Technical Information of China (English)

    Shoushu Jiao; Jue Wang Gal Hever; Rongzheng Kuang; Jean-Claude Louis; Ella Magal

    2000-01-01

    @@In the early phase of cerebral ischemia, factors threatening neuronal survival in the penumbra include mainly glutamate excitotoxicity, free radical damage and energy failure resulting from recurrent depolarization waves. However, at later times, other mechanisms come into play. The initial ischemic event activates a variety of genetic programs that unfold over the course of hours and days. Both positron emission tomography and magnetic resonance based techniques demonstrate that the development of irretrievable tissue damage is relatively slow, progressing over the course of several days in some cases, and a viable tissue, defined by hemodynamic and metabolic criteria,is still present many hours after stroke in human or in monkey. These findings suggest that the brain can potentially be “rescued” from infarction many hours after onset of ischemia and challenge the widespread notion of an early and short “therapeutic window” (~3-6h). This realization is of critical importance for stroke therapy because most patients reach medical attention at a time when current therapeutic strategies may no longer be effective. Therefore, it would be highly desirable to develop therapeutic interventions that can be instituted many hours after the onset of ischemia. We believe that addressing the mechanisms of delayed cell death is key to a successful therapy. The studies presented here were designed to document the potential contribution of apoptosis to ischemia induced neuronal death. We will discuss the morphological, biochemical and pharmacological evidence for apoptosis in the ischemic stroke.

  4. Expression of brain-derived neurotrophic factor in rat hippocampus following focal cerebral ischemic injury

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    Yingping Li; Ruifang Guo; Kaifeng Lu

    2008-01-01

    BACKGROUND: The functional role of brain-derived neurotrophic factor (BDNF) is enhanced following cerebral ischemic injury providing neurons with an important self-protection mechanism in early stage ischemia/hypoxia.OBJECTIVE: To investigate the expression pattern of BDNF in different rat hippocampal regions following focal cerebral ischemic injury.DESIGN, TIME AND SETTING: We performed a comparative and neurobiological study of animals in the Department of Histology and Embryology and the Central Laboratory, Hebei Medical University from March to December 2003.MATERIALS: Forty healthy Sprague Dawley rats were randomly divided into a cerebral ischemla group and a sham operation group, with 20 rats per group.METHODS: In the cerebral ischemia group, we occluded the right middle cerebral artery with a suture,threading it to a depth of 17-19 mm. In the sham operation group, the threading depth was approximately 10 mm.MAIN OUTCOME MEASURES: We analyzed the expression of BDNF in different hippocampal regions by immunohistochemical staining of brain sections taken on post-operative days 7, 14, 21 and 30.RESULTS: Sham operation group: We observed a number of a few BDNF-positive cells with light staining in the hippocampal CAI CA4 regions and dentate gyrus. Cerebral ischemia group: compared with the sham operation group, BDNF increased on day 7, significantly increased on day 14, and reached a peak on day 21 (P < 0.05). Furthermore, immunologically reactive products were darkly stained, and neurons had long axons.BDNF was particularly highly expressed in the hippocampal CA3 and CA4 regions and dentate gyrus.CONCLUSION: Cerebral ischemic injury can damage hippocampal neurons. Neurons can increase their anti-ischemic capacity by increasing BDNF expression in the hippocampal CA3 and CA4 regions and dentate gyrus.

  5. Protein nitration impairs the myogenic tone of rat middle cerebral arteries in both ischemic and nonischemic hemispheres after ischemic stroke.

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    Coucha, Maha; Li, Weiguo; Johnson, Maribeth H; Fagan, Susan C; Ergul, Adviye

    2013-12-01

    The myogenic response is crucial for maintaining vascular resistance to achieve constant perfusion during pressure fluctuations. Reduced cerebral blood flow has been reported in ischemic and nonischemic hemispheres after stroke. Ischemia-reperfusion injury and the resulting oxidative stress impair myogenic responses in the ischemic hemisphere. Yet, the mechanism by which ischemia-reperfusion affects the nonischemic side is still undetermined. The goal of the present study was to determine the effect of ischemia-reperfusion injury on the myogenic reactivity of cerebral vessels from both hemispheres and whether protein nitration due to excess peroxynitrite production is the underlying mechanism of loss of tone. Male Wistar rats were subjected to sham operation or 30-min middle cerebral artery occlusion/45-min reperfusion. Rats were administered saline, the peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(4-sulfonatophenyl)prophyrinato iron (III), or the nitration inhibitor epicatechin at reperfusion. Middle cerebral arteries isolated from another set of control rats were exposed to ex vivo oxygen-glucose deprivation with and without glycoprotein 91 tat (NADPH oxidase inhibitor) or N(ω)-nitro-l-arginine methyl ester. Myogenic tone and nitrotyrosine levels were determined. Ischemia-reperfusion injury impaired the myogenic tone of vessels in both hemispheres compared with the sham group (P nitration improved the myogenic tone of vessels from ischemic (P Nitration was significantly increased in both hemispheres versus the sham group and was normalized with epicatechin treatment. In conclusion, ischemia-reperfusion injury impairs vessel reactivity in both hemispheres via nitration. We suggest that sham operation rather than the nonischemic side should be used as a control in preclinical stroke studies.

  6. Expression of hypoxia inducible factor-1 alpha and ischemic erythropoietin tolerance in the brain of cerebral ischemic tolerance model rats

    Institute of Scientific and Technical Information of China (English)

    Renliang Zhao; Ruijian Dong; Zhongling Sun

    2006-01-01

    BACKGROUND: Hypoxia inducible factor-1 alpha (HIF-1 α) and erythropoietin(EPO), possessing neuroprotective effect in the cerebral ischemia, might play an important role in the formation of cerebral ischemic tolerance (IT).OBJECTIVE:To observe the neuroprotective effect of cerebral ischemic preconditioning(IPC) of rats, and the expression and mechanism of HIF-1α and target gene erythropoietin in the brain tissue following the formation of cerebral IT.DESIGN :A randomized and controlled observation.SETTING: Department of Neurology, the Affiliated Hospital of Medical College, Qingdao University.MATERIALS: Totally 84 enrolled adult healthy male Wistar rats of clean grade, weighing 250 to 300 g, were provided by the Animal Experimental Department, Tongji Medical College of Huazhong University of Science and Technology. Ready-to-use SABC reagent kit and rabbit anti-rat HIF-1α monoclonal antibody were purchased from Boshide Bioengineering Co. Ltd (Wuhan); Rabbit anti-rat EPO monoclonal antibody was purchased from Santa Cruz Company (USA).METHODS: This experiment was carried out in the Department of Anatomy, Medical College, Qingdao University during March 2005 to March 2006. ① The 84 rats were divided into 3 groups by a lot: IPC group (n=40),sham-operation group (n=40) and control group (n=4). In the IPC group, middle cerebral artery was occluded for 2 hours respectively on the 1st, 3rd, 7th, 14th and 21st days of the reperfusion following 10-minute preischemia was made using a modified middle cerebral artery second suture method from Zea-Longa. The rats were sacrificed 22 hours after reperfusion in the end of middle cerebral artery occlusion (MCAO). That was to say,after 10-minute preischemia, suture was exited to the external carotid artery and embedded subcutaneously.Middle cerebral artery was occluded again to form the second reperfusion at the set time point after reperfusion. Twenty-two hours later, rats were sacrificed; In the sham-operation group

  7. Antileukocyte therapy of cerebral ischemic stroke in MCAO model in rats

    Institute of Scientific and Technical Information of China (English)

    Zuming Luo; Xiaohui Zeng; Huiling Chen

    2000-01-01

    OBJECTIVE To Study protecting effect of antileukocytic drugs on cerebrol ischemic injury. BACKGROUND The purposes of prcsent study aimed at comparing the protecting effect of some antileukocytic drugs: chloroquine, Colchieine, Cyclophosphamid (CTX) ,Cyclosporin A, Multiglycoside tripteygil against cerebral ischemic injury in MCAO models in the rats. METHODS 130 SD rats with MCAO model randomly divided into one control group and 10 treatment groups. The observation items were as follows: (1) The infarction volume. (2) Brain edema. (3) Histopathoiogical evaluation. (4) The count of neurons and microglia cells in the infarction area. (5) Neurological dysfunction score. (6) The determination of serum lL-1 β and TNF- α levels. RESULTS Antileukocytic drugs can decrease the volume of infarction, brain edema, inflammatory reaction and neuron death of ischemic injury, the low dose of chloroquine plus colchicine plus CTX had better effects, and prolonged therapeutic time windows. DISCUSSION The accumulation of infiammatory cell and cytoking release from them can promote and increase neuron death in infarction area. CONCLUSION Antileukocytic drugs are of protecting effect on ischemic neuron in MCAO model in rats.

  8. Inhibition of autophagy contributes to ischemic postconditioning-induced neuroprotection against focal cerebral ischemia in rats.

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    Li Gao

    Full Text Available BACKGROUND: Ischemic postconditioning (IPOC, or relief of ischemia in a stuttered manner, has emerged as an innovative treatment strategy to reduce programmed cell death, attenuate ischemic injuries, and improve neurological outcomes. However, the mechanisms involved have not been completely elucidated. Recent studies indicate that autophagy is a type of programmed cell death that plays elusive roles in controlling neuronal damage and metabolic homeostasis. This study aims to determine the role of autophagy in IPOC-induced neuroprotection against focal cerebral ischemia in rats. METHODOLOGY/PRINCIPAL FINDINGS: A focal cerebral ischemic model with permanent middle cerebral artery (MCA occlusion plus transient common carotid artery (CCA occlusion was established. The autophagosomes and the expressions of LC3/Beclin 1/p62 were evaluated for their contribution to the activation of autophagy. We found that autophagy was markedly induced with the upregulation of LC3/Beclin 1 and downregulation of p62 in the penumbra at various time intervals following ischemia. IPOC, performed at the onset of reperfusion, reduced infarct size, mitigated brain edema, inhibited the induction of LC3/Beclin 1 and reversed the reduction of p62 simultaneously. Rapamycin, an inducer of autophagy, partially reversed all the aforementioned effects induced by IPOC. Conversely, autophagy inhibitor 3-methyladenine (3-MA attenuated the ischemic insults, inhibited the activation of autophagy, and elevated the expression of anti-apoptotic protein Bcl-2, to an extent comparable to IPOC. CONCLUSIONS/SIGNIFICANCE: The present study suggests that inhibition of the autophagic pathway plays a key role in IPOC-induced neuroprotection against focal cerebral ischemia. Thus, pharmacological inhibition of autophagy may provide a novel therapeutic strategy for the treatment of stroke.

  9. Acute ischemic cerebral attack

    OpenAIRE

    Franco-Garcia Samir; Barreiro-Pinto Belis

    2010-01-01

    The decrease of the cerebral blood flow below the threshold of autoregulation led to changes of cerebral ischemia and necrosis that traduce in signs and symtoms of focal neurologic dysfunction called acute cerebrovascular symdrome (ACS) or stroke. Two big groups according to its etiology are included in this category the hemorragic that constitue a 20% and the ischemic a 80% of cases. Great interest has wom the ischemic ACS because of its high social burden, being the third cause of no violen...

  10. Learning and memory changes in rats following exogenous human hepatocyte growth factor gene injection into cerebral ischemic penumbra

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    Zhijun You; Yong Liu; Jianye Yang; Qingping Jiang

    2011-01-01

    Human hepatocyte growth factor can be used to treat cerebral infarction, administered by lateral ventricular, cerebellomedullary cistern or subarachnoid injections. However, the target gene expression product is scarcely found in the ischemic penumbra, but extensively distributes in other regions, increasing the risks of gene therapy. The present study directly transfected hepatocyte growth factor gene into the ischemic penumbra of rats with transient middle cerebral artery occlusion. Immunohistochemical analysis revealed that infarct volume was significantly decreased, hepatocyte growth factor protein expression level and vessel quantity in the ischemic penumbra were significantly increased, and learning and memory were significantly improved.

  11. Effects of NG-nitro-L-arginine on focal cerebral ischemic injury in rats

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    Jianxin Zhang; Huixin Zhang; Lanfang Li; Yonghui Li

    2006-01-01

    BACKGROUND: Previous researches have proved that aminoguanidin can cure cerebral ischemic injury remarkably as a selective induced nitricoxide synthase (iNOS) inhibitor. However, whether nonselective NOS inhibitor could protect cerebral ischemic injury or not is unclear.OBJECTIVE: To investigate the effects of NG-nitro-L-arginine (L-NA), a nonselective nitricoxide synthase (NOS) inhibitor, on cerebral ischemic injury of rats and the possible mechanism.DESIGN: Randomized controlled study.SETTING: Pharmacological Department of Medical Academy of Science of Hebei Province.MATERIALS: A total of 56 male healthy SD rats, of grade II, weighting 250-290 g, were provided by the Experimental Animal Center of Hebei Province (certification: 04036).METHODS: The experiment was completed in the Pharmacological Department of Medical Academy of Science of Hebei Province from March 2005 to January 2006. ① Grouping: Rats were randomly divided into 3 groups: sham operation group (n=8), model group (n=24) and L-NA group (n=24). ② Modeling:Middle cerebral artery (MCA) was established on rats in model group and L-NA group with intraluminal line occlusion methods, and rats in sham operation group were separated their external carotid arteries without occlusion of internal carotid artery. ③ Intervention study: Rats in model group and L-NA group were injected intraperitoneally with 10 mL/kg and 20 mg/kg L-NA at 2, 6 and 12 hours respectively after ischemia twice a day for 3 consecutive days. ④ Rats were sacrificed on the third day for measuring volume of cerebral infarction with image analysis and swelling degrees and activities of mitochondria with electron microscope. Effect of L-NA on ultrastructural changes of neurons in cortex was observed after ischemia.MAIN OUTCOME MEASURES: ① Volume of cerebral infarction; ② Swelling degrees, contents of nitric oxide (NO) and malondialdehyde (MDA) and activities of adenosine triphosphatase (ATPase), superoxide dismutase (SOD) and

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

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

    2015-07-01

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

  13. Neuroprotective effect of ginkgolide K against acute ischemic stroke on middle cerebral ischemia occlusion in rats.

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    Ma, Shuwei; Yin, Huafeng; Chen, Lvyi; Liu, Hongxia; Zhao, Ming; Zhang, Xiantao

    2012-01-01

    Ginkgolide K, a natural platelet-activating factor receptor antagonist, was isolated from the leaves of Ginkgo biloba. However, little is known about its neuroprotective effect in ischemia-reperfusion (I/R)-induced cerebral injury. Hence, the present study was carried out to investigate the effect of ginkgolide K on neuroprotection and the potential mechanisms in the rat I/R model induced by middle cerebral artery occlusion (MCAO). The rats were pretreated with ginkgolide K 2, 4 and 8 mg/kg (i.v.) once a day for 5 days before MCAO. Neurological deficit score (NDS), brain water content, 2,3,5-triphenyltetrazolium chloride (TTC) staining and pathology of brain tissue, as well as indexes of oxidative stress [superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO) and nitric oxide synthase (NOS)] were measured at 24 h after ischemia. The results indicated that pretreatment with ginkgolide K significantly diminished the volume of infarction and brain water content, and improved NDS. Moreover, ginkgolide K markedly reversed the level of MDA, NO, NOS and SOD to their normal state in serum or cerebral ischemic section. In addition, hematoxylin and eosin staining showed the neuronal injury was significantly improved after being pretreated with ginkgolide K. These findings demonstrate that ginkgolide K exhibits neuroprotective properties through its antioxidative action in MCAO rats.

  14. Expression of bone morphogenetic protein 7 in the cerebral cortex of rats after ischemic-hypoxic injury

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    2007-01-01

    BACKGROUND: Some researches demonstrate that exogenous bone morphogenetic protein 7 (BMP-7) can protect ischemic cerebral nerve tissue and promote recovery of motor energy function; however, there is lack of direct evidences of endogenous BMP-7 effect.OBJECTIVE: To observe the expression of endogenous BMP-7 in nerve tissue with ischemic-hypoxic injury and investigate the possible effects on damaged nerve tissue.DESIGN: Observational contrast animal study.SETTING: Department of Anatomy and Histoembryology, Peking University Health Science Center.MATERIALS: The experiment was carried out in the Nerve Researching Laboratory of Anatomy Department, Peking University Health Science Center from October 2006 to March 2007. A total of 25 adult male SD rats weighing 250 - 300 g and several newborn SD rats were selected from Experimental Animal Center, Peking University Health Science Center. Rabbit-anti-BMP-7 polyclonal antibody was provided by Wuhan Boster Company.METHODS: ① Adult rats were randomly divided into ischemia group (n =10), sham operation group (n =10) and normal group (n =5). Right external-internal carotid artery occlusion was used to infarct middle cerebral artery of adult rats in the ischemia group so as to copy focal cerebral infarction models. Line cork was inserted in crotch of internal and external carotid artery of adult rats in the sham operation group, while adult rats in the normal group were not given any treatments. ② Cerebral cortex of newborn rats was separated to obtain cell suspension. Cells which were cultured for 10 days were divided into control group and hypoxia/reoxygenation group. And then, cells in the hypoxia/reoxygenation group were cultured in hypoxic incubator for 4 hours and given reoxygenation for 24 hours.MAIN OUTCOME MEASURES: Immunohistochemical method was used to measure expression of BMP-7 in cerebral cortex at 24 hours after ischemia/reperfusion culture and in primary hypoxic culture.RESULTS: ① At 24 hours after

  15. Pre, intra and post-ischemic hypothermic neuroprotection in temporary focal cerebral ischemia in rats: morphometric analysis

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    Roberto Alexandre Dezena

    2012-08-01

    Full Text Available OBJECTIVE: To evaluate the neuroprotection of mild hypothermia, applied in different moments, in temporary focal cerebral ischemia in rats. METHODS: Rats was divided into Control (C, Sham (S, Ischemic-control(IC, Pre-ischemic Hypothermia (IH1, Intra-ischemic Hypothermia (IH2, and Post-ischemic Hypothermia (IH3 groups. Morphometry was performed using the KS400 software (Carl Zeiss® in coronal sections stained by Luxol Fast Blue. Ischemic areas and volumes were obtained. RESULTS: Statistically, blue areas showed difference for C vs. IC, IC vs. IH1 and IC vs. IH2 (p=0.0001; p=0.01; p=0.03, and no difference between C vs. S, IC vs. IH3 and IH vs. IH2 (p=0.39; p=0.85; p=0.63. Red areas showed difference between C vs. IC, IC vs. IH1 and IC vs. IH2 (p=0.0001; p=0.009; p=0.03, and no difference between C vs. S, IC vs. IH3 and IH1 vs. IH2 (p=0.48; p=0.27; p=0.68. Average ischemic areas and ischemic volumes showed difference between IC vs. IH1 and IC vs. IH2 (p=0.0001 and p=0.0011, and no difference between IC vs. IH3 and IH1 vs. IH2 (p=0.57; p=0.79. CONCLUSION: Pre-ischemic and intra-ischemic hypothermia were shown to be similarly neuroprotective, but this was not true for post-ischemic hypothermia.

  16. Relationship between AQP4 expression and DWI of the cerebral ischemic edema in rats

    Institute of Scientific and Technical Information of China (English)

    鲁宏; 孙善全

    2003-01-01

    Objective: To study the correlation between aquaporin-4(AQP4) expression and diffusion-weighted imaging (DWI) in the process of ischemic brain edema for the molecular biologic mechanism of DWI. Methods: A total of 34 Wistar rats were divided into 8 groups randomly: Non-operated group (n=4), sham-operated group (n=6), and operated group, receiving right middle cerebral artery occlusion (MCAO) for 15 and 30 min, and 1, 3, 6 and 24 h respectively (6 subgroups, n=4). All groups were imaged with DWI and T2WI. The apparent diffusion coefficient (ADC), relevant density (rd) and relevant area (rs) of hyperintensity of the lesions on DWI and T2WI were measured. Relevant ADC (rADC), relevant area of immunohistochemical staining for AQP4 (rS), optical density of AQP4 hybridization (α) were calculated. After that the animals were sacrificed and perfused at different time intervals, correlations between DWI, ADC, and AQP4 expression (rS, α) in ischemic tissue was made. Results: There was a significant correlation between rS and α (r=0.949). The abnormal high intensity was found in DWI of the ipsilateral MAC territory at 15 min after MCAO. The ADC value decreased quickly within 1 h after MCAO, the rd and rs of DWI increased rapidly and the expression of AQP4 increased quickly, too. However, there was no change on the T2WI. In the period of time (15 min-1 h), the AQP4 expression(α) had a strong relation to the rd and rs( r=0.914, 0.895). With the progress of the time, the ADC value of MCAO decreased further to (2.1±0.6)×10-4 mm2/s at 3 h, and then followed an increased slowly till 24 h, but the rd and the rs as well as the expression of AQP4 continuously increased during the stage. The T2WI detected the lesion at the average time (1.4 h) after MCAO, and the rs of T2WI was less than that of DWI at the same time in the same layer (P<0.05). Conclusion: The results imply that high expression of AQP4 may play a key role in ischemic brain edema. It is, certainly, one of the

  17. PET Demonstrates Functional Recovery after Treatment by Danhong Injection in a Rat Model of Cerebral Ischemic-Reperfusion Injury.

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    Wang, Zefeng; Song, Fahuan; Li, Jinhui; Zhang, Yuyan; He, Yu; Yang, Jiehong; Zhou, Huifen; Zhao, Tao; Fu, Wei; Xing, Panke; Wan, Haitong; Tian, Mei; Zhang, Hong

    2014-01-01

    This study aimed to investigate neuroprotection of Danhong injection (DHI) in a rat model of cerebral ischemia using (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET). Method. Rats were divided into 5 groups: sham group, ischemia-reperfusion untreated (IRU) group, DHI-1 group (DHI 1 mL/kg/d), DHI-2 group (DHI 2 mL/kg/d), and DHI-4 group (DHI 4 mL/kg/d). AII the treated groups were intraperitoneally injected with DHI daily for 14 days. The therapeutic effects in terms of cerebral infarct volume, neurological function, and cerebral glucose metabolism were evaluated. Expression of TNF-α and IL-1β was detected with enzyme-linked immunosorbent assay (ELISA). Levels of mature neuronal marker (NeuN), glial marker (GFAP), vascular density factor (vWF), and glucose transporter 1 (GLUT1) were assessed by immunohistochemistry. Results. Compared with the IRU group, rats treated with DHI showed dose dependent reductions in cerebral infarct volume and levels of proinflammatory cytokines, improvement of neurological function, and recovery of cerebral glucose metabolism. Meanwhile, the significantly increased numbers of neurons, gliocytes, and vessels and the recovery of glucose utilization were found in the peri-infarct region after DHI treatment using immunohistochemical analysis. Conclusion. This study demonstrated the metabolic recovery after DHI treatment by micro-PET imaging with (18)F-FDG and the neuroprotective effects of DHI in a rat model of cerebral ischemic-reperfusion injury.

  18. PET Demonstrates Functional Recovery after Treatment by Danhong Injection in a Rat Model of Cerebral Ischemic-Reperfusion Injury

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    Zefeng Wang

    2014-01-01

    Full Text Available This study aimed to investigate neuroprotection of Danhong injection (DHI in a rat model of cerebral ischemia using 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET. Method. Rats were divided into 5 groups: sham group, ischemia-reperfusion untreated (IRU group, DHI-1 group (DHI 1 mL/kg/d, DHI-2 group (DHI 2 mL/kg/d, and DHI-4 group (DHI 4 mL/kg/d. AII the treated groups were intraperitoneally injected with DHI daily for 14 days. The therapeutic effects in terms of cerebral infarct volume, neurological function, and cerebral glucose metabolism were evaluated. Expression of TNF-α and IL-1β was detected with enzyme-linked immunosorbent assay (ELISA. Levels of mature neuronal marker (NeuN, glial marker (GFAP, vascular density factor (vWF, and glucose transporter 1 (GLUT1 were assessed by immunohistochemistry. Results. Compared with the IRU group, rats treated with DHI showed dose dependent reductions in cerebral infarct volume and levels of proinflammatory cytokines, improvement of neurological function, and recovery of cerebral glucose metabolism. Meanwhile, the significantly increased numbers of neurons, gliocytes, and vessels and the recovery of glucose utilization were found in the peri-infarct region after DHI treatment using immunohistochemical analysis. Conclusion. This study demonstrated the metabolic recovery after DHI treatment by micro-PET imaging with 18F-FDG and the neuroprotective effects of DHI in a rat model of cerebral ischemic-reperfusion injury.

  19. Periodic 17β-estradiol pretreatment protects rat brain from cerebral ischemic damage via estrogen receptor-β.

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    Ami P Raval

    Full Text Available Although chronic 17β-estradiol (E2 has been shown to be a cognition-preserving and neuroprotective agent in animal brain injury models, concern regarding its safety was raised by the failed translation of this phenomenon to the clinic. Previously, we demonstrated that a single bolus of E2 48 hr prior to ischemia protected the hippocampus from damage in ovariectomized rats via phosphorylation of cyclic-AMP response element binding protein, which requires activation of estrogen receptor subtype beta (ER-β. The current study tests the hypothesis that long-term periodic E2-treatment improves cognition and reduces post-ischemic hippocampal injury by means of ER-β activation. Ovariectomized rats were given ten injections of E2 at 48 hr intervals for 21 days. Hippocampal-dependent learning, memory and ischemic neuronal loss were monitored. Results demonstrated that periodic E2 treatments improved spatial learning, memory and ischemic neuronal survival in ovariectomized rats. Additionally, periodic ER-β agonist treatments every 48 hr improved post-ischemic cognition. Silencing of hippocampal ER-β attenuated E2-mediated ischemic protection suggesting that ER-β plays a key role in mediating the beneficial effects of periodic E2 treatments. This study emphasizes the need to investigate a periodic estrogen replacement regimen to reduce cognitive decline and cerebral ischemia incidents/impact in post-menopausal women.

  20. Lysine and arginine reduce the effects of cerebral ischemic insults and inhibit glutamate-induced neuronal activity in rats

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    Takashi Kondoh

    2010-06-01

    Full Text Available Intravenous administration of arginine was shown to be protective against cerebral ischemic insults via nitric oxide production and possibly via additional mechanisms. The present study aimed at evaluating the neuroprotective effects of oral administration of lysine (a basic amino acid, arginine, and their combination on ischemic insults (cerebral edema and infarction and hemispheric brain swelling induced by transient middle cerebral artery occlusion/reperfusion in rats. Magnetic resonance imaging and 2,3,5-triphenyltetrazolium chloride staining were performed two days after ischemia induction. In control animals, the major edematous areas were observed in the cerebral cortex and striatum. The volumes associated with cortical edema were significantly reduced by lysine (2.0 g/kg, arginine (0.6 g/kg, or their combined administration (0.6 g/kg each. Protective effects of these amino acids on infarction were comparable to the inhibitory effects on edema formation. Interestingly, these amino acids, even at low dose (0.6 g/kg, were effective to reduce hemispheric brain swelling. Additionally, the effects of in vivo microiontophoretic (juxtaneuronal applications of these amino acids on glutamate-evoked neuronal activity in the ventromedial hypothalamus were investigated in awake rats. Glutamate-induced neuronal activity was robustly inhibited by microiontophoretic applications of lysine or arginine onto neuronal membranes. Taken together, our results demonstrate the neuroprotective effects of oral ingestion of lysine and arginine against ischemic insults (cerebral edema and infarction, especially in the cerebral cortex, and suggest that suppression of glutamate-induced neuronal activity might be the primary mechanism associated with these neuroprotective effects.

  1. Protective Effects of Focal Ischemic Preconditioning and HSP70 Expression on Middle Cerebral Artery Occlusion in Rats

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    ZHAO Jianhua; SUN Senggang; CHEN Xiaowu

    2006-01-01

    To systematically evaluate the importance of protein synthesis in ischemic preconditioning (PC)-induced ischemic tolerance (IT), temporary middle cerebral artery occlusion (MCAO)by Longa (20 min) was used for PC (ischemic precondioning). Twenty-four hours of reperfusion was allowed after PC and before permanent MCAO to establish ischemic tolerance (IT) to compare with non-PC (sham-operated) rats (n=5 for each group). Infarct size and neurological deficits were measured 24 h after PMCAO. Samples of brain were taken for the determination of HSP70 expression by Western blot analysis. The effects of the protein synthesis inhibitor cycloheximide administered just before PC or administered long after PC but just before PMCAO on IT were also determined (n=5 for each group). Our results showed that hemispheric infarct was significantly reduced (P<0.01) only if PC was performed after 24 h, and PC significantly (P<0.05) reduced neurological deficits (similar to reductions in infarct size). Cycloheximide eliminated ischemic PC-induced IT effects on both brain injury and neurological deficits if administered before PC but not if administered long after PC but before PMCAO. PC produced no brain injury but did increase HSP70 protein 24 h after PC. Cycloheximide eliminated that effect. The results suggest that PC is a powerful inducer of ischemic brain tolerance as reflected by the preservation of brain tissue and motor function. PC induces IT that is dependent on de novo protein synthesis.

  2. Fullerenols and glucosamine fullerenes reduce infarct volume and cerebral inflammation after ischemic stroke in normotensive and hypertensive rats.

    Science.gov (United States)

    Fluri, Felix; Grünstein, Dan; Cam, Ertugrul; Ungethuem, Udo; Hatz, Florian; Schäfer, Juliane; Samnick, Samuel; Israel, Ina; Kleinschnitz, Christoph; Orts-Gil, Guillermo; Moch, Holger; Zeis, Thomas; Schaeren-Wiemers, Nicole; Seeberger, Peter

    2015-03-01

    Cerebral inflammation plays a crucial role in the pathophysiology of ischemic stroke and is involved in all stages of the ischemic cascade. Fullerene derivatives, such as fullerenol (OH-F) are radical scavengers acting as neuroprotective agents while glucosamine (GlcN) attenuates cerebral inflammation after stroke. We created novel glucosamine-fullerene conjugates (GlcN-F) to combine their protective effects and compared them to OH-F regarding stroke-induced cerebral inflammation and cellular damage. Fullerene derivatives or vehicle was administered intravenously in normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) immediately after transient middle cerebral artery occlusion (tMCAO). Infarct size was determined at day 5 and neurological outcome at days 1 and 5 after tMCAO. CD68- and NeuN-staining were performed to determine immunoreactivity and neuronal survival respectively. Cytokine and toll like receptor 4 (TLR-4) expression was assessed using quantitative real-time PCR. Magnetic resonance imaging revealed a significant reduction of infarct volume in both, WKY and SHR that were treated with fullerene derivatives. Treated rats showed an amelioration of neurological symptoms as both OH-F and GlcN-F prevented neuronal loss in the perilesional area. Cerebral immunoreactivity was reduced in treated WKY and SHR. Expression of IL-1β and TLR-4 was attenuated in OH-F-treated WKY rats. In conclusion, OH-F and GlcN-F lead to a reduction of cellular damage and inflammation after stroke, rendering these compounds attractive therapeutics for stroke.

  3. Effects of angiopoietin-1 on hemorrhagic transformation and cerebral edema after tissue plasminogen activator treatment for ischemic stroke in rats.

    Science.gov (United States)

    Kawamura, Kunio; Takahashi, Tetsuya; Kanazawa, Masato; Igarashi, Hironaka; Nakada, Tsutomu; Nishizawa, Masatoyo; Shimohata, Takayoshi

    2014-01-01

    An angiogenesis factor, angiopoietin-1 (Ang1), is associated with the blood-brain barrier (BBB) disruption after focal cerebral ischemia. However, whether hemorrhagic transformation and cerebral edema after tissue plasminogen activator (tPA) treatment are related to the decrease in Ang1 expression in the BBB remains unknown. We hypothesized that administering Ang1 might attenuate hemorrhagic transformation and cerebral edema after tPA treatment by stabilizing blood vessels and inhibiting hyperpermeability. Sprague-Dawley rats subjected to thromboembolic focal cerebral ischemia were assigned to a permanent ischemia group (permanent middle cerebral artery occlusion; PMCAO) and groups treated with tPA at 1 h or 4 h after ischemia. Endogenous Ang1 expression was observed in pericytes, astrocytes, and neuronal cells. Western blot analyses revealed that Ang1 expression levels on the ischemic side of the cerebral cortex were decreased in the tPA-1h, tPA-4h, and PMCAO groups as compared to those in the control group (P = 0.014, 0.003, and 0.014, respectively). Ang1-positive vessel densities in the tPA-4h and PMCAO groups were less than that in the control group (p = 0.002 and cerebral homogenate (p = 0.007) and cerebral edema due to BBB damage (p = 0.038), as compared to administering COMP protein alone. In conclusion, Ang1 might be a promising target molecule for developing vasoprotective therapies for controlling hemorrhagic transformation and cerebral edema after tPA treatment.

  4. Protective and super-imposing effects of Estradiol , Breviscapini, Lumbrokinase In focal cerebral ischemic-reperfusion injury on rats

    Institute of Scientific and Technical Information of China (English)

    Shang huiFang; Luo ZuMing

    2000-01-01

    Baekgrouad: Postmenopausal estrogen replacement therapy is always associated with a decrease in risk of stroke incidence and mortality. The breviscapini and lumbrokinase can protect brain from ischemic injury..Experiments in animal models suggest estradiol can protect brain from ischemic injury. But we know little about the mechanism of brain protection role of estradiol. Espectically we don't know if estrodiol plus other brain protective drugs such as breviscapini and lumbrokinase have superimposing protection. Objective: To study protective function and its mechanism of estradio breviscapini and lumbrokinase after cerebral ischemic reperfusion tn overiectimiaed rat. Methods: We made the local ischemic repenfusion model with thread emgolism of right middle cerebral artery (MCA) of young female SD rars which werc bilaterally ovariectomized two weeks ago were used. These rats were randomized into sham-operated group, control group, estrodiol group, brevisacapini group, 10 SD rats each group. We admistrated each group with reseponsed treatment when rats were subjected to half an hour of MCAO. MCA were oecluded 2 hours and followed by 70 hours of reperfusion. Sham-poerated group were exposed cervical common artery and weren't occluded MCA. The rats were killed at 72 hours. The observed patameters each group listed: 1) The neurological deficit scores were made after MCAO 2 hours and bcforc killed. 2) Each group excluded sham operaated group were caculaled cerebral infarct volume ratio and edema volume with stereological microscoppe. 3) The level of Nitrc oxide (NO) in serum were determined with nitrate redutase method. 4) The level of Interlukin-I (IL-1) and tumor necrosis factot (TNF) were determined by biological activity method. 5) Ultrastructure of neuron were observed with electron microscope. All the rcsults from different groups were compared with each other. The drugs identified effictive in formcr study plus estradiot wcre admistratcd to rats to obscrvcd

  5. Cerebral ischemia-induced mitochondrial changes in a global ischemic rat model by AFM.

    Science.gov (United States)

    Park, Eunkuk; Choi, Seok Keun; Kang, Sung Wook; Pak, Youngmi Kim; Lee, Gi-Ja; Chung, Joo-Ho; Park, Hun-Kuk

    2015-04-01

    Mitochondria play a central role in cell survival, and apoptotic cell death is associated with morphological changes in mitochondria. Quantification of the morphological and mechanical property changes in brain mitochondria is useful for evaluating the degree of ischemic injury and the neuroprotective effects of various drugs. This study was performed to investigate the changes in brain mitochondria in an 11-vessel occlusion ischemic model treated with magnesium sulfate (MgSO4), utilizing atomic force microscopy (AFM). Rats were randomly divided into three groups consisting of sham (n=6), global ischemia (GI, n=6), and MgSO4-treated global ischemia (MgSO4, n=6). The biophysical properties of brain mitochondria determined from AFM topographic images and adhesion force from force-distance measurements. The mean perimeter of ischemic mitochondria significantly increased to 2,396±541 nm (vs. 1,006±318 nm in control group, PAFM could be effective for evaluating neuronal injury and drug effects.

  6. Post-hypoxic and ischemic neuroprotection of BMP-7 in the cerebral cortex and caudate-putamen tissue of rat.

    Science.gov (United States)

    Luan, Liju; Yang, Xiaomei; Zhou, Changman; Wang, Ke; Qin, Lihua

    2015-03-01

    Previous reports have indicated that exogenous bone morphogenetic protein-7 (BMP-7) has a neuroprotective effect after cerebral ischemia injury and promotes motor function recovery, but the appropriate BMP-7 concentration and time course are unclear. Here, we assessed endogenous BMP-7 expression in hypoxia and ischemia-damaged brain tissues and investigated the effects of different BMP-7 concentrations in pre- and post-hypoxic primary rat neurons. The results showed that BMP-7 expression was significantly higher in the ischemic hemisphere. The expressions of BMP-7 and caspase-3 were localized in the cytoplasm of the primary cerebral cortical and caudate-putamen neurons 24h after hypoxia/reoxygenation. After BMP-7 treatment, the number of caspase-3 positive neurons began to decrease with increasing BMP-7 concentrations up to 80ng/ml, but not beyond. Although the numbers of caspase-3-positive neurons between pre- and post-hypoxia/reoxygenation were not significantly different, more dendrites were observed in the groups treated prior to hypoxia/reoxygenation. These results suggest that increased BMP-7 expression can be induced in the cerebral cortex and caudate-putamen both in vivo and in vitro in hypoxic-ischemic states. The neuroprotective mechanism of BMP-7 may include apoptosis suppression, and its effect was enhanced from 40 to 80ng/ml. Pre-hypoxic BMP-7 treatment may be useful to stimulate dendrite sprouting in non-injured neurons.

  7. Protective and super-imposing effects of Estradiol , Breviscapini, Lumbrokinase In focal cerebral ischemic-reperfusion injury on rats

    Institute of Scientific and Technical Information of China (English)

    Shang huiFang; Luo ZuMing

    2000-01-01

    Baekgrouad: Postmenopausal estrogen replacement therapy is always associated with a decrease in risk of stroke incidence and mortality. The breviscapini and lumbrokinase can protect brain from ischemic injury..Experiments in animal models suggest estradiol can protect brain from ischemic injury. But we know little about the mechanism of brain protection role of estradiol. Espectically we don't know if estrodiol plus other brain protective drugs such as breviscapini and lumbrokinase have superimposing protection. Objective: To study protective function and its mechanism of estradio breviscapini and lumbrokinase after cerebral ischemic reperfusion tn overiectimiaed rat. Methods: We made the local ischemic repenfusion model with thread emgolism of right middle cerebral artery (MCA) of young female SD rars which werc bilaterally ovariectomized two weeks ago were used. These rats were randomized into sham-operated group, control group, estrodiol group, brevisacapini group, 10 SD rats each group. We admistrated each group with reseponsed treatment when rats were subjected to half an hour of MCAO. MCA were oecluded 2 hours and followed by 70 hours of reperfusion. Sham-poerated group were exposed cervical common artery and weren't occluded MCA. The rats were killed at 72 hours. The observed patameters each group listed: 1) The neurological deficit scores were made after MCAO 2 hours and bcforc killed. 2) Each group excluded sham operaated group were caculaled cerebral infarct volume ratio and edema volume with stereological microscoppe. 3) The level of Nitrc oxide (NO) in serum were determined with nitrate redutase method. 4) The level of Interlukin-I (IL-1) and tumor necrosis factot (TNF) were determined by biological activity method. 5) Ultrastructure of neuron were observed with electron microscope. All the rcsults from different groups were compared with each other. The drugs identified effictive in formcr study plus estradiot wcre admistratcd to rats to obscrvcd

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

    Directory of Open Access Journals (Sweden)

    Jintanaporn Wattanathorn

    2011-01-01

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

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

    Science.gov (United States)

    Guo, Zongjun; Wang, Lumin

    2012-07-25

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

  10. 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.

  11. Effect of restraint stress on depression-like behaviors in rats after transient focal cerebral ischemic injury

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: Restraint stress is a typical psychophysiological stressor. Simulating the early passion and difficulty in walking of patients after attack of stroke meets onset features.OBJECTIVE: To evaluate the effect of restraint stress on depression-like behaviors in rats after transient focal cerebral ischemic injury, and to investigate the feasibility for its being as modeling method of depression model after stroke.DESIGN: A randomized controlled animal experiment.SETTING: Department of Clinical Medicine, Faculty of Aerospace Medicine of the Fourth Military Medical University of Chinese PLA.MATERIALS: Forty-eight male Sprague-Dawley rats, weighing 240 - 270 g, provided by the Experimental Animal Center of the Fourth Military Medical University of Chinese PLA were used in the current study.METHODS: The experiments were carried out in the Faculty of Aerospace Medicine of the Fourth Military Medical University of Chinese PLA between August 2005 and August 2006. ①Experiment intervention: The rats were randomized into middle cerebral artery occlusion-reperfusion (MCAO) +stress group, simple MCAO group, sham-operation + stress group and simple sham-operation group, with 12 rats in each group.Rats in the first two groups were developed into cerebral ischemia/reperfusion models by suture-occluded method. Rats in the MCAO+stress group were modeled and restraint stress scheme was performed. At week 5 after modeling, the rats were placed in self-made restraining tubes, 2 hours/time, once a day, for 2 successive weeks. The common carotid artery, external and internal carotid arteries of rats in the latter two groups were exposed. The stress way of sham-operation+ stress group was the same as that of MCAO+ stress group. ②The neurological status grading and motor performance evaluation (screen test, rota-rod test and balance beam test) were conducted in rats with simple sham-operation group and MCAO group before, 1st and 28th days after modeling. Depression-like behavior

  12. Anti-CD11b monoclonal antibody reduces ischemic cell damage after transient focal cerebral ischemia in rat.

    Science.gov (United States)

    Chen, H; Chopp, M; Zhang, R L; Bodzin, G; Chen, Q; Rusche, J R; Todd, R F

    1994-04-01

    We investigated the effect of an anti-CD11b monoclonal antibody (1B6c) on ischemic cell damage after transient middle cerebral artery occlusion. We divided animals into three groups: MAb 1 group (n = 5)--rats were subjected to 2 hours of transient occlusion and 1B6c (1 mg/kg) was administered intravenously at 0 and 22 hours of reperfusion; MAb 2 group (n = 5)--same experimental protocol as MAb 1 group, except that the initial dose of 1B6c was increased to 2 mg/kg; and control group (n = 5)--same experimental protocol as MAb 2 group, except that an isotype-matched control antibody was administered. Animals were weighed and tested for neurological function before and after occlusion of the middle cerebral artery. Forty-six hours after reperfusion, brain sections were stained with hematoxylin and eosin for histology evaluation. We observed a significant reduction of weight loss and improvement in neurological function after ischemia in the MAb 2 animals compared to MAb 1 and vehicle-treated animals (p < 0.05). The lesion volume was significantly smaller in the MAb 2 group (19.5 +/- 1.9%) compared to MAb 1 (29.9 +/- 2.6%) and vehicle-treated (34.2 +/- 5.4%) groups (p < 0.01). Tissue polymorphonuclear cell numbers were reduced in both 1B6c-administered groups. Our data demonstrate that administration of anti-CD11b antibody results in a dose-dependent, significant functional improvement and reduction of ischemic cell damage after transient focal cerebral ischemia in the rat.

  13. Light scattering change precedes loss of cerebral adenosine triphosphate in a rat global ischemic brain model.

    Science.gov (United States)

    Kawauchi, Satoko; Sato, Shunichi; Ooigawa, Hidetoshi; Nawashiro, Hiroshi; Ishihara, Miya; Kikuchi, Makoto

    2009-08-14

    Measurement of intrinsic optical signals (IOSs) is an attractive technique for monitoring tissue viability in brains since it enables noninvasive, real-time monitoring of morphological characteristics as well as physiological and biochemical characteristics of tissue. We previously showed that light scattering signals reflecting cellular morphological characteristics were closely related to the IOSs associated with the redox states of cytochrome c oxidase in the mitochondrial respiratory chain. In the present study, we examined the relationship between light scattering and energy metabolism. Light scattering signals were transcranially measured in rat brains after oxygen and glucose deprivation, and the results were compared with concentrations of cerebral adenosine triphosphate (ATP) measured by luciferin-luciferase bioluminescence assay. Electrophysiological signal was also recorded simultaneously. After starting saline infusion, EEG activity ceased at 108+/-17s, even after which both the light scattering signal and ATP concentration remained at initial levels. However, light scattering started to change in three phases at 236+/-15s and then cerebral ATP concentration started to decrease at about 260s. ATP concentration significantly decreased during the triphasic scattering change, indicating that the start of scattering change preceded the loss of cerebral ATP. The mean time difference between the start of triphasic scattering change and the onset of ATP loss was about 24s in the present model. DC potential measurement showed that the triphasic scattering change was associated with anoxic depolarization. These findings suggest that light scattering signal can be used as an indicator of loss of tissue viability in brains.

  14. Protection by the gross saponins of Tribulus terrestris against cerebral ischemic injury in rats involves the NF-κB pathway

    Directory of Open Access Journals (Sweden)

    En-ping Jiang

    2011-06-01

    Full Text Available The aim of this study was to investigate whether the gross saponins of Tribulus terrestris (GSTT, a traditional Chinese herbal medicine, have neuroprotective effects on rats subjected to middle cerebral artery occlusion (MCAO, through nuclear factor-κB (NF-κB pathway and inflammatory mediators. Cerebral ischemia was produced by MCAO in either untreated (control or GSTT-pretreated rats, and the animals were examined for infarct volume, cerebral edema, neuro-behavioral abnormality and pathological changes. Meanwhile, the expression of NF-κB protein in brain tissue was analyzed on Western blots and the serum levels of TNF-α and IL-1 were determined by ELISA. The experimental results demonstrated that, compared with the control MCAO group, GSTT-pretreated MCAO group had significantly reduced infarct volume, brain edema and neuro-behavioral abnormality, and lesser degree of pathologic changes in the brain, as well as had lower levels of serum TNF-α and IL-1β, and higher levels of brain NF-κB (P<0.05. Furthermore, treatment with an NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC abolished the protective effects of GSTT against MCAO-induced cerebral ischemic injury. These results indicated that GSTT's ability to protect against cerebral ischemic injury was mediated through the NF-κB signaling pathway, and that GSTT may act through inhibition of the production of inflammatory mediators.

  15. Involvement of δ-and μ-opioid receptors in the delayed cerebral ischemic tolerance induced by repeated electroacupuncture preconditioning in rats

    Institute of Scientific and Technical Information of China (English)

    XIONG Li-ze; YANG Jing; WANG Qiang; LU Zhi-hong

    2007-01-01

    Background Preconditioning with repeated electroacupuncture (EA) could mimic ischemic preconditioning to induce cerebral ischemic tolerance in rats. The present study was designed to investigate whether mu(μ)-, delta(δ)- or kappa(κ)-opioid receptors are involved in the neuroprotection induced by repeated EA preconditioning.Methods The rats were pretreated with naltrindole (NTI), nor-binaltorphimine (nor-BNI) or D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), which is a highly selective δ-, κ- or μ-opioid receptor antagonist respectively, before each EA preconditioning (30 minutes per day, 5 days). Twenty-four hours after the last EA treatment, the middle cerebral artery occlusion (MCAO) was induced for 120 minutes. The brain infarct volume was determined with 2,3,5-triphenyltetrazolium chloride staining at 24 hours after MCAO and compared with that in rats which only received EA preconditioning. In another experiment, the met-enkephalin-like immunoreactivity in rat brain was investigated by immunohistochemistry in both EA preconditioning and control rats.Results The EA preconditioning reduced brain infarct volume compared with the control rats (P=0.000). Administration of both NTI and CTOP attenuated the brain infarct volume reduction induced by EA preconditioning, presenting with larger infarct volume than that in the EA preconditioning rats (P<0.001). But nor-BNI administration did not block the infarct volume reduction induced by EA preconditioning, presenting with smaller infarct volume than the control group rats(P=0.000). The number of met-enkephalin-like immunoreactivity positive neurons in the EA preconditioning rats was more than that of the control rats (P=0.000).Conclusion Repeated EA preconditioning stimulates the release of enkephalins, which may bind δ- and μ-opioid receptors to induce the tolerance against focal cerebral ischemia.

  16. Mechanism of functional recovery after repetitive transcranial magnetic stimulation (rTMS) in the subacute cerebral ischemic rat model: neural plasticity or anti-apoptosis?

    Science.gov (United States)

    Yoon, Kyung Jae; Lee, Yong-Taek; Han, Tai Ryoon

    2011-10-01

    Repetitive transcranial magnetic stimulation (rTMS) has been studied increasingly in recent years to determine whether it has a therapeutic benefit on recovery after stroke. However, the underlying mechanisms of rTMS in stroke recovery remain unclear. Here, we evaluated the effect of rTMS on functional recovery and its underlying mechanism by assessing proteins associated with neural plasticity and anti-apoptosis in the peri-lesional area using a subacute cerebral ischemic rat model. Twenty cerebral ischemic rats were randomly assigned to the rTMS or the sham group at post-op day 4. A total of 3,500 impulses with 10 Hz frequency were applied to ipsilesional cortex over a 2-week period. Functional outcome was measured before (post-op day 4) and after rTMS (post-op day 18). The rTMS group showed more functional improvement on the beam balance test and had stronger Bcl-2 and weaker Bax expression on immunohistochemistry compared with the sham group. The expression of NMDA and MAP-2 showed no significant difference between the two groups. These results suggest that rTMS in subacute cerebral ischemia has a therapeutic effect on functional recovery and is associated with an anti-apoptotic mechanism in the peri-ischemic area rather than with neural plasticity.

  17. Anti-apoptotic effects of recombinant human granulocyte colony-stimulating factor in focal cerebral ischemic rats

    Institute of Scientific and Technical Information of China (English)

    Xia Yuan; Shiming Zhang; Wanli Dong; Qi Fang

    2011-01-01

    The neuroprotective effects of granulocyte colony-stimulating factor in cerebral ischemia/reperfusion injury are currently contentious. The present study examined the effects of subcutaneous injection of recombinant human granulocyte colony-stimulating factor (50 μg/kg) over 5 days in a model of cerebral ischemia/reperfusion with intraluminal filament occlusion in rats. The results indicated that recombinant human granulocyte colony-stimulating factor reduced brain infarct volume following cerebral ischemia/reperfusion injury in rats, down-regulated the expression of caspase-3 mRNA (a key protease for apoptosis in the cerebral ischemia zone), lowered the rate of neuronal apoptosis in the cerebral ischemia zone, and notably ameliorated neurological function. These results indicate that recombinant human granulocyte colony-stimulating factor has anti-apoptotic effects on neurons following focal cerebral ischemia/reperfusion injury, and exerts neuroprotective effects.

  18. 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;

    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 re...

  19. Electroacupuncture pretreatment attenuates cerebral ischemic injury through α7 nicotinic acetylcholine receptor-mediated inhibition of high-mobility group box 1 release in rats

    Directory of Open Access Journals (Sweden)

    Wang Qiang

    2012-01-01

    Full Text Available Abstract Background We have previously reported that electroacupuncture (EA pretreatment induced tolerance against cerebral ischemic injury, but the mechanisms underlying this effect of EA are unknown. In this study, we assessed the effect of EA pretreatment on the expression of α7 nicotinic acetylcholine receptors (α7nAChR, using the ischemia-reperfusion model of focal cerebral ischemia in rats. Further, we investigated the role of high mobility group box 1 (HMGB1 in neuroprotection mediated by the α7nAChR and EA. Methods Rats were treated with EA at the acupoint "Baihui (GV 20" 24 h before focal cerebral ischemia which was induced for 120 min by middle cerebral artery occlusion. Neurobehavioral scores, infarction volumes, neuronal apoptosis, and HMGB1 levels were evaluated after reperfusion. The α7nAChR agonist PHA-543613 and the antagonist α-bungarotoxin (α-BGT were used to investigate the role of the α7nAChR in mediating neuroprotective effects. The roles of the α7nAChR and HMGB1 release in neuroprotection were further tested in neuronal cultures exposed to oxygen and glucose deprivation (OGD. Results Our results showed that the expression of α7nAChR was significantly decreased after reperfusion. EA pretreatment prevented the reduction in neuronal expression of α7nAChR after reperfusion in the ischemic penumbra. Pretreatment with PHA-543613 afforded neuroprotective effects against ischemic damage. Moreover, EA pretreatment reduced infarct volume, improved neurological outcome, inhibited neuronal apoptosis and HMGB1 release following reperfusion, and the beneficial effects were attenuated by α-BGT. The HMGB1 levels in plasma and the penumbral brain tissue were correlated with the number of apoptotic neurons in the ischemic penumbra. Furthermore, OGD in cultured neurons triggered HMGB1 release into the culture medium, and this effect was efficiently suppressed by PHA-543,613. Pretreatment with α-BGT reversed the inhibitory effect

  20. Effects of movement training on synaptic interface structure in the sensorimotor cortex and hippocampal CA3 area of the ischemic hemisphere in cerebral infarction rats

    Institute of Scientific and Technical Information of China (English)

    Min Yang; Jiyan Cheng

    2008-01-01

    BACKGROUND: Movement is an effective way to provide sensory, movement and reflectivity afferent stimulation to the central nervous system. Movement plays an important role in functional recombination and compensation in the brain. OBJECTIVE: To observe movement training effects on texture parameters of synaptic interfaces in the sensorimotor cortex and hippocampal CA3 area of the ischemic hemisphere and on motor function in cerebral infarction rats. DESIGN, TIME AND SETTING: This neural morphology and pathology randomized controlled animal experiment was performed at the Center Laboratory, Affiliated Hospital of Luzhou Medical College, China from November 2004 to April 2005. MATERIALS: A total of 32 healthy male Wistar rats aged 8 weeks were equally and randomly assigned into model and movement training groups. METHODS: Rat models of right middle cerebral artery occlusion were established using the suture occlusion method in both groups. Rats in the movement training group underwent balance training, screen training, and rotating rod training starting on day 5 after surgery, for 40 minutes every day, 6 days per week, for 4 weeks. MAIN OUTCOME MEASURES: Texture parameters of synaptic interfaces were determined using a transmission electron microscope and image analyzer during week 5 following model induction. The following parameters were measured: synaptic cleft width; postsynaptic density thickness; synaptic interface curvature; and active zone length. Motor function was assessed using balance training, screen training, and rotating rod training. The lower score indicated a better motor function. RESULTS: The postsynaptic density thickness, synaptic interface curvature, and active zone length were significantly increased in the sensorimotor cortex and hippocampal CA3 area of the ischemic hemisphere of rats from the movement training group compared with the model group (P < 0.05 or 0.01). Curved synapses and perforated synapses were seen in the sensorimotor cortex

  1. In vivo imaging of hemodynamics and oxygen metabolism in acute focal cerebral ischemic rats with laser speckle imaging and functional photoacoustic microscopy

    Science.gov (United States)

    Deng, Zilin; Wang, Zhen; Yang, Xiaoquan; Luo, Qingming; Gong, Hui

    2012-08-01

    Stroke is a devastating disease. The changes in cerebral hemodynamics and oxygen metabolism associated with stroke play an important role in pathophysiology study. But the changes were difficult to describe with a single imaging modality. Here the changes in cerebral blood flow (CBF), cerebral blood volume (CBV), and oxygen saturation (SO2) were yielded with laser speckle imaging (LSI) and photoacoustic microscopy (PAM) during and after 3-h acute focal ischemic rats. These hemodynamic measures were further synthesized to deduce the changes in oxygen extraction fraction (OEF). The results indicate that all the hemodynamics except CBV had rapid declines within 40-min occlusion of middle cerebral artery (MCAO). CBV in arteries and veins first increased to the maximum value of 112.42±36.69% and 130.58±31.01% by 15 min MCAO; then all the hemodynamics had a persistent reduction with small fluctuations during the ischemic. When ischemia lasted for 3 h, CBF in arteries, veins decreased to 17±14.65%, 24.52±20.66%, respectively, CBV dropped to 62±18.56% and 59±18.48%. And the absolute SO2 decreased by 40.52±22.42% and 54.24±11.77%. After 180-min MCAO, the changes in hemodynamics and oxygen metabolism were also quantified. The study suggested that combining LSI and PAM provides an attractive approach for stroke detection in small animal studies.

  2. Melatonin Counteracts at a Transcriptional Level the Inflammatory and Apoptotic Response Secondary to Ischemic Brain Injury Induced by Middle Cerebral Artery Blockade in Aging Rats.

    Science.gov (United States)

    Paredes, Sergio D; Rancan, Lisa; Kireev, Roman; González, Alberto; Louzao, Pedro; González, Pablo; Rodríguez-Bobada, Cruz; García, Cruz; Vara, Elena; Tresguerres, Jesús A F

    2015-01-01

    Aging increases oxidative stress and inflammation. Melatonin counteracts inflammation and apoptosis. This study investigated the possible protective effect of melatonin on the inflammatory and apoptotic response secondary to ischemia induced by blockade of the right middle cerebral artery (MCA) in aging male Wistar rats. Animals were subjected to MCA obstruction. After 24 h or 7 days of procedure, 14-month-old nontreated and treated rats with a daily dose of 10 mg/kg melatonin were sacrificed and right and left hippocampus and cortex were collected. Rats aged 2 and 6 months, respectively, were subjected to the same brain injury protocol, but they were not treated with melatonin. mRNA expression of interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), Bcl-2-associated death promoter (BAD), Bcl-2-associated X protein (BAX), glial fibrillary acidic protein (GFAP), B-cell lymphoma 2 (Bcl-2), and sirtuin 1 was measured by reverse transcription-polymerase chain reaction. In nontreated animals, a significant time-dependent increase in IL-1β, TNF-α, BAD, and BAX was observed in the ischemic area of both hippocampus and cortex, and to a lesser extent in the contralateral hemisphere. Hippocampal GFAP was also significantly elevated, while Bcl-2 and sirtuin 1 decreased significantly in response to ischemia. Aging aggravated these changes. Melatonin administration was able to reverse significantly these alterations. In conclusion, melatonin may ameliorate the age-dependent inflammatory and apoptotic response secondary to ischemic cerebral injury.

  3. Effect of electroacupuncture on synaptic transmission in dentate gyrus of the hippocampus in cerebral ischemic injured rats

    Institute of Scientific and Technical Information of China (English)

    Haibo Yu; Zhuoxin Yang; Ling Wang; Min Pi; Jiawei Zhang

    2006-01-01

    BACKGROUND: Some studies suggest that the long-term potentiation (LTP) of synaptic transmission may be the basis for the neural synaptic plasticity of hippocampus, but can be evoked by various factors including electroacupuncture.OBJECTIVE: To observe the effect of electroacupuncture on the activities of basic synaptic transmission in dentate gyrus of hippocampus and the changes of high frequency stimulation (HFS) induced activity of synaptic transmission in cerebral ischemic injured rats.DESIGN: A randomized control trial.SETTING: Shenzhen Hospital of Traditional Chinese Medicine affiliated to Guangzhou University of Traditional Chinese Medicine.MATERIALS: Sixty healthy male Wistar rats, weighing 150-250 g, were provided by the Experimental Animal Center of Guangzhou University of Traditional Chinese Medicine. The experiment began after adaptation of environment for 1 week under standard experimental environment. The main experimental instruments included the programming electrical acupuncture apparatus (PCEA, product of the Institute of Acupuncture and Meridians, Anhui College of Traditional Chinese Medicine) and multichannel physiologic recorder (RM-86, Nihon Konden).METHODS: The experiment was carried out in Guangzhou University of Traditional Chinese Medicine between July 2003 and July 2004. ① Embedding of brain electrodes: In reference of the Pellegrino's rat brain atlas, the bipolar electrode stimulator was embedded into the perforant path (PP) anterior to the entorhinal area with location coordinates of AP 7.5 mm, L 4.2 mm and H 3.0 mm, that is, 7.5 mm posterior to the anterior fontanelle, 4.2 mm laterally on the right side and 3.0 mm under the subcortex. The subcortex recorder electrode coordinates are AP 3.8 mm, L 2.5 mm and H 3.5 mm, located in the granular cell layer of the unilateral dentate gyrus (DG) of hippocampus, at the site of which an opening with the diameter of 1.5 mm was drilled for the purpose of embedding of the stimulating and recording

  4. Ischemia preconditioning is neuroprotective in a rat cerebral ischemic injury model through autophagy activation and apoptosis inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Xia, D.Y. [Department of Neurology, Navy General Hospital of PLA, Beijing (China); Li, W. [General Hospital of Shenyang Military Command, Department of Neurology, Shenyang, China, Department of Neurology, General Hospital of Shenyang Military Command, Shenyang (China); Qian, H.R.; Yao, S.; Liu, J.G.; Qi, X.K. [Department of Neurology, Navy General Hospital of PLA, Beijing (China)

    2013-08-10

    Sublethal ischemic preconditioning (IPC) is a powerful inducer of ischemic brain tolerance. However, its underlying mechanisms are still not well understood. In this study, we chose four different IPC paradigms, namely 5 min (5 min duration), 5×5 min (5 min duration, 2 episodes, 15-min interval), 5×5×5 min (5 min duration, 3 episodes, 15-min intervals), and 15 min (15 min duration), and demonstrated that three episodes of 5 min IPC activated autophagy to the greatest extent 24 h after IPC, as evidenced by Beclin expression and LC3-I/II conversion. Autophagic activation was mediated by the tuberous sclerosis type 1 (TSC1)-mTor signal pathway as IPC increased TSC1 but decreased mTor phosphorylation. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and hematoxylin and eosin staining confirmed that IPC protected against cerebral ischemic/reperfusion (I/R) injury. Critically, 3-methyladenine, an inhibitor of autophagy, abolished the neuroprotection of IPC and, by contrast, rapamycin, an autophagy inducer, potentiated it. Cleaved caspase-3 expression, neurological scores, and infarct volume in different groups further confirmed the protection of IPC against I/R injury. Taken together, our data indicate that autophagy activation might underlie the protection of IPC against ischemic injury by inhibiting apoptosis.

  5. Ischemia preconditioning is neuroprotective in a rat cerebral ischemic injury model through autophagy activation and apoptosis inhibition

    Directory of Open Access Journals (Sweden)

    D.Y. Xia

    2013-08-01

    Full Text Available Sublethal ischemic preconditioning (IPC is a powerful inducer of ischemic brain tolerance. However, its underlying mechanisms are still not well understood. In this study, we chose four different IPC paradigms, namely 5 min (5 min duration, 5×5 min (5 min duration, 2 episodes, 15-min interval, 5×5×5 min (5 min duration, 3 episodes, 15-min intervals, and 15 min (15 min duration, and demonstrated that three episodes of 5 min IPC activated autophagy to the greatest extent 24 h after IPC, as evidenced by Beclin expression and LC3-I/II conversion. Autophagic activation was mediated by the tuberous sclerosis type 1 (TSC1-mTor signal pathway as IPC increased TSC1 but decreased mTor phosphorylation. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL and hematoxylin and eosin staining confirmed that IPC protected against cerebral ischemic/reperfusion (I/R injury. Critically, 3-methyladenine, an inhibitor of autophagy, abolished the neuroprotection of IPC and, by contrast, rapamycin, an autophagy inducer, potentiated it. Cleaved caspase-3 expression, neurological scores, and infarct volume in different groups further confirmed the protection of IPC against I/R injury. Taken together, our data indicate that autophagy activation might underlie the protection of IPC against ischemic injury by inhibiting apoptosis.

  6. Rehabilitation Training and Resveratrol Improve the Recovery of Neurological and Motor Function in Rats after Cerebral Ischemic Injury through the Sirt1 Signaling Pathway

    Science.gov (United States)

    Shi, Na; Zhu, Chongtian

    2016-01-01

    This study was conducted to investigate the recovery of motor function in rats through the silent information regulator factor 2-related enzyme 1 (Sirt1) signal pathway-mediated rehabilitation training. Middle cerebral artery occlusion (MACO) was used to induce ischemia/reperfusion injury. The rats were subjected to no treatment (model), rehabilitation training (for 21 days), resveratrol (5 mg/kg for 21 days), and rehabilitation training plus resveratrol treatment. 24 h later, They were assessed for neurobehavioral score and motor behavior score and expression of brain derived-nerve neurotrophic factor (BDNF) and tyrosine kinase receptor B (TrkB). Compared with sham group, models had significantly higher neurobehavioral scores, balance beam, and rotary stick scores. Compared with the model group, rats in rehabilitation training and resveratrol groups had significantly reduced scores. Compared with rehabilitation training or resveratrol treatment alone, rehabilitation plus resveratrol further reduced the scores significantly. The percentage of cells expressing BDNF and TrkB and expression levels of BDNF and TrkB were similar between the model and sham groups, significantly increased in rehabilitation training and resveratrol groups, and further increased in rehabilitation training plus resveratrol group. These results indicate that rehabilitation raining plus resveratrol can significantly improve the recovery of motor function in rats after cerebral ischemic injury, which is likely related to the upregulation of the BDNF/TrkB signaling pathway. PMID:28116292

  7. Rehabilitation Training and Resveratrol Improve the Recovery of Neurological and Motor Function in Rats after Cerebral Ischemic Injury through the Sirt1 Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Na Shi

    2016-01-01

    Full Text Available This study was conducted to investigate the recovery of motor function in rats through the silent information regulator factor 2-related enzyme 1 (Sirt1 signal pathway-mediated rehabilitation training. Middle cerebral artery occlusion (MACO was used to induce ischemia/reperfusion injury. The rats were subjected to no treatment (model, rehabilitation training (for 21 days, resveratrol (5 mg/kg for 21 days, and rehabilitation training plus resveratrol treatment. 24 h later, They were assessed for neurobehavioral score and motor behavior score and expression of brain derived-nerve neurotrophic factor (BDNF and tyrosine kinase receptor B (TrkB. Compared with sham group, models had significantly higher neurobehavioral scores, balance beam, and rotary stick scores. Compared with the model group, rats in rehabilitation training and resveratrol groups had significantly reduced scores. Compared with rehabilitation training or resveratrol treatment alone, rehabilitation plus resveratrol further reduced the scores significantly. The percentage of cells expressing BDNF and TrkB and expression levels of BDNF and TrkB were similar between the model and sham groups, significantly increased in rehabilitation training and resveratrol groups, and further increased in rehabilitation training plus resveratrol group. These results indicate that rehabilitation raining plus resveratrol can significantly improve the recovery of motor function in rats after cerebral ischemic injury, which is likely related to the upregulation of the BDNF/TrkB signaling pathway.

  8. Activation of peroxisome proliferator-activated receptor β/δ attenuates acute ischemic stroke on middle cerebral ischemia occlusion in rats.

    Science.gov (United States)

    Chao, Xiaodong; Xiong, Chunlei; Dong, Weifeng; Qu, Yan; Ning, Weidong; Liu, Wei; Han, Feng; Ma, Yijie; Wang, Rencong; Fei, Zhou; Han, Hua

    2014-07-01

    Peroxisome proliferator-activated receptor (PPAR)-β/δ is a transcription factor that belongs to the nuclear hormone receptor family. There is little information about the effects of the immediate administration of specific ligands of PPAR-β/δ (GW0742) in animal models of acute ischemic stroke. Using a rat model of middle cerebral ischemia occlusion (MCAO) in vivo, we have investigated the effect of pretreatment with GW0742 before MCAO. The neuroprotective effect of GW0742 against acute ischemic stroke was evaluated by the neurologic deficit score (NDS), dry-wet weight, and 2,3,5-triphenyltetrazolium chloride staining. The levels of interleukin (IL)-1β, nuclear factor (NF)-κB, and tumor necrosis factor (TNF)-α were detected by an enzyme-linked immunosorbent assay. The expressions of inducible nitric oxide synthase (iNOS), Bax, and Bcl-2 were detected by Western blot. The apoptotic cells were counted by in situ terminal deoxyribonucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling assay. The pretreatment with GW0742 significantly increased the expression of Bcl-2, and significantly decreased in the volume of infarction, NDS, edema, expressions of IL-1β, NF-κB, TNFα, and Bax, contents of iNOS and the apoptotic cells in infarct cerebral hemisphere compared with rats in the vehicle group at 24 hours after MCAO. The study suggests the neuroprotective effect of the PPAR-β/δ ligand GW0742 in acute ischemic stroke by a mechanism that may involve its anti-inflammatory and antiapoptotic action. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

  9. Amelioration of cognitive, motor and endogenous defense functions with silymarin, piracetam and protocatechuic acid in the cerebral global ischemic rat model.

    Science.gov (United States)

    Muley, Milind M; Thakare, Vishnu N; Patil, Rajesh R; Bafna, Pallavi A; Naik, Suresh R

    2013-07-19

    The neuroprotective activities of silymarin, piracetam and protocatechuic acid ethyl ester (PCA) on cerebral global ischemic/reperfusion were evaluated in a rat model. A midline ventral incision was made in the throat region. The right and left common carotid arteries were located and a bilateral common carotid artery occlusion (BCCAO) was performed for 30min using atraumatic clamps followed by a 24h period of reperfusion. Neurological/behavioral functions (cognitive and motor), endogenous defense systems (lipid peroxidation, glutathione, catalase, and superoxide dismutase), reduced water content and infarct size and histopathological alterations were then studied. Silymarin and PCA treatments significantly improved cognitive, motor and endogenous defense functions, histopathological alterations, and, reduced both water content and infarct size compared to the vehicle-treated ischemic control group. Piracetam treatment improved neurological and histopathological alterations, reduced water content and infarct size, but failed to restore/prevent the impaired endogenous defense functions significantly. Silymarin showed better neuroprotection than piracetam and PCA in experimentally induced global ischemic/reperfusion and was able to facilitate mnemonic performance. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Therapeutic time window of hypothermia is broader than cerebral artery flushing in carotid saline infusion after transient focal ischemic stroke in rats.

