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Sample records for brain ischemia

  1. Review on herbal medicine on brain ischemia and reperfusion简

    Institute of Scientific and Technical Information of China (English)

    Nahid; Jivad; Zahra; Rabiei

    2015-01-01

    Brain ischemia and reperfusion is the leading cause of serious and long-range disability in the world. Clinically significant changes in central nervous system function are observed following brain ischemia and reperfusion. Stroke patients exhibit behavioral, cognitive,emotional, affective and electrophysiological changes during recovery phase. Brain injury by transient complete global brain ischemia or by transient incomplete brain ischemia afflicts a very large number of patients in the world with death or permanent disability. In order to reduce this damage, we must sufficiently understand the mechanisms involved in brain ischemia and reperfusion and repair to design clinically effective therapy.Cerebral ischemia and reperfusion is known to induce the generation of reactive oxygen species that can lead to oxidative damage of proteins, membrane lipids and nucleic acids.A decrease in tissue antioxidant capacity, an increase in lipid peroxidation as well as an increase in lipid peroxidation inhibitors have been demonstrated in several models of brain ischemia. This paper reviews the number of commonly used types of herbal medicines effective for the treatment of stroke. The aim of this paper was to review evidences from controlled studies in order to discuss whether herbal medicine can be helpful in the treatment of brain ischemia and reperfusion.

  2. Review on herbal medicine on brain ischemia and reperfusion

    Institute of Scientific and Technical Information of China (English)

    Nahid Jivad; Zahra Rabiei

    2015-01-01

    Brain ischemia and reperfusion is the leading cause of serious and long-range disability in the world. Clinically significant changes in central nervous system function are observed following brain ischemia and reperfusion. Stroke patients exhibit behavioral, cognitive, emotional, affective and electrophysiological changes during recovery phase. Brain injury by transient complete global brain ischemia or by transient incomplete brain ischemia afflicts a very large number of patients in the world with death or permanent disability. In order to reduce this damage, we must sufficiently understand the mechanisms involved in brain ischemia and reperfusion and repair to design clinically effective therapy. Cerebral ischemia and reperfusion is known to induce the generation of reactive oxygen species that can lead to oxidative damage of proteins, membrane lipids and nucleic acids. A decrease in tissue antioxidant capacity, an increase in lipid peroxidation as well as an increase in lipid peroxidation inhibitors have been demonstrated in several models of brain ischemia. This paper reviews the number of commonly used types of herbal medicines effective for the treatment of stroke. The aim of this paper was to review evidences from controlled studies in order to discuss whether herbal medicine can be helpful in the treatment of brain ischemia and reperfusion.

  3. CSF transthyretin neuroprotection in a mouse model of brain ischemia

    DEFF Research Database (Denmark)

    Santos, Sofia Duque; Lambertsen, Kate Lykke; Clausen, Bettina Hjelm;

    2010-01-01

    Brain injury caused by ischemia is a major cause of human mortality and physical/cognitive disability worldwide. Experimentally, brain ischemia can be induced surgically by permanent middle cerebral artery occlusion. Using this model, we studied the influence of transthyretin in ischemic stroke....... Transthyretin (TTR) is normally responsible for the transport of thyroid hormones and retinol in the blood and CSF. We found that TTR null mice (TTR(-/-) ) did not show significant differences in cortical infarction 24 h after permanent middle cerebral artery occlusion compared with TTR(+/+) control littermates...

  4. N-Acetylaspartate distribution in rat brain striatum during acute brain ischemia

    DEFF Research Database (Denmark)

    Sager, T.N.; Laursen, H; Fink-Jensen, A;

    1999-01-01

    Brain N-acetylaspartate (NAA) can be quantified by in vivo proton magnetic resonance spectroscopy (1H-MRS) and is used in clinical settings as a marker of neuronal density. It is, however, uncertain whether the change in brain NAA content in acute stroke is reliably measured by 1H-MRS and how NAA......]e increased linearly to 4 mmol/L after 3 hours and this level was maintained for the next 4 h. From the change in in vivo recovery of the interstitial space volume marker [14C]mannitol, the relative amount of NAA distributed in the interstitial space was calculated to be 0.2% of the total brain NAA during...... normal conditions and only 2 to 6% during ischemia. It was concluded that the majority of brain NAA is intracellularly located during ischemia despite large increases of interstitial [NAA]. Thus, MR quantification of NAA during acute ischemia reflects primarily changes in intracellular levels of NAA...

  5. Adenosine receptors in the immature brain : with special reference to their role in hypoxic ischemia

    OpenAIRE

    Ådén, Ulrika

    2001-01-01

    Although the newborn brain tolerates a much longer period of oxygen deprivation and ischemia than does the adult brain, perinatal hypoxic ischemia probably is an important cause of neurological dysfunction, cerebral palsy and epilepsy later in life. Hence it is important to investigate the mechanisms that modulate the extent of perinatal ischernic brain damage. There is good evidence that endogenous adenosine acts as a neuroprotective agent in models of ischemia in the m...

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

    Science.gov (United States)

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

    2012-03-15

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

  7. Expression of neuropeptide Y in rat brain ischemia

    Directory of Open Access Journals (Sweden)

    Babović Siniša S.

    2013-01-01

    Full Text Available Introduction. The immunohistochemical method was used to follow the expression of neuropeptide Y in the course of pre ischemia of the rat brain. The aim of the study was to define all the areas of expression of this protein, show their localization, their map of distribution and histological types. Material and Methods. All the sections of telencephalon, diencephalon and midbrain were studied in resistant, and transitory ischemia, which enabled us to observe the reaction of neurons to an ischemic attack or to repeated attacks. The mapping was done for all three proteins by introducing our results into the maps of rat brain atlas, George Paxinos, Charles Watson. Photographing and protein expression was done using Analysis program. Results. The results of this research show that there is a differens in reaction between the resistant and transitory ischemia groups of rats, especially in the caudoputamen, gyrus dentatus, corpus amygdaloideum, particularly in the medial nucleus. The mapping shows the reaction in caudoputamen, gyrusdentatus, corpus amygdaloideum - especially in the central nucleus, then in the sensitive and secondary auditory cortex, mostly in the laminae V/VI, but less in neuron groups CA1, CA2, CA3 of hippocampus. Discussion. The phylogenetically older parts of the brain-rhinencephalon, also showed reaction, which lead us to conclude that both newer and older brain structures reacted immunohistochemically. Histological data have shown that small neurons are most commonly found while the second most common ones are big pyramidal cells of multipolar and bipolar type, with a different body shape. Conclusion. Our findings have confirmed the results obtained in some rare studies dealing with this issue, and offered a precise and detailed map of cells expressing neuropeptide Y in the rat brain following ischemic attack.

  8. Effects ofAstragalus Membranaceus on Ischemia Brain Damage

    Institute of Scientific and Technical Information of China (English)

    Yumin Luo; Zhen Qin

    2000-01-01

    We observed the protective effects of Astragalus Membranaceus on cerebral ischemia. Method: 1. We used intravascular thread rat models with 72hs reperfusion of lh tMCAO for our studies. Astragalus Membranaceus was administrated intraperitoneally in different interval. The rats were sacrificed 72 hours after l h tMCAO. 2. Cerebral infarction volume was determined by TTC staining and image analysis. 3. DTNB method and TBA method were applied to measure the activity of GSH-px and the concentration of MDA respectively. 4. The blood brain barrier damage was evaluated by the area of Evans Blue extravasation. Results:l.The whole brain volume of protective group is larger than its control, but the average infarction volume is significantly less than that of control, and the percentage of average infarction volume to the whole brain is obviously decreased. 2. We found mildly enhanced GSH-px activity and markedly decreased MDA concentration in the protective group compared with its control. But there are no significant changes of GSH-px activity and MDA concentration in the therapy group compared with its control. 3. The area of Evans Blue staining in the protective group is significantly less than that of its control. Conclusion:l.Astragalus Membranaceus can decrease the infarction volume. 2.Astragalus Membranaceus may reduce MDA concentration after cerebral ischemia. 3.Astragalus Membranaceus can protect blood brain barrier.

  9. Agmatine attenuates brain edema through reducing the expression of aquaporin-1 after cerebral ischemia

    OpenAIRE

    Kim, Jae Hwan; Lee, Yong Woo; Park, Kyung Ah; Lee, Won Taek; Jong Eun LEE

    2009-01-01

    Brain edema is frequently shown after cerebral ischemia. It is an expansion of brain volume because of increasing water content in brain. It causes to increase mortality after stroke. Agmatine, formed by the decarboxylation of -arginine by arginine decarboxylase, has been shown to be neuroprotective in trauma and ischemia models. The purpose of this study was to investigate the effect of agmatine for brain edema in ischemic brain damage and to evaluate the expression of aquaporins (AQPs). Res...

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

    OpenAIRE

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

    2014-01-01

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

  11. Brain ischemia changes the long term response to antidepressant drugs in mice.

    Science.gov (United States)

    Deplanque, Dominique; Venna, Venugopal Reddy; Bordet, Régis

    2011-06-01

    Depression is a frequent but often unrecognized and under treated complication of stroke that has scarcely been investigated in animal models particularly regarding treatment issues. Using the Forced Swim Test (FST) and testing spontaneous motor activity, we studied whether a transient focal cerebral ischemia modifies mice behaviours and antidepressant drug effects. We first evaluated whether FST realized 2 days or 1 week after brain reperfusion may be routinely used in male Swiss mice previously submitted to a 15, 30 or 60-min transient occlusion of the right middle cerebral artery. We then evaluated behavioural changes up to 5 weeks in mice previously submitted to a 15-min ischemia. Behaviours according to the administration of imipramine or fluvoxamine at 1 and 5 weeks after a 15-min ischemia were finally evaluated. Transient ischemia was associated with a decrease in immobility in the FST performed 2 days after reperfusion while no changes were observed in 1 and 5 weeks post-ischemia groups. Changes were related neither to brain ischemia duration nor to infarct volume. At both 1 and 5 weeks after brain ischemia, a dramatic decrease in the antidepressant response to imipramine related to a decrease in climbing behaviour was observed while the effects of fluvoxamine were improved through an increase in both climbing and swimming. Behaviours in the FST were unrelated to any spontaneous motor activity changes. Responses to anti-depressant drugs are strongly modified in mice previously submitted to brain ischemia. Present results underline that not all antidepressant drugs are appropriate after ischemic stroke.

  12. Expression of Bcl-2 and NF-κB in brain tissue after acute renal ischemia-reperfusion in rats

    Institute of Scientific and Technical Information of China (English)

    Na Zhang; Gen-Yang Cheng; Xian-Zhi Liu; Feng-Jiang Zhang

    2014-01-01

    Objective:To investigate the effect of acute renal ischemia reperfusion on brain tissue. Methods:Fourty eight rats were randomly divided into four groups(n=12): sham operation group,30 min ischemia60 min reperfusion group,60 min ischemia60 min reperfusion group, and 120 min ischemia60 min reperfusion group.The brain tissues were taken after the experiment. TUNEL assay was used to detect the brain cell apoptosis, and western blot was used to detect the expression of apoptosis-related proteins and inflammatory factors.Results:Renal ischemia-reperfusion induced apoptosis of brain tissues, and the apoptosis increased with prolongation of ischemia time.The detection at the molecular level showed decreasedBcl-2 expression, increasedBax expression, upregulated expression ofNF-κB and its downstream factor COX-2/PGE2.Conclusions:Acute renal ischemia-reperfusion can cause brain tissue damage, manifested as induced brain tissues apoptosis and inflammation activation.

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

    Directory of Open Access Journals (Sweden)

    Theresa Ann Lusardi

    2014-02-01

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

  14. Cerebral white matter injury and damage to myelin sheath following whole-brain ischemia.

    Science.gov (United States)

    Chen, Yingzhu; Yi, Qiong; Liu, Gang; Shen, Xue; Xuan, Lihui; Tian, Ye

    2013-02-01

    Myelin sheath, either in white matter or in other regions of brain, is vulnerable to ischemia. The specific events involved in the progression of ischemia in white matter have not yet been elucidated. The aim of this study was to determine histopathological alterations in cerebral white matter and levels of myelin basic protein (MBP) in ischemia-injured brain tissue during the acute and subacute phases of central nervous injury following whole-brain ischemia. The whole cerebral ischemia model (four-vessel occlusion (4-VO)) was established in adult Sprague-Dawley rats and MBP gene expression and protein levels in the brain tissue were measured using reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA) at 2 days, 4 days, 7 days, 14 days, and 28 days following ischemia. Demyelination was determined by Luxol fast blue myelin staining, routine histopathological staining, and electron microscopy in injured brain tissue. Results showed that edema, vascular dilation, focal necrosis, demyelination, adjacent reactive gliosis and inflammation occurred 7 days after ischemia in HE staining and recovered to control levels at 28 days. The absence of Luxol fast blue staining and vacuolation was clearly visible at 7 days, 14 days, and 28 days. Semiquantitative analysis showed that the transparency of myelin had decreased significantly by 7 days, 14 days, and 28 days. Demyelination and ultrastructual changes were detected 7 days after ischemia. The relative levels of MBP mRNA decreased 2 days after ischemia and this trend continued throughout the remaining four points in time. The MBP levels measured using ELISA also decreased significantly at 2 days and 4 days, but they recovered by 7 days and returned to control levels by 14 days. These results suggest that the impact of ischemia on cerebral white matter is time-sensitive and that different effects may follow different courses over time.

  15. Phosphorylation of tau protein over time in rats subjected to transient brain ischemia

    Institute of Scientific and Technical Information of China (English)

    Bo Song; Qiang Ao; Zhen Wang; Weiqiang Liu; Ying Niu; Qin Shen; Huancong Zuo; Xiufang Zhang; Yandao Gong

    2013-01-01

    Transient brain ischemia has been shown to induce hyperphosphorylation of the microtu-bule-associated protein tau. To further determine the mechanisms underlying these processes, we investigated the interaction between tau, glycogen synthase kinase (GSK)-3β and protein phos-phatase 2A. The results confirmed that tau protein was dephosphorylated during brain ischemia;in addition, the activity of GSK-3βwas increased and the activity of protein phosphatase 2A was de-creased. After reperfusion, tau protein was hyperphosphorylated, the activity of GSK-3β was de-creased and the activity of protein phosphatase 2A remained low. Importantly, the interaction of tau with GSK-3β and protein phosphatase 2A was altered during ischemia and reperfusion. Lithium chloride could affect tau phosphorylation by regulating the interaction of tau with GSK-3βand pro-tein phosphatase 2A, and improve learning and memory ability of rats after transient brain ischemia. The present study demonstrated that it was the interaction of tau with GSK-3β and protein phos-phatase 2A, rather than their individual activities, that dominates the phosphorylation of tau in tran-sient brain ischemia. Hyperphosphorylated tau protein may play an important role in the evolution of brain injury in ischemic stroke. The neuroprotective effects of lithium chloride partly depend on the inhibition of tau phosphorylation during transient brain ischemia.