    Science.gov (United States)

    Ji, Yabin; Hu, Yafang; Wu, Yongming; Ji, Zhong; Song, Wei; Wang, Shengnan; Pan, Suyue

    2012-09-01

    Intracarotid cold saline infusion (ICSI) protects against ischemic stroke not only due to the resulting hypothermia, but also as a result of the cerebral artery flushing. To assess the relative benefit of hypothermia and cerebral artery flushing in neuroprotection, hypothermic and normothermic saline infusions were administrated over a serial time points after the initiation of reperfusion in a rat ischemia model. Ischemic strokes were induced in Sprague-Dawley rats (n = 115) by occluding the middle cerebral artery for 2 hours using an intraluminal filament. In the hypothermic groups, the brain temperature was lowered to 33-34°C for 20 minutes by ICSI at three time points (0, 1, and 2 hours) after reperfusion. Correspondingly, in the normothermic groups, the brain temperature was maintained at normal levels during intracarotid normothermic saline infusion (INSI) for 20 minutes at the same time points. After 48-hour reperfusion, infarct sizes and brain water contents were determined using 2,3,5-triphenyltetrazolium chloride (TTC) staining and the dry-wet weight method, respectively. Levels of neuron-specific enolase (NSE), S100beta, and matrix metalloproteinase 9 (MMP9) in the serum were measured by enzyme-linked immunoassay (ELISA). Neurological deficits were also evaluated. Immediate infusion after the onset of reperfusion (0 hour) did not result in significant difference for reductions of infarct sizes, neurological deficits or S100beta serum levels between ICSI and INSI groups, compared with the non-infusion group. However, brain water content and NSE serum level were significantly lower in the ICSI group than the non-infusion group. When the infusions were started 1 hour after reperfusion, both ICSI and INSI infusions still reduced the infarct sizes, but only ICSI significantly decreased the brain water content, neurological deficits and S100beta serum level. All therapeutic effects of INSI disappeared when infusions were started 2 hours after reperfusion

  11. Role of Centella asiatica on cerebral post-ischemic reperfusion and long-term hypoperfusion in rats

    Directory of Open Access Journals (Sweden)

    Raghavendra M

    2009-01-01

    Full Text Available Centella asiatica (CA, a well known adaptogenic agent in Indian system of Medicine (Ayurveda, is believed to have beneficial effects in improving memory, treating anxiety and eczema. It also possesses antioxidant, cognitive enhancing and antiepileptic properties. Acute ischemia followed by reperfusion is known to bring about biochemical and histopathological alterations. In the present study the effect of Centella asiatica on acute cerebral reperfusion and long-term cerebral hypoperfusion in rats was investigated. Transient cerebral ischemia was induced under Ketamine anaesthesia by blocking bilateral common carotid arteries (BCCAO for 30 min and then reperfusion was allowed for 45 min by releasing the block. Lipid peroxidation, superoxide dismutase (SOD and brain protein were estimated, behavioral and histopathological studies were done for both acute ischemia-reperfusion and chronic hypoperfusion studies. One way ANOVA followed by post hoc Tukey test was used. In the present study, acute ischemia-reperfusion induced increases in lipid peroxidation and superoxide SOD activity. CA pre-treatment (100 mg/kg p.o. for 5 days attenuated the reperfusion induced biochemical alterations. Long-term cerebral hypoperfusion in rats caused a propensity towards anxiety and listlessness (open field paradigm and elevated plus maze test accompanied by deficits in learning and memory (Morris′ water maze testing and tendency towards depression (Porsolts swim test. Additionally, histopathological observations in forebrain revealed changes like gliosis, astrocytosis, cellular edema and inflammatory changes. CA treatment (100 mg/kg p.o. for 28 days alleviated these behavioral, cognitive and histopathological changes. The results suggest that CA may be useful in cerebrovascular insufficiency conditions.

  12. The time course changes in expression of aquaporin 4 and aquaporin 1 following global cerebral ischemic edema in rat

    OpenAIRE

    Gürsoy- Özdemir, Yasemin; Akdemir, G.; Kaymaz, F,; Akalan, N,; Akdemir, E.S.

    2016-01-01

    Background: The aim of this global cerebral ischemia study was to study the changes in expression levels of aquaporin 4 (AQP4) and AQP1 over time. Methods: Sprague-Dawley type male rats were divided into six groups. Sham group and ischemia/reperfusion were performed on five other groups using the four-vessel occlusion model. Reperfusion was done 30 min after the occlusion, and each group was tested at 1, 6, 12, 24, and 48 h for brain wet-dry weight ratio and AQP4 and AQP1 expression levels us...

  13. The expression of angiotensin-converting enzyme 2-angiotensin-(1-7)-Mas receptor axis are upregulated after acute cerebral ischemic stroke in rats.

    Science.gov (United States)

    Lu, Jie; Jiang, Teng; Wu, Liang; Gao, Li; Wang, Yao; Zhou, Feng; Zhang, Shugang; Zhang, Yingdong

    2013-10-01

    There is now unequivocal evidence that the angiotensin-converting enzyme 2(ACE2)-Ang-(1-7)-Mas axis is a key component of the renin-angiotensin system (RAS) cascade, which is closely correlated with ischemic insult occurrence. Our previous studies demonstrated that the Ang-(1-7), was an active member of the brain RAS. However, the ACE2-Ang-(1-7)-Mas axis expression after cerebral ischemic injury are currently unclear. In the present study, we investigated the time course of ACE2-Ang-(1-7) and Mas receptor expression in the acute stage of cerebral ischemic stroke. The content of Ang-(1-7) in ischemic tissues and blood serum was measured by specific EIA kits. Real-time PCR and western blot were used to determine messenger RNA (mRNA) and protein levels of the ACE2 and Mas. The cerebral ischemic lesion resulted in a significant increase of regional cerebral and circulating Ang-(1-7) at 6-48 h compared with sham operation group following focal ischemic stroke (12h: 7.276±0.320 ng/ml vs. 2.466±0.410 ng/ml, serum; 1.024±0.056 ng/mg vs. 0.499±0.032, brain) (PMas expression were markedly enhanced compared to the control in the ischemic tissues (PMas immunopositive neurons were also seen stronger expression in the ischemic cortex (19.167±2.858 vs. 7.833±2.483) (PMas axis are upregulated after acute ischemic stroke and would play a pivotal role in the regulation of acute neuron injury in ischemic cerebrovascular diseases. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  14. Gene interference regulates aquaporin-4 expression in swollen tissue of rats with cerebral ischemic edema: Correlation with variation in apparent diffusion coefficient.

    Science.gov (United States)

    Hu, Hui; Lu, Hong; He, Zhanping; Han, Xiangjun; Chen, Jing; Tu, Rong

    2012-07-25

    To investigate the effects of mRNA interference on aquaporin-4 expression in swollen tissue of rats with ischemic cerebral edema, and diagnose the significance of diffusion-weighted MRI, we injected 5 μL shRNA- aquaporin-4 (control group) or siRNA- aquaporin-4 solution (1:800) (RNA interference group) into the rat right basal ganglia immediately before occlusion of the middle cerebral artery. At 0.25 hours after occlusion of the middle cerebral artery, diffusion-weighted MRI displayed a high signal; within 2 hours, the relative apparent diffusion coefficient decreased markedly, aquaporin-4 expression increased rapidly, and intracellular edema was obviously aggravated; at 4 and 6 hours, the relative apparent diffusion coefficient slowly returned to control levels, aquaporin-4 expression slightly increased, and angioedema was observed. In the RNA interference group, during 0.25-6 hours after injection of siRNA- aquaporin-4 solution, the relative apparent diffusion coefficient slightly fluctuated and aquaporin-4 expression was upregulated; during 0.5-4 hours, the relative apparent diffusion coefficient was significantly higher, while aquaporin-4 expression was significantly lower when compared with the control group, and intracellular edema was markedly reduced; at 0.25 and 6 hours, the relative apparent diffusion coefficient and aquaporin-4 expression were similar when compared with the control group; obvious angioedema remained at 6 hours. Pearson's correlation test results showed that aquaporin-4 expression was negatively correlated with the apparent diffusion coefficient (r = -0.806, P coefficient. Aquaporin-4 gene interference can effectively inhibit the upregulation of aquaporin-4 expression during the stage of intracellular edema with time-effectiveness. Moreover, diffusion-weighted MRI can accurately detect intracellular edema.

  15. Gene interference regulates aquaporin-4 expression in swollen tissue of rats with cerebral ischemic edema Correlation with variation in apparent diffusion coefficient

    Institute of Scientific and Technical Information of China (English)

    Hui Hu; Hong Lu; Zhanping He; Xiangjun Han; Jing Chen; Rong Tu

    2012-01-01

    To investigate the effects of mRNA interference on aquaporin-4 expression in swollen tissue of rats with ischemic cerebral edema, and diagnose the significance of diffusion-weighted MRI, we injected 5 μL shRNA- aquaporin-4 (control group) or siRNA- aquaporin-4 solution (1:800) (RNA interference group) into the rat right basal ganglia immediately before occlusion of the middle cerebral artery. At 0.25 hours after occlusion of the middle cerebral artery, diffusion-weighted MRI displayed a high signal; within 2 hours, the relative apparent diffusion coefficient decreased markedly, aquaporin-4 expression increased rapidly, and intracellular edema was obviously aggravated; at 4 and 6 hours, the relative apparent diffusion coefficient slowly returned to control levels, aquaporin-4 expression slightly increased, and angioedema was observed. In the RNA interference group, during 0.25- 6 hours after injection of siRNA- aquaporin-4 solution, the relative apparent diffusion coefficient slightly fluctuated and aquaporin-4 expression was upregulated; during 0.5-4 hours, the relative apparent diffusion coefficient was significantly higher, while aquaporin-4 expression was significantly lower when compared with the control group, and intracellular edema was markedly reduced; at 0.25 and 6 hours, the relative apparent diffusion coefficient and aquaporin-4 expression were similar when compared with the control group; obvious angioedema remained at 6 hours. Pearson's correlation test results showed that aquaporin-4 expression was negatively correlated with the apparent diffusion coefficient (r = -0.806, P < 0.01). These findings suggest that upregulated aquaporin-4 expression is likely to be the main molecular mechanism of intracellular edema and may be the molecular basis for decreased relative apparent diffusion coefficient. Aquaporin-4 gene interference can effectively inhibit the upregulation of aquaporin-4 expression during the stage of intracellular edema with time

  16. Immune mechanisms in cerebral ischemic tolerance

    Directory of Open Access Journals (Sweden)

    Lidia eGarcia-Bonilla

    2014-03-01

    Full Text Available Stressor-induced tolerance is a central mechanism in the response of bacteria, plants, and animals to potentially harmful environmental challenges. This response is characterized by immediate changes in cellular metabolism and by the delayed transcriptional activation or inhibition of genetic programs that are not generally stressor specific (cross-tolerance. These programs are aimed at countering the deleterious effects of the stressor. While induction of this response (preconditioning can be established at the cellular level, activation of systemic networks is essential for the protection to occur throughout the organs of the body. This is best signified by the phenomenon of remote ischemic preconditioning, whereby application of ischemic stress to one tissue or organ induces ischemic tolerance in remote organs through humoral, cellular and neural signaling. The immune system is an essential component in cerebral ischemic tolerance acting simultaneously both as mediator and target. This dichotomy is based on the fact that activation of inflammatory pathways is necessary to establish ischemic tolerance and that ischemic tolerance can be, in part, attributed to a subdued immune activation after index ischemia. Here we describe the components of the immune system required for induction of ischemic tolerance and review the mechanisms by which a reprogrammed immune response contributes to the neuroprotection observed after preconditioning. Learning how local and systemic immune factors participate in endogenous neuroprotection could lead to the development of new stroke therapies.

  17. Interventional effect of laser acupoint radiation on the expression of Nissl body and brain-derived neurotrophic factor in newborn rat models with ischemic/hypoxic cerebral injury

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND:Some researches report that He-Ne laser can activate function of erythrocytes and increase content of blood and oxygen via bio-stimulating effect;therefore,it suspects that laser radiation at Baihui and Dazhui can partially increase blood circulation for oxygen-supplying content of brain and improve functional status of neurons.OBJECTIVE:To verify the effects of laser radiation at Baihui and Dazhui on the expression of Nissl body of brain tissue neurons and brain-derived neurotrophic factor (BDNF) in newborn rats with ischemic/hypoxic cerebral injury.DESIGN:Randomized controlled animal study.SETTING:Department of Neurological Histochemistry,Xianning University.MATERIALS:Forty Wistar rats of 7 - 8 days old,weighing 15 - 20 g and of both genders,were selected from Wuhan Experimental Animal Center.All the rats were randomly divided into sham operation group (n =8),model group (n =16) and radiation group (n =16).The experimental animals were disposed according to ethical criteria.BDNF kit was provided by Wuhan Boster Bioengineering Co.,Ltd.METHODS:The experiment was carried out in the Department of Neurological Histochemistry,Xianning University from April 2005 to October 2006.Rats in the radiation group and model group were performed with ligation of left common carotid artery,recovered at room temperature for 1-6 days,maintained in self-made hypoxic cabin under normal pressure and injected mixture gas (0.05 volume fraction of O2 and 0.92 volume fraction of N2) for 2 hours.In addition,rats in the sham operation group were treated with separation of left common carotid artery but not ligation and hypoxia.Rats in the model group were not given any treatment;while,rats in the radiation group were exposed with He-Ne laser of 63.28 nm in the wave length at Baihui and Dazhui acupoints on the second day after ischemia-hypoxia.The radiation was given for 10 minutes per day and once a day.Ten days were regarded as a course and the rats were exposed for 2 courses in

  18. Sulforaphane improves outcomes and slows cerebral ischemic/reperfusion injury via inhibition of NLRP3 inflammasome activation in rats.

    Science.gov (United States)

    Yu, Chang; He, Qi; Zheng, Jing; Li, Ling Yu; Hou, Yang Hao; Song, Fang Zhou

    2017-04-01

    Ischemia/reperfusion (I/R) injury has been correlated with systemic inflammatory response. In addition, NLRP3 has been suggested as a cause in many inflammatory processes. Sulforaphane (SFN) is a naturally occurring isothiocyanate found in cruciferous vegetables, such as broccoli and cabbage. While recent studies have demonstrated that Sulforaphane has protective effects against cerebral ischemia/reperfusion injury, little is known about how those protective effects work. In this study, we focus our investigation on the role and process of Sulforaphane in the inhibition of NLRP3 inflammasome activation, as well as its effect on brain ischemia/reperfusion injury. Adult male Sprague-Dawley rats were injected with Sulforaphane (5 or 10mg/kg) intraperitoneally at the beginning of reperfusion, after a 60min period of occlusion. A neurological score and infarct volume were assessed at 24h after the administration of Sulforaphane. Myeloperoxidase (MPO) activity was measured at 24h to assess neutrophil infiltration in brain tissue. ELISA, RT-PCR and Western blot analyses were used to measure any inflammatory reaction. Sulforaphane treatment significantly reduced infarct volume and improved neurological scores when compared to a vehicle-treated group. Neutrophil infiltration was significantly higher in the vehicle-treated group than in the Sulforaphane treatment group. Sulforaphane treatment inhibits NLRP3 inflammasome activation and the downregulation of cleaved caspase-1, while reducing IL-1β and IL-18 expression. The inhibition of inflammatory response with Sulforaphane treatment improves outcomes after focal cerebral ischemia. This neuroprotective effect is likely exerted by Sulforaphane inhibited NLRP3 inflammasome activation caused by the downregulation of NLRP3, the induction of cleaved caspase-1, and thus the reduction of IL-1β and IL-18. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Effect of the antibody of brain-derived neurotrophic factor on the rat with ischemic injury from obstruction of middle cerebral artery%脑源性神经营养因子抗体对大脑中动脉阻塞大鼠缺血损伤的影响

    Institute of Scientific and Technical Information of China (English)

    陈英辉; 王根发; 陈兴华; 姚革; 陈伟; 周永炜

    2003-01-01

    AIM:To observe the effect of the antibody of brain derived neurotrophic factor(BDNF) by cortical microinjection on hippocampal ischemic injury rats.METHODS:Preparation of local cerebral ischemic reperfusion injury model: cortical stereostaxic approach, microinjection of BDNF antibody. Applied immunohistochemical method to observe distribution of BDNF in cortex after injection of the antibody,to observe the alteration of ischemic injury between control group and BDNF antibody group.RESULT: The volume of cerebral infarction in BDNF antibody group was larger than control group.CONCLUSION: BDNF has protection function for cerebral ischemia.

  20. Effects of combined ischemic postconditioning, remote ischemic postconditioning and naloxone postconditioning on focal cerebral ischemia-reperfusion injury in rats%联合应用缺血后处理、远隔缺血后处理和纳洛酮后处理对大鼠脑缺血-再灌注损伤的影响

    Institute of Scientific and Technical Information of China (English)

    刘毅; 廖旭; 薛富善; 许亚超; 熊军; 袁玉静; 王强; 刘建华; 赵嘉训

    2011-01-01

    Objective To assess the effects of ischemic postconditioning, remote ischemic postconditioning and naloxone postconditioning on focal cerebral ischemia-reperfusion injury in rats.Methods A total of 110 adult SD rats were randomly divided into 5 groups (n =22 each). The focal cerebral ischemia-reperfusion injury was induced by a 90-minute occlusion of right middle cerebral artery (MCA) and a 24-hour reperfusion sequentially. Group 1 was of ischemia-reperfusion control; Group 2 ischemic postconditioning induced by three 30-second cycles of MCA occlusion followed by a 30-second reperfusion; Group 3 remote ischemic postconditioning performed via a transient occlusion of right femoralartery at 5 min before the initiatlon of reperfusion:Group 4 naloxone posteonditioning with naloxone 10 mg/kg intraperitoneaUy injected at the initiation of reperfusion;Group 5 combined ischemic,remote ischernic & naloxone postconditioning performed simultaneously in accordance with the methods used in Groups 2,3 & 4.The neumlogie deftcit scores(NDS)were obtained at 2 h & 24 h post-reperfusion.At 24 h post-reperfusion.the anesthetized rat was sacrificed by decapitation and the brain rapidly extracted to asseSS the size ofcerebral infaret(n=10),detect the cerebral expression of microtubule-associated protein2(MAP2)(n=6),measure the plasma volume of cerebral tissues and quantify the diameter and segment artery at 5 min before the initiation of reperfusion; Group 4 naloxone postconditioning with naloxone 10 mg/kg intraperitoneally injected at the initiation of reperfusion; Group 5 combined ischemic, remote ischemic & naloxone postconditioning performed simultaneously in accordance with the methods used in Groups 2, 3 & 4. The neurologic deficit scores ( NDS) were obtained at 2 h & 24 h post-reperfusion. At 24 h post-reperfusion, the anesthetized rat was sacrificed by decapitation and the brain rapidly extracted to assess the size of cerebral infarct (n = 10), detect the cerebral expression of

  1. Cerebral perfusion SPECT in transient ischemic attack

    Energy Technology Data Exchange (ETDEWEB)

    You, D.-L. E-mail: dlyou@mail.kfcc.org.tw; Shieh, F.-Y.; Tzen, K.-Y.; Tsai, M.-F.; Kao, P.-F

    2000-04-01

    Purpose: The purpose of our study is to evaluate the efficacy of cerebral perfusion single photon emission computerized tomography (SPECT) in patients with transient ischemic attack (TIA). Methods: Thirty-seven patients with TIA were collected for study. All patients had transient focal neurological symptoms or signs with complete recovery within 24 h after onset. The patients underwent cerebral perfusion SPECT between 6 h and 11 days after onset, with 10 cases performed within 24 h (group A), nine cases performed between 1 and 3 days (group B), 11 cases performed between 3 and 5 days (group C), and seven cases performed after more than 5 days (group D). A semi-quantitative method was used for analyzing the SPECT data, and the difference ratios between lesion side and contralateral normal side were calculated on each pair of regions of interest. Results: In total, 78.4% (29/37) of patients had reduced perfusion in the cerebral cortical regions or deep nuclei, and the regions with reduced perfusion corresponded with clinical presentations of the patients. The abnormal rate with reduced perfusion was 90.0% in group A, 77.8% in group B, 72.7% in group C and 71.4% in group D. Cross cerebellar diaschisis (CCD) was present in seven patients, and all of the primary cerebral perfusion defects of these patients were located at the territory of left or right middle cerebral artery. Conclusion: Cerebral perfusion SPECT is a potential tool to detect cerebral perfusion defects and CCD in patients with TIA. Although the perfusion defect may persist more than 5 days after onset, we suggest cerebral perfusion SPECT should be performed as soon as possible.

  2. [Cerebral infarction and transient ischemic attack].

    Science.gov (United States)

    Sahara, Noriyuki; Kuwashiro, Takahiro; Okada, Yasushi

    2016-04-01

    Japanese Guidelines for the Management of Stroke 2015 was published. Here, we describe several points revised from the 2009 edition about "Cerebral infarction and transient ischemic attack (TIA)". The revision points are as follows; 1. Extension of possible time window of intravenous recombinant tissue-plasminogen activator treatment (from within 3 hours to within 4.5 hours); 2. Antiplatelet therapy in acute stage (dual antiplatelet therapy (DAPT) for non-cardioembolic ischemic stroke or TIA); 3. Endovascular recanalization therapy in acute stage; 4. Antiplatelet therapy in chronic stage (Cilostazol is recommended similar to aspirin or clopidogrel); 5. Non-vitamin K antagonist oral anticoagulants (NOACs) for non-valvular atrial fibrillation (NVAF) stroke or TIA patients; 6. Management of TIA. We explain the revised points of the guideline in the text.

  3. Influence of remote ischemic preconditioning on cerebral oxygen metabolism and cerebral blood flow indexes of patients with ischemic cerebrovascular disease

    Institute of Scientific and Technical Information of China (English)

    Hui Lu; Ning-Ning Cui; Bin-Cheng Wang

    2016-01-01

    Objective:To study the influence of remote ischemic preconditioning on cerebral oxygen metabolism and cerebral blood flow indexes of patients with ischemic cerebrovascular disease. Methods:A total of 58 patients with ischemic cerebrovascular disease in our hospital from April 2015 to January 2016 were selected as the study object, and 58 patients were randomly divided into two groups, 29 patients in control group were treated with routine treatment, 29 patients in observation group were treated with remote ischemic preconditioning on the basic treatment of control group, then the cerebral oxygen metabolism and cerebral blood flow indexes of two groups before the treatment and at first, third and sixth month after the treatment were respectively detected and compared.Results:The cerebral oxygen metabolism and cerebral blood flow indexes of two groups before the treatment all showed no significant differences (allP>0.05), while the cerebral oxygen metabolism and cerebral blood flow indexes of observation group at first, third and sixth month after the treatment were all significantly better than those before the treatment, and the results were all significantly better than those of control group at the same time too (allP>0.05).Conclusions: The influence of remote ischemic preconditioning on cerebral oxygen metabolism and cerebral blood flow indexes of patients with ischemic cerebrovascular disease are better, and its application value for the patients with ischemic cerebrovascular disease is higher.

  4. Reduction of mitochondrial electron transport complex activity is restricted to the ischemic focus after transient focal cerebral ischemia in rats

    DEFF Research Database (Denmark)

    Christensen, Thomas; Diemer, Nils Henrik

    2003-01-01

    in the ipsilateral cortex and caudate putamen were measured by densitometric image analysis. Reductions in complex I, II, and IV activity were restricted to areas in the ischemic foci in cortex and caudate putamen, which microscopically displayed signs of early morphological damage. In cortex, the tissue volume...

  5. The Effects of Different Repetitive Transcranial Magnetic Stimulation (rTMS) Protocols on Cortical Gene Expression in a Rat Model of Cerebral Ischemic-Reperfusion Injury.

    Science.gov (United States)

    Ljubisavljevic, Milos R; Javid, Asma; Oommen, Joji; Parekh, Khatija; Nagelkerke, Nico; Shehab, Safa; Adrian, Thomas E

    2015-01-01

    Although repetitive Transcranial Magnetic Stimulation (rTMS) in treatment of stroke in humans has been explored over the past decade the data remain controversial in terms of optimal stimulation parameters and the mechanisms of rTMS long-term effects. This study aimed to explore the potential of different rTMS protocols to induce changes in gene expression in rat cortices after acute ischemic-reperfusion brain injury. The stroke was induced by middle cerebral artery occlusion (MCAO) with subsequent reperfusion. Changes in the expression of 96 genes were examined using low-density expression arrays after MCAO alone and after MCAO combined with 1Hz, 5Hz, continuous (cTBS) and intermittent (iTBS) theta-burst rTMS. rTMS over the lesioned hemisphere was given for two weeks (with a 2-day pause) in a single daily session and a total of 2400 pulses. MCAO alone induced significant upregulation in the expression of 44 genes and downregulation in 10. Two weeks of iTBS induced significant increase in the expression of 52 genes. There were no downregulated genes. 1Hz and 5Hz had no significant effects on gene expression, while cTBS effects were negligible. Upregulated genes included those involved in angiogenesis, inflammation, injury response and cellular repair, structural remodeling, neuroprotection, neurotransmission and neuronal plasticity. The results show that long-term rTMS in acute ischemic-reperfusion brain injury induces complex changes in gene expression that span multiple pathways, which generally promote the recovery. They also demonstrate that induced changes primarily depend on the rTMS frequency (1Hz and 5Hz vs. iTBS) and pattern (cTBS vs. iTBS). The results further underlines the premise that one of the benefits of rTMS application in stroke may be to prime the brain, enhancing its potential to cope with the injury and to rewire. This could further augment its potential to favorably respond to rehabilitation, and to restore some of the loss functions.

  6. The Effects of Different Repetitive Transcranial Magnetic Stimulation (rTMS Protocols on Cortical Gene Expression in a Rat Model of Cerebral Ischemic-Reperfusion Injury.

    Directory of Open Access Journals (Sweden)

    Milos R Ljubisavljevic

    Full Text Available Although repetitive Transcranial Magnetic Stimulation (rTMS in treatment of stroke in humans has been explored over the past decade the data remain controversial in terms of optimal stimulation parameters and the mechanisms of rTMS long-term effects. This study aimed to explore the potential of different rTMS protocols to induce changes in gene expression in rat cortices after acute ischemic-reperfusion brain injury. The stroke was induced by middle cerebral artery occlusion (MCAO with subsequent reperfusion. Changes in the expression of 96 genes were examined using low-density expression arrays after MCAO alone and after MCAO combined with 1Hz, 5Hz, continuous (cTBS and intermittent (iTBS theta-burst rTMS. rTMS over the lesioned hemisphere was given for two weeks (with a 2-day pause in a single daily session and a total of 2400 pulses. MCAO alone induced significant upregulation in the expression of 44 genes and downregulation in 10. Two weeks of iTBS induced significant increase in the expression of 52 genes. There were no downregulated genes. 1Hz and 5Hz had no significant effects on gene expression, while cTBS effects were negligible. Upregulated genes included those involved in angiogenesis, inflammation, injury response and cellular repair, structural remodeling, neuroprotection, neurotransmission and neuronal plasticity. The results show that long-term rTMS in acute ischemic-reperfusion brain injury induces complex changes in gene expression that span multiple pathways, which generally promote the recovery. They also demonstrate that induced changes primarily depend on the rTMS frequency (1Hz and 5Hz vs. iTBS and pattern (cTBS vs. iTBS. The results further underlines the premise that one of the benefits of rTMS application in stroke may be to prime the brain, enhancing its potential to cope with the injury and to rewire. This could further augment its potential to favorably respond to rehabilitation, and to restore some of the loss

  7. Electroacupuncture Pretreatment Attenuates Cerebral Ischemic Injury via Notch Pathway-Mediated Up-Regulation of Hypoxia Inducible Factor-1α in Rats.

    Science.gov (United States)

    Zhao, Yu; Deng, Bin; Li, Yichong; Zhou, Lihua; Yang, Lei; Gou, Xingchun; Wang, Qiang; Chen, Guozhong; Xu, Hao; Xu, Lixian

    2015-11-01

    We have reported electroacupuncture (EA) pretreatment induced the tolerance against focal cerebral ischemia through activation of canonical Notch pathway. However, the underlying mechanisms have not been fully understood. Evidences suggest that up-regulation of hypoxia inducible factor-1α (HIF-1α) contributes to neuroprotection against ischemia which could interact with Notch signaling pathway in this process. Therefore, the current study is to test that up-regulation of HIF-1α associated with Notch pathway contributes to the neuroprotection of EA pretreatment. Sprague-Dawley rats were treated with EA at the acupoint "Baihui (GV 20)" 30 min per day for successive 5 days before MCAO. HIF-1α levels were measured before and after reperfusion. Then, HIF-1α antagonist 2ME2 and γ-secretase inhibitor MW167 were used. Neurologic deficit scores, infarction volumes, neuronal apoptosis, and Bcl2/Bax were evaluated. HIF-1α and Notch1 intracellular domain (NICD) were assessed. The results showed EA pretreatment enhanced the neuronal expression of HIF-1α, reduced infarct volume, improved neurological outcome, inhibited neuronal apoptosis, up-regulated expression of Bcl-2, and down-regulated expression of Bax after reperfusion in the penumbra, while the beneficial effects were attenuated by 2ME2. Furthermore, intraventricular injection with MW167 efficiently suppressed both up-regulation of NICD and HIF-1α after reperfusion. However, administration with 2ME2 could only decrease the expression of HIF-1α in the penumbra. In conclusion, EA pretreatment exerts neuroprotection against ischemic injury through Notch pathway-mediated up-regulation of HIF-1α.

  8. Protection of electrical stimulation on cerebral ischemic injury in rats%电刺激对大鼠缺血性脑卒中的保护作用

    Institute of Scientific and Technical Information of China (English)

    刘竞辉; 李江; 马炜; 邱新毓; 崔颖; 邓剑平; 于嘉; 赵振伟

    2013-01-01

    Objective To investigate the neuroprotection of electrical stimulation on permanent middle cerebral artery occlusion model (pMCAO).Methods Adult male rats were randomly divided into two groups; control group and experimental group. Then the experimental group was further divided into four sub-groups: 2 Hz group, 20 Hz group, 100 Hz group and 100/2 Hz group. Three hours after occlusion, electrodes were implanted into the ischemic area in right cortex of the rats. Stroke animals were conducted the behavioral test at 5 h and 24 h after pMCAO. The hemispheric infarct ratio was evaluated by staining with 2,3,5-triphenyltetrazolium chloride at 24 h after pMCAO. One hour after electrical stimulation, the rats were euthanized under deep anesthesia using chloralic hydras and then Western-blot analysis was used to analyze the expressions of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF).Results Compared with other experimental groups, the hemispheric infarct ratio was significantly decreased and the function recovery was improved significantly in 2 Hz stimulation group. Furthermore, the levels of VEGF were down-regulated and there was no significant change of BDNF levels among the experimental groups. Conclusion Cortical stimulation after pMCAO can decrease the hemispheric ratio and promote the functional recovery. Cortical electric stimulation may be a potent therapeutic tool for cerebral ischemia.%目的 探讨皮层电刺激对大鼠永久性缺血性脑卒中的保护作用.方法 雄性SD大鼠随机分成对照组和实验组.实验组根据刺激频率不同分成2Hz组,20Hz组,100Hz组,100/2Hz组.建立永久性梗塞模型.梗塞3h后,电极植入右侧大脑缺血区皮层进行刺激.分别在梗塞5h和24h进行行为学评分.在梗塞24h行2%氯化三苯基四氮唑溶液染色测量脑梗死比.于刺激结束1h后取脑组织Western blot分析脑源性神经营养因子(BDNF)和血管内皮生长因

  9. Recovery of neurological function of ischemic stroke by application of conditioned medium of bone marrow mesenchymal stem cells derived from normal and cerebral ischemia rats

    OpenAIRE

    2014-01-01

    Background Several lines of evidence have demonstrated that bone marrow-derived mesenchymal stem cells (BM-MSC) release bioactive factors and provide neuroprotection for CNS injury. However, it remains elusive whether BM-MSC derived from healthy donors or stroke patients provides equal therapeutic potential. The present work aims to characterize BM-MSC prepared from normal healthy rats (NormBM-MSC) and cerebral ischemia rats (IschBM-MSC), and examine the effects of their conditioned medium (C...

  10. Ischemic postconditioning fails to protect against neonatal cerebral stroke.

    Directory of Open Access Journals (Sweden)

    Pierre-Louis Leger

    Full Text Available The lack of efficient neuroprotective strategies for neonatal stroke could be ascribed to pathogenic ischemic processes differentiating adults and neonates. We explored this hypothesis using a rat model of neonatal ischemia induced by permanent occlusion of the left distal middle cerebral artery combined with 50 min of occlusion of both common carotid arteries (CCA. Postconditioning was performed by repetitive brief release and occlusion (30 s, 1 and/or 5 min of CCA after 50 min of CCA occlusion. Alternative reperfusion was generated by controlled release of the bilateral CCA occlusion. Blood-flow velocities in the left internal carotid artery were measured using color-coded pulsed Doppler ultrasound imaging. Cortical perfusion was measured using laser Doppler. Cerebrovascular vasoreactivity was evaluated after inhalation with the hypercapnic gas or inhaled nitric oxide (NO. Whatever the type of serial mechanical interruptions of blood flow at reperfusion, postconditioning did not reduce infarct volume after 72 hours. A gradual perfusion was found during early re-flow both in the left internal carotid artery and in the cortical penumbra. The absence of acute hyperemia during early CCA re-flow, and the lack of NO-dependent vasoreactivity in P7 rat brain could in part explain the inefficiency of ischemic postconditioning after ischemia-reperfusion.

  11. ischemic brain injury in neonatal rats

    African Journals Online (AJOL)

    Keywords: Hypoxic–ischemic brain injury, α-Lipoic acid, Cerebral infarct area, Edema, Antioxidants,. Inflammatory markers .... were then moved back to their respective dams and immediately ..... various pro-inflammatory cytokines is stimulated.

  12. Recombinant human erythropoietin increases cerebral cortical width index and neurogenesis following ischemic stroke

    Institute of Scientific and Technical Information of China (English)

    Zhongmin Wen; Peiji Wang

    2012-01-01

    The cerebral cortical expansion index refers to the ratio between left and right cortex width and is recognized as an indicator for cortical hyperplasia. Cerebral ischemia was established in CB-17 mice in the present study, and the mice were subsequently treated with recombinant human erythropoietin via subcutaneous injection. Results demonstrated that cerebral cortical width index significantly increased. Immunofluorescence detection showed that the number of nuclear antigen antibody/5-bromodeoxyuridine-positive cells at the infarction edge significantly increased. Correlation analysis revealed a negative correlation between neurological scores and cortical width indices in rats following ischemic stroke. These experimental findings suggested that recombinant human erythropoietin promoted cerebral cortical hyperplasia, increased cortical neurogenesis, and enhanced functional recovery following ischemic stroke.

  13. Changes of resting cerebral activities in subacute ischemic stroke patients

    Directory of Open Access Journals (Sweden)

    Ping Wu

    2015-01-01

    Full Text Available This study aimed to detect the difference in resting cerebral activities between ischemic stroke patients and healthy participants, define the abnormal site, and provide new evidence for pathological mechanisms, clinical diagnosis, prognosis prediction and efficacy evaluation of ischemic stroke. At present, the majority of functional magnetic resonance imaging studies focus on the motor dysfunction and the acute stage of ischemic stroke. This study recruited 15 right-handed ischemic stroke patients at subacute stage (15 days to 11.5 weeks and 15 age-matched healthy participants. A resting-state functional magnetic resonance imaging scan was performed on each subject to detect cerebral activity. Regional homogeneity analysis was used to investigate the difference in cerebral activities between ischemic stroke patients and healthy participants. The results showed that the ischemic stroke patients had lower regional homogeneity in anterior cingulate and left cerebrum and higher regional homogeneity in cerebellum, left precuneus and left frontal lobe, compared with healthy participants. The experimental findings demonstrate that the areas in which regional homogeneity was different between ischemic stroke patients and healthy participants are in the cerebellum, left precuneus, left triangle inferior frontal gyrus, left inferior temporal gyrus and anterior cingulate. These locations, related to the motor, sensory and emotion areas, are likely potential targets for the neural regeneration of subacute ischemic stroke patients.

  14. Changes of resting cerebral activities in subacute ischemic stroke patients

    Institute of Scientific and Technical Information of China (English)

    Ping Wu; Fang Zeng; Yong-xin Li; Bai-li Yu; Li-hua Qiu; Wei Qin; Ji Li; Yu-mei Zhou; Fan-rong Liang

    2015-01-01

    This study aimed to detect the difference in resting cerebral activities between ischemic stroke pa-tients and healthy participants, deifne the abnormal site, and provide new evidence for pathological mechanisms, clinical diagnosis, prognosis prediction and efifcacy evaluation of ischemic stroke. At present, the majority of functional magnetic resonance imaging studies focus on the motor dysfunc-tion and the acute stage of ischemic stroke. This study recruited 15 right-handed ischemic stroke patients at subacute stage (15 days to 11.5 weeks) and 15 age-matched healthy participants. A rest-ing-state functional magnetic resonance imaging scan was performed on each subject to detect cerebral activity. Regional homogeneity analysis was used to investigate the difference in cerebral activities between ischemic stroke patients and healthy participants. The results showed that the ischemic stroke patients had lower regional homogeneity in anterior cingulate and left cerebrum and higher regional homogeneity in cerebellum, left precuneus and left frontal lobe, compared with healthy participants. The experimental ifndings demonstrate that the areas in which regional homogeneity was different between ischemic stroke patients and healthy participants are in the cerebellum, left precuneus, left triangle inferior frontal gyrus, left inferior temporal gyrus and anterior cingulate. These locations, related to the motor, sensory and emotion areas, are likely po-tential targets for the neural regeneration of subacute ischemic stroke patients.

  15. Study on the Mechanism of mTOR-Mediated Autophagy during Electroacupuncture Pretreatment against Cerebral Ischemic Injury

    Science.gov (United States)

    Wu, Zhou-Quan; Cui, Su-yang; Zhu, Liang

    2016-01-01

    This study is aimed at investigating the association between the electroacupuncture (EA) pretreatment-induced protective effect against early cerebral ischemic injury and autophagy. EA pretreatment can protect cerebral ischemic and reperfusion injuries, but whether the attenuation of early cerebral ischemic injury by EA pretreatment was associated with autophagy is not yet clear. This study used the middle cerebral artery occlusion model to monitor the process of ischemic injury. For rats in the EA pretreatment group, EA pretreatment was conducted at Baihui acupoint before ischemia for 30 min for 5 consecutive days. The results suggested that EA pretreatment significantly increased the expression of autophagy in the cerebral cortical area on the ischemic side of rats. But the EA pretreatment-induced protective effects on the brain could be reversed by the specific inhibitor 3-methyladenine of autophagy. Additionally, the Pearson correlation analysis indicated that the impact of EA pretreatment on p-mTOR (2481) was negatively correlated with its impact on autophagy. In conclusion, the mechanism of EA pretreatment at Baihui acupoint against cerebral ischemic injury is mainly associated with the upregulation of autophagy expression, and its regulation of autophagy may depend on mTOR-mediated signaling pathways. PMID:27547233

  16. Neuroprotective effect of salvianolic acid B against cerebral ischemic injury in rats via the CD40/NF-κB pathway associated with suppression of platelets activation and neuroinflammation.

    Science.gov (United States)

    Xu, Shixin; Zhong, Aiqin; Ma, Huining; Li, Dan; Hu, Yue; Xu, Yingzhi; Zhang, Junping

    2017-04-15

    Neuroinflammation plays a critical role in the pathogenesis of ischemia/reperfusion (I/R) injury. Activated platelets are increasingly regarded as initiators and/or amplifiers of inflammatory processes in cerebral I/R injury. Salvianolic acid B (SAB) is the most abundant bioactive compound of Salviae miltiorrhizae, a well-known Chinese herb used to promote blood circulation and eliminating blood stasis. S. miltiorrhizae has been used clinically in Asia for the treatment of ischemic cerebrovascular diseases. In the present study, a rat model of transient middle cerebral artery occlusion (tMCAO) was established to investigate the neuroprotective effects and mechanisms of SAB treatment against focal cerebral I/R insult. The results showed that SAB treatment (3mg/kg, 6mg/kg and 12mg/kg, i.p.) dose-dependently decreased I/R-induced neurological deficits at 24, 48, and 72h after reperfusion and decreased plasma-soluble P-selectin and soluble CD40 ligand as early as 6h after onset of I/R insult. At 24h after reperfusion, SAB treatment significantly reduced neuronal and DNA damage in the hippocampal CA1 region and decreased neural cell loss in the ischemic core. The I/R-induced pro-inflammatory mediator mRNA and protein overexpression in the penumbra cortex, including ICAM-1, IL-1β, IL-6, IL-8, and MCP-1, were significantly inhibited by SAB in a dose-dependent manner. Further studies suggested SAB treatment attenuated CD40 expression and NF-κB activation, which involved NF-κB/p65 phosphorylation and IκBα phosphorylation and degradation. In conclusion, our findings indicated that the neuroprotective effects of SAB post cerebral I/R injury are associated with the inhibition of both platelets activation and production of pro-inflammatory mediators and the downregulation of the CD40/NF-κB pathway.

  17. Early electrocortical changes consistent with ischemic preconditioning in rat

    DEFF Research Database (Denmark)

    Zagrean, L.; Moldovan, M.; Munteanu, Ana-Maria

    2002-01-01

    Ischemic preconditioning (IPC) of the brain describes the neuroprotection induced by a short, conditioning ischemic episode (CIE) to a subsequent severe (test) ischemic episode (TIE). Most of the supporting evidence for IPC is based on histological assessment, several days after TIE. The aim...... of this study is to investigate if changes induced by IPC can be detected within 30 min of reperfusion following the ischemic episode. A rat model of "four-vessel occlusion" transient global cerebral ischemia and parametric analysis of electrocorticogram were used. A control group was subjected directly to a 10...... min TIE, and in a preconditioned group TIE was induced 48 h after a 3 min CIE. Quantitative histology was performed 48 h after TIE. Our key finding is that, 30 min after reperfusion, there is a significant increase in the electrocortical slow activity in the control group but not in the preconditioned...

  18. Neuroprotective effects of the immunomodulatory drug Setarud on cerebral ischemia in male rats

    Institute of Scientific and Technical Information of China (English)

    Farzaneh Vafaee; Nasser Zangiabadi; Fatemeh Mehdi Pour; Farzaneh Dehghanian; Majid Asadi-Shekaari; Hossein Karimi Afshar

    2012-01-01

    Anti-inflammatory and anti-oxidant agents can alleviate ischemic cerebral injury. The immunomodulary drug Setarud, which is composed of herbal extracts including Rosa canina, Urtica dioica and Tanacetum vulgare, supplemented with selenium exhibits anti-inflammatory and anti-oxidant properties. Therefore, we hypothesized that Setarud will have a neuroprotective effect against ischemic cerebral injury. To validate this hypothesis, rats were intraperitoneally administered with 0.66 mL/kg Setarud for 30 minutes after middle cerebral artery occlusion. Triphenyltetrazolium chloride staining showed that Setarud could reduce cerebral infarct volume of rats subjected to cerebral ischemia. Transmission electron microscopy and hematoxylin-eosin staining results showed that Setarud could alleviate the degenerative changes in cortical neurons of rats with cerebral ischemia. The inclined plate test and prehensile test showed that Setarud could significantly improve the motor function of rats with cerebral ischemia. These findings suggest that Setarud shows neuroprotective effects against ischemic brain injury.

  19. Changes in synapse quantity and growth associated protein 43 expression in the motor cortex of focal cerebral ischemic rats following catalpol treatment

    Institute of Scientific and Technical Information of China (English)

    Dong Wan; Huifeng Zhu; Yong Luo; Peng Xie

    2011-01-01

    The present study investigated the effects of catalpol, the main constituent of the Chinese herb Rehmannia root, on neurons following brain ischemia. A rat model of focal permanent brain ischemia was established using electrocoagulation. The rats were intraperitoneally injected with catalpol, at a dose of 5 mg/kg, daily for 1 week. Results showed that the number of neuronal synapses in the motor cortex and growth associated protein 43 expression were increased following catalpol treatment, indicating that catalpol might contribute to neuroplasticity and ameliorate functional neurological deficits induced by cerebral ischemia.

  20. Imaging of cerebral ischemic edema and neuronal death

    Energy Technology Data Exchange (ETDEWEB)

    Kummer, Ruediger von [Universitaetsklinikum Carl Gustav Carus, Institut fuer Diagnostische und Interventionelle Neuroradiologie, Dresden (Germany); Dzialowski, Imanuel [Elblandklinikum Meissen, Neurologische Rehabilitationsklinik Grossenhain, Meissen (Germany)

    2017-06-15

    In acute cerebral ischemia, the assessment of irreversible injury is crucial for treatment decisions and the patient's prognosis. There is still uncertainty how imaging can safely differentiate reversible from irreversible ischemic brain tissue in the acute phase of stroke. We have searched PubMed and Google Scholar for experimental and clinical papers describing the pathology and pathophysiology of cerebral ischemia under controlled conditions. Within the first 6 h of stroke onset, ischemic cell injury is subtle and hard to recognize under the microscope. Functional impairment is obvious, but can be induced by ischemic blood flow allowing recovery with flow restoration. The critical cerebral blood flow (CBF) threshold for irreversible injury is ∝15 ml/100 g x min. Below this threshold, ischemic brain tissue takes up water in case of any residual capillary flow (ionic edema). Because tissue water content is linearly related to X-ray attenuation, computed tomography (CT) can detect and measure ionic edema and, thus, determine ischemic brain infarction. In contrast, diffusion-weighted magnetic resonance imaging (DWI) detects cytotoxic edema that develops at higher thresholds of ischemic CBF and is thus highly sensitive for milder levels of brain ischemia, but not specific for irreversible brain tissue injury. CT and MRI are complimentary in the detection of ischemic stroke pathology and are valuable for treatment decisions. (orig.)

  1. Migration of neural stem cells to ischemic brain regions in ischemic stroke in rats.

    Science.gov (United States)

    Dai, Jiong; Li, Shan-Quan; Qiu, Yong-Ming; Xiong, Wen-Hao; Yin, Yu-Hua; Jia, Feng; Jiang, Ji-Yao

    2013-09-27

    An established rat model of ischemic stroke, produced by temporary middle cerebral artery occlusion and reperfusion (MCAO/R), was used in the evaluation of organ migration of intra-arterial (IA) transplantation of neural stem cells (NSCs). Immediately after transplantation, ischemic rats (n=8) transplanted with either NSCs (MCAO/R+NSC group) or NSC growth medium (MCAO/R+medium group) exhibited neurological dysfunction but rats in a sham+NSCs group (n=5) did not. During the post-operative period, neurological function improved to a similar extent in both MCAO/R groups. At 10 and 14 days post-transplantation, neurological function in the MCAO/R+NSC group was superior to that in the MCAO/R+medium group (pcells had begun differentiating into neurons and astrocytes. Rat NSCs can migrate into the ischemic region, survive, and differentiate into astrocytes and neurons, and thereby potentially improve neurologic function after cerebral ischemia. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  2. A Pilot Study for the Neuroprotective Effect of Gongjin-dan on Transient Middle Cerebral Artery Occlusion-Induced Ischemic Rat Brain

    Directory of Open Access Journals (Sweden)

    Yun-Young Sunwoo

    2012-01-01

    Full Text Available In this study, we investigated whether gongjin-dan improves functional recovery and has neuroprotective effects on reducing the infarct volume after transient middle cerebral artery occlusion (MCAo. Infarct volume was measured using TTC staining and glucose utilization by F-18 FDG PET. Functional improvement was evaluated with the Rota-rod, treadmill, Garcia score test, and adhesive removal test. At 14 days after MCAo, neuronal cell survival, astrocytes expansion, and apoptosis were assessed by immunohistofluorescence staining in the peri-infarct region. Also, the expression of neurotrophic factors and inflammatory cytokines such as VEGF, BDNF, Cox-2, TNF-α, IL-1β, and IL-1α was measured in ischemic hemisphere regions. The gongjin-dan-treated group showed both reduced infarct volume and increased glucose utilization. Behavior tests demonstrated a significant improvement compared to the control. Also in the gongjin-dan treated group, NeuN-positive cells were increased and number of astrocytes, microglia, and apoptotic cells was significantly decreased compared with the control group in the ischemic peri-infarct area. Furthermore, the expression of VEGF and BDNF was increased and level of Cox-2, TNF-α, IL-1β, and IL-1α was decreased. These results suggest that gongjin-dan may improve functional outcome through the rapid restoration of metabolism and can be considered as a potential neuroprotective agent.

  3. Pre-ischemic treadmill training alleviates brain damage via GLT-1-mediated signal pathway after ischemic stroke in rats.

    Science.gov (United States)

    Wang, X; Zhang, M; Yang, S-D; Li, W-B; Ren, S-Q; Zhang, J; Zhang, F

    2014-08-22

    Physical exercise could play a neuroprotective role in both human and animals. However, the involved signal pathways underlying the neuroprotective effect are still not well established. This study was to investigate the possible signal pathways involved in the neuroprotection of pre-ischemic treadmill training after ischemic stroke. Seventy-two SD rats were randomly assigned into three groups (n=24/group): sham surgery group, middle cerebral artery occlusion (MCAO) group and MCAO with exercise group. Following three weeks of treadmill training exercise, ischemic stroke was induced by occluding the middle cerebral artery (MCA) in rat for 2 h, followed by reperfusion. Twenty-four hours after MCAO/reperfusion, 12 rats in each group were evaluated for neurological deficit scores and then sacrificed to measure the infarct volume (n=6) and cerebral edema (n=6). Six rats in each group were sacrificed to measure the expression level of glutamate transporter-1 (GLT-1), protein kinase C-α (PKC-α), Akt, and phosphatidylinositol 3 kinase (PI3K) (n=6). Two hundred and eighty minutes (4.67 h) after occlusion, six rats in each group were decapitated to detect the mRNA expression level of metabotropic glutamate receptor 5 (mGluR5) and N-methyl-D-aspartate receptor subunit type 2B (NR2B) (n=6).The results demonstrated that pre-ischemic treadmill training exercise reduced brain infarct volume, cerebral edema and neurological deficits, also decreased the over expression of PKC-α and increased the expression level of GLT-1, Akt and PI3K after ischemic stroke (pdamage after ischemic stroke, which might be involved in two signal pathways: PKC-α-GLT-1-Glutamate and PI3K/Akt-GLT-1-Glutamate.

  4. Inlfammatory response and neuronal necrosis in rats with cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Lingfeng Wu; Kunnan Zhang; Guozhu Hu; Haiyu Yang; Chen Xie; Xiaomu Wu

    2014-01-01

    In the middle cerebral artery occlusion model of ischemic injury, inlfammation primarily occurs in the infarct and peripheral zones. In the ischemic zone, neurons undergo necrosis and apop-tosis, and a large number of reactive microglia are present. In the present study, we investigated the pathological changes in a rat model of middle cerebral artery occlusion. Neuronal necrosis appeared 12 hours after middle cerebral artery occlusion, and the peak of neuronal apoptosis ap-peared 4 to 6 days after middle cerebral artery occlusion. Inlfammatory cytokines and microglia play a role in damage and repair after middle cerebral artery occlusion. Serum intercellular cell adhesion molecule-1 levels were positively correlated with the permeability of the blood-brain barrier. These ifndings indicate that intercellular cell adhesion molecule-1 may be involved in blood-brain barrier injury, microglial activation, and neuronal apoptosis. Inhibiting blood-brain barrier leakage may alleviate neuronal injury following ischemia.

  5. Post-ischemic treatment of WIB801C, standardized Cordyceps extract, reduces cerebral ischemic injury via inhibition of inflammatory cell migration.

    Science.gov (United States)

    Hwang, Sunyoung; Cho, Geum-Sil; Ryu, Sangwoo; Kim, Hoon J; Song, Hwa Young; Yune, Tae Y; Ju, Chung; Kim, Won-Ki

    2016-06-20

    Anti-inflammatory therapy has been intensively investigated as a potential strategy for treatment of cerebral stroke. However, despite many positive outcomes reported in animal studies, anti-inflammatory treatments have not proven successful in humans as yet. Although immunomodulatory activity and safety of Cordyceps species (Chinese caterpillar fungi) have been proven in clinical trials and traditional Asian prescriptions for inflammatory diseases, its anti-ischemic effect remains elusive. In the present study, therefore, we investigated the potential therapeutic efficacy of WIB801C, the standardized extract of Cordyceps militaris, for treatment of cerebral ischemic stroke. The anti-chemotactic activity of WIB801C was assayed in cultured rat microglia/macrophages. Sprague-Dawley rats were subjected to ischemic stroke via either transient (1.5-h tMCAO and subsequent 24-h reperfusion) or permanent middle cerebral artery occlusion (pMCAO for 24-h without reperfusion). WIB801C was orally administered twice at 3- and 8-h (50mg/kg each) after the onset of MCAO. Infarct volume, edema, blood brain barrier and white matter damages, neurological deficits, and long-term survival rates were investigated. The infiltration of inflammatory cells into ischemic lesions was assayed by immunostaining. WIB801C significantly decreased migration of cultured microglia/macrophages. This anti-chemotactic activity of WIB-801C was not mediated via adenosine A3 receptors, although cordycepin, the major ingredient of WIB801C, is known as an adenosine receptor agonist. Post-ischemic treatment with WIB801C significantly reduced the infiltration of ED-1-and MPO-positive inflammatory cells into ischemic lesions in tMCAO rats. WIB801C-treated rats exhibited significantly decreased infarct volume and cerebral edema, less white matter and blood-brain barrier damages, and improved neurological deficits. WIB801C also improved survival rates over 34 days after ischemia onset. A significant reduction in

  6. The effect of ischemic postconditioning on cerebral ischemia-reperfusion injury in diabetic rats%缺血后处理对糖尿病大鼠局灶性脑缺血再灌注损伤的影响

    Institute of Scientific and Technical Information of China (English)

    卢英云; 王翠兰; 刘颖; 李燕

    2008-01-01

    Objective To observe the effect of ischemic postconditioning on cerebral ischemia-reperfusion (I/R)injury in diabetic rats. Methods A rat model of diabetes was established using a single intraperitoneal injection of streptozotocin in 40 male Spragne-Dawley rats.Focal ischemia was induced by transient middle cerebral artery occlusion(MCAO)using a thread.The rats were randomly assigned to a control group,a sham-operated group,an I/R group and an Ⅰ-Post group.The animals in the I/R group were subjected to MCAO for 90 min and then reperfusion.Those in the Ⅰ-post group were subjected to MCAO and 3 cycles of transient ischemia-reperfusion(15 seconds ischemia then 15 seconds reperfusion)before persistent reperfusion.Neurological deficit scores,infarct volume,histological changes in the brain and the number of apoptotic cells were measured 6 hours later.Results There was no significant difference in neurological deficit scores between the I/R group and the Ⅰ-post group.The histological changes and apoptotic cells were significantly less in the Ⅰ-post group compared with the I/R group.Conclusion Ischemic postconditioning can inhibit cell apoptosis and reduce cerebral I/R injury after focal cerebral ischemia-reperfusion in diabetic rats.%目的 探讨缺血后处理(Ⅰ-Post)对糖尿病大鼠局灶性脑缺血再灌注(L/R)损伤的影响.方法 采用链脲佐菌(STZ)腹腔注射方式建立糖尿病大鼠模型,将制模成功的糖尿病大鼠随机分为4组,即空白对照组、假手术组、缺血再灌注组(Ⅰ/R组)及缺血后处理组(Ⅰ-Post组).Ⅰ/R组及Ⅰ-Post组均通过线栓法制作大鼠大脑中动脉阻塞(MCAO)模型,并且Ⅰ-Post组于大脑中动脉阻塞90 min后,反复进行3次短暂再灌注干预(灌注15 s后缺血15 s);假手术组手术步骤同上,但不插入线栓;空白对照组不给予任何处理.于缺血90 min、再灌注6 h后对所有大鼠进行神经功能评分(NDS)、脑梗死体积测定、观察脑组织神经

  7. 氨基胍对大鼠缺血性脑损伤的保护作用及其机制%Mechanism of protective effect of aminoguanidine on experimental cerebral ischemic injury in rats

    Institute of Scientific and Technical Information of China (English)

    张会欣; 张建新; 李兰芳; 李永辉

    2006-01-01

    目的 观察选择性一氧化氮合酶抑制剂氨基胍(AG)保护大鼠缺血性脑损伤的可能机制.方法 采用线栓法复制大鼠大脑中动脉梗塞模型,缺血后2, 6或12 h 开始给予AG(100 mg·kg-1,ip,每天2次,给药3 d)治疗.测定脑梗死体积,脑线粒体肿胀度和呼吸链的完整性,脑线粒体内NO和丙二醛(MDA)含量,总ATP酶、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活性;培养大鼠神经元细胞,观察AG(10,20和100 μmol·L-1)对神经元细胞形态、活力及乳酸脱氢酶(LDH)释放和NO含量的影响. 结果 AG显著降低脑缺血后脑梗死体积,改善缺血后神经元超微结构变化,减轻脑线粒体肿胀度和呼吸链损伤;降低NO和MDA含量,增加总ATP酶、SOD和GSH-Px活性.AG使体外培养的缺血神经细胞损伤程度明显减轻,NO含量降低,LDH释放减少,细胞活力增加.结论 AG可能通过抑制氧自由基生成,增加线粒体抗氧化作用,改善线粒体能量代谢和保护线粒体形态与功能的完整而对大鼠脑缺血损伤产生保护作用.%AIM To investigate the beneficial effects of aminoguanidine(AG), a selective inducible nitric oxide synthase (iNOS) inhibitor, on cerebral ischemic injury of rats and the possible mechanism. METHODS The middle cerebral artery occlusion model was prepared with thread embolism. AG 100 mg·kg-1 was injected ip first at 2, 6 and 12 h, respectively, after ischemia, then 2 times a day for 3 consecutive days. The infarct volume of brain tissue was determined with tetrazolium chloride staining. The mitochondria in brain tissue were isolated for measuring integrity of electron transport chain (ETC), mitochondrial swelling, NO and malondialdehyde (MDA) contents, ATPase, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities. In addition, the neuronal cells of newborn rats were cultured in glucose-free medium with sodium hydrosulfite for cell viability, lactate dehydrogenease (LDH) and NO

  8. AQP4 expression of the cerebral ischemic tissue following its mRNA silence in rat%基因沉默对缺血脑组织水通道蛋白4表达的影响

    Institute of Scientific and Technical Information of China (English)

    鲁宏; 胡惠; 何占平; 涂蓉; 舒庆杰

    2012-01-01

    To investigate the effect of RNA interference targeting AQP4 on its expression in the cerebral ischemic tissues. Methods: Total 108 Wistar rats were divided into three groups randomly: ischemic groups (MCAO), control group (shRNA-AQP4 + MCAO) and interference groups (siRNA-AQP4 + MCAO). Each group was subdivided into six sub groups according to the different interval of time points: 0. 25 h, 0. 5 h, 1 h, 2 h, 4 h and 6 h (n = 6 for each group). The right middle cerebral artery of rats was unilaterally occluded (MCAO) in ischemic groups. The reagent including nonsense short hairpin (shRNA) liposomes and short interference (siRNA)-AQP4 liposomes were injected to the right basal ganglia of the rats of MCAO served as a control group and an interference group, respectively. The animals were sacrificed and per fused with the mixture solution consisting formalin. The right basal ganglia tissues were examined with pathology, immuno histochemistry, real time fluorescence quantitative reverse transcript polymerase chain reaction (RT-PCR) and Western blot ting. Results: There was no significant change in AQP4 expression between the control group and the ischemic group. The expression of AQP4 increased rapidly within 2 h, and then increased slowly during 4-6 h. Whereas, there was no significant change in AQP4 expression between the control group and the interference group at 0. 25 h and 6 h after MCAO. But there was significant change in AQP4 expression between the control group and the interference group during 0. 5-4 h. The AQP4 expression could be inhibited efficiently by RNA silencing technique during 0. 5-4 h, but it became unconspicuous during 4-6 h. The corresponding histological changes within 4 h were intracellular edema in the ischemic group and the control group, but this pathological change was obviously mitigated in the interference group during the same period of time. With the pro gress of the time (4-6 h), The vasogenic brain edema was mostly observed in

  9. 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.

  10. 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.

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

    Science.gov (United States)

    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 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. PMID:20955613

  12. Improvement of intraluminal suture method for establishment of focal cerebral ischemic rat models%线栓法建立大鼠局灶性脑缺血模型的改进

    Institute of Scientific and Technical Information of China (English)

    包新杰; 赵浩; 魏俊吉; 冯铭; 杜世伟; 李桂林; 窦万臣; 王任直

    2011-01-01

    Objectives To improve the procedures for establishment of focal cerebral ischemic rat models with the intraluminal suture method and to elevate the survival rate of the models.Methods Sixty male SD rats (weight, 250 -270 g) were randomly allocated into 3 groups (n = 20 in each group ).Control group used the conventional surgical method, the pterygopalatine arteries were exposed and ligated during the procedure, and the rats had free access to food after the procedure; gavage group used the same method as the control group, but postoperative gavage was performed; protective group did not ligate the pterygopalatine arteries, but the carotid arteries and vagus nerves were carefully separated.Trying to avoid stretching the vagus nerves during the procedure and postoperative gavage was performed.The body weight of the rats in each group was weighed continuously before and after modeling, and the neurological deficit scores were measured; the survival rate of rats in each group was calculated at day 3, 14, and 28, respectively after modeling; the brain infarct volume in each group was calculated at day 28 after modeling.Results ①The mean time of model production was 19.5 min in the protective group, and it was shorter than that in the control and gavage groups.The differences were statistically significant ( P < 0.05 ); ②At day 3 after modeling, the survival rate of the rats in the protective group was higher than that in the control and gavage groups.The differences were statistically significant ( P < 0.05 ); ③After modeling, the body weight of the rats in the 3 groups were all decreased.The body weight of the rats in each group began to increase from day 7 after modeling.The body weight of the rats in the protective group was all higher than that in the control and gavage groups at day 7, 14, 21, and 28 after the procedure.The differences were statistically significant ( P < 0.05 ); ④there were no significant differences comparing the neurological

  13. An unusual cause of ischemic stroke - Cerebral air embolism

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    Vinit Suri

    2014-01-01

    Full Text Available Air embolism is a preventable, often undiagnosed but potentially treatable cause of ischemic stroke with a high morbidity and mortality. It is usually iatrogenic ocurring especially in patients in ICU setting. We describe the case and neuroimaging of a patient with ischaemic stroke due to air embolism during manipulation of central venous line. We also review the literature with respect to aetiology, incidence pathophysiology, diagnosis, and treatment options for venous and air embolism. Cerebral air embolism should be considered in patients with sudden neurological deterioration after central venous or arterial manipulations or certain neurological procedures. Prevention, as well as early diagnosis and management, may reduce morbidity and mortality.

  14. Edema and vascular permeability in cerebral ischemia: comparison between ischemic neuronal damage and infarction.

    Science.gov (United States)

    Petito, C K; Pulsinelli, W A; Jacobson, G; Plum, F

    1982-07-01

    The respective influences of ischemic neuronal damage and infarction on the development of abnormal blood-brain barrier (BBB) permeability and cerebral edema were evaluated in a rat model of temporary four-vessel occlusion in which ischemic neuronal damage with only infrequent infarction is produced. Survival times ranged from 40 minutes to 5 days after ischemia. Evans blue and horseradish peroxidase (HRP) were given before sacrifice. The majority of brain showed moderate ischemic neuronal damage inthe striatum. In these areas there was neither leakage of Evans blue nor extravasation of HRP. Astrocytic processes were moderately swollen. Large, grossly-visible unilateral infarcts were present in only 5 animals, and all showed abnormal BBB permeability of HRP which occurred via enchanced pinocytosis, and occasionally via diffuse leakage through necrotic vessels. Astrocytic processes were markedly swollen and their plasma membranes were disrupted. Whole brain and regional water content in a parallel series of animals were measured from 15 minutes (min) to 48 hours (h) postischemia. They showed a transient, 1% increase in whole brain water content from 15 to 60 min postischemia, but no increase in regional water content at any postischemic interval. These studies suggest that ischemia produces BBB permeability to large molecules, and sustained cerebral edema only when the process damages blood vessels and astrocytes; neuronal necrosis alone is insufficient.

  15. Eriodictyol-7-O-glucoside activates Nrf2 and protects against cerebral ischemic injury

    Energy Technology Data Exchange (ETDEWEB)

    Jing, Xu [Department of Pharmacology, School of Medicine, Shandong University, Jinan 250012 (China); Ren, Dongmei [Department of Natural Product Chemistry, Key Lab of Chemical Biology of Ministry of Education, Shandong University, Jinan 250012 (China); Wei, Xinbing; Shi, Huanying; Zhang, Xiumei [Department of Pharmacology, School of Medicine, Shandong University, Jinan 250012 (China); Perez, Ruth G. [Health Science Center, Paul L. Foster School of Medicine, Texas Tech University, El Paso, TX, 79905 (United States); Lou, Haiyan, E-mail: louhaiyan@sdu.edu.cn [Department of Pharmacology, School of Medicine, Shandong University, Jinan 250012 (China); Lou, Hongxiang [Department of Natural Product Chemistry, Key Lab of Chemical Biology of Ministry of Education, Shandong University, Jinan 250012 (China)

    2013-12-15

    Stroke is a complex disease that may involve oxidative stress-related pathways in its pathogenesis. The nuclear factor erythroid-2-related factor 2/antioxidant response element (Nrf2/ARE) pathway plays an important role in inducing phase II detoxifying enzymes and antioxidant proteins and thus has been considered a potential target for neuroprotection in stroke. The aim of the present study was to determine whether eriodictyol-7-O-glucoside (E7G), a novel Nrf2 activator, can protect against cerebral ischemic injury and to understand the role of the Nrf2/ARE pathway in neuroprotection. In primary cultured astrocytes, E7G increased the nuclear localization of Nrf2 and induced the expression of the Nrf2/ARE-dependent genes. Exposure of astrocytes to E7G provided protection against oxygen and glucose deprivation (OGD)-induced oxidative insult. The protective effect of E7G was abolished by RNA interference-mediated knockdown of Nrf2 expression. In vivo administration of E7G in a rat model of focal cerebral ischemia significantly reduced the amount of brain damage and ameliorated neurological deficits. These data demonstrate that activation of Nrf2/ARE signaling by E7G is directly associated with its neuroprotection against oxidative stress-induced ischemic injury and suggest that targeting the Nrf2/ARE pathway may be a promising approach for therapeutic intervention in stroke. - Highlights: • E7G activates Nrf2 in astrocytes. • E7G stimulates expression of Nrf2-mediated cytoprotective proteins in astrocytes. • E7G protects astrocytes against OGD-induced cell death and apoptosis. • The neuroprotective effect of E7G involves the Nrf2/ARE pathway. • E7G protects rats against cerebral ischemic injury.

  16. Racial Difference in Cerebral Microbleed Burden among Ischemic Stroke Patients.

    Science.gov (United States)

    Shahjouei, Shima; Tsivgoulis, Georgios; Singh, Mantinderpreet; McCormack, Michael; Noorbakhsh-Sabet, Nariman; Goyal, Nitin; Alexandrov, Anne W; Alexandrov, Andrei V; Zand, Ramin

    2017-08-21

    Data on the epidemiology of cerebral microbleeds (CMBs) among patients with ischemic stroke are limited. This study compared the number, associated factors, and topography of CMBs between African American and Caucasian ischemic stroke patients in the Mid-South United States. We evaluated consecutive ischemic stroke patients admitted to our tertiary stroke center, University of Tennessee Health Science Center, Memphis, Tennessee, in a two-year period. We analyzed T2*-weighted magnetic resonance images for the number, location, and topography of CMBs, as well as patients' demographic and clinical information. Among 760 ischemic stroke patients who were included (mean age was 62.1 ± 13.9 years, 51.4% men), 450 (59.2%) were African American. In comparison with Caucasians, African Americans were about five years younger (P = .000) and had a higher rate of hypertension (80.9% vs. 74.5%, P = .036). Similarly, African Americans had a higher prevalence of diabetes mellitus (P = .001). There was no significant difference between African-Americans and Caucasians in terms of CMBs presence and location. African Americans had a higher number of CMBs in comparison with Caucasians, but the difference was not significant. African Americans were more likely to have CMBs ≥5 (P = .047). Although African American stroke patients had a higher rate of large confluent white matter lesions, there was no significant racial difference regarding the rate and severity of deep white matter lesions. We did not observe any differences between African American and Caucasian patients with ischemic stroke patients regarding the presence, number, and location of CMBs. However, our results suggested that the prevalence of multiple CMBs (CMBs ≥5) might be higher among African American stroke patients. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  17. Nitroxyl exacerbates ischemic cerebral injury and oxidative neurotoxicity.

    Science.gov (United States)

    Choe, Chi-un; Lewerenz, Jan; Fischer, Gerry; Uliasz, Tracy F; Espey, Michael Graham; Hummel, Friedhelm C; King, Stephen Bruce; Schwedhelm, Edzard; Böger, Rainer H; Gerloff, Christian; Hewett, Sandra J; Magnus, Tim; Donzelli, Sonia

    2009-09-01

    Nitroxyl (HNO) donor compounds function as potent vasorelaxants, improve myocardial contractility and reduce ischemia-reperfusion injury in the cardiovascular system. With respect to the nervous system, HNO donors have been shown to attenuate NMDA receptor activity and neuronal injury, suggesting that its production may be protective against cerebral ischemic damage. Hence, we studied the effect of the classical HNO-donor, Angeli's salt (AS), on a cerebral ischemia/reperfusion injury in a mouse model of experimental stroke and on related in vitro paradigms of neurotoxicity. I.p. injection of AS (40 mumol/kg) in mice prior to middle cerebral artery occlusion exacerbated cortical infarct size and worsened the persistent neurological deficit. AS not only decreased systolic blood pressure, but also induced systemic oxidative stress in vivo indicated by increased isoprostane levels in urine and serum. In vitro, neuronal damage induced by oxygen-glucose-deprivation of mature neuronal cultures was exacerbated by AS, although there was no direct effect on glutamate excitotoxicity. Finally, AS exacerbated oxidative glutamate toxicity - that is, cell death propagated via oxidative stress in immature neurons devoid of ionotropic glutamate receptors. Taken together, our data indicate that HNO might worsen cerebral ischemia-reperfusion injury by increasing oxidative stress and decreasing brain perfusion at concentrations shown to be cardioprotective in vivo.

  18. Prevalence of cerebral microbleeds in Thai patients with ischemic stroke

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    Artit Potigumjon

    2017-01-01

    Full Text Available Background: With the widespread use of magnetic resonance imaging (MRI, cerebral microbleeds (CMBs are commonly detected. Ethnicity seems to play a role in the prevalence of CMB, with higher prevalence in participants from Asian origin. The purpose of the study is to look for the prevalence of CMBs and associated factors in Thai patients with ischemic stroke. Methods: Patients with acute ischemic stroke who had MRI and magnetic resonance angiography during January–August 2014 were included in the study. T2*-weighted gradient-recalled echo was used to define CMBs. Baseline characteristics, stroke subtypes, and severity of white matter lesions were compared between patients with and without CMBs. Results: Two hundred patients were included in the study. Mean age of the patients was 61-year-old. Mean National Institutes of Health Stroke Scale was 8. The prevalence of CMBs was 20% (39/200 patients. Hypertension (odds ratio [OR] 3.05, 95% confidence interval [CI] 1.07–8.68, P = 0.037, and moderate-to-severe white matter lesions (Fazekas 2–3, OR 7.61, 95% CI 3.06–18.95, P < 0.001 were related to the presence of CMBs. Conclusions: CMBs were found in 20% of patients with ischemic stroke, which was lower than those reported from Japanese studies but comparable to a Chinese study. CMBs were associated with hypertension and severity of the white matter lesions.

  19. Prevalence of Cerebral Microbleeds in Thai Patients with Ischemic Stroke.

    Science.gov (United States)

    Potigumjon, Artit; Watcharakorn, Arvemas; Dharmasaroja, Pornpatr A

    2017-01-01

    With the widespread use of magnetic resonance imaging (MRI), cerebral microbleeds (CMBs) are commonly detected. Ethnicity seems to play a role in the prevalence of CMB, with higher prevalence in participants from Asian origin. The purpose of the study is to look for the prevalence of CMBs and associated factors in Thai patients with ischemic stroke. Patients with acute ischemic stroke who had MRI and magnetic resonance angiography during January-August 2014 were included in the study. T2*-weighted gradient-recalled echo was used to define CMBs. Baseline characteristics, stroke subtypes, and severity of white matter lesions were compared between patients with and without CMBs. Two hundred patients were included in the study. Mean age of the patients was 61-year-old. Mean National Institutes of Health Stroke Scale was 8. The prevalence of CMBs was 20% (39/200 patients). Hypertension (odds ratio [OR] 3.05, 95% confidence interval [CI] 1.07-8.68, P = 0.037), and moderate-to-severe white matter lesions (Fazekas 2-3, OR 7.61, 95% CI 3.06-18.95, P CMBs. CMBs were found in 20% of patients with ischemic stroke, which was lower than those reported from Japanese studies but comparable to a Chinese study. CMBs were associated with hypertension and severity of the white matter lesions.

  20. Proprotein convertase 1 mRNA and protein expression in ischemic rat cortex after reperfusion

    Institute of Scientific and Technical Information of China (English)

    Shuqin Zhan; An Zhou; Jingquan Lan; Tao Yang

    2011-01-01

    Proprotein convertase 1 (PC1) is a member of the family of proprotein convertases (PCs), which are the processing enzymes of neuropeptides. Previous studies have addressed PC1 effects with regard to the neuroendocrine system. In this study, the developing changes of PC1 mRNA and PC1 protein in rat cortices after transient focal cerebral ischemia were investigated by fluorescent double labeling (both in situ hybridization and immunocytochemistry) using a transient focal cerebral ischemia model in rats. The results were compared with those of sham-operated rat cortices. Both the mRNA and protein levels of PC1 in ischemic cortices decreased gradually at 4, 8, and 16 hours of reperfusion after 100 minutes of middle cerebral artery occlusion. After 24 hours of reperfusion, enhanced intensities of signals for PC1 protein were observed, while signals for PC1 mRNA remained low. These results suggest that transient focal cerebral ischemia influences PC1 mRNA and protein expression in cortices of ischemic rats. Thus, PC1 is regulated by ischemic stress.

  1. Transplantation of human embryonic neural stem cells protects rats against cerebral ischemic injury%人源胚胎神经干细胞移植可对抗大鼠的脑缺血/再灌注损伤

    Institute of Scientific and Technical Information of China (English)

    刘晓燕; 王昌鹏; 刘铭; 季刚; 郭景春

    2014-01-01

    本文旨在研究人源胚胎神经干细胞(human embryonic neural stem cells,hNSCs)移植到脑缺血/再灌注损伤大鼠脑内后的迁移、分化,以及对大鼠脑卒中的疗效.我们在大脑中动脉栓塞(middle cerebral artery occlusion,MCAO)1 h的大鼠模型上,于血流再灌注后第7天注射hNSCs到缺血侧侧脑室,通过焦油紫染色测量大鼠的脑梗死体积,通过检测大鼠的感觉运动行为评估其神经功能的恢复水平,通过免疫荧光共标观察移植后的hNSCs在脑内的迁移与分化.结果显示,hNSCs移植后能够显著减小脑卒中大鼠脑梗死体积,并改善脑卒中大鼠的转棒、错步和转角等运动行为能力;侧脑室注射的hNSCs优先向胼胝体以及梗死区周边迁移,迁移到胼胝体的hNSCs可以分化成少突胶质细胞和星形胶质细胞,迁移到梗死区周边的细胞能够分化成神经元.以上这些结果提示,侧脑室移植的hNSCs可能通过向特定脑区的迁移和分化发挥对脑缺血/再灌注损伤大鼠的保护作用.%The purpose of this study is to explore the fate and effect of human embryonic neural stem cells (hNSCs) after transplantation into ipsilateral lateral ventricle of stroke rats.Adult rats were exposed to one-hour transient middle cerebral artery occlusion (MCAO),and then hNSCs were transplanted into ipsilateral lateral ventricle 7 days after reperfusion.Infarct volume was calculated by cresyl violet staining.The improvements of neural functions were assessed by behavioral tests.Immunofluorescence staining was performed to observe the migration and differentiation of transplanted hNSCs.The results showed that transplanted hNSCs significantly reduced ischemia-induced infarction in MCAO rats,and improved neural functional restoration when assessed by rotarod,footfault and comer-turn tests.The grafted cells migrated predominantly to several specific brain regions,such as corpus callosum and peri-infarct area.Furthermore,these cells

  2. Cerebral Microbleeds and Cognitive Function in Ischemic Stroke or Transient Ischemic Attack Patients.

    Science.gov (United States)

    Wang, Zhaolu; Wong, Adrian; Liu, Wenyan; Yang, Jie; Chu, Winnie C W; Au, Lisa; Lau, Alexander; Chan, Anne; Xiong, Yunyun; Soo, Yannie; Leung, Thomas; Wong, Lawrence K S; Mok, Vincent C T

    2015-01-01

    We explored the association between cerebral microbleeds (CMBs) and cognitive impairment in patients with ischemic stroke/transient ischemic attack (TIA). A total of 488 ischemic stroke/TIA patients received magnetic resonance imaging. Montreal Cognitive Assessment (MoCA) was used to evaluate global cognitive function and cognitive domains. The association of CMB quantity with cognitive function and the impact of CMB locations (strictly lobar, strictly deep, and mixed regions) on cognitive impairment were examined in regression models with adjustments for confounders. A total of 113 subjects (23.2%) had ≥1 CMB. Strictly lobar, strictly deep, and mixed CMBs were identified in 36, 40, and 37 patients, respectively. The presence of ≥5 CMBs or strictly deep CMBs was associated with the MoCA total score (p = 0.007 and 0.020, respectively). Of all MoCA domains tested, a lower score in the attention domain was related to the presence of ≥5 CMBs (p = 0.014) and strictly deep CMBs (p = 0.028). CMBs were associated with cognitive dysfunction in stroke/TIA patients, especially in the attention domain. This association was mainly driven by CMBs in the deep region, underlining the role of hypertensive microangiopathy in stroke-related cognitive impairment.

  3. Influence of Electroacupuncture on the Expressions of BDNF and TrkB in Ischemic Cortex of Rats With Local Cerebral Ischemia%电针对局灶性脑缺血模型大鼠皮层BDNF、TrkB的影响

    Institute of Scientific and Technical Information of China (English)

    王彦春; 陈剑明; 梁少荣; 马骏; 甘水咏; 王述菊; 姜拯坤; 雷俊; 王培峻; 许永海

    2012-01-01

    Objective: To observe the influence of dectroacupuncture( EA)on the expressions of BDNF and its receptor TrkB in ischemic cortex of rats with local cerebral ischemia. Methods : The model of focal cerebral ischemia was set up by blocking up the middle cerebral artery(MCA) with filament in rats. The expressions of BDNF and TrkB positive neurons in ischemic cortex was observed with the method of immunocytochemistry SABC. Results: BDNF and TrkB positive neurons were mainly distributed in cortex around the ischemic focus. In pseudo - operation groups ,BDNF and TrkB positive neurons were few and low - expression in identical area. The expressions of BDNF and TrkB around ischemic cortex of model groups were significantly higher than that of pseudo - operation group( P < 0. 05); BDNF and TrkB positive neurons in EA group were more than that of model group(P<0. 05). Conclusion ;EA at Fengfu has a protective effect on ischemic brain injury by increasing the BDNF and its receptor TrkB expressions in cortex around the ischemic focus.%目的:观察电针对不同时间点局灶性脑缺血模型大鼠缺血区皮层BDNF、TrkB的影响.方法:采用线栓改良法复制大脑中动脉缺血模型(MCAO),采用免疫组化SABC法观察缺血皮层BDNF、TrkB表达情况.结果:BDNF、TrkB阳性神经元主要分布在梗死灶周围皮质区.假手术组大鼠相应区域可见少量阳性神经元表达,且强度较弱;模型组各时间点梗死周围皮质BDNF、TrkB阳性神经元比假手术组明显增多,差异有统计学意义(P<0.05);电针组各时间点梗死周围皮质BDNF、TrkB比相同时间点模型组显著增多,差异有统计学意义(P<0.05).结论:电针风府穴可以增加急性脑缺血后缺血周围皮质BDNF、TrkB阳性神经元,对缺血性脑损伤起修复和保护作用.

  4. Electrical stimulation of the vagus nerve protects against cerebral ischemic injury through an anti-infammatory mechanism

    Directory of Open Access Journals (Sweden)

    Yao-xian Xiang

    2015-01-01

    Full Text Available Vagus nerve stimulation exerts protective effects against ischemic brain injury; however, the underlying mechanisms remain unclear. In this study, a rat model of focal cerebral ischemia was established using the occlusion method, and the right vagus nerve was given electrical stimulation (constant current of 0.5 mA; pulse width, 0.5 ms; frequency, 20 Hz; duration, 30 seconds; every 5 minutes for a total of 60 minutes 30 minutes, 12 hours, and 1, 2, 3, 7 and 14 days after surgery. Electrical stimulation of the vagus nerve substantially reduced infarct volume, improved neurological function, and decreased the expression levels of tumor necrosis factor-and interleukin- 6 in rats with focal cerebral ischemia. The experimental findings indicate that the neuroprotective effect of vagus nerve stimulation following cerebral ischemia may be associated with the inhibition of tumor necrosis factor- and interleukin-6 expression.

  5. electrical stimulation of the vagus nerve protects against cerebral ischemic injury through an anti-inlfammatory mechanism

    Institute of Scientific and Technical Information of China (English)

    Yao-xian Xiang; Wen-xin Wang; Zhe Xue; Lei Zhu; Sheng-bao Wang; Zheng-hui Sun

    2015-01-01

    Vagus nerve stimulation exerts protective effects against ischemic brain injury; however, the underlying mechanisms remain unclear. In this study, a rat model of focal cerebral ischemia was established using the occlusion method, and the right vagus nerve was given electrical stimula-tion (constant current of 0.5 mA; pulse width, 0.5 ms; frequency, 20 Hz; duration, 30 seconds; every 5 minutes for a total of 60 minutes) 30 minutes, 12 hours, and 1, 2, 3, 7 and 14 days after surgery. Electrical stimulation of the vagus nerve substantially reduced infarct volume, improved neurological function, and decreased the expression levels of tumor necrosis factor-α and in-terleukin-6 in rats with focal cerebral ischemia. The experimental findings indicate that the neuroprotective effect of vagus nerve stimulation following cerebral ischemia may be associated with the inhibition of tumor necrosis factor-α and interleukin-6 expression.

  6. 缺血后处理对全脑缺血损伤后神经元结构可塑性及记忆的影响%Effects of ischemic postconditioning on neuron structure plasticity and memory after global cerebral ischemia injury in rats

    Institute of Scientific and Technical Information of China (English)

    李鑫; 秦新月; 郭振委; 吴小慧

    2010-01-01

    目的 观察缺血后处理(Ischemic postconditioning)对全脑缺血损伤后神经元结构可塑性及记忆的影响,从形态学的角度对缺血后处理的保护作用机制进行探讨.方法 SD成年雄性大鼠36只,随机数字表法分为为假手术组、全脑缺血15 min组、全脑缺血+后处理组,每组12只,处理方式为缺血/再灌注各15 s,循环3次.每组6只以Morris水迷宫观察学习记忆,重复性方差分析处理数据,另外6只以高尔基(golgi)银染观察神经元形态与树突棘密度变化,使用方差分析进行统计分析.结果 缺血后处理组逃避潜伏期较全脑缺血组明显缩短(第3天P=0.014,第4天P=0.040第5天P=0.001),缺血后处理组树突棘密度较全脑缺血组明显增多(F=562.820,P<0.01) 结论缺血后处理对脑缺血所致的记忆损伤有明显的保护作用,其机制可能与减少树突棘的损伤有关.%Objective To observe the effect of ischemic postconditioning on neuron structure plasticity and memory after global cerebral ischemia injury in rats and discuss the protection mechanism from aspect of Morphology. Methods A total of 36 SD male rats were randomly divided into sham operation group, global cerebral ischemia for 15 min group and global cerebral ischemia plus postconditioning group, 12 rats per group. The pullsinelli 4 vessel occlusion was applied to produce the models of global cerebral ischemia reperfusion injury, common carotid arteries (CCA) occlusion with 15 min and postconditioning with three cycles, of 15 sec release and 15 sec occlusion (15s/15s). Six rats from each group were evaluated by Morris Maze test for the ability of space learning and memory and the other six rats were evaluated by golgi stain for morphologic change of neuron. Results The ischemic postcondtioning group showed significant shorter mean escape latency compared with the sham operated group ( at day 3, P =0. 014; at day 4, P =0.040; at day 5, P =0.001 ). The density of dendritic

  7. Influences of ischemic preconditioning on autophagy in rats with cerebral ischemia reperfusion injury%缺血预处理对大鼠脑缺血再灌注自噬的影响

    Institute of Scientific and Technical Information of China (English)

    石秋艳; 刘冰; 张春阳; 范亚霞; 孙原; 杨斌

    2014-01-01

    Objective To observe the effect of ischemic preconditioning ( IPC) effect on cerebral ischemia reperfusion in rat hippocampus of autophagy .Methods According to method of Zea-Longa filamene , rats middle cerebral artery ischemi-a-reperfusion model were established , the experimental animal were randomly divided into 3 groups: sham operation group (Sham group, n =10), ischemia reperfusion group (I/R group, n =10), IPC treatment group (IPC group, n =30), in IPC group, according to ischemic preconditioning time , rats were divided into 1 d, 3 d, 5 d subgroups, 10 rats in each group.Af-ter ischemia 2 h and reperfusion 24 h, immunohistochemical method was used to detect the autophagy associated protein BEC -LIN L, LC3-II expression, transmission electron microscope in nerve cell autophagy and lysosomal activation and cell ultra -structure changes .Results ( 1 ) Neurological dysfunction score: compared with Sham group , I/R group and IPC group showed varying degrees of nerve dysfunction ( P <0.01), I/R group of symptoms in IPC subgroups ( P <0.05).(2) The volume of cerebral infarction:compared with Sham group , I/R group and IPC group had different degree of infarction ( P <0.01);IPC group was lower than that in I/R group ( P <0.01), 3 d subgroup was less than 1 d and 5 d subgroup ( P <0.01).(3) Immunohistochemical staining:compared with Sham group , I/R group and IPC group, the number of BECLIN 1 and LC3-II positive cells ( P <0.01), the expression of IPC positive cells was significantly lower than that of I /R group (P <0.01), IPC 3 d subgroup was less than 1 d, 5 d subgroup ( P <0.01).(4) The change of brain tissue ultrastructure morphology of cells:Sham group was normal;I/R group and IPC group showed varying amounts of autophagy , in different peri-od and or autophagic lysosome , mitochondria swelling, rupture of membranes, vesicles, lysosomes increased significantly ,visi-ble deformation of secondary lysosomes ,Golgi fragmentation;IPC group autophagy and the number

  8. Actualities on molecular pathogenesis and repairing processes of cerebral damage in perinatal hypoxic-ischemic encephalopathy.

    Science.gov (United States)

    Distefano, Giuseppe; Praticò, Andrea D

    2010-09-16

    Hypoxic-ischemic encephalopathy (HIE) is the most important cause of cerebral damage and long-term neurological sequelae in the perinatal period both in term and preterm infant. Hypoxic-ischemic (H-I) injuries develop in two phases: the ischemic phase, dominated by necrotic processes, and the reperfusion phase, dominated by apoptotic processes extending beyond ischemic areas. Due to selective ischemic vulnerability, cerebral damage affects gray matter in term newborns and white matter in preterm newborns with the typical neuropathological aspects of laminar cortical necrosis in the former and periventricular leukomalacia in the latter. This article summarises the principal physiopathological and biochemical processes leading to necrosis and/or apoptosis of neuronal and glial cells and reports recent insights into some endogenous and exogenous cellular and molecular mechanisms aimed at repairing H-I cerebral damage.

  9. Actualities on molecular pathogenesis and repairing processes of cerebral damage in perinatal hypoxic-ischemic encephalopathy

    Directory of Open Access Journals (Sweden)

    Praticò Andrea D

    2010-09-01

    Full Text Available Abstract Hypoxic-ischemic encephalopathy (HIE is the most important cause of cerebral damage and long-term neurological sequelae in the perinatal period both in term and preterm infant. Hypoxic-ischemic (H-I injuries develop in two phases: the ischemic phase, dominated by necrotic processes, and the reperfusion phase, dominated by apoptotic processes extending beyond ischemic areas. Due to selective ischemic vulnerability, cerebral damage affects gray matter in term newborns and white matter in preterm newborns with the typical neuropathological aspects of laminar cortical necrosis in the former and periventricular leukomalacia in the latter. This article summarises the principal physiopathological and biochemical processes leading to necrosis and/or apoptosis of neuronal and glial cells and reports recent insights into some endogenous and exogenous cellular and molecular mechanisms aimed at repairing H-I cerebral damage.

  10. Free radical reaction in ischemic rat brain. ESR-CT imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kayama, Takamasa [Yamagata Univ. (Japan). School of Medicine

    1998-07-01

    Free radical change in images of rat brain during brain ischemia was observed by using a rapid scan L-band ESR-CT system. Male Wistar rats weighing 200 g were used. Rats were divided into three groups according to the duration of occlusion of 2, 4, and 8 hr as well as a control, sham-operated group. C-PROXYL dissolved in saline solution was used as an imaging agent and injected intraperitoneally in a volume of 3 ml at a concentration of 0.3 M at the beginning of reperfusion. ESR-CT imaging was performed 20 min after injection of C-PROXYL. In the sham-operated group, histological examination disclosed no ischemic lesion. Because C-PROXYL does not pass the blood-brain barrier, no brain image was obtained. In the 2 hr occlusion ischemic group, histological findings revealed spongioid change at the dorsal putamen. The ESR-CT image showed a small spot of uptake of nitroxide radicals in the area of the presumed left putamen which corresponded to the histological ischemic lesion. In the 8 hr occlusion group, the ischemic lesion was found even in the cerebral cortex. The image of nitroxide radical in the brain again closely corresponded to the histological ischemic area and occupied most of the left cerebral hemisphere. However, the area of ESR-CT image was wider than that of histological ischemic lesion. This may be because C-PROXYL leakage in the ischemic lesion diffuses and also because the extent of the efficiency of scavenging free radicals may decline. (K.H.)

  11. Acute hyperglycemia worsens ischemic stroke-induced brain damage via high mobility group box-1 in rats.

    Science.gov (United States)

    Huang, Jingyang; Liu, Baoyi; Yang, Chenghui; Chen, Haili; Eunice, Dzivor; Yuan, Zhongrui

    2013-10-16

    Hyperglycemia adversely affects the outcome of ischemic stroke. Extracellular HMGB1 plays a role in aggravating brain damage in the postischemic brain. The aim of this study was to determine whether the extracellular HMGB1 is involved in the worsened ischemic damage during hyperglycemic stroke. Male Wistar rats underwent middle cerebral artery occlusion (MCAO) for 90 min with reperfusion. Acute hyperglycemia was induced by an injection of 50% dextrose. Rats received glycyrrhizin, a specific HMGB1 inhibitor, or vehicle. HMGB-1 in cerebrospinal fluid and in brain parenchyma was detected at 2 or 4 h post-reperfusion. Neurological deficits, infarct volume and cerebral edema were assessed 24 h post-MCAO the disruption of blood-brain barrier (BBB) and the expression of tight junction protein Occludin were measured at 4 h post-reperfusion. Hyperglycemia enhanced the early release of HMGB1 from ischemic brain tissue, which was accompanied by increased infarct volume, neurological deficit, cerebral edema and BBB disruption. Glycyrrhizin alleviated the aggravation of infarct volume, neurological deficit, cerebral edema and BBB disruption by decreasing the degradation of tight junction protein Occludin in the ischemic hemisphere of hyperglycemic rats. In conclusion, enhanced early extracellular release of HMGB1 might represent an important mechanism for worsened ischemic damage, particularly early BBB disruption, during hyperglycemic stroke. An HMGB1 inhibitor glycyrrhizin is a potential therapeutic option for hyperglycemic stroke.

  12. Intracranial transplantation of monocyte-derived multipotential cells enhances recovery after ischemic stroke in rats.

    Science.gov (United States)

    Hattori, Hidenori; Suzuki, Shigeaki; Okazaki, Yuka; Suzuki, Norihiro; Kuwana, Masataka

    2012-02-01

    Cell transplantation has emerged as a potential therapy to reduce the neurological deficits caused by ischemic stroke. We previously reported a primitive cell population, monocyte-derived multipotential cells (MOMCs), which can differentiate into mesenchymal, neuronal, and endothelial lineages. In this study, MOMCs and macrophages were prepared from rat peripheral blood and transplanted intracranially into the ischemic core of syngeneic rats that had undergone a left middle cerebral artery occlusion procedure. Neurological deficits, as evaluated by the corner test, were less severe in the MOMC-transplanted rats than in macrophage-transplanted or mock-treated rats. Histological evaluations revealed that the number of microvessels that had formed in the ischemic boundary area by 4 weeks after transplantation was significantly greater in the MOMC-transplanted rats than in the control groups. The blood vessel formation was preceded by the appearance of round CD31(+) cells, which we confirmed were derived from the transplanted MOMCs. Small numbers of bloodvessels incorporating MOMC-derived endothelial cells expressing a mature endothelial marker RECA-1 were detected at 4 weeks after transplantation. In addition, MOMCs expressed a series of angiogenic factors, including vascular endothelial growth factor, angiopoetin-1, and placenta growth factor (PlGF). These findings provide evidence that the intracranial delivery of MOMCs enhances functional recovery by promoting neovascularization in a rat model for ischemic stroke.

  13. Difference in the Location and Risk Factors of Cerebral Microbleeds According to Ischemic Stroke Subtypes

    OpenAIRE

    Kim, Bum Joon; Yoon, Youngshin; Sohn, Hoyon; Kang, Dong-Wha; Kim, Jong S.; Kwon, Sun U.

    2016-01-01

    Background and Purpose The location of cerebral microbleeds (CMBs) may differ according to ischemic stroke subtype, and the underlying pathomechanism may differ by their location. Here, we investigated the characteristics of CMBs according to various ischemic stroke subtypes to verify this issue. Methods Patients with acute ischemic stroke were consecutively included. The presence of CMBs was determined by gradient echo image sequence. The distribution of CMBs was classified as deep, lobar, o...

  14. 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.

  15. Hyperlipidemia exacerbates cerebral injury through oxidative stress, inflammation and neuronal apoptosis in MCAO/reperfusion rats.

    Science.gov (United States)

    Cao, Xiao-Lu; Du, Jing; Zhang, Ying; Yan, Jing-Ting; Hu, Xia-Min

    2015-10-01

    Recent studies showed that hyperglycemia enhanced brain damage when subjected to transient cerebral ischemic stroke. However, the etiologic link between them has been less known. In the present study, based on an experimental rat's model of hyperlipidemia combined with cerebral ischemia-reperfusion injury (I/R), we herein showed that hyperlipidemia induced by high-fat diet (HFD) resulted in considerable increase in serum triglycerides, cholesterol and low-density lipoprotein cholesterol, and remarkable decrease in serum high-density lipoprotein cholesterol, which associated with an exacerbation on neurological deficit, cerebral infarct and terminal deoxynucleotidyl transferase-mediated nick end labeling-positive cells in the ischemic hemisphere of cerebral I/R rats treated with HFD diet. The data showed that serum superoxide dismutase activity and glutathione peroxides content were significantly decreased, while malondialdehyde level was obviously increased by hyperlipidemia or cerebral I/R alone, especially by coexistence of hyperlipidemia and cerebral I/R; meantime, hyperlipidemia also enhanced cerebral I/R-induced protein expression of cytochrome P450 2E1 (CYP2E1) and the levels of pro-inflammatory factors tumor necrosis factor-α and IL-6 in the ischemic hemispheres. Furthermore, the combined action of hyperlipidemia and cerebral I/R resulted in a protein increase expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 compared to hyperlipidemia or cerebral I/R alone. Meanwhile, this study also showed that hyperlipidemia significantly enhanced cerebral I/R-induced transfer of cytochrome c from mitochondria to cytosolic and the protein expressions of Apaf-1 and caspase-3, but also decreased cerebral I/R-induced bcl-2 protein expression. The results reveal that hyperlipidemia exacerbates cerebral I/R-induced injury through the synergistic effect on CYP2E1 induction, which further induces reactive oxygen species formation, oxidative

  16. Identification of ischemic regions in a rat model of stroke.

    Directory of Open Access Journals (Sweden)

    Anke Popp

    Full Text Available BACKGROUND: Investigations following stroke first of all require information about the spatio-temporal dimension of the ischemic core as well as of perilesional and remote affected tissue. Here we systematically evaluated regions differently impaired by focal ischemia. METHODOLOGY/PRINCIPAL FINDINGS: Wistar rats underwent a transient 30 or 120 min suture-occlusion of the middle cerebral artery (MCAO followed by various reperfusion times (2 h, 1 d, 7 d, 30 d or a permanent MCAO (1 d survival. Brains were characterized by TTC, thionine, and immunohistochemistry using MAP2, HSP72, and HSP27. TTC staining reliably identifies the infarct core at 1 d of reperfusion after 30 min MCAO and at all investigated times following 120 min and permanent MCAO. Nissl histology denotes the infarct core from 2 h up to 30 d after transient as well as permanent MCAO. Absent and attenuated MAP2 staining clearly identifies the infarct core and perilesional affected regions at all investigated times, respectively. HSP72 denotes perilesional areas in a limited post-ischemic time (1 d. HSP27 detects perilesional and remote impaired tissue from post-ischemic day 1 on. Furthermore a simultaneous expression of HSP72 and HSP27 in perilesional neurons was revealed. CONCLUSIONS/SIGNIFICANCE: TTC and Nissl staining can be applied to designate the infarct core. MAP2, HSP72, and HSP27 are excellent markers not only to identify perilesional and remote areas but also to discriminate affected neuronal and glial populations. Moreover markers vary in their confinement to different reperfusion times. The extent and consistency of infarcts increase with prolonged occlusion of the MCA. Therefore interindividual infarct dimension should be precisely assessed by the combined use of different markers as described in this study.

  17. Cardiological evaluation of patients with a cerebral ischemic event: the relation between heart and brain

    NARCIS (Netherlands)

    G.A.M. Pop (Gheorghe)

    1992-01-01

    textabstractIn this study several aspects of the cardiological evaluation of patients with cerebral ischemia are described; its usefulness for diagnosis and treatment is discussed. The aim of this thesis is to approach the clinical and epidemiological aspects of patients with cerebral ischemic event

  18. 尤瑞克林对大鼠局灶性脑缺血再灌注损伤后APE/Ref-1表达的影响%Effect of Urinary kallikrein on the expression of apurinic apyrimidinic endonuclease/redox factor 1(APE/Ref-1) in cerebral tissue of rats subjected to cerebral ischemic-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    王言理; 陈晓兵; 许锁; 刘克喜; 石远峰

    2014-01-01

    ObjectiveTo investigate the effect of Urinary kallikrein on the expression of apurinic apyrimidinic endonuclease/redox factor 1 (APE/Ref-1) in rats which were subjected to reperfusion after middle cerebral artery occlusion (MCAO) for two hours. To explore the protective mechanism of Urinary kallikrein against ischemic/reperfusion brain injury.Methods 54 male Sprague-Dawley rats were randomly divided into three groups with 18 mice each group: control group (Con group), ischemic/reperfusion group (Model group), ischemic/reperfusion plus Urinary kallikrein group (URK group). Six rats from each group randomly selected were respectively subjected to the detection of APE/Ref-1 positive cell count in CA1 region of hippocampus by immunohistochernistry, the detection of cerebral infarct volume by TTC staining and the detection of the expression of protein APE/Ref-1 in hippocampus by Western blot.ResultsCompared with Con group, the levels of protein of expression of APE/Ref-1 in hippocampus significantly decreased (P<0.05), with the APE/Ref-1 positive cell count in CA3 region of hippocampus significantly lower (P<0.05), Urinary kallikreincan increase the protein of expression of APE/Ref-1 and the APE/Ref-1 positive cell count in CA1 region of hippocampus, but lower than that of Con group, Urinary kallikrein can decrease thecerebral infarct volume induced by the reperfusion after middle cerebral occlusion (MCAO).ConclusionUrinary kallikreincan increase the protein of expression of APE/Ref-1 after focal cerebral ischemia/reperfusion, that may be the other protective mechanism of Urinary kallikrein against ischemic/reperfusion brain injury.%目的:探讨尤瑞克林对大鼠局造性脑缺血再灌注损伤(I/R)后无嘌呤/无嘧啶核酸内切酶/氧化还原因子1(APE/Ref-1)表达的影响,进一步探讨尤瑞克林脑保护作用的机制。方法健康成年雄性SD大鼠54只,采用随机数字表法分为3组:空白对照组(Con组)(n=18),

  19. Nimodipine pretreatment improves cerebral blood flow and reduces brain edema in conscious rats subjected to focal cerebral ischemia.

    Science.gov (United States)

    Jacewicz, M; Brint, S; Tanabe, J; Wang, X J; Pulsinelli, W A

    1990-11-01

    The effect of nimodipine pretreatment on CBF and brain edema was studied in conscious rats subjected to 2.5 h of focal cortical ischemia. An infusion of nimodipine (2 micrograms/kg/min i.v.) or its vehicle, polyethylene glycol 400, was begun 2 h before the ischemic interval and was continued throughout the survival period. Under brief halothane anesthesia, the animals' right middle cerebral and common carotid arteries were permanently occluded, and 2.5 h later, they underwent a quantitative CBF study ([14C]iodoantipyrine autoradiography followed by Quantimet 970 image analysis). Nimodipine treatment improved blood flow to the middle cerebral artery territory without evidence of a "vascular steal" and reduced the volume of the ischemic core (cortex with CBF of less than 25 ml/100 g/min) and accompanying edema by approximately 50% when compared with controls (p = 0.006 and 0.0004, respectively). Mild hypotension induced by nimodipine did not aggravate the ischemic insult. The ischemic core volumes, however, were 50-75% smaller than the 24-h infarct volumes generated in a similar paradigm that demonstrated 20-30% infarct reduction with continuous nimodipine treatment. These results suggest that nimodipine pretreatment attenuates the severity of early focal cerebral ischemia, but that with persistent ischemia, cortex surrounding the ischemic core undergoes progressive infarction and the early benefit of nimodipine treatment is only partly preserved.

  20. 胡黄连苷Ⅱ对脑缺血损伤后神经细胞凋亡和超微结构的影响%Effect of picroside II on neuronal apoptosis and ultrastructure in cerebral ischemic injury in rats

    Institute of Scientific and Technical Information of China (English)

    王婷婷; 赵丽; 李晓丹; 张美增; 郭云良

    2015-01-01

    Aim To explore the effect of picroside II on neuronal apoptosis and ultrastructure after cerebral ischemic injury in rats. Methods The focal cerebral ischemic models were established by inserting a mono-filament thread into middle cerebral artery occlusion ( MCAO) in 60 Wistar rats and treated by injecting picroside Ⅱ ( 20 mg · kg-1 ) intraperitoneally. The neurobehavioral function was evaluated by modified neurological severity score test. The cerebral infarct volume was measured by tetrazolium chloride staining. The morphology and ultrastructure of brain tissue were observed by hematoxylin-eosin staining and transmis-sion electron microscopy respectively. The apoptotic cells were counted by terminal deoxynucleotidyl trans-ferase dUTP nick end labeling assay and the expression of p-ERK1/2 was determined by immunohistochemical assay and Western blot. Results The neurological be- havioral malfunction and the cerebral infarct appeared in rats with MCAO. In model group, the damage of neurons and blood brain barrier ( BBB) in cortex wors-ened, while the number of apoptotic cells and the ex-pression of p-ERK1/2 increased more significantly than those in control group ( P   端标记法检测细胞凋亡,免疫组织化学和Western blot检测p-ERK1/2表达水平。结果大鼠脑缺血损伤后表现出神经功能障碍和脑梗死病灶,皮质区神经元和血脑屏障结构损伤较重,皮质区凋亡细胞数量和p-ERK1/2蛋白表达较对照组明显增多(P<0.05)。治疗组大鼠mNSS评分和脑梗死体积较模型组明显降低(P<0.05),皮质区神经元和血脑屏障损伤减轻,凋亡细胞与p-ERK1/2表达水平较模型组明显降低(P<0.05)。结论胡黄连苷Ⅱ可能抑制神经细胞凋亡,改善缺血区脑组织的形态结构,促进大鼠神经行为功能恢复。

  1. Limb remote ischemic per-conditioning in combination with post-conditioning reduces brain damage and promotes neuroglobin expression in the rat brain after ischemic stroke

    Science.gov (United States)

    Ren, Changhong; Wang, Pengcheng; Wang, Brian; Li, Ning; Li, Weiguang; Zhang, Chenggang; Jin, Kunlin; Ji, Xunming

    2015-01-01

    Abstract Purpose: Limb remote ischemic per-conditioning or post-conditioning has been shown to be neuroprotective after cerebral ischemic stroke. However, the effect of combining remote per-conditioning with post-conditioning on ischemic/reperfusion injury as well as the underlying mechanisms are largely unexplored. Methods: Here, adult male Sprague Dawley rats were subjected to middle cerebral artery occlusion (MCAO). The limb ischemic stimulus was immediately applied after onset of focal ischemia (per-conditioning), followed by repeated short episodes of remote ischemia 24 hr after reperfusion (post-conditioning). The infarct volume, motor function, and the expression of neuroglobin (Ngb) were measured at different durations after reperfusion. Results: We found that a single episode of limb remote per-conditioning afforded short-term protection, but combining repeated remote post-conditioning during the 14 days after reperfusion significantly ameliorated cerebral ischemia/reperfusion injury. Interestingly, we also found that ischemic per- and post-conditioning significantly increased expression of Ngb, an oxygen-binding globin protein that has been demonstrated to be neuroprotective against stroke, at peri-infarct regions from day 1 to day 14 following ischemia/reperfusion. Conclusion: Our results suggest that the conventional per-conditioning combined with post-conditioning may be used as a novel neuroprotective strategy against ischemia-reperfusion injury, and Ngb seems to be one of the important players in limb remote ischemia-mediated neuroprotection. PMID:25868435

  2. Exercise promotes axon regeneration of newborn striatonigral and corticonigral projection neurons in rats after ischemic stroke.

    Directory of Open Access Journals (Sweden)

    Qiu-Wan Zhang

    Full Text Available Newborn striatal neurons induced by middle cerebral artery occlusion (MCAO can form functional projections targeting into the substantia nigra, which should be very important for the recovery of motor function. Exercise training post-stroke improves motor recovery in clinic patients and increases striatal neurogenesis in experimental animals. This study aimed to investigate the effects of exercise on axon regeneration of newborn projection neurons in adult rat brains following ischemic stroke. Rats were subjected to a transient MCAO to induce focal cerebral ischemic injury, followed by 30 minutes of exercise training daily from 5 to 28 days after MCAO. Motor function was tested using the rotarod test. We used fluorogold (FG nigral injection to trace striatonigral and corticonigral projection neurons, and green fluorescent protein (GFP-targeting retroviral vectors combined with FG double labeling (GFP(+ -FG(+ to detect newborn projection neurons. The results showed that exercise improved the recovery of motor function of rats after MCAO. Meanwhile, exercise also increased the levels of BDNF and VEGF, and reduced Nogo-A in ischemic brain. On this condition, we further found that exercise significantly increased the number of GFP(+ -FG(+ neurons in the striatum and frontal and parietal cortex ipsilateral to MCAO, suggesting an increase of newborn striatonigral and corticonigral projection neurons by exercise post-stroke. In addition, we found that exercise also increased NeuN(+ and FG(+ cells in the striatum and frontal and parietal cortex, the ischemic territory, and tyrosine hydroxylase (TH immunopositive staining cells in the substantia nigra, a region remote from the ischemic territory. Our results provide the first evidence that exercise can effectively enhance the capacity for regeneration of newborn projection neurons in ischemic injured mammalian brains while improving motor function. Our results provide a very important cellular mechanism

  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. Changes of Nitric Oxide Synthase Activity in Penumbral and Core Area during Focal Cerebral Ischemia and Reperfusion in Rats

    Institute of Scientific and Technical Information of China (English)

    GUZhen; ZHOUJian-ping; WUWen-zhong; ZHANGYong-jie; HANQun-ying; WANGHe-ming

    2004-01-01

    Objecivee: To study the changes of nitric oxide synthase (NOS) activity in penumbral and core area during focal cerebral ischemia and reperfusion, and to explore the therapeutic window of focal cerebral ischemia. Methods:The middle cerebral artery of rats was occluded for 15, 30,60,90 and 120 min by an inraluminal filament respectively,and recirculation was instituted for 24 h. The changes of NOS activity in ischemic core area(parietal cortex and caudoputamen) and penumbral area ( frontal cortex)were examined after focal cerebral ischemla and reperfusion using NADPH-d histochemistry, technique. Results. The NOS activity of the ischemic penumbral area peaked at 60 min while the ischemic core area peaked at 30 min then declined at 90-120 rain sharply. Conclusion: NOS takes part in cerebral ischemic damage during focal cerebral ischemia and reperfusion. The NOS activity of the ischemic penmnbral area is different from the ischemic core area. The peak time of the penumbral area is delayed comparing with the core area. The data suggest that the best time to apply NOS inhibitor is within 30 min in ischemic core area, and 60 rain in penumbral area.

  5. The role of exogenous neural stem cells transplantation in cerebral ischemic stroke.

    Science.gov (United States)

    Chen, Lukui; Qiu, Rong; Li, Lushen; He, Dan; Lv, Haiqin; Wu, Xiaojing; Gu, Ning

    2014-11-01

    transplantation group. The Nissl dyeing showed that there was a large area of neuronal necrosis and apoptosis in the ischemia and PBS transplantation groups, and damage was mainly focused in the striatum. Degeneration and damage of nerve cells were significantly reduced in the NSCs transplantation group. The Tunel assay showed that the number of apoptosis-positive cells in the NSCs transplantation group was less than that in the PBS transplantation group at each time point. Double immunofluorescent labeling showed that the proliferation of endogenous neural stem cells began at the third day, reaching the peak at the 7th day, and was significantly reduced at the 14th day in the SVZ. The number of BrdU/NeuN increased significantly in the NSCs transplantation group compared to that in the PBS transplantation group (P cells in the striatum was observed to be much more in the PBS transplantation group than in the NSCs transplantation group. Both neurological deficits and coordination capacity of rats with cerebral ischemia were significantly improved via transplantation of the neural stem cells. In conclusion, transplantation of neural stem cells can therefore possibly promote the differentiation of endogenous NSCs into neurons and reduce their differentiation towards glial cells. Transplantation of the neural stem cells may also change the ischemic microenvironment of striatum, possibly inhibiting the proliferation of glial cells.

  6. 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.

  7. Effect of chlorimipramine on recovery of motor function of rats with focal cerebral ischemic injury%氯丙米嗪促进局灶性脑缺血损伤大鼠运动功能恢复的特点

    Institute of Scientific and Technical Information of China (English)

    郭俊; 刘学东; 张晓梅; 周永清; 刘立

    2006-01-01

    BACKGROUND: Amfetamine, one of the levarterenols, can improve the recovery of motor function of animals after cerebral ischemia. Chlorimipramine can inhibit the re-intake of 5-serotonin and levarterenol and improve the level of them in brain. OBJECTIVE: To observe the effect of chlorimipramine on motor function of rats with focal cerebral ischemic injury.DESIGN: Randomized grouping and controlled animal study. SETTING: Neuropsychiatry Team of Aerial Clinical Medical Department of the Fourth Military Medical University of Chinese PLA. MATERIALS: The experiment was completed in the Morphological Laboratory of Aerial Aerospace Medical Department of the Fourth Military Medical University of Chinese PLA. All the 24 SD rats were divided into sham operation group, ischemia group and ischemic medication group with 8 in each group. Rats in ischemic medication group were perfused with 10 mg/kg chlorimipramine solution (2.5 g/L) once a day through mouth 24 hours after ischemia, and rats in sham operation group and ischemia group were perfused with the same volume of distilled water through mouth. METHODS: Middle cerebral artery (MCA) models of ischemia/reperfusion rats were established with inserted lining method. After modeling, the operations were performed as followed: ① holding test of net screen: Net screen was put horizontally, and then rats were put on it. One side of the screen was raised gradually; then it was turned over 125° within 2 s, and maintained at this placement. Time of holding rats on net screen was recorded. ② Test of struggling to tear off rubberized cloth: 0.5 cm2 medical rubberized cloth was adhered to the ventral of anterior claws of rats, and then rats were sent to the observing box to record the time of tearing off rubberized cloth. 1, 3, 7, 14 and 28 days after operation were the observing time points. MAIN OUTCOME MEASURES: Times of holding rats on the net screen and tearing off the rubberized cloth of rats with focal cerebral is chemia

  8. Mechanical thrombectomy for acute ischemic stroke with cerebral microbleeds.

    Science.gov (United States)

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

    2016-06-01

    The influence of cerebral microbleeds (CMBs) on post-thrombolytic hemorrhagic transformation (HT) in patients with acute ischemic stroke remains controversial. To investigate the association of CMBs with HT and clinical outcomes among patients with large-vessel occlusion strokes treated with mechanical thrombectomy. We analyzed patients with acute stroke treated with Merci Retriever, Penumbra system or stent-retriever devices. CMBs were identified on pretreatment T2-weighted, gradient-recall echo MRI. We analyzed the association of the presence, burden, and distribution of CMBs with HT, procedural complications, in-hospital mortality, and clinical outcome. CMBs were detected in 37 (18.0%) of 206 patients. Seventy-three foci of microbleeds were identified. Fourteen patients (6.8%) had ≥2 CMBs, only 1 patient had ≥5 CMBs. Strictly lobar CMBs were found in 12 patients, strictly deep CMBs in 12 patients, strictly infratentorial CMBs in 2 patients, and mixed CMBs in 11 patients. There were no significant differences between patients with CMBs and those without CMBs in the rates of overall HT (37.8% vs 45.6%), parenchymal hematoma (16.2% vs 19.5%), procedure-related vessel perforation (5.4% vs 7.1%), in-hospital mortality (16.2% vs 18.3%), and modified Rankin Scale score 0-3 at discharge. CMBs were not independently associated with HT or in-hospital mortality in patients treated with either thrombectomy or intravenous thrombolysis followed by thrombectomy. Patients with CMBs are not at increased risk for HT and mortality following mechanical thrombectomy for acute stroke. Excluding such patients from mechanical thrombectomy is unwarranted. The risk of HT in patients with ≥5 CMBs requires further study. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  9. WIN55,212-2 protects oligodendrocyte precursor cells in stroke penumbra following permanent focal cerebral ischemia in rats

    OpenAIRE

    SUN, JING; Fang, Yin-quan; Ren, Hong; Tao CHEN; Guo, Jing-Jing; Yan, Jun; SONG, SHU; Zhang, Lu-yong; Liao, Hong

    2012-01-01

    Aim: To explore whether the synthetic cannabinoid receptor agonist WIN55,212-2 could protect oligodendrocyte precursor cells (OPCs) in stroke penumbra, thereby providing neuroprotection following permanent focal cerebral ischemia in rats. Methods: Adult male SD rats were subjected to permanent middle cerebral artery occlusion (p-MCAO). The animals were administered WIN55,212-2 at 2 h, and sacrificed at 24 h after the ischemic insult. The infarct volumes and brain swelling were assessed. The e...

  10. The Neuroprotective Effect of Rosemary (Rosmarinus officinalis L.) Hydro-alcoholic Extract on Cerebral Ischemic Tolerance in Experimental Stroke

    Science.gov (United States)

    Seyedemadi, Parisa; Rahnema, Mehdi; Bigdeli, Mohammad Reza; Oryan, Shahrebano; Rafati, Hassan

    2016-01-01

    The prevention of BBB breakdown and the subsequent vasogenic edema are important parts of the medical management of ischemic stroke. The purpose of this study was to investigate the ischemic tolerance effect of Rosmarinus officinalis leaf hydro-alcoholic extract (RHE). Five groups of animals were designed: sham (underwent surgery without MCAO) and MCAO groups, the MCAO groups were pretreated orally by gavages with RHE (50, 75, and 100 mg/Kg/day), daily for 30 days. Two hours after the last dose, serum lipid levels were determined and then the rats were subjected to 60 min of middle cerebral artery occlusion followed by 24 h of reperfusion. Subsequently, brain infarct size, brain edema and Evans Blue dye extravasations were measured and neurological deficits were scored. Dietary RHE could significantly reduce cortical and sub-cortical infarct volumes (211.55 ± 24.88 mm3 vs. 40.59 ± 10.04 mm3 vs. 29.96 ± 12.19 mm3vs. 6.58 ± 3.2 mm3), neurologic deficit scores, cerebral edema (82.34 ± 0.42% vs. 79.92 ± 0.49% vs. 79.45 ± 0.26% vs. 79.30 ± 0.19%), blood–brain barrier (BBB) permeability (7.73 ± 0.4 μg/g tissue vs. 4.1 ± 0.23 μg/g tissue vs. 3.58 ± 0.3 μg/g tissue vs. 3.38 ± 0.25 μg/g tissue) in doses of 50, 75 and 100 mg/Kg/day as compared with the control group in the transient model of focal cerebral ischemia. Although pretreatment with RHE plays an important role in the generation of tolerance against cerebral I/R injury, further studies are needed to clarify the mechanism of the ischemic tolerance. PMID:28243285

  11. 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.

  12. A Microarray Study of Middle Cerebral Occlusion Rat Brain with Acupuncture Intervention

    Directory of Open Access Journals (Sweden)

    Chao Zhang

    2015-01-01

    Full Text Available Microarray analysis was used to investigate the changes of gene expression of ischemic stroke and acupuncture intervention in middle cerebral artery occlusion (MCAo rat brain. Results showed that acupuncture intervention had a remarkable improvement in neural deficit score, cerebral blood flow, and cerebral infarction volume of MCAo rats. Microarray analysis showed that a total of 627 different expression genes were regulated in ischemic stroke. 417 genes were upregulated and 210 genes were downregulated. A total of 361 different expression genes were regulated after acupuncture intervention. Three genes were upregulated and 358 genes were downregulated. The expression of novel genes after acupuncture intervention, including Tph1 and Olr883, was further analyzed by Real-Time Quantitative Polymerase Chain Reaction (RT-PCR. Upregulation of Tph1 and downregulation of Olr883 indicated that the therapeutic effect of acupuncture for ischemic stroke may be closely related to the suppression of poststroke depression and regulation of olfactory transduction. In conclusion, the present study may enrich our understanding of the multiple pathological process of ischemic brain injury and indicate possible mechanisms of acupuncture on ischemic stroke.

  13. Age-related reduction of cerebral ischemic preconditioning: myth or reality?

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    Della-Morte D

    2013-08-01

    Full Text Available David Della-Morte,1,2 Francesco Cacciatore,3 Elisa Salsano,4 Gilda Pirozzi,4 Maria Teresa Del Genio,4 Iole D'Antonio,4 Gaetano Gargiulo,5 Raffaele Palmirotta,2 Fiorella Guadagni,2 Tatjana Rundek,1 Pasquale Abete41Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL, USA; 2Department of Advanced Biotechnologies and Bioimaging, IRCCS San Raffaele, Rome, Italy; 3Istituto Scientifico di Campoli/Telese, Fondazione Salvatore Maugeri, IRCCS, Benevento, Italy; 4Dipartimento di Scienze Mediche Traslazionali, Università di Napoli "Federico II," Naples, Italy; 5AON, SS Antonio e Biagio e Cesare Arrigo, Struttura Complessa di Geriatria, Alessandria, ItalyAbstract: Stroke is one of the leading causes of death in industrialized countries for people older than 65 years of age. The reasons are still unclear. A reduction of endogenous mechanisms against ischemic insults has been proposed to explain this phenomenon. The “cerebral” ischemic preconditioning mechanism is characterized by a brief episode of ischemia that renders the brain more resistant against subsequent longer ischemic events. This ischemic tolerance has been shown in numerous experimental models of cerebral ischemia. This protective mechanism seems to be reduced with aging both in experimental and clinical studies. Alterations of mediators released and/or intracellular pathways may be responsible for age-related ischemic preconditioning reduction. Agents able to mimic the “cerebral” preconditioning effect may represent a new powerful tool for the treatment of acute ischemic stroke in the elderly. In this article, animal and human cerebral ischemic preconditioning, its age-related difference, and its potential therapeutical applications are discussed.Keywords: ischemic preconditioning, stroke, transient cerebral ischemic attack, mortality, elderly

  14. LXW7 ameliorates focal cerebral ischemia injury and attenuates inflammatory responses in activated microglia in rats

    Energy Technology Data Exchange (ETDEWEB)

    Fang, T.; Zhou, D.; Lu, L.; Tong, X.; Wu, J.; Yi, L. [Department of Neurology, Shenzhen Hospital, Peking University, Shenzhen (China)

    2016-08-01

    Inflammation plays a pivotal role in ischemic stroke, when activated microglia release excessive pro-inflammatory mediators. The inhibition of integrin αvβ3 improves outcomes in rat focal cerebral ischemia models. However, the mechanisms by which microglia are neuroprotective remain unclear. This study evaluated whether post-ischemic treatment with another integrin αvβ3 inhibitor, the cyclic arginine-glycine-aspartic acid (RGD) peptide-cGRGDdvc (LXW7), alleviates cerebral ischemic injury. The anti-inflammatory effect of LXW7 in activated microglia within rat focal cerebral ischemia models was examined. A total of 108 Sprague-Dawley rats (250–280 g) were subjected to middle cerebral artery occlusion (MCAO). After 2 h, the rats were given an intravenous injection of LXW7 (100 μg/kg) or phosphate-buffered saline (PBS). Neurological scores, infarct volumes, brain water content (BWC) and histology alterations were determined. The expressions of pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β)], and Iba1-positive activated microglia, within peri-ischemic brain tissue, were assessed with ELISA, western blot and immunofluorescence staining. Infarct volumes and BWC were significantly lower in LXW7-treated rats compared to those in the MCAO + PBS (control) group. The LXW7 treatment lowered the expression of pro-inflammatory cytokines. There was a reduction of Iba1-positive activated microglia, and the TNF-α and IL-1β expressions were attenuated. However, there was no difference in the Zea Longa scores between the ischemia and LXW7 groups. The results suggest that LXW7 protected against focal cerebral ischemia and attenuated inflammation in activated microglia. LXW7 may be neuroprotective during acute MCAO-induced brain damage and microglia-related neurodegenerative diseases.

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

    Institute of Scientific and Technical Information of China (English)

    Qiu Fen; Liu Yong; Zhang Pengbo; Kang Qianyan; Tian Yingfang; Chen Xinlin; Zhao Jianjun; Qi Cunfang

    2006-01-01

    Objective To explore the effect of Ligustrazine on neurogenesis in cortex after focal cerebral ischemia in rats. Methods Focal cerebral ischemia was induced by left middle cerebral arteryocclusion with asuture. Two hours later, injection of Ligustrazine (80 mg/kg, 1 time/d) was performed peritoneally. Four hours after the ischemia,5-bromodeoxyuridine (BrdU) (50 mg/kg, 1 time/d) was injected peritoneally. At 7 d, 14 d and 21 d after ischemia,BrdU positive cells in the cortex were observed by immunohistochemical staining. Results In ischemic model group, at 7 day, sparsely-distributed BrdU positive cells were observed in the Ⅱ - Ⅵ layers of the ipsilateral cortex, with a band-like distribution in ischemic penumbra. With the prolongation of ischemia, the number of BrdU positive cells increased.In Ligustrazine group, BrdU positive cells were also observed in the Ⅱ - Ⅵ layers of the cortex, with an intense distribution in ischemic penumbra. The numbers of BrdU positive cells at 7 d, 14 d and 21 d were more than those in ischemic model group respectively. Conclusion Ligustrazine increases the proliferated cells in cortex after focal cerebral ischemia in rats. The results suggest that it may be useful for promoting self-repair after ischemia.

  16. Temporal thresholds for neocortical infarction in rats subjected to reversible focal cerebral ischemia.

    Science.gov (United States)

    Kaplan, B; Brint, S; Tanabe, J; Jacewicz, M; Wang, X J; Pulsinelli, W

    1991-08-01

    We investigated the temporal threshold for focal cerebral infarction in the spontaneously hypertensive rat. The right middle cerebral artery and common carotid artery were occluded for 0, 1, 2, 3, 4, or 24 hours, and all the animals were sacrificed 24 hours after the onset of ischemia. Cortical infarct volumes and edema volumes were quantified in serial frozen sections of hematoxylin and eosin-stained tissue using image analysis. Upon occlusion, blood flow in the core of the ischemic zone, measured with laser-Doppler flowmetry, fell to a mean +/- standard deviation of 21 +/- 7% of the preocclusion baseline value (n = 26). During the first hour of ischemia, blood flow in the densely ischemic zone rose to 27 +/- 8% of baseline (n = 25). Release of the middle cerebral artery and common carotid artery occlusions rapidly restored cortical blood flow to 213 +/- 83% of baseline (n = 21). Focal ischemia of 1 hour's duration caused little or no infarction, while ischemic intervals of 2 and 3 hours produced successively larger volumes of infarcted cortex. Ischemic intervals of 3-4 hours' duration followed by approximately 20 hours of recirculation yielded infarct volumes that were not significantly different from those after 24 hours of permanent focal ischemia. The results indicate that 3-4 hours of focal cerebral ischemia in this rat model is sufficient to attain maximal infarction and suggest that recirculation or pharmacological interventions after this time will provide little benefit.

  17. Protein kinase C inhibition attenuates vascular ETB receptor upregulation and decreases brain damage after cerebral ischemia in rat

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    Vikman Petter

    2007-01-01

    Full Text Available Abstract Background Protein kinase C (PKC is known to be involved in the pathophysiology of experimental cerebral ischemia. We have previously shown that after transient middle cerebral artery occlusion, there is an upregulation of endothelin receptors in the ipsilateral middle cerebral artery. The present study aimed to examine the effect of the PKC inhibitor Ro-32-0432 on endothelin receptor upregulation, infarct volume and neurology outcome after middle cerebral artery occlusion in rat. Results At 24 hours after transient middle cerebral artery occlusion (MCAO, the contractile endothelin B receptor mediated response and the endothelin B receptor protein expression were upregulated in the ipsilateral but not the contralateral middle cerebral artery. In Ro-32-0432 treated rats, the upregulated endothelin receptor response was attenuated. Furthermore, Ro-32-0432 treatment decreased the ischemic brain damage significantly and improved neurological scores. Immunohistochemistry showed fainter staining of endothelin B receptor protein in the smooth muscle cells of the ipsilateral middle cerebral artery of Ro-32-0432 treated rats compared to control. Conclusion The results suggest that treatment with Ro-32-0432 in ischemic stroke decreases the ischemic infarction area, neurological symptoms and associated endothelin B receptor upregulation. This provides a new perspective on possible mechanisms of actions of PKC inhibition in cerebral ischemia.

  18. siRNA-mediated silence of protease-activated receptor-1 minimizes ischemic injury of cerebral cortex through HSP70 and MAP2.

    Science.gov (United States)

    Zhang, Jun; Wang, Ying; Zhu, Ping; Wang, Xudong; Lv, Manhua; Feng, Honglin

    2012-09-15

    Cerebral ischemic stroke is a prevalent disease in senior individuals. The anticoagulation and thrombolysis to recover blood supply as well as the diminution of neural excitotoxicity to protect brain cells have not shown to fully improve stroke patients. The comprehensive mechanisms and medication specificity remain to be addressed. The silence of specific mRNAs by RNA interference provides revenues for such goals. We examined whether the silence of protease-activated receptor-1 (PAR-1) by siRNA protects brain tissues from ischemic injury. In three groups of Wistar rats, their lateral ventricles received the injections of lentiviral vectors carrying siRNA for PAR1, small RNA in mismatching PAR1 or saline. A week after the injections, these rats were treated by one side of middle cerebral artery occlusion (MCAO). The scores of neurological deficits, the volume of ischemic infarction and the expressions of PAR-1, HSP-70 and MAP-2 were measured in 24h of MCAO. Our results show that the silence of PAR-1 significantly reduces neurological deficits and infarction volume, as well as elevates HSP-70 and MAP-2 expressions. Thus, the knock-down of PAR1 minimizes the ischemic impairments of cerebral cortex via HSP70 and MAP-2 pathways. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. 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

  20. 灯盏细辛与赤芍配伍对永久性脑缺血损伤大鼠的保护作用%Compatibility of erigeron breviscapus and radix paeoniae rubra protects rats against cerebral ischemic injury

    Institute of Scientific and Technical Information of China (English)

    范娅丹; 韩江全; 邓才洪

    2016-01-01

    目的:探讨灯盏细辛与赤芍配伍药对脑缺血性损伤大鼠的保护作用及可能机制。方法方法48只成年SD雄性大鼠随机分为4组:假手术组、脑缺血组、配伍药物治疗组、阻滞剂组,每组12只。采用线栓法制作大脑中动脉闭塞模型。于缺血后24 h后行神经功能缺损评分,断头取脑行TTC染色检测脑梗死面积,实时荧光定量PCR法、蛋白质免疫印记法测缺血区脑皮质SHH、Patched-1、Gli-1mRNA及蛋白的表达。结果配伍药物组缺损评分、脑组织梗死面积显著低于脑缺血组和阻滞剂组。脑组织shh、Patched-1、Gli-1 mRNA及蛋白表达量显著高于脑缺血组,阻滞剂组Gli-1mRNA及蛋白表达量显著低于配伍药物组。结论灯盏乙素与芍药苷配伍对大鼠局灶性脑缺血损伤具有一定的保护作用,其机制与上调Sonic Hedgehog ( Shh)通路关键蛋白分子表达量有关。%Objective To investigate the protective effect of the compatibility of Erigeron breviscapus and Radix Paeoniae Rubra on cerebral ischemia injury rats and its possible mechanisms .Methods Forty-eight adult male Sprague-Dawley rats were divided into four groups randomly:a sham operation group ,a cerebral ischemia group ,a treatment group and an inhibitor group,12 in each group.MCAO model was performed according to Zea-longa’s report.Neurological deficit scores were performed after 24 h of the operation .Then decapitated the rats and took out their brain .Detected infarct size by 2,3,5-triphenyltetrazolium chloride (TTC) staining,and detected the expression of the mRNA levels of Shh、Patched-1、Gli-1 by RT-PCR and assessed the proteins expression of them by Western blotting .Results The neurological deficit score and the infarct size in the treatment group were lower than that in the cerebral ischemia and inhibitors groups ,both of the differences were statistically significant .RT-PCR and Western blotting suggested that the mRNA and

  1. Cortical neurogenesis in adult rats after ischemic brain injury:most new neurons fail to mature

    Institute of Scientific and Technical Information of China (English)

    Qing-quan Li; Guan-qun Qiao; Jun Ma; Hong-wei Fan; Ying-bin Li

    2015-01-01

    The present study examines the hypothesis that endogenous neural progenitor cells isolated from the neocortex of ischemic brain can differentiate into neurons or glial cells and contribute to neural regeneration. We performed middle cerebral artery occlusion to establish a model of cerebral ischemia/reperfusion injury in adult rats. Immunohistochemical staining of the cortex 1, 3, 7, 14 or 28 days after injury revealed that neural progenitor cells double-positive for nestin and sox-2 appeared in the injured cortex 1 and 3 days post-injury, and were also positive for glial ifbrillary acidic protein. New neurons were labeled using bromodeoxyuridine and different stages of maturity were identiifed using doublecortin, microtubule-associated protein 2 and neuronal nuclei antigen immunohistochemistry. Immature new neurons coexpressing doublecortin and bromodeoxyuridine were observed in the cortex at 3 and 7 days post-injury, and semi-mature and mature new neurons double-positive for microtubule-associated protein 2 and bromode-oxyuridine were found at 14 days post-injury. A few mature new neurons coexpressing neuronal nuclei antigen and bromodeoxyuridine were observed in the injured cortex 28 days post-injury. Glial ifbrillary acidic protein/bromodeoxyuridine double-positive astrocytes were also found in the injured cortex. Our ifndings suggest that neural progenitor cells are present in the damaged cortex of adult rats with cerebral ischemic brain injury, and that they differentiate into astrocytes and immature neurons, but most neurons fail to reach the mature stage.

  2. Expression of Clock genes in the pineal glands of newborn rats with hypoxic-ischemic encephalopathy

    Institute of Scientific and Technical Information of China (English)

    Bin Sun; Xing Feng; Xin Ding; Li Bao; Yongfu Li; Jun He; Meifang Jin

    2012-01-01

    Clock genes are involved in circadian rhythm regulation,and surviving newborns with hypoxic-ischemic encephalopathy may present with sleep-wake cycle reversal.This study aimed to determine the expression of the clock genes Clock and Bmall,in the pineal gland of rats with hypoxic-ischemic brain damage.Results showed that levels of Clock mRNA were not significantly changed within 48 hours after cerebral hypoxia and ischemia.Expression levels of CLOCK and BMAL1 protein were significantly higher after 48 hours.The levels of Bmall mRNA reached a peak at 36 hours,but were significantly reduced at 48 hours.Experimental findings indicate that Clock and Bmall genes were indeed expressed in the pineal glands of neonatal rats.At the initial stage (within 36 hours) of hypoxic-ischemic brain damage,only slight changes in the expression levels of these two genes were detected,followed by significant changes at 36 48 hours.These changes may be associated with circadian rhythm disorder induced by hypoxic-ischemic brain damage.

  3. [Diagnosis and prognosis of cerebral ischemic disturbances course using a method of artificial neuronal networks].

    Science.gov (United States)

    Ivanov, Iu S; Semin, G F

    2004-01-01

    Based on the data of examination of 224 patients with different stages of cerebral ischemic disturbances (CID) and 84 age-matched controls, an artificial neuronal network was constructed and tried in differential diagnosis of CID stages according to the data of transcranial ultrasonic dopplerography. Diagnostic efficacy of the network was 80% for sensitivity, 100% for specificity and 82.7% for reliability. A modeling of the influence of the main risk factors for cerebral ischemia and of the reserve state of cerebral hemodynamics for establishing the stage of CID was performed.

  4. miR-455 inhibits neuronal cell death by targeting TRAF3 in cerebral ischemic stroke

    Directory of Open Access Journals (Sweden)

    Yao ST

    2016-12-01

    Full Text Available Shengtao Yao,* Bo Tang,* Gang Li, Ruiming Fan, Fang Cao Department of Cerebrovascular Disease, The First Affiliated Hospital of Zunyi Medical College, Zunyi, People’s Republic of China *These authors contributed equally to this work Abstract: Ischemic stroke is one of the leading causes of brain disease, with high morbidity, disability, and mortality. MicroRNAs (miRNAs have been identified as vital gene regulators in various types of human diseases. Accumulating evidence has suggested that aberrant expression of miRNAs play critical roles in the pathologies of ischemic stroke. Yet, the precise mechanism by which miRNAs control cerebral ischemic stroke remains unclear. In the present study, we explored whether miR-455 suppresses neuronal death by targeting TRAF3 in cerebral ischemic stroke. The expression levels of miR-455 and TRAF3 were detected by quantitative real-time polymerase chain reaction and Western blot. The role of miR-455 in cell death caused by oxygen–glucose deprivation (OGD was assessed using Cell Counting Kit-8 (CCK-8 assay. The influence of miR-455 on infarct volume was evaluated in mouse brain after middle cerebral artery occlusion (MCAO. Bioinformatics softwares and luciferase analysis were used to find and confirm the targets of miR-455. The results showed that the expression levels of miR-455 significantly decreased in primary neuronal cells subjected to OGD and mouse brain subjected to MCAO. In addition, forced expression of miR-455 inhibited neuronal death and weakened ischemic brain infarction in focal ischemia-stroked mice. Furthermore, TRAF3 was proved to be a direct target of miR-455, and miR-455 could negatively suppress TRAF3 expression. Biological function analysis showed that TRAF3 silencing displayed the neuroprotective effect in ischemic stroke and could enhance miR-455-induced positive impact on ischemic injury both in vitro and in vivo. Taken together, miR-455 played a vital role in protecting neuronal

  5. Cerebral microbleeds in a neonatal rat model

    Science.gov (United States)

    Carusillo Theriault, Brianna; Woo, Seung Kyoon; Karimy, Jason K.; Keledjian, Kaspar; Stokum, Jesse A.; Sarkar, Amrita; Coksaygan, Turhan; Ivanova, Svetlana; Gerzanich, Volodymyr

    2017-01-01

    Background In adult humans, cerebral microbleeds play important roles in neurodegenerative diseases but in neonates, the consequences of cerebral microbleeds are unknown. In rats, a single pro-angiogenic stimulus in utero predisposes to cerebral microbleeds after birth at term, a time when late oligodendrocyte progenitors (pre-oligodendrocytes) dominate in the rat brain. We hypothesized that two independent pro-angiogenic stimuli in utero would be associated with a high likelihood of perinatal microbleeds that would be severely damaging to white matter. Methods Pregnant Wistar rats were subjected to intrauterine ischemia (IUI) and low-dose maternal lipopolysaccharide (mLPS) at embryonic day (E) 19. Pups were born vaginally or abdominally at E21-22. Brains were evaluated for angiogenic markers, microhemorrhages, myelination and axonal development. Neurological function was assessed out to 6 weeks. Results mRNA (Vegf, Cd31, Mmp2, Mmp9, Timp1, Timp2) and protein (CD31, MMP2, MMP9) for angiogenic markers, in situ proteolytic activity, and collagen IV immunoreactivity were altered, consistent with an angiogenic response. Vaginally delivered pups exposed to prenatal IUI+mLPS had spontaneous cerebral microbleeds, abnormal neurological function, and dysmorphic, hypomyelinated white matter and axonopathy. Pups exposed to the same pro-angiogenic stimuli in utero but delivered abdominally had minimal cerebral microbleeds, preserved myelination and axonal development, and neurological function similar to naïve controls. Conclusions In rats, pro-angiogenic stimuli in utero can predispose to vascular fragility and lead to cerebral microbleeds. The study of microbleeds in the neonatal rat brain at full gestation may give insights into the consequences of microbleeds in human preterm infants during critical periods of white matter development. PMID:28158198

  6. [Application of peloidotherapy at the early stage of rehabilitation after cerebral ischemic stroke].

    Science.gov (United States)

    Gorbunov, F E; Penionzhkevich, D Iu; Kotenko, E P

    2010-01-01

    The objective of the present study was to evaluate clinical efficiency of peloidotherapy in the early reconvalescence period following cerebral ischemic stroke. A rationale for the application of peloidotherapy is presented based on the results of follow-up of 60 patients (26 men and 34 women) aged from 43 to 70 years at the early stage of recovery (within 10 weeks and more after stroke). Special attention was given to clinical dynamics of the post-stroke condition and the influence of peloidotherapy on the mechanisms underlying formation of cerebral hemodynamic effects, adaptive changes in the functional systems of hemostasis and microcirculation, and development of pathophysiological cascade of metabolic processes in the brain. All therapeutic procedures were fairly well tolerated by the patients. Neither allergic reactions nor other adverse effects of the treatment were documented which testifies to the safety of peloidotherapy at the early stage of rehabilitation after cerebral ischemic stroke.

  7. 灯盏细辛对大鼠急性脑缺血BDNF及其受体trkB表达的影响%Effect of breviscapine with BDNF and TrkB in cerebral ischemic rat

    Institute of Scientific and Technical Information of China (English)

    周弋人; 何柳; 张仲; 曾仲; 高励; 沈富伟; 罗祖明

    2011-01-01

    Objective To observe the effect of breviscapine on exspression of brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor B (trkB) of focal cerebral iscbemia in rats.Methods 45 SD rats were randomized into 3 groups including model group, treatment group and sham group.The expressions of BDNF and trkB neurons were observed with immunochemical method.Results The expressions of BDNF and trkB neurons of treatment group was different from that of model group and treatment group, P<0.05.Conclusion Breviscapine may be related with the upregulation expression of BDNF and trkB.%目的 观察灯盖细辛在急性脑缺血期对内源性脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)及酪氨酸激酶受体B(tyrosine kinase receptor B receptor,trkB)合成的影响.方法 采用改良的 Zealonga法建立大鼠大脑中动脉局灶缺血/再灌注梗死(Middle cerebral artery occlusion/reperfusion,MCAO)模型.45只SD大鼠随机分为MCA0模型组(A组),给药组2.7ml/kg×7天(B组)及对照组(C组).然后制作冰冻切片对BDNF,trkB免疫组化测量.结果 BDNF及trkB免疫组化检测结果均提示,给药组与模型组比较有显著性差异(P<0.05).结论 灯盏细辛可诱导脑梗死后BDNF及其高亲和性受体trkB表达上调.