  16. Modulation of IκB kinase autophosphorylation and activity following brain ischemia

    Institute of Scientific and Technical Information of China (English)

    SHENWan-Hua; ZHANGHun-Yi; 等

    2003-01-01

    ATIM:To investigate the effects of different antagonists on the alteration of IκB kinase(IKK)activity in rat hipoocampus folluwing global brain ischemia,METHODS:Using 4-vessel occlusion(4-VO)as brain ischemia model,IKK protein expression was examined by immunoblotting and immunoprecipitation,and IKK activity was assayed by in vitro kinase assay.RESULTS:There was no alteration of IKK protein expression following ischemia or ischemia/reperfusion different time points,but IKK activity reached its peak level at ischemia 30min.Pretreatment with N-methyl-D-aspartate(NMDA)receptor antagonist ketamine,non-NMDA receptor antagonist DNQX,or NFκB inhibitor PDTC decreased the IKK activity following brain ischemia 30min.The increase in substrate myelin basic protein(MBP)phosphorylation by IKK is associated with an increase in autophosphorylation of IKK,which can also be antagonized by ketamine,DNQX,and PDTC,CONCLUSION:NMDA receptor and non-NMDA receptor mediate the increase of IKK activity following global brain ischemia in rat hippocampus,which contributes to the alterations of expression and activity of downstream factor NF-κB.

  17. Using laser confocal scanning microscope to study ischemia-hypoxia injury in rat brain slice

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The level of lipid peroxidation and cellular necrosis in rat living brain slices during brain ischemia-hypoxia injury have been observed using a laser confocal scanning microscope (LCSM) with double labeling of fluorescent probes D-399 (2,7-dichlorofluorescin diacetate) and propidium iodide (PI).The hypoxia and/or reoxygenation injury in rat brain slices is markedly decreased by pretreatment with L-NG-nitro-arginine (L-NNA) and N-acetylcysteine (NAC),showing that the nitric oxide (NO) and other free radicals play an important role in brain ischemia-hypoxia injury.

  18. 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.

  19. Protective effects of acupuncture on brain tissue following ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Mingshan Wang; Fuguo Ma; Huailong Chen

    2008-01-01

    BACKGROUND: In patients with cerebrovascular disease, by means of the neuroendocrine system, acupuncture supports the transformation of a local pathological status into a physiological status. Recently, great progress has been made in studying the protective effects of acupuncture on brain ischemia/reperfusion injury. OBJECTIVE: To summarize research advances in the protective effects of acupuncture on brain ischemia/reperfusion injury. RETRIEVAL STRATEGY: Using the terms "acupuncture, transcutaneous electrical acupoint stimulation, cerebral ischemia/reperfusion injury, and cerebral protection", we retrieved articles from the PubMed database published between January 1991 and June 1994. Meanwhile, we searched the China National Knowledge Infrastructure with the same terms. Altogether, 114 articles and their results were analyzed. Inclusive criteria: studies that were closely related to the protective effects of acupuncture on brain ischemia/reperfusion injury, or studies, whose contents were in the same study field and were published recently, or in the authorized journals. Exclusive criteria: repetitive studies. LITERATURE EVALUATION: Thirty articles that related to the protective effects of acupuncture on brain ischemia/reperfusion injury were included. Among them, 7 were clinical studies, and the remaining 23 articles were animal experimental studies. DATA SYNTHESIS: ① Animal experimental studies have demonstrated that acupuncture improves brain blood perfusion and brain electrical activity, influences pathomorphological and ultramicrostructural changes in ischemic brain tissue, is beneficial in maintaining the stability of intracellular and extracellular ions, resists free radical injury and lipid peroxidation, and influences cytokine, neurotransmitter, brain cell signal transduction, and apoptosis-regulating genes. ② Clinical studies have demonstrated that acupuncture not only promotes nutritional supply to local brain tissue in patients with cerebral

  20. Alleviation of ischemia-induced brain edema by activation of the central histaminergic system in rats.

    Science.gov (United States)

    Irisawa, Yumi; Adachi, Naoto; Liu, Keyue; Arai, Tatsuru; Nagaro, Takumi

    2008-09-01

    We have reported that facilitation of central histaminergic activity prevents the development of ischemia-induced brain injury. Since cerebral edema is a major cause of brain damage, we studied effects on brain edema of postischemic administration of L-histidine, a precursor of histamine, and thioperamide, a histamine H(3)-receptor antagonist, both of which enhance central histaminergic activity. Focal cerebral ischemia for 2 h was provoked by transient occlusion of the right middle cerebral artery in rats, and the water content and infarct size were determined 24 h after reperfusion. Changes in the extracellular concentration of histamine were examined in the striatum by a microdialysis procedure, and effects of these compounds were evaluated. Repeated administration of L-histidine (1000 mg/kg x 2, i.p.), immediately and 6 h after reperfusion, reduced the increase in the water contents in ischemic regions. Simultaneous administration of thioperamide (5 mg/kg, s.c.) with L-histidine (1000 mg/kg, i.p.) completely prevented edema formation and alleviated brain infarction, although a single dose of L-histidine, immediately after reperfusion, showed no benefits. The striatal histamine level was gradually increased after reperfusion as well as during ischemia. Simultaneous administration of thioperamide with L-histidine markedly increased the brain histamine concentration, and the value increased up to 230% of that in the saline group 5 - 6 h after reperfusion. L-Histidine alone did not affect the increase in the histamine output after ischemia. These findings suggest that further activation of the central histaminergic system after initiation of cerebral ischemia prevents development of ischemia-induced brain edema.

  1. Effects of Moxibustion Pretreating on SOD and MDA in the Rat of Global Brain Ischemia

    Institute of Scientific and Technical Information of China (English)

    HUA Jin-shuang; LI Li-ping; ZHU Xian-min

    2008-01-01

    objective;To probe into the mechanism of moxibustion preconditioning in preventive brain-protecting effect.Methods;The global brain ischemia rat model was developed by blocking 4 artenes.Seventy-eight Wistarmale rats were randomly divided into 5 groups;a nomal control group,a sham-operation group,a brain ischemia group,a brain ischemia preconditioning group,a moxibustion pretreating group.The brains in the 5groups were taken at 24 h,48h,and 72h after operation respectively Superoxide dismulase(SOD)activity was determined with xanthine oxidase method and malondialdehyde(MDA)content with thiobarbituric acid method.Results;After the operation,in the moxibustion preconditioning group,SOD activity significantly increased,especially 24h after moxibustion preconditioning;and MDA content decreased,with a very significant difference as compared with that of the cerebral ischemia group(P<0.01).Conclusion;Moxibustion preconditioning protects the ischemic and anoxic brain tissue by increasing the activity of endogenous antioxidase.

  2. Matrix metalloproteinase-9 expression and blood brain barrier permeability in the rat brain after cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Lifang Lei; Xiaohong Zi; Qiuyun Tu

    2008-01-01

    BACKGROUND: The integrity of the blood brain barrier (BBB) plays an important role in the patho-physiological process of cerebral ischemia/reperfusion injury. It has been recently observed that metalloproteinase-9 (MMP-9) is closely related to cerebral ischemia/reperfusion injuryOBJECTIVE: This study was designed to observe MMP-9 expression in the rat brain after cerebral ischemia/reperfusion injury and to investigate its correlation to BBB permeability.DESIGN, TIME AND SETTING: This study, a randomized controlled animal experiment, was performed at the Institute of Neurobiology, Central South University between September 2005 and March 2006.MATERIALS: Ninety healthy male SD rats, aged 3-4 months, weighing 200-280g, were used in the present study. Rabbit anti-rat MMP-9 polyclonal antibody (Boster, Wuhan, China) and Evans blue (Sigma, USA) were also used.METHODS: All rats were randomly divided into 9 groups with 10 rats in each group: normal control group, sham-operated group, and ischemia for 2 hours followed by reperfusion for 3,6,12 hours, 1,2,4 and 7 days groups. In the ischemia/reperfusion groups, rats were subjected to ischemia/reperfusion injury by suture occlusion of the right middle cerebral artery. In the sham-operated group, rats were merely subjected to vessel dissociation. In the normal control group, rats were not modeled.MAIN OUTCOME MEASURES: BBB permeability was assessed by determining the level of effusion of Evans blue. MMP-9 expression was detected by an immunohistochemical method.RESULTS: All 90 rats were included in the final analysis. BBB permeability alteration was closely correlated to ischemia/reperfusion time. BBB permeability began to increase at ischemia/reperfusion for 3 hours, then it gradually reached a peak level at ischemia/reperfusion for 1 day, and thereafter it gradually decreased. MMP-9 expression began to increase at ischemia/reperfusion for 3 hours, then gradually reached its peak level 2 days after perfusion, and thereafter

  3. Role of morphine preconditioning and nitric oxide following brain ischemia reperfusion injury in mice

    Directory of Open Access Journals (Sweden)

    Maedeh Arabian

    2015-01-01

    Full Text Available Objective(s: Morphine dependence (MD potently protects heart against ischemia reperfusion (IR injury through specific signaling mechanisms, which are different from the pathways involved in acute morphine treatment or classical preconditioning. Since opioid receptor density changes post cerebral ischemia strongly correlated with brain histological damage, in the present study, we tried to elucidate the possible role of opioid receptors in IR injury among morphine-dependent mice. Materials and Methods: Accordingly, incremental doses (10 mg/kg/day to 30 mg/kg/day of morphine sulphate were subcutaneously administered for 5 days before global brain ischemia induction through bilateral common carotid artery occlusion. Animals were received naloxone (5 mg/kg or L-NAME (20 mg/kg 30 min after the last morphine dose. Twenty four hr after the ischemia induction, Retention trial of passive avoidance test and western blot analysis were done. histological analysis (TUNEL and NISSL staining performed 72 hr after ischemia. Results: MD improved post ischemia memory performance (P

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

    DEFF Research Database (Denmark)

    Spulber, S.; Moldovan, Mihai; Oprica, M.;

    2005-01-01

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

  5. A TIGAR-regulated metabolic pathway is critical for protection of brain ischemia.

    Science.gov (United States)

    Li, Mei; Sun, Meiling; Cao, Lijuan; Gu, Jin-hua; Ge, Jianbin; Chen, Jieyu; Han, Rong; Qin, Yuan-Yuan; Zhou, Zhi-Peng; Ding, Yuqiang; Qin, Zheng-Hong

    2014-05-28

    TP53-induced glycolysis and apoptosis regulator (TIGAR) inhibits glycolysis and increases the flow of pentose phosphate pathway (PPP), which generates NADPH and pentose. We hypothesized that TIGAR plays a neuroprotective role in brain ischemia as neurons do not rely on glycolysis but are vulnerable to oxidative stress. We found that TIGAR was highly expressed in brain neurons and was rapidly upregulated in response to ischemia/reperfusion insult in a TP53-independent manner. Overexpression of TIGAR in normal mice with lentivirus reduced ischemic neuronal injury, whereas lentivirus-mediated TIGAR knockdown aggravated it. In cultured primary neurons, increasing TIGAR expression reduced oxygen and glucose deprivation (OGD)/reoxygenation-induced injury, whereas decreasing its expression worsened the injury. The glucose 6-phosphate dehydrogenase was upregulated in mouse and cellular models of stroke, and its upregulation was further enhanced by overexpression of TIGAR. Supplementation of NADPH also reduced ischemia/reperfusion brain injury and alleviated TIGAR knockdown-induced aggravation of ischemic injury. In animal and cellular stroke models, ischemia/reperfusion increased mitochondrial localization of TIGAR. OGD/reoxygenation-induced elevation of ROS, reduction of GSH, dysfunction of mitochondria, and activation of caspase-3 were rescued by overexpression of TIGAR or supplementation of NADPH, while knockdown of TIGAR aggravated these changes. Together, our results show that TIGAR protects ischemic brain injury via enhancing PPP flux and preserving mitochondria function, and thus may be a valuable therapeutic target for ischemic brain injury.

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

    Institute of Scientific and Technical Information of China (English)

    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

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

    Science.gov (United States)

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

    2016-03-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Zhen-qiang Zhang

    2016-01-01

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

  10. Uptake of radiolabeled ions in normal and ischemia-damaged brain

    International Nuclear Information System (INIS)

    The regional concentrations of nine radiochemicals were measured in rat brain after induction of cerebral ischemia to identify tracers concentrated by brain undergoing selective neuronal necrosis. Transient (30 minute) forebrain ischemia was produced in the rat; 24 hours after cerebral recirculation the radiochemicals were injected intravenously and allowed to circulate for 5 hours. The brain concentrations of the radiochemicals in dissected regions were determined by scintillation counting. Forebrain ischemia of this nature will produce extensive injury to striatal neurons but will spare the great majority of neocortical neurons at 24 hours. The regional concentrations of these radiochemicals varied considerably in both control and ischemic animals. In postischemic animals, 4 radionuclides (63Ni, 99TcO4, 22Na, and [3H]tetracycline) were concentrated in the irreversibly damaged striatum in amounts ranging from 1.4 to 2.4 times greater than in normal tissue. The concentrations of 65Zn, 59Fe, 32PO4, and 147Pm in postischemic brain were similar to or less than those in normal brain. The concentration of [14C]EDTA was increased in injured and uninjured brain of postischemic rats. Autoradiographic analysis of the distribution patterns of some of these ions in normal animals showed that 99TcO4, 22Na, 65Zn, and 59Fe were distributed more uniformly throughout the brain than were 32PO4, 63Ni, and 147Pm. At 24 or 48 hours after ischemia, 63Ni, 99TcO4, and 22Na were preferentially concentrated in the damaged striatum and hippocampus, whereas 65Zn, 59Fe, 32PO4, and 147Pm did not accumulate in irreversibly injured tissue. Of the radiochemicals tested to date, Ni, TcO4, and tetracycline may be useful for diagnosing ischemic brain injury in humans, using positron emission tomography

  11. Adenosine A2A Receptors Modulate Acute Injury and Neuroinflammation in Brain Ischemia

    Directory of Open Access Journals (Sweden)

    Felicita Pedata

    2014-01-01

    Full Text Available The extracellular concentration of adenosine in the brain increases dramatically during ischemia. Adenosine A2A receptor is expressed in neurons and glial cells and in inflammatory cells (lymphocytes and granulocytes. Recently, adenosine A2A receptor emerged as a potential therapeutic attractive target in ischemia. Ischemia is a multifactorial pathology characterized by different events evolving in the time. After ischemia the early massive increase of extracellular glutamate is followed by activation of resident immune cells, that is, microglia, and production or activation of inflammation mediators. Proinflammatory cytokines, which upregulate cell adhesion molecules, exert an important role in promoting recruitment of leukocytes that in turn promote expansion of the inflammatory response in ischemic tissue. Protracted neuroinflammation is now recognized as the predominant mechanism of secondary brain injury progression. A2A receptors present on central cells and on blood cells account for important effects depending on the time-related evolution of the pathological condition. Evidence suggests that A2A receptor antagonists provide early protection via centrally mediated control of excessive excitotoxicity, while A2A receptor agonists provide protracted protection by controlling massive blood cell infiltration in the hours and days after ischemia. Focus on inflammatory responses provides for adenosine A2A receptor agonists a wide therapeutic time-window of hours and even days after stroke.