  8. Dynamic change of collateral flow varying with distribution of regional blood flow in acute ischemic rat cortex

    Science.gov (United States)

    Wang, Zhen; Luo, Weihua; Zhou, Fangyuan; Li, Pengcheng; Luo, Qingming

    2012-12-01

    Cerebral blood flow (CBF) is critical for the maintenance of cerebral function by guaranteed constant oxygen and glucose supply to brain. Collateral channels (CCs) are recruited to provide alternatives to CBF to ischemic regions once the primary vessel is occluded during ischemic stroke. However, the knowledge of the relationship between dynamic evolution of collateral flow and the distribution of regional blood flow remains limited. In this study, laser speckle imaging was used to assess dynamic changes of CCs and regional blood flow in a rat cortex with permanent middle cerebral artery occlusion (MCAo). We found that CCs immediately provided blood flow to ischemic territories after MCAo. More importantly, there were three kinds of dynamic changes of CCs during acute stroke: persistent CC, impermanent CC, and transient CC, respectively, related to different distributions of regional blood flow. Although there was the possible occurrence of peri-infarct depolarization (PID) during ischemia, there was no obvious significance about the onset time and duration of CCs between rats with and without PID. These results suggest that the initial arising of CCs does not ensure their persistence, and that collateral flow could be varied with distribution of regional blood flow in acute ischemic stroke, which may facilitate the understanding of collateral recruitment and promote the development of collateral therapeutics in the future.

  9. Cerebroprotective Effect of Moringa oleifera against Focal Ischemic Stroke Induced by Middle Cerebral Artery Occlusion

    Directory of Open Access Journals (Sweden)

    Woranan Kirisattayakul

    2013-01-01

    Full Text Available The protection against ischemic stroke is still required due to the limitation of therapeutic efficacy. Based on the role of oxidative stress in stroke pathophysiology, we determined whether Moringa oleifera, a plant possessing potent antioxidant activity, protected against brain damage and oxidative stress in animal model of focal stroke. M. oleifera leaves extract at doses of 100, 200 and 400 mg·kg−1 was orally given to male Wistar rats (300–350 g once daily at a period of 2 weeks before the occlusion of right middle cerebral artery (Rt.MCAO and 3 weeks after Rt.MCAO. The determinations of neurological score and temperature sensation were performed every 7 days throughout the study period, while the determinations of brain infarction volume, MDA level, and the activities of SOD, CAT, and GSH-Px were performed 24 hr after Rt.MCAO. The results showed that all doses of extract decreased infarction volume in both cortex and subcortex. The protective effect of medium and low doses of extract in all areas occurred mainly via the decreased oxidative stress. The protective effect of the high dose extract in striatum and hippocampus occurred via the same mechanism, whereas other mechanisms might play a crucial role in cortex. The detailed mechanism required further exploration.

  10. Protein Kinase C Epsilon Promotes Cerebral Ischemic Tolerance Via Modulation of Mitochondrial Sirt5

    Science.gov (United States)

    Morris-Blanco, Kahlilia C.; Dave, Kunjan R.; Saul, Isabel; Koronowski, Kevin B.; Stradecki, Holly M.; Perez-Pinzon, Miguel A.

    2016-01-01

    Sirtuin 5 (SIRT5) is a mitochondrial-localized NAD+-dependent lysine desuccinylase and a major regulator of the mitochondrial succinylome. We wanted to determine whether SIRT5 is activated by protein kinase C epsilon (PKCε)-mediated increases in mitochondrial Nampt and whether SIRT5 regulates mitochondrial bioenergetics and neuroprotection against cerebral ischemia. In isolated mitochondria from rat cortical cultures, PKCε activation increased SIRT5 levels and desuccinylation activity in a Nampt-dependent manner. PKCε activation did not lead to significant modifications in SIRT3 activity, the major mitochondrial lysine deacetylase. Assessments of mitochondrial bioenergetics in the cortex of wild type (WT) and SIRT5−/− mice revealed that SIRT5 regulates oxygen consumption in the presence of complex I, complex II, and complex IV substrates. To explore the potential role of SIRT5 in PKCε-mediated protection, we compared WT and SIRT5−/− mice by employing both in vitro and in vivo ischemia paradigms. PKCε-mediated decreases in cell death following oxygen-glucose deprivation were abolished in cortical cultures harvested from SIRT5−/− mice. Furthermore, PKCε failed to prevent cortical degeneration following MCAO in SIRT5−/− mice. Collectively this demonstrates that SIRT5 is an important mitochondrial enzyme for protection against metabolic and ischemic stress following PKCε activation in the brain. PMID:27435822

  11. Cerebroprotective Effect of Moringa oleifera against Focal Ischemic Stroke Induced by Middle Cerebral Artery Occlusion

    Science.gov (United States)

    Wattanathorn, Jintanaporn; Tong-Un, Terdthai; Muchimapura, Supaporn; Wannanon, Panakaporn; Jittiwat, Jinatta

    2013-01-01

    The protection against ischemic stroke is still required due to the limitation of therapeutic efficacy. Based on the role of oxidative stress in stroke pathophysiology, we determined whether Moringa oleifera, a plant possessing potent antioxidant activity, protected against brain damage and oxidative stress in animal model of focal stroke. M. oleifera leaves extract at doses of 100, 200 and 400 mg·kg−1 was orally given to male Wistar rats (300–350 g) once daily at a period of 2 weeks before the occlusion of right middle cerebral artery (Rt.MCAO) and 3 weeks after Rt.MCAO. The determinations of neurological score and temperature sensation were performed every 7 days throughout the study period, while the determinations of brain infarction volume, MDA level, and the activities of SOD, CAT, and GSH-Px were performed 24 hr after Rt.MCAO. The results showed that all doses of extract decreased infarction volume in both cortex and subcortex. The protective effect of medium and low doses of extract in all areas occurred mainly via the decreased oxidative stress. The protective effect of the high dose extract in striatum and hippocampus occurred via the same mechanism, whereas other mechanisms might play a crucial role in cortex. The detailed mechanism required further exploration. PMID:24367723

  12. Cerebroprotective effect of Moringa oleifera against focal ischemic stroke induced by middle cerebral artery occlusion.

    Science.gov (United States)

    Kirisattayakul, Woranan; Wattanathorn, Jintanaporn; Tong-Un, Terdthai; Muchimapura, Supaporn; Wannanon, Panakaporn; Jittiwat, Jinatta

    2013-01-01

    The protection against ischemic stroke is still required due to the limitation of therapeutic efficacy. Based on the role of oxidative stress in stroke pathophysiology, we determined whether Moringa oleifera, a plant possessing potent antioxidant activity, protected against brain damage and oxidative stress in animal model of focal stroke. M. oleifera leaves extract at doses of 100, 200 and 400 mg·kg(-1) was orally given to male Wistar rats (300-350 g) once daily at a period of 2 weeks before the occlusion of right middle cerebral artery (Rt.MCAO) and 3 weeks after Rt.MCAO. The determinations of neurological score and temperature sensation were performed every 7 days throughout the study period, while the determinations of brain infarction volume, MDA level, and the activities of SOD, CAT, and GSH-Px were performed 24 hr after Rt.MCAO. The results showed that all doses of extract decreased infarction volume in both cortex and subcortex. The protective effect of medium and low doses of extract in all areas occurred mainly via the decreased oxidative stress. The protective effect of the high dose extract in striatum and hippocampus occurred via the same mechanism, whereas other mechanisms might play a crucial role in cortex. The detailed mechanism required further exploration.

  13. Hyperpolarized 129Xe magnetic resonance imaging of a rat model of transient Ischemic Stroke

    Science.gov (United States)

    Walvick, Ronn P.; Bastan, Birgul; Reno, Austin; Mansour, Joey; Sun, Yanping; Zhou, Xin; Mazzani, Mary; Fisher, Marc; Sotak, Christopher H.; Albert, Mitchell S.

    2009-02-01

    Ischemic stroke accounts for nearly 80% of all stroke cases. Although proton diffusion and perfusion magnetic resonance imaging (MRI) are the gold standards in ischemic stroke diagnostics, the use of hyperpolarized 129Xe MRI has a potential role to contribute to the diagnostic picture. The highly lipophilic hyperpolarized 129Xe can be non-invasively delivered via inhalation into the lungs where it is dissolved into the blood and delivered to other organs such as the brain. As such, we expect hyperpolarized 129Xe to act as a perfusion tracer which will result in a signal deficit in areas of blood deprived tissue. In this work, we present imaging results from an animal model of transient ischemic stroke characterized through 129Xe MRI. In this model, a suture is used to occlude the middle cerebral artery (MCA) in the rat brain, thus causing an ischemic event. After a period of MCA occlusion, the suture can then be removed to reperfuse the ischemic area. During the ischemic phase of the stroke, a signal void was observed in the MCA territory; which was subsequently restored by normal 129Xe MRI signal once perfusion was reinstated. Further, a higher resolution one-dimensional chemical shift image shows a sharp signal drop in the area of ischemia. Validation of ischemic damage was shown through both proton diffusion-weighted MRI (DWI) and by 2,3,5-triphenyltetrazoliumchloride (TTC) staining. The results show the potential of 129Xe to act as a perfusion tracer; information that may add to the diagnostic and prognostic utility of the clinical picture of stroke.

  14. Ischemic postconditioning alleviates rat cerebral ischemia-reperfusion injury through the phosphoinositide 3-kinase signaling pathway%缺血后处理通过PI3K信号通路抑制脑缺血再灌注损伤

    Institute of Scientific and Technical Information of China (English)

    宫利; 王志; 肖松华; 刘运林; 周海红; 邢诒刚

    2009-01-01

    Objective To investigate the neuroprotective effect of ischcmic posteonditioning (IP)against cerebral ischemia-reperfusion injury and the role of phosphoinositide 3-kinase(P13K)signaling pathway in the neuroprotection. Methods Focal cerebral ischernia was induced in 24 SD rats by permanent distal middle cerebral artery occlusion and transient bilateral comlllOn carotid artery occlusion.The rats were then randomized into 4 groups for treatment with IP,LY294002+IP,DMSO+IP,or without IP.In LY294002+IP and DMSO+IP groups,LY294002 or DMSO was injcoted into the ventricular space on the ischemic side 1 h before ischemia.The cerebral infarct sizes wgre measured in all the 4 groups at 48h after the reperfusion.Results Cerebral infarcts were observed in all the groups on theischemic side,all locating in the left neocortex and the middle cerebral artery territory.At48h after reperfusion,the infarct size was significantly smaller in rats with IP(34.02%±7.17%)than in those without IP(57.05%±10.05%)(P<0.05),and significantly larger in LY294002+IP group(73.41%±2.06%)than in DMSO+IP group(35.76%±1.51%)(P<0.05).No significant difference was found in the infarctsize between DMSO+IP group and IP group(P>0.05).Conclusion IP ameliorates cerebral reperfusion mjury in rats,and the mechanism of this neuroprotective effect involves the preservation of PI3K activity.%目的 研究缺血后处理(IP)对脑缺血再灌注损伤的影响及其机制.方法 采用开颅机械闭塞法建立SD大鼠局灶性脑缺血模型,通过开放/夹闭双侧颈总动脉实现IP.24只大鼠按照随机数字表法分为IP组、非IP组、LY294002+IP组、DMSO+IP组,每组6只,再灌注48 h后测脑梗死面积;其中LY294002、DMSO于建模前1 h侧脑室注入.结果 各组左侧大脑皮层均可见清晰梗死灶,符合血管分布范围.其中IP组腩梗死面积(34.02%±7.17%)明显小于非IP组(57.05%±10.05%),差异有统计学意义(P<0.05);LY294002+IP组脑梗死面积(73.41%±2.06%)

  15. Ischemic cerebral changes in the chronic chagasic cardiopathy

    Directory of Open Access Journals (Sweden)

    José Eymard Homem Pitella

    1984-06-01

    Full Text Available The pathological systematized study of the brain of 31 cases of the chronic cardiac form of Chagas' disease was undertaken. Elective parenchymatous necrosis was found in 64.5% of cases, mainly in cerebellar Purkinje cells, and in thalamic nuclei. Also found were multiple foci of old micronecrosis (51.6% mostly in the cerebral cortex, old cerebral infarcts (22.6%, cortical laminar necrosis (16.1% and cerebral cortical atrophy (3.2%. These findings are not specific and can be explained by thromboembolic phenomena and hypoxemia following from congestive heart failure and disturbances of the cardiac rhythm.

  16. Scalp electroacupuncture at the Baihui acupoint (DU 20) improves functional recovery in rats with cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Min-Wook Kim; Seung Chan Kim; Woo-Seok Im; Jin Young Chung; Minky Kim; Manho Kim; You Chul Chung; Hee Chan Jung; Moon-Seo Park; Young-Min Han; Yong-An Chung; Lee-So Maeng; Sang-In Park; Jiyeon Lim

    2011-01-01

    In this study, we induced cerebral infarction in rats by occluding the right middle cerebral artery, and tested the effects of electroacupuncture at the Baihui acupoint (DU 20). Motor and sensory function was tested using Garcia's scale and motor weakness grading, and the expression of vascular endothelial growth factor in the brain was quantified using immunoblotting and immunohistochemistry. We found that scalp electroacupuncture at DU 20 significantly improved motor performance and sensory function in rats with stroke, and this was accompanied by an increased expression of vascular endothelial growth factor in the ischemic brain tissue and peri-ischemic area. In addition, Pearson correlation analysis showed that the improvements in functional recovery were correlated with the increased expression of vascular endothelial growth factor.

  17. Effects of Graded Hypothermia on Hypoxic-ischemic Brain Damage in the Neonatal Rat

    Institute of Scientific and Technical Information of China (English)

    Xiao-yan Xia; Yi-xin Xia

    2011-01-01

    Objective To investigate the effect of graded hypothermia on neuropathologic alteratiors of neonatal rat brain after exposed to hypoxic-ischemic insult at 37℃, 33℃, 31℃, and 28℃, respectively, and to observe the effect of hypothermia on 72-kDa heat shock protein (HSP72) expression after hypoxic-ischemic insult. Methods Seven days old Wistar rats were subjected to unilateral common carotid artery ligation followed by exposure to hypoxia in 8% oxygen for 2 hours at 37℃, 33℃, 31℃, and 28℃, respectively. The brain temperature was monitored indirectly by inserting a mini-thermocouple probe into the temporal muscle during hypoxia. After hypoxia-ischemia their mortality was assessed. Neuronal damage was assessed with HE staining 72 hours after hypoxia. HSP72 expression at 0.5, 24, and 72 hours of recovery was immunohistochemically assessed using a monoclonal antibody to HSP72. Results Hypoxia-ischemia caused 10.5% (2/19) of mortality in rat of 37℃ group, but no death occurred in 33℃, 31℃ or 28℃ groups. HE staining showed neuropathologic damage was extensive in rats exposed to hypoxia-ischemia at 37℃ (more than 80.0%). The incidence of severe brain damage was significantly decreased in 33℃ (53.3%) and 31℃ groups (44.4%), and no histologic injury was seen in the 28℃ group of rats. Expression of HSP72 was manifest and persistent in the rat brain of 37℃ group, but minimum in the rat brain of 28℃ group. Conclusion Mild and moderate hypothermia might prevent cerebral visible neuropathologic damage associated with hypoxic-ischemic injury by decreasing stress response.

  18. Effect of intracranial transplantation of CD34+ cells derived from human umbilical cord blood in rats with cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    LIU Hai-ying; ZHANG Qing-jun; LI Hong-jun; HAN Zhong-chao

    2006-01-01

    @@ As a source of transplantable stem cells, the CD34+ subpopulation in human umbilical cord blood (HUCB) has been used extensively to treat some hematopoietic system diseases. However,whether CD34+ cells hold the therapeutic potential to cerebral ischemia is unknown. The purpose of this study was to observe the recovery of neural function after transplantation of CD34+ cells derived from HUCB into ischemic cerebral tissue in rats.

  19. 电针百会、风府穴对脑I/R损伤大鼠海马区CPG15表达影响的实验研究%Effects of Eiectroacupuncture Bai Hui, Feng Fu on CPG15 Expression of Hippocampus in Rats with Cerebral Ischemic Reperfusion

    Institute of Scientific and Technical Information of China (English)

    唐晓敏; 秦正玉; 何宗宝; 王家琳; 吴生兵; 汪克明

    2011-01-01

    目的 探讨电针对局灶性脑缺血再灌注大鼠神经功能的恢复及海马区神经可塑性相关基因15(CPG15)表达影响的情况.方法 60只SD大鼠,雌雄各半,随机分为正常对照组、模型组、电针经穴组、电针非经穴组、西药对照组.采用线栓法制备局灶性脑缺血再灌注模型,电针经穴组电针百会、风府穴,电针非经穴组电针大鼠臀部非经非穴位置,电针以疏波2Hz,强度3 mA~5mA,持续电针30 min,每天1次,连续治疗2周.西药对照组以尼莫地平20 mg/(kg·d)灌胃,每日2次,连续灌胃2周.2周后Longa5分法对大鼠神经功能缺损评分,并取材,运用免疫组化法检测大鼠缺血侧海马区CPG15表达情况.结果 模型组大鼠神经功能缺损评分及缺血侧海马区CPG15表达显著高于正常对照组(P<0.01);电针经穴组与西药治疗组大鼠神经功能评分及海马区CPG15表达差异无统计学意义(P>0.05),而与模型组比较,电针经穴组与西药治疗组神经功能评分及海马区CPG15表达均有统计学意义(P<0.01);电针非经穴组大鼠神经功能缺损评分及缺血侧海马区CPG15表达与模型组比较差异无统计学意义(P>0.05).结论 电针可改善脑缺血再灌注大鼠神经功能,并提高海马区CPG15的表达,电针对脑缺血再灌注后脑细胞的神经可塑性有促进作用.%Objective To investigate the effects of electroacupuncture on canidate plasticity- related gene 15CCPG15) expression of hippocampus in rats with cerebral ischemic reperfusion(I/R). Methods Sixty sprague - dawley rats were randomly divided into normal group (group 1) ,cerebral ischemic reperfusion model group (group 2) .electroacupuncture on meridian acupoints group (group 3),electroacupuncture on non - meridian acupoints group (group 4) .and nimodiping group (group 5). Rat models with cerebral ischemia reperfusion were prepared by modified suture. Electroacupuncture was applied on Bai Hui(TV20) and .Feng Fu

  20. Citicoline Protects Against Cognitive Impairment in a Rat Model of Chronic Cerebral Hypoperfusion

    OpenAIRE

    Lee, Hyun Joon; Kang, Ji Seung; Kim, Yeong In

    2008-01-01

    Background and purpose Cerebral white matter (WM) lesions are frequently observed in human cerebrovascular diseases, and are believed to be responsible for cognitive impairment. Various neuroprotective agents can suppress this type of WM or neuronal damage. In this study, we investigated whether citicoline, a drug used to treat acute ischemic stroke, can attenuate WM lesions and cognitive decline caused by chronic hypoperfusion in the rat. Methods Animals were divided into immediate- and dela...

  1. Imaging experimental cerebral malaria in vivo: significant role of ischemic brain edema.

    Science.gov (United States)

    Penet, Marie-France; Viola, Angèle; Confort-Gouny, Sylviane; Le Fur, Yann; Duhamel, Guillaume; Kober, Frank; Ibarrola, Danielle; Izquierdo, Marguerite; Coltel, Nicolas; Gharib, Bouchra; Grau, Georges E; Cozzone, Patrick J

    2005-08-10

    The first in vivo magnetic resonance study of experimental cerebral malaria is presented. Cerebral involvement is a lethal complication of malaria. To explore the brain of susceptible mice infected with Plasmodium berghei ANKA, multimodal magnetic resonance techniques were applied (imaging, diffusion, perfusion, angiography, spectroscopy). They reveal vascular damage including blood-brain barrier disruption and hemorrhages attributable to inflammatory processes. We provide the first in vivo demonstration for blood-brain barrier breakdown in cerebral malaria. Major edema formation as well as reduced brain perfusion was detected and is accompanied by an ischemic metabolic profile with reduction of high-energy phosphates and elevated brain lactate. In addition, angiography supplies compelling evidence for major hemodynamics dysfunction. Actually, edema further worsens ischemia by compressing cerebral arteries, which subsequently leads to a collapse of the blood flow that ultimately represents the cause of death. These findings demonstrate the coexistence of inflammatory and ischemic lesions and prove the preponderant role of edema in the fatal outcome of experimental cerebral malaria. They improve our understanding of the pathogenesis of cerebral malaria and may provide the necessary noninvasive surrogate markers for quantitative monitoring of treatment.

  2. Validation of hyperintense middle cerebral artery sign in acute ischemic stroke

    Institute of Scientific and Technical Information of China (English)

    Gang Guo; Yonggui Yang; Weiqun Yang

    2012-01-01

    We performed a retrospective analysis of non-contrast computed tomography (CT) scans, immediately subsequent magnetic resonance imaging (MRI), and cerebral angiography data from 30 consecutive patients with acute ischemic stroke within 6 hours after symptom onset. Results showed that eleven patients developed subsequent hemorrhagic transformation at follow-up. A hyperintense middle cerebral artery sign on MRI was found in six hemorrhagic patients, all of who had acute thrombosis formation on magnetic resonance angiography and digital subtraction angiography. No patients in the non-hemorrhagic group had hyperintense middle cerebral artery sign on MRI. The sensitivity, specificity, and positive predictive values of the hyperintense middle cerebral artery sign on MRI T1-weighted image for subsequent hemorrhagic transformation were 54.5%, 100%, and 100% respectively. Hyperdense middle cerebral artery sign on non-contrast CT was observed in nine patients, five of who developed hemorrhagic transformation. These data suggest that hyperintense middle cerebral artery sign on MRI T1-weighted image is a highly specific and moderately sensitive indicator of subsequent hemorrhagic transformation in patients after acute ischemic stroke, and its specificity is superior to CT.

  3. Reperfusion promotes mitochondrial dysfunction following focal cerebral ischemia in rats.

    Directory of Open Access Journals (Sweden)

    Jun Li

    Full Text Available BACKGROUND AND PURPOSE: Mitochondrial dysfunction has been implicated in the cell death observed after cerebral ischemia, and several mechanisms for this dysfunction have been proposed. Reperfusion after transient cerebral ischemia may cause continued and even more severe damage to the brain. Many lines of evidence have shown that mitochondria suffer severe damage in response to ischemic injury. The purpose of this study was to observe the features of mitochondrial dysfunction in isolated mitochondria during the reperfusion period following focal cerebral ischemia. METHODS: Male Wistar rats were subjected to focal cerebral ischemia. Mitochondria were isolated using Percoll density gradient centrifugation. The isolated mitochondria were fixed for electron microscopic examination; calcium-induced mitochondrial swelling was quantified using spectrophotometry. Cyclophilin D was detected by Western blotting. Fluorescent probes were used to selectively stain mitochondria to measure their membrane potential and to measure reactive oxidative species production using flow cytometric analysis. RESULTS: Signs of damage were observed in the mitochondrial morphology after exposure to reperfusion. The mitochondrial swelling induced by Ca(2+ increased gradually with the increasing calcium concentration, and this tendency was exacerbated as the reperfusion time was extended. Cyclophilin D protein expression peaked after 24 hours of reperfusion. The mitochondrial membrane potential was decreased significantly during the reperfusion period, with the greatest decrease observed after 24 hours of reperfusion. The surge in mitochondrial reactive oxidative species occurred after 2 hours of reperfusion and was maintained at a high level during the reperfusion period. CONCLUSIONS: Reperfusion following focal cerebral ischemia induced significant mitochondrial morphological damage and Ca(2+-induced mitochondrial swelling. The mechanism of this swelling may be mediated by

  4. Limb Ischemic Perconditioning Attenuates Blood-Brain Barrier Disruption by Inhibiting Activity of MMP-9 and Occludin Degradation after Focal Cerebral Ischemia

    Science.gov (United States)

    Ren, Changhong; Li, Ning; Wang, Brian; Yang, Yong; Gao, Jinhuan; Li, Sijie; Ding, Yuchuan; Jin, Kunlin; Ji, Xunming

    2015-01-01

    Remote ischemic perconditioning (PerC) has been proved to have neuroprotective effects on cerebral ischemia, however, the effect of PerC on the BBB disruption and underlying mechanisms remains largely unknown. To address these issues, total 90 adult male Sprague Dawley (SD) rats were used. The rats underwent 90-min middle cerebral artery occlusion (MCAO), and the limb remote ischemic PerC was immediately applied after the onset of MCAO. We found that limb remote PerC protected BBB breakdown and brain edema, in parallel with reduced infarct volume and improved neurological deficits, after MCAO. Immunofluorescence studies revealed that MCAO resulted in disrupted continuity of claudin-5 staining in the cerebral endothelial cells with significant gap formation, which was significantly improved after PerC. Western blot analysis demonstrated that expression of tight junction (TJ) protein occludin was significantly increased, but other elements of TJ proteins, claudin-5 and ZO-1, in the BBB endothelial cells were not altered at 48 h after PerC, compared to MCAO group. The expression of matrix metalloproteinase (MMP-9), which was involved in TJ protein degradation, was decreased after PerC. Interestingly, phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2), an upstream of MMP-9 signaling, was significantly reduced in the PerC group. Our data suggest that PerC inhibits MMP-9-mediated occludin degradation, which could lead to decreased BBB disruption and brain edema after ischemic stroke. PMID:26618042

  5. Analysis of the XRCC1 gene as a modifier of the cerebral response in ischemic stroke

    Directory of Open Access Journals (Sweden)

    Juo Suh-Hang H

    2006-11-01

    Full Text Available Abstract Background Although there have been studies of the genetic risk factors in the development of stroke, there have been few investigations of role of genes in the cerebral response to ischemia. The brain responds to ischemia in a series of reactions that ultimately influence the volume of a stroke that, in general, correlates with disability. We hypothesize that polymorphisms in genes encoding proteins involved in these reactions could act as modifiers of this response and impact stroke volume. One of the pathways participating in the cerebral ischemic response involves reactive oxygen species which can cause oxidative damage to nucleic acids. DNA repair mechanisms are in place to protect against such damage and imply a role for DNA repair genes in the response of the brain to ischemia and are potential candidate genes for further investigation. Methods We studied two common polymorphisms in the DNA repair gene, XRCC1, C26304T and G28152A, in 134 well characterized patients with non lacunar ischemic strokes. We also performed a case control association study with 113 control patients to assess whether these variants represent risk factors in the development of ischemic stroke. Results Independent of etiology, the "T" allele of the C26304T polymorphism is significantly associated with larger stroke volumes (T-test analysis, p Conclusion Our study suggests a major gene effect of the "T" allele of the C26304T polymorphism modulating the cerebral response to ischemia in non lacunar ischemic stroke.

  6. A Randomized trial comparing ticlopidine with aspirin fof the prevention of ischemic cerebral stroke

    Institute of Scientific and Technical Information of China (English)

    Li Yizhao; Li Danian; Wang Lei

    2000-01-01

    OBJECTIVE To assess the effect and cafety of t iclopidine in the prevention of ischemic cerebral stroke and to compare theeffect of low-dose aspirin with t iclopidine. BACKGROUND The effect and safety of ticlopidine irn the prevention of ischemic cerebral stroke in China has not been reported. METHODS 329 patients with TIA or mild ischemic cevebral stroke wasrandonmly assigned to ticlopidine group(165 case) or aspirin group (164 case) in this study.These patrents were randomly allocated to receive either 250mg trclopidine or 50mg aspirin daily and didnd take any other platelet antiaggregating drugs. Time of eacn follow up visit was one to two months. Follow up lasted for 6 to 18 months. RESULTS The event rate for stroke or death from any cause was 8.3% in ticlopidine group arid 14.9% in aspirin group. This repesented a risk reduction of 44.3%(95% cofidence interval, 0.29-0.94) for ticiopidine group as compared with aspirin group. The event raite for ischemic cerebral stroke or myocarction of ticlopidine group(7.0%)was lower than that cf aspirin group(14.8%)(P<0.05).A riskreduction of 52.7%(95% confidence interval,0.24-0.92) for ticlopidine group compared with aspirin group. The rate of adverse effects of ticlopidine group and aspirin group were 6.9% and 11.0% during the trial ,but this was not statistically significant(P<0.05).DISCUSSION and CONCLUSION Therapeutic efficacy for the prevention oi ischemic stroke of ticlopidine was better than that of aspirin, the rate of side effects in ticlopidine group and aspirin group are not statistically significant. So ticiopidine could serve as a first-line drug for the prevention of ischemic stroke.

  7. Effects of pre- and postnatal protein malnutrition in hypoxic-ischemic rats.

    Science.gov (United States)

    Sanches, Eduardo Farias; Arteni, Nice Sarmento; Spindler, Christiano; Moysés, Felipe; Siqueira, Ionara Rodrigues; Perry, Marcos Luis; Netto, Carlos Alexandre

    2012-02-15

    Neonatal hypoxic-ischemic encephalopathy (HI) is a major cause of nervous system damage and neurological morbidity. Perinatal malnutrition affects morphological, biochemical and behavioral aspects of neural development, including pathophysiological cascades of cell death triggered by ischemic events, so modifying resulting brain damage. Female Wistar rats were subjected to protein restriction during pregnancy and lactation (control group: 25% soybean protein; malnourished group: 7%). Seven days after delivery (PND7), their offspring were submitted to unilateral cerebral HI; rats were then tested for sensorimotor (PND7 and PND60) and memory (PND60) functions. Offspring of malnourished mothers showed marked reduction in body weight starting in lactation and persisting during the entire period of observation. There was a greater sensorimotor deficit after HI in malnourished (M) animals, in righting reflex and in home bedding task, indicating an interaction between diet and hypoxia-ischemia. At PND60, HI rats showed impaired performance when compared to controls in training and test sessions of rota-rod task, however there was no effect of malnutrition per se. In the open field, nourished HI (HI-N) presented an increase in crossings number; this effect was not present in HI-M group. Surprisingly, HI-M rats presented a better performance in inhibitory avoidance task and a smaller hemispheric brain damage as compared to HI-N animals. Our data points to a possible metabolic adaptation in hypoxic-ischemic animals receiving protein malnutrition during pregnancy and lactation; apparently we observed a neuroprotective effect of diet, possibly decreasing the brain energy demand, under a hypoxic-ischemic situation. Copyright © 2011 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2012-02-29

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

  9. Microglia preconditioned by oxygen-glucose deprivation promote functional recovery in ischemic rats

    Science.gov (United States)

    Kanazawa, Masato; Miura, Minami; Toriyabe, Masafumi; Koyama, Misaki; Hatakeyama, Masahiro; Ishikawa, Masanori; Nakajima, Takashi; Onodera, Osamu; Takahashi, Tetsuya; Nishizawa, Masatoyo; Shimohata, Takayoshi

    2017-01-01

    Cell-therapies that invoke pleiotropic mechanisms may facilitate functional recovery in stroke patients. We hypothesized that a cell therapy using microglia preconditioned by optimal oxygen-glucose deprivation (OGD) is a therapeutic strategy for ischemic stroke because optimal ischemia induces anti-inflammatory M2 microglia. We first delineated changes in angiogenesis and axonal outgrowth in the ischemic cortex using rats. We found that slight angiogenesis without axonal outgrowth were activated at the border area within the ischemic core from 7 to 14 days after ischemia. Next, we demonstrated that administration of primary microglia preconditioned by 18 hours of OGD at 7 days prompted functional recovery at 28 days after focal cerebral ischemia compared to control therapies by marked secretion of remodelling factors such as vascular endothelial growth factor, matrix metalloproteinase-9, and transforming growth factor-β polarized to M2 microglia in vitro/vivo. In conclusion, intravascular administration of M2 microglia preconditioned by optimal OGD may be a novel therapeutic strategy against ischemic stroke. PMID:28195185

  10. Blood-Brain Barrier Alterations Provide Evidence of Subacute Diaschisis in an Ischemic Stroke Rat Model

    Science.gov (United States)

    Garbuzova-Davis, Svitlana; Rodrigues, Maria C. O.; Hernandez-Ontiveros, Diana G.; Tajiri, Naoki; Frisina-Deyo, Aric; Boffeli, Sean M.; Abraham, Jerry V.; Pabon, Mibel; Wagner, Andrew; Ishikawa, Hiroto; Shinozuka, Kazutaka; Haller, Edward; Sanberg, Paul R.; Kaneko, Yuji; Borlongan, Cesario V.

    2013-01-01

    Background Comprehensive stroke studies reveal diaschisis, a loss of function due to pathological deficits in brain areas remote from initial ischemic lesion. However, blood-brain barrier (BBB) competence in subacute diaschisis is uncertain. The present study investigated subacute diaschisis in a focal ischemic stroke rat model. Specific focuses were BBB integrity and related pathogenic processes in contralateral brain areas. Methodology/Principal Findings In ipsilateral hemisphere 7 days after transient middle cerebral artery occlusion (tMCAO), significant BBB alterations characterized by large Evans Blue (EB) parenchymal extravasation, autophagosome accumulation, increased reactive astrocytes and activated microglia, demyelinization, and neuronal damage were detected in the striatum, motor and somatosensory cortices. Vascular damage identified by ultrastuctural and immunohistochemical analyses also occurred in the contralateral hemisphere. In contralateral striatum and motor cortex, major ultrastructural BBB changes included: swollen and vacuolated endothelial cells containing numerous autophagosomes, pericyte degeneration, and perivascular edema. Additionally, prominent EB extravasation, increased endothelial autophagosome formation, rampant astrogliosis, activated microglia, widespread neuronal pyknosis and decreased myelin were observed in contralateral striatum, and motor and somatosensory cortices. Conclusions/Significance These results demonstrate focal ischemic stroke-induced pathological disturbances in ipsilateral, as well as in contralateral brain areas, which were shown to be closely associated with BBB breakdown in remote brain microvessels and endothelial autophagosome accumulation. This microvascular damage in subacute phase likely revealed ischemic diaschisis and should be considered in development of treatment strategies for stroke. PMID:23675488

  11. Blood-brain barrier alterations provide evidence of subacute diaschisis in an ischemic stroke rat model.

    Directory of Open Access Journals (Sweden)

    Svitlana Garbuzova-Davis

    Full Text Available BACKGROUND: Comprehensive stroke studies reveal diaschisis, a loss of function due to pathological deficits in brain areas remote from initial ischemic lesion. However, blood-brain barrier (BBB competence in subacute diaschisis is uncertain. The present study investigated subacute diaschisis in a focal ischemic stroke rat model. Specific focuses were BBB integrity and related pathogenic processes in contralateral brain areas. METHODOLOGY/PRINCIPAL FINDINGS: In ipsilateral hemisphere 7 days after transient middle cerebral artery occlusion (tMCAO, significant BBB alterations characterized by large Evans Blue (EB parenchymal extravasation, autophagosome accumulation, increased reactive astrocytes and activated microglia, demyelinization, and neuronal damage were detected in the striatum, motor and somatosensory cortices. Vascular damage identified by ultrastuctural and immunohistochemical analyses also occurred in the contralateral hemisphere. In contralateral striatum and motor cortex, major ultrastructural BBB changes included: swollen and vacuolated endothelial cells containing numerous autophagosomes, pericyte degeneration, and perivascular edema. Additionally, prominent EB extravasation, increased endothelial autophagosome formation, rampant astrogliosis, activated microglia, widespread neuronal pyknosis and decreased myelin were observed in contralateral striatum, and motor and somatosensory cortices. CONCLUSIONS/SIGNIFICANCE: These results demonstrate focal ischemic stroke-induced pathological disturbances in ipsilateral, as well as in contralateral brain areas, which were shown to be closely associated with BBB breakdown in remote brain microvessels and endothelial autophagosome accumulation. This microvascular damage in subacute phase likely revealed ischemic diaschisis and should be considered in development of treatment strategies for stroke.

  12. Epsilon PKC increases brain mitochondrial SIRT1 protein levels via heat shock protein 90 following ischemic preconditioning in rats.

    Directory of Open Access Journals (Sweden)

    John W Thompson

    Full Text Available Ischemic preconditioning is a neuroprotective mechanism whereby a sublethal ischemic exposure is protective against a subsequent lethal ischemic attack. We previously demonstrated that SIRT1, a nuclear localized stress-activated deacetylase, is vital for ischemic preconditioning neuroprotection. However, a recent study demonstrated that SIRT1 can also localize to the mitochondria. Mitochondrial localized SIRT1 may allow for a direct protection of mitochondria following ischemic preconditioning. The objective of this study was to determine whether ischemic preconditioning increases brain mitochondrial SIRT1 protein levels and to determine the role of PKCɛ and HSP90 in targeting SIRT1 to the mitochondria. Here we report that preconditioning rats, with 2 min of global cerebral ischemia, induces a delayed increase in non-synaptic mitochondrial SIRT1 protein levels which was not observed in synaptic mitochondria. This increase in mitochondrial SIRT1 protein was found to occur only in neuronal cells and was mediated by PKCε activation. Inhibition of HSP90, a protein chaperone involved in mitochondrial protein import, prevented preconditioning induced increases in mitochondrial SIRT1 and PKCε protein. Our work provides new insights into a possible direct role of SIRT1 in modulating mitochondrial function under both normal and stress conditions, and to a possible role of mitochondrial SIRT1 in activating preconditioning induced ischemic tolerance.

  13. Compensatory cerebral motor control following presumed perinatal ischemic stroke

    NARCIS (Netherlands)

    van der Hoorn, Anouk; Potgieser, Adriaan R E; Brouwer, Oebele F; de Jong, Bauke M

    2014-01-01

    Case: A fifteen year-old left-handed girl presented with right-sided focal motor seizures. Neuroimaging showed a large left hemisphere lesion compatible with a middle cerebral artery stroke of presumed perinatal origin. She was not previously diagnosed with a motor deficit, although neurological exa

  14. Posthoc phosphorylation of proteins derived from ischemic rat hippocampus, striatum and neocortex.

    Science.gov (United States)

    Kirschenbaum, B; Pulsinelli, W A

    1990-03-12

    Disruption of the brain's protein phosphorylation system by ischemia may cause irreversible metabolic and structural alterations leading eventually to cell death. To examine the effect of ischemia on the phosphorylation state of brain proteins, tissue homogenates derived from the hippocampus, striatum and neocortex of normal rats and rats subjected to severe forebrain ischemia were phosphorylated with [gamma-32P]ATP. The phosphorylated proteins were separated by two-dimensional polyacrylamide gel electrophoresis and changes were assessed by autoradiography. Cerebral ischemia caused marked alterations of the phosphorylation state of many brain proteins; phosphorylation of some proteins was increased while phosphorylation of others was decreased. Despite differences in the sensitivity of the hippocampus, striatum and neocortex to ischemic injury the direction and approximate magnitude of protein phosphorylation changes caused by ischemia were similar in all three regions. Since the pattern of protein phosphorylation in the ischemia-vulnerable hippocampus was identical to that in the ischemia-resistant paramedian neocortex we conclude that abnormalities of protein phosphorylation may be necessary for ischemic injury to neurons but none are sufficient to explain the selective vulnerability of certain brain regions to ischemic damage.

  15. Arctigenin protects focal cerebral ischemia-reperfusion rats through inhibiting neuroinflammation.

    Science.gov (United States)

    Fan, Tao; Jiang, Wei Long; Zhu, Jian; Feng Zhang, Yu

    2012-01-01

    Stroke is the third leading cause of death in industrialized countries and the most important cause of acquired adult disability. Many evidences suggest that inflammation accounts for the progression of cerebral ischemic injury. Arctigenin, a phenylpropanoid dibenzylbutyrolactone lignin isolated from certain plants, has shown anti-inflammatory activity against diabetes and Alzheimer's disease. In this study, we tested whether arctigenin can protect middle cerebral artery occluded (MCAO) rats. Male Sprague-Dawley rats were pretreated with arctigenin or vehicle for 7 d before being subjected to transient occlusion of middle cerebral artery and reperfusion. Rats were evaluated at 24 h after MCAO for neurological deficit scoring. Furthermore, the mechanism of the anti-inflammatory effect of arctigenin was investigated with a focus on inflammatory cells, proinflammatory cytokines, and transcriptional factors. Arctigenin significantly reduced cerebral infarction and improved neurological outcome. Arctigenin suppressed the activation of microglia and decreased the expression of interleukin (IL)- 1β and tumor necrosis factor (TNF)-α. These results revealed that arctigenin has a promising therapeutic effect in ischemic stroke treatment through an anti-inflammatory mechanism.

  16. Vascular endothelial growth factor improves recovery of sensorimotor and cognitive deficits after focal cerebral ischemia in the rat.

    Science.gov (United States)

    Wang, Yaoming; Galvan, Veronica; Gorostiza, Olivia; Ataie, Marina; Jin, Kunlin; Greenberg, David A

    2006-10-18

    Vascular endothelial growth factor (VEGF) is an angiogenesis factor with neurotrophic, neuroprotective and neuroproliferative effects. Depending on the dose, route and time of administration in relation to focal cerebral ischemia, VEGF can improve histological outcome and sensorimotor function in rodents. However, VEGF also increases vascular permeability, which can lead to brain edema and exacerbate ischemic brain injury. Thus, although VEGF is a candidate therapeutic for stroke and other ischemic disorders, its benefit relative to risk is uncertain. Considering that functional rather than histological measures of outcome are probably most relevant to therapeutic prospects for human stroke, we investigated the effects of VEGF after middle cerebral artery occlusion in rats using a series of behavioral tests. We report that VEGF improves functional outcome in ischemic rats, including both sensorimotor and cognitive deficiencies.

  17. Post-ischemic administration of progesterone reduces caspase-3 activation and DNA fragmentation in the hippocampus following global cerebral ischemia.

    Science.gov (United States)

    Espinosa-García, Claudia; Vigueras-Villaseñor, Rosa María; Rojas-Castañeda, Julio César; Aguilar-Hernández, Alejandra; Monfil, Tomas; Cervantes, Miguel; Moralí, Gabriela

    2013-08-29

    Delayed death of hippocampal CA1 pyramidal neurons following global cerebral ischemia/reperfusion may be mediated, in part, by caspase-3 activation resulting in DNA fragmentation. Progesterone (P4) is known to exert neuroprotective effects in several models of brain injury. This study was designed to assess the effect of P4 on caspase-3 levels and activation, and DNA fragmentation in the hippocampus following global cerebral ischemia/reperfusion. Adult male Sprague-Dawley rats were subjected to global ischemia by the four-vessel occlusion model. P4 (8 mg/kg), or its vehicle were administered i.v. at 15 min, 2, 6, 24, 48 and 70 h of reperfusion. Remaining pyramidal neurons were assesed by the Nissl staining technique, caspase-3 levels and activation by immunohistochemistry and an in situ activity assay, and DNA fragmentation by the TUNEL method. Post-ischemic progesterone treatment significantly reduced the ischemia/reperfusion-induced increase in caspase-3 levels and activation at 72 h, and DNA fragmentation and CA1 neuronal loss at 7 days. Present results suggest the reduction of caspase-3 levels/activation, and DNA fragmentation, as a part of the neuroprotective effects of progesterone against global cerebral ischemia/reperfusion injury. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  18. Rolipram stimulates angiogenesis and attenuates neuronal apoptosis through the cAMP/cAMP-responsive element binding protein pathway following ischemic stroke in rats.

    Science.gov (United States)

    Hu, Shouye; Cao, Qingwen; Xu, Peng; Ji, Wenchen; Wang, Gang; Zhang, Yuelin

    2016-03-01

    Rolipram, a phosphodiesterase-4 inhibitor, can activate the cyclic adenosine monophosphate (cAMP)/cAMP-responsive element binding protein (CREB) pathway to facilitate functional recovery following ischemic stroke. However, to date, the effects of rolipram on angiogenesis and cerebral ischemia-induced neuronal apoptosis are yet to be fully elucidated. In this study, the aim was to reveal the effect of rolipram on the angiogenesis and neuronal apoptosis following brain cerebral ischemia. Rat models of ischemic stroke were established following transient middle cerebral artery occlusion and rolipram was administered for three, seven and 14 days. The results were examined using behavioral tests, triphenyl tetrazolium chloride staining, immunostaining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) to evaluate the effects of rolipram therapy on functional outcome, angiogenesis and apoptosis. Western blot analysis was used to show the phosphorylated- (p-)CREB protein level in the ischemic hemisphere. The rolipram treatment group exhibited a marked reduction in infarct size and modified neurological severity score compared with the vehicle group, and rolipram treatment significantly promoted the microvessel density in the ischemic boundary region and increased p-CREB protein levels in the ischemic hemisphere. Furthermore, a significant reduction in the number of TUNEL-positive cells was observed in the rolipram group compared with the vehicle group. These findings suggest that rolipram has the ability to attenuate cerebral ischemic injury, stimulate angiogenesis and reduce neuronal apoptosis though the cAMP/CREB pathway.

  19. Effects of treadmill training on matrix metalloproteinases-2 and vascular endotheliar growth factor in ischemic brain of rats after cerebral ischemia-reperfusion%跑台训练对大鼠脑缺血再灌注后脑组织基质金属蛋白酶-2和血管内皮生长因子表达的影响

    Institute of Scientific and Technical Information of China (English)

    马跃文; 强琳

    2012-01-01

    Objective: To study the effects of treadmill training on the recovery of neurological function and the expression of MMP-2 and VEGF in ischemic brain of rats after cerebral ischemia-reperfusion. Method: A total of thirty-five male adult Wistar rats were given cerebral ischemia-reperfusion and were randomly divided into sham-operated group, control group and exercise group, with treadmill running. Neurological function was measured at the 24h after the operation, the 3rd, the 7th and the 14th day after the beginning of exercise respectively. RT-PCR was used to detect the expression of MMP-2 and VEGF in the ischemic brain at the 3rd, 7th and 14th day. Result: Compared with those in the control group, the behavior scores in exercise group was much lower at the 7th and 14th day (P < 0.05). MMP-2 expression in exercises group was higher than in the control group at the 7th and 14th day (P<0.05). The expression of VEGF in the exercise group was greater than that in the control group at all points (P < 0.05). Conclusion: The expression of MMP-2 and VEGF in the brain ischemic area can be improved through treadmill training. It can promote recovery of neurological function by developing neurogenesis and promoting vascularization after cerebral infarction.%目的:探讨跑台训练对大鼠脑缺血再灌注神经功能恢复和缺血脑组织中MMP-2和VEGF表达的影响.方法:用线栓法制作Wistar大鼠大脑中动脉梗死再灌注模型,35只大鼠随机分为假手术组、跑台训练组和手术对照组.跑台训练和手术对照组又分为跑3天、跑7天、跑14天3个亚组,各业组及假手术组每组5只大鼠.跑台组于术后第3天开始给予跑台训练,假手术组及手术对照组不予跑台训练.于跑3天、跑7天、跑14天3个时间点进行神经功能评估后处死大鼠.采用RT-PCR技术测定缺血区脑组织中MMP-2及VEGF的水平.结果:跑台训练组在跑7天、跑14天神经功能评分明显低于对照组(P<0.05).

  20. Therapeutic effects of different durations of acupuncture on rats with middle cerebral artery occlusion

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    Chao Zhang

    2015-01-01

    Full Text Available Acupuncture is regarded as an effective therapy for cerebral ischemia. Different acupuncture manipulations and durations may result in different therapeutic effects. In the present study, the Neiguan (PC6 acupoint of rats with occluded middle cerebral arteries was needled at a fixed frequency (3 Hz with different durations, i.e., 5, 60 and 180 seconds under a twisting-rotating acupuncture method. Results showed that different durations of acupuncture had different therapeutic effects, with 60 seconds yielding a better therapeutic effect than the other two groups. This duration of treatment demonstrated rapid cerebral blood flow, encouraging recovery of neurological function, and small cerebral infarct volume. Experimental findings indicated that under 3 Hz frequency, the treatment of needling Neiguan for 60 seconds is effective for ischemic stroke

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

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    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.

  2. Endogenous neurogenesis and neovascularization in the neocortex of the rat after focal cerebral ischemia.

    Science.gov (United States)

    Shin, Hye Young; Kim, Jin Hyun; Phi, Ji Hoon; Park, Chul-Kee; Kim, Jung Eun; Kim, Jong-Hoon; Paek, Sun Ha; Wang, Kyu-Chang; Kim, Dong Gyu

    2008-02-01

    The present study was designed to examine whether endogenous neurogenesis and neovascularization occur in the neocortex of the ischemic rat brain after unilateral middle cerebral artery occlusion (MCAO). Sprague-Dawley rats were divided into six groups (n = 29): one control group (n = 4) and five groups composed of animals sacrificed at increasing times post-MCAO (2 days and 1, 2, 4, and 8 weeks; n = 5 per group). To determine the presence of neurogenesis and neovascularization in the ischemic brain, nestin, Tuj1, NeuN, GFAP, Tie2, RECA, and 5-bromo-2'-deoxyuridine (BrdU) were analyzed immunohistochemically. In addition, nestin, GFAP, and Tie2 expression was determined by Western blotting. Triple-labeling of nestin, BrdU, and laminin was performed to visualize the interaction between endogenous neurogenesis and neovascularization. The number of BrdU- and nestin-colabeled cells increased markedly in the neocortex and border zone of the ischemic area up to 1 week after MCAO and decreased thereafter. Western blot analysis revealed that the expression of nestin, Tie-2, and GFAP was amplified in the ipsilateral hemisphere 2 days after MCAO and peaked 1 week after MCAO, compared with that in the normal brain. After ischemic injury, nestin- and BrdU-colabeled cells were observed in the vicinity of the endothelial cells lining cerebral vessels in the ipsilateral neocortex of the ischemic brain. Endogenous neurogenesis and neovascularization were substantially activated and occurred in close proximity to one other in the ipsilateral neocortex of the ischemic rat brain. (c) 2007 Wiley-Liss, Inc.

  3. Effects of minocycline on learning and memory of mice following ischemic-hypoxic cerebral injuries

    Institute of Scientific and Technical Information of China (English)

    Hongling Fan; Yuanyin Zheng; Lijuan Xu; Zhichao Zhong; Shining Cai; Shuling Zhang; Quanzhong Chang

    2012-01-01

    An ischemic-hypoxic animal model was established using right common carotid artery occlusions and inhalation of low concentrations of oxygen in mice. At 10 days after the ischemic-hypoxic injuries, saline-treated mice exhibited significantly prolonged escape latencies in water-maze tests and significantly shorter memory latencies and more mistakes in step-down tests. In contrast, mice treated with 5 mg/kg minocycline exhibited significant reversals of each of these effects compared with the saline-treated control mice. Moreover, we found that minocycline can relieve brain water content and morphological changes in mice following ischemic-hypoxic cerebral injuries. Accordingly, our findings indicate that minocycline provides some protections against the deleterious effects of these injuries in mice.

  4. Growth factor-and cytokine-stimulated endothelial progenitor cells in post-ischemic cerebral neovascularization

    Institute of Scientific and Technical Information of China (English)

    Philip V.Peplow

    2014-01-01

    Endothelial progenitor cells are resident in the bone marrow blood sinusoids and circulate in the peripheral circulation. They mobilize from the bone marrow after vascular injury and home to the site of injury where they differentiate into endothelial cells. Activation and mobilization of endothelial progenitor cells from the bone marrow is induced via the production and release of endothelial progenitor cell-activating factors and includes speciifc growth factors and cytokines in response to peripheral tissue hypoxia such as after acute ischemic stroke or trauma. Endotheli-al progenitor cells migrate and home to speciifc sites following ischemic stroke via growth factor/cytokine gradients. Some growth factors are less stable under acidic conditions of tissue isch-emia, and synthetic analogues that are stable at low pH may provide a more effective therapeutic approach for inducing endothelial progenitor cell mobilization and promoting cerebral neovas-cularization following ischemic stroke.

  5. A pathophysiological role of TRPV1 in ischemic injury after transient focal cerebral ischemia in mice

    Energy Technology Data Exchange (ETDEWEB)

    Miyanohara, Jun [Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University (Japan); Shirakawa, Hisashi, E-mail: shirakaw@pharm.kyoto-u.ac.jp [Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University (Japan); Sanpei, Kazuaki [Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University (Japan); Nakagawa, Takayuki [Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University (Japan); Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital (Japan); Kaneko, Shuji [Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University (Japan)

    2015-11-20

    Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel with high Ca{sup 2+} permeability, which functions as a polymodal nociceptor activated by heat, protons and several vanilloids, including capsaicin and anandamide. Although TRPV1 channels are widely distributed in the mammalian brain, their pathophysiological roles in the brain remain to be elucidated. In this study, we investigated whether TRPV1 is involved in cerebral ischemic injury using a middle cerebral artery (MCA) occlusion model in wild-type (WT) and TRPV1-knockout (KO) mice. For transient ischemia, the left MCA of C57BL/6 mice was occluded for 60 min and reperfused at 1 and 2 days after ischemia. We found that neurological and motor deficits, and infarct volumes in TRPV1-KO mice were lower than those of WT mice. Consistent with these results, intracerebroventricular injection of a TRPV1 antagonist, capsazepine (20 nmol), 30 min before the onset of ischemia attenuated neurological and motor deficits and improved infarct size without influencing cerebral blood flow in the occluded MCA territory. The protective effect of capsazepine on ischemic brain damage was not observed in TRPV1-KO mice. WT and TRPV1-KO mice did not show any differences with respect to the increased number of Iba1-positive microglia/macrophages, GFAP-positive astrocytes, and Gr1-positive neutrophils at 1 and 2 days after cerebral ischemia. Taken together, we conclude that brain TRPV1 channels are activated by ischemic stroke and cause neurological and motor deficits and infarction after brain ischemia. - Highlights: • We investigated whether TRPV1 is involved in transient ischemic brain damage in mice. • Neurological deficits and infarct volumes were lower in TRPV1-KO mice than in WT mice. • Injection of a TRPV1 antagonist, capsazepine, attenuated neurological deficits and improved infarct size. • No differences in astrocytic or microglial activation were observed between WT and TRPV1-KO mice.

  6. Meta Analysis of Protective Effect of Cerebral Ischemic Preconditioning on Ischemia-Reperfusion Injury in Rats%脑缺血预处理对大鼠脑缺血再灌注损伤保护作用的 Meta 分析

    Institute of Scientific and Technical Information of China (English)

    曾晓鹏; 邹晓峰; 陈丽

    2016-01-01

    目的:系统评价脑缺血预处理对大鼠脑缺血再灌注损伤的保护作用。方法计算机检索 PubMed(1999年1月至2015年2月)、中国生物医学文献数据库(2003年1月至2015年2月)、中国期刊全文数据库(1999年1月至2015年2月)、万方数据库(2002年10月至2015年2月)获取相关随机对照实验,按照 Cochrane 系统评价的方法评价纳入研究,并使用 Cochrane 协作网提供的 RevMan5.1统计软件进行结果统计分析。结果本 Meta 分析最终纳入11个随机对照试验,均对脑缺血预处理组和脑缺血再灌注组进行了比较。随机效应模型分析结果显示,与脑缺血再灌注组比较,脑缺血预处理组脑梗死体积减少(MD=-79.70,95%CI -111.97、-47.42,P <0.05),脑梗死体积百分比降低(MD=-11.60,95%CI -16.24、-6.95,P <0.05),神经功能缺失评分降低(MD=-1.41,95%CI -1.75、-1.07,P <0.05),血清神经元特异性烯醇化酶活性降低(MD=-3.23,95%CI -3.96、-2.50, P <0.05)。2组脑组织中白细胞介素-1β、肿瘤坏死因子-α水平比较差异无统计学意义(P >0.05)。结论脑缺血预处理对大鼠脑缺血再灌注损伤具有脑保护作用,但本系统评价的不足之处在于纳入的文献数量较少,还需通过开展更多的随机对照实验来验证本研究的结论。%Objective To systematically evaluate the protective effect of cerebral ischemic pre-conditioning on cerebral ischemia reperfusion injury in rats.Methods We searched PubMed(Jan-uary 1999-February 2015 ),Chinese Biomedical Literature Database (January 2003-February 2015),China Academic Journal CNKI(January 1999-February 2015)and Wanfang Database(Oc-tober 2002-February 2015)to obtain relevant randomized controlled trials,which were included in the study according to the Cochrane systematic reviews.The RevMan5

  7. Novel MRI approaches for assessing cerebral hemodynamics in ischemic cerebrovascular disease.

    Science.gov (United States)

    Donahue, Manus J; Strother, Megan K; Hendrikse, Jeroen

    2012-03-01

    Changes in cerebral hemodynamics underlie a broad spectrum of ischemic cerebrovascular disorders. An ability to accurately and quantitatively measure hemodynamic (cerebral blood flow and cerebral blood volume) and related metabolic (cerebral metabolic rate of oxygen) parameters is important for understanding healthy brain function and comparative dysfunction in ischemia. Although positron emission tomography, single-photon emission tomography, and gadolinium-MRI approaches are common, more recently MRI approaches that do not require exogenous contrast have been introduced with variable sensitivity for hemodynamic parameters. The ability to obtain hemodynamic measurements with these new approaches is particularly appealing in clinical and research scenarios in which follow-up and longitudinal studies are necessary. The purpose of this review is to outline current state-of-the-art MRI methods for measuring cerebral blood flow, cerebral blood volume, and cerebral metabolic rate of oxygen and provide practical tips to avoid imaging pitfalls. MRI studies of cerebrovascular disease performed without exogenous contrast are synopsized in the context of clinical relevance and methodological strengths and limitations.

  8. Regional cerebral blood flow during hypoxia-ischemia in immature rats

    Energy Technology Data Exchange (ETDEWEB)

    Vannucci, R.C.; Lyons, D.T.; Vasta, F.

    1988-02-01

    Immature rats subjected to a combination of unilateral common carotid artery ligation and hypoxia sustain brain damage confined largely to the ipsilateral cerebral hemisphere. To ascertain the extent and distribution of ischemic alterations in the brains of these small animals, we modified the Sakurada technique to measure regional cerebral blood flow using carbon-14 autoradiography. Seven-day-old rats underwent right common carotid artery ligation following which they were rendered hypoxic with 8% O2 at 37 degrees C. Before and during hypoxia, the rat pups received an injection of iodo(/sup 14/C)antipyrine for determination of regional cerebral blood flow. Blood flows to individual structures of the ipsilateral cerebral hemisphere were not influenced by arterial occlusion alone; flows to the contralateral hemisphere and to the brainstem and cerebellum actually increased by 25-50%. Hypoxia-ischemia was associated with decreases in regional cerebral blood flow of the ipsilateral hemisphere such that by 2 hours, flows to subcortical white matter, neocortex, striatum, and thalamus were 15, 17, 34, and 41% of control, respectively. The hierarchy of the blood flow reductions correlated closely with the distribution and extent of ischemic neuronal necrosis. However, unlike the pathologic pattern of this model, the degree of ischemia appeared homogeneous within each brain region. Blood flows to contralateral cerebral hemispheric structures were relatively unchanged from prehypoxic values, whereas flows to the brainstem and cerebellum nearly doubled and tripled, respectively. Thus, ischemia is the predominant factor that determines the topography of tissue injury to major regions of immature rat brain, whereas metabolic factors may influence the heterogeneous pattern of damage seen within individual structures.

  9. 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.

  10. Protective Effect of Isoflurane and Sevoflurane on Ischemic Neurons and Expression of Bcl-2 and ICE Genes in Rat Brain

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    To study the protective effect of volatile anesthetics, isoflurane and sevoflurane, on ischemic neurons after cerebral ischemia-reperfusion in rats and its possible molecular mechanism. Methods Rat cerebral ischemia-reperfusion model was developed by occlusion of the middle cerebral artery (MCA) and bilateral common carotid arteries (CCAs) 1 h after reperfusion. Using flow cytometry (FCM) and Northern blot hybridization, we calculated the number of apoptotic bodies and detected the expression of bcl-2 mRNA and interleukin-1 β converting enzyme (ICE) mRNA. Results The apoptotic bodies in hippocampus analyzed by FCM peaked at appeared 24 h after reperfusion, and decreased about 54% and 40%, respectively,after treatment with isoflurane and sevoflurane, as compared with ischemic group. There was no significant difference in the expression of bcl-2 mRNA and ICE mRNA between the inhaled anesthetic groups and ischemic group in hippocampus 24 hafter MCA/CCAs occlusion. Conclusion Isoflurane and sevoflurane partially inhibit apoptosis but have no significant effect on the expression of bcl-2 and ICE genes.

  11. Evaluation of Hypoxic Tissue Dynamics with F-18-FMISO PET in a Rat Model of Permanent Cerebral Ischemia

    OpenAIRE

    Rojas, Santiago; Herance, José Raul; Abad, Sergio; Jiménez, Xavier; Pareto, Deborah; Ruiz, Alba; Torrent, Èlia; Figueiras, Francisca P.; Popota, Foteini; Fernández-Soriano, Francisco J.; Planas, Anna M; Gispert, Juan D.

    2011-01-01

    Purpose: [18F]Fluoromisonidazole (18F-FMISO) is a nitroimidazole derivative that has been proposed as a positron emission tomography (PET) radiotracer to detect hypoxic tissue in vivo. This compound accumulates in hypoxic but viable tissue and may be a good candidate for evaluating the ischemic penumbra. We evaluated the time course of 18F-FMISO uptake using PET in a rat model of permanent cerebral ischemia and the correlation with histological changes. Procedures: Rats (n = 14) were subjecte...

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

    Directory of Open Access Journals (Sweden)

    Adem Bozkurt Aras

    2015-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

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

  14. Compromised Wound Healing in Ischemic Type 2 Diabetic Rats.

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    Peilang Yang

    Full Text Available Ischemia is one of the main epidemic factors and characteristics of diabetic chronic wounds, and exerts a profound effect on wound healing. To explore the mechanism of and the cure for diabetic impaired wound healing, we established a type 2 diabetic rat model. We used an 8 weeks high fat diet (HFD feeding regimen followed by multiple injections of streptozotocin (STZ at a dose of 10mg/kg to induce Wister rat to develop type 2 diabetes. Metabolic characteristics were assessed at the 5th week after the STZ injections to confirm the establishment of diabetes mellitus on the rodent model. A bipedicle flap, with length to width ratio 1.5, was performed on the back of the rat to make the flap area ischemic. Closure of excisional wounds on this bipedicle flap and related physiological and pathological changes were studied using histological, immunohistochemical, real time PCR and protein immunoblot approaches. Our results demonstrated that a combination of HFD feeding and a low dose of STZ is capable of inducing the rats to develop type 2 diabetes with noticeable insulin resistance, persistent hyperglycemia, moderate degree of insulinemia, as well as high serum cholesterol and high triglyceride levels. The excision wounds on the ischemic double pedicle flap showed deteriorative healing features comparing with non-ischemic diabetic wounds, including: delayed healing, exorbitant wound inflammatory response, excessive and prolonged ROS production and excessive production of MMPs. Our study suggested that HFD feeding combined with STZ injection could induce type 2 diabetes in rat. Our ischemic diabetic wound model is suitable for the investigation of human diabetic related wound repair; especically for diabetic chronic wounds.

  15. Effects of ischemic preconditioning on cyclinD1 expression during early ischemic reperfusion in rats

    Institute of Scientific and Technical Information of China (English)

    Fang-Gang Cai; Jian-Sheng Xiao; Qi-Fa Ye

    2006-01-01

    AIM: To observe the effect of ischemic preconditioning on cyclinD1 expression in rat liver cells during early ischemic reperfusion.METHODS: Fifty-four SD rats were randomly divided into ischemic preconditioning group (IP), ischemia/reperfusion group (IR) and sham operation group (SO). The IP and IR groups were further divided into four sub-groups (n = 6). Sham operation group (SO)served as the control group (n = 6). A model of partial liver ischemia/reperfusion was used, in which rats were subjected to liver ischemia for 60 min prior to reperfusion. The animals in the IP group underwent ischemic preconditioning twice for 5 min each time prior to the ischemia/reperfusion challenge. After 0, 1, 2, and 4 h of reperfusion, serum and liver tissue in each group were collected to detect the level of serum ALT, liver histopathology and expression of cyclinD1 mRNA and protein. Flow cytometry was used to detect cell cycle as the quantity indicator of cell regeneration.RESULTS: Compared with IR group, IP group showed asignificantly lower ALT level in 1 h to 4 h sub-groups (P< 0.05). Proliferation index(PI) indicated by the S-phase and G2/M-phase ratio [(S+G2/M)/(G0/G1+S+G2/M)] was significantly increased in IP group at 0 and 1 h (26.44± 7.60% vs 18.56 ± 6.40%,41.87 ± 7.27% vs 20.25 ±6.70%, P < 0.05). Meanwhile, cyclinD1 protein expression could be detected in IP group. But in IR group, cyclinD1 protein expression occurred 2 h after reperfusion. The expression of cyclinD1 mRNA increased significantly in IP group at 0 and 1 h (0.568 ± 0.112 vs 0.274 ± 0.069, 0.762± 0.164 vs 0.348 ± 0.093, P < 0.05).CONCLUSION: Ischemic preconditioning can protect liver cells against ischemia/reperfusion injury, which may be related to cell proliferation and expression of cyclinD1 during early ischemic reperfusion.

  16. Ischemic tolerance protects the rat retina from glaucomatous damage.

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    Nicolás Belforte

    Full Text Available Glaucoma is a leading cause of acquired blindness which may involve an ischemic-like insult to retinal ganglion cells and optic nerve head. We investigated the effect of a weekly application of brief ischemia pulses (ischemic conditioning on the rat retinal damage induced by experimental glaucoma. Glaucoma was induced by weekly injections of chondroitin sulfate (CS in the rat eye anterior chamber. Retinal ischemia was induced by increasing intraocular pressure to 120 mmHg for 5 min; this maneuver started after 6 weekly injections of vehicle or CS and was weekly repeated in one eye, while the contralateral eye was submitted to a sham procedure. Glaucoma was evaluated in terms of: i intraocular pressure (IOP, ii retinal function (electroretinogram (ERG, iii visual pathway function (visual evoked potentials, (VEPs iv histology of the retina and optic nerve head. Retinal thiobarbituric acid substances levels were assessed as an index of lipid peroxidation. Ischemic conditioning significantly preserved ERG, VEPs, as well as retinal and optic nerve head structure from glaucomatous damage, without changes in IOP. Moreover, ischemia pulses abrogated the increase in lipid peroxidation induced by experimental glaucoma. These results indicate that induction of ischemic tolerance could constitute a fertile avenue for the development of new therapeutic strategies in glaucoma treatment.

  17. Imaging findings and cerebral perfusion in arterial ischemic stroke due to transient cerebral arteriopathy in children; Achados de imagem e perfusao arterial cerebral em acidente vascular cerebral isquemico devido a arteriopatia transitoria em crianca

    Energy Technology Data Exchange (ETDEWEB)

    Barbosa Junior, Alcino Alves, E-mail: alcinojr@uol.com.br [Departamento de Diagnostico por Imagem, Hospital Israelita Albert Einstein - HIAE, Sao Paulo, SP (Brazil); Ellovitch, Saada Resende de Souza [Neuropediatria, Hospital Israelita Albert Einstein - HIAE, Sao Paulo, SP (Brazil); Pincerato, Rita de Cassia Maciel [Hospital Samaritano, Sao Paulo, SP (Brazil)

    2012-04-15

    We report the case of a 4-year-old female child who developed an arterial ischemic stroke in the left middle cerebral artery territory, due to a proximal stenosis of the supraclinoid internal carotid artery, most probably related to transient cerebral arteriopathy of childhood. Computed tomography scan, magnetic resonance imaging, perfusion magnetic resonance and magnetic resonance angiography are presented, as well as follow-up by magnetic resonance and magnetic resonance angiography exams. Changes in cerebral perfusion and diffusion-perfusion mismatch call attention. As far as we know, this is the first report of magnetic resonance perfusion findings in transient cerebral arteriopathy. (author)

  18. Attenuation of Cerebral Ischemic Injury in Smad1 Deficient Mice.

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    Jamie K Wong

    Full Text Available Stroke results in brain tissue damage from ischemia and oxidative stress. Molecular regulators of the protective versus deleterious cellular responses after cerebral ischemia remain to be identified. Here, we show that deletion of Smad1, a conserved transcription factor that mediates canonical bone morphogenetic protein (BMP signaling, results in neuroprotection in an ischemia-reperfusion (I/R stroke model. Uninjured mice with conditional deletion of Smad1 in the CNS (Smad1 cKO displayed upregulation of the reactive astrocyte marker GFAP and hypertrophic morphological changes in astrocytes compared to littermate controls. Additionally, cultured Smad1(-/- astrocytes exhibited an enhanced antioxidant capacity. When subjected to I/R injury by transient middle cerebral artery occlusion (tMCAO, Smad1 cKO mice showed enhanced neuronal survival and improved neurological recovery at 7 days post-stroke. This neuroprotective phenotype is associated with attenuated reactive astrocytosis and neuroinflammation, along with reductions in oxidative stress, p53 induction, and apoptosis. Our data suggest that Smad1-mediated signaling pathway is involved in stroke pathophysiology and may present a new potential target for stroke therapy.

  19. Wavelet coherence analysis of dynamic cerebral autoregulation in neonatal hypoxic–ischemic encephalopathy

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    Fenghua Tian

    2016-01-01

    Full Text Available Cerebral autoregulation represents the physiological mechanisms that keep brain perfusion relatively constant in the face of changes in blood pressure and thus plays an essential role in normal brain function. This study assessed cerebral autoregulation in nine newborns with moderate-to-severe hypoxic–ischemic encephalopathy (HIE. These neonates received hypothermic therapy during the first 72 h of life while mean arterial pressure (MAP and cerebral tissue oxygenation saturation (SctO2 were continuously recorded. Wavelet coherence analysis, which is a time-frequency domain approach, was used to characterize the dynamic relationship between spontaneous oscillations in MAP and SctO2. Wavelet-based metrics of phase, coherence and gain were derived for quantitative evaluation of cerebral autoregulation. We found cerebral autoregulation in neonates with HIE was time-scale-dependent in nature. Specifically, the spontaneous changes in MAP and SctO2 had in-phase coherence at time scales of less than 80 min (<0.0002 Hz in frequency, whereas they showed anti-phase coherence at time scales of around 2.5 h (~0.0001 Hz in frequency. Both the in-phase and anti-phase coherence appeared to be related to worse clinical outcomes. These findings suggest the potential clinical use of wavelet coherence analysis to assess dynamic cerebral autoregulation in neonatal HIE during hypothermia.