  12. Ischemic preconditioning reduces peripheral oxidative damage associated with brain ischemia in rats

    Directory of Open Access Journals (Sweden)

    S.S. Frassetto

    1999-10-01

    Full Text Available Brain ischemia followed by reperfusion causes neuronal death related to oxidative damage. Furthermore, it has been reported that subjects suffering from ischemic cerebrovascular disorders exhibit changes in circulating platelet aggregation, a characteristic that might be important for their clinical outcome. In the present investigation we studied tert-butyl hydroperoxide-initiated plasma chemiluminescence and thiol content as measures of peripheral oxidative damage in naive and preconditioned rats submitted to forebrain ischemia produced by the 4-vessel occlusion method. Rats were submitted to 2 or 10 min of global transient forebrain ischemia followed by 60 min or 1, 2, 5, 10 or 30 days of reperfusion. Preconditioned rats were submitted to a 10-min ischemic episode 1 day after a 2-min ischemic event (2 + 10 min, followed by 60 min or 1 or 2 days of reperfusion. It has been demonstrated that such preconditioning protects against neuronal death in rats and gerbils submitted to a lethal (10 min ischemic episode. The results show that both 2 and 10 min of ischemia cause an increase of plasma chemiluminescence when compared to control and sham rats. In the 2-min ischemic group, the effect was not present after reperfusion. In the 10-min ischemic group, the increase was present up to 1 day after recirculation and values returned to control levels after 2 days. However, rats preconditioned to ischemia (2 + 10 min and reperfusion showed no differences in plasma chemiluminescence when compared to controls. We also analyzed plasma thiol content since it has been described that sulfhydryl (SH groups significantly contribute to the antioxidant capacity of plasma. There was a significant decrease of plasma thiol content after 2, 10 and 2 + 10 min of ischemia followed by reperfusion when compared to controls. We conclude that ischemia may cause, along with brain oxidative damage and cell death, a peripheral oxidative damage that is reduced by the

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

    Science.gov (United States)

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

    2008-06-01

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

  14. Changes in the permeability of blood brain barrier and endothelial cell damage after cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Ke Liu; Jiansheng Li

    2006-01-01

    OBJECTIVE: To investigate the effect of endothelial cells on the permeability of blood brain barrier (BBB) after brain injury and its effect mechanism.DATA SOURCES: We searched for the articles of permeability of BBB and endothelial cell injury after brain ischemia, which were published between January 1982 and December 2005, with the key words of "cerebral ischemia damage,blood brain barrier ( BBB),permeability,effect of endothelial cell (EC) and its variation mechanism"in English.STUDY SELECTION: The materials were primarily selected. The articles related to the changes in the permeability of BBB and the effect of endothelial cells as well as the change mechanism after cerebral ischemia damage were chosen. Repetitive studies or review articles were excluded.DATA EXTRACTION: Totally 55 related articles were collected, and 35 were excluded due to repetitive or review articles, finally 20 articles were involved.DATA SYNTHESIS: The content or viewpoints of involved literatures were analyzed. Cerebral ischemia had damage for endothelial cells, such as the inflow of a lot of Ca2+, the production of nitrogen monoxide and oxygen free radical, and aggravated destruction of BBB. After acceptors of inflammatory mediators on cerebrovascular endothelial cell membrane, such as histamine, bradykinin , 5-hydroxytryptamine and so on are activated, endothelial cells shrink and the permeability of BBB increases. Its mechanism involves in the inflow of extracellular Ca2+and the release of intracellular Ca2+ in the cells. Glycocalyx molecule on the surface of endothelial cell, having structural polytropy, is the determinative factor of the permeability of BBB. VEGF, intensively increasing the vasopermeability and mainly effecting on postcapillary vein and veinlet, is the strongest known blood vessel permeation reagent. Its chronic overexpression in the brain can lead the destruction of BBB.CONCLUSION: The injury of endothelial cell participants in the pathological mechanism of BBB

  15. Continuous and simultaneous electrochemical measurements of glucose, lactate, and ascorbate in rat brain following brain ischemia.

    Science.gov (United States)

    Lin, Yuqing; Yu, Ping; Hao, Jie; Wang, Yuexiang; Ohsaka, Takeo; Mao, Lanqun

    2014-04-15

    Developing new tools and technologies to enable recording the dynamic changes of multiple neurochemicals is the essence of better understanding of the molecular basis of brain functions. This study demonstrates a microfluidic chip-based online electrochemical system (OECS) for in vivo continuous and simultaneous monitoring of glucose, lactate, and ascorbate in rat brain. To fabricate the microfluidic chip-based detecting system, a microfluidic chip with patterned channel is developed into an electrochemical flow cell by incorporating the chip with three surface-modified indium-tin oxide (ITO) electrodes as working electrodes, a Ag/AgCl wire as reference electrode, and a stainless steel tube as counter electrode. Selective detection of ascorbate is achieved by the use of single-walled carbon nanotubes (SWNTs) to largely facilitate the electrochemical oxidation of ascorbate, while a dehydrogenase-based biosensing mechanism with methylene green (MG) adsorbed onto SWNTs as an electrocatalyst for the oxidation of dihydronicotiamide adenine dinucleotide (NADH) is employed for biosensing of glucose and lactate. To avoid the crosstalk among three sensors, the sensor alignment is carefully designed with the SWNT-modified electrode in the upstream channel and paralleled glucose and lactate biosensors in the downstream channels. With the microfluidic chip-based electrochemical flow cell as the detector, an OECS is successfully established by directly integrating the microfluidic chip-based electrochemical flow cell with in vivo microdialysis. The OECS exhibits a good linear response toward glucose, lactate, and ascorbate with less crosstalk. This property, along with the high stability and selectivity, enables the OECS for continuously monitoring three species in rat brain following brain ischemia. PMID:24621127

  16. CHANGES OF ENDOTHELIN-1 GENE EXPRESSION IN RAT BRAINS DURING ISCHEMIA AND ISCHEMIC REPERFUSION

    Institute of Scientific and Technical Information of China (English)

    吴卫平; 匡培根; 李振洲

    1996-01-01

    Objective. The experiment was designed to study the association of cerebral ischemia and reperfusion with endothelin-1 (ET-1) gene expression of rat brain.s and time dependent changes of ET 1 gene expression during cerebral isehemia.Materials and methods.Thirty-three male SD rats were divided into dor blot hybridization (n=27) and in situ hybridization groups (n=6).The focal cerebral ischemis and reperfusion models were made with suture embolism of middle cerebral artery.Dot blot hybridization groups were redivided into control and ischemic subgroups (ischemia for 0.5,1,1.5,3,6,12,24,48 and 72h respectively).In situ hybridization groups were redivided into ischemia and reperfusion groups.After 24 h ischemia and 24 h reperfusion,ET-1 gene expressions were investigated with in situ hybridization and the results were analyaed with IBAS 2000 Image Analysis System.Results.Dot blot hybridization showed that ET-1 mRNA of cerbral cortex and caudate-putamen was increased at 6 h of ischemis and reached peak at 24h(3.9 and 3.7 fold respectively),and at 72h of ischmia it remsined at high levels(3.5and 2.1 fold respectively).In situ hybridization showed that the levels of ET-1 mRNA of cerebral cortex and caudate-puramen were also markedly increased both in 24 h ischemia and 24 h reperfusion groups(P<0.01,P<0.05 respectively).Conclusins.ET-1 gene expression in focal ischcmic brain tissue were markedly and progressively increased during cerbral ischemia and reperfusion and down-regulation of ET-1 expression may be a new approsch to the treatment of ischmic cerebrova scular diseases.

  17. Ischemia/reperfusion mediated oxygen free radical production in rat brain endothelium

    Energy Technology Data Exchange (ETDEWEB)

    Grammas, P.; Wood, K. (Univ. of Oklahoma, Oklahoma City (United States)); Liu, G.J.; Floyd, R.A. (Oklahoma Medical Research Foundation, Oklahoma City (United States)); Wood, K. (Univ. of Oklahoma Health Sciences Center, Oklahoma City (United States) Oklahoma Medical Research Foundation, Oklahoma City (United States))

    1991-03-11

    Oxygen free radicals have been increasingly implicated in ischemia/reperfusion mediated injury to tissue. Recent methods of assessing tissue oxygen free radical flux including spin trapping, salicylate hydroxylation, protein oxidation and specific enzymatic activity loss have clearly shown that ischemia/reperfusion mediates oxidative damage in brain. Vascular endothelia cells are increasingly implicated in inactivating oxidative damage. The authors have used salicylate to assess hydroxyl free radical flux during an anoxia-reoxygenation insult in isolated brain microvessels. Brain microvessels that were subjected to a 20 min anoxia period and then reoxygenated for 20 min hydroxylated salicylate to form tissue localized 2,3-dihydroxybenzoic acid (2,3-DHBA) whereas microvessels that remained oxygenated throughout contained very little 2,3-DHBA. The data suggest that anoxia/reoxygenation of microvessels produces tissue localized hydroxyl free radical flux.

  18. Does closure of acid-sensing ion channels reduce ischemia/reperfusion injury in the rat brain?

    Institute of Scientific and Technical Information of China (English)

    Jie Wang; Yinghui Xu; Zhigang Lian; Jian Zhang; Tingzhun Zhu; Mengkao Li; Yi Wei; Bin Dong

    2013-01-01

    Acidosis is a common characteristic of brain damage. Because studies have shown that permeable Ca2+-acid-sensing ion channels can mediate the toxic effects of calcium ions, they have become new targets against pain and various intracranial diseases. However, the mechanism associated with expression of these channels remains unclear. This study sought to observe the expression characteristics of permeable Ca2+-acid-sensing ion channels during different reperfusion inflows in rats after cerebral ischemia. The rat models were randomly divided into three groups: adaptive ischemia/reperfusion group, one-time ischemia/reperfusion group, and severe cerebral ischemic injury group. Western blot assays and immunofluorescence staining results exhibited that when compared with the one-time ischemia/reperfusion group, acid-sensing ion channel 3 and Bcl-x/l expression decreased in the adaptive ischemia/reperfusion group. Calmodulin expression was lowest in the adaptive ischemia/reperfusion group. Following adaptive reperfusion, common carotid artery flow was close to normal, and the pH value improved. Results verified that adaptive reperfusion following cerebral ischemia can suppress acid-sensing ion channel 3 expression, significantly reduce Ca2+ influx, inhibit calcium overload, and diminish Ca2+ toxicity. The effects of adaptive ischemia/reperfusion on suppressing cell apoptosis and relieving brain damage were better than that of one-time ischemia/reperfusion.

  19. Increased expression of receptor for advanced glycation end-products worsens focal brain ischemia in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Ying Xing; Jinting He; Weidong Yu; Lingling Hou; Jiajun Chen

    2012-01-01

    A rat model of diabetes mellitus was induced by a high fat diet, followed by focal brain ischemia induced using the thread method after 0.5 month. Immunohistochemistry showed that expression of receptor for advanced glycation end-products was higher in the ischemic cortex of diabetic rats compared with non-diabetic rats with brain ischemia. Western blot assay revealed increased phosphorylated c-Jun N-terminal kinase expression, and unchanged phosphorylated extracellular signal-regulated protein kinase protein expression in the ischemic cortex of diabetic rats compared with non-diabetic rats with brain ischemia. Additionally, phosphorylated p38 mitogen-activated protein kinase protein was not detected in any rats in the two groups. Severity of limb hemiplegia was worse in diabetic rats with brain ischemia compared with ischemia alone rats. The results suggest that increased expression of receptor for advanced glycation end-products can further activate the c-Jun N-terminal kinase pathway in mitogen-activated protein kinase, thereby worsening brain injury associated with focal brain ischemia in diabetic rats.

  20. Recruitment of neutrophils across the blood-brain barrier: the role of posttraumatic hepatic ischemia

    Directory of Open Access Journals (Sweden)

    Mantovani Mario

    2003-01-01

    Full Text Available PURPOSE: To study the effects of total hepatic ischemia, and reperfusion on the accumulation of neutrophils in the brain of rats submitted to normovolemic conditions as well as to controlled hemorrhagic shock state. METHODS: Thirty two adult male Wistar rats, were divided into four groups: the Control group, was submitted to the standard procedures for a period of 60 min of observation; Shock group, was submitted to controlled hemorrhagic shock (mean arterial blood pressure=40mmHg, 20min followed by volemic resuscitation (lactated Ringer's solution + blood, 3:1 and reperfusion for 60min; Pringle group, was submitted to total hepatic ischemia for 15min and reperfusion for 60min. The total group was submitted to controlled hemorrhagic shock for 20min followed by volemic resuscitation (lactated Ringer's solution + blood, 3:1, total hepatic ischemia for 15min and reperfusion for 60min. Measurements of serum lactate and base excess were used to characterize the hemorrhagic shock state with low tissue perfusion. The counting of neutrophils on the brain was performed after the euthanasia of animals. RESULTS: The values for the counting of neutrophils on the brain indicate that did not occur difference among studied groups (p=0.196 (Control 0.12± 0.11, Shock 0.12± 0.13, Pringle 0.02± 0.04, Total 0.14± 0.16. CONCLUSION: Hemorrhagic shock associated to total hepatic ischemia for 15 minutes, followed by 60 minutes of reperfusion, did not causes significant neutrophils accumulation in the brain of rats.

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

    Directory of Open Access Journals (Sweden)

    Woranan Kirisattayakul

    2012-01-01

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

  2. Cortisol in plasma and cerebrospinal fluid of patients with brain ischemia

    Directory of Open Access Journals (Sweden)

    Selaković Vesna M.

    2004-01-01

    Full Text Available Introduction One of the reactions to ischemia is increased release of glucocorticoid hormones, included in regulation of effects of numerous mediators/modulators that could be released in the acute phase of brain ischemia. The aim of our investigation was to define temporal dynamics of cortisol concentrations in plasma and cerebrospinal fluid of patients with different types of ischemic brain disease. Material and methods The study included 263 patients of both sexes, aged 55-68 years. History, clinical examination and cerebral computerized tomography were performed to establish the diagnosis. 97 patients had brain infarction, 66 had a reversible ischemic attack, 66 had a transient ischemic attack, and 34 patients had chronic encephalopathy. The control group included 22 age- and sex- matched patients, subjected to diagnostic lumbar radiculography, without disturbances in the cerebrospinal fluid passage. Cortisol concentrations were measured by direct radioimmunoassay. Results and discussion Results obtained in this research showed that in acute brain ischemic period there was a significant increase of cortisol concentration in plasma and cerebrospinal fluid. The increase was highest in patients with brain infarction, somewhat lower in reversible ischemic attack, and the lowest in transient ischemic attack compared to controls (331.7±92.8 pmol/ml of plasma and 2.5±1.1 pmol/ml of cerebrospinal fluid. Maximum concentrations were found during the first two days after insult. The main potentially protective effects of increased cortisol concentrations in patients with acute stroke could be the decrease of effects of deleterious reactions induced by ischemia. This mechanism might be an attempt of organism to compensate for disturbed homeostasis. Conclusion Measurement of cortisol in plasma and cerebrospinal fluid in patients with acute stroke is significant for monitoring the intensity of response of an organism to acute brain damage.

  3. Accumulation of N-acyl-ethanolamine phospholipids in rat brains during post-decapitative ischemia

    DEFF Research Database (Denmark)

    Moesgaard, B.; Hansen, Harald S.; Jaroszewski, J.W.

    1999-01-01

    Phosphorus-31 nuclear magnetic resonance (P NMR) spectroscopy has been used to study accumulation of N-acyl-ethanolamine phospholipids in rat brains during post-decapitative ischemia. Lipids were extracted from rat brain homogenates and the extracts were thoroughly washed with aq. potassium......-phospho(N-acyl)-ethanolamine (NAPE(PLAS)), respectively, by spiking with authentic materials. Additionally, the identification was verified by thin-layer chromatography, which also showed the accumulation of N-acyl-ethanolamine phospholipids. The use of K-EDTA instead of the commonly used Cs...

  4. Uptake of radiolabeled ions in normal and ischemia-damaged brain

    Energy Technology Data Exchange (ETDEWEB)

    Dienel, G.A.; Pulsinelli, W.A.

    1986-05-01

    The regional concentrations of nine radiochemicals were measured in rat brain after induction of cerebral ischemia to identify tracers concentrated by brain undergoing selective neuronal necrosis. Transient (30 minute) forebrain ischemia was produced in the rat; 24 hours after cerebral recirculation the radiochemicals were injected intravenously and allowed to circulate for 5 hours. The brain concentrations of the radiochemicals in dissected regions were determined by scintillation counting. Forebrain ischemia of this nature will produce extensive injury to striatal neurons but will spare the great majority of neocortical neurons at 24 hours. The regional concentrations of these radiochemicals varied considerably in both control and ischemic animals. In postischemic animals, 4 radionuclides (/sup 63/Ni, /sup 99/TcO/sub 4/, /sup 22/Na, and (/sup 3/H)tetracycline) were concentrated in the irreversibly damaged striatum in amounts ranging from 1.4 to 2.4 times greater than in normal tissue. The concentrations of /sup 65/Zn, /sup 59/Fe, /sup 32/PO/sub 4/, and /sup 147/Pm in postischemic brain were similar to or less than those in normal brain. The concentration of (14C)EDTA was increased in injured and uninjured brain of postischemic rats. Autoradiographic analysis of the distribution patterns of some of these ions in normal animals showed that /sup 99/TcO/sub 4/, /sup 22/Na, /sup 65/Zn, and /sup 59/Fe were distributed more uniformly throughout the brain than were /sup 32/PO/sub 4/, /sup 63/Ni, and /sup 147/Pm. At 24 or 48 hours after ischemia, /sup 63/Ni, /sup 99/TcO/sub 4/, and /sup 22/Na were preferentially concentrated in the damaged striatum and hippocampus, whereas /sup 65/Zn, /sup 59/Fe, /sup 32/PO/sub 4/, and /sup 147/Pm did not accumulate in irreversibly injured tissue. Of the radiochemicals tested to date, Ni, TcO/sub 4/, and tetracycline may be useful for diagnosing ischemic brain injury in humans, using positron emission tomography.

  5. Blockade of brain angiotensin II AT1 receptors ameliorates stress, anxiety, brain inflammation and ischemia: Therapeutic implications.

    Science.gov (United States)

    Saavedra, Juan M; Sánchez-Lemus, Enrique; Benicky, Julius

    2011-01-01

    Poor adaptation to stress, alterations in cerebrovascular function and excessive brain inflammation play critical roles in the pathophysiology of many psychiatric and neurological disorders such as major depression, schizophrenia, post traumatic stress disorder, Parkinson's and Alzheimer's diseases and traumatic brain injury. Treatment for these highly prevalent and devastating conditions is at present very limited and many times inefficient, and the search for novel therapeutic options is of major importance. Recently, attention has been focused on the role of a brain regulatory peptide, Angiotensin II, and in the translational value of the blockade of its physiological AT(1) receptors. In addition to its well-known cardiovascular effects, Angiotensin II, through AT(1) receptor stimulation, is a pleiotropic brain modulatory factor involved in the control of the reaction to stress, in the regulation of cerebrovascular flow and the response to inflammation. Excessive brain AT(1) receptor activity is associated with exaggerated sympathetic and hormonal response to stress, vulnerability to cerebrovascular ischemia and brain inflammation, processes leading to neuronal injury. In animal models, inhibition of brain AT(1) receptor activity with systemically administered Angiotensin II receptor blockers is neuroprotective; it reduces exaggerated stress responses and anxiety, prevents stress-induced gastric ulcerations, decreases vulnerability to ischemia and stroke, reverses chronic cerebrovascular inflammation, and reduces acute inflammatory responses produced by bacterial endotoxin. These effects protect neurons from injury and contribute to increase the lifespan. Angiotensin II receptor blockers are compounds with a good margin of safety widely used in the treatment of hypertension and their anti-inflammatory and vascular protective effects contribute to reduce renal and cardiovascular failure. Inhibition of brain AT(1) receptors in humans is also neuroprotective

  6. MLKL inhibition attenuates hypoxia-ischemia induced neuronal damage in developing brain.

    Science.gov (United States)

    Qu, Yi; Shi, Jing; Tang, Ying; Zhao, Fengyan; Li, Shiping; Meng, Junjie; Tang, Jun; Lin, Xuemei; Peng, Xiaodong; Mu, Dezhi

    2016-05-01

    Mixed lineage kinase domain-like protein (MLKL) is a critical molecule mediating cell necroptosis. However, its role in brain injury remains obscure. We first investigated the functions and mechanisms of MLKL in mediating neuronal damage in developing brain after hypoxia-ischemia. Neuronal necroptosis was induced by oxygen-glucose deprivation (OGD) plus caspase inhibitor zVAD treatment (OGD/zVAD). We found that two important necroptosis related proteins, receptor-interacting protein 1 and 3 (RIP1, RIP3) were upregulated. Furthermore, the interaction of RIP1-RIP3 with MLKL increased. Inhibition of MLKL through siRNA diminished RIP1-RIP3-MLKL interaction and attenuated neuronal death induced by OGD/zVAD. The translocation of oligomerized MLKL to the neuronal membrane leading to the injury of cellular membrane is the possible new mechanism of neuronal necroptosis. Animal experiment with neonatal rats further proved that MLKL inhibition attenuated brain damage induced by hypoxia-ischemia. These findings suggest that MLKL is a target to attenuate brain damage in developing brain.

  7. Effect of MCI-186 on ischemia-induced changes in monoamine metabolism in rat brain.

    Science.gov (United States)

    Oishi, R; Itoh, Y; Nishibori, M; Watanabe, T; Nishi, H; Saeki, K

    1989-11-01

    We examined the effects of MCI-186 (3-methyl-1-phenyl-2-pyrazolin-5-one), a novel free radical scavenger and an inhibitor of ischemia-induced brain edema, on monoamine metabolism in the brains of both normal and ischemic rats. In normal rats, 3 mg/kg i.v. MCI-186, a dose that prevents ischemic brain edema, had no significant effect on brain concentrations of dopamine, norepinephrine, 5-hydroxytryptamine, or their metabolites. After the injection of 5 microliters of 3% polyvinyl acetate into the left internal carotid artery, concentrations of 3,4-dihydroxyphenylacetic acid and homovanillic acid markedly increased, but that of norepinephrine decreased, in the left telencephalon of embolized rats compared with control rats injected with vehicle; the concentration of 5-hydroxyindoleacetic acid also increased slightly. These effects were maximal 2 hours after embolization. The turnover rate of dopamine between 6 and 8 hours after embolization was significantly higher but that of norepinephrine was slightly lower than that in vehicle-treated rats. When rats were treated with 3 mg/kg i.v. MCI-186 immediately after the injection of polyvinyl acetate, the embolization-induced changes in monoamine metabolism were less marked. Our results suggest that MCI-186 attenuates ischemia-induced changes in brain monoamine metabolism, probably due to its free radical scavenging action, although it has no marked effect in normal rats. PMID:2815191

  8. 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.

  9. Neuroprotective mechanism of the novel melatonin derivative Neu-P11 in brain ischemia related models.

    Science.gov (United States)

    Buendia, Izaskun; Gómez-Rangel, Vanessa; González-Lafuente, Laura; Parada, Esther; León, Rafael; Gameiro, Isabel; Michalska, Patrycja; Laudon, Moshe; Egea, Javier; López, Manuela G

    2015-12-01

    Stopping the ischemic cascade by targeting its components is a potential strategy for acute ischemic stroke treatment. During ischemia and especially over reperfusion, oxidative stress plays a major role in causing neuronal cell death. Melatonin has been previously reported to provide neuroprotective effects in in vivo models of stroke by a mechanism that implicates melatonin receptors. In this context, this study was planned to test the potential neuroprotective effects of the novel melatonin MT1/MT2 receptor agonist, Neu-P11, against brain ischemia in in vitro and in vivo models, and to elucidate its underlying mechanism of action. Neu-P11 proved to be a good antioxidant, to protect against glutamate-induced excitotoxicity and oxygen and glucose deprivation in hippocampal slices, and to reduce infarct volume in an in vivo stroke model. Regarding its mechanism of action, the protective effect of Neu-P11 was reverted by luzindole (melatonin receptor antagonist), AG490 (JAK2 inhibitor), LY294002 (PI3/AKT inhibitor) and PD98059 (MEK/ERK1/2 inhibitor). In conclusion, Neu-P11 affords neuroprotection against brain ischemia in in vitro and in vivo models by activating a pro-survival signaling pathway that involves melatonin receptors, JAK/STAT, PI3K/Akt and MEK/ERK1/2.

  10. Pretreatment with Danhong injection protects the brain against ischemia-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Shaoxia Wang; Hong Guo; Xumei Wang; Lijuan Chai; Limin Hu; Tao Zhao; Buchang Zhao; Xiaoxu Tan; Feifei Jia

    2014-01-01

    Danhong injection (DHI), a Chinese Materia Medica standardized product extracted from Radix Salviae miltiorrhizae and Flos Carthami tinctorii, is widely used in China for treating acute isch-emic stroke. In the present study, we explored the neuroprotective efifcacy of DHI in a rat model of temporary middle cerebral artery occlusion, and evaluated the potential mechanisms under-lying its effects. Pretreatment with DHI (0.9 and 1.8 mL/kg) resulted in a signiifcantly smaller infarct volume and better neurological scores than pretreatment with saline. Furthermore, DHI significantly reduced the permeability of the blood-brain barrier, increased occludin protein expression and decreased neutrophil inifltration, as well as profoundly suppressing the upreg-ulation of matrix metallopeptidase-9 expression seen in rats that had received vehicle. Matrix metallopeptidase-2 expression was not affected by ischemia or DHI. Moreover, DHI (1.8 mL/kg) administered 3 hours after the onset of ischemia also improved neurological scores and reduced infarct size. Our results indicate that the neuroprotective efifcacy of DHI in a rat model of ce-rebral ischemia-reperfusion injury is mediated by a protective effect on the blood-brain barrier and the reversal of neutrophil inifltration.

  11. Pretreatment with Danhong injection protects the brain against ischemia-reperfusion injury.

    Science.gov (United States)

    Wang, Shaoxia; Guo, Hong; Wang, Xumei; Chai, Lijuan; Hu, Limin; Zhao, Tao; Zhao, Buchang; Tan, Xiaoxu; Jia, Feifei

    2014-08-01

    Danhong injection (DHI), a Chinese Materia Medica standardized product extracted from Radix Salviae miltiorrhizae and Flos Carthami tinctorii, is widely used in China for treating acute ischemic stroke. In the present study, we explored the neuroprotective efficacy of DHI in a rat model of temporary middle cerebral artery occlusion, and evaluated the potential mechanisms underlying its effects. Pretreatment with DHI (0.9 and 1.8 mL/kg) resulted in a significantly smaller infarct volume and better neurological scores than pretreatment with saline. Furthermore, DHI significantly reduced the permeability of the blood-brain barrier, increased occludin protein expression and decreased neutrophil infiltration, as well as profoundly suppressing the upregulation of matrix metallopeptidase-9 expression seen in rats that had received vehicle. Matrix metallopeptidase-2 expression was not affected by ischemia or DHI. Moreover, DHI (1.8 mL/kg) administered 3 hours after the onset of ischemia also improved neurological scores and reduced infarct size. Our results indicate that the neuroprotective efficacy of DHI in a rat model of cerebral ischemia-reperfusion injury is mediated by a protective effect on the blood-brain barrier and the reversal of neutrophil infiltration.

  12. Transplantation of human neural stem/progenitor cells overexpressing galectin-1 improves functional recovery from focal brain ischemia in the mongolian gerbil

    Directory of Open Access Journals (Sweden)

    Yamane Junichi

    2011-09-01

    Full Text Available Abstract Transplantation of human neural stem/progenitor cells (hNSPCs is a promising method to regenerate tissue from damage and recover function in various neurological diseases including brain ischemia. Galectin-1(Gal1 is a lectin that is expressed in damaged brain areas after ischemia. Here, we characterized the detailed Gal1 expression pattern in an animal model of brain ischemia. After brain ischemia, Gal1 was expressed in reactive astrocytes within and around the infarcted region, and its expression diminished over time. Previously, we showed that infusion of human Gal1 protein (hGal1 resulted in functional recovery after brain ischemia but failed to reduce the volume of the ischemic region. This prompted us to examine whether the combination of hNSPCs-transplantation and stable delivery of hGal1 around the ischemic region could reduce the ischemic volume and promote better functional recovery after brain ischemia. In this study, we transplanted hNSPCs that stably overexpressed hGal1 (hGal1-hNSPCs in a model of unilateral focal brain ischemia using Mongolian gerbils. Indeed, we found that transplantation of hGal1-hNSPCs both reduced the ischemic volume and improved deficits in motor function after brain ischemia to a greater extent than the transplantation of hNSPCs alone. This study provides evidence for a potential application of hGal1 with hNSPCs-transplantation in the treatment of brain ischemia.

  13. IMPACT OF SEVOFLURANE AND ACETYLCYSTEINE ON ISCHEMIA-REPERFUSION INJURY OF THE LIVER FROM BRAIN-DEAD DONOR

    Directory of Open Access Journals (Sweden)

    A. E. Shcherba

    2013-01-01

    Full Text Available Aim. The purpose of our work was to estimate the impact of preconditioning with acetylcysteine and sevoflurane on ischemia-reperfusion injury of cadaveric donor liver with marginal features. Methods and results. In this prospective randomized controlled trial we recruited 21 heart beating donors with brain death. We assigned 11 donors to the study group, and 10 donors to the control group. Morphological characteristics of ischemia- reperfusion injury in both groups were analyzed. Conclusion. Use of pharmacological preconditioning with acetylcysteine and sevoflurane resulted in necrosis and hepatocyte apoptosis reduction as compared to the control group, thereby had a protective effect against ischemia-reperfusion injury. 

  14. Developmental changes of glutamate acid decarboxylase 67 in mouse brain after hypoxia ischemia

    Institute of Scientific and Technical Information of China (English)

    Fa-Lin XU; Chang-Lian ZHU; Xiao-Yang WANG

    2006-01-01

    Objective To study the developmental changes of glutamic acid decarboxylase-67 ( GAD-67, a GABA synthetic enzyme) in normal and hypoxic ischemic (HI) brain. Methods C57/BL6 mice on postnatal day (P) 5, 9, 21and 60, corresponding developmentally to premature, term, juvenile and adult human brain were investigated by using both Western blot and immunohistochemistry methods either in normal condition or after hypoxic ischemic insult. Results The immunoreactivity of GAD67 was up regulated with brain development and significant difference was seen between mature (P21, P60) and immature (P5, P9) brain. GAD67 immunoreactivity decreased in the ipsilateral hemisphere in all the ages after hypoxia ischemia (HI) insult, but, significant decrease was only seen in the immature brain. Double labeling of GAD67 and cell death marker, TUNEL, in the cortex at 8h post-HI in the P9 mice showed that (15.6 ±7.0)%TUNEL positive cells were GAD67 positive which was higher than that of P60 mice. Conclusion These data suggest that GABAergic neurons in immature brain were more vulnerable to HI insult than that of mature brain.