  20. Doppler examination and cerebral arterial stricture in patients with ischemic stroke

    Institute of Scientific and Technical Information of China (English)

    Shouchun Wang; Yingqi Xing; Fang Deng; Yuerong Cao; Jiachun Feng

    2006-01-01

    BACKGROUND: With the development of interventional therapy, it is necessary for evaluating cerebral vessels to instruct treatment and determine prognosis of patients with ischemic stroke; however, correlation of distribution of infarction focus and clinical symptoms with degrees of cerebrovasoular stricture is still unclear.OBJECTIVE: To evaluate the characteristics of cerebral arterial stricture of patients with ischemic stroke with transcranial Doppler (TCD) and color duplex flow imaging (CDFI) and compare the correlation between distribution of cerebral infarction focus and clinical types with magnetic resonance imaging (MRI).DESIGN: Contrast observation.SETTING: Department of Neurology, the First Hospital of Jilin University.PARTICIPANTS: A total of 159 patients with ischemic stroke were selected from the Department of Neurology, the First Hospital of Jilin University from January to December 2005, including 106 males and 53 females aged from 27 to 88 years. Bases on diagnostic criteria of cerebrovascular disease established by Rao et al, clinical manifestations of all patients were evaluated with CT or nuclear magnetic resonance. All patients provided the confirmed consent.METHODS: The accepted patients received TCD and CDFI examination at 1 week after onset of ischemic stroke. Among them, 112 patients received cerebrovascular imaging examination simultaneously. MRI was used to check cerebral infarction focus and cerebrovascular stricture > 50% was regarded as the accepted vessels. In addition, DWI-T2 TCD (Germany) was used to check middle cerebral artery, and degrees of middle cerebral artery were classified into mild, moderate and severe stricture based on blood velocity (140 cm/s,180 cm/s). Stroke was classified based on characteristics of infarction focus and clinical symptoms showed with MRI and correlation with degrees of cerebrovascular stricture was analyzed simultaneously.MAIN OUTCOME MEASURES: Correlation between the characteristics of ischemic

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

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    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.

  2. Exercise pre‑conditioning alleviates brain damage via excitatory amino acid transporter 2 and extracellular signal‑regulated kinase 1/2 following ischemic stroke in rats.

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    Wang, Xiao; Zhang, Min; Feng, Rui; Li, Wen-Bin; Ren, Shi-Qing; Zhang, Feng

    2015-02-01

    Previous studies have reported that physical exercise may exert a neuroprotective effect in humans as well as animals. However, the detailed mechanisms underlying the neuroprotective effect of exercise has remained to be elucidated. The aim of the present study was to explore the possible signaling pathways involved in the protective effect of pre‑ischemic treadmill training for ischemic stroke in rats. A total of 36 male Sprague‑Dawley rats were divided at random into three groups as follows (n=12 for each): Sham surgery group; middle cerebral artery occlusion (MCAO) group; and exercise with MCAO group. Following treadmill training for three weeks, the middle cerebral artery was occluded for 90 min in order to induce ischemic stroke, followed by reperfusion. Following 24 h post‑reperfusion, six rats from each group were assessed for neurological deficits and then sacrificed to calculate the infarct volume. The remaining rats (n=6 for each group) were sacrificed and the expression levels of excitatory amino acid transporter 2 (EAAT‑2) and extracellular signal‑regulated kinase 1/2 (ERK1/2) were detected using western blot analysis. The results of the present study demonstrated that rats that underwent pre‑ischemic exercise intervention had a significantly decreased brain infarct volume and neurological deficits; in addition, the pre‑ischemic exercise group showed decreased overexpression of phosphorylated ERK1/2 and increased expression of EAAT‑2 following ischemic stroke. In conclusion, treadmill training exercise prior to ischemic stroke alleviated brain damage in rats via regulation of EAAT‑2 and ERK1/2.

  3. [Uncaria tomentosa and acute ischemic kidney injury in rats].

    Science.gov (United States)

    de Fátima Fernandes Vattimo, Maria; da Silva, Natalia Oliveira

    2011-03-01

    The objective of this study was to evaluate the renoprotective effects of Uncaria Tomentosa (cat's claw) on ischemic acute kidney injury induced by renal clamping in rats. The hypoxia and hypoperfusion increase the production of reactive species already present in the inflammatory process. Results showed that the renal function evaluated by creatinine clearance, the urinary excretion of peroxides and malondealdehyde indexes demonstrated that UT induced renoprotection, probably related to its antioxidant activities.

  4. Copolymer-1 promotes neurogenesis and improves functional recovery after acute ischemic stroke in rats.

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    Yolanda Cruz

    Full Text Available Stroke triggers a systemic inflammatory response that exacerbates the initial injury. Immunizing with peptides derived from CNS proteins can stimulate protective autoimmunity (PA. The most renowned of these peptides is copolymer-1 (Cop-1 also known as glatiramer acetate. This peptide has been approved for use in the treatment of multiple sclerosis. Cop-1-specific T cells cross the blood-brain barrier and secrete neurotrophins and anti-inflammatory cytokines that could stimulate proliferation of neural precursor cells and recruit them to the injury site; making it an ideal therapy for acute ischemic stroke. The aim of this work was to evaluate the effect of Cop-1 on neurogenesis and neurological recovery during the acute phase (7 days and the chronic phase of stroke (60 days in a rat model of transient middle cerebral artery occlusion (tMCAo. BDNF and NT-3 were quantified and infarct volumes were measured. We demonstrated that Cop-1 improves neurological deficit, enhances neurogenesis (at 7 and 60 days in the SVZ, SGZ, and cerebral cortex through an increase in NT-3 production. It also decreased infarct volume even at the chronic phase of tMCAo. The present manuscript fortifies the support for the use of Cop-1 in acute ischemic stroke.

  5. Gender and post-ischemic recovery of hypertrophied rat hearts

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    Popov Kirill M

    2006-03-01

    Full Text Available Abstract Background Gender influences the cardiac response to prolonged increases in workload, with differences at structural, functional, and molecular levels. However, it is unknown if post-ischemic function or metabolism of female hypertrophied hearts differ from male hypertrophied hearts. Thus, we tested the hypothesis that gender influences post-ischemic function of pressure-overload hypertrophied hearts and determined if the effect of gender on post-ischemic outcome could be explained by differences in metabolism, especially the catabolic fate of glucose. Methods Function and metabolism of isolated working hearts from sham-operated and aortic-constricted male and female Sprague-Dawley rats before and after 20 min of no-flow ischemia (N = 17 to 27 per group were compared. Parallel series of hearts were perfused with Krebs-Henseleit solution containing 5.5 mM [5-3H/U-14C]-glucose, 1.2 mM [1-14C]-palmitate, 0.5 mM [U-14C]-lactate, and 100 mU/L insulin to measure glycolysis and glucose oxidation in one series and oxidation of palmitate and lactate in the second. Statistical analysis was performed using two-way analysis of variance. The sequential rejective Bonferroni procedure was used to correct for multiple comparisons and tests. Results Female gender negatively influenced post-ischemic function of non-hypertrophied hearts, but did not significantly influence function of hypertrophied hearts after ischemia such that mass-corrected hypertrophied heart function did not differ between genders. Before ischemia, glycolysis was accelerated in hypertrophied hearts, but to a greater extent in males, and did not differ between male and female non-hypertrophied hearts. Glycolysis fell in all groups after ischemia, except in non-hypertrophied female hearts, with the reduction in glycolysis after ischemia being greatest in males. Post-ischemic glycolytic rates were, therefore, similarly accelerated in hypertrophied male and female hearts and higher in

  6. Vagus nerve stimulation attenuates cerebral ischemia and reperfusion injury via endogenous cholinergic pathway in rat.

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    Ying Jiang

    Full Text Available Inflammation and apoptosis play critical roles in the acute progression of ischemic injury pathology. Emerging evidence indicates that vagus nerve stimulation (VNS following focal cerebral ischemia and reperfusion (I/R may be neuroprotective by limiting infarct size. However, the underlying molecular mechanisms remain unclear. In this study, we investigated whether the protective effects of VNS in acute cerebral I/R injury were associated with anti-inflammatory and anti-apoptotic processes. Male Sprague-Dawley (SD rats underwent VNS at 30 min after focal cerebral I/R surgery. Twenty-four h after reperfusion, neurological deficit scores, infarct volume, and neuronal apoptosis were evaluated. In addition, the levels of pro-inflammatory cytokines were detected using enzyme-linked immune sorbent assay (ELISA, and immunofluorescence staining for the endogenous "cholinergic anti-inflammatory pathway" was also performed. The protein expression of a7 nicotinic acetylcholine receptor (a7nAchR, phosphorylated Akt (p-Akt, and cleaved caspase 3 in ischemic penumbra were determined with Western blot analysis. I/R rats treated with VNS (I/R+VNS had significantly better neurological deficit scores, reduced cerebral infarct volume, and decreased number of TdT mediated dUTP nick end labeling (TUNEL positive cells. Furthermore, in the ischemic penumbra of the I/R+VNS group, the levels of pro-inflammatory cytokines and cleaved caspase 3 protein were significantly decreased, and the levels of a7nAchR and phosphorylated Akt were significantly increased relative to the I/R alone group. These results indicate that VNS is neuroprotective in acute cerebral I/R injury by suppressing inflammation and apoptosis via activation of cholinergic and a7nAchR/Akt pathways.

  7. 丹参酮ⅡA对脑缺血再灌注损伤大鼠P-选择素和细胞间黏附分子-1表达的影响%Effect of tanshinone ⅡA on the expression of P-selectin and ICAM-1 after cerebral ischemic reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    李浩; 刘开祥; 俸军林; 蒋静子; 林小慧

    2008-01-01

    目的 探讨丹参酮ⅡA(Tan ⅡA)对脑缺血再灌注损伤大鼠P-选择素和细胞间黏附分子-1(ICAM-1)表达的影响.方法 将大鼠随机分为假手术组、缺血再灌注组、Tan ⅡA低剂量治疗组和Tan ⅡA高剂量治疗组,线栓法建立局灶性脑缺血再灌注模型.Tan ⅡA治疗组于术前连续灌胃给药3 d,1次/d.用免疫组化法观察缺血90 min再灌注24 h大鼠额顶部皮质P-选择素和ICAM-1表达,进行2,3,5-三苯基氯化四氮唑(TYC)染色和HE染色观察脑梗死体积及病理形态学变化.结果 脑缺血再灌注24h,缺血再灌注组P-选择素和ICAM-1表达均明显增加,与假手术组比较,差异具有统计学意义(均P<0.01);与缺血再灌注组比较,Tan ⅡA低、高剂量治疗组均显著减少P-选择素和ICAM-1表达(均P<0.01),低、高剂量组之间差异亦具有统计学意义(P<0.01);Tan ⅡA低、高剂量治疗组脑梗死体积较缺血再灌注组减小,低、高剂量组之间差异亦具有统计学意义(P<0.01);Tan ⅡA低、高剂量治疗组脑组织缺血损伤病理学改变明显轻于缺血再灌注组,Tan ⅡA高剂量治疗组缺血改变亦轻于低剂量治疗组.结论 TanⅡA对缺血再灌注脑损伤具有保护作用,其机制可能与减轻脑缺血再灌注损伤阶段P-选择素和ICAM-1所介导的炎症反应有关,高剂量Tan ⅡA(30 mg/kg)的保护效果更显著.%Objective To study the effect of tanshinone ⅡA on the expression of P-selectin and ICAM-1 after cerebral ischemia reperfusion (I/R)injury in rats. Methods Rats were randomly divided into 4 groups: Sham operated group, I/R group, low dose Tan ⅡA treated group and high dose Tan ⅡA treated group. The focal middle cerebral artery occlusion (MCAO) model was made by suture-occluded method. Rats were pretreated with Tan ⅡA, ig for 3d,respectively before MCAO. After 90min MCAO following 24 hours of reperfusion, the expression of P-selectin and ICAM-1 was detected with using

  8. Regional cerebral blood flow in acute stage ischemic cerebrovascular disease by xenon-133 inhalation and single photon emission computerized tomography

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    Kurokawa, Hiroyuki (Akita Univ. (Japan). School of Medicine)

    1989-03-01

    During the period from February 1984 through June 1985, single photon emission computerized tomography (SPECT) with xenon-133 inhalation method has been performed for the measurement of regional cerebral blood flow (rCBF) during the first 48 hours of onset of cerebral infarction (n=71) and transient ischemic attack (n=21). X-ray CT (CT) and carotid arteriography were concurrently performed in all the patients. In repeated studies performed for 15 normal volunteers, rCBF measurement by SPECT was found reproducible. Mean values of rCBF for the right and left cerebral hemispheres were 60.3{plus minus}6.52 and 61.8{plus minus}6.91 ml/100 g/min, respectively. For cerebral infarction, ischemic foci corresponding to clinical symptoms were detected more frequently on SPECT than on CT (93% vs 63%). In all of the evaluable 35 patients with cerebral infarction, rCBF within the first 8 hours of onset was decreased: 31.0 ml/100 g/min for the internal carotid artery (ICA) occlusion and 36.0 ml/100 g/min for the middle cerebral artery (MCA) occlusion. Crossed cerebellar diaschisis was observed in 50% (9/18) for ICA occlusion and 37% (14/38) for MCA occlusion. For transient ischemic attack, there was no significant difference in the detection of ischemic foci between SPECT and CT (38% vs 43%). In detecting small foci especially in the deep regions such as the basal ganglia, SPECT was inferior to CT. Mean rCBF for transient ischemic attack tended to be lower than the normal rCBF (50.7 ml/100 g/min for the right cerebral hemisphere and 50.6 ml/100 g/min for the left cerebral hemisphere). SPECT may aid in predicting prognosis and chosing treatment strategy, as well as in determining cerebral hemodynamics. (N.K.).

  9. Expression of NMDA receptor and microRNA-219 in rats submitted to cerebral ischemia associated with alcoholism

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    Cristiane Iozzi Silva

    Full Text Available ABSTRACT Alcohol consumption aggravates injuries caused by ischemia. Many molecular mechanisms are involved in the pathophysiology of cerebral ischemia, including neurotransmitter expression, which is regulated by microRNAs. Objective: To evaluate the microRNA-219 and NMDA expression in brain tissue and blood of animals subjected to cerebral ischemia associated with alcoholism. Methods: Fifty Wistar rats were divided into groups: control, sham, ischemic, alcoholic, and ischemic plus alcoholic. The expression of microRNA-219 and NMDA were analyzed by real-time PCR. Results: When compared to the control group, the microRNA-219 in brain tissue was less expressed in the ischemic, alcoholic, and ischemic plus alcoholic groups. In the blood, this microRNA had lower expression in alcoholic and ischemic plus alcoholic groups. In the brain tissue the NMDA gene expression was greater in the ischemic, alcoholic, and ischemic plus alcoholic groups. Conclusion: A possible modulation of NMDA by microRNA-219 was observed with an inverse correlation between them.

  10. Decreased uric acid levels correlate with poor outcomes in acute ischemic stroke patients, but not in cerebral hemorrhage patients.

    Science.gov (United States)

    Wu, Hongliang; Jia, Qian; Liu, Gaifen; Liu, Liping; Pu, Yuehua; Zhao, Xingquan; Wang, Chunxue; Wang, Yilong; Wang, Yongjun

    2014-03-01

    The relationship between uric acid and stroke prognosis is ambiguous. Some studies have explored this relationship in acute stroke but have different results. In this study, we explored the relationship between uric acid levels and 1-year outcomes and vascular events of acute ischemic stroke patients and cerebral hemorrhage patients. In all, 1452 continued first, acute ischemic stroke patients and 380 continued cerebral hemorrhage patients were admitted to our hospitals. Serum uric acid concentrations were measured in 1351 ischemic stroke patients and 380 cerebral hemorrhage patients at admission. We evaluated the relationship between uric acid levels and outcomes (modified Rankin scale [mRS] > 2, all-cause death, vascular events, stroke recurrent) at 14 days, 90 days, and 1 year after stroke onset. The median uric acid concentration was 303.0 μmol/L in ischemic stroke patients and 269 μmol/L in cerebral hemorrhage patients. In univariate analysis, uric acid levels were not correlated with outcomes in cerebral hemorrhage patients. We used multiple logistic regression analysis to show that lower serum uric acid levels independently predicted poor functional outcomes (mRS >2) at 1 year after ischemic stroke onset (odds ratio [OR] = .335, 95% confidence interval [CI]: .164-.684, P = .003). Also, lower serum uric acid levels were independently correlated with vascular events in the first year in ischemic stroke patients. By multiple cox proportional hazards analysis, we obtained data which reveal that serum uric acid levels were not correlated with all-cause death (OR = .992, 95% CI: .683-1.443, P = .969) in ischemic stroke patients. Serum uric acid may be neuroprotective in acute ischemic stroke patients. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  11. Intranasal administration of aTf protects and repairs the neonatal white matter after a cerebral hypoxic-ischemic event.

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    Guardia Clausi, Mariano; Paez, Pablo M; Campagnoni, Anthony T; Pasquini, Laura A; Pasquini, Juana M

    2012-10-01

    Our previous studies showed that the intracerebral injection of apotransferrin (aTf) attenuates white matter damage and accelerates the remyelination process in a neonatal rat model of cerebral hypoxia-ischemia (HI) injury. However, the intracerebral injection of aTf might not be practical for clinical treatments. Therefore, the development of less invasive techniques capable of delivering aTf to the central nervous system would clearly aid in its effective clinical use. In this work, we have determined whether intranasal (iN) administration of human aTf provides neuroprotection to the neonatal mouse brain following a cerebral hypoxic-ischemic event. Apotransferrin was infused into the naris of neonatal mice and the HI insult was induced by right common carotid artery ligation followed by exposure to low oxygen concentration. Our results showed that aTf was successfully delivered into the neonatal HI brain and detected in the olfactory bulb, forebrain and posterior brain 30 min after inhalation. This treatment successfully reduced white matter damage, neuronal loss and astrogliosis in different brain regions and enhanced the proliferation and survival of oligodendroglial progenitor cells (OPCs) in the subventricular zone and corpus callosum (CC). Additionally, using an in vitro hypoxic model, we demonstrated that aTf prevents oligodendrocyte progenitor cell death by promoting their differentiation. In summary, these data suggest that iN administration of aTf has the potential to be used for clinical treatment to protect myelin and to induce remyelination in demyelinating hypoxic-ischemic events in the neonatal brain. Copyright © 2012 Wiley Periodicals, Inc.

  12. Influence of rotating magnetic field on cerebral infarction volume, cerebral edema and free radicals metabolism after cerebral ischemia/reperfusion injury in rats

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    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

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

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    Subhabrata Mitra

    2016-08-01

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

  14. Subarachnoid hemorrhage with transient ischemic attack: Another masquerader in cerebral venous thrombosis

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    Bhawna Sharma

    2010-01-01

    Full Text Available Cerebral venous thrombosis has a wide spectrum of clinical manifestations that may mimic many other neurological disorders and lead to frequent misdiagnoses or delay in diagnosis. The most frequent symptoms and signs are headache, seizures, focal deficits, and papilledema. A number of rare atypical manifestations have been described. Cerebral venous thrombosis may present with an isolated intracranial hypertension type picture, thunderclap headache, attacks of migraine with aura, isolated psychiatric disturbances, pulsatile tinnitus, isolated or multiple cranial nerve involvement, and occasionally as subarachnoid hemorrhage (SAH or transient ischemic attack. Our patient presented with thunderclap headache and transient ischemic attack like episode with obvious SAH on CT scan. Acute SAH suggests the presence of a vascular lesion, such as ruptured aneurysm, and CVT is not generally considered in the diagnostic workup of SAH. The case emphasizes the importance of cerebral venous study in nonaneurysmal cases of SAH. It is important to have a high index of suspicion in such atypical cases to avoid delay in diagnosis.

  15. Imaging Evidence for Cerebral Hyperperfusion Syndrome after Intravenous Tissue Plasminogen Activator for Acute Ischemic Stroke

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    Yi Zhang

    2016-01-01

    Full Text Available Background. Cerebral hyperperfusion syndrome (CHS, a rare complication after cerebral revascularization, is a well-described phenomenon after carotid endarterectomy or carotid artery stenting. However, the imaging evidence of CHS after intravenous tissue plasminogen activator (iv tPA for acute ischemic stroke (AIS has not been reported. Case Report. Four patients were determined to have manifestations of CHS with clinical deterioration after treatment with iv tPA, including one patient who developed seizure, one patient who had a deviation of the eyes toward lesion with worsened mental status, and two patients who developed worsened hemiparesis. In all four patients, postthrombolysis head CT examinations were negative for hemorrhage; CT angiogram showed patent cervical and intracranial arterial vasculature; CT perfusion imaging revealed hyperperfusion with increased relative cerebral blood flow and relative cerebral blood volume and decreased mean transit time along with decreased time to peak in the clinically related artery territory. Vascular dilation was also noted in three of these four cases. Conclusions. CHS should be considered in patients with clinical deterioration after iv tPA and imaging negative for hemorrhage. Cerebral angiogram and perfusion studies can be useful in diagnosing CHS thereby helping with further management.

  16. Biochemical and histopathological alterations in TAR DNA-binding protein-43 after acute ischemic stroke in rats.

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    Kanazawa, Masato; Kakita, Akiyoshi; Igarashi, Hironaka; Takahashi, Tetsuya; Kawamura, Kunio; Takahashi, Hitoshi; Nakada, Tsutomu; Nishizawa, Masatoyo; Shimohata, Takayoshi

    2011-03-01

    Nuclear factor TAR DNA-binding protein-43 (TDP-43) is considered to play roles in pathogenesis of human neurodegenerative diseases, so-called TDP-43 proteinopathy, via its proteolytic cleavage, abnormal phosphorylation, subcellular redistribution, and insolubilization generating TDP-43-positive neuronal intracellular inclusions. The purpose of this study was to elucidate biochemical and histopathological alternations in TDP-43 specific to acute ischemic stroke. Adult male rats were subjected to a 90-min middle cerebral artery occlusion. We examined the proteolytic cleavage, phosphorylation, subcellular localization, and solubility of TDP-43 by immunoblottings and histopathological examinations using the ischemic and sham-operated cortex. The level of full-length TDP-43 (43 kDa) decreased and that of the 25-kDa C-terminal fragment increased after acute ischemic stroke, which can be explained by proteolytic cleavage of TDP-43. Cytoplasmic redistribution and altered nuclear distribution of TDP-43 was observed after acute ischemic stroke, whereas abnormal phosphorylation and insolubilization of TDP-43 as well as formation of intracellular inclusions were not observed. Ischemic neurons with the cytoplasmic redistribution of TDP-43 expressed ubiquitin and activated caspase 3 and were terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling-positive. In conclusion, biochemical and histopathological alterations in TDP-43 were identified in rats after acute ischemic stroke, although there was very less similarity between TDP-43 alterations observed in acute ischemic stroke and those observed in TDP-43 proteinopathy. © 2010 The Authors. Journal Compilation © 2010 International Society for Neurochemistry.

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

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    Huang Yen

    2011-09-01

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

  18. Early cerebral hemodynamic, metabolic and histological changes in hypoxic-ischemic fetal lambs during postnatal life

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    Carmen eRey-Santano

    2011-09-01

    Full Text Available The hemodynamic, metabolic and biochemical changes produce during transition from fetal to neonatal life could be aggravated if asphyctic event occur during fetal life. The aim of the study was to examine the regional cerebral blood flow (RCBF, histological changes, and cerebral brain metabolism in preterm lambs, and to analyze the role of oxidative stress for the first hours of postnatal life following severe fetal asphyxia. 18 chronically instrumented fetal lambs were assigned to: hypoxic-ischemic group, following fetal asphyxia animals were delivered and maintained on intermittent-positive-pressure-ventilation for 3 hours, and non-injured animals that were managed similarly to the previous group and used as control group. During hypoxic-ischemic insult, injured group developed acidosis, hypoxia, hypercapnia, latacidaemia and tachycardia in comparison to control group, without hypotension. Intermittent-positive-pressure-ventilation transiently improved gas exchange and cardiovascular parameters. After HI injury and during ventilation-support, the increased RCBF in inner zones was maintained for hypoxic-ischemic group, but cortical flow did not exhibit differences compared to the control group. Also, the increase of TUNEL positive cells (apoptosis and antioxidant enzymes, and decrease of ATP reserves was significantly higher in the brain regions where the RCBF were not increased.In conclusion, early metabolic, histological and hemodynamic changes involved in brain damage have been intensively investigated and reported in premature asphyctic lambs for the first 3 hours of postnatal life. Those changes have been described in human neonates, so our model could be useful to test the security and the effectiveness of different neuroprotective or ventilatory strategies when are applied in the first hours after fetal hypoxic-ischemic injury.

  19. Protective effects of remote ischemic preconditioning in rat hindlimb on ischemia-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Ying Zhang; Xiangrong Liu; Feng Yan; Lianqiu Min; Xunming Ji; Yumin Luo

    2012-01-01

    Three cycles of remote ischemic pre-conditioning induced by temporarily occluding the bilateral femoral arteries (10 minutes) prior to 10 minutes of reperfusion were given once a day for 3 days before the animal received middle artery occlusion and reperfusion surgery. The results showed that brain infarct volume was significantly reduced after remote ischemic pre-conditioning. Scores in the forelimb placing test and the postural reflex test were significantly lower in rats having undergone remote ischemic pre-conditioning compared with those who did not receive remote ischemic pre-conditioning. Thus, neurological function was better in rats having undergone remote ischemic pre-conditioning compared with those who did not receive remote ischemic pre-conditioning. These results indicate that remote ischemic pre-conditioning in rat hindlimb exerts protective effects in ischemia-reperfusion injury.

  20. Melatonin protects against ischemic heart failure in rats.

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    Şehirli, Ahmet Özer; Koyun, Derya; Tetik, Şermin; Özsavcı, Derya; Yiğiner, Ömer; Çetinel, Şule; Tok, Olgu Enis; Kaya, Zehra; Akkiprik, Mustafa; Kılıç, Ertugrul; Şener, Göksel

    2013-09-01

    Ischemic injury, which occurs as a result of sympathetic hyperactivity, plays an important role in heart failure. Melatonin is thought to have antiatherogenic, antioxidant, and vasodilatory effects. In this study, we investigated whether melatonin protects against ischemic heart failure (HF). In Wistar albino rats, HF was induced by left anterior descending (LAD) coronary artery ligation and rats were treated with either vehicle or melatonin (10 mg/kg) for 4 weeks. At the end of this period, echocardiographic measurements were recorded and the rats were decapitated to obtain plasma and cardiac tissue samples. Lactate dehydrogenase, creatine kinase, aspartate aminotransferase, alanine aminotransferase, and lysosomal enzymes (β-D-glucuronidase, β-galactosidase, β-D-N-acetyl-glucosaminidase, acid phosphatase, and cathepsin-D) were studied in plasma samples, while malondialdehyde and glutathione levels and Na+, K+-ATPase, caspase-3 and myeloperoxidase activities were determined in the cardiac samples. Sarco/endoplasmic reticulum calcium ATPase (SERCA) and caveolin-3 levels in cardiac tissues were evaluated using Western blot analyses. Furthermore, caveolin-3 levels were also determined by histological analyses. In the vehicle-treated HF group, cardiotoxicity resulted in decreased cardiac Na+, K+-ATPase and SERCA activities, GSH contents and caveolin-3 levels, while plasma LDH, CK, and lysosomal enzyme activities and cardiac MDA and Myeloperoxidase (MPO) activities were found to be increased. On the other hand, melatonin treatment reversed all the functional and biochemical changes. The present results demonstrate that Mel ameliorates ischemic heart failure in rats. These observations highlight that melatonin is a promising supplement for improving defense mechanisms in the heart against oxidative stress caused by heart failure.

  1. 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

  2. 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.

  3. 大鼠局灶性脑缺血后少突胶质前体细胞激活及髓鞘再生的实验研究%Experimental research on activation of oligodendrocyte progenitor cells and myelination in the focal cerebral ischemic rat brain

    Institute of Scientific and Technical Information of China (English)

    赵红; 张拥波; 王得新; 王苏平

    2012-01-01

    目的 探讨脑缺血再灌注大鼠少突胶质前体细胞(oligodendrocyte progenitor cells,OPCs)及髓鞘的表达变化.方法 线栓法建立大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)模型,免疫组化方法检测脑缺血再灌注后不同时间点1d、1w和2w不同脑区(梗死中心区、梗死周边区和梗死对侧区)OPCs特异性细胞标志物NG2的阳性细胞数及和髓鞘标志物碱性髓鞘蛋白(myelin basic protein,MBP)的表达变化.结果 脑缺血后梗死中心区NG2阳性细胞数和MBP的表达随着再灌注时间延长而逐渐减少;梗死周边区NG2阳性细胞数在1w~2w增加,MBP的表达在24h~1w内降低,2w恢复到正常水平;梗死对侧区NG2阳性细胞数和MBP的表达无明显变化.梗死周边区OPCs细胞呈“单极”或“双极”分裂状,并从梗死灶的外带迁移到内带,提示OPCs细胞激活、增生并发生迁移.结论 脑缺血再灌注后梗死周边区NG2细胞增多,使得一度缺失的成熟少突胶质细胞及髓鞘得到补充,提示NG2细胞可能参与缺血损伤的修复过程.%Objective To explore the expression of oligodendrocyte progenitor cells ( OPCs) and myelin after focal . cerebral ischemic in the rat brain. Methods Transient focal ischemia was induced by middle cerebral artery occlusion (MCAO) for 120 minutes with a nylon filament. By immunohistochemistry technique, NG2 positive cells and MBP were detected at different time points in the different brain area(infarcl core,pcri-infarct area and contralateral area) after MCAO. Results The infarct core showed a progressive decrease in the number of NG2 and MBP density from 24h to 2w after MCAO. The peri-infarct area exhibited a slight increase in NG2 positive cells from 1w to 2w and showed a decrease in the myelin density from 24h to lw,then return to the normal level after 2w of recirculalion. No difference of NG2 positive cells and MBP density in the contralateral area at any time points was found after

  4. Pentoxifylline attenuates TNF-α protein levels and brain edema following temporary focal cerebral ischemia in rats.

    Science.gov (United States)

    Vakili, Abedin; Mojarrad, Somye; Akhavan, Maziar Mohammad; Rashidy-Pour, Ali

    2011-03-04

    Cerebral edema is the most common cause of neurological deterioration and mortality during acute ischemic stroke. Despite the clinical importance of cerebral ischemia, the underlying mechanisms remain poorly understood. Recent studies suggest a role for TNF-α in the brain edema formation. To further investigate whether TNF-α would play a role in brain edema formation, we examined the effects of pentoxifylline (PTX, an inhibitor of TNF-α synthesis) on the brain edema and TNF-α levels in a model of transient focal cerebral ischemia. The right middle cerebral artery (MCA) of rats was occluded for 60 min using the intraluminal filament method. The animals received PTX (60 mg/kg) immediately, 1, 3, or 6h post-ischemic induction. Twenty-four hours after induction of ischemic injury, permeability of the blood-brain barrier (BBB) and brain edema were determined by in situ brain perfusion of Evans Blue (EB) and wet-to-dry weight ratio, respectively. TNF-α protein levels in ischemic cortex were also measured at 1, 4, and 24h after the beginning of an ischemic stroke by using an enzyme-linked immunosorbent assay method. The administration of PTX up to 6h after occlusion of the MCA significantly reduced the brain edema. Moreover, PTX significantly reduced the concentration of TNF-α in ischemic brain cortex up to 4h post-transient focal stroke (Pedema in a model of transient focal cerebral ischemia. The beneficial effects of PTX may be mediated, at least in part, through a decline in TNF-α production and BBB breakdown.

  5. Neuroprotective Effect of Scutellarin on Ischemic Cerebral Injury by Down-Regulating the Expression of Angiotensin-Converting Enzyme and AT1 Receptor.

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    Wenjuan Wang

    Full Text Available Previous studies have demonstrated that angiotensin-converting enzyme (ACE is involved in brain ischemic injury. In the present study, we investigated whether Scutellarin (Scu exerts neuroprotective effects by down-regulating the Expression of Angiotensin-Converting Enzyme and AT1 receptor in a rat model of permanent focal cerebral ischemia.Adult Sprague-Dawley rats were administrated with different dosages of Scu by oral gavage for 7 days and underwent permanent middle cerebral artery occlusion (pMCAO. Blood pressure was measured 7 days after Scu administration and 24 h after pMCAO surgery by using a noninvasive tail cuff method. Cerebral blood flow (CBF was determined by Laser Doppler perfusion monitor and the neuronal dysfunction was evaluated by analysis of neurological deficits before being sacrificed at 24 h after pMCAO. Histopathological change, cell apoptosis and infarct area were respectively determined by hematoxylin-eosin staining, terminal deoxynucleotidyl transfer-mediated dUTP nick end labeling (TUNEL analysis and 2,3,5-triphenyltetrazolium chloride staining. Tissue angiotensin II (Ang II and ACE activity were detected by enzyme-linked immunosorbent assays. The expression levels of ACE, Ang II type 1 receptor (AT1R, tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6, and interleukin-1β (IL-1β were measured by Western blot and real-time PCR. ACE inhibitory activity of Scu in vitro was detected by the photometric determination.Scu treatment dose-dependently decreased neurological deficit score, infarct area, cell apoptosis and morphological changes induced by pMCAO, which were associated with reductions of ACE and AT1R expression and the levels of Ang II, TNF-α, IL-6, and IL-1β in ischemic brains. Scu has a potent ACE inhibiting activity.Scu protects brain from acute ischemic injury probably through its inhibitory effect on the ACE/Ang II/AT1 axis, CBF preservation and proinflammation inhibition.

  6. Bryostatin improves survival and reduces ischemic brain injury in aged rats following acute ischemic stroke

    Science.gov (United States)

    Tan, Zhenjun; Turner, Ryan C.; Leon, Rachel L.; Li, Xinlan; Hongpaisan, Jarin; Zheng, Wen; Logsdon, Aric F.; Naser, Zachary J.; Alkon, Daniel L.; Rosen, Charles L.; Huber, Jason D.

    2014-01-01

    Background and Purpose Bryostatin, a potent protein kinase C (PKC) activator, has demonstrated therapeutic efficacy in preclinical models of associative memory, Alzheimer's disease, global ischemia, and traumatic brain injury. In this study, we tested the hypothesis that administration of bryostatin provides a therapeutic benefit in reducing brain injury and improving stroke outcome using a clinically relevant model of cerebral ischemia with tissue plasminogen activator (tPA) reperfusion in aged rats. Methods Acute cerebral ischemia was produced by reversible occlusion of the right middle cerebral artery (MCAO) in 18-20 month old female Sprague-Dawley rats using an autologous blood clot with tPA-mediated reperfusion. Bryostatin was administered at 6 h post-MCAO then at 3, 6, 9, 12, 15, and 18 d after MCAO. Functional assessment was conducted at 2, 7, 14, and 21 d after MCAO. Lesion volume and hemispheric swelling/atrophy were performed at 2, 7, and 21 d post-MCAO. Histological assessment of PKC isozymes was performed at 24 h post-MCAO. Results Bryostatin-treated rats showed improved survival post-MCAO, especially during the first 4 d. Repeated administration of bryostatin post-MCAO resulted in reduced infarct volume, hemispheric swelling/atrophy, and improved neurological function at 21 d post-MCAO. Changes in PKC alpha expression and PKC epsilon expression in neurons were noted in bryostatin-treated rats at 24 h post-MCAO. Conclusions Repeated bryostatin administration post-MCAO protected the brain from severe neurological injury post-MCAO. Bryostatin treatment improved survival rate, reduced lesion volume, salvaged tissue in infarcted hemisphere by reducing necrosis and peri-infarct astrogliosis, and improved functional outcome following MCAO. PMID:24172582

  7. Bryostatin improves survival and reduces ischemic brain injury in aged rats after acute ischemic stroke.

    Science.gov (United States)

    Tan, Zhenjun; Turner, Ryan C; Leon, Rachel L; Li, Xinlan; Hongpaisan, Jarin; Zheng, Wen; Logsdon, Aric F; Naser, Zachary J; Alkon, Daniel L; Rosen, Charles L; Huber, Jason D

    2013-12-01

    Bryostatin, a potent protein kinase C (PKC) activator, has demonstrated therapeutic efficacy in preclinical models of associative memory, Alzheimer disease, global ischemia, and traumatic brain injury. In this study, we tested the hypothesis that administration of bryostatin provides a therapeutic benefit in reducing brain injury and improving stroke outcome using a clinically relevant model of cerebral ischemia with tissue plasminogen activator reperfusion in aged rats. Acute cerebral ischemia was produced by reversible occlusion of the right middle cerebral artery (MCAO) in 18- to 20-month-old female Sprague-Dawley rats using an autologous blood clot with tissue plasminogen activator-mediated reperfusion. Bryostatin was administered at 6 hours post-MCAO, then at 3, 6, 9, 12, 15, and 18 days after MCAO. Functional assessment was conducted at 2, 7, 14, and 21 days after MCAO. Lesion volume and hemispheric swelling/atrophy were performed at 2, 7, and 21 days post-MCAO. Histological assessment of PKC isozymes was performed at 24 hours post-MCAO. Bryostatin-treated rats showed improved survival post-MCAO, especially during the first 4 days. Repeated administration of bryostatin post-MCAO resulted in reduced infarct volume, hemispheric swelling/atrophy, and improved neurological function at 21 days post-MCAO. Changes in αPKC expression and εPKC expression in neurons were noted in bryostatin-treated rats at 24 hours post-MCAO. Repeated bryostatin administration post-MCAO protected the brain from severe neurological injury post-MCAO. Bryostatin treatment improved survival rate, reduced lesion volume, salvaged tissue in infarcted hemisphere by reducing necrosis and peri-infarct astrogliosis, and improved functional outcome after MCAO.

  8. Ischemic Postconditioning Protects Neuronal Death Caused by Cerebral Ischemia and Reperfusion via Attenuating Protein Aggregation

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    Jianmin Liang, Jihang Yao, Guangming Wang, Ying Wang, Boyu Wang, Pengfei Ge

    2012-01-01

    Full Text Available Objective: To investigate the effect of ischemic postconditioning on protein aggregation caused by transient ischemia and reperfusion and to clarify its underlying mechanism.Methods: Two-vessel-occluded transient global ischemia rat model was used. The rats in ischemic postconditioning group were subjected to three cycles of 30-s/30-s reperfusion/clamping after 15min of ischemia. Neuronal death in the CA1 region was observed by hematoxylin-eosin staining, and number of live neurons was assessed by cell counting under a light microscope. Succinyl-LLVY-AMC was used as substrate to assay proteasome activity in vitro. Protein carbonyl content was spectrophotometrically measured to analyze protein oxidization. Immunochemistry and laser scanning confocal microscopy were used to observe the distribution of ubiquitin in the CA1 neurons. Western blotting was used to analyze the quantitative alterations of protein aggregates, proteasome, hsp70 and hsp40 in cellular fractions under different ischemic conditions.Results: Histological examination showed that the percentage of live neurons in the CA1 region was elevated from 5.21%±1.21% to 55.32%±5.34% after administration of ischemic postconditioning (P=0.0087. Western blotting analysis showed that the protein aggregates in the ischemia group was 32.12±4.87, 41.86±4.71 and 34.51±5.18 times higher than that in the sham group at reperfusion 12h, 24h and 48h, respectively. However, protein aggregates were alleviated significantly by ischemic postconditioning to 2.84±0.97, 13.72±2.13 and 14.37±2.42 times at each indicated time point (P=0.000032, 0.0000051 and 0.0000082. Laser scanning confocal images showed ubiquitin labeled protein aggregates could not be discerned in the ischemic postconditioning group. Further study showed that ischemic postconditioning suppressed the production of carbonyl derivatives, elevated proteasome activity that was damaged by ischemia and reperfusion, increased the expression

  9. Electroacupuncture acutely improves cerebral blood flow and attenuates moderate ischemic injury via an endothelial mechanism in mice.

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    Ji Hyun Kim

    Full Text Available Electroacupuncture (EA is a novel therapy based on traditional acupuncture combined with modern eletrotherapy that is currently being investigated as a treatment for acute ischemic stroke. Here, we studied whether acute EA stimulation improves tissue and functional outcome following experimentally induced cerebral ischemia in mice. We hypothesized that endothelial nitric oxide synthase (eNOS-mediated perfusion augmentation was related to the beneficial effects of EA by interventions in acute ischemic injury. EA stimulation at Baihui (GV20 and Dazhui (GV14 increased cerebral perfusion in the cerebral cortex, which was suppressed in eNOS KO, but there was no mean arterial blood pressure (MABP response. The increased perfusion elicited by EA were completely abolished by a muscarinic acetylcholine receptor (mAChR blocker (atropine, but not a β-adrenergic receptor blocker (propranolol, an α-adrenergic receptor blocker (phentolamine, or a nicotinic acetylcholine receptor (nAChR blocker (mecamylamine. In addition, EA increased acetylcholine (ACh release and mAChR M3 expression in the cerebral cortex. Acute EA stimulation after occlusion significantly reduced infarct volume by 34.5% when compared to a control group of mice at 24 h after 60 min-middle cerebral artery occlusion (MCAO (moderate ischemic injury, but not 90-min MCAO (severe ischemic injury. Furthermore, the impact of EA on moderate ischemic injury was totally abolished in eNOS KO. Consistent with a smaller infarct size, acute EA stimulation led to prominent improvement of neurological function and vestibule-motor function. Our results suggest that acute EA stimulation after moderate focal cerebral ischemia, but not severe ischemia improves tissue and functional recovery and ACh/eNOS-mediated perfusion augmentation might be related to these beneficial effects of EA by interventions in acute ischemic injury.

  10. 慢性脑缺血大鼠海马CA1区锥体细胞树突形态及树突棘密度的变化%Changes of dendritic morphology and spine density in hippocampal CA1 pyramidal cells of chronic cerebral ischemic rats

    Institute of Scientific and Technical Information of China (English)

    贾贺; 张博爱; 刘宇; 张小敏; 姬亚杰; 李星; 刘荣丽

    2012-01-01

    目的:研究慢性脑缺血大鼠海马CA1区锥体细胞树突形态及树突棘密度的变化.方法:对大鼠进行双侧颈总动脉永久性结扎(2VO)制备慢性脑缺血模型,分别于2周、4周、8周通过Morris水迷宫对各组大鼠进行行为学评价,筛选造模成功大鼠,进行Golgi染色,光镜下观察海马CA1区锥体细胞树突的分支、长度及树突棘密度的变化.结果:与对照组相比,4周、8周模型组树突的分支及长度显著减少(P<0.01),各周模型组树突棘的密度均有显著减少(P<0.01);模型组内随着缺血时间延长,树突的分支及长度、树突棘密度均显著减少(P<0.05).结论:慢性脑缺血可导致海马CA1区锥体细胞树突及树突棘损伤性变化,从而构成进展性认知功能障碍的病理生理学基础.%AIM:To investigate the changes of dendritic morphology and spine density in hippocampal CA1 pyramidal cells of the chronic cerebral ischemic rats. METHODS:The model of chronic cerebral ischemia was established by permanent occlusion of the bilateral common carotid arteries ( 2VO ) in rats. Two weeks, 4 weeks or 8 weeks later, the behavior of the rats in each group was evaluated through the Morris water maze to select the successful modeling, and the brains were collected for processing Golgi staining. The changes in dendritic branch and length, and spine density in hippocampal CA1 pyramidal cells were observed under optical microscope. RESULTS: Compared with sham - operated group, dendritic branch and length in model group was significantly reduced in 4 -week group and 8 -week group ( P <0. 01 ), and spine density in model group were significantly reduced in 2 -week, 4 -week and 8 -week groups ( P <0. 01 ). With prolonged ischemia, dendritic branch and length, and spine density in model group were all significantly reduced ( P < 0. 05 ). CONCLUSION: Chronic cerebral ischemia leads to traumatic changes in dendrites and spines in hippocampal CA1 pyramidal cells, which

  11. Cerebrolysin effects on neurological outcomes and cerebral blood flow in acute ischemic stroke

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    Amiri-Nikpour MR

    2014-12-01

    Full Text Available Mohammad Reza Amiri-Nikpour,1 Surena Nazarbaghi,1 Babak Ahmadi-Salmasi,1 Tayebeh Mokari,2 Urya Tahamtan,2 Yousef Rezaei3 1Department of Neurology, Imam Khomeini Hospital, 2School of Medicine, 3Seyyed-al-Shohada Heart Center, Urmia University of Medical Sciences, Urmia, Iran Background: Cerebrolysin, a brain-derived neuropeptide, has been shown to improve the neurological outcomes of stroke, but no study has demonstrated its effect on cerebral blood flow. This study aimed to determine the cerebrolysin impact on the neurological outcomes and cerebral blood flow. Methods: In a randomized, double-blinded, placebo-controlled trial, 46 patients who had acute focal ischemic stroke were randomly assigned into two groups to receive intravenously either 30 mL of cerebrolysin diluted in normal saline daily for 10 days (n=23 or normal saline alone (n=23 adjunct to 100 mg of aspirin daily. All patients were examined using the National Institutes of Health Stroke Scale and transcranial Doppler to measure the mean flow velocity and pulsatility index (PI of their cerebral arteries at baseline as well as on days 30, 60, and 90. Results: The patients’ mean age was 60±9.7 years, and 51.2% of patients were male. The National Institutes of Health Stroke Scale was significantly lower in the cerebrolysin group compared with the placebo group on day 60 (median 10, interquartile range 9–11, P=0.008 and day 90 (median 11, interquartile range 10–13.5, P=0.001. The median of PI in the right middle cerebral artery was significantly lower in the cerebrolysin group compared with the placebo group on days 30, 60, and 90 (P<0.05. One patient in the cerebrolysin group and two patients in the placebo group died before day 30 (4.3% versus 8.7%. Conclusion: Cerebrolysin can be useful to improve the neurological outcomes and the PI of middle cerebral artery in patients with acute focal ischemic stroke. Keywords: ischemic stroke, cerebrolysin, neuroprotection, NIHSS, mean

  12. Difference in the Location and Risk Factors of Cerebral Microbleeds According to Ischemic Stroke Subtypes.

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    Kim, Bum Joon; Yoon, Youngshin; Sohn, Hoyon; Kang, Dong-Wha; Kim, Jong S; Kwon, Sun U

    2016-09-01

    The location of cerebral microbleeds (CMBs) may differ according to ischemic stroke subtype, and the underlying pathomechanism may differ by their location. Here, we investigated the characteristics of CMBs according to various ischemic stroke subtypes to verify this issue. Patients with acute ischemic stroke were consecutively included. The presence of CMBs was determined by gradient echo image sequence. The distribution of CMBs was classified as deep, lobar, or diffuse (both deep and lobar). The prevalence, risk factors, and distribution of CMBs were compared among patients with different stroke subtypes. Factors associated with the distribution of CMBs were investigated. Among the 1033 patients included in this study, ischemic stroke subtypes were classified as large artery atherosclerosis (LAA; n=432), small vessel occlusion (SVO; n=304), and cardioembolism (CE; n=297). The prevalence of CMBs was highest in patients with SVO (40.5%), followed by CE (33.0%) and LAA (24.8%; PCMBs was different according to subtype (P=0.004). CE [odds ratio (OR)=1.85 (1.02-3.34); P=0.042] and the use of antithrombotics [OR=1.80 (1.10-2.94); P=0.019] were associated with lobar CMBs, and old age [OR=1.02 (1.00-1.04); P=0.015] and hypertension [OR=1.61 (1.08-2.40); P=0.020] were associated with deep CMBs. CMBs were frequently located in the lobar area in patients with CE. Previous use of antithrombotic agents is associated with lobar CMBs. The pathogenic mechanism of CMB may differ according to ischemic stroke subtype and location.

  13. Compromised Blood-Brain Barrier Competence in Remote Brain Areas in Ischemic Stroke Rats at Chronic Stage

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    Garbuzova-Davis, Svitlana; Haller, Edward; Williams, Stephanie N.; Haim, Eithan D.; Tajiri, Naoki; Hernandez-Ontiveros, Diana G.; Frisina-Deyo, Aric; Boffeli, Sean M.; Sanberg, Paul R.; Borlongan, Cesario V.

    2014-01-01

    Stroke is a life threatening disease leading to long-term disability in stroke survivors. Cerebral functional insufficiency in chronic stroke might be due to pathological changes in brain areas remote from initial ischemic lesion, i.e. diaschisis. Previously, we showed that the damaged blood-brain barrier (BBB) was implicated in subacute diaschisis. The present study investigated BBB competence in chronic diaschisis using a transient middle cerebral artery occlusion (tMCAO) rat model. Our results demonstrated significant BBB damage mostly in the ipsilateral striatum and motor cortex in rats at 30 days after tMCAO. The BBB alterations were also determined in the contralateral hemisphere via ultrastructural and immunohistochemical analyses. Major BBB pathological changes in contralateral remote striatum and motor cortex areas included: (1) vacuolated endothelial cells containing large autophagosomes, (2) degenerated pericytes displaying mitochondria with cristae disruption, (3) degenerated astrocytes and perivascular edema, (4) Evans Blue extravasation, and (5) appearance of parenchymal astrogliosis. Importantly, discrete analyses of striatal and motor cortex areas revealed significantly higher autophagosome accumulation in capillaries of ventral striatum and astrogliosis in dorsal striatum in both cerebral hemispheres. These widespread microvascular alterations in ipsilateral and contralateral brain hemispheres suggest persistent and/or continued BBB damage in chronic ischemia. The pathological changes in remote brain areas likely indicate chronic ischemic diaschisis, which should be considered in the development of treatment strategies for stroke. PMID:24610730

  14. A Voxel-based Morphometric Analysis of Cerebral Gray Matter in Subcortical Ischemic Vascular Dementia Patients and Normal Aged Controls

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    Chuanming Li, Hanjian Du, Jian Zheng, Jian Wang

    2011-01-01

    Full Text Available BACKGROUND AND PURPOSE: The present study was designed to detect the abnormalities of the cerebral grey-matter density in subcortical ischemic vascular dementia patients by FSL-VBM method to promote the early diagnosis of it.METHODS: Nine subcortical ischemic vascular dementia patients and nine age-matched normal controls underwent MRI brain structure scanning that was performed on a SIEMENS AVANTO 1.5 Tesla scanner and standard T1-weighted high-resolution anatomic scans of MPRAGE sequence were obtained. The 3-demensional MPRAGE images were processed with FSL-VBM package and the cerebral gray matter density was compared between the subcortical ischemic vascular dementia patients and normal controls.RESULTS: Compared with the normal control group, the cerebral gray matter density of subcortical ischemic vascular dementia patients was found significantly decreasing, including brain regions of thalamus, parietal lobe, frontal lobe and temporal lobe (P<0.05.CONCLUSIONS: The cerebral gray matter density alterations have closed correlation with cognitive dysfunction in subcortical ischemic vascular dementia patient and can be detected by MRI. MRI has some potential value in the diagnosis of them.

  15. Impaired cerebral autoregulation is associated with brain atrophy and worse functional status in chronic ischemic stroke.

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    Mikio C Aoi

    Full Text Available Dynamic cerebral autoregulation (dCA is impaired following stroke. However, the relationship between dCA, brain atrophy, and functional outcomes following stroke remains unclear. In this study, we aimed to determine whether impairment of dCA is associated with atrophy in specific regions or globally, thereby affecting daily functions in stroke patients.We performed a retrospective analysis of 33 subjects with chronic infarctions in the middle cerebral artery territory, and 109 age-matched non-stroke subjects. dCA was assessed via the phase relationship between arterial blood pressure and cerebral blood flow velocity. Brain tissue volumes were quantified from MRI. Functional status was assessed by gait speed, instrumental activities of daily living (IADL, modified Rankin Scale, and NIH Stroke Score.Compared to the non-stroke group, stroke subjects showed degraded dCA bilaterally, and showed gray matter atrophy in the frontal, parietal and temporal lobes ipsilateral to infarct. In stroke subjects, better dCA was associated with less temporal lobe gray matter atrophy on the infracted side ([Formula: see text] = 0.029, faster gait speed ([Formula: see text] = 0.018 and lower IADL score ([Formula: see text]0.002. Our results indicate that better dynamic cerebral perfusion regulation is associated with less atrophy and better long-term functional status in older adults with chronic ischemic infarctions.

  16. Continuous nimodipine treatment attenuates cortical infarction in rats subjected to 24 hours of focal cerebral ischemia.

    Science.gov (United States)

    Jacewicz, M; Brint, S; Tanabe, J; Pulsinelli, W A

    1990-01-01

    Focal cerebral infarction and edema were measured in rats (Wistar, Fisher 344, and spontaneously hypertensive strains) pretreated with nimodipine (2 micrograms/kg/min i.v.) or its vehicle and subjected to the tandem occlusion of the middle cerebral and common carotid arteries. Animals awoke from anesthesia 10-15 min after onset of ischemia and continued to receive treatment over a 24-h survival period. Cortical infarction and edema were quantified by image analysis of frozen brain sections processed for histology. Nimodipine-treated rats developed 20-60% smaller cortical infarct volumes than controls (p less than 0.002). Cortical edema was reduced proportionately to the decrease in infarct volume and constituted approximately 36% of the infarct volume. Nimodipine caused a mild hypotensive response that did not aggravate ischemic brain damage. The results indicate that continuous nimodipine treatment, started before induction of focal cerebral ischemia, can attenuate ischemic brain damage and edema as late as 24 h after the onset of ischemia.

  17. 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.

  18. Real-time ischemic condition monitoring in normoglycemic and hyperglycemic rats.

    Science.gov (United States)

    Choi, Samjin; Kang, Sung Wook; Lee, Gi-Ja; Choi, Seok Keun; Chae, Su-Jin; Park, Hun-Kuk; Chung, Joo-Ho

    2010-03-01

    An increase in excitotoxic amino acid glutamate (GLU) concentration associated with neuronal damage might be the cause of the ischemic damage observed in stroke patients suffering from hyperglycemia. However, the effect has never been investigated by real-time in vivo monitoring. Therefore, this study examined the effects of the functional responses of ischemia-evoked electroencephalography (EEG), cerebral blood flow (%CBF) and DeltaGLU in hyperglycemia through real-time in vivo monitoring. Five Sprague-Dawley rats were treated with streptozocin (hyperglycemia) and five normal rats were used as the controls. Global ischemia was induced using an 11-vessel occlusion model. The experimental protocols consisting of 10 min pre-ischemic, 10 min ischemic and 40 min reperfusion periods were applied to both groups. Under these conditions, the responses of the ischemia-evoked EEG, %CBF and DeltaGLU were monitored in real time. The EEG showed flat patterns during ischemia followed by poor recovery during reperfusion. The peak reperfusion %CBF was decreased significantly in the hyperglycemia group compared to the control group (p < 0.05, n = 5). The extracellular DeltaGLU releases increased significantly during ischemia (p < 0.0001, n = 5) and reperfusion (p < 0.001, n = 5) in the hyperglycemia group compared to the control group. The decrease in reperfusion %CBF during short-term hyperglycemia might be related to the increased plasma osmolality, decreased adenosine levels and swollen endothelial cells with decreased vascular luminal diameters under hyperglycemic conditions. And, the increase in DeltaGLU during short-term hyperglycemia might be related to the neurotoxic effects of the high extracellular concentrations of DeltaGLU and the inhibition of GLU uptake.

  19. Caffeic acid ameliorates early and delayed brain injuries after focal cerebral ischemia in rats

    Institute of Scientific and Technical Information of China (English)

    Yu ZHOU; San-hua FANG; Yi-lu YE; Li-sheng CHU; Wei-ping ZHANG; Meng-ling WANG; Er-qing WEI

    2006-01-01

    Aim: To investigate the effects of caffeic acid on early and delayed injuries after focal cerebral ischemia in rats, and the possible relation to 5-lipoxygenase inhibition. Methods: Transient focal cerebral ischemia was induced by middle cerebral artery occlusion in Sprague-Dawley rats. Caffeic acid (10 and 50 mg/kg) was ip injected for 5 d after ischemia. The brain injuries were observed, and the levels of cysteinyl leukotrienes and leukotriene B4 in the brain tissue were measured. Results: Caffeic acid (50 mg/kg) ameliorated neurological dysfunction and neuron loss, and decreased infarct volume 24 h after ischemia; it attenuated brain atrophy, infarct volume, and particularly astrocyte proliferation 14 d after ischemia. In addition, it reduced the production of leukotrienes (5-lipoxygenase metabolites) in the ischemic hemispheres 3 h and 7 d after ischemia. Conclusion: Caffeic acid has protective effect on both early and delayed injuries after focal cerebral ischemia in rats; and this effect may partly relate to 5-lipoxygenase inhibition.

  20. Iloprost reduces colonic injury in ischemic colitis in rats.

    Science.gov (United States)

    Karatepe, Oguzhan; Cakir, Affan; Unal, Orçun; Battal, Muharrem; Adas, Gokhan; Kamali, Gülcin; Kemik, Ahu; Aydin, Timucin; Kamali, Sedat; Karahan, Servet R; Aksoy, Murat

    2011-06-01

    Evaluate the effects of iloprost administration in the early period of ischemic colitis and the mechanism that how these effects develop. Thirty two Wistar albino female rats with an average weight of 220g were divided into four groups of eight rats. In group 1 the rats were given iloprost and sacrificed after 24 hours and in group 2 they were sacrificed after 24 hours without any iloprost. The rats in group 3 were administrated iloprost and sacrificed after 72 hours and in group 4 they were sacrificed at 72th hour without iloprost. The differences between the groups as tissue damage, vascularization or apoptosis were assessed statistically. Oxidative damage and apoptosis were less pronounced and vascularization was better developed in rats that were given iloprost and sacrificed at 24th hour later in contrast to the rats that were not treated with iloprost. But there was no statistical difference among the groups at 72th hour. Iloprost inhibited leucocyte infiltration, decreased proinflammatory cytokines and enhanced angiogenesis so that the oxidative stress and inflammatory response decreased resulting in lesser tissue damage.

  1. Progressive Ischemic Stroke due to Thyroid Storm-Associated Cerebral Venous Thrombosis

    Science.gov (United States)

    Tanabe, Natsumi; Hiraoka, Eiji; Hoshino, Masataka; Deshpande, Gautam A.; Sawada, Kana; Norisue, Yasuhiro; Tsukuda, Jumpei; Suzuki, Toshihiko

    2017-01-01

    Patient: Female, 49 Final Diagnosis: Cerebral venous thrombosis Symptoms: Altered mental state • weakness in limbs Medication: — Clinical Procedure: — Specialty: Endocrinology and Metabolic Objective: Rare co-existance of disease or pathology Background: Cerebral venous thrombosis (CVT) is a rare but fatal complication of hyperthyroidism that is induced by the hypercoagulable state of thyrotoxicosis. Although it is frequently difficult to diagnose CVT promptly, it is important to consider it in the differential diagnosis when a hyperthyroid patient presents with atypical neurologic symptoms. Care Report: A 49-year-old Japanese female with unremarkable medical history came in with thyroid storm and multiple progressive ischemic stroke identified at another hospital. Treatment for thyroid storm with beta-blocker, glucocorticoid, and potassium iodide-iodine was started and MR venography was performed on hospital day 3 for further evaluation of her progressive ischemic stroke. The MRI showed CVT, and anticoagulation therapy, in addition to the anti-thyroid agents, was initiated. The patient’s thyroid function was successfully stabilized by hospital day 10 and further progression of CVT was prevented. Conclusions: Physicians should consider CVT when a patient presents with atypical course of stroke or with atypical MRI findings such as high intensity area in apparent diffusion coefficient (ADC) mapping. Not only is an early diagnosis and initiation of anticoagulation important, but identifying and treating the underlying disease is essential to avoid the progression of CVT. PMID:28228636

  2. Lower Serum Caveolin-1 Is Associated with Cerebral Microbleeds in Patients with Acute Ischemic Stroke

    Science.gov (United States)

    Zhang, Jun; Zhu, Wusheng; Xiao, Lulu; Cao, Qinqin; Zhang, Hao; Wang, Huaiming; Ye, Zusen; Hao, Yonggang; Dai, Qiliang; Sun, Wen; Liu, Xinfeng; Ye, Ruidong

    2016-01-01

    Caveolin-1 (Cav-1) plays pivotal roles in the endothelial damage following stroke. The present study aimed to investigate whether serum Cav-1 level is associated with the presence of cerebral small vessel disease (cSVD) in patients with acute ischemic stroke. To this end, 156 patients were consecutively enrolled. Cranial magnetic resonance imaging was analyzed to determine the surrogates of cSVD, including cerebral microbleeds (CMBs), silent lacunar infarcts (SLIs), and white matter hyperintensities (WMHs). After adjusting for potential confounders, patients with low Cav-1 level had a higher risk of CMBs than patients with high Cav-1 level (OR: 4.05, 95% CI: 1.77–9.30). However, there was no relationship between Cav-1 and the presence of SLIs or WMHs. When CMBs were stratified by location and number, a similar association was found in patients with deep or infratentorial CMBs (OR: 4.04, 95% CI: 1.59–10.25) and with multiple CMBs (OR: 3.18, 95% CI: 1.16–8.72). These results suggest lower serum Cav-1 levels may be associated with CMBs, especially those that are multiple and located in deep brain or infratentorial structures, in patients with acute ischemic stroke. Cav-1 may be involved in the pathophysiology of CMBs, and may act as a potential target for treating cSVD. PMID:27119011

  3. Lower Serum Caveolin-1 Is Associated with Cerebral Microbleeds in Patients with Acute Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Jun Zhang

    2016-01-01

    Full Text Available Caveolin-1 (Cav-1 plays pivotal roles in the endothelial damage following stroke. The present study aimed to investigate whether serum Cav-1 level is associated with the presence of cerebral small vessel disease (cSVD in patients with acute ischemic stroke. To this end, 156 patients were consecutively enrolled. Cranial magnetic resonance imaging was analyzed to determine the surrogates of cSVD, including cerebral microbleeds (CMBs, silent lacunar infarcts (SLIs, and white matter hyperintensities (WMHs. After adjusting for potential confounders, patients with low Cav-1 level had a higher risk of CMBs than patients with high Cav-1 level (OR: 4.05, 95% CI: 1.77–9.30. However, there was no relationship between Cav-1 and the presence of SLIs or WMHs. When CMBs were stratified by location and number, a similar association was found in patients with deep or infratentorial CMBs (OR: 4.04, 95% CI: 1.59–10.25 and with multiple CMBs (OR: 3.18, 95% CI: 1.16–8.72. These results suggest lower serum Cav-1 levels may be associated with CMBs, especially those that are multiple and located in deep brain or infratentorial structures, in patients with acute ischemic stroke. Cav-1 may be involved in the pathophysiology of CMBs, and may act as a potential target for treating cSVD.

  4. Modulation of The Balance Between Cannabinoid CB1 and CB2 Receptor Activation During Cerebral Ischemic/Reperfusion Injury

    OpenAIRE

    ZHANG, Ming; Martin, Billy R.; Adler, Martin W.; Razdan, Raj K.; Ganea, Doina; Tuma, Ronald F.

    2008-01-01

    Cannabinoid receptor activation has been shown to modulate both neurotransmission (CB1) and neuroinflammatory (CB2) responses. There are conflicting reports in the literature describing the influence of cannabinoid receptor activation on ischemic/reperfusion injury. The goal of this study was to evaluate how changing the balance between CB1 and CB2 activation following cerebral ischemia influences outcome. CB1 and CB2 expression were tested at different times after transient middle cerebral a...

  5. Healing of colonic ischemic anastomoses in the rat: role of superoxide radicals.

    Science.gov (United States)

    Garcia, J G; Criado, F J; Persona, M A; Alonso, A G

    1998-07-01

    The aim of this study was to evaluate the role of superoxide radicals in the healing of ischemic colonic anastomoses in the rat. Adult male Wistar rats were used in a factorial design with two factors (normal or ischemic colonic anastomoses) each having two levels (treatment with saline or allopurinol). Colonic anastomoses were performed either in normal or previously devascularized colons (ischemic anastomoses) at identical locations, using the same technique. On the fourth postoperative day, animals were killed, and specimens were taken for determinations. Ischemic anastomoses displayed significant increases in superoxide radical (assayed as superoxide anion), superoxide dismutase, and glutathione peroxidase concentrations. Bursting strength and hydroxyproline levels were also significantly lower in these anastomoses. Allopurinol administration elicited a significant decrease in superoxide anions and raised both bursting strength and hydroxyproline levels only in ischemic anastomoses. Superoxide radicals are involved in the delay in healing of ischemic anastomoses. Allopurinol lowers superoxide anion production and has beneficial effects on the cicatrization of ischemic anastomoses.

  6. Combination of early and delayed ischemic postconditioning enhances brain-derived neurotrophic factor production by upregulating the ERK-CREB pathway in rats with focal ischemia.

    Science.gov (United States)

    Wu, Hui; Yang, Shao-Feng; Dai, Jiong; Qiu, Yong-Ming; Miao, Yi-Feng; Zhang, Xiao-Hua

    2015-11-01

    Ischemic postconditioning, including early and delayed ischemic postconditioning, has been recognized as a simple and promising strategy in the treatment of stroke. However, the effects of the combination of early and delayed ischemic postconditioning, and the mechanisms underlying these effects, remain unclear. The aim of the present study was to determine whether the combination of early and delayed ischemic postconditioning offers greater protection against stroke, and enhances the production of brain‑derived neurotrophic factor (BDNF). A combination of early and delayed ischemic postconditioning was established by repeated, transient occlusion and reperfusion of the ipsilateral common carotid artery in a rat model of middle cerebral artery occlusion. Infarct size, motor function, cerebral blood flow and brain edema were then evaluated, in order to confirm the effects of combinative ischemic postconditioning. TUNEL staining was used to analyze the rate of apoptosis of cells in the penumbral area. BDNF, extracellular signal‑regulated kinases 1/2 (ERK1/2) and cAMP response element‑binding protein (CREB) expression was detected using immunofluorescence staining and western blot analysis. The results of the present study indicated that the combination of early and delayed ischemic postconditioning further reduced the infarct volume, stabilized cerebral blood disturbance and attenuated neuronal apoptosis, compared with either alone. However, combinative postconditioning exerted the same effect on neurological function and brain edema, compared with early or delayed ischemic postconditioning alone. Further investigation indicated that combinative ischemic postconditioning increased the expression of BDNF, and a significantly higher number of BDNF‑positive cells was observed in neurons and astrocytes from the combined group than in the early or delayed groups. Combinative ischemic postconditioning also induced the phosphorylation of ERK1/2 and CREB in the

  7. Relationship between serum S-100 protein level and ischemic damage degree in patients with acute cerebral infarction

    Institute of Scientific and Technical Information of China (English)

    HE Ming-li; XU Bing-chao; HUANG Guo-sheng

    2005-01-01

    Objective: To investigate the time course of serum S-100 concentrations of patients with acute cerebral infarction,and their relation with the clinical data and the prognosis. Methods: Serum S-100 levels were serially determined in 35 patients with acute cerebral infarction within 12 h, at 24 h and day 2, 3, 4, 5,7 and 10 after acute cerebral infarction and in 20 age- and sex-matched control subjects. An S-100 content assay was performed using a two-site radioimmunoassay technique. The clinical status was assessed using NIH Stroke Scale. The functional deficit at 4 weeks after acute cerebral infarction was scored using the modified Rankin scale. A cranial computed tomography was performed initially. Results: Elevated concentrations of S100 (>0.2 μg/L) were observed in 29 of 36 patients with acute cerebral infarction,but none of the control subjects. The S-100 peak levels were at day 2 and 3 after acute cerebral infarction and were significantly high in those patients with severe neurological deficit at admission, with extensive infarction or with space-occupying effect of ischemic edema as compared with the rest of the populations. Conclusion: Serum S-100 level assay can be used as a peripheral marker of ischemic brain damage, and may be helpful for evaluation of therapeutic effects in acute ischemic stroke.

  8. Effect of cerebral lymphatic block on cerebral morphology and cortical evoked potential in rats

    Institute of Scientific and Technical Information of China (English)

    Zuoli Xia; Baoling Sun; Mingfeng Yang; Dongmei Hu; Tong Zhao; Jingzhong Niu

    2006-01-01

    BACKGROUND: It has been shown that although brain does not contain lining endothelial lymphatic vessel,it has lymphatic drain.Anterior lymphatic vessel in brain tissue plays a key role in introducing brain interstitial fluid to lymphatic system;however,the significance of lymphatic drain and the affect on cerebral edema remains unclear.OBJECTIVE: To investigate the effect of cerebral lymphatic block on cerebral morphology and cortical evoked potential in rats.DESIGN: Randomized controlled animal study.SETTING: Institute of Cerebral Microcirulation of Taishan Medical College and Department of Neurology of Affiliated Hospital.MATERIALS:A total of 63 healthy adult male Wistar rats weighing 300-350 g were selected in this study.Forty-seven rats were used for the morphological observation induced by lymphatic drain and randomly divided into three groups:general observation group(n=12),light microscopic observation group(n=21)and electronic microscopic observation group(n=14).The rats in each group were divided into cerebral lymphatic block subgroup and sham-operation control subgroup.Sixteen rats were divided into cerebral the effect of cerebral lymphatic block on cortical evoked potential,in which the animals were randomly divided into sham-operation group(n=6)and cerebral lymphatic block group(n=10).METHODS:The experiment was carried out in the Institute of Cerebral Microcirculation of Taishan Medical College from January to August 2003.Rats in cerebral lymphatic block group were anesthetized and separated bilateral superficial and deep cervical lymph nodes under sterile condition. Superior and inferior boarders of lymph nodes were ligated the inputting and outputting channels, respectively, and then lymph node was removed so as to establish cerebral lymphatic drain disorder models. Rats in sham-operation control group were not ligated the lymphatic vessel and removed lymph nodes.and other operations were as the same as those in cerebral lymphatic block group

  9. Combined prostaglandin E1 and lithium exert potent neuroprotection in a rat model of cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Rui SHENG; Li-sha ZHANG; Rong HAN; Bo GAO; Xiao-qian LIU; Zheng-hong QIN

    2011-01-01

    Alm: To examine the effects of a mixed formulation composed of prostaglandin E1 and lithium (PGE1+Li mixture) on brain damage after cerebral ischemia. The effects of the mixture on protein expression of heat shock proteins (HSPs), p53, and Bcl-2 were also determined.Methods: Brain ischemia was induced with a permanent middle cerebral artery occlusion (pMCAO) in rats. Rats were treated with a single intravenous administration of PGE1, lithium or a PGE1+Li mixture immediately after the ischemic insult. The infarct volume and motor behavior deficits were analyzed 24 h after the ischemic insult. The protein levels of HSP70, glucose-regulated protein 78 (GRP78), HSP60, Bcl-2, and p53 in the striatum of the ipsilateral hemisphere were examined using immunoblotting.Results: The mixture (PGE1 22.6 nmol/kg+Li 0.5 mmol/kg) reduced infarct volume and neurological deficits induced by focal cerebral ischemia. Moreover, the mixture had a greater neuroprotective effect against cerebral ischemia compared with PGE1 or lithium alone.The mixture was effective even if it was administered 3 h after ischemia. PGE1+Li also significantly upregulated cytoprotective HSP70,GRP78, HSP60, and Bcl-2 protein levels, while decreasing p53 expression.Conclusion: These results demonstrated a PGE1+Li mixture with a therapeutic window of up to 3 h for clinical treatment of cerebral ischemia. The PGE1+Li mixture potentially exerts a protective effect after stroke through the induction of HSPs and Bcl-2 proteins.