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

  17. Cortical and brain stem changes in neural activity during static handgrip and postexercise ischemia in humans

    DEFF Research Database (Denmark)

    Sander, Mikael; Macefield, Vaughan G; Henderson, Luke A

    2010-01-01

    , and to differentiate between central command and reflex inputs, we used blood oxygen level-dependent (BOLD) functional MRI (fMRI) of the whole brain (3 T). Subjects performed submaximal static handgrip exercise for 2 min followed by 6 min of PEI; MSNA was recorded on a separate day. During the contraction phase......Static isometric exercise increases muscle sympathetic nerve activity (MSNA) and mean arterial pressure, both of which can be maintained at the conclusion of the exercise by occlusion of the arterial supply [postexercise ischemia (PEI)]. To identify the cortical and subcortical sites involved...

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

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

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

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

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    Jinatta Jittiwat

    2009-01-01

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

  20. Neuroprotective effects of consuming bovine colostrum after focal brain ischemia/reperfusion injury in rat model

    Science.gov (United States)

    Choi, Han Sung; Ko, Young Gwan; Lee, Jong Seok; Kwon, Oh Young; Kim, Sun-Kyu; Cheong, Chul; Jang, Ki-Hyo

    2010-01-01

    To investigate the neuroprotective effects of bovine colostrums (BC), we evaluate the ability of consuming BC after focal brain ischemia/reperfusion injury rat model to reduce serum cytokine levels and infarct volume, and improve neurological outcome. Sprague-Dawley rats were randomly divided into 4 groups; one sham operation and three experimental groups. In the experimental groups, MCA occlusion (2 h) and subsequent reperfusion (O/R) were induced with regional cerebral blood flow monitoring. One hour after MCAO/R and once daily during the experiment, the experimental group received BC while the other groups received 0.9% saline or low fat milk (LFM) orally. Seven days later, serum pro-inflammatory cytokine (IL-1β, IL-6, and TNF-α) and anti-inflammatory cytokine (IL-10) levels were assessed. Also, the infarct volume was assessed by using a computerized image analysis system. Behavioral function was also assessed using a modified neurologic severity score and corner turn test during the experiment. Rats receiving BC after focal brain I/R showed a significant reduction (-26%/-22%) in infarct volume compared to LFM/saline rats, respectively (P < 0.05). Serum IL-1β, IL-6, and TNF-α levels were decreased significantly in rats receiving BC compared to LFM/saline rats (P < 0.05). In behavioral tests, daily BC intake showed consistent and significant improvement of neurological deficits for 7 days after MCAO/R. BC ingestion after focal brain ischemia/reperfusion injury may prevent brain injury by reducing serum pro-inflammatory cytokine levels and brain infarct volume in a rat model. PMID:20607064

  1. Antimicrobial peptides and complement in neonatal hypoxia-ischemia induced brain damage

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    Eridan eRocha-Ferreira

    2015-02-01

    Full Text Available Hypoxic-ischemic encephalopathy (HIE is a clinical condition in the neonate, resulting from oxygen deprivation around the time of birth. HIE affects 1-5 per 1000 live births worldwide and is associated with the development of neurological deficits, including cerebral palsy, epilepsy and cognitive disabilities. Even though the brain is considered an immune-privileged site, it has innate and adaptive immune response and can produce complement (C components and antimicrobial peptides (AMPs. Dysregulation of cerebral expression of AMPs and C can exacerbate or ameliorate the inflammatory response within the brain.Brain ischemia triggers a prolonged inflammatory response affecting the progression of injury and secondary energy failure and involves both innate and adaptive immune systems, including immune-competent and non-competent cells. Following injury to the central nervous system (CNS, including neonatal hypoxia-ischemia (HI, resident microglia and astroglia are the main cells providing immune defence to the brain in a stimulus-dependent manner. They can express and secrete pro-inflammatory cytokines and therefore trigger prolonged inflammation resulting in neurodegeneration. Microglial cells express and release a wide range of inflammation-associated molecules including several components of the complement system. Complement activation following neonatal HI-injury has been reported to contribute to neurodegeneration. Astrocytes can significantly affect the immune response of the CNS under pathological conditions through production and release of pro-inflammatory cytokines and immunomodulatory AMPs. Astrocytes express β-defensins which can chemoattract and promote maturation of dendritic cells, and can also limit inflammation by controlling the viability of these same dendritic cells. This review will focus on the balance of complement components and AMPs within the CNS following neonatal HI-injury and the effect of that balance on the

  2. 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

  3. Look into brain energy crisis and membrane pathophysiology in ischemia and reperfusion.

    Science.gov (United States)

    Chomova, Maria; Zitnanova, Ingrid

    2016-07-01

    In an ischemic environment, brain tissue responds to oxygen deprivation with the initiation of rapid changes in bioenergetic metabolism to ensure ion and metabolic homeostasis. At the same time, the accelerated cleavage of membrane phospholipids changes membrane composition and increases free fatty acid concentration. Phospholipid breakdown also generates specific messengers that participate in signaling cascades that can either promote neuronal protection or cause injury. The net impact of signaling events affects the final outcome of the stroke. While reoxygenation is a life-saving intervention, it can exacerbate brain damage. Although compromised energy metabolism is restored shortly after reperfusion, alterations in membrane phospholipid composition with subsequent accumulation of lipid oxoderivates are neurotoxic, causing oxidative stress and ischemia-reperfusion (IR) injury. Thus, plasma and mitochondrial membranes are the first responders as well as mediators of IR-induced stress signals. In this review, we focus on ischemia-induced changes in brain energy metabolism and membrane functions as the causal agents of cell stress responses upon reoxygenation. The first part of the review deals with the specificities of neuronal bioenergetics during IR and their impact on metabolic processes. The second part is concentrated on involvement of both plasma and mitochondrial membranes in the production of messengers which can modulate neuroprotective pathways or participate in oxidative/electrophilic stress responses. Although the etiology of IR injury is multifactorial, deciphering the role of membrane and membrane-associated processes in brain damage will uncover new therapeutic agents with the ability to stabilize neuronal membranes and modulate their responses in favor of prosurvival pathways. PMID:27095435

  4. [Effect of salvianolic acid B on neural cells damage and neurogenesis after brain ischemia-reperfusion in rats].

    Science.gov (United States)

    Zhong, Jing; Tang, Min-ke; Zhang, Yan; Xu, Qiu-ping; Zhang, Jun-tian

    2007-07-01

    This study is to observe the effect of salvianolic acid B (Sal B) on neural cells damage and neurogenesis in sub-granular zone (SGZ) and sub-ventricular zone (SVZ) after brain ischemia-reperfusion (I/R) in rats. A modified middle cerebral artery occlusion (MCAO) model of focal cerebral ischemia-reperfusion was used. The rats were divided into four groups: sham control group, ischemia-reperfusion group, Sal B 1 and 10 mg x kg(-1) groups. Sal B was consecutively administrated once a day by ip injection after MCAO. The neurogenesis in SGZ and SVZ was investigated by BrdU method 7 days after MCAO. The Nissl staining for neurons in the hippocampal CA1 and cerebral cortex was performed 14 days after MCAO. A beam-walking test was used to monitor the motor function recovery. We found that brain ischemia resulted in an increase of BrdU positive cells both in ipsilateral SGZ and SVZ at 7th day after MCAO. Sal B (10 mg x kg(-1)) significantly increased further the number of BrdU positive cells both in SGZ and SVZ (P loss and improved motor function recovery after brain ischemia in rats.

  5. 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

  6. Microglial involvement in neuroplastic changes following focal brain ischemia in rats.

    Directory of Open Access Journals (Sweden)

    Alexandre Madinier

    Full Text Available The pathogenesis of ischemic stroke is a complex sequence of events including inflammatory reaction, for which the microglia appears to be a major cellular contributor. However, whether post-ischemic activation of microglial cells has beneficial or detrimental effects remains to be elucidated, in particular on long term brain plasticity events. The objective of our study was to determine, through modulation of post-stroke inflammatory response, to what extent microglial cells are involved in some specific events of neuronal plasticity, neurite outgrowth and synaptogenesis. Since microglia is a source of neurotrophic factors, the identification of the brain-derived neurophic factor (BDNF as possible molecular actor involved in these events was also attempted. As a means of down-regulating the microglial response induced by ischemia, 3-aminobenzamide (3-AB, 90 mg/kg, i.p. was used to inhibit the poly(ADP-ribose polymerase-1 (PARP-1. Indeed, PARP-1 contributes to the activation of the transcription factor NF-kB, which is essential to the upregulation of proinflammatory genes, in particular responsible for microglial activation/proliferation. Experiments were conducted in rats subjected to photothrombotic ischemia which leads to a strong and early microglial cells activation/proliferation followed by an infiltration of macrophages within the cortical lesion, events evaluated at serial time points up to 1 month post-ictus by immunostaining for OX-42 and ED-1. Our most striking finding was that the decrease in acute microglial activation induced by 3-AB was associated with a long term down-regulation of two neuronal plasticity proteins expression, synaptophysin (marker of synaptogenesis and GAP-43 (marker of neuritogenesis as well as to a significant decrease in tissue BDNF production. Thus, our data argue in favour of a supportive role for microglia in brain neuroplasticity stimulation possibly through BDNF production, suggesting that a targeted

  7. Preventive administration of cromakalim reduces aquaporin-4 expression and blood-brain barrier permeability in a rat model of cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Shilei Wang; Yanting Wang; Yan Jiang; Qingxian Chang; Peng Wang; Shiduan Wang

    2011-01-01

    Cromakalim, an adenosine triphosphate-sensitive potassium channel opener, exhibits protective effects on cerebral ischemia/reperfusion injury. However, there is controversy as to whether this effect is associated with aquaporin-4 and blood-brain barrier permeability. Immunohistochemistry results show that preventive administration of cromakalim decreased aquaporin-4 and IgG protein expression in rats with ischemia/reperfusion injury; it also reduced blood-brain barrier permeability, and alleviated brain edema, ultimately providing neuroprotection.

  8. Inhibition of chemokine-like factor 1 improves blood-brain barrier dysfunction in rats following focal cerebral ischemia.

    Science.gov (United States)

    Kong, Ling-Lei; Wang, Zhi-Yuan; Hu, Jin-Feng; Yuan, Yu-He; Li, Hua; Chen, Nai-Hong

    2016-08-01

    Disruption of blood-brain barrier (BBB) and subsequent edema are major contributors to the pathogenesis of ischemic stroke, and the current clinical therapy remains unsatisfied. Chemokine-like factor 1 (CKLF1), as a novel C-C chemokine, plays important roles in immune response. The expression of CKLF1 increased after focal cerebral ischemia and inhibition of CKLF1 activity showed neuroprotective effect by alleviating infiltration of neutrophil and neuron apoptosis in cerebral ischemia. However, few studies have focused on the role of CKLF1 on BBB integrity. The objective of present study was to investigate the role of CKLF1 on BBB integrity by applying anti-CKLF1 antibodies in rat focal cerebral ischemia and reperfusion model. Brain water content, Evans blue leakage and the expression of aquaporin-4 (AQP-4), matrix metalloproteinase-9 (MMP-9), Zonula Occludens-1 (ZO-1) and Occludin were measured. After treatment with anti-CKLF1 antibody, brain water content and Evans blue leakage in ipsilateral hemisphere were decreased in a dose-dependent manner at 24h after reperfusion, but not changed in contralateral hemisphere. Anti-CKLF1 antibody reduced the expression of AQP-4 and MMP-9, and upregulated the expression of ZO-1 and Occludin. These results suggest that CKLF1 is involved in BBB disruption after reperfusion. Inhibition of CKLF1 protects against cerebral ischemia by maintaining BBB integrity, possibly via inhibiting the expression of AQP-4 and MMP-9, and increasing the expression of tight junction protein. PMID:27283776

  9. Brain immune cell composition and functional outcome after cerebral ischemia: Comparison of two mouse strains

    Directory of Open Access Journals (Sweden)

    Hyun Ah eKim

    2014-11-01

    Full Text Available Inflammatory cells may contribute to secondary brain injury following cerebral ischemia. The C57Bl/6 mouse strain is known to exhibit a T helper 1-prone, pro-inflammatory type response to injury, whereas the FVB strain is relatively T helper 2-prone, or anti-inflammatory, in its immune response. We tested whether stroke outcome is more severe in C57Bl/6 than FVB mice. Male mice of each strain underwent sham surgery or 1 h occlusion of the middle cerebral artery followed by 23 h of reperfusion. Despite no difference in infarct size, C57Bl/6 mice displayed markedly greater functional deficits than FVB mice after stroke, as assessed by neurological scoring and hanging wire test. Total numbers of CD45+ leukocytes tended to be larger in the brains of C57Bl/6 than FVB mice after stroke, but there were marked differences in leukocyte composition between the two mouse strains. The inflammatory response in C57Bl/6 mice primarily involved T and B lymphocytes, whereas neutrophils, monocytes and macrophages were more prominent in FVB mice. Our data are consistent with the concept that functional outcome after stroke is dependent on the immune cell composition which develops following ischemic brain injury.

  10. How does the motor relearning program improve neurological function of brain ischemia monkeys?

    Institute of Scientific and Technical Information of China (English)

    Yong Yin; Zhongtang Feng; Zhen Gu; Lei Pan; Lu Gan; Dongdong Qin; Bo Yang; Jin Guo; Xintian Hu; Tinghua Wang

    2013-01-01

    The motor relearning program can significantly improve various functional disturbance induced by ischemic cerebrovascular diseases. However, its mechanism of action remains poorly understood. In injured brain tissues, glial fibrillary acidic protein and neurofilament protein changes can reflect the condition of injured neurons and astrocytes, while vascular endothelial growth factor and basic fibroblast growth factor changes can indicate angiogenesis. In the present study, we induced ischemic brain injury in the rhesus macaque by electrocoagulation of the M1 segment of the right middle cerebral artery. The motor relearning program was conducted for 60 days from the third day after model establishment. Immunohistochemistry and single-photon emission CT showed that the numbers of glial fibrillary acidic protein-, neurofilament protein-, vascular endothelial growth factorand basic fibroblast growth factor-positive cells were significantly increased in the infarcted side compared with the contralateral hemisphere following the motor relearning program. Moreover, cerebral blood flow in the infarcted side was significantly improved. The clinical rating scale for stroke was used to assess neurological function changes in the rhesus macaque following the motor relearning program. Results showed that motor function was improved, and problems with consciousness, self-care ability and balance function were significantly ameliorated. These findings indicate that the motor relearning program significantly promoted neuronal regeneration, repair and angiogenesis in the surroundings of the infarcted hemisphere, and improve neurological function in the rhesus macaque following brain ischemia.

  11. Mechanisms of oxidative stress in brain ischemia injury%氧化应激在脑缺血损伤中的作用机制

    Institute of Scientific and Technical Information of China (English)

    赵丹洋; 吴伟康

    2004-01-01

    Oxidative stress has been implicated in brain injury after ischemia, which is a complex cascade. These oxidants produced by oxidative stress are directly involved in oxidative damage with cellular macromolecules such as lipids, proteins and nucleic acids, which lead to cell death. Oxidants are also mediators in signaling involving mitochondria pathway, DNA repair enzymes, and transcription factor that may lead to apoptosis after cerebral ischemia. Antioxidangt enzymes (such as superoxide dismutase,etc) provide useful tools in dissecting the events involving oxidative stress in signaling and damage in ischemic brain injury. This review focuses on the mechanisms of oxidative stress during brain ischemia.