  10. 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 (Phyperglycemia (9.43 ± 1.39-10.13 ± 1.24 mM). Our findings indicate that severe instead of mild hyperglycemia exacerbates ischemic injury and inhibits stroke-induced SVZ neurogenesis by a mechanism involving suppression of CREB and BDNF signaling.

  11. Serum uric acid levels and cerebral microbleeds in patients with acute ischemic stroke.

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    Wi-Sun Ryu

    Full Text Available Unlike experimental studies indicating a neuroprotective property of uric acid, clinical studies have shown that elevated levels of uric acid are associated with a risk of ischemic stroke. However, the association of uric acid with cerebral hemorrhage has seldom been tested. We aimed to elucidate the association between uric acid and cerebral microbleeds (CMBs, a hemorrhage-prone cerebral microangiopathy. Seven hundred twenty-four patients with ischemic stroke who were consecutively admitted to our hospital were included in this study. We collected demographic, clinical, and laboratory data, including uric acid level, and examined the presence of CMBs using T2*-weighted gradient-echo MRI. We used logistic regression analysis to examine an independent association between uric acid and CMBs. Two-hundred twenty-six patients had CMBs (31.2%. After adjusting for possible confounders, elevated uric acid was independently associated with the presence of CMBs (the highest quartile vs. lowest quartile, adjusted odd ratio [OR], 1.98; 95% confidence interval [CI], 1.16-3.39. This association retained in patients with deep or infratentorial CMBs (with or without lobar CMBs but not among those with lobar CMBs. In addition, this association was robust among patients with hypertension (the highest quartile vs. lowest quartile, adjusted OR, 2.74; 95% CI, 1.43-5.24. In contrast, we did not find the association in patients without hypertension. We demonstrated that serum uric acid is independently associated with the presence of CMBs. In particular, the relation between uric acid and CMBs was robust in hypertensive patients.

  12. Serum Uric Acid Levels and Cerebral Microbleeds in Patients with Acute Ischemic Stroke

    Science.gov (United States)

    Ryu, Wi-Sun; Kim, Chi Kyung; Kim, Beom Joon; Lee, Seung-Hoon

    2013-01-01

    Unlike experimental studies indicating a neuroprotective property of uric acid, clinical studies have shown that elevated levels of uric acid are associated with a risk of ischemic stroke. However, the association of uric acid with cerebral hemorrhage has seldom been tested. We aimed to elucidate the association between uric acid and cerebral microbleeds (CMBs), a hemorrhage-prone cerebral microangiopathy. Seven hundred twenty-four patients with ischemic stroke who were consecutively admitted to our hospital were included in this study. We collected demographic, clinical, and laboratory data, including uric acid level, and examined the presence of CMBs using T2*-weighted gradient-echo MRI. We used logistic regression analysis to examine an independent association between uric acid and CMBs. Two-hundred twenty-six patients had CMBs (31.2%). After adjusting for possible confounders, elevated uric acid was independently associated with the presence of CMBs (the highest quartile vs. lowest quartile, adjusted odd ratio [OR], 1.98; 95% confidence interval [CI], 1.16–3.39). This association retained in patients with deep or infratentorial CMBs (with or without lobar CMBs) but not among those with lobar CMBs. In addition, this association was robust among patients with hypertension (the highest quartile vs. lowest quartile, adjusted OR, 2.74; 95% CI, 1.43–5.24). In contrast, we did not find the association in patients without hypertension. We demonstrated that serum uric acid is independently associated with the presence of CMBs. In particular, the relation between uric acid and CMBs was robust in hypertensive patients. PMID:23372838

  13. Cardioprotection of ischemic preconditioning in rats involves upregulating adiponectin.

    Science.gov (United States)

    Wang, Hui; Wu, Wenjing; Duan, Jun; Ma, Ming; Kong, Wei; Ke, Yuannan; Li, Gang; Zheng, Jingang

    2017-02-20

    It has been reported that ischemic preconditioning (IPC) and adiponectin (APN) are cardioprotective in many cardiovascular disorders. However, whether APN mediates the effect of IPC on myocardial injury has not been elucidated. This study was conducted to investigate whether IPC affects myocardial ischemic injury by increasing APN expression. Male adult rats with cardiac knockdowns of APN and its receptors via intramyocardial small-interfering RNA injection were subjected to IPC and then myocardial infarction (MI) at 24 h post-IPC. Globular APN (gAd) was injected at 10 min before MI. APN mRNA and protein levels in myocardium as well as the plasma APN concentration were markedly high at 6 and 12 h after IPC. IPC ameliorated myocardial injury as evidenced by improved cardiac functions and a reduced infarct size. Compared with the control MI group, rats in the IPC + MI group had elevated levels of left ventricular ejection fraction and fractional shortening, and a smaller MI size (PIPC are partially due to upregulation of APN, and provide a further insight into IPC-mediated signaling effects.

  14. The Effect of Photoluminescence of Bioceramic Irradiation on Middle Cerebral Arterial Occlusion in Rats

    Directory of Open Access Journals (Sweden)

    Lei Zhang

    2016-01-01

    Full Text Available The purpose of this study is to determine the possible effect of photoluminescence of bioceramic (PLB on ischemic cerebral infarction (stroke, by using an animal model of transient middle cerebral artery occlusion (MCAO. Sprague-Dawley rats were used to induce MCAO to block the origin of the left MCAO; three months later, the positive chronic stroke rats were selected by running tunnel maze; the MCAO rats with significant chronic stroke and neurological defects were used for treadmill experiments with varying speed settings to test their capability for restoration after muscular fatigue under conditions of with and without PLB irradiation. As a result, PLB irradiation could improve exercise completion rate and average running speed during slow and fast treadmill settings. After PLB irradiation, the selected MCAO rats successfully completed all the second-round treadmill exercises at the maximum speed setting, and they had better restoration from muscular fatigue. An in vitro cell study on astrocytes of rats by bioceramic irradiation further demonstrated increased intracellular nitric oxide. To explain these results, we suggest that cortical brain stimulation of microcirculation and enhancement of peripheral muscular activity are the main causes of the improved exercise performance in MCAO rats by PLB.

  15. Aortic arch and intra-/extracranial cerebral arterial atherosclerosis in patients suffering acute ischemic strokes

    Institute of Scientific and Technical Information of China (English)

    郭毅; 姜昕; 陈实; 张少文; 赵宏文; 吴瑛

    2003-01-01

    Objective To determine the distribution of aortic arch and intra/extracranial cerebral arterial atherosclerosis in Chinese patients who had suffered acute ischemic strokes. Methods Eighty-nine patients with acute ischemic strokes were included in this study. Transesophageal echocardiography (TEE) was used to evaluate potential sources of embolisms in the aortic arch and in the heart; duplex ultrasound was used for the carotid artery; and intracranial Doppler (TCD) imaging was used for the middle cerebral artery (MCA), anterior cerebral artery (ACA), posterior cerebral artery (PCA), and basilar artery (BA). An atherosclerotic lesion in the aortic arch was defined as normal (0); mild plaque (1); moderate plaque (2); and protruding plaque or mobile plaque (3). A lesion in the carotid artery was considered a plaque if the maximal carotid plaque thickness was 1.2 mm. TCD results were deemed abnormal if flow velocity was either greater or lower than normal, and, in the case of the MCA, if an asymmetry index above 21% was measured. Results Of the 89 patients, 52 (58.43%) patients showed evidence of aortic arch atherosclerosis (AAA), including 11 (12.36%) patients graded mild, 18 (20.22%) patients graded moderate, and 23 (25.84%) patients graded severe. Of the 23 patients with severe AAA, AAA was determined to be an important potential embolic source in 14 patients. Forty-nine (50.56%) patients had carotid arterial plaques (CAPs). The incidence of carotid plaques was higher among patients with AAA than among patients without AAA (71.15% vs 21.62%, OR=3.291, 95% CI=1.740-6.225, P<0.001). TCD abnormalities affecting the MCA were found in 54 (60.67%) patients. Differences in incidence of TCD abnormalities between patients with AAA and without AAA (69.23% vs 48.65%) were not significant (OR=1.423, 95% CI=0.976-2.076, P=0.05). There was a higher incidence of AAA in older, male patients with a history of diabetes and smoking. Conclusions AAA is an important potential source of

  16. Effect of Electroacupuncture on Rat Ischemic Brain Injury: Importance of Stimulation Duration

    Directory of Open Access Journals (Sweden)

    Fei Zhou

    2013-01-01

    Full Text Available We explored the optimal duration of electroacupuncture (EA stimulation for protecting the brain against ischemic injury. The experiments were carried out in rats exposed to right middle cerebral artery occlusion (MCAO for 60 min followed by 24-hr reperfusion. EA was delivered to “Shuigou” (Du 26 and “Baihui” (Du 20 acupoints with sparse-dense wave (5/20 Hz at 1.0 mA for 5, 15, 30, and 45 min, respectively. The results showed that 30 min EA, starting at 5 minutes after the onset of MCAO (EA during MCAO or 5 minutes after reperfusion (EA after MCAO, significantly reduced ischemic infarct volume, attenuated neurological deficits, and decreased death rate with a larger reduction of the ischemic infarction in the former group. Also in the group of EA during MCAO, this protective benefit was positively proportional to the increase in the period of stimulation, that is, increased protection in response to EA from 5- to 30-min stimulation. In all groups, EA induced a significant increase in cerebral blood flow and promoted blood flow recovery after reperfusion, and both blood flow volume and blood cell velocity returned to the preischemia level in a short period of time. Surprisingly, EA for 45 min did not show reduction in the neurological deficits or the infarct volume and instead demonstrated an increase in death rate in this group. Although EA for 45 min still increased the blood flow during MCAO, it led to a worsening of perfusion after reperfusion compared to the group subjected only to ischemia. The neuroprotection induced by an “optimal” period (30 min of EA was completely blocked by Naltrindole, a δ-opioid receptor (DOR antagonist (10 mg/kg, i.v.. These findings suggest that earlier EA stimulation leads to better outcomes, and that EA-induced neuroprotection against ischemia depends on an optimal EA-duration via multiple pathways including DOR signaling, while “over-length” stimulation exacerbates the ischemic

  17. Electrical coupling of astrocytes in rat hippocampal slices under physiological and simulated ischemic conditions.

    Science.gov (United States)

    Xu, Guangjin; Wang, Wei; Kimelberg, Harold K; Zhou, Min

    2010-03-01

    Mammalian protoplasmic astrocytes are extensively coupled through gap junction channels but the biophysical properties of these channels under physiological and ischemic conditions in situ are not well defined. Using confocal morphometric analysis of biocytin-filled astrocytic syncytia in rat hippocampal CA1 stratum radiatum we found that each astrocyte directly couples, on average, to 11 other astrocytes with a mean interastrocytic distance of 45 microm. Voltage-independent and bidirectional transjunctional currents were always measured between directly coupled astrocyte pairs in dual voltage-clamp recordings, but never from astrocyte-NG2 glia or astrocyte-interneuron pairs. The electrical coupling ratio varied considerably among astrocytes in developing postnatal day 14 rats (P14, 0.5-12.4%, mean = 3.6%), but became more constant in young adult P21 rats (0.18-3.9%, mean = 1.6%), and the coupling ratio declined exponentially with increasing pair distance. Electrical coupling was not affected by short-term oxygen-glucose deprivation (OGD) treatment, but showed delayed inhibition in an acidic extracellular pH of 6.4. Combination of acidic pH (6.4) and OGD, a condition that better represents cerebral ischemia in vivo, accelerated the inhibition of electrical coupling. Our results show that, under physiological conditions, 20.7-24.2% of K(+) induced currents can travel from any astrocytic soma in CA1 stratum radiatum to the gap junctions of the nearest neighbor astrocytes, but this should be severely inhibited as a consequence of the OGD and acidosis seen in the ischemic brain.

  18. Glucocorticoids Protect Neonatal Rat Brain in Model of Hypoxic-Ischemic Encephalopathy (HIE)

    Science.gov (United States)

    Harding, Benjamin; Conception, Katherine; Li, Yong; Zhang, Lubo

    2016-01-01

    Hypoxic-ischemic encephalopathy (HIE) resulting from asphyxia in the peripartum period is the most common cause of neonatal brain damage and can result in significant neurologic sequelae, including cerebral palsy. Currently therapeutic hypothermia is the only accepted treatment in addition to supportive care for infants with HIE, however, many additional neuroprotective therapies have been investigated. Of these, glucocorticoids have previously been shown to have neuroprotective effects. HIE is also frequently compounded by infectious inflammatory processes (sepsis) and as such, the infants may be more amenable to treatment with an anti-inflammatory agent. Thus, the present study investigated dexamethasone and hydrocortisone treatment given after hypoxic-ischemic (HI) insult in neonatal rats via intracerebroventricular (ICV) injection and intranasal administration. In addition, we examined the effects of hydrocortisone treatment in HIE after lipopolysaccharide (LPS) sensitization in a model of HIE and sepsis. We found that dexamethasone significantly reduced rat brain infarction size when given after HI treatment via ICV injection; however it did not demonstrate any neuroprotective effects when given intranasally. Hydrocortisone after HI insult also significantly reduced brain infarction size when given via ICV injection; and the intranasal administration showed to be protective of brain injury in male rats at a dose of 300 µg. LPS sensitization did significantly increase the brain infarction size compared to controls, and hydrocortisone treatment after LPS sensitization showed a significant decrease in brain infarction size when given via ICV injection, as well as intranasal administration in both genders at a dose of 300 µg. To conclude, these results show that glucocorticoids have significant neuroprotective effects when given after HI injury and that these effects may be even more pronounced when given in circumstances of additional inflammatory injury, such

  19. Alterations in gene expression and steroidogenesis in the testes of transient cerebral ischemia in male rats

    Institute of Scientific and Technical Information of China (English)

    ZHAO Bing-hai; GUO Yan-qin; LI Hong-zhi; LIU Jie-ting; WU Dan; YUAN Xiao-huan; LI Rong-wen; GUAN Li-xin

    2012-01-01

    Background Serum testosterone levels have been found lower in acute ischemic stroke male patients.However,the exact mechanism remains unclear.In the present study,we measured serum testosterone levels,steroidogenesisrelated genes and Leydig cells number in experimental transient cerebral ischemia male rats to elucidate the mechanism.Methods The middle cerebral arteries of adult male Sprague-Dawley rats were sutured for 120 minutes and then sacrificed after 24 hours.Blood was collected for measurement of serum testosterone,follicular stimulating hormone and estradiol levels,and testes were collected for measurement of steroidogenesis-retated gene mRNA levels and number of Leydig cells.Results Serum testosterone levels in rats after cerebral ischemia were significantly lower (0.53±0.16) ng/ml,n=7,mean±SE) compared with control ((2.33±0.60) ng/ml,n=7),while serum estradiol and follicular stimulating hormone levels did not change.The mRNA levels for luteinizing hormone receptor (Lhcgr),scavenger receptor class B member 1 (Scarb1),steroidogenic acute regulatory protein (StAR),cholesterol side chain cleavage enzyme (Cyp11a1),3β-hydroxysteroid dehydrogenase 1 (HSD311),17α-hydroxylese/20-lyase (Cyp17a1) and membrane receptor c-kit (kit) were significantly downregulated by cerebral ischemia,while luteinizing hormone,Kit ligand (KitL),17β-hydrosteroid dehydrogenase 3 (HSD17β3) and 5α-reductase (Srd5a1) were not affected.We also observed that,relative to control,the Leydig cell number did not change.Conclusions These results indicate that transient cerebral ischemia in the brain results in lower expression levels of steroidogenesis-related genes and thus lower serum testosterone level.Transient cerebral ischemia did not lower the number of Leydig cells.

  20. Modulation of cerebral RAGE expression following nitric oxide synthase inhibition in rats subjected to focal cerebral ischemia.

    Science.gov (United States)

    Greco, Rosaria; Demartini, Chiara; Zanaboni, Anna Maria; Blandini, Fabio; Amantea, Diana; Tassorelli, Cristina

    2017-04-05

    The receptor for advanced glycation endproducts (RAGE) is a key mediator of neuroinflammation following cerebral ischemia. Nitric oxide (NO) plays a dualistic role in cerebral ischemia, depending on whether it originates from neuronal, inducible or endothelial synthase. Although a dynamic interplay between RAGE and NO pathways exists, its relevance in ischemic stroke has not been investigated. The aim of this study is to evaluate the effect of the NO synthase (NOS) inhibition on RAGE expression in rats subjected to transient middle cerebral artery occlusion (tMCAo). Full-length (fl-RAGE) gene expression was elevated in the striatum and, to a lesser extent, in the cortex of rats undergone tMCAo. The exacerbation of cortical damage caused by systemic administration of L-N-(1-iminoethyl)ornithine (L-NIO), a relatively selective inhibitor of endothelial NOS (eNOS), was associated with elevated mRNA levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α and fl-RAGE in both the cortex and the striatum. Conversely, NG-nitro-l-arginine methyl ester (L-NAME), a non-selective NOS inhibitor, decreased cortical damage, did not affect cerebral cytokine mRNA levels, while it increased fl-RAGE mRNA expression only in the striatum. Fl-RAGE striatal protein levels varied accordingly with observed mRNA changes in the striatum, while in the cortex, RAGE protein levels were reduced by tMCAo and further decreased following L-NIO treatment. Modulation of RAGE expression by different inhibitors of NOS may have opposite effects on transient cortical ischemia: the non selective inhibition of NOS activity is protective, while the selective inhibition of eNOS is harmful, probably via the activation of inflammatory pathways. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. 胞二磷胆碱结合康复训练对脑缺血大鼠半暗带区存活素表达的影响%The effect of drugs in combination with rehabilitative training on the expression of survivin in the ischemic penumbra after focal cerebral ischemia in rats

    Institute of Scientific and Technical Information of China (English)

    毕然然; 孙强三; 孙丽

    2013-01-01

    Objective To investigate the effect of drugs in combination with rehabilitative training on motor function and the expression of survivin in the ischemic penumbra after focal cerebral ischemia.Methods One hundred and twenty male,adult,Sprague-Dawley rats were subjected to left middle cerebral artery occlusion (MCAO)by suturing.Ninety-six of them were then randomly divided into a control group,a drug group,a rehabilitative trainiug group,and a drugs in combination with rehabilitative training group,with 24 in each.For three days the rats in the control group received no treatment,while those in the drug group received 500 mg/kg of citicoline daily,those in the rehabilitative training group received motor training including balancing,grasping,rotating and walking exercises,aud those in the drug and rehabilitative training group received both citicoline and the motor training.Behavioral tests were administered to all groups,and immunohistochemistry was used to detect the expression of survivin in the ischemic penumbra.Results Average behavior scores in the drug group and the control group were not significantly different at day 7,14 or 21 after the MCAO.Average behavior scores in the rehabilitative training and drug in combination with rehabilitative training groups were significantly superior to those of the control and drug groups at day 14 and 21.At those time points the average scores in the drug in combination with rehabilitative training group were also significantly better than those of the rehabilitation training group.Compared with control group,at the 7th,14th and 21st day after MCAO,expression of survivin in the other three groups had increased significantly.Expression of survivin in the group where drug treatment was combined with rehabilitative training was significantly greater than in the drug and rehabilitative training groups.Conclusions Citicoline in combination with rehabilitative training can improve the recovery of motor function in rats

  2. The Effect of Treadmill Training Pre-Exercise on Glutamate Receptor Expression in Rats after Cerebral Ischemia

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    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.

  3. The Expression of Cyclins in Neurons of Rats after Focal Cerebral Ischelma

    Institute of Scientific and Technical Information of China (English)

    Bin CHEN; WANG Wei

    2008-01-01

    The change of the expression of Cyclins in neurons of rats after focal cerebral ischemia was investigated. Ischemia was induced by temporary middle cerebral artery occlusion (MCAO). The experimental rats induced by MCAO were sacrificed on 7th and 14th day after reperfusion. The brain was taken out at 7th and 14th day after injury, and the expression of Cyclin D1>, E, A and B1> in neu- rons of cerebral cortex or hippocampal Cal region was detected by immunofluorescence and confo- cai microscope. The results showed that after MCAO, in the ipsilateral CAI subfield of hippocampus the expression of Cyclin D1, E, A and B1 in neurons was significantly gradually up-regulated at 7th and 14th day after reperfusion (P<0.05) as compared with that in control group. In the ipsilateral cerebral cortex the expression of Cyclin D1 and B1 in neurons was notably gradually down-regulated at 7th and 14th day, and that of Cyclin E and A was significantly up-regulated at 14th day after reper- fusion as compared with that in control group (all P<0.05). It was concluded that there was a differ- ential sensitivity among neurons from different brain regions to ischemic injury. But all of them re-enter into cell cycle after MCAO.

  4. Luoyutong Treatment Promotes Functional Recovery and Neuronal Plasticity after Cerebral Ischemia-Reperfusion Injury in Rats

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    Ning-qun Wang

    2015-01-01

    Full Text Available Luoyutong (LYT capsule has been used to treat cerebrovascular diseases clinically in China and is now patented and approved by the State Food and Drug Administration. In this retrospective validation study we investigated the ability of LYT to protect against cerebral ischemia-reperfusion injury in rats. Cerebral ischemia-reperfusion injury was induced by middle cerebral artery occlusion followed by reperfusion. Capsule containing LYT (high dose and medium dose as treatment group and Citicoline Sodium as positive control treatment group were administered daily to rats 30 min after reperfusion. Treatment was continued for either 3 days or 14 days. A saline solution was administered to control animals. Behavior tests were performed after 3 and 14 days of treatment. Our findings revealed that LYT treatment improved the neurological outcome, decreased cerebral infarction volume, and reduced apoptosis. Additionally, LYT improved neural plasticity, as the expression of synaptophysin, microtubule associated protein, and myelin basic protein was upregulated by LYT treatment, while neurofilament 200 expression was reduced. Moreover, levels of brain derived neurotrophic factor and basic fibroblast growth factor were increased. Our results suggest that LYT treatment may protect against ischemic injury and improve neural plasticity.

  5. Tracing neuronal tracts in the olfactory pathway of rat and detecting ischemic core in a rat model of focal ischemia using manganese enhanced magnetic resonance imaging

    Institute of Scientific and Technical Information of China (English)

    FANG Ke; LI Yingxia; LIU Hua; LIAO Weijing; LEI Hao

    2004-01-01

    Manganese enhanced magnetic resonance im aging (MRI) is a novel neuroimaging technique that can be used in vivo to trace neuronal tract and to study brain functions dynamically. In this study, manganese enhanced MRI was used to trace the neuronal tracts between the laminar structures of the olfactory bulb (OB) in rat and to study the so-called "calcium overload" phenomenon in a rat model of cerebral ischemia. High spatial resolution images of the OB were obtained and used to measure the transportation rate of Mn2+ among the laminar structures of the OB, which was shown to be approximately 0.2 mm/h under resting condition. In the rat focal ischemia study, it was found that the total area of brain regions with Mnz+ accumulation (representing brain regions with calcium overload) was only 55%±15% of the area of the ischemic brain regions shown by diffusion-weighted imaging (DWI). Manganese enhanced MRI might be more accurate than DWI in detecting the ischemic core at the early stage of experimental cerebral ischemia.

  6. Remote ischemic preconditioning provides neuroprotection: impact on ketamine-induced neuroapoptosis in the developing rat brain.

    Science.gov (United States)

    Ma, W; Cao, Y-Y; Qu, S; Ma, S-S; Wang, J-Z; Deng, L-Q; Yuan, W-J; Meng, J-H

    2016-12-01

    Previous studies have demonstrated that the commonly used anesthetic ketamine can acutely increase apoptosis and have long-lasting detrimental effects on cognitive function as the animal matures. Remote ischemic preconditioning (RIPC) has been confirmed to have a cerebral protective role in animal models of brain damage. The aim of this study was to investigate whether RIPC can protect the developing brain from anesthetic-induced neurotoxicity. To investigate the protective properties of RIPC, 60 new-born Sprague-Dawley (SD) rats were randomly allocated into four groups: ketamine (20 mg/kg was diluted in saline, six times at an interval of 2 hours); RIPC (left hind row ischemia 5 min, reperfusion 5 min, a total of four cycles); ketamine + RIPC: RIPC was induced at postnatal day 5 and rats underwent the same treatment with the ketamine group after 48 hours; and saline (group vehicle). Neuronal apoptosis in the frontal cortex and hippocampal CA1 region was measured 24 h after treatment using immunohistochemistry of cleaved caspase-3. Learning and memory abilities were tested at the age of 60 days by Morris water maze test. The percentage of cleaved caspase-3 immunohistochemical staining positive cells in the ketamine + RIPC group showed a more marked decline in neuronal apoptosis of the CA1 region than that in the ketamine group (p 0.05). The mice exposed to RIPC alone showed no difference from the saline-treated mice. Moreover, RIPC significantly reversed the learning and memory deficits observed at 60 days of age. Our data indicate that RIPC treatment provides protection against ketamine-induced neuroapoptosis in the frontal cerebral cortex but not in the hippocampal CA1 region in developing rats and attenuates long-term behavioural deficits as the animals mature, suggesting a new possible strategy for neuroprotection.

  7. Impaired Cerebral Mitochondrial Oxidative Phosphorylation Function in a Rat Model of Ventricular Fibrillation and Cardiopulmonary Resuscitation

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    Jun Jiang

    2014-01-01

    Full Text Available Postcardiac arrest brain injury significantly contributes to mortality and morbidity in patients suffering from cardiac arrest (CA. Evidence that shows that mitochondrial dysfunction appears to be a key factor in tissue damage after ischemia/reperfusion is accumulating. However, limited data are available regarding the cerebral mitochondrial dysfunction during CA and cardiopulmonary resuscitation (CPR and its relationship to the alterations of high-energy phosphate. Here, we sought to identify alterations of mitochondrial morphology and oxidative phosphorylation function as well as high-energy phosphates during CA and CPR in a rat model of ventricular fibrillation (VF. We found that impairment of mitochondrial respiration and partial depletion of adenosine triphosphate (ATP and phosphocreatine (PCr developed in the cerebral cortex and hippocampus following a prolonged cardiac arrest. Optimal CPR might ameliorate the deranged phosphorus metabolism and preserve mitochondrial function. No obvious ultrastructural abnormalities of mitochondria have been found during CA. We conclude that CA causes cerebral mitochondrial dysfunction along with decay of high-energy phosphates, which would be mitigated with CPR. This study may broaden our understanding of the pathogenic processes underlying global cerebral ischemic injury and provide a potential therapeutic strategy that aimed at preserving cerebral mitochondrial function during CA.

  8. Neuroprotective effect of pretreatment with ganoderma lucidum in cerebral ischemia/reperfusion injury in rat hippocampus.

    Science.gov (United States)

    Zhang, Wangxin; Zhang, Quiling; Deng, Wen; Li, Yalu; Xing, Guoqing; Shi, Xinjun; Du, Yifeng

    2014-08-01

    Ganoderma lucidum is a traditional Chinese medicine, which has been shown to have both anti-oxidative and anti-inflammatory 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 ganoderma 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 factor-α and interleukin-8 in the hippocampus, and increased the activity of superoxide dismutase in the hippocampus and serum. These results suggest that pretreatment with ganoderma lucidum was protective against cerebral ischemia/reperfusion injury through its anti-oxidative and anti-inflammatory actions.

  9. Intranasal brain-derived neurotrophic factor protects brain from ischemic insult via modulating local inflammation in rats.

    Science.gov (United States)

    Jiang, Y; Wei, N; Lu, T; Zhu, J; Xu, G; Liu, X

    2011-01-13

    Inflammation plays a vital role in the pathogenesis of ischemic stroke. Brain-derived neurotrophic factor (BDNF) may protect brain tissues from ischemic injury. In this study, we investigated whether intranasal BDNF exerted neuroprotection against ischemic insult by modulating the local inflammation in rats with ischemic stroke. Rats were subjected to temporary occlusion of the right middle cerebral artery (120 min) and intranasal BDNF or vehicle was adminstrated 2 h after reperfusion. Infarct volume and neuron injury were measured using triphenyltetrazolium chloride, Nissl staining and TUNEL assay, respectively. Microglia were detected by immunohistofluorescence. Tumor necrosis factor-α, interleukin10 and mRNAs were evaluated by enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction. DNA-binding activity of nuclear factor-kappa B was measured by electrophoretic mobility shift assay. BDNF level in brain tissues was markedly raised following intranasal administration. There were more Nissl positive and less TUNEL positive neurons in BDNF group than in control group while intranasal BDNF did not reduce the infarct volume significantly (n=6, 0.27±0.04 vs. 0.24±0.05, P>0.05). BDNF increased the number of activated microglia (OX-42 positive) and phagocytotic microglia (ED1 positive). BDNF suppressed tumor necrosis factor-α and mRNA expression while increasing the interleukin10 and mRNA expression. BDNF also increased DNA-binding activity of nuclear factor-kappa B (n=6, 49.78±1.23 vs. 52.89±1.64, PBDNF might protect the brain against ischemic insult by modulating local inflammation via regulation of the levels of cellular, cytokine and transcription factor in the experimental stroke.

  10. Green Tea Extract Ameliorates Learning and Memory Deficits in Ischemic Rats via Its Active Component Polyphenol Epigallocatechin-3-gallate by Modulation of Oxidative Stress and Neuroinflammation

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    Kuo-Jen Wu

    2012-01-01

    Full Text Available Ischemic stroke results in brain damage and behavioral deficits including memory impairment. Protective effects of green tea extract (GTex and its major functional polyphenol (−-epigallocatechin gallate (EGCG on memory were examined in cerebral ischemic rats. GTex and EGCG were administered 1 hr before middle cerebral artery ligation in rats. GTex, EGCG, and pentoxifylline (PTX significantly improved ishemic-induced memory impairment in a Morris water maze test. Malondialdehyde (MDA levels, glutathione (GSH, and superoxide dismutase (SOD activity in the cerebral cortex and hippocampus were increased by long-term treatment with GTex and EGCG. Both compounds were also associated with reduced cerebral infraction breakdown of MDA and GSH in the hippocampus. In in vitro experiments, EGCG had anti-inflammatory effects in BV-2 microglia cells. EGCG inhibited lipopolysaccharide- (LPS- induced nitric oxide production and reduced cyclooxygenase-2 and inducible nitric oxide synthase expression in BV-2 cells. GTex and its active polyphenol EGCG improved learning and memory deficits in a cerebral ischemia animal model and such protection may be due to the reduction of oxidative stress and neuroinflammation.

  11. Neuroprotective Effect of Xueshuantong for Injection (Lyophilized in Transient and Permanent Rat Cerebral Ischemia Model

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    Xumei Wang

    2015-01-01

    Full Text Available Xueshuantong for Injection (Lyophilized (XST, a Chinese Materia Medica standardized product extracted from Panax notoginseng (Burk., is used extensively for the treatment of cerebrovascular diseases such as acutely cerebral infarction clinically in China. In the present study, we evaluated the acute and extended protective effects of XST in different rat cerebral ischemic model and explored its effect on peroxiredoxin (Prx 6-toll-like receptor (TLR 4 signaling pathway. We found that XST treatment for 3 days could significantly inhibit transient middle cerebral artery occlusion (MCAO induced infarct volume and swelling percent and regulate the mRNA expression of interleukin-1β (IL-1β, IL-17, IL-23p19, tumor necrosis factor-α (TNFα, and inducible nitric oxide synthase (iNOS in brain. Further study demonstrated that treatment with XST suppressed the protein expression of peroxiredoxin (Prx 6-toll-like receptor (TLR 4 and phosphorylation level of p38 and upregulated the phosphorylation level of STAT3. In permanent MCAO rats, XST could reduce the infarct volume and swelling percent. Moreover, our results revealed that XST treatment could increase the rats’ weight and improve a batch of functional outcomes. In conclusion, the present data suggested that XST could protect against ischemia injury in transient and permanent MCAO rats, which might be related to Prx6-TLR4 pathway.

  12. Impact of coexisting coronary artery disease on the occurrence of cerebral ischemic lesions after carotid stenting.

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    Kuo-Lun Huang

    Full Text Available BACKGROUND: Coronary artery disease (CAD may coexist with extracranial carotid artery stenosis (ECAS, but the influence of CAD on procedure-related complications after carotid artery stenting (CAS has not been well investigated. The study aimed to determine the impact of CAD on the occurrence of peri-CAS cerebral ischemic lesions on diffusion-weighted imaging (DWI scanning. METHODS: Coronary angiography was performed within six months before CAS. DWI scanning was repetitively done within 1 week before and after CAS. Clinical outcome measures were stroke, angina, myocardial infarction and death within 30 days. RESULTS: Among 126 patients (69.5±9.0 years recruited for unilateral protected CAS, 33 (26% patients had peri-CAS DWI-positive lesions. CAD was noted in 79% (26 in 33 and 48% (45 in 93 of patients with and without peri-CAS DWI-positive lesions (OR, 4.0; 95% CI, 1.6-10.0; P = .0018, and the number of concomitant CAD on coronary angiography was positively correlated with the risk for peri-CAS DWI-positive lesions (P = .0032. In patients with no CAD (n = 55, asymptomatic CAD (n = 41 and symptomatic CAD (n = 30, the occurrence rates of peri-CAS DWI-positive lesions were 13%, 41% and 30% (P = .0048, and the peri-CAS stroke rates were 2%, 7% and 0% (P = .2120. CONCLUSIONS: The severity of morphological CAD and the presence of either symptomatic or asymptomatic CAD are associated with the occurrence of peri-CAS cerebral ischemic lesions.

  13. 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

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

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    Zhihua Sun

    2012-01-01

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

  15. Continuous measurement of cerebral cortical blood flow by laser-Doppler flowmetry in a rat stroke model

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    Dirnagl, U.; Kaplan, B.; Jacewicz, M.; Pulsinelli, W. (Cornell Univ. Medical College, New York, NY (USA))

    1989-10-01

    Laser-Doppler flowmetry (LDF), a new method allowing instantaneous, continuous, and noninvasive measurements of microcirculatory blood flow in a small tissue sample, was evaluated for its accuracy in monitoring regional cerebral blood flow (rCBF) in the cortical microcirculation after focal cerebral ischemia. Wistar and spontaneously hypertensive rats (SHR, n = 19) were subjected to permanent occlusion of the middle cerebral and common carotid arteries. Absolute rCBF in a tissue sample of the ischemic hemisphere was measured autoradiographically with ({sup 14}C)iodoantipyrine as a tracer and compared to rCBF measured by LDF. Additionally, the percent change in rCBF between baseline and ischemic values was compared for both methods. Absolute rCBF values recorded with LDF correlated poorly (r = 0.54) with ({sup 14}C)iodoantipyrine measurements. In contrast LDF readings expressed as a percentage of ischemic vs. preocclusion readings (relative LDF readings) correlated very well (r = 0.91) with the percent change in (14C)iodoantipyrine measurements. We conclude that LDF does not provide accurate measurements of absolute rCBF values but this method allows accurate measurements of changes in rCBF due to induction of focal cerebral ischemia.

  16. Continuous measurement of cerebral cortical blood flow by laser-Doppler flowmetry in a rat stroke model.

    Science.gov (United States)

    Dirnagl, U; Kaplan, B; Jacewicz, M; Pulsinelli, W

    1989-10-01

    Laser-Doppler flowmetry (LDF), a new method allowing instantaneous, continuous, and noninvasive measurements of microcirculatory blood flow in a small tissue sample, was evaluated for its accuracy in monitoring regional cerebral blood flow (rCBF) in the cortical microcirculation after focal cerebral ischemia. Wistar and spontaneously hypertensive rats (SHR, n = 19) were subjected to permanent occlusion of the middle cerebral and common carotid arteries. Absolute rCBF in a tissue sample of the ischemic hemisphere was measured autoradiographically with [14C]iodoantipyrine as a tracer and compared to rCBF measured by LDF. Additionally, the percent change in rCBF between baseline and ischemic values was compared for both methods. Absolute rCBF values recorded with LDF correlated poorly (r = 0.54) with [14C]iodoantipyrine measurements. In contrast LDF readings expressed as a percentage of ischemic vs. preocclusion readings (relative LDF readings) correlated very well (r = 0.91) with the percent change in [14C]iodoantipyrine measurements. We conclude that LDF does not provide accurate measurements of absolute rCBF values but this method allows accurate measurements of changes in rCBF due to induction of focal cerebral ischemia.

  17. New cerebral microbleeds in ischemic stroke patients on warfarin treatment: two-year follow-up.

    Science.gov (United States)

    Orken, D Necioglu; Uysal, E; Timer, E; Kuloglu-Pazarcı, N; Mumcu, S; Forta, H

    2013-09-01

    Cerebral microbleeds (CMBs) are known to be indicative of bleeding-prone microangiopathy. Little is known about the significance of CMBs in anticoagulated patients. We determined the frequency of new CMBs in ischemic stroke patients who had been receiving warfarin treatment for 2 years. A total of 204 ischemic stroke patients on warfarin therapy for 2 years underwent a repeat MRI. We compared demographic features, vascular risk factors, and radiological findings of patients with and without new CMBs. New CMBs on gradient-echo MRI were found in 29 of 204 patients (10%). Of 35 patients who had CMBs in the original study, 9 developed new CMBs after 2 years (26%), compared with 20 of the 169 patients (12%) who did not have CMBs at baseline (p=0.03). Patients with new CMBs were older than patients without CMBs (p=0.04), and the frequency of leukoaraiosis was significantly higher (p=0.02). The mean duration of warfarin treatment was not significantly different between the patients with and without new CMBs (p=0.28). This longitudinal study suggested that the presence of CMBs at baseline increased the frequency of new CMBs in patients on warfarin therapy. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. 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

  19. Protective effects of tumor necrosis factor antibody and ulinastatin on liver ischemic reperfusion in rats

    Institute of Scientific and Technical Information of China (English)

    Yan-Ling Yang; Ji-Peng Li; Xiao-Ping Xu; Ke-Feng Dou; Shu-Qiang Yue; Kai-Zong Li

    2004-01-01

    AIM: To study the protective effects of tumor necrosis factor α(TNFα) antibody and ulinastatin on liver ischemic reperfusion in rats.METHODS: One hundred and twenty male SD rats were randomly divided into four groups: normal control group,ischemic group, TNFα antibody group and TNFα antibody + ulinastatin group. The animals were killed at 0, 3, 6, 9,12 h after ischemia for 60 min and followed by reperfusion.Serum alanine aminotransferase (ALT), malondialdehyde (MDA) and liver histopathology were observed.RESULTS: After ischemic reperfusion, the serum ALT and MDA were remarkably increased, and the hepatic congestion was obvious. Treatment of TNFα antibody and ulinastatin could significantly decrease serum ALT and MDA levels,and relieve hepatic congestion.CONCLUSION: Ulinastatin and TNFα antibody can suppress the inflammatory reaction induced by hepatic ischemic reperfusion, and have protective effects on rat hepatic ischemic reperfusion injury.

  20. Interleukin-1beta mediates ischemic injury in the rat retina.

    Science.gov (United States)

    Yoneda, S; Tanihara, H; Kido, N; Honda, Y; Goto, W; Hara, H; Miyawaki, N

    2001-11-01

    Two types of experiment were performed to examine the role of interleukin-1beta in ischemia-induced damage in the rat retina. In the in vivo study, enzyme-linked immunosorbent assay was used to investigate the expression of immunoreactive interleukin-1beta in the rat retina following a hypertension-induced ischemia/reperfusion, while the effect of a recombinant human interleukin-1 receptor antagonist or an anti-interleukin-1beta neutralizing antibody on the ischemia-induced damage was examined histologically. A transient increase in the expression of immunoreactive interleukin-1beta was observed in the retina 3-12 hr after reperfusion, and morphometric evaluation at 7 days after the ischemia showed a decrease in cell numbers in the ganglion cell layer and a decreased thickness of the inner plexiform layer with no change in the other retinal layers. Intravitreal injection of interleukin-1 receptor antagonist (1 or 10 ng per eye) or anti-interleukin-1beta antibody (50 or 500 ng per eye) 5 min before the onset of the ischemia reduced the damage. In the in vitro study, interleukin-1 receptor antagonist (500 ng ml(-1)) significantly reduced glutamate-induced neurotoxicity in rat cultured retinal neurons. These results suggest that interleukin-1 plays an important role in mediating ischemic and excitotoxic damage in the retina, and that interleukin-1 inhibitors may be therapeutically useful against neuronal injury caused by optic nerve or retinal diseases such as glaucoma and central retinal artery or vein occlusion.

  1. 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

  2. Protective effect of liver ischemic preconditioning on rat hepatocytes

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Ischemic preconditioning (IPC) protects liver graft function following ischemia in liver transplantation and liver resection. The aim of this study was to assess the advantages and any potential disadvantages of liver IPC prior to isolation for rat hepatocytes during isolation and cryopreservation. After isolating and thawing the cryopreserved hepatocytes after 14 and 28 d,cell viability,efficiency,and lactate dehydrogenase (LDH) levels in preserve solution were examined for every group. Groups treated with IPC had better cell viability determination,assessment of plating efficiency and lactate dehydrogenase (LDH) assay than Group without IPC,suggesting that IPC prior to isolation may have a significant protective effect on hepatocytes subjected to isolation and short period cryopreservation.

  3. Treadmill Exercise Promotes Neurogenesis in Ischemic Rat Brains via Caveolin-1/VEGF Signaling Pathways.

    Science.gov (United States)

    Zhao, Yun; Pang, Qiongyi; Liu, Meixia; Pan, Jingzi; Xiang, Bingwu; Huang, Tingting; Tu, Fengxia; Liu, Chan; Chen, Xiang

    2017-02-01

    Using a model of middle cerebral artery occlusion (MCAO), we have previously demonstrated that treadmill exercise promotes angiogenesis in the ischemic penumbra through caveolin-1/VEGF signaling pathways. However, the function of caveolin-1/VEGF signaling in neurogenesis after MCAO has not been determined. In this study, we aimed to investigate the potential of treadmill exercise to promote neurogenesis after MCAO and whether caveolin-1/VEGF signaling pathways are involved. After MCAO, rats were subjected to a program of treadmill exercise. Daidzein (a specific inhibitor of caveolin-1 protein expression, 0.4 mg/kg) was used to confirm the effect of caveolin-1/VEGF signaling on exercise-mediated neurogenesis. We found that the total protein expression of both caveolin-1 and VEGF was increased by exercise and consistent with the improved neurological recovery, decreased infarct volumes and increased 5-bromo-2'-deoxyuridine (BrdU) in the ipsilateral Subventricular zone (SVZ), as well as increased numbers of BrdU/DCX and BrdU/Neun-positive cells in the peri-infarct region. Furthermore, we observed that the treadmill exercise-induced increased VEGF expression, improved neurological recovery, decreased infarct volumes, increased BrdU/DCX and BrdU/Neun-positive cells were significantly inhibited by the caveolin-1 inhibitor. Our results indicate that treadmill exercise improves neurological recovery in ischemic rats, possibly by enhancement of SVZ-derived neural stem cell (NSC) proliferation, migration and differentiation in the penumbra. Moreover, caveolin-1/VEGF signaling is involved in exercise-mediated NSC migration and neuronal differentiation.

  4. Citicoline and postconditioning provides neuroprotection in a rat model of ischemic spinal cord injury.

    Science.gov (United States)

    Turkkan, Alper; Alkan, Tulin; Goren, Bulent; Kocaeli, Hasan; Akar, Eylem; Korfali, Ender

    2010-06-01

    Ischemic spinal cord injury is a chain of events caused by the reduction and/or cessation of spinal cord blood flow, which results in neuronal degeneration and loss. Ischemic postconditioning is defined as a series of intermittent interruptions of blood flow in the early phase of reperfusion and has been shown to reduce the infarct size in cerebral ischemia. Our study aimed to characterize the relationship between the neuronal injury-decreasing effects of citicoline and ischemic postconditioning, which were proven to be effective against the apoptotic process. Spinal cord ischemia was produced in rats using an intrathoracic approach to implement the synchronous arcus aorta and subclavian artery clipping method. In our study, 42 male Sprague-Dawley rats (309 +/- 27 g) were used. Animals were divided into sham operated, spinal ischemia, citicoline, postconditioning, and postconditioning citicoline groups. Postconditioning was generated by six cycles of 1 min occlusion/5 min reperfusion. A 600 mmol/kg dose of citicoline was given intraperitoneally before ischemia in the citicoline and postconditioning citicoline groups. All rats were sacrificed 96 h after reperfusion. For immunohistochemical analysis, bcl-2, caspase 3, caspase 9, and bax immune staining were performed. Caspase 3, caspase 9, bax, and bcl-2 were used as apoptotic and antiapoptotic markers, respectively. The blood pressure values obtained at the onset of reperfusion were significantly lower than the preischemic values. A difference in immunohistochemical scoring was detected between the caspase 3, caspase 9, bax, and bcl-2 groups. When comparisons between the ischemia (groups 2, 3, 4, and 5) and sham groups (group 1) were performed, a significant increase in caspase 3, caspase 9, bax, and bcl-2 was detected. When comparing the subgroups, the average score of caspase 9 was found to be significantly higher in ischemia group 2. The average score of bcl-2 was also found to be significantly higher in

  5. Investigation of cerebral iron deposition in aged patients with ischemic cerebrovascular disease using susceptibility-weighted imaging

    Science.gov (United States)

    Liu, Yin; Liu, Jun; Liu, Huanghui; Liao, Yunjie; Cao, Lu; Ye, Bin; Wang, Wei

    2016-01-01

    Objective The aim of this study was to investigate focal iron deposition level in the brain in patients with ischemic cerebrovascular disease and its correlation with cerebral small vessel disease imaging markers. Patients and methods Seventy-four patients with first-ever transient ischemic attack (median age: 69 years; 30 males and 44 females) and 77 patients with positive ischemic stroke history (median age: 72 years; 43 males and 34 females) were studied retrospectively. On phase image of susceptibility-weighted imaging and regions of interest were manually drawn at the bilateral head of the caudate nucleus, lenticular nucleus (LN), thalamus (TH), frontal white matter, and occipital white matter. The correlation between iron deposition level and the clinical and imaging variables was also investigated. Results Iron deposition level at LN was significantly higher in patients with previous stroke history. It linearly correlated with the presence and number of cerebral microbleeds (CMBs) but not with white matter hyperintensity and lacunar infarct. Multiple linear regression analysis showed that deep structure CMBs were the most relevant in terms of iron deposition at LN. Conclusion Iron deposition at LN may increase in cases of more severe ischemia in aged patients with transient ischemic attack, and it may be an imaging marker for CMB of ischemic origin. PMID:27574434

  6. Anti-Inflammatory Effects of Traditional Chinese Medicines against Ischemic Injury in In Vivo Models of Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    Chin-Yi Cheng

    2016-01-01

    Full Text Available Inflammation plays a crucial role in the pathophysiology of acute ischemic stroke. In the ischemic cascade, resident microglia are rapidly activated in the brain parenchyma and subsequently trigger inflammatory mediator release, which facilitates leukocyte-endothelial cell interactions in inflammation. Activated leukocytes invade the endothelial cell junctions and destroy the blood-brain barrier integrity, leading to brain edema. Toll-like receptors (TLRs stimulation in microglia/macrophages through the activation of intercellular signaling pathways secretes various proinflammatory cytokines and enzymes and then aggravates cerebral ischemic injury. The secreted cytokines activate the proinflammatory transcription factors, which subsequently regulate cytokine expression, leading to the amplification of the inflammatory response and exacerbation of the secondary brain injury. Traditional Chinese medicines (TCMs, including TCM-derived active compounds, Chinese herbs, and TCM formulations, exert neuroprotective effects against inflammatory responses by downregulating the following: ischemia-induced microglial activation, microglia/macrophage-mediated cytokine production, proinflammatory enzyme production, intercellular adhesion molecule-1, matrix metalloproteinases, TLR expression, and deleterious transcription factor activation. TCMs also aid in upregulating anti-inflammatory cytokine expression and neuroprotective transcription factor activation in the ischemic lesion in the inflammatory cascade during the acute phase of cerebral ischemia. Thus, TCMs exert potent anti-inflammatory properties in ischemic stroke and warrant further investigation.

  7. Anti-Inflammatory Effects of Traditional Chinese Medicines against Ischemic Injury in In Vivo Models of Cerebral Ischemia

    Science.gov (United States)

    2016-01-01

    Inflammation plays a crucial role in the pathophysiology of acute ischemic stroke. In the ischemic cascade, resident microglia are rapidly activated in the brain parenchyma and subsequently trigger inflammatory mediator release, which facilitates leukocyte-endothelial cell interactions in inflammation. Activated leukocytes invade the endothelial cell junctions and destroy the blood-brain barrier integrity, leading to brain edema. Toll-like receptors (TLRs) stimulation in microglia/macrophages through the activation of intercellular signaling pathways secretes various proinflammatory cytokines and enzymes and then aggravates cerebral ischemic injury. The secreted cytokines activate the proinflammatory transcription factors, which subsequently regulate cytokine expression, leading to the amplification of the inflammatory response and exacerbation of the secondary brain injury. Traditional Chinese medicines (TCMs), including TCM-derived active compounds, Chinese herbs, and TCM formulations, exert neuroprotective effects against inflammatory responses by downregulating the following: ischemia-induced microglial activation, microglia/macrophage-mediated cytokine production, proinflammatory enzyme production, intercellular adhesion molecule-1, matrix metalloproteinases, TLR expression, and deleterious transcription factor activation. TCMs also aid in upregulating anti-inflammatory cytokine expression and neuroprotective transcription factor activation in the ischemic lesion in the inflammatory cascade during the acute phase of cerebral ischemia. Thus, TCMs exert potent anti-inflammatory properties in ischemic stroke and warrant further investigation. PMID:27703487

  8. Preconditioning in globally ischemic isolated rat hearts: effect on function and metabolic indices of myocardial damage

    NARCIS (Netherlands)

    M. Arad; J.W. de Jong (Jan Willem); R. de Jonge (Robert); T. Huizer (Tom); B. Rabinowitz

    1996-01-01

    textabstractWe assessed the effects of ischemic preconditioning on heart recovery and metabolic indices of damage following global ischemia and reperfusion, in relationship to post-ischemic lactate release. Three groups of Langendorff rat hearts were studied: (1) A control group of

  9. Preconditioning in globally ischemic isolated rat hearts: effect on function and metabolic indices of myocardial damage

    NARCIS (Netherlands)

    M. Arad; J.W. de Jong (Jan Willem); R. de Jonge (Robert); T. Huizer (Tom); B. Rabinowitz

    1996-01-01

    textabstractWe assessed the effects of ischemic preconditioning on heart recovery and metabolic indices of damage following global ischemia and reperfusion, in relationship to post-ischemic lactate release. Three groups of Langendorff rat hearts were studied: (1) A control group of

  10. Early retinal inflammatory biomarkers in the middle cerebral artery occlusion model of ischemic stroke

    Science.gov (United States)

    Ritzel, Rodney M.; Pan, Sarah J.; Verma, Rajkumar; Wizeman, John; Crapser, Joshua; Patel, Anita R.; Lieberman, Richard; Mohan, Royce

    2016-01-01

    Purpose The transient middle cerebral artery occlusion (MCAO) model of stroke is one of the most commonly used models to study focal cerebral ischemia. This procedure also results in the simultaneous occlusion of the ophthalmic artery that supplies the retina. Retinal cell death is seen days after reperfusion and leads to functional deficits; however, the mechanism responsible for this injury has not been investigated. Given that the eye may have a unique ocular immune response to an ischemic challenge, this study examined the inflammatory response to retinal ischemia in the MCAO model. Methods Young male C57B/6 mice were subjected to 90-min transient MCAO and were euthanized at several time points up to 7 days. Transcription of inflammatory cytokines was measured with quantitative real-time PCR, and immune cell activation (e.g., phagocytosis) and migration were assessed with ophthalmoscopy and flow cytometry. Results Observation of the affected eye revealed symptoms consistent with Horner’s syndrome. Light ophthalmoscopy confirmed the reduced blood flow of the retinal arteries during occlusion. CX3CR1-GFP reporter mice were then employed to evaluate the extent of the ocular microglia and monocyte activation. A significant increase in green fluorescent protein (GFP)-positive macrophages was seen throughout the ischemic area compared to the sham and contralateral control eyes. RT–PCR revealed enhanced expression of the monocyte chemotactic molecule CCL2 early after reperfusion followed by a delayed increase in the proinflammatory cytokine TNF-α. Further analysis of peripheral leukocyte recruitment by flow cytometry determined that monocytes and neutrophils were the predominant immune cells to infiltrate at 72 h. A transient reduction in retinal microglia numbers was also observed, demonstrating the ischemic sensitivity of these cells. Blood–eye barrier permeability to small and large tracer molecules was increased by 72 h. Retinal microglia exhibited enhanced

  11. The role of the cerebral capillaries in acute ischemic stroke: the extended penumbra model.

    Science.gov (United States)

    Østergaard, Leif; Jespersen, Sune Nørhøj; Mouridsen, Kim; Mikkelsen, Irene Klærke; Jonsdottír, Kristjana Ýr; Tietze, Anna; Blicher, Jakob Udby; Aamand, Rasmus; Hjort, Niels; Iversen, Nina Kerting; Cai, Changsi; Hougaard, Kristina Dupont; Simonsen, Claus Z; Von Weitzel-Mudersbach, Paul; Modrau, Boris; Nagenthiraja, Kartheeban; Riisgaard Ribe, Lars; Hansen, Mikkel Bo; Bekke, Susanne Lise; Dahlman, Martin Gervais; Puig, Josep; Pedraza, Salvador; Serena, Joaquín; Cho, Tae-Hee; Siemonsen, Susanne; Thomalla, Götz; Fiehler, Jens; Nighoghossian, Norbert; Andersen, Grethe

    2013-05-01

    The pathophysiology of cerebral ischemia is traditionally understood in relation to reductions in cerebral blood flow (CBF). However, a recent reanalysis of the flow-diffusion equation shows that increased capillary transit time heterogeneity (CTTH) can reduce the oxygen extraction efficacy in brain tissue for a given CBF. Changes in capillary morphology are typical of conditions predisposing to stroke and of experimental ischemia. Changes in capillary flow patterns have been observed by direct microscopy in animal models of ischemia and by indirect methods in humans stroke, but their metabolic significance remain unclear. We modeled the effects of progressive increases in CTTH on the way in which brain tissue can secure sufficient oxygen to meet its metabolic needs. Our analysis predicts that as CTTH increases, CBF responses to functional activation and to vasodilators must be suppressed to maintain sufficient tissue oxygenation. Reductions in CBF, increases in CTTH, and combinations thereof can seemingly trigger a critical lack of oxygen in brain tissue, and the restoration of capillary perfusion patterns therefore appears to be crucial for the restoration of the tissue oxygenation after ischemic episodes. In this review, we discuss the possible implications of these findings for the prevention, diagnosis, and treatment of acute stroke.

  12. Protective reactions of Silybin-phosphatidylcholine compound on cerebral ischemic reperfusion injury in rats%水飞蓟宾-磷脂酰胆碱复合物对大鼠脑缺血再灌注损伤的保护作用

    Institute of Scientific and Technical Information of China (English)

    陈正跃; 许建文; 张光军

    2004-01-01

    also has anti-free radical and anti-lipoid peroxidation reaction, and therefore, theoretically, SPC has better pharmacological reactions.OBJECTIVE: To understand the protective reaction of SPC in cerebral ischemic reperfusion injury in rats.DESIGN: A complete randomized controlled study.SETTING and PARTICIPANTS: Study was conducted in the Department of Pharmacy of Xinxiang Medical College. Silybin(98% ) was obtained from Panjin No. 3 Pharmaceutical Factory of Liaoning Province. SPC(> 95% ) was synthesized by our department. MDA reagent box was obtained from Nanjing Jiancheng Bioengineering Institute. Instruments: SHIMADZU 2550 model Ultraviolet-visible light spectrophotometer, DL-6 model low-temperature centrifuge(Wuhan Scientific Instrument Factory) . Experimental animals were obtained from the Experimental Animal Center of Xinxiang Medical College.INTERVENTIONS: Sample medications were given through stomach-perfusion to the rats in each group. The volume of stomach-perfusion was 0.5 mL/100 g. SPC and Silybin were suspended separately in 5 g/L of CMC group(model group): stomach-perfusion were conducted twice a day with 5 g/L ach-perfusion were conducted twice a day with 10 rg/100 g SPC(5 g/L of twice a day with 10 mg/100 g of Silybin(5 g/L of CMC suspension) . At 2hours after the sixth stomach-perfusion(on the third day), surgeries were operated in the rats of each group. 100 g/L of urathane was used for anesthesia through abdominal injection in a dose of 125 mg/100 g and a central incision was made along the neck. Trachea and common carotid arteries on both sides were carefully bluntly separated and exposed. Non-traumatic arterial clamps were used to clamp common carotid arteries and pneumogastric nerves of both sides to induce incomplete cerebral ischemia and the clamps were relieved after 60 minutes. Animals were executed after 6-hour of reperfusion and blood and brain were taken immediately for detection. The common carotid arties in sham-operation group were

  13. Erythropoietin reduces apoptosis of brain tissue cells in rats after cerebral ischemia/reperfusion injury: a characteristic analysis using magnetic resonance imaging

    Directory of Open Access Journals (Sweden)

    Chun-juan Jiang

    2016-01-01

    Full Text Available Some in vitro experiments have shown that erythropoietin (EPO increases resistance to apoptosis and facilitates neuronal survival following cerebral ischemia. However, results from in vivo studies are rarely reported. Perfusion-weighted imaging (PWI and diffusion-weighted imaging (DWI have been applied successfully to distinguish acute cerebral ischemic necrosis and penumbra in living animals; therefore, we hypothesized that PWI and DWI could be used to provide imaging evidence in vivo for the conclusion that EPO could reduce apoptosis in brain areas injured by cerebral ischemia/reperfusion. To validate this hypothesis, we established a rat model of focal cerebral ischemia/reperfusion injury, and treated with intra-cerebroventricular injection of EPO (5,000 U/kg 20 minutes before injury. Brain tissue in the ischemic injury zone was sampled using MRI-guided localization. The relative area of abnormal tissue, changes in PWI and DWI in the ischemic injury zone, and the number of apoptotic cells based on TdT-mediated dUTP-biotin nick end-labeling (TUNEL were assessed. Our findings demonstrate that EPO reduces the relative area of abnormally high signal in PWI and DWI, increases cerebral blood volume, and decreases the number of apoptotic cells positive for TUNEL in the area injured by cerebral ischemia/reperfusion. The experiment provides imaging evidence in vivo for EPO treating cerebral ischemia/reperfusion injury.

  14. Erythropoietin reduces apoptosis of brain tissue cells in rats after cerebral ischemia/reperfusion injury:a characteristic analysis using magnetic resonance imaging

    Institute of Scientific and Technical Information of China (English)

    Chun-juan Jiang; Zhong-juan Wang; Yan-jun Zhao; Zhui-yang Zhang; Jing-jing Tao; Jian-yong Ma

    2016-01-01

    Somein vitro experiments have shown that erythropoietin (EPO) increases resistance to apoptosis and facilitates neuronal survival follow-ing cerebral ischemia. However, results fromin vivo studies are rarely reported. Perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) have been applied successfully to distinguish acute cerebral ischemic necrosis and penumbra in living animals; therefore, we hypothesized that PWI and DWI could be used to provide imaging evidencein vivo for the conclusion that EPO could reduce apoptosis in brain areas injured by cerebral ischemia/reperfusion. To validate this hypothesis, we established a rat model of focal cerebral ischemia/reperfusion injury, and treated with intra-cerebroventricular injection of EPO (5,000 U/kg) 20 minutes before injury. Brain tissue in the ischemic injury zone was sampled using MRI-guided localization. The relative area of abnormal tissue, changes in PWI and DWI in the ischemic injury zone, and the number of apoptotic cells based on TdT-mediated dUTP-biotin nick end-labeling (TUNEL) were assessed. Our ifndings demonstrate that EPO reduces the relative area of abnormally high signal in PWI and DWI, increases cerebral blood volume, and decreases the number of apoptotic cells positive for TUNEL in the area injured by cerebral ischemia/reperfusion. The experiment pro-vides imaging evidencein vivo for EPO treating cerebral ischemia/reperfusion injury.

  15. Erythropoietin reduces apoptosis of brain tissue cells in rats after cerebral ischemia/reperfusion injury: a characteristic analysis using magnetic resonance imaging.

    Science.gov (United States)

    Jiang, Chun-Juan; Wang, Zhong-Juan; Zhao, Yan-Jun; Zhang, Zhui-Yang; Tao, Jing-Jing; Ma, Jian-Yong

    2016-09-01

    Some in vitro experiments have shown that erythropoietin (EPO) increases resistance to apoptosis and facilitates neuronal survival following cerebral ischemia. However, results from in vivo studies are rarely reported. Perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) have been applied successfully to distinguish acute cerebral ischemic necrosis and penumbra in living animals; therefore, we hypothesized that PWI and DWI could be used to provide imaging evidence in vivo for the conclusion that EPO could reduce apoptosis in brain areas injured by cerebral ischemia/reperfusion. To validate this hypothesis, we established a rat model of focal cerebral ischemia/reperfusion injury, and treated with intra-cerebroventricular injection of EPO (5,000 U/kg) 20 minutes before injury. Brain tissue in the ischemic injury zone was sampled using MRI-guided localization. The relative area of abnormal tissue, changes in PWI and DWI in the ischemic injury zone, and the number of apoptotic cells based on TdT-mediated dUTP-biotin nick end-labeling (TUNEL) were assessed. Our findings demonstrate that EPO reduces the relative area of abnormally high signal in PWI and DWI, increases cerebral blood volume, and decreases the number of apoptotic cells positive for TUNEL in the area injured by cerebral ischemia/reperfusion. The experiment provides imaging evidence in vivo for EPO treating cerebral ischemia/reperfusion injury.

  16. Effect of Electroacupuncture on TRPM7 mRNA Expression after Cerebral Ischemia/reperfusion in Rats via TrkA Pathway

    Institute of Scientific and Technical Information of China (English)

    ZHAO Li; SHI Jing; SUN Ning; TIAN Shunlian; MENG Xianfang; LIU Xiaochun; LI Lingli

    2005-01-01

    Summary: The effect of electroacupuncture (EA) on TRPM7 mRNA expression of focal cerebral ischemia in rats and further the role of EA in the relationship between TRPM7 and trkA pathway was investigated. Thirty SD rats were randomly divided into 5 groups : normal group, ischemia/reperfusion group, EA treated group (ischemic rats with EA treatment), TE infusion group (ischemic rats with EA treatment and TE buffer infusion),AS-ODN group (ischemic rats with EA treatment and antisense trkA oligonucleotide infusion). The stroke animal model was established by the modified method of middle cerebral artery occlusion. Antisense trkA oligonucleotide that blocked NGF's effects was injected into cerebroventricle before EA. The TRPM7 mRNA was detected by RT-PCR method. The results showed that there were low TRPM7 mRNA levels in cortex and hippocampus in normal group. Compared with normal group, TRPM7 mRNA expression was increased significantly in ischemia/reperfusion group (P<0.05). A significant reduction in the expression of TRPM7 mRNA was found in EA treated group in contrast to ischemia/reperfusion group (P<0.05). The expression of TRPM7 mRNA in AS-ODN group was remarkably increased compared with EA treated group and TE infusion group (P<0.05). The results indicated that TRPM7 channels in the ischemic cortex and hippocampus in rats might play a key role in ischemic brain injury. EA could reverse the overexpression of TRPM7 in cerebral ischemia/reperfusion rats. And the inhibitory effect of EA on TRPM7 channels might be through trkA pathway.

  17. Cerebral blood flow response to propranolol in streptozotocin diabetic rats

    DEFF Research Database (Denmark)

    Lass, Preben; Knudsen, G M

    1990-01-01

    The influence of propranolol on cerebral blood flow (CBF) was tested in streptozotocin diabetic rats and in control animals. Resting CBF values were 40% lower in the diabetic rats compared with controls. Intravenous injection of propranolol (2 mg kg-1) decreased CBF significantly in the control...

  18. The Chinese herbal formula Tongluo Jiunao promotes expression of brain-derived neurotrophic factor/tropomyosin-related kinase B pathways in a rat model of ischemic brain injury

    Institute of Scientific and Technical Information of China (English)

    Peiman Alesheikh; Yangyang Yan; Huiling Tang; Pengtao Li; Wei Zhang; Yanshu Pan; Arezou Mashoufi; Liyun Zhao; Runjun Wang; Bo Di

    2011-01-01

    The neurotrophin-Trk receptor pathway is an intrinsic pathway to relieve damage to the central nervous system. The present study observed the effects of Tongluo Jiunao (TLJN), which comprises Panax Notoginseng and Gardenia Jasminoides, on expression of brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase B (TrkB) in a rat model of focal cerebral ischemic injury. Xue Sai Tong (XST), comprising Panax Notoginseng, served as the positive control. Mechanisms of neuroprotection were analyzed following TLJN injection. Following establishment of the middle cerebral artery occlusion models, TLJN and XST were intraperitoneally injected, and 2, 3, 5-triphenyltetrazolium chloride staining results revealed that TLJN injection reduced infarct volume, suggesting that TLJN exerted a neuroprotective effect. Enzyme-linked immunosorbent assay results showed that TLJN elevated BDNF and growth associated protein-43 expression in ischemic brain tissues, as well as serum BDNF levels. Reverse-transcription polymerase chain reaction and western blot results showed that TLJN injection did not affect TrkB expression in the ischemic brain tissues of rats. These results suggested that TLJN injection reduced damage to ischemic brain tissues and increased BDNF expression. In addition, TLJN injection resulted in better promoting effects on neurotrophic factor expression compared with XST.

  19. Characteristics and dynamics of cognitive impairment in patients with primary and recurrent cerebral ischemic hemispheric stroke

    Directory of Open Access Journals (Sweden)

    A. A. Kozyolkin

    2014-08-01

    Full Text Available Acute cerebrovascular disease is a global medical and social problem of the modern angioneurology, occupying leading positions in the structure of morbidity and mortality among adult population of the world. Ischemic stroke – is one of the most common pathology. Today this disease took out the world pandemic. More than 16 million new cases of cerebral infarction recorded in the world each year and it “kills” about 7 million of people. About 111,953 cases of cerebral stroke were registered in 2013 in Ukraine. Cognitive impairment, t hat significantly disrupt daily activities and life of the patient, is one of the most significant post-stroke complications that have social, medical and biological significance. Aim. The purpose of this investigation was to study features and dynamics of cognitive impairments in patients with primary and recurrent cerebral hemispheric ischemic stroke (CHIS in the acute stage of the disease. Materials and methods. To achieve the aim, and the decision of tasks in the clinic of nervous diseases Zaporozhye State Medical University (supervisor - Doctor of Medicine, Professor Kozelkin A. based on the department of acute cerebrovascular disease were performed comparative, prospective cohort study, which included comprehensive clinical and paraclinical examinations of 41 patients (26 men and 15 women aged 45 to 85 years (mean age 66,4 ± 1,4 years with acute left-hemispheric (2 patients and right - hemispheric (39 patients CHIS . First up was a group of 28 patients (19 men and 9 women, mean age 65,6 ± 1,6 years, who suffered from primary CHIS. The second group consisted of 13 patients (7 men and 6 women, mean age 68,1 ± 2,5 years with recurrent CHIS. The groups were matched by age, sex, localization of the lesion and the initial level of neurological deficit. All patients underwent physical examination, neurological examination. Dynamic clinical neurological examination assessing the severity of stroke was conducted

  20. Point application withAngong Niuhuang sticker protects hippocampal and cortical neurons in rats with cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Dong-shu Zhang; Yuan-liang Liu; Dao-qi Zhu; Xiao-jing Huang; Chao-hua Luo

    2015-01-01

    Angong Niuhuang pill, a Chinese materia medica preparation, can improve neurological func-tions after acute ischemic stroke. Because of its inconvenient application and toxic components (Cinnabaris andRealgar), we used transdermal enhancers to deliverAngong 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 theDazhui (DU14), Qihai(RN6) andMingmen (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 ofAngong Niuhuangstickers attenuated neuronal damage in the cortex and hippocampal CA1 region, and improved the memory of rats with chronic cerebral ischemia with an efifcacy similar to interventions by electroacupuncture at Dazhui (DU14),Qihai (RN6) andMingmen (DU4). Our experimental ifndings indicate that point application withAngong Niuhuang stickers can improve cognitive function after chronic cerebral ischemia in rats and is neuroprotective with an equivalent efifcacy to acupuncture.

  1. Matrine attenuates focal cerebral ischemic injury by improving antioxidant activity and inhibiting apoptosis in mice.

    Science.gov (United States)

    Zhao, Peng; Zhou, Ru; Zhu, Xiao-Yun; Hao, Yin-Ju; Li, Nan; Wang, Jie; Niu, Yang; Sun, Tao; Li, Yu-Xiang; Yu, Jian-Qiang

    2015-09-01

    cerebral ischemic injury and that these effects are associated with its antioxidant and anti-apoptotic properties.