  12. Whole brain CT perfusion in acute anterior circulation ischemia: coverage size matters

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    Emmer, B.J. [Erasmus Medical Centre, Department of Radiology, Postbus 2040, Rotterdam (Netherlands); Rijkee, M.; Walderveen, M.A.A. van [Leiden University Medical Centre, Department of Radiology, Leiden (Netherlands); Niesten, J.M.; Velthuis, B.K. [University Medical Centre Utrecht, Department of Radiology, Utrecht (Netherlands); Wermer, M.J.H. [Leiden University Medical Centre, Department of Neurology, Leiden (Netherlands)

    2014-12-15

    Our aim was to compare infarct core volume on whole brain CT perfusion (CTP) with several limited coverage sizes (i.e., 3, 4, 6, and 8 cm), as currently used in routine clinical practice. In total, 40 acute ischemic stroke patients with non-contrast CT (NCCT) and CTP imaging of anterior circulation ischemia were included. Imaging was performed using a 320-multislice CT. Average volumes of infarct core of all simulated partial coverage sizes were calculated. Infarct core volume of each partial brain coverage was compared with infarct core volume of whole brain coverage and expressed using a percentage. To determine the optimal starting position for each simulated CTP coverage, the percentage of infarct coverage was calculated for every possible starting position of the simulated partial coverage in relation to Alberta Stroke Program Early CT Score in Acute Stroke Triage (ASPECTS 1) level. Whole brain CTP coverage further increased the percentage of infarct core volume depicted by 10 % as compared to the 8-cm coverage when the bottom slice was positioned at the ASPECTS 1 level. Optimization of the position of the region of interest (ROI) in 3 cm, 4 cm, and 8 cm improved the percentage of infarct depicted by 4 % for the 8-cm, 7 % for the 4-cm, and 13 % for the 3-cm coverage size. This study shows that whole brain CTP is the optimal coverage for CTP with a substantial improvement in accuracy in quantifying infarct core size. In addition, our results suggest that the optimal position of the ROI in limited coverage depends on the size of the coverage. (orig.)

  13. Effect of PAMd on proteins expression of Bax and Bcl-2 of nerve cells in the brain tissue of ischemia-reperfusion mice

    Institute of Scientific and Technical Information of China (English)

    GUOLianjun; LVQing; QULing

    2004-01-01

    AIM : To study the effects of PAMd ( Phenolic alkaloids from Menispermum dauricum on Brain ischemia and ischemic reperfusion injury in mice. METHODS : Bilateral carotid arteries of mice were ligated and 0. 3ml blood was letted from post-eyeball venous jungle, one hour later the carotid arteries were loosed. After cerebral ischemia-reperfusion, mice

  14. Total Flavone of Hawthorn Leaf inhibits neuronal apoptosis in brain tissue of rat models of chronic cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Tan Rong-fang; Xia Ai-hua; Wu Xiao-guang; Cao Na-na; Li Meng-meng; Zhang Tian-ge; Wang Yi-ru; Yue Zhi-ling

    2014-01-01

    BACKGROUND: Cerebrovascular disease often causes dysfunction of the brain nerve, and nerve cel apoptosis is the important factor of cerebral nerve dysfunction. The excessive expression of c-fos can block the transduction of intracelular signal so that producing some apoptosis-promoting factors, which involve in nerve cel apoptosis process after ischemia injury of brain. Bcl-2 is an inhibited factor. It might to be the key to treat ischemic cerebrovascular disease by inhibiting or reducing the apoptosis of nerve cels after ischemia injury. OBJECTIVE: To investigate the therapeutic effect and mechanism of the Total Flavone of Hawthorn Leaf on chronic cerebral ischemia rats. METHODS: A total of 72 healthy male Sprague-Dawley rats were randomly divided into sham surgery group, model group, Total Flavone of Hawthorn Leaf group and ginkgo leaf group. Permanent bilateral carotid artery ligation was used to prepare chronic cerebral ischemia model in the model group, Total Flavone of Hawthorn Leaf group and ginkgo leaf group. Total Flavone of Hawthorn Leaf group and ginkgo leaf group respectively received 140 mg/kg Total Flavone of Hawthorn Leaf and 12.3 mg/kg ginkgo leaf intragastricaly for 36 days from 36 days after model induction. Model group and sham surgery group received 3.5 mL/kg physiological saline intragastricaly. RESULTS AND CONCLUSION: Compared with the model group, the expression of c-fos protein significantly deceased in the Total Flavone of Hawthorn Leaf group (P 0.05). These data indicated that the protective effect of Total Flavone of Hawthorn Leaf on chronic cerebral ischemia was associated with its inhibition of neuronal apoptosis. Its mechanism of anti-apoptosis might be associated with up-regulating expression of Bcl-2, down-regulating expression of c-fos and decreasing Ca2+ content in brain.

  15. Placental ischemia-induced increases in brain water content and cerebrovascular permeability: role of TNF-α.

    Science.gov (United States)

    Warrington, Junie P; Drummond, Heather A; Granger, Joey P; Ryan, Michael J

    2015-12-01

    Cerebrovascular complications and increased risk of encephalopathies are characteristic of preeclampsia and contribute to 40% of preeclampsia/eclampsia-related deaths. Circulating tumor necrosis factor-α (TNF-α) is elevated in preeclamptic women, and infusion of TNF-α into pregnant rats mimics characteristics of preeclampsia. While this suggests that TNF-α has a mechanistic role to promote preeclampsia, the impact of TNF-α on the cerebral vasculature during pregnancy remains unclear. We tested the hypothesis that TNF-α contributes to cerebrovascular abnormalities during placental ischemia by first infusing TNF-α in pregnant rats (200 ng/day ip, from gestational day 14 to 19) at levels to mimic those reported in preeclamptic women. TNF-α increased mean arterial pressure (MAP, P blood-brain barrier (BBB) permeability in the anterior cerebrum or posterior cerebrum. We then assessed the role of endogenous TNF-α in mediating these abnormalities in a model of placental ischemia induced by reducing uterine perfusion pressure followed by treatment with the soluble TNF-α receptor (etanercept, 0.8 mg/kg sc) on gestational day 18. Etanercept reduced placental ischemia-mediated increases in MAP, anterior brain water content (P permeability (202 ± 44% in placental ischemic rats to 101 ± 28% of normal pregnant rats). Our results indicate that TNF-α mechanistically contributes to cerebral edema by increasing BBB permeability and is an underlying factor in the development of cerebrovascular abnormalities associated with preeclampsia complicated by placental ischemia.

  16. 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.

  17. Puerarin protects brain tissue against cerebral ischemia/reperfusion injur y by inhibiting the inlfammator y response

    Institute of Scientific and Technical Information of China (English)

    Feng Zhou; Liang Wang; Panpan Liu; Weiwei Hu; Xiangdong Zhu; Hong Shen; Yuanyuan Yao

    2014-01-01

    Puerarin, a traditional Chinese medicine, exerts a powerful neuroprotective effect in cerebral isch-emia/reperfusion injury, but its mechanism is unknown. Here, we established rat models of middle cerebral artery ischemia/reperfusion injury using the suture method. Puerarin (100 mg/kg) was administered intraperitoneally 30 minutes before middle cerebral artery occlusion and 8 hours after reperfusion. Twenty-four hours after reperfusion, we found that puerarin signiifcantly im-proved neurological deifcit, reduced infarct size and brain water content, and notably diminished the expression of Toll-like receptor-4, myeloid differentiation factor 88, nuclear factor kappa B and tumor necrosis factor-αin the ischemic region. These data indicate that puerarin exerts an anti-inlfammatory protective effect on brain tissue with ischemia/reperfusion damage by down-regulating the expression of multiple inlfammatory factors.

  18. Withania coagulans Extract Attenuates Histopathological Alteration and Apoptosis in Rat Brain Cortex Following Ischemia/Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Sarbishegi

    2016-01-01

    Full Text Available Background Cerebral ischemia and reperfusion (I/R is a pathological condition that arises by reduction or cessation in cerebral blood flow and return of oxygen and metabolites to brain cells, which cause oxidative damage. Objectives The aim of this study was to investigate the neuroprotective effects of Withania coagulans (WC extract on brain cortex in a rat model of I/R. Materials and Methods Thirty-two adult male Wistar rats weighing 280 - 300 g were used in this study. Animals were randomly divided to four groups (n = 8 as follow: sham operated group (I, I/R group (II, WCE500 + I/R (III and WCE1000 + I/R groups (IV. Pretreatment with WC extract (500, 1000 mg/kg was done by oral gavage for 30 days and global brain ischemia was induced by the common carotid occlusion for 30 minutes. After 72 hours, the animals were perfused transcardially and then the brains were prepared for histological study (H & E and TUNEL staining. Results The I/R group showed a significant increase in pycnotic (dying neurons and pretreatment with WC at doses of 500 mg/kg and 1000 mg/kg significantly reduced pycnotic and TUNEL positive neurons, in a dose dependent manner in ischemic brain cortex. Conclusions Our findings indicated that WC has neuroprotective effects and is able to reduce histopathological alterations and apoptosis in brain cortex I/R in rats.

  19. Dietary Virgin Olive Oil Reduces Blood Brain Barrier Permeability, Brain Edema, and Brain Injury in Rats Subjected to Ischemia-Reperfusion

    Directory of Open Access Journals (Sweden)

    Fatemeh Mohagheghi

    2010-01-01

    Full Text Available Recent studies suggest that dietary virgin olive oil (VOO reduces hypoxia-reoxygenation injury in rat brain slices. We sought to extend these observations in an in vivo study of rat cerebral ischemia-reperfusion injury. Four groups, each consisting of 18 Wistar rats, were studied. One group (control received saline, while three treatment groups received oral VOO (0.25, 0.5, and 0.75 mL/kg/day, respectively. After 30 days, blood lipid profiles were determined, before a 60-min period of middle cerebral artery occlusion (MCAO. After 24-h reperfusion, neurological deficit scores, infarct volume, brain edema, and blood brain barrier permeability were each assessed in subgroups of six animals drawn from each main group. VOO reduced the LDL/HDL ratio in doses of 0.25, 0.5, and 0.75 mL/kg/day in comparison to the control group (p < 0.05, and offered cerebroprotection from ischemia-reperfusion. For controls vs. doses of 0.25 vs. 0.5 vs. 0.75 mL/kg/day, attenuated corrected infarct volumes were 207.82 ± 34.29 vs. 206.41 ± 26.23 vs. 124.21 ± 14.73 vs. 108.46 ± 31.63 mm3; brain water content of the infarcted hemisphere was 82 ±± 0.25 vs. 81.5 ± 0.56 vs. 80.5 ± 0.22 vs. 80.5 ± 0.34%; and blood brain barrier permeability of the infarcted hemisphere was 11.31 ± 2.67 vs. 9.21 ± 2.28 vs. 5.83 ± 1.6 vs. 4.43 ± 0.93 µg/g tissue (p < 0.05 for measures in doses 0.5 and 0.75 mL/kg/day vs. controls. Oral administration of VOO reduces infarct volume, brain edema, blood brain barrier permeability, and improves neurologic deficit scores after transient MCAO in rats.

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

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

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

  2. Alteration in rectification of potassium channels in perinatal hypoxia ischemia brain damage.

    Science.gov (United States)

    Chen, Penghui; Wang, Liyan; Deng, Qiyue; Ruan, Huaizhen; Cai, Wenqin

    2015-01-15

    Oligodendrocyte progenitor cells (OPCs) are susceptible to perinatal hypoxia ischemia brain damage (HIBD), which results in infant cerebral palsy due to the effects on myelination. The origin of OPC vulnerability in HIBD, however, remains controversial. In this study, we defined the HIBD punctate lesions by MRI diffuse excessive high signal intensity (DEHSI) in postnatal 7-day-old rats. The electrophysiological functional properties of OPCs in HIBD were recorded by patch-clamp in acute cerebral cortex slices. The slices were intracellularly injected with Lucifer yellow and immunohistochemically labeled with NG2 antibody to identify local OPCs. Passive membrane properties and K(+) channel functions in OPCs were analyzed to estimate the onset of vulnerability in HIBD. The resting membrane potential, membrane resistance, and membrane capacitance of OPCs were increased in both the gray and white matter of the cerebral cortex. OPCs in both the gray and white matter exhibited voltage-dependent K(+) currents, which consisted of the initiated rectified potassium currents (IA) and the sustained rectified currents (IK). The significant alternation in membrane resistance was influenced by the diversity of potassium channel kinetics. These findings suggest that the rectification of IA and IK channels may play a significant role in OPC vulnerability in HIBD.

  3. Ophthalmoplegic migraine with reversible thalamic ischemia by Tc-99m ethylcysteinate dimer brain SPECT

    International Nuclear Information System (INIS)

    Two patients presented with ophthalmoplegic migraine (OM) underwent EEG, Brain-MRI, cerebral angiography, and Tc-99m ECD SPECT during an attack. Follow-up SPECT was performed after neurologic symptoms resolved. In both cases, SPECT during an attack of ophthalmoplegia and headache demonstrated a significantly decreased regional cerebral blood flow in the thalamus to the side of ophthalmoplegia, which was normalized on the follow-up SPECT during a symptom free recovery phase (Lesion to Non-lesion thalamic ratio=1.19 to 0.96 and 1.16 to 0.98, respectively). The other roentgenographic and laboratory findings were normal. These findings are suggestive the ischemia in the perforators of PCA results in third nerve palsy because the portion of oculomotor nerve behind the cavernous sinus derives its blood supply from small perforating branches of the basilar and PCA. Matched ictal hypoperfusion of the thalamus to the site of ophthalmoplegic migraine is suggestive of the ischemic neuropathy as an etiology of OM

  4. Ophthalmoplegic migraine with reversible thalamic ischemia by Tc-99m ethylcysteinate dimer brain SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jong Ho; Shin, Dong Jin; Kang, Sung Soo [Gachon Medical School, Gil Medical Center, Inchon (Korea, Republic of)

    1999-07-01

    Two patients presented with ophthalmoplegic migraine (OM) underwent EEG, Brain-MRI, cerebral angiography, and Tc-99m ECD SPECT during an attack. Follow-up SPECT was performed after neurologic symptoms resolved. In both cases, SPECT during an attack of ophthalmoplegia and headache demonstrated a significantly decreased regional cerebral blood flow in the thalamus to the side of ophthalmoplegia, which was normalized on the follow-up SPECT during a symptom free recovery phase (Lesion to Non-lesion thalamic ratio=1.19 to 0.96 and 1.16 to 0.98, respectively). The other roentgenographic and laboratory findings were normal. These findings are suggestive the ischemia in the perforators of PCA results in third nerve palsy because the portion of oculomotor nerve behind the cavernous sinus derives its blood supply from small perforating branches of the basilar and PCA. Matched ictal hypoperfusion of the thalamus to the site of ophthalmoplegic migraine is suggestive of the ischemic neuropathy as an etiology of OM.

  5. 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.

  6. Pranlukast reduces neutrophil but not macrophage/microglial accumulation in brain after focal cerebral ischemia in mice

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

    Aim:To determine whether pranlukast.a cysteinyl leukotriene receptor-1 antagonist,exerts an anti-inflammatory effect on focal cerebral ischemia in mice.Methods:Focal cerebral ischemia in mice was induced by permanent middle cerebral artery occlusion(MCAO).In addition to neurological deficits,infarct volume,degenerated neurons and endogenous IgG exudation,we detected accumulation of neutrophils and macrophage/microglia in the ischemic brain tissue 72 h after MCAO.Pranlukast was iP injected 30 min before and after MCAO.Results:Pranlukast significantly attenuated neurological deficits,infarct volume,neuron degeneration and IgG exudation.Importantly,pranlukast(0.01 and 0.1 mg/kg) inhibited myeloperoxidase-positive neutrophil,but not CDllb-positive macrophage/microglial accumulation in the ischemic cortical tissue.Conclusion:Pranlukast exerts an anti-inflammatory effect on focal cerebral ischemia in the subacute phase that is limited to neutrophil recruitment through the disrupted blood-brain barrier.

  7. Effect of Polyphenols on Oxidative Stress and Mitochondrial Dysfunction in Neuronal Death and Brain Edema in Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    Richard A. Anderson

    2011-11-01

    Full Text Available Polyphenols are natural substances with variable phenolic structures and are elevated in vegetables, fruits, grains, bark, roots, tea, and wine. There are over 8000 polyphenolic structures identified in plants, but edible plants contain only several hundred polyphenolic structures. In addition to their well-known antioxidant effects, select polyphenols also have insulin-potentiating, anti-inflammatory, anti-carcinogenic, anti-viral, anti-ulcer, and anti-apoptotic properties. One important consequence of ischemia is neuronal death and oxidative stress plays a key role in neuronal viability. In addition, neuronal death may be initiated by the activation of mitochondria-associated cell death pathways. Another consequence of ischemia that is possibly mediated by oxidative stress and mitochondrial dysfunction is glial swelling, a component of cytotoxic brain edema. The purpose of this article is to review the current literature on the contribution of oxidative stress and mitochondrial dysfunction to neuronal death, cell swelling, and brain edema in ischemia. A review of currently known mechanisms underlying neuronal death and edema/cell swelling will be undertaken and the potential of dietary polyphenols to reduce such neural damage will be critically reviewed.

  8. Information entropy-based fitting of the disease trajectory of brain ischemia-induced vascular cognitive impairment

    Institute of Scientific and Technical Information of China (English)

    Lin Liu; Ju Huo; Ying Zhao; Yu Tian

    2012-01-01

    The present study investigated the disease trajectory of vascular cognitive impairment using the entropy of information in a neural network mathematical simulation based on the free radical and excitatory amino acids theories.Glutamate, malondialdehyde, and inducible nitric oxide synthase content was significantly elevated, but acetylcholine, catalase, superoxide dismutase, glutathione peroxidase and constitutive nitric oxide synthase content was significantly decreased in our vascular cognitive impairment model.The fitting curves for each factor were obtained using Matlab software.Nineteen, 30 and 49 days post ischemia were the main output time frames of the influence of these seven factors.Our results demonstrated that vascular cognitive impairment involves multiple factors.These factors include excitatory amino acid toxicity and nitric oxide toxicity.These toxicities disrupt the dynamic equilibrium of the production and removal of oxygen free radicals after cerebral ischemia, reducing the ability to clear oxygen free radicals and worsening brain injury.

  9. Pre-existing interleukin 10 in cerebral arteries attenuates subsequent brain injury caused by ischemia/reperfusion.

    Science.gov (United States)

    Liang, Qiu-Juan; Jiang, Mei; Wang, Xin-Hong; Le, Li-Li; Xiang, Meng; Sun, Ning; Meng, Dan; Chen, Si-Feng

    2015-09-01

    Recurrent stroke is difficult to treat and life threatening. Transfer of anti-inflammatory gene is a potential gene therapy strategy for ischemic stroke. Using recombinant adeno-associated viral vector 1 (rAAV1)-mediated interleukin 10 (IL-10), we investigated whether transfer of beneficial gene into the rat cerebral vessels during interventional treatment for initial stroke could attenuate brain injury caused by recurrent stroke. Male Wistar rats were administered rAAV1-IL-10, rAAV1-YFP, or saline into the left cerebral artery. Three weeks after gene transfer, rats were subjected to occlusion of the left middle cerebral artery (MCAO) for 45 min followed by reperfusion for 24 h. IL-10 levels in serum were significantly elevated 3 weeks after rAAV1-IL-10 injection, and virus in the cerebral vessels was confirmed by in situ hybridization. Pre-existing IL-10 but not YFP decreased the neurological dysfunction scores, brain infarction volume, and the number of injured neuronal cells. AAV1-IL-10 transduction increased heme oxygenase (HO-1) mRNA and protein levels in the infarct boundary zone of the brain. Thus, transduction of the IL-10 gene in the cerebral artery prior to ischemia attenuates brain injury caused by ischemia/reperfusion in rats. This preventive approach for recurrent stroke can be achieved during interventional treatment for initial stroke.

  10. Phycocyanin for protecting brain ischemia-reperfusion injury and its effect on the expression of Caspase-3 mRNA

    Institute of Scientific and Technical Information of China (English)

    Xuewei Yang; Yunliang Guo; Hongbing Chen

    2006-01-01

    BACKGROUND: Phycocyanin can anti-oxidize and clear free radial. Whether its protective effect on brain is related to Caspase-3, the promoter and operator of apoptosis, is highly concerned.OBJECTIVE: To observe phycocyanin for protecting nerve function and reducing the size of cerebral infarction of rats with brain ischemia-reperfusion and its effect on the expression of Caspase-3 mRNA.DESIGN: A randomized controlled experiment.SETrING: Institute of Cerebrovascular Disease, Affiliated Hospital of Medical College of Qingdao University.MATERIALS: Totally 84 adult healthy female Wistar rats, weighing 210 to 250 g, of clean grade, were provided by the Animal Experimental Center of Shandong University. Phycocyanin (Institute of Oceanography of Chinese Academy of Sciences) was used.METHODS: This experiment was carried out in the Key Laboratory for Prevention and Treatment of Brain Diseases during May to December 2005. ① The rats were randomized into sham-operation group (n=4),control group (n=40) and phycocyanin-treated group (n=40). Middle cerebral artery occlusion/reperfusion (MACO/R) models were created on the rats of control and phycocyanin-treated groups with suture-occluded method by inserting a thread into left side external-internal carotid artery. In the sham-operation group, inserting suture was omitted. After ischemia for 1 hour and reperfusion for 2 hours, suspension of phycocyanin was intragastrically administrated into the rats of the phycocyanin-treated group at 100 mg/kg , and the same volume of normal saline was isochronously administrated into the rats of control group as the same. ② Six rats were chosen respectively from the control group and phycocyanin-treated group, then neurologic impairment degrees of rats were evaluated according to Bederson's grading. ③ Six rats were chosen respectively from the control and phycocyanin-treated groups. The isolated brain tissue was stained with triphenyltetrazolium chloride, and then the size of cerebral

  11. 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.

  12. The Effects of Antecedent Exercise on Motor Function Recovery and Brain-derived Neurotrophic Factor Expression after Focal Cerebral Ischemia in Rats

    OpenAIRE

    KIM, GYEYEOP; Kim, Eunjung

    2013-01-01

    [Purpose] In the present study, we investigated the effect of antecedent exercise on functional recovery and brain-derived neurotrophic factor (BDNF) expression following focal cerebral ischemia injury. [Subjects] The rat middle cerebral artery occlusion (MCAO) model was employed. Adult male Sprague-Dawley rats were randomly divided into 4 groups. Group I included untreated normal rats (n=10); Group II included untreated rats with focal cerebral ischemia (n=10); Group III included rats that p...

  13. [Effect of phenibut and its composition with nicotinic acid on hemostasis in rats with brain ischemia].

    Science.gov (United States)

    Tiurenkov, I N; Volotova, E V; Kurkin, D V; Litvinov, A A; Tarasov, A S

    2012-01-01

    It is shown that, in rats with global cerebral ischemia modeled by a complete irreversible occlusion of the common carotid artery and forced hypotension, the hemostasis is characterized by a shift toward hypercoagulation. A single preventive introduction of phenibut and, to a greater degree, a composition of phenibut with nicotinic acid, in rats with acute cerebral ischemia reduced the extent of disturbances in the hemostasis system of experimental animals. PMID:22702103

  14. Butylphthalide Suppresses Neuronal Cells Apoptosis and Inhibits JNK-Caspase3 Signaling Pathway After Brain Ischemia /Reperfusion in Rats.

    Science.gov (United States)

    Wen, Xiang-Ru; Tang, Man; Qi, Da-Shi; Huang, Xiao-Jing; Liu, Hong-Zhi; Zhang, Fang; Wu, Jian; Wang, Yi-Wen; Zhang, Xun-Bao; Guo, Ji-Qiang; Wang, Shu-Ling; Liu, Yong; Wang, Yu-Lan; Song, Yuan-Jian

    2016-10-01

    Although Butylphthalide (BP) has protective effects that reduce ischemia-induced brain damage and neuronal cell death, little is known about the precise mechanisms occurring during cerebral ischemia/reperfusion (I/R). Therefore, the aim of this study was to investigate the neuroprotective mechanisms of BP against ischemic brain injury induced by cerebral I/R through inhibition of the c-Jun N-terminal kinase (JNK)-Caspase3 signaling pathway. BP in distilled non-genetically modified Soybean oil was administered intragastrically three times a day at a dosage of 15 mg/(kg day) beginning at 20 min after I/R in Sprague-Dawley rats. Immunohistochemical staining and Western blotting were performed to examine the expression of related proteins, and TUNEL-staining was used to detect the percentage of neuronal apoptosis in the hippocampal CA1 region. The results showed that BP could significantly protect neurons against cerebral I/R-induced damage. Furthermore, the expression of p-JNK, p-Bcl2, p-c-Jun, FasL, and cleaved-caspase3 was also decreased in the rats treated with BP. In summary, our results imply that BP could remarkably improve the survival of CA1 pyramidal neurons in I/R-induced brain injury and inhibit the JNK-Caspase3 signaling pathway. PMID:27015680

  15. Effects of exogenous ganglioside-1 on learning and memory in a neonatal rat model of hypoxia-ischemia brain injury

    Institute of Scientific and Technical Information of China (English)

    Shizhi Li; Nong Xiao; Xiaoping Zhang; Ling Liu; Liyun Lin; Siyuan Chen; Yuxia Chen; Bei Xu

    2008-01-01

    BACKGROUND: Exogenous ganglioside-1 (GM1) can cross the blood-brain barrier and play a protective role against hypoxia-ischemia-induced brain damage. OBJECTIVE: To examine the possible mechanisms of exogenous GM1 protection in hypoxia-ischemia-induced brain damage in a neonatal rat model by measuring changes in brain mass, pathological morphology, growth-associated protein-43 expression, and neurobehavioral manifestations. DESIGN, TIME AND SETTING: A randomized block-design study was performed at the lmmunohistochemistry Laboratory of the Pediatric Research Institute, Children's Hospital of Chongqing Medical University from August 2005 to August 2006. MATERIALS: A total of 36 neonatal, 7-day-old, Sprague Dawley rats were used in this experiment. The hypoxia-ischemia-induced brain damage model was established by permanently occluding the right carotid artery, followed by oxygen inhalation at a low concentration (8% O2, 92% N2) for 2 hours. METHODS: All rats were randomly divided into the following groups: GM1, model, and sham operation, with 12 rats each group. Rats in the GM1 and model groups received hypoxic/ischemic-induced brain damage. Rats in the GM1 group received injections ofGM1 (i.p., 20 mg/kg) at 0, 24, 48, 72, 96, 120, and 144 hours following models established, and rats in the model group were administered (i.p.) the same amount of saline. The right carotid artery was separated, but not ligated, in the sham operation group rats. MAIN OUTCOME MEASURES: At 1 week after surgery, expression of growth-associated protein-43, a marker of neural development and plasticity, was detected in the hippocampal CA3 region by immunohistochemistry. Brain mass was measured, and the pathological morphology was observed. At 4 weeks after surgery, behavioral changes in the remaining rats were tested by Morris water maze, and growth-associated protein-43 expression was measured. RESULTS: (1) In the GM 1 and sham operation groups, growth-associated protein-43 expression was

  16. Effect of propofol on brain-derived neurotrophic factor and tyrosine kinase receptor B in the hippocampus of aged rats with chronic cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Gang Chen; Qiang Fu; Jiangbei Cao; Weidong Mi

    2012-01-01

    We intraperitoneally injected 10 and 50 mg/kg of propofol for 7 consecutive days to treat a rat model of chronic cerebral ischemia. A low-dose of propofol promoted the expression of brain-derived neurotrophic factor, tyrosine kinase receptor B, phosphorylated cAMP response element binding protein, and cAMP in the hippocampus of aged rats with chronic cerebral ischemia, but a high-dose of propofol inhibited their expression. Results indicated that the protective effect of propofol against cerebral ischemia in aged rats is related to changes in the expression of brain-derived neurotrophic factor and tyrosine kinase receptor B in the hippocampus, and that the cAMP-cAMP responsive element binding protein pathway is involved in the regulatory effect of propofol on brain-derived neurotrophic factor expression.

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

    Directory of Open Access Journals (Sweden)

    Giuliani Patricia

    2010-02-01

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

  18. Phycocyanin for protecting brain ischemia-reperfusion injury and its effect on the expression of Caspase-3 mRNA

    Institute of Scientific and Technical Information of China (English)

    Xuewei Yang; Yunliang Guo; Hongbing Chen

    2006-01-01

    BACKGROUND: Phycocyanin can anti-oxidize and clear free radial. Whether its protective effect on brain is related to Caspase-3, the promoter and operator of apoptosis, is highly concerned.OBJECTIVE: To observe phycocyanin for protecting nerve function and reducing the size of cerebral infarction of rats with brain ischemia-reperfusion and its effect on the expression of Caspase-3 mRNA.DESIGN: A randomized controlled experiment.SETrING: Institute of Cerebrovascular Disease, Affiliated Hospital of Medical College of Qingdao University.MATERIALS: Totally 84 adult healthy female Wistar rats, weighing 210 to 250 g, of clean grade, were provided by the Animal Experimental Center of Shandong University. Phycocyanin (Institute of Oceanography of Chinese Academy of Sciences) was used.METHODS: This experiment was carried out in the Key Laboratory for Prevention and Treatment of Brain Diseases during May to December 2005. ① The rats were randomized into sham-operation group (n=4),control group (n=40) and phycocyanin-treated group (n=40). Middle cerebral artery occlusion/reperfusion (MACO/R) models were created on the rats of control and phycocyanin-treated groups with suture-occluded method by inserting a thread into left side external-internal carotid artery. In the sham-operation group, inserting suture was omitted. After ischemia for 1 hour and reperfusion for 2 hours, suspension of phycocyanin was intragastrically administrated into the rats of the phycocyanin-treated group at 100 mg/kg , and the same volume of normal saline was isochronously administrated into the rats of control group as the same. ② Six rats were chosen respectively from the control group and phycocyanin-treated group, then neurologic impairment degrees of rats were evaluated according to Bederson's grading. ③ Six rats were chosen respectively from the control and phycocyanin-treated groups. The isolated brain tissue was stained with triphenyltetrazolium chloride, and then the size of cerebral

  19. Early-Onset Convulsive Seizures Induced by Brain Hypoxia-Ischemia in Aging Mice: Effects of Anticonvulsive Treatments.