  2. Orally Administrated Ascorbic Acid Suppresses Neuronal Damage and Modifies Expression of SVCT2 and GLUT1 in the Brain of Diabetic Rats with Cerebral Ischemia-Reperfusion

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    Naohiro Iwata

    2014-04-01

    Full Text Available Diabetes mellitus is known to exacerbate cerebral ischemic injury. In the present study, we investigated antiapoptotic and anti-inflammatory effects of oral supplementation of ascorbic acid (AA on cerebral injury caused by middle cerebral artery occlusion and reperfusion (MCAO/Re in rats with streptozotocin-induced diabetes. We also evaluated the effects of AA on expression of sodium-dependent vitamin C transporter 2 (SVCT2 and glucose transporter 1 (GLUT1 after MCAO/Re in the brain. The diabetic state markedly aggravated MCAO/Re-induced cerebral damage, as assessed by infarct volume and edema. Pretreatment with AA (100 mg/kg, p.o. for two weeks significantly suppressed the exacerbation of damage in the brain of diabetic rats. AA also suppressed the production of superoxide radical, activation of caspase-3, and expression of proinflammatory cytokines (tumor necrosis factor-α and interleukin-1β in the ischemic penumbra. Immunohistochemical staining revealed that expression of SVCT2 was upregulated primarily in neurons and capillary endothelial cells after MCAO/Re in the nondiabetic cortex, accompanied by an increase in total AA (AA + dehydroascorbic acid in the tissue, and that these responses were suppressed in the diabetic rats. AA supplementation to the diabetic rats restored these responses to the levels of the nondiabetic rats. Furthermore, AA markedly upregulated the basal expression of GLUT1 in endothelial cells of nondiabetic and diabetic cortex, which did not affect total AA levels in the cortex. These results suggest that daily intake of AA attenuates the exacerbation of cerebral ischemic injury in a diabetic state, which may be attributed to anti-apoptotic and anti-inflammatory effects via the improvement of augmented oxidative stress in the brain. AA supplementation may protect endothelial function against the exacerbated ischemic oxidative injury in the diabetic state and improve AA transport through SVCT2 in the cortex.

  3. Hyperlipidemia affects neuronal nitric oxide synthase expression in brains of focal cerebral ischemia rat model

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    Jianji Pei; Liqiang Liu; Jinping Pang; Xiaohong Tian

    2008-01-01

    BACKGROUND: Hyperlipidemia, a risk factor for ischemic cerebrovascular disease, may mediate production of neuronal nitric oxide synthase (nNOS) to induce increased nitric oxide levels, resulting in brain neuronal injury. OBJECTIVE: To investigate effects of hyperlipidemia on brain nNOS expression, and to verify changes in infarct volume and pathology during reperfusion, as well as neuronal injury following ischemia/reperfusion in a rat model of focal cerebral ischemia. DESIGN, TIME AND SETTING: Complete, randomized grouping experiment was performed at the Laboratory of Physiology, Shanxi Medical University from March 2005 to March 2006. MATERIALS: A total of 144 eight-week-old, male, Wistar rats, weighing 160-180 g, were selected. A rat model of middle cerebral artery occlusion was established by suture method after 4 weeks of formulated diet. Nitric oxide kit and rabbit anti-rat nNOS kit were respectively purchased from Nanjing Jiancheng Bioengineering Institute, China and Wuhan Boster Biological Technology, Ltd., China. METHODS: The rats were equally and randomly divided into high-fat diet and a normal diet groups. Rats in the high-fat diet group were fed a high-fat diet, consisting of 10% egg yolk powder, 5% pork fat, and 0.5% pig bile salt combined with standard chow to create hyperlipidemia. Rats in the normal diet group were fed a standard rat chow. A total of 72 rats in both groups were randomly divided into 6 subgroups: sham-operated, 4-hour ischemia, 4-hour ischemia/2-hour reperfusion, 4-hour ischemia/4-hour reperfusion, 4-hour ischemia/6-hour reperfusion, and 4-hour ischemia/12-hour reperfusion, with 12 rats in each subgroup. MAIN OUTCOME MEASURES: nNOS expression was measured by immunohistochemistry, and pathomorphology changes were detected by hematoxylin-eosin staining. Infarct volume and nitric oxide levels were respectively measured using 2, 3, 5-triphenyltetrazolium chloride (TTC) and immunohistochemistry. RESULTS: In the ischemic region, pathology

  4. Environmental enrichment promotes neural remodeling in newborn rats with hypoxic-ischemic brain damage

    Institute of Scientific and Technical Information of China (English)

    Chuanjun Liu; Yankui Guo; Yalu Li; Zhenying Yang

    2011-01-01

    We evaluated the effect of hypoxic-ischemic brain damage and treatment with early environmental enrichment intervention on development of newborn rats, as evaluated by light and electron microscopy and morphometry. Early intervention with environmental enrichment intelligence training attenuated brain edema and neuronal injury, promoted neuronal repair, and increased neuronal plasticity in the frontal lobe cortex of the newborn rats with hypoxic-ischemic brain damage.

  5. The follow-up research on the value of the plasma homocystine after methionine loading test on the recurrent ischemic vascular event in cerebral infarction

    Institute of Scientific and Technical Information of China (English)

    刘怀翔

    2014-01-01

    Objective To evaluate the effect of the plasma homocystine(Hcy)after methionine loading test(MLT)on the recurrence of ischemic vascular event,including cerebral infarction,transient ischemic attack(TIA),acute coronary syndrome,other vascular embolism in cerebral infarction patients.Methods The fasting plasma homocystine(FHcy)and homocystine after MLT(PHcy)levels were measured by high-performance liquid chromatog-

  6. A comparative study on the efficacy of 10% hypertonic saline and equal volume of 20% mannitol in the treatment of experimentally induced cerebral edema in adult rats

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    Fang Ming

    2010-12-01

    Full Text Available Abstract Background Hypertonic saline and mannitol are commonly used in the treatment of cerebral edema and elevated intracranial pressure (ICP at present. In this connection, 10% hypertonic saline (HS alleviates cerebral edema more effectively than the equal volume of 20% mannitol. However, the exact underlying mechanism for this remains obscure. This study aimed to explore the possible mechanism whereby 10% hypertonic saline can ameliorate cerebral edema more effectively than mannitol. Results Adult male Sprague-Dawley (SD rats were subjected to permanent right-sided middle cerebral artery occlusion (MCAO and treated with a continuous intravenous infusion of 10% HS, 20% mannitol or D-[1-3H(N]-mannitol. Brain water content (BWC as analyzed by wet-to-dry ratios in the ischemic hemisphere of SD rats decreased more significantly after 10% HS treatment compared with 20% mannitol. Concentration of serum Na+ and plasma crystal osmotic pressure of the 10% HS group at 2, 6, 12 and 18 h following permanent MCAO increased significantly when compared with 20% mannitol treated group. Moreover, there was negative correlation between the BWC of the ipsilateral ischemic hemisphere and concentration of serum Na+, plasma crystal osmotic pressure and difference value of concentration of serum Na+ and concentration of brain Na+ in ipsilateral ischemic hemisphere in the 10% HS group at the various time points after MCAO. A remarkable finding was the progressive accumulation of mannitol in the ischemic brain tissue. Conclusions We conclude that 10% HS is more effective in alleviating cerebral edema than the equal volume of 20% mannitol. This is because 10% HS contributes to establish a higher osmotic gradient across BBB and, furthermore, the progressive accumulation of mannitol in the ischemic brain tissue counteracts its therapeutic efficacy on cerebral edema.

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

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    Tao-Jie Ren

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

  8. Down regulation of cyclooxygenase-2 is involved in delayed neuroprotec-tion by ischemic preconditioning in rats

    Institute of Scientific and Technical Information of China (English)

    Liang XIAO; Fei-li ZHAO; Xing-zu ZHU

    2005-01-01

    Aim: To examine whether the prostaglandins (PGs) pathway is involved in triggering delayed neuroprotection by ischemic preconditioning (IPC) and evaluate the effects of IPC on cyclooxygenase-2 (COX-2) expression following focal cerebral ischemia and reperfusion in rats. Methods: IPC was induced by 10 min of saline infusion into the left internal carotid artery with the right common carotid artery clamped at the same time. Middle cerebral artery occlusion (MCAO) and reperfusion model was produced using intraluminal filament method. Results: IPC 48 h prior to MCAO significantly reduced infarct area as compared with MCAO alone. A nonselective inhibitor of COX indomethacin (3 mg/kg ip) applied 1 h prior to or 1 h after IPC failed to affect its protective effects. IPC had no direct effect on the cortex COX-2 mRNA and protein expression 72 h later, but decreased the expres sion of COX-2 mRNA and protein following ischemia and reperfusion insult. Conclusion: PGs pathways was not involved in triggering delayed neuroprotection by IPC, and IPC induced down-regulation of COX-2 following focal cerebral ischemia and reperfusion in rats in vivo.

  9. Excess salt increases infarct size produced by photothrombotic distal middle cerebral artery occlusion in spontaneously hypertensive rats.

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    Hiroshi Yao

    Full Text Available Cerebral circulation is known to be vulnerable to high salt loading. However, no study has investigated the effects of excess salt on focal ischemic brain injury. After 14 days of salt loading (0.9% saline or water, spontaneously hypertensive rats (SHR and normotensive Wistar-Kyoto rats (WKY were subjected to photothrombotic middle cerebral artery occlusion (MCAO, and infarct volume was determined at 48 h after MCAO: albumin and hemoglobin contents in discrete brain regions were also determined in SHR. Salt loading did not affect blood pressure levels in SHR and WKY. After MCAO, regional cerebral blood flow (CBF, determined with two ways of laser-Doppler flowmetry (one-point measurement or manual scanning, was more steeply decreased in the salt-loaded group than in the control group. In SHR/Izm, infarct volume in the salt-loaded group was 112±27 mm3, which was significantly larger than 77±12 mm3 in the control group (p = 0.002, while the extents of blood-brain barrier disruption (brain albumin and hemoglobin levels were not affected by excess salt. In WKY, salt loading did not significantly increase infarct size. These results show the detrimental effects of salt loading on intra-ischemic CBF and subsequent brain infarction produced by phototrhombotic MCAO in hypertensive rats.

  10. Nanoliposome containing cyclosporine A reduced neuroinflammation responses and improved neurological activities in cerebral ischemia/reperfusion in rat.

    Science.gov (United States)

    Partoazar, Alireza; Nasoohi, Sanaz; Rezayat, Sayed M; Gilani, Kambiz; Mehr, Shahram E; Amani, Amir; Rahimi, Nastaran; Dehpour, Ahmad R

    2017-04-01

    Cyclosporine A (CsA) is known as a neuroprotective agent against cerebral ischemia/reperfusion (I/R) in animal models. However, the significant therapeutic effects of CsA have been observed in high systemic doses or manipulating the blood-brain barrier, resulting in systemic side effects and toxicity. As the liposome nanocarriers have been developed for efficient delivery of peptide and proteins, liposomal CsA (Lipo-CsA) could improve cerebral (I/R) injuries. In this study, the liposomal CsA formulation (CsA at dose of 2.5 mg/kg) was prepared to assess the brain injury outcomes in 90 min middle cerebral artery occlusion (MCAO) stroke model followed by 48 h reperfusion in treating rats. Five minutes after induction of cerebral ischemia in rats, intravenous (iv) administration of Lipo-CsA significantly (P < 0.001) recovered the infarct size, the brain edema, and the neurological activities compared to corresponding control groups following 48 h I/R. In addition, after 48 h cerebral I/R, Lipo-CsA potentially (P < 0.001) inhibited the inflammation responses including MPO activity and tumor necrosis factor-alpha level in comparison to other groups. In conclusion, the results indicate that the low dose of CsA in liposomal formulation is more effective compared to higher dose of free form of CsA in treatment of ischemic brain in rats.

  11. Transient ischemic attack induced by melted solid lipid microparticles protects rat brains from permanent focal ischemia.

    Science.gov (United States)

    Tsai, M-J; Kuo, Y-M; Tsai, Y-H

    2014-09-01

    This study aims to develop a transient ischemic attack (TIA) model in conscious animals and uses this model to investigate the effect of TIA on subsequent permanent ischemia. TIA was induced by injecting designed temperature-sensitive melted solid lipid microparticles with a melting point around body temperature into male Wistar rats via arterial cannulation. Neurologic deficit was monitored immediately after the injection without anesthesia. According to the clinical definition of TIA, rats were divided into neurologic symptom durations ischemic stroke was induced 3d after the induction of TIA by injecting a different kind of embolic particle manufactured by blending chitin and PLGA. The ischemic stroke.

  12. Inhibiting p38 mitogen-activated protein kinase attenuates cerebral ischemic injury in Swedish mutant amyloid precursor protein transgenic mice

    Institute of Scientific and Technical Information of China (English)

    Liangyu Zou; Haiyan Qin; Yitao He; Heming Huang; Yi Lu; Xiaofan Chu

    2012-01-01

    Cerebral ischemia was induced using photothrombosis 1 hour after intraperitoneal injection of the p38 mitogen-activated protein kinase (MAPK) inhibitor SB239063 into Swedish mutant amyloid precursor protein (APP/SWE) transgenic and non-transgenic mice. The number of surviving neurons in the penumbra was quantified using Nissl staining, and the activity of p38 MAPKs was measured by western blotting. The number of surviving neurons in the penumbra was significantly reduced in APP/SWE transgenic mice compared with non-transgenic controls 7 days after cerebral ischemia, but the activity of p38 MAPKs was significantly elevated compared with the non-ischemic hemisphere in the APP/SWE transgenic mice. SB239063 prevented these changes. The APP/SWE mutation exacerbated ischemic brain injury, and this could be alleviated by inhibiting p38 MAPK activity.

  13. 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.

  14. 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.

  15. Investigation of cerebral iron deposition in aged patients with ischemic cerebrovascular disease using susceptibility-weighted imaging

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    Liu Y

    2016-08-01

    Full Text Available Yin Liu, Jun Liu, Huanghui Liu, Yunjie Liao, Lu Cao, Bin Ye, Wei Wang Department of Radiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China Objective: The aim of this study was to investigate focal iron deposition level in the brain in patients with ischemic cerebrovascular disease and its correlation with cerebral small vessel disease imaging markers.Patients and methods: Seventy-four patients with first-ever transient ischemic attack (median age: 69 years; 30 males and 44 females and 77 patients with positive ischemic stroke history (median age: 72 years; 43 males and 34 females were studied retrospectively. On phase image of susceptibility-weighted imaging and regions of interest were manually drawn at the bilateral head of the caudate nucleus, lenticular nucleus (LN, thalamus (TH, frontal white matter, and occipital white matter. The correlation between iron deposition level and the clinical and imaging variables was also investigated.Results: Iron deposition level at LN was significantly higher in patients with previous stroke history. It linearly correlated with the presence and number of cerebral microbleeds (CMBs but not with white matter hyperintensity and lacunar infarct. Multiple linear regression analysis showed that deep structure CMBs were the most relevant in terms of iron deposition at LN.Conclusion: Iron deposition at LN may increase in cases of more severe ischemia in aged patients with transient ischemic attack, and it may be an imaging marker for CMB of ischemic origin. Keywords: cerebral microbleed, ischemia, susceptibility-weighted imaging, iron, lenticular nucleus

  16. [Heart disorders secondary to cerebral ischemic infarct. A clinical study of 20 patients and diagnostico-therapeutic considerations].

    Science.gov (United States)

    Cosentino, F; Salvati, M; Artizzu, S; Caruso, R; Fiorenza, F; Ramundo, E O; Cosentino, F

    1990-01-01

    The role of heart disorders in the onset of stroke has been examined in depth, but scarce attention has been paid to the relationship between cerebral ischemic stroke and subsequent heart disorders. The paper reports the results of a study of this relationship. The present state of knowledge is outlined together with the possible risk factors which might be useful in constructing a suitable therapeutic-prophylactic protocol to reduce the cardiological risks of "acute" neurosurgical treatment.

  17. Synthesis of Lipoamino Acids and Their Activity against Cerebral Ischemic Injury

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    Yang Lu

    2009-10-01

    Full Text Available A series of lipoamino acids were synthesized and their neuroprotective effect against brain ischemia induced by oxygen-glucose deprivation (OGD on rat cerebral slices was evaluated. Among these compounds, N-stearoyl-L-tyrosine (4, N-stearoyl-L-serine (5 and N-stearoyl-L-threonine (6 exhibited good neuroprotective activity. We found that the neuroprotective activity of lipoamino acids depended on the acyl group, the presence of a free carboxylic function and a free hydroxyl group at the branched chain of the amino acids. The results also showed that 5 was the most active compound, protecting rat brain slices against OGD as well as hydrogen peroxide (H2O2 insult at the range of 1–10 M.

  18. Melatonin pretreatment protects against focal cerebral ischemia in the rat

    OpenAIRE

    Ho, HTS; Pei, Z; Pang, SF; Cheung, RTF

    2000-01-01

    Melatonin (MT) possesses many properties of an ideal neuroprotectant. In this study, the neuroprotective effects of exogenous MT were tested in a middle cerebral artery occlusion (MCAO) stroke model. Adult male Sprague-Dawley rats (280 to 360 g) were anesthetized with sodium pentobarbital (60 mg/kg, I.P.) to undergo reversible right-sided endovascular MCAO for 3 hours. Arterial blood pressure, heart rate and cerebral blood flow (CBF) were monitored, and rectal temperature was kept between 36....

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

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    Jingchun Guo

    2012-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Hori Motohide

    2012-11-01

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

  1. Deep cerebral microbleeds are negatively associated with HDL-C in elderly first-time ischemic stroke patients.

    Science.gov (United States)

    Igase, Michiya; Kohara, Katsuhiko; Igase, Keiji; Yamashita, Shiro; Fujisawa, Mutsuo; Katagi, Ryosuke; Miki, Tetsuro

    2013-02-15

    Cerebral microbleeds (CMBs) detected on T2*-weighted MRI gradient-echo have been associated with increased risk of cerebral infarction. We evaluated risk factors for these lesions in a cohort of first-time ischemic stroke patients. Presence of CMBs in consecutive first-time ischemic stroke patients was evaluated. The location of CMBs was classified by cerebral region as strictly lobar (lobar CMBs) and deep or infratentorial (deep CMBs). Logistic regression analysis was performed to determine the contribution of lipid profile to the presence of CMBs. One hundred and sixteen patients with a mean age of 70±10years were recruited. CMBs were present in 74 patients. The deep CMBs group had significantly lower HDL-C levels than those without CMBs. In univariable analysis, advanced periventricular hyperintensity grade (PVH>2) and decreased HDL-C were significantly associated with the deep but not the lobar CMB group. On logistic regression analysis, HDL-C (beta=-0.06, p=0.002) and PVH grade >2 (beta=3.40, p=0.005) were independent determinants of deep CMBs. Low HDL-C may be a risk factor of deep CMBs, including advanced PVH status, in elderly patients with acute ischemic stroke. Management of HDL-C levels might be a therapeutic target for the prevention of recurrence of stroke. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Toward fully automated processing of dynamic susceptibility contrast perfusion MRI for acute ischemic cerebral stroke.

    Science.gov (United States)

    Kim, Jinsuh; Leira, Enrique C; Callison, Richard C; Ludwig, Bryan; Moritani, Toshio; Magnotta, Vincent A; Madsen, Mark T

    2010-05-01

    We developed fully automated software for dynamic susceptibility contrast (DSC) MR perfusion-weighted imaging (PWI) to efficiently and reliably derive critical hemodynamic information for acute stroke treatment decisions. Brain MR PWI was performed in 80 consecutive patients with acute nonlacunar ischemic stroke within 24h after onset of symptom from January 2008 to August 2009. These studies were automatically processed to generate hemodynamic parameters that included cerebral blood flow and cerebral blood volume, and the mean transit time (MTT). To develop reliable software for PWI analysis, we used computationally robust algorithms including the piecewise continuous regression method to determine bolus arrival time (BAT), log-linear curve fitting, arrival time independent deconvolution method and sophisticated motion correction methods. An optimal arterial input function (AIF) search algorithm using a new artery-likelihood metric was also developed. Anatomical locations of the automatically determined AIF were reviewed and validated. The automatically computed BAT values were statistically compared with estimated BAT by a single observer. In addition, gamma-variate curve-fitting errors of AIF and inter-subject variability of AIFs were analyzed. Lastly, two observes independently assessed the quality and area of hypoperfusion mismatched with restricted diffusion area from motion corrected MTT maps and compared that with time-to-peak (TTP) maps using the standard approach. The AIF was identified within an arterial branch and enhanced areas of perfusion deficit were visualized in all evaluated cases. Total processing time was 10.9+/-2.5s (mean+/-s.d.) without motion correction and 267+/-80s (mean+/-s.d.) with motion correction on a standard personal computer. The MTT map produced with our software adequately estimated brain areas with perfusion deficit and was significantly less affected by random noise of the PWI when compared with the TTP map. Results of image

  3. 缺血后处理对脑缺血再灌注损伤大鼠的脑保护作用及其最佳时间窗的探讨%Neuroprotection and optimal time window of ischemic postconditioning against cerebral ischemia reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    刘佳丽; 王晔; 张迎

    2011-01-01

    Objective To investigate the optimal time window of ischemic postconditioning (IP) against focal cerebral ischemia-reper-fusion (I/R) injury. Methods Eighty male SD rats were randomly assigned into five groups: a sham-operated, a control and three IP (different time intervals: 15 s, 30 s and 1 min). Focal cerebral ischemia model was established via middle cerebral artery occlusion (MCAO) with the intraluminal filament technique. The neurological deficit scores (NDS) were evaluated 24 hours after reperfusion.The apoptosis of brain cells and the levels of TNF-α in the hippocampal CAl area were evaluated by TUNEL and immune stained method respectively. Results The behavioral tests showed IP attenuated neurological deficits after I/R. The NDS in the IP groups decreased significantly compared with the control group (P<0.05), and the NDS in the IP 15s and IP 30s groups were lower than in the IP 1 min group ( P< 0.05 ). The number of surviving neurons increased significantly in the IP groups as compared with the control group (P<0.05). IP significantly decreased the level of TNF-α in the hippocampal CA1 area compared with the control group (P <O.05 ). The level of TNF-α was significantly higher in the IPl min group than in the IP 15s and IP 30s groups (P< 0.05). Conclusions IP could improve functional outcomes, decrease the expression of TNF-α and reduce the nerve cell apoptosis. The optimal time window of IP against cerebral I/R injury may be 15 s and 30 s.%目的 探讨缺血后处理(IP)对大鼠局灶性脑缺血再灌注(I/R)神经保护作用的最佳时间窗.方法 80只雄性SD大鼠,随机分为5组(假手术组、对照组、IP 15s组、IP 30s组和IP 1mim组).假手术组和对照组行单纯I/R;IP 15s 组、IP 30s组和IP 1min组,反复3次缺血再灌注.除假手术组外的大鼠均采用线栓法闭塞大鼠大脑中动脉(MACO)建立脑缺血SD大鼠模型.所有大鼠行神经功能障碍评分(NDS),并应用组织原位标记凋亡细胞

  4. Picroside Ⅱ down-regulates matrix metalloproteinase-9 expression following cerebral ischemia/reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    Xiang Li; Xinying Xu; Zhen Li; Yunliang Guo; Qin Li; Xiaodan Li; Zhen Zhou

    2010-01-01

    Studies have shown that Picroside Ⅱ attenuates inflammatory reactions following brain ischemia through the inhibition of the TLR-4-NF-κB signal transduction pathway,and ameliorates cerebral edema through the reduction of aquaporin-4 expression.Matrix metalloproteinase-9(MMP-9),located downstream of the TLR-4-NF-κB signal transduction pathway,can degrade the neurovascular matrix,damage the blood-brain barrier to induce cerebral edema,and directly result in neuronal apoptosis and brain injury.Therefore,the present study further observed MMP-9expression in the brain tissues of rats with cerebral ischemia/reperfusion injury following Picroside Ⅱtreatment.Results demonstrated that Picroside Ⅱ significantly reduced MMP-9 expression in ischemic brain tissues,as well as neuronal apoptosis and brain infarct volume,suggesting PicrosideⅡ exhibits neuroprotection by down-regulating MMP-9 expression and inhibiting cell apoptosis.

  5. Hippocampal mitochondrial cytochrome C oxidase activity and gene expression in a rat model of chronic cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Qing Zhao; Yingli Zhang; Mingming Zhao; Yu Wang; Ming Ma; Xinquan Gu; Xia Cao

    2011-01-01

    The present study established a rat model of chronic cerebral ischemia using bilateral common carotid artery permanent ligation to analyze cytochrome C oxidase activity and mRNA expression in hippocampal mitochondria.Results showed significantly decreased cytochrome C oxidase activity and cytochrome C oxidase II mRNA expression with prolonged ischemia time.Further analysis revealed five mitochondrial cytochrome C oxidase II gene mutations, two newly generated mutations, and four absent mutational sites at 1 month after cerebral ischemia, as well as three mitochondrial cytochrome C oxidase III gene mutations, including two newly generating mutations, and one disappeared mutational site at 1 month after cerebral ischemia.Results demonstrated that decreased cytochrome C oxidase gene expression and mutations, as well as decreased cytochrome C oxidase activity, resulting in energy dysmetabolism, which has been shown to be involved in the pathological process of ischemic brain injury.

  6. Liposome-encapsulated hemoglobin reduces the size of cerebral infarction in rats: effect of oxygen affinity.

    Science.gov (United States)

    Fukumoto, Dai; Kawaguchi, Akira T; Haida, Munetaka; Yamano, Mariko; Ogata, Yoshitaka; Tsukada, Hideo

    2009-02-01

    Liposome-encapsulated hemoglobin (LEH) with a low oxygen affinity (l-LEH, P(50) = 45 mm Hg) was found to be protective in the rodent and primate models of ischemic stroke. This study investigated the role of LEH with a high O(2) affinity (h-LEH, P(50) = 10 mm Hg) in its protective effect on brain ischemia. The extent of cerebral infarction was determined 24 h after photochemically induced thrombosis of the middle cerebral artery from the integrated area of infarction detected by triphenyltetrazolium chloride staining in rats receiving various doses of h-LEH as well as l-LEH. Both h-LEH and l-LEH significantly reduced the extent of cortical infarction. h-LEH remained protective at a lower concentration (minimal effective dose [MED]: 0.08 mL/kg) than l-LEH (MED: 2 mL/kg) in the cortex. h-LEH reduced the infarction extent in basal ganglia as well (MED: 0.4 mL/kg), whereas l-LEH provided no significant protection. h-LEH provided better protection than l-LEH. The protective effect of both high- and low-affinity LEH may suggest the importance of its small particle size (230 nm) as compared to red blood cells. The superiority of h-LEH over l-LEH supports an optimal O(2) delivery to the ischemic penumbra as the mechanism of action in protecting against brain ischemia and reperfusion.

  7. 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.

  8. 15d-PGJ2 Reduced Microglia Activation and Alleviated Neurological Deficit of Ischemic Reperfusion in Diabetic Rat Model

    Directory of Open Access Journals (Sweden)

    Lihong Huang

    2015-01-01

    Full Text Available To investigate the effect of PPARγ agonist 15d-PGJ2 treatment on the microglia activation and neurological deficit of ischemia reperfusion in diabetic rat model, adult Sprague-Dawley rats were sacrificed for the research. The rats were randomly categorized into four groups: (1 sham-operated group; (2 standard ischemia group; (3 diabetic ischemia group; (4 diabetic ischemia group with diabetes and treated with 15d-PGJ2. Compared to the sham-operated group, all the ischemic groups have significantly severer neurological deficits, more TNF-α and IL-1 expression, increased labeling of apoptotic cells, increased CD68 positive staining of brain lesion, and increased volume of infarct and cerebral edema in both 24 hours and 7 days after reperfusion. Interestingly, reduced neurological deficits, decreased TNF-α and IL-1 expression, less apoptotic cells and CD68 positive staining, and alleviated infarct and cerebral edema volume were observed when 15d-PGJ2 was intraperitoneally injected after reperfusion in diabetic ischemia group, suggesting its neuroprotective role in regulating microglia activation, which may have a therapeutic application in the future.

  9. 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

  10. WIN55,212-2 protects oligodendrocyte precursor cells in stroke penumbra following permanent focal cerebral ischemia in rats

    Institute of Scientific and Technical Information of China (English)

    Jing SUN; Yin-quan FANG; Hong REN; Tao CHEN; Jing-jing GUO; Jun YAN; Shu SONG; Lu-yong ZHANG; Hong LIAO

    2013-01-01

    Aim:To explore whether the synthetic cannabinoid receptor agonist WIN55,212-2 could protect oligodendrocyte precursor cells (OPCs)in stroke penumbra,thereby providing neuroprotection following permanent focal cerebral ischemia in rats.Methods:Adult male SD rats were subjected to permanent middle cerebral artery occlusion (p-MCAO).The animals were administered WIN55,212-2 at 2 h,and sacrificed at 24 h after the ischemic insult.The infarct volumes and brain swelling were assessed.The expression of cannabinoid receptor type 1 (CB1) in the stroke penumbra was examined using Western blot assay.The pathological changes and proliferation of neural glial antigen 2-positive OPCs (NG2+ cells) in the stroke penumbra were studied using immunohistochemistry staining.Results:p-MCAO significantly increased the expression of CB1 within the stroke penumbra with the highest level appearing at 2 h following the ischemic insult.Administration of WIN55,212-2 (9 mg/kg,iv) significantly attenuated the brain swelling,and reduced the infarct volume as well as the number of tau-immunoreactive NG2+ cells (tau-1+/NG2+ cells) in the stroke penumbra.Moreover,WIN55,212-2 significantly promoted the proliferation of NG2+ cells in the stroke penumbra and in the ipsilateral subventricular zone at 24 h following the ischemic insult.Administration of the selective CB1 antagonist rimonabant (1 mg/kg,iv) partially blocked the effects caused by WIN55,212-2.Conclusion:Tau-1 is expressed in NG2+ cells following permanent focal cerebral ischemic injury.Treatment with WIN55,212-2 reduces the number of tau-1+/NG2+ cells and promotes NG2+ cell proliferation in the stroke penumbra,which are mediated partially via CB1 and may contribute to its neuroprotective effects.

  11. 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.

  12. The accumulation of brain water-free sodium is associated with ischemic damage independent of the blood pressure in female rats.

    Science.gov (United States)

    Sumiyoshi, Manabu; Kitazato, Keiko T; Yagi, Kenji; Miyamoto, Takeshi; Kurashiki, Yoshitaka; Matsushita, Nobuhisa; Kinouchi, Tomoya; Kuwayama, Kazuyuki; Satomi, Junichiro; Nagahiro, Shinji

    2015-08-01

    Estrogen deficiency worsens ischemic stroke outcomes. In ovariectomized (OVX(+)) rats fed a high-salt diet (HSD), an increase in the body Na(+)/water ratio, which characterizes water-free Na(+) accumulation, was associated with detrimental vascular effects independent of the blood pressure (BP). We hypothesized that an increase in brain water-free Na(+) accumulation is associated with ischemic brain damage in OVX(+)/HSD rats. To test our hypothesis we divided female Wistar rats into 4 groups, OVX(+) and OVX(-) rats fed HSD or a normal diet (ND), and subjected them to transient cerebral ischemia. The brain Na(+)/water ratio was increased even in OVX(+)/ND rats and augmented in OVX(+)/HSD rats. The increase in the brain Na(+)/water ratio was positively correlated with expansion of the cortical infarct volume without affecting the BP. Interestingly, OVX(+) was associated with the decreased expression of ATP1α3, a subtype of the Na(+) efflux pump. HSD increased the expression of brain Na(+) influx-related molecules and the mineralocorticoid receptor (MR). The pretreatment of OVX(+)/HSD rats with the MR antagonist eplerenone reduced brain water-free Na(+) accumulation, up-regulated ATP1α3, down-regulated MR, and reduced the cortical infarct volume. Our findings show that the increase in the brain Na(+)/water ratio elicited by estrogen deficiency or HSD is associated with ischemic brain damage BP-independently, suggesting the importance of regulating the accumulation of brain water-free Na(+). The up-regulation of ATP1α3 and the down-regulation of MR may provide a promising therapeutic strategy to attenuate ischemic brain damage in postmenopausal women.

  13. Elevated global SUMOylation in Ubc9 transgenic mice protects their brains against focal cerebral ischemic damage.

    Directory of Open Access Journals (Sweden)

    Yang-Ja Lee

    Full Text Available We have previously shown that a massive increase in global SUMOylation occurs during torpor in ground squirrels, and that overexpression of Ubc9 and/or SUMO-1 in cell lines and cortical neurons protects against oxygen and glucose deprivation. To examine whether increased global SUMOylation protects against ischemic brain damage, we have generated transgenic mice in which Ubc9 is expressed strongly in all tissues under the chicken β-actin promoter. Ubc9 expression levels in 10 founder lines ranged from 2 to 30 times the endogenous level, and lines that expressed Ubc9 at modestly increased levels showed robust resistance to brain ischemia compared to wild type mice. The infarction size was inversely correlated with the Ubc9 expression levels for up to five times the endogenous level. Although further increases showed no additional benefit, the Ubc9 expression level was highly correlated with global SUMO-1 conjugation levels (and SUMO-2,3 levels to a lesser extent up to a five-fold Ubc9 increase. Most importantly, there were striking reciprocal relationships between SUMO-1 (and SUMO-2,3 conjugation levels and cerebral infarction volumes among all tested animals, suggesting that the limit in cytoprotection by global SUMOylation remains undefined. These results support efforts to further augment global protein SUMOylation in brain ischemia.

  14. Cerebral Functional Reorganization in Ischemic Stroke after Repetitive Transcranial Magnetic Stimulation: An fMRI Study.

    Science.gov (United States)

    Li, Jing; Zhang, Xue-Wei; Zuo, Zhen-Tao; Lu, Jie; Meng, Chun-Ling; Fang, Hong-Ying; Xue, Rong; Fan, Yong; Guan, Yu-Zhou; Zhang, Wei-Hong

    2016-12-01

    Our study aimed to figure out brain functional reorganization evidence after repetitive transcranial magnetic stimulation (rTMS) using the resting-state functional magnetic resonance imaging (rsfMRI). Twelve patients with unilateral subcortex lesion in the middle cerebral artery territory were recruited. Seven of them received a 10-day rTMS treatment beginning at about 5 days after stroke onset. The remaining five received sham treatment. RsfMRI and motor functional scores were obtained before and after rTMS or sham rTMS. The rTMS group showed motor recovery according to the behavioral testing scores, while there was no significant difference of motor functional scores in the sham group before and after the sham rTMS. It proved that rTMS facilitates motor recovery of early ischemic stroke patients. Compared with the sham, the rTMS treatment group achieved increased functional connectivity (FC) between ipsilesional M1 and contralesional M1, supplementary motor area, bilateral thalamus, and contralesional postcentral gyrus. And decreased FC was found between ipsilesional M1 and ipsilesional M1, postcentral gyrus and inferior and middle frontal gyrus. Increased or decreased FC detected by rsfMRI is an important finding to understand the mechanism of brain functional reorganization. The rTMS treatment is a promising therapeutic approach to facilitate motor rehabilitation for early stroke patients. © 2016 John Wiley & Sons Ltd.

  15. Characters of MR diffusion tensor imaging in cerebral ischemic corticospinal tract injury

    Institute of Scientific and Technical Information of China (English)

    Ziqian Chen; Ping Ni; Hui Xiao; Youqiang Ye; Gennian Qian; Shangwen Xu; Xizhang Yang; Jinhua Chen; Biyun Zhang

    2006-01-01

    BACKGROUND: Diffusion tensor imaging (DTI) is one of the noninvasive methods to study the morphological structure of brain white matter fibrous bands in vivo, and it has been applied primarily in clinic. DTI is acknowledged as the more effective imaging method to diagnose ultra-acute and/or acute cerebral infarction.OBJECTIVE: To observe the anisotropic characters of cerebral white matter fibrous bands in patients with ischemic stroke by using DTI, and investigate the correlation between the damage of corticospinal tract and muscle strength in patients with ischemic stroke at acute period.DESIGN: A case-control observation.SETTING: Department of Medical Imaging, Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA.PARTICIpANTS: Nine inpatients with injury of motor function induced by acute ischemic stroke (patient group) at 6 hours to 2 weeks after the attack were selected from the Department of Neurology, Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA from September 2005 to March 2006,and they all accorded with the present diagnostic standard for cerebrovascular disease in China. There were 5 males and 4 females, aged 16-87 years. At the same time, nine healthy right-handed physical examinees matched by age and sex with the patients were taken as the control group, and they all had no nervous disease, mental diseases, cerebrovascular abnormalities and injury history, etc. All the subjects were informed with the detected items and agreed to participate in the study.METHODS: All the 9 patients with ischemic stroke at acute period and 9 healthy subjects were examined with MRI, T1 weighted imaging, T2 weighted imaging and DTI. And the data were processed offline with dTV.Ⅱ software, the images of fractional anisotropy and directional encoded color (DEC) were obtained, and the three-dimensional fibrous band images of bilateral corticospinal tracts were reconstructed. In the control group, the values of fractional anisotropy

  16. Electroacupuncture ameliorates learning and memory in rats with cerebral ischemia-reperfusion injury by inhibiting oxidative stress and promoting p-CREB expression in the hippocampus.

    Science.gov (United States)

    Lin, Ruhui; Lin, Yukun; Tao, Jing; Chen, Bin; Yu, Kunqiang; Chen, Jixiang; Li, Xiaojie; Chen, Li-Dian

    2015-11-01

    The present study aimed to investigate the mechanisms by which electroacupuncture (EA) ameliorates learning and memory in rats with cerebral ischemic‑reperfusion (I/R) injury. Focal cerebral ischemia was induced in adult male Sprague‑Dawley (SD) rats by transient middle cerebral artery occlusion (MCAO). Following MCAO surgery, the rats received EA at the Shenting (DU24) and Baihui (DU20) acupoints. The results of the present study demonstrated that treatment with EA significantly ameliorated neurological deficits and reduced cerebral infarct volume (Plearning and memory ability of the rats, and markedly activated the cyclic adenosine monophosphate (cAMP) response element‑binding protein (CREB) signaling pathway, resulting in the inhibition of cerebral cell apoptosis in the ischemic penumbra. Furthermore, EA increased the activity of superoxide dismutase and glutathione peroxidase, the protein expression levels of phosphorylated‑CREB and B‑cell lymphoma 2 (Bcl‑2), and the mRNA expression levels of Bcl‑2. Conversely, EA decreased the levels of malondialdehyde and inhibited the expression levels of Bcl2‑associated X protein. The results of the present study suggest that treatment with EA may result in the amelioration of learning and memory ability in rats with cerebral I/R injury.

  17. Persimmon leaf flavonoid promotes brain ischemic tolerance**

    Institute of Scientific and Technical Information of China (English)

    Mingsan Miao; Xuexia Zhang; Ming Bai; Linan Wang

    2013-01-01

    Persimmon leaf flavonoid has been shown to enhance brain ischemic tolerance in mice, but its mechanism of action remains unclear. The bilateral common carotid arteries were occluded using a micro clip to block blood flow for 10 minutes. After 10 minutes of ischemic preconditioning, 200, 100, and 50 mg/kg persimmon leaf flavonoid or 20 mg/kg ginaton was intragastrical y administered per day for 5 days. At 1 hour after the final administration, ischemia/reperfusion models were estab-lished by blocking the middle cerebral artery for 2 hours. At 24 hours after model establishment, compared with cerebral ischemic rats without ischemic preconditioning or drug intervention, plasma endothelin, thrombomodulin and von Wil ebrand factor levels significantly decreased and intercel-lular adhesion molecule-1 expression markedly reduced in brain tissue from rats with ischemic pre-conditioning. Simultaneously, brain tissue injury reduced. Ischemic preconditioning combined with drug exposure noticeably improved the effects of the above-mentioned indices, and the effects of 200 mg/kg persimmon leaf flavonoid were similar to 20 mg/kg ginaton treatment. These results indicate that ischemic preconditioning produces tolerance to recurrent severe cerebral ischemia. However, persimmon leaf flavonoid can elevate ischemic tolerance by reducing inflammatory reactions and vascular endothelial injury. High-dose persimmon leaf flavonoid showed an identical effect to ginaton.

  18. Filtrate of Phellinus linteus Broth Culture Reduces Infarct Size Significantly in a Rat Model of Permanent Focal Cerebral Ischemia.

    Science.gov (United States)

    Suzuki, Sakiko; Kawamata, Takakazu; Okada, Yoshikazu; Kobayashi, Tomonori; Nakamura, Tomoyuki; Hori, Tomokatsu

    2011-01-01

    Phellinus linteus, a natural growing mushroom, has been known to exhibit anti-tumor, anti-inflammatory, anti-allergic and anti-oxidant effects. Aiming to exploit the neuroprotective effects of P. linteus, we evaluated its effects on infarct volume reduction in a rat model of focal cerebral ischemia. Male Sprague-Dawley rats were subjected to right middle cerebral artery occlusion. Filtrate of P. linteus broth culture (various doses), fractionated filtrate (based on molecular weight) or control medium was administered intraperitoneally to rats before or after ischemia induction. Rats were killed at 24 h after the stroke surgery. Cortical and caudoputaminal infarct volumes were determined separately using an image analysis program following staining with 2,3,5-triphenyltetrazolium chloride. Significant cortical infarct volume reductions were found in the pre-treatment groups (30 and 60 minutes before onset of cerebral ischemia) compared with the control group, showing dose dependence. Posttreatment (30 minutes after ischemic onset) also significantly reduced cortical infarct volume. Furthermore, the higher molecular weight (≥12 000) fraction of the culture filtrate was more effective compared with the lower molecular weight fraction. The present findings suggest that P. linteus may be a new promising approach for the treatment of focal cerebral ischemia, with the additional benefit of a wide therapeutic time window since significant infarct volume reduction is obtained by administration even after the ischemic event. Our finding that the higher molecular weight fraction of the P. linteus culture filtrate demonstrated more prominent effect may provide a clue to identify the neuroprotective substances and mechanisms.

  19. Filtrate of Phellinus linteus Broth Culture Reduces Infarct Size Significantly in a Rat Model of Permanent Focal Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    Sakiko Suzuki

    2011-01-01

    Full Text Available Phellinus linteus, a natural growing mushroom, has been known to exhibit anti-tumor, anti-inflammatory, anti-allergic and anti-oxidant effects. Aiming to exploit the neuroprotective effects of P. linteus, we evaluated its effects on infarct volume reduction in a rat model of focal cerebral ischemia. Male Sprague-Dawley rats were subjected to right middle cerebral artery occlusion. Filtrate of P. linteus broth culture (various doses, fractionated filtrate (based on molecular weight or control medium was administered intraperitoneally to rats before or after ischemia induction. Rats were killed at 24 h after the stroke surgery. Cortical and caudoputaminal infarct volumes were determined separately using an image analysis program following staining with 2,3,5-triphenyltetrazolium chloride. Significant cortical infarct volume reductions were found in the pre-treatment groups (30 and 60 minutes before onset of cerebral ischemia compared with the control group, showing dose dependence. Posttreatment (30 minutes after ischemic onset also significantly reduced cortical infarct volume. Furthermore, the higher molecular weight (≥12 000 fraction of the culture filtrate was more effective compared with the lower molecular weight fraction. The present findings suggest that P. linteus may be a new promising approach for the treatment of focal cerebral ischemia, with the additional benefit of a wide therapeutic time window since significant infarct volume reduction is obtained by administration even after the ischemic event. Our finding that the higher molecular weight fraction of the P. linteus culture filtrate demonstrated more prominent effect may provide a clue to identify the neuroprotective substances and mechanisms.

  20. Naoxintong dose effects on inflammatory factor expression in the rat brain following focal cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Xiangjian Zhang; Li Xü; Zuoran Chen; Shuchao Hu; Liying Zhang; Haiyan Li; Ruichun Liu

    2008-01-01

    BACKGROUND: Certain components of tetramethylpyrazine, a traditional Chinese medicine, exhibit protective effects against brain injury.OBJECTIVE: To investigate the effects of different Naoxintong doses on expression of nuclear factor-kappa B (κ B), interleukin-6, tumor necrosis factor-α, and complement 3 in rats following focal cerebral ischemia.DESIGN, TIME AND SETTING: The randomized experiment was performed at the Laboratory of Neurology, Second Hospital of Hebei Medical University from June 2004 to June 2006. MATERIAIS: A total of 150 adult, healthy, male, Sprague Dawley rats, weighing 280-320 g, were selected. Naoxintong powder (mainly comprising szechwan lovage rhizome, milkvetch root, danshen root, and radix angelicae sinensis) was obtained from Buchang Pharmacy Co., Ltd. in Xianyang City of Shanxi Province of China, lot number 040608.METHODS: The rats were randomly assigned into sham operation, saline, high-dose Naoxintong, moderate-dose Naoxintong, and low-dose Naoxintong groups, with 30 rats in each group. Rat models of middle cerebral artery occlusion were established using the suture method, with the exception of the sham operation group. Rats in the high-dose, moderate-dose and low-dose Naoxintong groups received 4, 2, and 1 glkg Naoxintong respectively, by gavage. Rats in the saline group were treated with 1 mL saline by gavage. All rats were administered by garage at 5 and 23 hours following surgery, and subsequently, once per day.MAIN OUTCOME MEASURES: At 6, 24, 48, 72 hours, and 7 days following model establishment, brain water content was measured. Histopathological changes in brain tissues were detected using hematoxylin-eosin staining. Expression of nuclear factor- κB, interleukin-6, tumor necrosis factor-α, and complement 3 was examined by immunohistochemistry.RESULTS: A total of 150 rats were included in the final analysis with no loss. Brain water content was significantly increased in the ischemic hemisphere of rats from the saline, as

  1. Sesamin attenuates behavioral, biochemical and histological alterations induced by reversible middle cerebral artery occlusion in the rats.

    Science.gov (United States)

    Khan, Mohd Moshahid; Ishrat, Tauheed; Ahmad, Ajmal; Hoda, Md Nasrul; Khan, M Badruzzaman; Khuwaja, Gulrana; Srivastava, Pallavi; Raza, Syed Shadab; Islam, Fakhrul; Ahmad, Saif

    2010-01-05

    Restoration of blood flow to an ischemic brain region is associated with generation of reactive oxygen species (ROS) with consequent reperfusion injury. ROS cause lipid peroxidation, protein oxidation, and DNA damage, all of which are deleterious to cells. So diminishing the production of free radicals and scavenging them may be a successful therapeutic strategy for the protection of brain tissue in cerebral stroke. The present study investigated the neuroprotective effect of sesamin (Sn) to reduce brain injury after middle cerebral artery occlusion (MCAO). The middle cerebral artery (MCA) of adult male Wistar rat was occluded for 2h and reperfused for 22h. Sesamin is the most abundant lignan in sesame seed oil is a potent antioxidant. Sesamin (30 mg/kg) was given orally twice, 30 min before the onset of ischemia and 12h after reperfusion. The initial investigations revealed that sesamin reduced the neurological deficits in terms of behavior and reduced the level of thiobarbituric acid reactive species (TBARS), and protein carbonyl (PC) in the different areas of the brain when compared with the MCAO group. A significantly depleted level of glutathione and its dependent enzymes (glutathione peroxidase [GPx] and glutathione reductase [GR]) in MCAO group were protected significantly in MCAO group treated with sesamin. The present study suggests that sesamin may be able to attenuate the ischemic cell death and plays a crucial role as a neuroprotectant in regulating levels of reactive oxygen species in the rat brain. Thus, sesamin may be a potential compound in stroke therapy.

  2. Regional cerebral glucose utilization during morphine withdrawal in the rat.

    OpenAIRE

    Wooten, G.F.; DiStefano, P.; Collins, R. C.

    1982-01-01

    Regional cerebral glucose utilization was studied by 2-deoxy[14C]glucose autoradiography in morphine-dependent rats and during naloxone-induced morphine withdrawal. In morphine-dependent rats, glucose utilization was increased compared with naive controls uniformly (23-54%) in hippocampus, dentate gyrus, and subiculum and reduced in frontal cortex, striatum, anterior ventral thalamus, and medial habenular nucleus. On precipitation of morphine withdrawal by subcutaneous administration of nalox...

  3. [Ca2+]i change in hippocampal neuron s influenced by preconditioning of etomidate fat emulsion following cerebral ischemia in rats

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    . Fluorescence pixel value in the model group was significantly higher than that in the sham-operation group (P < 0.01). Fluorescence pixel value in the etomidate preconditioning group was significantly lower than that in the model group (P < 0.01).CONCLUSION: The protection of etomidate fat emulsion to the transient cerebral ischemic injury in rats is associated with the inhibition to the increase of [Ca2+]i to some extent.

  4. Inhibition of Peripheral TNF-α and Downregulation of Microglial Activation by Alpha-Lipoic Acid and Etanercept Protect Rat Brain Against Ischemic Stroke.

    Science.gov (United States)

    Wu, Ming-Hsiu; Huang, Chao-Ching; Chio, Chung-Ching; Tsai, Kuen-Jer; Chang, Ching-Ping; Lin, Nan-Kai; Lin, Mao-Tsun

    2016-09-01

    Ischemic stroke, caused by obstruction of blood flow to the brain, would initiate microglia activation which contributes to neuronal damage. Therefore, inhibition of microglia-mediated neuroinflammation could be a therapeutic strategy for ischemic stroke. This study was aimed to elucidate the anti-inflammatory effects of alpha-lipoic acid and etanercept given either singly or in combination in rats subjected to middle cerebral artery occlusion. Both α-lipoic acid and etanercept markedly reduced cerebral infarct, blood-brain barrier disruption, and neurological motor deficits with the former drug being more effective with the dosage used. Furthermore, when used in combination, the reduction was more substantial. Remarkably, a greater diminution in the serum levels of tumor necrosis factor-alpha as well as the brain levels of microglial activation (e.g., microgliosis, amoeboid microglia, and microglial overexpression of tumor necrosis factor-α) was observed with the combined drug treatment as compared to the drugs given separately. We conclude that inhibition of peripheral tumor necrosis factor-alpha as well as downregulation of brain microglial activation by alpha-lipoic acid or etanercept protect rat brain against ischemic stroke. Moreover, when both drugs were used in combination, the stroke recovery was promoted more extensively.

  5. Ischemic preconditioning reduces ischemic brain injury by suppressing nuclear factor kappa B expression and neuronal apoptosis

    Institute of Scientific and Technical Information of China (English)

    Songsheng Shi; Weizhong Yang; Xiankun Tu; Chunmei Chen; Chunhua Wang

    2013-01-01

    Ischemic stroke induces a series of complex pathophysiological events including blood-brain barrier disruption, inflammatory response and neuronal apoptosis. Previous studies demonstrate that ischemic preconditioning attenuates ischemic brain damage via inhibiting blood-brain barrier disruption and the inflammatory response. Rats underwent transient (15 minutes) occlusion of the bilateral common carotid artery with 48 hours of reperfusion, and were subjected to permanent middle cerebral artery occlusion. This study explored whether ischemic preconditioning could reduce ischemic brain injury and relevant molecular mechanisms by inhibiting neuronal apoptosis. Results found that at 72 hours following cerebral ischemia, myeloperoxidase activity was enhanced, malondialdehyde levels increased, and neurological function was obviously damaged. Simultaneously, neuronal apoptosis increased, and nuclear factor-κB and cleaved caspase-3 expression was significantly increased in ischemic brain tissues. Ischemic preconditioning reduced the cerebral ischemia-induced inflammatory response, lipid peroxidation, and neurological function injury. In addition, ischemic preconditioning decreased nuclear factor-κB p65 and cleaved caspase-3 expression. These results suggested that ischemic preconditioning plays a protective effect against ischemic brain injury by suppressing the inflammatory response, reducing lipid peroxidation, and neuronal apoptosis via inhibition of nuclear factor-κB and cleaved caspase-3 expression.

  6. 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-

  7. Damaged Neocortical Perineuronal Nets Due to Experimental Focal Cerebral Ischemia in Mice, Rats and Sheep.

    Science.gov (United States)

    Härtig, Wolfgang; Mages, Bianca; Aleithe, Susanne; Nitzsche, Björn; Altmann, Stephan; Barthel, Henryk; Krueger, Martin; Michalski, Dominik

    2017-01-01

    As part of the extracellular matrix (ECM), perineuronal nets (PNs) are polyanionic, chondroitin sulfate proteoglycan (CSPG)-rich coatings of certain neurons, known to be affected in various neural diseases. Although these structures are considered as important parts of the neurovascular unit (NVU), their role during evolution of acute ischemic stroke and subsequent tissue damage is poorly understood and only a few preclinical studies analyzed PNs after acute ischemic stroke. By employing three models of experimental focal cerebral ischemia, this study was focused on histopathological alterations of PNs and concomitant vascular, glial and neuronal changes according to the NVU concept. We analyzed brain tissues obtained 1 day after ischemia onset from: (a) mice after filament-based permanent middle cerebral artery occlusion (pMCAO); (b) rats subjected to thromboembolic MACO; and (c) sheep at 14 days after electrosurgically induced focal cerebral ischemia. Multiple fluorescence labeling was applied to explore simultaneous alterations of NVU and ECM. Serial mouse sections labeled with the net marker Wisteria floribunda agglutinin (WFA) displayed largely decomposed and nearly erased PNs in infarcted neocortical areas that were demarcated by up-regulated immunoreactivity for vascular collagen IV (Coll IV). Subsequent semi-quantitative analyses in mice confirmed significantly decreased WFA-staining along the ischemic border zone and a relative decrease in the directly ischemia-affected neocortex. Triple fluorescence labeling throughout the three animal models revealed up-regulated Coll IV and decomposed PNs accompanied by activated astroglia and altered immunoreactivity for parvalbumin, a calcium-binding protein in fast-firing GABAergic neurons which are predominantly surrounded by neocortical PNs. Furthermore, ischemic neocortical areas in rodents simultaneously displayed less intense staining of WFA, aggrecan, the net components neurocan, versican and the cartilage link

  8. Damaged Neocortical Perineuronal Nets Due to Experimental Focal Cerebral Ischemia in Mice, Rats and Sheep

    Directory of Open Access Journals (Sweden)

    Wolfgang Härtig

    2017-08-01

    Full Text Available As part of the extracellular matrix (ECM, perineuronal nets (PNs are polyanionic, chondroitin sulfate proteoglycan (CSPG-rich coatings of certain neurons, known to be affected in various neural diseases. Although these structures are considered as important parts of the neurovascular unit (NVU, their role during evolution of acute ischemic stroke and subsequent tissue damage is poorly understood and only a few preclinical studies analyzed PNs after acute ischemic stroke. By employing three models of experimental focal cerebral ischemia, this study was focused on histopathological alterations of PNs and concomitant vascular, glial and neuronal changes according to the NVU concept. We analyzed brain tissues obtained 1 day after ischemia onset from: (a mice after filament-based permanent middle cerebral artery occlusion (pMCAO; (b rats subjected to thromboembolic MACO; and (c sheep at 14 days after electrosurgically induced focal cerebral ischemia. Multiple fluorescence labeling was applied to explore simultaneous alterations of NVU and ECM. Serial mouse sections labeled with the net marker Wisteria floribunda agglutinin (WFA displayed largely decomposed and nearly erased PNs in infarcted neocortical areas that were demarcated by up-regulated immunoreactivity for vascular collagen IV (Coll IV. Subsequent semi-quantitative analyses in mice confirmed significantly decreased WFA-staining along the ischemic border zone and a relative decrease in the directly ischemia-affected neocortex. Triple fluorescence labeling throughout the three animal models revealed up-regulated Coll IV and decomposed PNs accompanied by activated astroglia and altered immunoreactivity for parvalbumin, a calcium-binding protein in fast-firing GABAergic neurons which are predominantly surrounded by neocortical PNs. Furthermore, ischemic neocortical areas in rodents simultaneously displayed less intense staining of WFA, aggrecan, the net components neurocan, versican and the

  9. Continuous adenosine A2A receptor antagonism after focal cerebral ischemia in spontaneously hypertensive rats.

    Science.gov (United States)

    Fronz, Ulrike; Deten, Alexander; Baumann, Frank; Kranz, Alexander; Weidlich, Sarah; Härtig, Wolfgang; Nieber, Karen; Boltze, Johannes; Wagner, Daniel-Christoph

    2014-02-01

    Antagonism of the adenosine A2A receptor (A2AR) has been shown to elicit substantial neuroprotective properties when given immediately after cerebral ischemia. We asked whether the continuous application of a selective A2AR antagonist within a clinically relevant time window will be a feasible and effective approach to treat focal cerebral ischemia. To answer this question, we subjected 20 male spontaneously hypertensive rats to permanent middle cerebral artery occlusion and randomized them equally to a verum and a control group. Two hours after stroke onset, the animals received a subcutaneous implantation of an osmotic minipump filled with 5 mg kg(-1) day(-1) 8-(3-chlorostyryl) caffeine (CSC) or vehicle solution. The serum level of CSC was measured twice a day for three consecutive days. The infarct volume was determined at days 1 and 3 using magnetic resonance imaging. We found the serum level of CSC showing a bell-shaped curve with its maximum at 36 h. The infarct volume was not affected by continuous CSC treatment. These results suggest that delayed and continuous CSC application was not sufficient to treat acute ischemic stroke, potentially due to unfavorable hepatic elimination and metabolization of the pharmaceutical.

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

    Science.gov (United States)

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

    2012-01-15

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

  11. Inhibition of Histone Deacetylase 3 (HDAC3) Mediates Ischemic Preconditioning and Protects Cortical Neurons against Ischemia in Rats

    Science.gov (United States)

    Wu, Qimei; Zhang, Lei; Feng, Linyin

    2016-01-01

    Brain ischemic preconditioning (PC) provides vital insights into the endogenous protection against stroke. Genomic and epigenetic responses to PC condition the brain into a state of ischemic tolerance. Notably, PC induces the elevation of histone acetylation, consistent with evidence that histone deacetylase (HDAC) inhibitors protect the brain from ischemic injury. However, less is known about the specific roles of HDACs in this process. HDAC3 has been implicated in several neurodegenerative conditions. Deletion of HDAC3 confers protection against neurotoxicity and neuronal injury. Here, we hypothesized that inhibition of HDAC3 may contribute to the neuronal survival elicited by PC. To address this notion, PC and transient middle cerebral artery occlusion (MCAO) were conducted in Sprague-Dawley rats. Additionally, primary cultured cortical neurons were used to identify the modulators and effectors of HDAC3 involved in PC. We found that nuclear localization of HDAC3 was significantly reduced following PC in vivo and in vitro. Treatment with the HDAC3-specific inhibitor, RGFP966, mimicked the neuroprotective effects of PC 24 h and 7 days after MCAO, causing a reduced infarct volume and less Fluoro-Jade C staining. Improved functional outcomes were observed in the neurological score and rotarod test. We further showed that attenuated recruitment of HDAC3 to promoter regions following PC potentiates transcriptional initiation of genes including Hspa1a, Bcl2l1, and Prdx2, which may underlie the mechanism of protection. In addition, PC-activated calpains were implicated in the cleavage of HDAC3. Pretreatment with calpeptin blockaded the attenuated nuclear distribution of HDAC3 and the protective effect of PC in vivo. Collectively, these results demonstrate that the inhibition of HDAC3 preconditions the brain against ischemic insults, indicating a new approach to evoke endogenous protection against stroke. PMID:27965534

  12. Inhibition of Histone Deacetylase 3 (HDAC3 Mediates Ischemic Preconditioning and Protects Cortical Neurons against Ischemia in Rats

    Directory of Open Access Journals (Sweden)

    Xiaoyu Yang

    2016-11-01

    Full Text Available Brain ischemic preconditioning (PC provides vital insights into the endogenous protection against stroke. Genomic and epigenetic responses to PC condition the brain into a state of ischemic tolerance. Notably, PC induces the elevation of histone acetylation, consistent with evidence that histone deacetylase (HDAC inhibitors protect the brain from ischemic injury. However, less is known about the specific roles of HDACs in this process. HDAC3 has been implicated in several neurodegenerative conditions. Deletion of HDAC3 confers protection against neurotoxicity and neuronal injury. Here, we hypothesized that inhibition of HDAC3 may contribute to the neuronal survival elicited by PC. To address this notion, PC and transient middle cerebral artery occlusion (MCAO were conducted in Sprague-Dawley rats. Additionally, primary cultured cortical neurons were used to identify the modulators and effectors of HDAC3 involved in PC. We found that nuclear localization of HDAC3 was significantly reduced following PC in vivo and in vitro. Treatment with the HDAC3-specific inhibitor, RGFP966, mimicked the neuroprotective effects of PC 24 h and 7 d after MCAO, causing a reduced infarct volume and less Fluoro-Jade C staining. Improved functional outcomes were observed in the neurological score and rotarod test. We further showed that attenuated recruitment of HDAC3 to promoter regions following PC potentiates transcriptional initiation of genes including Hspa1a, Bcl2l1, and Prdx2, which may underlie the mechanism of protection. In addition, PC-activated calpains were implicated in the cleavage of HDAC3. Pretreatment with calpeptin blockaded the attenuated nuclear distribution of HDAC3 and the protective effect of PC in vivo. Collectively, these results demonstrate that the inhibition of HDAC3 preconditions the brain against ischemic insults, indicating a new approach to evoke endogenous protection against stroke.

  13. Dynamic mislocalizations of nuclear pore complex proteins after focal cerebral ischemia in rat.

    Science.gov (United States)

    Li, Qian; Ohta, Yasuyuki; Yamashita, Toru; Shang, Jingwei; Deguchi, Kentaro; Feng, Tian; Sato, Kota; Hishikawa, Nozomi; Nakano, Yumiko; Abe, Koji

    2017-09-01

    Nuclear pore complexes (NPCs) play an important role in coordinating the transport of proteins and nucleic acids between the nucleus and cytoplasm, and are therefore essential for maintaining normal cellular function and liability. In the present study, we investigated the temporal immunohistochemical distribution of five representative components of NPCs-Ran GTPase-activating protein 1 (RanGap1), glycoprotein-210 (Gp210), nucleoporin 205 (Nup205), nucleoporin 107 (Nup107), and nucleoporin 50 (Nup50)-after 90 min of transient middle cerebral artery occlusion (tMCAO) up to 28 days after the reperfusion in rat brains. Single immunohistochemical analyses showed ring-like stainings along the periphery of the nucleus in sham control brains. After tMCAO, Gp210 and Nup107 immunoreactivity continuously increased from 1 day, and RanGap1, Nup205, and Nup50 increased from 2 days until 28 days, which also displayed progressive precipitations within the nucleus in the peri-ischemic area, while the ischemic core showed scarce expression with collapsed structure. Double immunofluorescent analyses revealed nuclear retention and apparent colocalization of RanGap1 with Nup205, Gp210 with Nup205, and partial colocalization of Nup205 with Nup107; most of the ischemic changes above were similar to those observed in patients with C9orf72-genetic amyotrophic lateral sclerosis. Taken together, these observations suggest that the mislocalization of these nucleoporins may be a common pathogenesis of both ischemic and neurodegenerative disease. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  14. Radiation-induced apoptosis in developing fetal rat cerebral cortex

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Woong Ki; Nam, Taek Keun; Lee, Min Cheol; Ahn, Sung Ja; Song, Ju Young; Park, Seung Jin; Nah, Byung Sik [College of Medicine, Chonnam National Univ., Gwangju (Korea, Republic of)

    2003-09-01

    The study was performed to investigate apoptosis by radiation in the developing fetal rat brain. Fetal brains were irradiated in utero between the 17th and 19th days of fetal life(E17-19) by linear accelerator. A dose of irradiation ranging from 1 Gy to 4 Gy was used to evaluate dose dependency. To test time dependency the rats were irradiated with 2 Gy and then the fetal brain specimens were removed at variable time course; 1, 3, 6, 12 and 24 hours after the onset of irradiation. Immunohistochemical staining using in situ TdT-mediated dUTP nick end labelling (TUNEL) technique was used for apoptotic cells. The cerebral cortex, including three zones of cortical zone (CZ), intermediate zone (IZ), and ventricular zone (VZ), was examined. TUNEL positive cells revealed typical features of apoptotic cells under light microscope in the fetal rat cerebral cortex. Apoptotic cells were not found in the cerebral cortex of non-irradiated fetal rats, but did appear in the entire cerebral cortex after 1 Gy irradiation, and were more extensive at the ventricular and intermediate zones than at the cortical zone. The extent of apoptosis was increased with increasing doses of radiation. Apoptosis reached the peak at 6 hours after the onset of 2 Gy irradiation and persisted until 24 hours. Typical morphologic features of apoptosis by irradiation were observed in the developing fetal rat cerebral cortex. It was more extensive at the ventricular and intermediate zones than at the cortical zone, which suggested that stem cells or early differentiating cells are more radiosensitive than differentiated cells of the cortical zone.

  15. Neuroprotective effects of intravenous transplantation of bone marrow mononuclear cells from 5-fluorouracil pre-treated rats on ischemic stroke.

    Science.gov (United States)

    Li, Y; Mao, W W; Zhang, C G; Wan, L; Jing, C H; Hua, X M; Li, S T; Cheng, J

    2016-03-15

    Our previous findings showed bone marrow mononuclear cells (BMMNCs) from 5- fluorouracil (5-FU) pre-treated rats (named BMRMNCs) had a better therapeutic efficacy in ischemia/reperfusion rats as compared to BMMNCs from untreated rats. This study was undertaken to explore the potential mechanisms underlying the neuroprotective effects of BMRMNCs in middle cerebral artery occlusion (MCAO) rat model. Rats were intravenously pre-treated with 5-FU and BMRMNCs were collected at different time points. The contents of growth factors in the supernatant and CXCR4 expression were detected by ELISA and flow cytometry, respectively. MCAO was introduced to rats, and BMMNCs and BMRMNCs collected at 7 days after 5-FU pre-treatment were independently transplanted via the tail vein 24h later. The neurological function was evaluated before cell transplantation and at 24h, 7d and 14d after cell transplantation. Rats were sacrificed at 14d after cell transplantation, the brains were collected for TTC staining, infarct volume detection, NISSL staining, counting of viable cells in the CA1 region, and observation of transplanted cells. BMRMNCs had elevated expressions of growth factors as well as CXCR4 expression. Our results confirmed the better therapeutic effects of BMRMNCs in MCAO rats, demonstrated by reduction in infarct volume, improvement of neurological function and more viable cells in the hippocampus. In addition, more transplanted cells were found after BMRMNCs transplantation at 7 days and 14 days although there was no marked difference at 14 days. These findings indicate that BMRMNCs transplantation may protect ischemic stroke, at least partially, via increasing the secretion of growth factors and migration to the injured site.

  16. Therapeutic time window of flurbiprofen axetil's neuroprotective effect in a rat model of transient focal cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Background The neuroprotective effect of the cyclooxygenase (COX) inhibitor has been demonstrated in acute and chronic neurodegenerative processes. But its function under cerebral ischemic conditions is unclear. This study was designed to evaluate the neuroprotective efficacy of emulsified flurbiprofen axetil (FA, COX inhibitor) and its therapeutic time window in a model of transient middle cerebral artery occlusion (MCAO) in rats. Methods Forty-eight male SD rats were randomly assigned into six groups (n=8 in each group); three FA groups, vehicle, sham and ischemia/reperfusion (I/R) groups. Three doses of FA (5, 10 or 20 mg/kg, intravenous infusion) were administered just after cerebral ischemia/reperfusion (I/R). The degree of neurological outcome was measured by the neurologic deficit score (NDS) at 24, 48 and 72 hours after I/R. Mean brain infarct volume percentage (MBIVP) was determined with 2,3,5-triphenyltetrazolium chloride (TTC) staining at 72 hours after I/R. In three other groups (n=8 in each group), the selected dosage of 10 mg/kg was administrated intravenously at 6, 12 and 24 hours after I/R. Results The three different doses of FA improved NDS at 24, 48 and 72 hours after I/R and significantly reduced MBIVP. However, the degree of MBIVP in the FA 20 mg/kg group differed from that in FA 10 mg/kg group. Of interest is the finding that the neuroprotective effect conferred by 10 mg/kg of FA was also observed when treatment was delayed until 12-24 hours after ischemia reperfusion. Conclusion COX inhibitor FA is a promising therapeutic strategy for cerebral ischemia and its therapeutic time window could last for 12--24 hours after cerebral ischemia reperfusion, which would help in lessening the initial ischemic brain damage.

  17. 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.

  18. Neuroprotective effects of Schisandrin B against transient focal cerebral ischemia in Sprague-Dawley rats.

    Science.gov (United States)

    Lee, Tae Hwa; Jung, Chang Hwa; Lee, Dae-Hee

    2012-12-01

    Fruits of Schisandra have been traditionally used in East Asia for the treatment of dyspnea, cough, dysentery, insomnia, tonic-clonic seizures, and amnesia. Schisandrin B, a dibenzocyclooctadiene derivative isolated from Fructus Schisandrae, has been shown to produce antioxidant effect on rodent liver and heart. In the present study, we investigated the neuroprotective effects of Schisandrin B, a constituent drug of the fruit of Schisandra, against focal cerebral ischemia in rats. Schisandrin B (10, 30 mg/kg, i.p.) was twice administered 30 min before the onset of ischemia and 2h after reperfusion. Schisandrin B 10 and 30 mg/kg treated groups showed infarct volumes reduced by 25.7% and 53.4%, respectively, 2h after occlusion. Also, Schisandrin B treated animal treatment abrogated protein expression of TNF-α and IL-1β and degradation of MMP-2 and MMP-9 in ischemic hemispheres. These results suggest that Schisandrin B treatment provides a neuroprotective effect to rats after transient focal cerebral ischemia by inhibiting inflammation and by protecting against metalloproteinase degradation.

  19. QUANTITATIVE CHANGES IN REGIONAL CEREBRAL BLOOD FLOW INDUCED BY COLD, HEAT AND ISCHEMIC PAIN: A CONTINUOUS ARTERIAL SPIN LABELING STUDY

    Science.gov (United States)

    Frölich, Michael A.; Deshpande, Hrishikesh; Ness, Timothy; Deutsch, Georg

    2012-01-01

    Background The development of arterial spin labeling methods, has allowed measuring regional cerebral blood flow (rCBF) quantitatively and to show the pattern of cerebral activity associated with any state such as a sustained pain state or changes due to a neurotropic drug. Methods We studied the differential effects of three pain conditions in ten healthy subjects on a 3T scanner during resting baseline, heat, cold and ischemic pain using continuous arterial spin labeling. Results Cold pain showed the greatest absolute rCBF increases in left anterior cingulate cortex, left amygdala, left angular gyrus, and Brodmann Area 6, and a significant rCBF decrease in the cerebellum. Changes in rCBF were characteristic of the type of pain condition: cold and heat pain showed increases, while the ischemic condition showed a reduction in mean absolute gray matter flow compared to rest. An association of subjects’ pain tolerance and cerebral blood flow was noted. Conclusions The observation that quantitative rCBF changes are characteristic of the pain task employed and that there is a consistent rCBF change in Brodman area 6, an area responsible for the integration of a motor response to pain, should provide extremely useful information in the quest to develop an imaging biomarker of pain. Conceivably, response in BA6 may serve as an objective measure of analgesic efficacy. PMID:22913924

  20. Proteomics analysis of cerebral cortex in Wistar rats

    Institute of Scientific and Technical Information of China (English)

    Xiaofeng ZHAO; Jingrong WEN; Shu WANG; Xuemin SHI

    2008-01-01

    To analyze the protein expression pattern of the cerebral cortex in Wistar rats using the proteomics approach, proteins were separated by two-dimensional gel electrophoresis, stained with Coomassie brilliant blue and digested with trypsin. Then, we analyzed the peptide section using a matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) and identified the protein by indexing special database (SwissProt) according to the finger printing of the peptide quality. Eighty-four protein spots were identified, includ-ing metabolic enzymes, skeleton proteins, heat shock pro-teins, antioxidant proteins, signaling proteins, proteasome related proteins, neuron and glial specific proteins and serum associated proteins. The result of this study enriches the database of the proteome in the cerebral cortex of rats and lays a foundation for further research of neurological disorders in rat models.

  1. Induction of interleukin-1β mRNA after focal cerebral ischaemia in the rat

    NARCIS (Netherlands)

    Buttini, M.; Sauter, A.; Boddeke, H.W.G.M.

    1994-01-01

    The expression of interleukin-1β (IL-1β) mRNA in the brain in response to cerebral ischaemia in rats was examined using in situ hybridization histochemistry. Focal cerebral ischaemia was induced in spontaneously hypertensive rats by permanent occlusion of the left middle cerebral artery (MCAO). Wher

  2. INDUCTION OF INTERLEUKIN-1-BETA MESSENGER-RNA AFTER FOCAL CEREBRAL-ISCHEMIA IN THE RAT

    NARCIS (Netherlands)

    BUTTINI, M; SAUTER, A; BODDEKE, HWGM

    1994-01-01

    The expression of interleukin-1beta (IL-1beta) mRNA in the brain in response to cerebral ischaemia in rats was examined using in situ hybridization histochemistry. Focal cerebral ischaemia was induced in spontaneously hypertensive rats by permanent occlusion of the left middle cerebral artery (MCAO)

  3. Induction of interleukin-1β mRNA after focal cerebral ischaemia in the rat

    NARCIS (Netherlands)

    Buttini, M.; Sauter, A.; Boddeke, H.W.G.M.

    1994-01-01

    The expression of interleukin-1β (IL-1β) mRNA in the brain in response to cerebral ischaemia in rats was examined using in situ hybridization histochemistry. Focal cerebral ischaemia was induced in spontaneously hypertensive rats by permanent occlusion of the left middle cerebral artery (MCAO). Wher

  4. Contraceptives and cerebral thrombosis: a five-year national case-control study

    DEFF Research Database (Denmark)

    Lidegaard, Øjvind; Kreiner, Svend

    2002-01-01

    Oral contraceptives; Cerebral thrombosis; Thrombotic stroke; Transitory cerebral ischemic attack; Thrombosis......Oral contraceptives; Cerebral thrombosis; Thrombotic stroke; Transitory cerebral ischemic attack; Thrombosis...

  5. Improving effect of Ginkgolide B on mitochondrial respiration of ischemic neuron after cerebral thrombosis in tree shrews

    Institute of Scientific and Technical Information of China (English)

    LI Shu-qing; ZHANG Ying; YANG Li-jun

    2007-01-01

    Background It has been known that platelet activating factor receptors (PAFR) may mediate many acute pathological responses and that PAFR antagonist Ginkgolide B (GB) possesses multiple effects, but the actions of GB on PAFR affinity and mitochondrial respiration in the ischemic neuron were unclear until now. This study explored the possible effects of GB on PAFR and the mitochondrial respiration of the neuron in the ischemic microenvironment.Methods Thrombotic cerebral ischemia in tree shrews was induced by a photochemical reaction; changes in the regional cerebral blood flow (rCBF, using 99mTc tracer technique ), the brain water content (specific gravimetric method), PAFR (3H-labelled PAF assay), the respiratory control rate (RCR), the phosphorus-oxygen (P/O) ratio of mitochondrial respiration (Clark oxygen electrode), mitochondrial permeability transition (MPT) pore, and the mitochondrial ultrastructure in the ischemic neurons were also observed. Data were compared between the two groups (the ischemia group vs the sham group, and the ischemia group vs the GB group).Results There were high affinity and low affinity sites for PAFR on the tree threws' brain cell membranes. The varying-affinity PAFR binding sites, the respiration state Ⅲ, the state Ⅳ, RCR, the P/O ratio of the mitochondria, and the rCBF all decreased markedly (respectively, P<0.01 and P<0.05), but the water content increased (P<0.01) in the ischemia group after the application of cerebral thrombosis. In tree shrews treated with GB (5 mg/kg I.v.) 6 hours after photochemical reaction, their PAFR binding sites and respiratory state increased markedly. The rCBF gradually increased and the brain edema ameliorated (P<0.01) at 24h after cerebral ischemia. There were significant differences between the ischemia group and sham group (P<0.01). In GB treated isolated neurons' mitochondria, with or without cerebral ischemia, the energy metabolism of the mitochondria had not been changed

  6. 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

  7. Preconditioning of intravenous parecoxib attenuates focal cerebral ischemia/reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    WANG Na; GUO Qu-lian; YE Zhi; XIA Ping-ping; WANG E; YUAN Ya-jing

    2011-01-01

    Background Several studies suggest that oyclooxygenase-2 (COX-2) contributes to the delayed progression of ischemic brain damage. This study was designed to investigate whether COX-2 inhibition with parecoxib reduces focal cerebral ischemia/reperfusion injury in rats.Methods Ninety male Sprague-Dawley rats were randomly assigned to three groups: the sham group, ischemia/reperfusion (I/R) group and parecoxib group. The parecoxib group received 4 mg/kg of parecoxib intravenously via the vena dorsalis penis 15 minutes before ischemia and again at 12 hours after ischemia. The neurological deficit scores (NDSs) were evaluated at 24 and 72 hours after reperfusion. The rats then were euthanized. Brains were removed and processed for hematoxylin and eosin staining, Nissl staining, and measurements of high mobility group Box 1 protein (HMGB1) and tumor necrosis factor-a (TNF-α) levels. Infarct volume was assessed with 2,3,5-triphenyltetrazolium chloride (TTC) staining.Results The rats in the I/R group had lower NDSs (P <0.05), larger infarct volume (P <0.05), lower HMGB1 levels (P<0.05), and higher TNF-α levels (P<0.05) compared with those in the sham group. Parecoxib administration significantly improved NDSs, reduced infarct volume, and decreased HMGB1 and TNF-α levels (P <0.05).Conclusions Pretreatment with intravenous parecoxib was neuroprotective. Its effects may be associated with the attenuation of inflammatory reaction and the inhibition of inflammatory mediators.

  8. Spinal Cord Blood Flow after Ischemic Preconditioning in a Rat Model of Spinal Cord Ischemia

    Directory of Open Access Journals (Sweden)

    David Zvara

    2004-01-01

    Full Text Available Spinal cord blood flow after ischemic preconditioning is poorly characterized. This study is designed to evaluate spinal cord blood flow patterns in animals after acute ischemic preconditioning. Experiment 1: After a laminectomy and placement of a laser Doppler probe over the lumbar spinal cord to measure spinal cord blood flow, 16 male Sprague-Dawley rats were randomized into two groups: ischemic preconditioning (IPC, n = 8, and control (CTRL, n = 8. Rats in the CTRL and the IPC groups were subjected to 12 min of ischemia directly followed by 60 min of reperfusion. IPC rats received 3 min of IPC and 30 min of reperfusion prior to the 12-min insult period. Experiment 2: After instrumentation, the rats were randomized into three groups: control (CTRL, n = 7, ischemic preconditioning (IPC, n = 7, and time control (TC, n = 4. Rats in the CTRL and the IPC groups were subjected to the same ischemia and reperfusion protocol as above. The TC group was anesthetized for the same time period as the CTRL and the IPC groups, but had no ischemic intervention. Microspheres were injected at baseline and at 15 and 60 min into the final reperfusion. All rats were euthanized and tissue harvested for spinal cord blood flow analysis. In Experiment 1, there was a slight, significant difference in spinal cord blood flow during the ischemic period; however, this difference soon disappeared during reperfusion. In experiment 2, there was no difference in blood flow at any experimental time. The results of these experiments demonstrate that IPC slightly enhances blood flow to the spinal cord during ischemia; however, this effect is not sustained during the reperfusion period.

  9. Response of the sensorimotor cortex of cerebral palsy rats receiving transplantation of vascular endothelial growth factor 165-transfected neural stem cells

    Institute of Scientific and Technical Information of China (English)

    Jielu Tan; Xiangrong Zheng; Shanshan Zhang; Yujia Yang; Xia Wang; Xiaohe Yu; Le Zhong

    2014-01-01

    Neural stem cells are characterized by the ability to differentiate and stably express exogenous ge-nes. Vascular endothelial growth factor plays a role in protecting local blood vessels and neurons of newborn rats with hypoxic-ischemic encephalopathy. Transplantation of vascular endothelial growth factor-transfected neural stem cells may be neuroprotective in rats with cerebral palsy. In this study, 7-day-old Sprague-Dawley rats were divided into ifve groups: (1) sham operation (control), (2) cerebral palsy model alone or with (3) phosphate-buffered saline, (4) vascular en-dothelial growth factor 165 + neural stem cells, or (5) neural stem cells alone. hTe cerebral palsy model was established by ligating the letf common carotid artery followed by exposure to hypox-ia. Phosphate-buffered saline, vascular endothelial growth factor + neural stem cells, and neural stem cells alone were administered into the sensorimotor cortex using the stereotaxic instrument and microsyringe. Atfer transplantation, the radial-arm water maze test and holding test were performed. Immunohistochemistry for vascular endothelial growth factor and histology using hematoxylin-eosin were performed on cerebral cortex. Results revealed that the number of vas-cular endothelial growth factor-positive cells in cerebral palsy rats transplanted with vascular endothelial growth factor-transfected neural stem cells was increased, the time for ifnding water and the ifnding repetitions were reduced, the holding time was prolonged, and the degree of cell degeneration or necrosis was reduced. hTese ifndings indicate that the transplantation of vascu-lar endothelial growth factor-transfected neural stem cells alleviates brain damage and cognitive deifcits, and is neuroprotective in neonatal rats with hypoxia ischemic-mediated cerebral palsy.

  10. Response of the sensorimotor cortex of cerebral palsy rats receiving transplantation of vascular endothelial growth factor 165-transfected neural stem cells.

    Science.gov (United States)

    Tan, Jielu; Zheng, Xiangrong; Zhang, Shanshan; Yang, Yujia; Wang, Xia; Yu, Xiaohe; Zhong, Le

    2014-10-01

    Neural stem cells are characterized by the ability to differentiate and stably express exogenous ge-nes. Vascular endothelial growth factor plays a role in protecting local blood vessels and neurons of newborn rats with hypoxic-ischemic encephalopathy. Transplantation of vascular endothelial growth factor-transfected neural stem cells may be neuroprotective in rats with cerebral palsy. In this study, 7-day-old Sprague-Dawley rats were divided into five groups: (1) sham operation (control), (2) cerebral palsy model alone or with (3) phosphate-buffered saline, (4) vascular endothelial growth factor 165 + neural stem cells, or (5) neural stem cells alone. The cerebral palsy model was established by ligating the left common carotid artery followed by exposure to hypoxia. Phosphate-buffered saline, vascular endothelial growth factor + neural stem cells, and neural stem cells alone were administered into the sensorimotor cortex using the stereotaxic instrument and microsyringe. After transplantation, the radial-arm water maze test and holding test were performed. Immunohistochemistry for vascular endothelial growth factor and histology using hematoxylin-eosin were performed on cerebral cortex. Results revealed that the number of vascular endothelial growth factor-positive cells in cerebral palsy rats transplanted with vascular endothelial growth factor-transfected neural stem cells was increased, the time for finding water and the finding repetitions were reduced, the holding time was prolonged, and the degree of cell degeneration or necrosis was reduced. These findings indicate that the transplantation of vascular endothelial growth factor-transfected neural stem cells alleviates brain damage and cognitive deficits, and is neuroprotective in neonatal rats with hypoxia ischemic-mediated cerebral palsy.

  11. 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

  12. Effects of anabolic steroid nandrolone decanoate on ischemic preconditioning in isolated heart of sedentary rats

    Directory of Open Access Journals (Sweden)

    Zahra Akbari

    2014-11-01

    Full Text Available Background: Previous studies have shown that use of supraphysiologocal doses of anabolic adrogenic steroids (AAS associated with detrimental cardiovascular effects including ventricular hypertrophy, increased susceptibility to ischaemia/reperfusion injury, impairment of exercise-induced cardioprotection and sudden cardiac death. The aim of the present study was to evaluate the impact of 8 weeks treatment of AAS nandrolone decanoate (10 mg/kg/week, on ischemic preconditioning (IPC phenomena in isolated hearts of sedentary rats. Materials and Methods: Three groups of animals were studied in the present study. Control ischemia/reperfusion injury group (IR, 2- Ischemic preconditioned group before main test ischemia and reperfusion (IPC+IR, and 3- Nandrolone treated ischemic preconditioned group before main test ischemia and reperfusion (Nan+IPC+IR. After two months of nandrolone and/or its solvent, the isolated Langendorff perfused rat hearts were subjected to 30 min of ischemia followed by 120 min reperfusion. The IPC was induced by three cycles of 3-min occlusion and 3-min reperfusion of the left anterior descending coronary artery (LAD before main test ischemia. Heart rate, left ventricular developed pressure (LVDP, rate pressure product (RPP, Max dp/dt, Min dp/dt and coronary flow were recorded during experiment. Infarction size was measured after 120 min reperfusion by TTC staining. Results: Eight weeks’ nandrolone treatment decreased body weight and increased cardiac to body weight ratio in treated rats. Nandrolone increased pre-ischemic base line cardiac function parameters in the rat hearts. Cardiac function recovery parameters in different time points during reperfusion were also greater in nandrolone treated rats compared to their respective controls. IPC decreased infarct size in the rats (P<0.05. Nandrolone could not significantly change the infarct size lowering effect of IPC in the rat heart. Conclusion: The present study revealed

  13. 丹酚酸 A 通过调节 Wnt/糖原合酶激酶3β/β-连环蛋白通路保护缺血性脑损伤大鼠%Salvianolic acid A protects rats against cerebral ischemic injury by regulation Wnt/glycogen synthase-kinase-3β/β-catenin signaling pathw ay

    Institute of Scientific and Technical Information of China (English)

    王正远; 韩江全

    2016-01-01

    性细胞数量分别为(26.722±26.722)个/HP、(16.556±1.854)个/HP 和(21.333±1.940)个/HP,3组间亦存在显著性差异( F =33.385,P <0.01),而且 SAA 组显著多于脑缺血组(P <0.01)。蛋白质印迹分析显示,假手术组、脑缺血组和 SAA 组 Wnt3a 表达水平分别为1.000±0.190、0.800±0.185和1.198±0.262,3组间存在显著性差异(F =9.621,P <0.001),而且 SAA 组显著高于脑缺血组(P <0.01);假手术组、脑缺血组和SAA 组 p-GSK-3β表达水平分别为0.650±0.150、1.290±0.250和1.190±0.250,3组间亦存在显著性差异(F =19.668,P <0.001),而且 SAA 组显著高于脑缺血组(P <0.01);假手术组、脑缺血组和SAA 组β-连环蛋白表达水平分别为1.200±0.210、0.500±0.120和1.100±0.220,3组间存在显著性差异(F =33.385,P <0.001)(P <0.01),而且 SAA 组显著高于脑缺血组(P <0.01)。结论 SAA 对缺血脑损伤大鼠具有一定的保护作用,其机制可能与上调 Wnt3a 和β-连环蛋白表达以及下调 p-GSK-3β表达有关。%Objective To investigate the protective effect of salvianolic acid A (SAA) on permanent focal cerebral ischemia in rats and its possible mechanisms. Methods Fifty-four adult male Sprague-Daw ley rats w ere randomly divided into a sham operation group, a cerebral ischemia group, and a SAA group ( n =18 in each group). A model of permanent middle cerebral artery occlusion w as induced by the intraluminal suture method.At 0 h and 6 h after modeling, the rats of the SAA groups w ere intraperitonealy injected SAA (3 mg/kg). The other groups w ere injected equal volume of saline. At 24 h after modeling, the neurological deficit scores w ere performed. 2,3,5-Triphenyl tetrazolium chloride (TTC) staining w as used to detect cerebral infarction volume. TUNEL staining w as used to detect cel apoptosis. Both immunohistochemical staining and Western blotting w ere used to detect the expressions of Wnt3a,

  14. Severe cerebral white matter lesions in ischemic stroke patients are associated with less time spent at home and early institutionalization.

    Science.gov (United States)

    Sibolt, Gerli; Curtze, Sami; Melkas, Susanna; Pohjasvaara, Tarja; Kaste, Markku; Karhunen, Pekka J; Oksala, Niku K J; Erkinjuntti, Timo

    2015-12-01

    Cerebral white matter lesions are one imaging surrogate for cerebral small vessel disease. These white matter lesions are associated with increased morbidity and mortality in both the general population and ischemic stroke patients. To investigate whether severe white matter lesions in a cohort of ischemic stroke patients are associated with fewer days spent at home and earlier permanent institutionalization. We included 391 consecutive patients aged 55-85 years with ischemic stroke admitted to the Helsinki University Central Hospital (the Stroke Aging Memory cohort) with a 21-year follow-up. Hospitalization and nursing home admissions were reviewed from national registers.white matter lesions were rated using magnetic resonance imaging performed three-months poststroke, dichotomized as none-to-moderate and severe. Kaplan-Meier plots log-rank and binary logistic regression (odds ratio) and Cox multivariable proportional hazards model were used to study the association of white matter lesions with days spent at home and the time of permanent institutionalization. Hazards and odds ratio with their 95% confidence intervals are reported. Severe white matter lesions were associated with fewer days spent at home, and more frequent, and earlier permanent institutionalization (1487 vs. 2354 days; log-rank P lesions were associated with fewer days spent at home (odds ratio 1·62; confidence interval 1·16-2·25), permanent institutionalization within five-years (odds ratio 2·29; confidence interval 1·23-4·29), and increased hazards ratio of permanent institutionalization during 21 years of follow-up (1·64; confidence interval 1·119-2·26). After ischemic stroke, patients with severe white matter lesions spend fewer days at home and become permanently institutionalized earlier, especially within the first five-years. © 2015 World Stroke Organization.

  15. Exacerbation of ischemic brain injury in hypercholesterolemic mice is associated with pronounced changes in peripheral and cerebral immune responses.

    Science.gov (United States)

    Herz, Josephine; Hagen, Sabine I; Bergmüller, Eileen; Sabellek, Pascal; Göthert, Joachim R; Buer, Jan; Hansen, Wiebke; Hermann, Dirk M; Doeppner, Thorsten R

    2014-02-01

    Inflammation contributes to ischemic brain injury. However, translation of experimental findings from animal models into clinical trials is still ineffective, since the majority of human stroke studies mainly focus on acute neuroprotection, thereby neglecting inflammatory mechanisms and inflammation-associated co-morbidity factors such as hypercholesterolemia. Therefore, both wildtype and ApoE(-/-) mice that exhibit increased serum plasma cholesterol levels fed with normal or high cholesterol diet were exposed to transient middle cerebral artery occlusion. Analysis of peripheral immune responses revealed an ischemia-induced acute leukocytosis in the blood, which was accompanied by enhanced myeloid cell and specifically granulocyte cell counts in the spleen and blood of ApoE(-/-) mice fed with Western diet. These cellular immune changes were further associated with increased levels of pro-inflammatory cytokines like IL-6 and TNF-α. Moreover, endogenous stroke-induced endothelial activation as well as CXCL-1 and CXCL-2 expression were increased, thus resulting in accelerated leukocyte, particularly granulocyte accumulation, and enhanced ischemic tissue damage. The latter was revealed by larger infarct volumes and increased local DNA fragmentation in ischemic brains of ApoE(-/-) mice on Western diet. These effects were not observed in wildtype mice on normal or Western diet and in ApoE(-/-) mice on normal diet. Our data demonstrate that the combination of both ApoE knockout and a high cholesterol diet leads to increased ischemia-induced peripheral and cerebral immune responses, which go along with enhanced cerebral tissue injury. Thus, clinically predisposing conditions related to peripheral inflammation such as hypercholesterolemia should be included in up-coming preclinical stroke research. © 2013.

  16. Histologic assessment of neurons in rat models of cerebral ischemia.

    Science.gov (United States)

    Eke, A; Conger, K A; Anderson, M; Garcia, J H

    1990-02-01

    We describe a method for typing neurons into four progressive stages of ischemic deterioration based on visual characterization of the nucleus in terms of its optical contrast, delineation along the nuclear-cytoplasmic interface, and its shape. Difficulty in assessing nuclear shape required the introduction of an angularity comparator chart to improve the investigator's accuracy. Three investigators typed neurons obtained from normal, ischemic, and ischemic-reperfused rat brains. Accuracy and reproducibility of the investigators' typing decisions with and without the angularity comparator charts were evaluated. The accuracy of subjective shape assessment was compared with objective digitizer measurements of the same. The angularity comparator charts reduced subjective shape classification error by two thirds, and group error (overall performance expressed by the coefficient of variance) decreased from 15.9% to 4.7% for Type I (normal cells), from 33.9% to 17.3% for Type II (cells with angular nuclei), from 15.5% to 14.1% for Type III (cells with smeared nuclei), and from 3.2% to 5.5% for Type IV (dead cells). Thus, Type I and IV neurons can be assessed at a higher reproducibility than the intermediate Types II and III. Our typing method can also be used to evaluate the effect of treatment regimes on ischemic neuronal damage.

  17. 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...

  18. Quantification of infarct size on focal cerebral ischemia model of rats using a simple and economical method.

    Science.gov (United States)

    Yang, Y; Shuaib, A; Li, Q

    1998-10-01

    Quantification of infarct size is a very useful index to assess models of focal cerebral ischemia and effects of new therapies. Currently-used image analysis systems to carry out this task usually involve dedicated and expensive equipment. We present a low-cost and simple method to perform the image acquisition and analysis. Twelve Wistar rats were subject to focal cerebral ischemia and scarified 24 h after the insult. 2,3,5-triphenyl tetrazolium chloride (TTC) stain was used as a conventional method to differentiate ischemic damage from healthy brain tissue. Digital images were captured from the stained coronal sections using a flatbed color scanner and analyzed with a commercial image processing software. To evaluate the accuracy and reproducibility of this method, the data obtained with the current procedure was correlated with those from a dedicated standard image analysis system and intra-observor correlation coefficient was estimated. Also the sensitivity of this method in quantification of infarct volume was tested in two different experimental settings. There was close correlation in the outcome of infarct size measurement between the current method and the standard system (r = 0.93, p < 0.001). A high agreement of measurement of the percentage of infarct volume between two different examiners with the same source of samples (r = 0.98, p < 0.001). We demonstrated that this method was sensitive in detection of difference of infarct sizes when placebo-treated animals (n = 6) were compared to the group treated with a neuroprotective agent (n = 6). Our data demonstrated that ischemic lesion of focal cerebral ischemia in rat can be accurately and reproducibly quantified using this method. The low-cost and simplicity of this method may facilitate the application in determination of ischemic damage.

  19. Neuroprotective effect of sodium ferulate on transient focal cerebral ischemia by weakening activation of postsynaptic density-95 in rats

    Institute of Scientific and Technical Information of China (English)

    WANG Qiang; CHEN Shao-yang; XIONG Li-ze; JIN Wei-lin; YANG Jing

    2005-01-01

    Objective: To investigate the effects of sodium ferulate (SF), an intravenous drug made from traditional Chinese herbs, on activation of postsynaptic density-95 (PSD-95) and neuroprotection after transient cerebral artery occlusion in rats. Methods: Forty-six male Sprague-Dawley rats were randomized into 2 groups (n=23 in each group): the control group and the SF group. After anesthesia, the middle cerebral artery occlusion (MCAO) was conducted with the intraluminal filament technique. The neurological deficit was assessed with the method devised by Bederson et al.8 The 2, 3, 4-triphenyltetrazolium chloride staining was used to assess the infarct volume. We adopted a modified six-point scale to conduct neurobehavioral evaluation. Immediately the activation of postsynaptic density-95 (PSD-95) was studied with Western blot analysis system in the cortex and striatum of rat brain. Results: The neurologic deficit score of the SF group decreased substantially compared with that of the control group (P<0.05). The infarct volume of the control group (168.1 mm3 ± 42.2 mm3) was significantly larger than that of the SF group (61.5 mm3 ± 28.7 mm3) at 24 hours after reperfusion (P<0.01). And the rats showed some neurological deficit. The activity of PSD-95 in the SF group at most timepoints was less than that in the control group. No upregulation of PSD-95 protein could be detected in the contralateral cortex.Conclusions: Sodium ferulate can induce a neuroprotective effect against the transient focal cerebral ischemic injury and weaken the activation of PSD-95 in ischemic area after MCAO.

  20. Propofol protects against focal cerebral ischemia via inhibition of microglia-mediated proinflammatory cytokines in a rat model of experimental stroke.

    Directory of Open Access Journals (Sweden)

    Rong Zhou

    Full Text Available Ischemic stroke induces microglial activation and release of proinflammatory cytokines, contributing to the expansion of brain injury and poor clinical outcome. Propofol has been shown to ameliorate neuronal injury in a number of experimental studies, but the precise mechanisms involved in its neuroprotective effects remain unclear. We tested the hypothesis that propofol confers neuroprotection against focal ischemia by inhibiting microglia-mediated inflammatory response in a rat model of ischemic stroke. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO for 2 h followed by 24 h of reperfusion. Propofol (50 mg/kg/h or vehicle was infused intravenously at the onset of reperfusion for 30 minutes. In vehicle-treated rats, MCAO resulted in significant cerebral infarction, higher neurological deficit scores and decreased time on the rotarod compared with sham-operated rats. Propofol treatment reduced infarct volume and improved the neurological functions. In addition, molecular studies demonstrated that mRNA expression of microglial marker Cd68 and Emr1 was significantly increased, and mRNA and protein expressions of proinflammatory cytokines tumor necrosis factor-α, interleukin-1β and interleukin-6 were augmented in the peri-infarct cortical regions of vehicle-treated rats 24 h after MCAO. Immunohistochemical study revealed that number of total microglia and proportion of activated microglia in the peri-infarct cortical regions were markedly elevated. All of these findings were ameliorated in propofol-treated rats. Furthermore, vehicle-treated rats had higher plasma levels of interleukin-6 and C-reactive protein 24 h after MCAO, which were decreased after treatment with propofol. These results suggest that propofol protects against focal cerebral ischemia via inhibition of microglia-mediated proinflammatory cytokines. Propofol may be a promising therapeutic agent for the treatment of ischemic stroke and other

  1. EFFECT OF ACUPUNCTURE ON EXPERIMENTAL CEREBRAL INFARCTION IN RATS

    Institute of Scientific and Technical Information of China (English)

    YUNG Qing; MA Ruiling; JIN Rui

    2002-01-01

    Objectives: To explore the effect of acupuncture on cerebral infarction in rats and to try providing some experimental parameters for clinical practice. Methods: 27 healthy Wistar rats were randomly divided into pseudo-operation (n = 10), model (n = 8) and acupuncture (n = 9) groups. Neuro-functional defect scoring, apoptosis of single brain slice and the number of bcl-2 immuno-reaction (IR)-positive neurons in CA1 area of the hippocampus were used as the indexes to investigate the possible mechanisms of acupuncture of "Nie San Zhen" (needling three acupoints in the temporal region) and "Si Shen Zhen" (needling four acupoints in the occiput region) in treating rats with cerebral infarction. Results: There existed significant differences between acupuncture group and model group in improving neurologic functional activities, inhibiting apoptosis of the brain cells and increasing bcl-2 IR-positive neurons in the hippocampal CA1 area (P < 0.01 ). Conclusion: Acupuncture therapy can improve cerebral infarction in the rat by suppressing apoptosis and up-regulation of the bcl-2 IR-positive neuron expression.

  2. EFFECT OF ACUPUNCTURE ON EXPERIMENTAL CEREBRAL INFARCTION IN RATS

    Institute of Scientific and Technical Information of China (English)

    袁青; 马瑞玲; 等

    2002-01-01

    Objectives:To explore the effect of acupuncture on cerebral infarction in rats and to try providing some experimental parameters for clinical practice.Methods:27 healthy Wistar rats were randomly divided into pseudo-operation (n=10),model (n=8) and acupuncture (n=9) groups.Neuro-functional defect scoring,apoptosis of single brain slice and the number of bcl-2 immuno-reaction (IR)-positive neurons in CA1 area of the hippocampus were used as the indexes to investigate the possible mechanisms of acupuncture of “Nie San Zhen”(needing three acupoints in the temporal region) and “Si Shen Zhen” (needling four acupoints in the occiput region) in treating rats with cerebral infarction.Results:There existed significant differences between acupuncture group and model group in improving neurologic functional activities,inhibiting apoptosis of the brain cells and increasing bcl-2 IR-positive neurons in the hippocampal CA1 area(P<0.01).Conclusion:Acupuncture therapy can improve cerebral infarction in the rat by suppressing apoptosis and up-regulation of the bcl-2 IR-positive neuron expression.

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

    Science.gov (United States)

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

    2013-05-01

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

  4. Hyperbaric oxygen suppresses hypoxic-ischemic brain damage in newborn rats.

    Science.gov (United States)

    Zhu, Min; Lu, Mengru; Li, Qing-Jie; Zhang, Zhuo; Wu, Zheng-Zheng; Li, Jie; Qian, Lai; Xu, Yun; Wang, Zhong-Yuan

    2015-01-01

    The optimal therapeutic time-window and protective mechanism of hyperbaric oxygen in hypoxic-ischemic brain damage remain unclear. This study aimed to determine the neuroprotective effects of hyperbaric oxygen. Following hypoxic-ischemic brain damage modeling in neonatal rats, hyperbaric oxygen was administered at 6, 24, 48, and 72 hours and 1 week after hypoxia, respectively, once daily for 1 week. Fourteen days after hypoxic-ischemic brain damage, cell density and apoptosis rate, number of Fas-L+, caspase-8+, and caspase-3+ neuronal cells, levels of nitric oxide, malondialdehyde, and superoxide dismutase in hippocampus were examined. Morris water maze test was conducted 28 days after insult. Significant improvements were found in cell density, rate of apoptosis, oxidative stress markers, FasL, and caspases in rats treated with hyperbaric oxygen within 72 hours compared to hypoxic-ischemic injury. Similarly, time-dependent behavioral amelioration was observed in pups treated with hyperbaric oxygen. Our findings suggest that hyperbaric oxygen protects against hypoxic-ischemic brain damage by inhibiting oxidative stress and FasL-induced apoptosis, and optimal therapeutic time window is within 72 hours after hypoxic-ischemic brain damage.

  5. Gait Impairment in a Rat Model of Focal Cerebral Ischemia

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    Saara Parkkinen

    2013-01-01

    Full Text Available The availability of proper tests for gait evaluation following cerebral ischemia in rats has been limited. The automated, quantitative CatWalk system, which was initially designed to measure gait in models of spinal cord injury, neuropathic pain, and peripheral nerve injury, is said to be a useful tool for the study of motor impairment in stroke animals. Here we report our experiences of using CatWalk XT with rats subjected to transient middle cerebral artery occlusion (MCAO, during their six-week followup. Large corticostriatal infarct was confirmed by MRI in all MCAO rats, which was associated with severe sensorimotor impairment. In contrast, the gait impairment was at most mild, which is consistent with seemingly normal locomotion of MCAO rats. Many of the gait parameters were affected by body weight, walking speed, and motivation despite the use of a goal box. In addition, MCAO rats showed bilateral compensation, which was developed to stabilize proper locomotion. All of these interferences may confound the data interpretation. Taken together, the translational applicability of CatWalk XT in evaluating motor impairment and treatment efficacy remains to be limited at least in rats with severe corticostriatal infarct and loss of body weight.

  6. The effects of Tanshinone IIA on blood-brain barrier and brain edema after transient middle cerebral artery occlusion in rats.

    Science.gov (United States)

    Tang, Chao; Xue, Hongli; Bai, Changlin; Fu, Rong; Wu, Anhua

    2010-12-01

    Disruption of blood-brain barrier (BBB) and edema formation play a key role in the development of neurological dysfunction after cerebral ischemia. In this study, the effects of Tanshinone IIA (Tan IIA), one of the active ingredients of Salvia miltiorrhiza root, on the BBB and brain edema after transient middle cerebral artery occlusion in rats were examined. Our study demonstrated that Tan IIA reduced brain infarct area, water content in the ischemic hemisphere. Furthermore, Tan IIA significantly decreased BBB permeability to Evans blue, suppressed the expression of intercellular adhesion molecule-1 (ICAM-1), matrix metalloproteinase-9 (MMP-9), inhibited the degradation of tight junction proteins zonula occludens-1 (ZO-1) and Occludin. These results demonstrated that Tan IIA was effective for attenuating the extent of brain edema formation in response to ischemia injury in rats, partly by Tan IIA's protective effect on the BBB. Our results may have implications in the treatment of brain edema in cerebral ischemia.

  7. Changes of Apoptosis in Rats of Acute Ischemic Renal Injury under Treatment of Tetrandrine

    Institute of Scientific and Technical Information of China (English)

    钱玲梅; 王笑云; 冷静

    2002-01-01

    ObjectiveTo elucidate the effect of tetrandrine on acute ischemic renal injury and its relation with apoptosis.MethodsA model for bilateral post-ischemic renal injury in rats was developed by clamping renal pedicles for 45 min.Renal tissular DNA fragmentation analysis and renal tissular HE staining were used.Also quantitative analysis of apoptosis in injured renal tubular epithelium was carried out by using TdT-mediated dUTP nick and labeling (TUNEL).ResultsApoptosis of renal tubular epithelium increased in acute ischemic renal injury.Tetrandrine could remarkably decrease the level of apoptosis in injured renal tubule while protecting renal tissue against the ischemic injuries.ConclusionTetrandrine could adjust the level of apoptosis in renal tubular epithelium and alleviate renal tissular injury.``

  8. Changes of Apoptosis in Rats of Acute Ischemic Renal Injury under Treatment of Tetrandrine

    Institute of Scientific and Technical Information of China (English)

    钱玲梅; 王笑云; 等

    2002-01-01

    Objective To elucidate the effect of tetrandrine on acute ischemic renal injury and its relation with apoptosis.Methods A model for bilateral post-ischemic renal injury in rats was developed by clamping renal pedicles for 45 min.Renal tissular DNA fragmentation analysis and renal tissular HE staining were used.Also quantitative analysis of apoptosis in injured renal tubular epithelium was carried out by using TdT-mediated dUTP nick and labeling(TUNEL).Results Apoptosis of renal tubular epithelium increased in acute ischemic renal injury.Tetrandrine could remarkably decrease the level of apoptosis in injured renal tubule while protecting renal tissue against the ischemic injuries.Conclusion Tetrandrine could adjust the level of apoptosis in renal tubular epithelium and alleviate renal tissular injury.

  9. 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.

  10. 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

  11. Computational identification of conserved transcription factor binding sites upstream of genes induced in rat brain by transient focal ischemic stroke.

    Science.gov (United States)

    Pulliam, John V K; Xu, Zhenfeng; Ford, Gregory D; Liu, Cuimei; Li, Yonggang; Stovall, Kyndra C; Cannon, Virginetta S; Tewolde, Teclemichael; Moreno, Carlos S; Ford, Byron D

    2013-02-07

    Microarray analysis has been used to understand how gene regulation plays a critical role in neuronal injury, survival and repair following ischemic stroke. To identify the transcriptional regulatory elements responsible for ischemia-induced gene expression, we examined gene expression profiles of rat brains following focal ischemia and performed computational analysis of consensus transcription factor binding sites (TFBS) in the genes of the dataset. In this study, rats were sacrificed 24 h after middle cerebral artery occlusion (MCAO) stroke and gene transcription in brain tissues following ischemia/reperfusion was examined using Affymetrix GeneChip technology. The CONserved transcription FACtor binding site (CONFAC) software package was used to identify over-represented TFBS in the upstream promoter regions of ischemia-induced genes compared to control datasets. CONFAC identified 12 TFBS that were statistically over-represented from our dataset of ischemia-induced genes, including three members of the Ets-1 family of transcription factors (TFs). Microarray results showed that mRNA for Ets-1 was increased following tMCAO but not pMCAO. Immunohistochemical analysis of Ets-1 protein in rat brains following MCAO showed that Ets-1 was highly expressed in neurons in the brain of sham control animals. Ets-1 protein expression was virtually abolished in injured neurons of the ischemic brain but was unchanged in peri-infarct brain areas. These data indicate that TFs, including Ets-1, may influence neuronal injury following ischemia. These findings could provide important insights into the mechanisms that lead to brain injury and could provide avenues for the development of novel therapies. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Sequential neuronal and astrocytic changes after transient middle cerebral artery occlusion in the rat.

    Science.gov (United States)

    Chen, H; Chopp, M; Schultz, L; Bodzin, G; Garcia, J H

    1993-09-01

    The temporal evolution and spatial distribution of ischemic cell injury was investigated after transient middle cerebral artery (MCA) occlusion. Male Wistar rats (n = 61) were subjected to 2 h of MCA occlusion induced by advancing a nylon monofilament into the right internal carotid artery. Animals were killed after different durations of reperfusion, ranging from 4 to 166 h (n = 6-11 for each group). Neuronal injury and astrocytic reaction were evaluated using hematoxylin and eosin (H & E) and glial fibrillary acidic protein (GFAP) immunohistochemistry, respectively. Eosinophilic neurons were detected at 4 h of reperfusion in the basal ganglia, and at 10 h of reperfusion in the cortex. Focal brain infarct developed by 46 h of reperfusion, both in the cortex and the basal ganglia, and the volume remained constant between 46 and 166 h of reperfusion. Significant differences in astrocytic reaction were detected between the lesion and the periphery of the lesion at reperfusion times from 46 to 166 h; GFAP staining decreased in the core of the lesion and increased in the peripheral areas. Our data suggest that, after 2 h of MCA occlusion, brain tissue progresses from isolated neuronal injury to infarct with a time course dependent on anatomical site; and astrocytic reactivity, expressed by GFAP staining, reflects the outcome of the ischemic injury.

  13. 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

  14. Acupuncture regulates the glucose metabolism in cerebral functional regions in chronic stage ischemic stroke patients---a PET-CT cerebral functional imaging study

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    Huang Yong

    2012-06-01

    Full Text Available Abstract Background Acupuncture has been applied to aid in the recovery of post-stroke patients, but its mechanism is unclear. This study aims to analyze the relationship between acupuncture and glucose metabolism in cerebral functional regions in post-stroke patients using 18 FDG PET-CT techniques. Forty-three ischemic stroke patients were randomly divided into 5 groups: the Waiguan (TE5 needling group, the TE5 sham needling group, the sham point needling group, the sham point sham needling group and the non-needling group. Cerebral functional images of all patients were then acquired using PET-CT scans and processed by SPM2 software. Results Compared with the non-needling group, sham needling at TE5 and needling/sham needling at the sham point did not activate cerebral areas. However, needling at TE5 resulted in the activation of Brodmann Area (BA 30. Needling/sham needling at TE5 and needling at the sham point did not deactivate any cerebral areas, whereas sham needling at the sham point led to deactivation in BA6. Compared with sham needling at TE5, needling at TE5 activated BA13, 19 and 47 and did not deactivate any areas. Compared with needling at the sham point, needling at TE5 had no associated activation but a deactivating effect on BA9. Conclusion Needling at TE5 had a regulating effect on cerebral functional areas shown by PET-CT, and this may relate to its impact on the recovery of post-stroke patients.

  15. Effects of Neural Stem Cell and Olfactory Ensheathing Cell Co-transplants on Tissue Remodelling After Transient Focal Cerebral Ischemia in the Adult Rat.

    Science.gov (United States)

    Augestad, Ingrid Lovise; Nyman, Axel Karl Gottfrid; Costa, Alex Ignatius; Barnett, Susan Carol; Sandvig, Axel; Håberg, Asta Kristine; Sandvig, Ioanna

    2017-01-24

    Effective transplant-mediated repair of ischemic brain lesions entails extensive tissue remodeling, especially in the ischemic core. Neural stem cells (NSCs) are promising reparative candidates for stroke induced lesions, however, their survival and integration with the host-tissue post-transplantation is poor. In this study, we address this challenge by testing whether co-grafting of NSCs with olfactory ensheathing cells (OECs), a special type of glia with proven neuroprotective, immunomodulatory, and angiogenic effects, can promote graft survival and host tissue remodelling. Transient focal cerebral ischemia was induced in adult rats by a 60-min middle cerebral artery occlusion (MCAo) followed by reperfusion. Ischemic lesions were verified by neurological testing and magnetic resonance imaging. Transplantation into the globus pallidus of NSCs alone or in combination with OECs was performed at two weeks post-MCAo, followed by histological analyses at three weeks post-transplantation. We found evidence of extensive vascular remodelling in the ischemic core as well as evidence of NSC motility away from the graft and into the infarct border in severely lesioned animals co-grafted with OECs. These findings support a possible role of OECs as part of an in situ tissue engineering paradigm for transplant mediated repair of ischemic brain lesions.

  16. Increased Expression of Slit2 and its Robo Receptors During Astroglial Scar Formation After Transient Focal Cerebral Ischemia in Rats.

    Science.gov (United States)

    Jin, Xuyan; Shin, Yoo-Jin; Riew, Tae-Ryong; Choi, Jeong-Heon; Lee, Mun-Yong

    2016-12-01

    Slit2, a secreted glycoprotein, has recently been implicated in the post-ischemic astroglial reaction. The objective of this study was to investigate the temporal changes and cellular localization of Slit2 and its receptors, Robo1, Robo2, and Robo4, in a rat transient focal ischemia model induced by middle cerebral artery occlusion. We used double- and triple-immunolabeling to determine the cell-specific changes in Slit2 and its receptors during a 10-week post-ischemia period. The expression profiles of Slit2 and the Robo receptors shared overlapping expression patterns in sham-operated and ischemic striatum. Constitutive expression of Slit2 and Robo receptors was observed in striatal neurons with weak intensity, whereas in rats reperfused after ischemic insults, these immunoreactivities were increased in reactive astrocytes. Astroglial induction of Slit2 and Robo in the peri-infarct region was distinct on days 7-14 after reperfusion and thereafter increased progressively throughout the 10-week experimental period. Slit2 and Robo were prominently expressed in the perinuclear cytoplasm and main processes of reactive astrocytes forming the astroglial scar. This observation was confirmed by quantification of the mean fluorescence intensity of Slit2 and Robo receptors over reactive astrocytes localized at the edge of the infarct area. However, activated microglia/macrophages in the peri-infarct area were devoid of any specific labeling for Slit2 and Robo. Thus, our data revealed a selective and sustained induction of Slit2 and Robo in astrocytes localized throughout the astroglial scar after ischemic stroke, suggesting that Slit2/Robo signaling participates in glial scar formation and brain remodeling following ischemic injury.

  17. Effect of zinc supplements in the attenuated cardioprotective effect of ischemic preconditioning in hyperlipidemic rat heart.

    Science.gov (United States)

    Kansal, Sunil Kumar; Jyoti, Uma; Sharma, Samridhi; Kaura, Arun; Deshmukh, Rahul; Goyal, Sandeep

    2015-06-01

    Hyperlipidemia is regarded as independent risk factor in the development of ischemic heart disease, and it can increase the myocardial susceptibility to ischemia-/reperfusion (I/R)-induced injury. Hyperlipidemia attenuates the cardioprotective response of ischemic preconditioning (IPC). The present study investigated the effect of zinc supplements in the attenuated cardioprotective effect of ischemic preconditioning in hyperlipidemic rat hearts. Hyperlipidemia was induced in rat by feeding high-fat diet (HFD) for 6 weeks then the serum lipid profile was observed. In experiment, the isolated Langendorff rat heart preparation was subjected to 4 cycles of ischemic preconditioning (IPC), then 30 min of ischemia followed by 120 min of reperfusion. Myocardial infarct size was elaborated morphologically by triphenyltetrazolium chloride (TTC) staining and biochemically by lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) release from coronary effluent and left ventricular collagen content. However, the effect of zinc supplement, i.e., zinc pyrithione (10 μM) perfused during reperfusion for 120 min, significantly abrogated the attenuated cardioprotective effect of ischemic preconditioning in hyperlipidemic rat heart whereas administration of chelator of this zinc ionophore, i.e., N,N,N',N'-tetrakis(2-pyridylmethyl)ethylene diamine (TPEN; 10 μM), perfused during reperfusion 2 min before the perfusion of zinc pyrithione abrogated the cardioprotective effect of zinc supplement during experiment in hyperlipidemic rat heart. Thus, the administration of zinc supplements limits the infarct size, LDH, and CK-MB and enhanced the collagen level which suggests that the attenuated cardioprotective effect of IPC in hyperlipidemic rat is due to zinc loss during reperfusion caused by ischemia/reperfusion.

  18. A correlative study between AQP4 expression and the manifestation of DWI after the acute ischemic brain edema in rats

    Institute of Scientific and Technical Information of China (English)

    鲁宏; 孙善全

    2003-01-01

    Objective To investigate the rule of the aquaporin-4 (AQP4) expression in acute ischemic brain edema, and to study the correlation between AQP4 expression and diffusion-weighted imaging (DWI).Methods Thirty-six Wistar rats were divided into 2 groups randomly, control group (n=12) and operation group (n=24) in which right middle cerebral artery of each animal had been occluded unilaterally (MCAO) at interval times of: 15 minutes, 30 minutes, 1 hours, 3 hours, 6 hours and 24 hours, respectively. The operation process of the control group was the same as the operation group except for the MCAO. All groups were examined using DWI. The apparent diffusion coefficient (ADC), relative density (rd) and relative area (rs) of the biggest hyperintensity signal layer on DWI were measured. After that the animals were sacrificed and perfused with the mixture solution consisting of TTC. The biggest layers of the ischemic cerebral tissues in each rat corresponding to the DWI were stained with TTC and examined with immunochemistry (△S) , in situ hybridization (α) and histology.Results There was no significant change in the control group. In the operation group, a hyperintensity signal was found in the DWI of the right MAC territory at 15 minutes after MCAO. The ADC value decreased quickly within one hour after MCAO, while the AQP4 expression, rd-DWI and rs-DWI increased rapidly during this stage. As time progressed, the ADC value decreased further to (2.1±0.6)×10-4 mm2/s at 3 hours, and then began to increase slowly till 24 hours. But the AQP4 expression (△S and α) and rd as well as the rs continuously increased slowly between 1 hour and 6 hours after MCAO, followed a peak after 6 hours. The AQP4 expression (α) showed a positive relationship with the rs-DWI, they all presented two peaks and a plateau. The corresponding sequential pathologic changes were a gradual increase of intracellular edema (within one hour), then an emergence of vasogenic edema (1-6 hours), and final

  19. Recurrent stroke risk and cerebral microbleed burden in ischemic stroke and TIA

    Science.gov (United States)

    Wilson, Duncan; Charidimou, Andreas; Ambler, Gareth; Fox, Zoe V.; Gregoire, Simone; Rayson, Phillip; Imaizumi, Toshio; Fluri, Felix; Naka, Hiromitsu; Horstmann, Solveig; Veltkamp, Roland; Rothwell, Peter M.; Kwa, Vincent I.H.; Thijs, Vincent; Lee, Yong-Seok; Kim, Young Dae; Huang, Yining; Wong, Ka Sing; Jäger, Hans Rolf

    2016-01-01

    Objective: To determine associations between cerebral microbleed (CMB) burden with recurrent ischemic stroke (IS) and intracerebral hemorrhage (ICH) risk after IS or TIA. Methods: We identified prospective studies of patients with IS or TIA that investigated CMBs and stroke (ICH and IS) risk during ≥3 months follow-up. Authors provided aggregate summary-level data on stroke outcomes, with CMBs categorized according to burden (single, 2–4, and ≥5 CMBs) and distribution. We calculated absolute event rates and pooled risk ratios (RR) using random-effects meta-analysis. Results: We included 5,068 patients from 15 studies. There were 115/1,284 (9.6%) recurrent IS events in patients with CMBs vs 212/3,781 (5.6%) in patients without CMBs (pooled RR 1.8 for CMBs vs no CMBs; 95% confidence interval [CI] 1.4–2.5). There were 49/1,142 (4.3%) ICH events in those with CMBs vs 17/2,912 (0.58%) in those without CMBs (pooled RR 6.3 for CMBs vs no CMBs; 95% CI 3.5–11.4). Increasing CMB burden increased the risk of IS (pooled RR [95% CI] 1.8 [1.0–3.1], 2.4 [1.3–4.4], and 2.7 [1.5–4.9] for 1 CMB, 2–4 CMBs, and ≥5 CMBs, respectively) and ICH (pooled RR [95% CI] 4.6 [1.9–10.7], 5.6 [2.4–13.3], and 14.1 [6.9–29.0] for 1 CMB, 2–4 CMBs, and ≥5 CMBs, respectively). Conclusions: CMBs are associated with increased stroke risk after IS or TIA. With increasing CMB burden (compared to no CMBs), the risk of ICH increases more steeply than that of IS. However, IS absolute event rates remain higher than ICH absolute event rates in all CMB burden categories. PMID:27590288

  20. Recurrent stroke risk and cerebral microbleed burden in ischemic stroke and TIA: A meta-analysis.

    Science.gov (United States)

    Wilson, Duncan; Charidimou, Andreas; Ambler, Gareth; Fox, Zoe V; Gregoire, Simone; Rayson, Phillip; Imaizumi, Toshio; Fluri, Felix; Naka, Hiromitsu; Horstmann, Solveig; Veltkamp, Roland; Rothwell, Peter M; Kwa, Vincent I H; Thijs, Vincent; Lee, Yong-Seok; Kim, Young Dae; Huang, Yining; Wong, Ka Sing; Jäger, Hans Rolf; Werring, David J

    2016-10-04

    To determine associations between cerebral microbleed (CMB) burden with recurrent ischemic stroke (IS) and intracerebral hemorrhage (ICH) risk after IS or TIA. We identified prospective studies of patients with IS or TIA that investigated CMBs and stroke (ICH and IS) risk during ≥3 months follow-up. Authors provided aggregate summary-level data on stroke outcomes, with CMBs categorized according to burden (single, 2-4, and ≥5 CMBs) and distribution. We calculated absolute event rates and pooled risk ratios (RR) using random-effects meta-analysis. We included 5,068 patients from 15 studies. There were 115/1,284 (9.6%) recurrent IS events in patients with CMBs vs 212/3,781 (5.6%) in patients without CMBs (pooled RR 1.8 for CMBs vs no CMBs; 95% confidence interval [CI] 1.4-2.5). There were 49/1,142 (4.3%) ICH events in those with CMBs vs 17/2,912 (0.58%) in those without CMBs (pooled RR 6.3 for CMBs vs no CMBs; 95% CI 3.5-11.4). Increasing CMB burden increased the risk of IS (pooled RR [95% CI] 1.8 [1.0-3.1], 2.4 [1.3-4.4], and 2.7 [1.5-4.9] for 1 CMB, 2-4 CMBs, and ≥5 CMBs, respectively) and ICH (pooled RR [95% CI] 4.6 [1.9-10.7], 5.6 [2.4-13.3], and 14.1 [6.9-29.0] for 1 CMB, 2-4 CMBs, and ≥5 CMBs, respectively). CMBs are associated with increased stroke risk after IS or TIA. With increasing CMB burden (compared to no CMBs), the risk of ICH increases more steeply than that of IS. However, IS absolute event rates remain higher than ICH absolute event rates in all CMB burden categories. © 2016 American Academy of Neurology.

  1. Neuroprotection by Methylene Blue in Cerebral Global Ischemic Injury Induced Blood-Brain Barrier Disruption and Brain Pathology: A Review.

    Science.gov (United States)

    Wiklund, Lars; Sharma, Aruna; Sharma, Hari Shanker

    2016-01-01

    Transient global ischemic cerebral injury is a consequence of cardiac arrest and accounts for approximately 450,000 annual deaths with a mortality of approximately 90%. Serious morbidity follows for many of the survivors and up to 16% of patients achieving restoration of spontaneous circulation develop brain death. Other survivors are left with persistent cognitive impairment such as memory and sensimotor deficits, reducing quality of life and resulting in heavy costs on society. Many studies over the years have been devoted to improving outcome after cardiac arrest and have, to a certain degree succeeded, especially locally in areas where improvement of ambulance organizations have been effective. In spite of this serious problems remain and the chances of cerebral survival need to increase if over-all results, i.e. survival as well as cognitive function, are to improve. Methylene blue, a textile dye synthesized in the late 19th century has also been used in medicine for different purposes. One of its effects is to increase systemic blood pressure, but other effects have been documented, among which are its neuroprotective effects well-noted during the last few years. In this review we have appraised these findings in relation to global ischemic injury.

  2. Splenectomy protects experimental rats from cerebral damage after stroke due to anti-inflammatory effects

    Institute of Scientific and Technical Information of China (English)

    ZHANG Bing-jun; MEN Xue-jiao; LU Zheng-qi; LI Hai-yan; QIU Wei; HU Xue-qiang

    2013-01-01

    Background A recent study demonstrated that the inflammatory response accompanying necrotic brain injury played an important role in stroke.Thus,inhibition of this response may help to stop the expansion of infarcts.It has been also shown that the spleen,a major peripheral immune organ,plays a role in stroke-induced immune responses.This study aimed to establish rat models of middle cerebral artery occlusion (MCAO) and to investigate the effect of splenectomy and possible mechanisms in that rat models.Methods Infarct size in a stroke model was measured with the Nissl body staining method,numbers of inflammatory cells in ischemic regions were detected by immunofluorescence staining,and inflammatory factors were assayed by enzyme-linked immunosorbent assay and real-time polymerase chain reaction (PCR) in brain homogenates and sera.The significance of differences was determined by one-way analysis of variance (ANOVA) followed by the least significant difference post hoc test.Results Infarct size in the brain of rats that underwent splenectomies 2 weeks before permanent MCAO ((34.93±3.23)%) was over 50% smaller than that of rats subjected to the stroke surgery alone ((74.33±2.36)%,P <0.001; (77.30±2.62)%,P <0.001).Lower numbers of T cells,neutrophils,and macrophages in brain tissue and lower levels of pro-inflammatory cytokines,such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α,were observed in rats that underwent splenectomies,compared with the two other groups,but splenectomized rats showed higher levels of the anti-inflammatory factor IL-10 in the brain.Conclusion The mechanism(s) by which splenectomy protects brain from damage induced by stroke may correlate with the decreased numbers of inflammatory cells and changes in inflammatory cytokines.

  3. The Protective Effect of Human Umbilical Cord Blood CD34+ Cells and Estradiol against Focal Cerebral Ischemia in Female Ovariectomized Rat: Cerebral MR Imaging and Immunohistochemical Study.

    Directory of Open Access Journals (Sweden)

    Ching-Chung Liang

    Full Text Available Human umbilical cord blood derived CD34+ stem cells are reported to mediate therapeutic effects in stroke animal models. Estrogen was known to protect against ischemic injury. The present study wished to investigate whether the protective effect of CD34+ cells against ischemic injury can be reinforced with complemental estradiol treatment in female ovariectomized rat and its possible mechanism. Experiment 1 was to determine the best optimal timing of CD34+ cell treatment for the neuroprotective effect after 60-min middle cerebral artery occlusion (MCAO. Experiment 2 was to evaluate the adjuvant effect of 17β-estradiol on CD34+ cell neuroprotection after MCAO. Experiment 1 showed intravenous infusion with CD34+ cells before MCAO (pre-treatment caused less infarction size than those infused after MCAO (post-treatment on 7T magnetic resonance T2-weighted images. Experiment 2 revealed infarction size was most significantly reduced after CD34+ + estradiol pre-treatment. When compared with no treatment group, CD34+ + estradiol pre-treatment showed significantly less ADC reduction at 2 h and 2 d, less CBF reduction at 2 h and less hyperperfusion at 2 d. The immunoreactivity of c-Fos, c-Jun and GFAP was attenuated, and BDNF showed significant recovery from 2 h to 2 d after MCAO, especially after CD34+ + estradiol pre-treatment. The present study suggests pre-treatment with CD34+ cells with complemental estradiol can be most protective against ischemic injury, which may act through stabilization of cerebral hemodynamics and normalization of the expressions of immediate early genes and BDNF.

  4. Effect of propofol on the reactivity of acetylcholinesterase, N-methyl-D-aspartate receptors, and gamma-aminobutyric acid receptors in the hippocampus of aged rats after chronic cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Gang Chen; Jiangbei Cao; Weidong Mi

    2011-01-01

    We induced ischemic brain injury in aging rats to examine the effects of varying doses of propofol on hippocampal activities of acetylcholinesterase, N-methyl-D-aspartate receptors, and γ-aminobutyric acid receptors. Propofol exhibited no obvious impact on acetylcholinesterase activity, but directly activated the γ-aminobutyric acid receptor. The neuroprotective function of propofol on the hippocampus of aging rats following cerebral ischemic injury may be related to altered activities of γ-aminobutyric acid receptors and N-methyl-D-aspartate receptors.

  5. Expression of glutamic acid decarboxylase and identification of GABAergic cells in the ischemic rat dentate gyrus

    DEFF Research Database (Denmark)

    Müller, Georg Johannes; Dogonowski, Anne-Marie; Finsen, Bente

    2006-01-01

    We have investigated the glutamic acid dexcarboxylase (GAD) mRNA and protein isoforms as markers for ischemic loss of GABAergic neurons in the dentate hilus. Stereological counts of these neurons were performed in rats surviving 8 days after 10 min of transient forebrain ischemia, and in control...

  6. Expression of glutamic acid decarboxylase and identification of GABAergic cells in the ischemic rat dentate gyrus

    DEFF Research Database (Denmark)

    Müller, Georg Johannes; Dogonowski, Anne-Marie; Finsen, Bente

    2006-01-01

    We have investigated the glutamic acid dexarboxylase (GAD) mRNA and protein isoforms as markers for ischemic loss of GABAergic neurons in the dentate hilus. Stereological counts of these neurons were performed in rats surviving 8 days after 10 min of transient forebrain ischemia, and in control...

  7. Expression of glutamic acid decarboxylase and identification of GABAergic cells in the ischemic rat dentate gyrus

    DEFF Research Database (Denmark)

    Müller, Georg Johannes; Dogonowski, Anne-Marie; Finsen, Bente;

    2006-01-01

    We have investigated the glutamic acid dexarboxylase (GAD) mRNA and protein isoforms as markers for ischemic loss of GABAergic neurons in the dentate hilus. Stereological counts of these neurons were performed in rats surviving 8 days after 10 min of transient forebrain ischemia, and in control...

  8. 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.

  9. Independent Correlation of Serum Homocysteine with Cerebral Microbleeds in Patients with Acute Ischemic Stroke due to Large-Artery Atherosclerosis.

    Science.gov (United States)

    Wang, Bian-Rong; Ou, Zhou; Jiang, Teng; Zhang, Ying-Dong; Zhao, Hong-Dong; Tian, You-Yong; Shi, Jian-Quan; Zhou, Jun-Shan

    2016-11-01

    The severity of cerebral microbleeds (CMBs) affected the prognosis of patients with acute cerebrovascular disease. Considering the impact of CMBs on clinical decision, it is necessary to assess the risk factors of CMBs. We aimed to evaluate the independent risk factors of CMBs in patients with acute ischemic stroke of large-artery atherosclerosis. 112 patients were enrolled in the study. The baseline information, the results of laboratory examination and cranial MRI were collected. The independent risk factors of CMBs in patients with acute ischemic stroke due to large-artery atherosclerosis were evaluated. CMBs were found in 56 (50%) patients. Older age and higher homocysteine (Hcy) level were associated with an elevated chance of occurrence of CMBs. Further, there was a positive correlation between CMBs grade and serum Hcy level. Serum Hcy level is strongly associated with the presence of CMBs in patients with acute ischemic stroke due to large-artery atherosclerosis. Serum Hcy level may be a potential therapeutic target for alleviating adverse clinical outcomes of CMBs. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  10. Herbal Formula Danggui-Shaoyao-San Promotes Neurogenesis and Angiogenesis in Rat Following Middle Cerebral Artery Occlusion

    Science.gov (United States)

    Ren, Changhong; Wang, Brian; Li, Ning; Jin, Kunlin; Ji, Xunming

    2015-01-01

    Current studies demonstrated that traditional Chinese herbal formula Danggui-Shaoyao-San (DSS) is not only used for the treatment of menstrual disorder, but has also found its use in neurological diseases. However, the neuroprotective role of DSS on ischemia-induced brain injury is still unclear. The aim of the present study is to explore the effect of DSS in ischemic brain injury. Total 30 adult female Sprague–Dawley rats underwent 90 min transient middle cerebral artery occlusion (MCAO). DSS (600 mg/kg) was administered through the intragastric route at the time of reperfusion and then performed every day thereafter until sacrifice. Results showed that DSS treatment significantly improved neurobehavioral outcomes (N=10 per group, P<0.05). Immunohistochemical staining showed that microvessel density in the perifocal region of DSS-treated rats was significantly increased compared to the saline-treated group (N=4 per group, P<0.01). Similarly, the numbers of BrdU+/DCX+ cells in the subventricular zone were increased in DSS-treated rats compared to the saline-treated group (P<0.05). Furthermore, we demonstrated that DSS treatment activated vascular endothelial growth factor (N=4 per group, P<0.05) and promoted eNOS phosphorylation (N=4 per group, P<0.05). Thus, we concluded that DSS promoted focal angiogenesis and neurogenesis, and attenuated ischemia-induced brain injury in rats after MCAO, suggesting that DSS is a potential drug for ischemic stroke therapy. PMID:26236546

  11. Influence of eye acupuncture therapy in expressions of BDNF and TrkB in corresponding penumbra brain tissue of ischemic area in rats with acute cerebral ischemia-reperfusion inj ury%眼针对MCAO/R大鼠大脑缺血区半暗带脑组织中BDNF和TrkB表达的影响及其脑保护作用机制

    Institute of Scientific and Technical Information of China (English)

    马贤德; 侯殿东; 张威

    2014-01-01

    目的:观察眼针对局灶性大脑中动脉缺血再灌注(MCAO/R)模型大鼠大脑缺血区半暗带脑组织中脑原性神经生长因子(BDNF)和酪氨酸激酶受体B(TrkB)表达水平的影响,探讨眼针对缺血性脑病的脑保护作用机制。方法:62只SD大鼠随机分为空白对照组(11只)、假手术组(11只)和模型复制组(40只)。模型复制组大鼠采用线栓法建立脑缺血再灌注模型,将模型复制成功的大鼠(32只)随机分为模型组(16只)及眼针组(16只);眼针组大鼠参照人体取穴方法,取肝区、上焦区、下焦区和肾区进行针刺干预。再灌注后2h即开始针刺,每8h 1次,连续针刺10次,末次干预后30 min,断髓处死大鼠,剥离缺血区域周围半暗带部位的脑组织,采用 RT-PCR和 Western blotting法检测大鼠脑组织中 BDNF和 TrkB mRNA及蛋白表达水平。结果:与空白对照组比较,假手术组大鼠半暗带脑组织中BDNF和TrkB mRNA和蛋白表达水平均无明显变化(P>0.05);与假手术组比较,模型组大鼠半暗带脑组织中BDNF和TrkB mRNA和蛋白表达水平均升高(P<0.01);与模型组比较,眼针组 MCAO/R模型大鼠半暗带脑组织中 BDNF和 TrkB mRNA和蛋白表达水平上升(P<0.05或P<0.01)。结论:脑缺血再灌注损伤发生后可促进 BDNF及其受体 TrkB表达以对抗损伤。眼针可通过上调 BDNF及其受体TrkB表达水平实现其脑保护作用。%Objective To investigate the influence of the eye acupuncture therapy in the expressions of brain derived neurophic factor(BDNF)and tyrosine kinase receptor B(TrkB)in penumbra brain tissue of ischemic area in the rats with acute cerebral ischemia reperfusion inj ury,and to explore the related mechanism of protective effect on brain of eye acupunture.Methods 62 SD rats were randomly divided into blank control group (n=11),sham operation group (n=11)and model copy

  12. Computer-aided diagnosis of acute ischemic stroke based on cerebral hypoperfusion using 4D CT angiography

    Science.gov (United States)

    Charbonnier, Jean-Paul; Smit, Ewoud J.; Viergever, Max A.; Velthuis, Birgitta K.; Vos, Pieter C.

    2013-02-01

    The presence of collateral blood flow is found to be a strong predictor of patient outcome after acute ischemic stroke. Collateral blood flow is defined as an alternative way to provide oxygenated blood to ischemic cerebral tissue. Assessment of collateral blood supply is currently performed by visual inspection of a Computed Tomography Angiogram (CTA) which introduces inter-observer variability and depends on the grading scale. Furthermore, variations in the arterial contrast arrival time may lead to underestimation of collateral blood supply in a CTA which exerts a negative influence on the prediction of patient outcome. In this study, the feasibility of a Computer-aided Diagnosis system is investigated capable of objectively predicting patient outcome. We present a novel automatic method for quantitative assessment of cerebral hypoperfusion in timing-invariant (i.e. delay insensitive) CTA (TI-CTA). The proposed Vessel Density Symmetry algorithm automatically generates descriptive maps based on hemispheric asymmetry of blood vessels. Intensity and symmetry based features are extracted from these descriptive maps and subjected to a best-first-search feature selection. Linear Discriminant Analysis is performed to combine selected features into a likelihood of good patient outcome. Receiver operating characteristic (ROC) analysis is conducted to evaluate the diagnostic performance of the CAD by leave-one- patient-out cross validation. A Positive Predicting Value of 1 was obtained at a sensitivity of 25% with an area under the ROC-curve of 0.86. The results show that the CAD is feasible to objectively predict patient outcome. The presented CAD could make an important contribution to acute ischemic stroke diagnosis and treatment.

  13. The CBF threshold and dynamics for focal cerebral infarction in spontaneously hypertensive rats.

    Science.gov (United States)

    Jacewicz, M; Tanabe, J; Pulsinelli, W A

    1992-05-01

    Two strategies were used to estimate the blood flow threshold for focal cerebral infarction in spontaneously hypertensive rats (SHRs) subjected to permanent middle cerebral artery and common carotid artery occlusion (MCA/CCAO). The first compared the volume of cortical infarction (24 h after ischemia onset) to the volumes of ischemic cortex (image analysis of [14C]iodoantipyrine CBF autoradiographs) perfused below CBF values less than 50 (VIC50) and less than 25 ml 100 g-1 min-1 (VIC25) at serial intervals during the first 3 h of ischemia. The infarct process becomes irreversible within 3 h in this model. In the second, measurements of CBF at the border separating normal from infarcted cortex at 24 h after ischemia onset were used as an index of the threshold. During the first 3 h of ischemia, VIC50 increased slightly to reach a maximum size at 3 h that closely matched the 24 h infarct volume. VIC25, in contrast, consistently underestimated the infarct volume by a factor of 2-3. CBF at the 24 h infarct border averaged 50 ml 100 g-1 min -1. Taken together, the results indicate that the CBF threshold for infarction in SHRs approaches 50 ml 100 g-1 min-1 when ischemia persists for greater than or equal to 3 h. This threshold value is approximately three times higher than in primates. Since cortical neuronal density is also threefold greater in rats than in primates, the higher injury threshold in the rat may reflect a neuronal primacy in determining the brain's susceptibility to partial ischemia.

  14. Imaging hemodynamic effects of ET-1 on cerebral blood flow in rats

    Science.gov (United States)

    Ponticorvo, Adrien; Tom, W. J.; Aura, M.; Jones, T. A.; Dunn, A. K.

    2007-02-01

    Endothelin-1 (ET-1) is a potent vasoconstrictor sometimes used in studies of cerebral ischemia. Its ability to create ischemic regions of various sizes with little additional damage has made it a popular tool in evaluating anti-stroke drugs. Despite its emergence in stroke models, it remains poorly characterized. Attempts to do this with Laser Doppler Flowmetry (LDF) or a histological analysis provide good temporal resolution or good spatial resolution respectively, but not both. An imaging modality that provides both temporal and spatial resolution would be able to better characterize the acute and chronic effects of ET-1 on cerebral blood flow. We have used laser speckle contrast imaging to study the effects of ET-1 after topical application on rats. We observed an immediate decrease in blood flow corresponding to the amount of ET-1 used. After the initial decrease, the blood flow slowly increases towards the baseline value with occasional vasospastic responses observed. Future studies involving multi-spectral reflectance imaging combined with the laser speckle contrast analysis would lead to a better understanding of the hemodynamic effects of ET-1.

  15. Resting-state Functional Magnetic Resonance Imaging Analysis of Brain Functional Activity in Rats with Ischemic Stroke Treated by Electro-acupuncture.

    Science.gov (United States)

    Liang, Shengxiang; Lin, Yunjiao; Lin, Bingbing; Li, Jianhong; Liu, Weilin; Chen, Lidian; Zhao, Shujun; Tao, Jing

    2017-09-01

    To evaluate whether electro-acupuncture (EA) treatment at acupoints of Zusanli (ST 36) and Quchi (LI 11) could reduce motor impairments and enhance brain functional recovery in rats with ischemic stroke. A rat model of middle cerebral artery occlusion (MCAO) was established. EA at ST 36 and LI 11was started at 24 hours (MCAO + EA group) after ischemic stroke. The nontreatment (MCAO) and sham-operated control (SC) groups were included as controls. The neurologic deficits of all groups were assessed by Zea Longa scores and the modified neurologic severity scores on 24 hours and 8 days after MCAO. To further investigate the effect of EA on infract volume and brain function, magnetic resonance imaging was used to estimate the brain lesion and brain neural activities of each gr