    Directory of Open Access Journals (Sweden)

    Justin Wang

    Full Text Available Aging is associated with an increased risk of seizures/epilepsy. Stroke (ischemic or hemorrhagic and cardiac arrest related brain injury are two major causative factors for seizure development in this patient population. With either etiology, seizures are a poor prognostic factor. In spite of this, the underlying pathophysiology of seizure development is not well understood. In addition, a standardized treatment regimen with anticonvulsants and outcome assessments following treatment has yet to be established for these post-ischemic seizures. Previous studies have modeled post-ischemic seizures in adult rodents, but similar studies in aging/aged animals, a group that mirrors a higher risk elderly population, remain sparse. Our study therefore aimed to investigate early-onset seizures in aging animals using a hypoxia-ischemia (HI model. Male C57 black mice 18-20-month-old underwent a unilateral occlusion of the common carotid artery followed by a systemic hypoxic episode (8% O2 for 30 min. Early-onset seizures were detected using combined behavioral and electroencephalographic (EEG monitoring. Brain injury was assessed histologically at different times post HI. Convulsive seizures were observed in 65% of aging mice post-HI but not in control aging mice following either sham surgery or hypoxia alone. These seizures typically occurred within hours of HI and behaviorally consisted of jumping, fast running, barrel-rolling, and/or falling (loss of the righting reflex with limb spasms. No evident discharges during any convulsive seizures were seen on cortical-hippocampal EEG recordings. Seizure development was closely associated with acute mortality and severe brain injury on brain histological analysis. Intra-peritoneal injections of lorazepam and fosphenytoin suppressed seizures and improved survival but only when applied prior to seizure onset and not after. These findings together suggest that seizures are a major contributing factor to acute

  20. Maternal hypertension during pregnancy modifies the response of the immature brain to hypoxia-ischemia: Sequential MRI and behavioral investigations

    International Nuclear Information System (INIS)

    Hypoxic-ischemic (HI) brain injury occurring during the perinatal period is still a major cause of mortality and morbidity. We assessed the impact of maternal hypertension, the most common medical disorder of pregnancy, on the anatomical and functional consequences of HI insult in the immature brain. Rat pups from spontaneously hypertensive (SHR) and normotensive (Wistar Kyoto - WKY) dams were subjected to HI brain damage at postnatal day 7 (P7). Brain lesion and functional deficits were analyzed from 10 min to 35 days after HI, using magnetic resonance imaging (MRI), sensorimotor and cognitive tests. MRI data revealed that SHR pups displayed less brain damage than WKY, attested by an initial smaller lesion followed by a reduced tissue loss at chronic stage (57.1±21.6 and 31.1±27% ipsilateral hemisphere atrophy in WKY and SHR, respectively). Behavioral analyses showed less HI-induced behavioral deficits in motor coordination (rotarod test) and spatial learning (Morris watermaze test) in pups from hypertensive dams compared to those from normotensive ones. The data suggest that maternal hypertension causes prenatal stress that may render the immature brain more resistant to subsequent hypoxia-ischemia, related to a preconditioning phenomenon. (authors)

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

  2. Shallow needling on Neiguan and Gongsun acupoints in rats with brain ischemia Changes in apoptosis regulating genes and vasoactive substances

    Institute of Scientific and Technical Information of China (English)

    Yushan Fan; Caijiao Zhao; Wei Huang; Yan Luo; Yong Pang; Huangsha Fan; Xingui Wu; Jinsheng Wang

    2011-01-01

    For the treatment of brain ischemia using acupuncture, the needle is predominantly inserted into muscular layers and deep tissue. However, few studies have investigated the outcomes of shallow needling. The present study established middle cerebral artery occlusion models in rats using the thrombosis method. Shallow needling and conventional needling at the bilateral Neiguan (PC 6) and Gongsun (SP 4) acupoints improved neurological function of middle cerebral artery occlusion rats, increased the expression of the anti-apoptotic Bcl-2, inhibited the expression of the pro-apoptotic Bax, and reduced the expression of the vasoactive substances nitric oxide synthase and endothelin-1. However, these changes were more pronounced in the shallow needling group, indicating that shallow needling is more effective in inhibiting brain ischemic injury.

  3. High-Resolution Magnetic Resonance Angiography of the Mouse Brain: Application to Murine Focal Cerebral Ischemia Models

    Science.gov (United States)

    Beckmann, Nicolau; Stirnimann, Roger; Bochelen, Damien

    1999-10-01

    Three-dimensional time-of-flight high-resolution magnetic resonance angiography was applied to visualize the cerebral vasculature of the mouse brain. In normal mice, angiograms of good quality, showing the essential details of the arterial cerebrovascular anatomy, could be obtained in only 2.5 min without the use of contrast agents. Signals from slowly flowing blood, e.g., in veins, could also be detected after administration of a blood pool contrast agent. The technique was applied to mouse models of permanent and transient brain ischemia, involving the occlusion of the middle cerebral artery. High-resolution magnetic resonance angiography proved to be a very useful tool for verifying the success of the occlusion in these models.

  4. Effect of monoamine nervous transmitter and neuropeptide Y in the aged rats with myocardial injury after brain ischemia-reperfusion

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    AIM: To study the mechanism of myocardial injury after brain ischemia-reperfusion in aged rats from the changes in Dopamine (DA), Noradrenalin (NE), Epinephrine(E) and Neuropeptide Y(NPY).METHODS: Young (5 months) and aged (20 months or more) rats were divided into model groups and normal control groups, respectively. We observed the following items in rats with 60 minute reperfusion after 30 minute brain ischemia: the pathological changed of myocardium, the activities of lactic dehydrrogenase(LDH), creatine phosphokinase(CPK), the contents of NE, DA, E, NPY. RESULTS:The CPK and LDH activities in the young model rats were higher than those in the young control rats was higher than that in the young control rats (P<0.05). The serum CPK activity in the aged control rats was higher than that in the young control rats (P<0.05). The myocardial CPK activity was higher in the aged model rats compared with the young molel rats (P<0.05) and was higher in aged control rats compared with the young control rats (P<0.01). The myocardial LDH activity was lower in the aged control rats than that in the young control rats (P<0.05) and aged model rats (P<0.01). The serum NE level, the level of NE and DA in the hypothalamus were higher obviously than those in the young control rats. The serum NE contents in the two model groups (young and aged) were higher respectively than the two control rats (young and aged). The following items’ contents were higher in the aged model rats than in the young model rats: serum NE, serum E, hypothalamus NE. The hypothalamus NE and E content was lower in the aged model rats than in te aged control rats. NPY level in the brain tissue was lower in the aged control rats than that in the young control rats and aged model rats (P<0.05).CONCLUSION: The myocardial injury after brain ischemia-reperfusion was concerned with the enhanced excitability of sympathetic-adrenal system, espectially in the aged rats. However, the change in myocardial

  5. Forced arm use is superior to voluntary training for motor recovery and brain plasticity after cortical ischemia in rats

    Science.gov (United States)

    2014-01-01

    Background and purpose Both the immobilization of the unaffected arm combined with physical therapy (forced arm use, FAU) and voluntary exercise (VE) as model for enriched environment are promising approaches to enhance recovery after stroke. The genomic mechanisms involved in long-term plasticity changes after different means of rehabilitative training post-stroke are largely unexplored. The present investigation explored the effects of these physical therapies on behavioral recovery and molecular markers of regeneration after experimental ischemia. Methods 42 Wistar rats were randomly treated with either forced arm use (FAU, 1-sleeve plaster cast onto unaffected limb at 8/10 days), voluntary exercise (VE, connection of a freely accessible running wheel to cage), or controls with no access to a running wheel for 10 days starting at 48 hours after photothrombotic stroke of the sensorimotor cortex. Functional outcome was measured using sensorimotor test before ischemia, after ischemia, after the training period of 10 days, at 3 and 4 weeks after ischemia. Global gene expression changes were assessed from the ipsi- and contralateral cortex and the hippocampus. Results FAU-treated animals demonstrated significantly improved functional recovery compared to the VE-treated group. Both were superior to cage control. A large number of genes are altered by both training paradigms in the ipsi- and contralateral cortex and the hippocampus. Overall, the extent of changes observed correlated well with the functional recovery obtained. One category of genes overrepresented in the gene set is linked to neuronal plasticity processes, containing marker genes such as the NMDA 2a receptor, PKC ζ, NTRK2, or MAP 1b. Conclusions We show that physical training after photothrombotic stroke significantly and permanently improves functional recovery after stroke, and that forced arm training is clearly superior to voluntary running training. The behavioral outcomes seen correlate with

  6. Silent Ischemia

    Science.gov (United States)

    ... Vulnerable Plaque Silent Ischemia | Share Related terms: ischemia, restricted blood flow Ischemia is a condition where the flow of ... used to diagnose silent ischemia: An exercise stress test can show blood flow through your coronary arteries in response to exercise. ...

  7. Human-derived physiological heat shock protein 27 complex protects brain after focal cerebral ischemia in mice.

    Directory of Open Access Journals (Sweden)

    Shinichiro Teramoto

    Full Text Available Although challenging, neuroprotective therapies for ischemic stroke remain an interesting strategy for countering ischemic injury and suppressing brain tissue damage. Among potential neuroprotective molecules, heat shock protein 27 (HSP27 is a strong cell death suppressor. To assess the neuroprotective effects of HSP27 in a mouse model of transient middle cerebral artery occlusion, we purified a "physiological" HSP27 (hHSP27 from normal human lymphocytes. hHSP27 differed from recombinant HSP27 in that it formed dimeric, tetrameric, and multimeric complexes, was phosphorylated, and contained small amounts of αβ-crystallin and HSP20. Mice received intravenous injections of hHSP27 following focal cerebral ischemia. Infarct volume, neurological deficit scores, physiological parameters, and immunohistochemical analyses were evaluated 24 h after reperfusion. Intravenous injections of hHSP27 1 h after reperfusion significantly reduced infarct size and improved neurological deficits. Injected hHSP27 was localized in neurons on the ischemic side of the brain. hHSP27 suppressed neuronal cell death resulting from cytochrome c-mediated caspase activation, oxidative stress, and inflammatory responses. Recombinant HSP27 (rHSP27, which was artificially expressed and purified from Escherichia coli, and dephosphorylated hHSP27 did not have brain protective effects, suggesting that the phosphorylation of hHSP27 may be important for neuroprotection after ischemic insults. The present study suggests that hHSP27 with posttranslational modifications provided neuroprotection against ischemia/reperfusion injury and that the protection was mediated through the inhibition of apoptosis, oxidative stress, and inflammation. Intravenously injected human HSP27 should be explored for the treatment of acute ischemic strokes.

  8. Evidence of CCR2-independent transmigration of Ly6C(hi) monocytes into the brain after permanent cerebral ischemia in mice.

    Science.gov (United States)

    Chu, Hannah X; Kim, Hyun Ah; Lee, Seyoung; Broughton, Brad R S; Drummond, Grant R; Sobey, Christopher G

    2016-04-15

    Previously we showed that INCB3344, a CCR2 antagonist, inhibits transmigration of Ly6C(hi) monocytes into the brain after ischemia-reperfusion. Here we tested the effect of CCR2 inhibition during permanent cerebral ischemia. Mice were administered either vehicle (dimethyl sulfoxide/carboxymethylcellulose) or INCB3344 (30 or 100mg/kg IP) 1h before middle cerebral artery occlusion and at 2 and 6h after the initiation of ischemia. After 24h, we assessed functional outcome, infarct volume and quantified immune cells in blood and brain. The increase in circulating bone marrow-derived Ly6C(hi) monocytes, but not the infiltration of those cells into the brain, was blocked by the CCR2 antagonist. INCB3344 had no effect on either neurological deficit or infarct volume. Our data confirm that cerebral ischemia triggers a CCR2-dependent increase in circulating Ly6C(hi) monocytes, but suggest that in the absence of reperfusion these cells may transmigrate into the ischemic brain in a CCR2-independent manner.

  9. ROS-Dependent Neuroprotective Effects of NaHS in Ischemia Brain Injury Involves the PARP/AIF Pathway

    Directory of Open Access Journals (Sweden)

    Qian Yu

    2015-07-01

    Full Text Available Background/Aims: Stroke is among the top causes of death worldwide. Neuroprotective agents are thus considered as potentially powerful treatment of stroke. Methods: Using both HT22 cells and male Sprague-Dawley rats as in vitro and in vivo models, we investigated the effect of NaHS, an exogenous donor of H2S, on the focal cerebral ischemia-reperfusion (I/R induced brain injury. Results: Administration of NaHS significantly decreased the brain infarcted area as compared to the I/R group in a dose-dependent manner. Mechanistic studies demonstrated that NaHS-treated rats displayed significant reduction of malondialdehyde content, and strikingly increased activity of superoxide dismutases and glutathione peroxidase in the brain tissues compared with I/R group. The enhanced antioxidant capacity as well as restored mitochondrial function are NaHS-treatment correlated with decreased cellular reactive oxygen species level and compromised apoptosis in vitro or in vivo in the presence of NaHS compared with control. Further analysis revealed that the inhibition of PARP-1 cleavage and AIF translocation are involved in the neuroprotective effects of NaHS. Conclusion: Collectively, our results suggest that NaHS has potent protective effects against the brain injury induced by I/R. NaHS is possibly effective through inhibition of oxidative stress and apoptosis.

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

    Directory of Open Access Journals (Sweden)

    Zheng Jiang

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

  11. Honokiol protects brain against ischemia-reperfusion injury in rats through disrupting PSD95-nNOS interaction.

    Science.gov (United States)

    Hu, Zhenyu; Bian, Xiling; Liu, Xiaoyan; Zhu, Yuanjun; Zhang, Xiaoyi; Chen, Shizhong; Wang, Kewei; Wang, Yinye

    2013-01-23

    Honokiol, a major bioactive constituent of the bark of Magnolia officinalis has been confirmed to have the neuroprotective effect on ischemic stroke in rats. This study was designed to observe the therapeutic time window of honokiol microemulsion on cerebral ischemia-reperfusion injury to support its potential for future clinical trials and further explore the underlying mechanisms. Honokiol microemulsion (50μg/kg, i.v. at 0, 1 or 3h after reperfusion) significantly reduced neurological deficit, infarct volume and brain water content in rats subjected to cerebral ischemia-reperfusion, and honokiol (0.1-10μM) significantly attenuated oxygen-glucose deprivation- or glutamate-induced injury of fetal rat cortical neurons. In co-immunoprecipitation and western blot test, honokiol decreased the intensity of nNOS related to PSD95 but failed to affect that of PSD95 related to NR2B in NR2B-PSD95-nNOS complex, and it also inhibited the translocation of nNOS from cytosol to membrane without affecting total nNOS expression, and then markedly decreased NO production in cortical neurons. Besides, the results of whole-cell patch-clamp recordings showed that honokiol reversibly inhibited the NMDA current by about 64%. In conclusion, honokiol has a therapeutic window of at least 5h after the onset of cerebral ischemia or 3h after reperfusion in rats, which may be in part ascribed to the disruption of the PSD95-nNOS interaction leading to the inhibition of neurotoxic NO production.

  12. [Treatment of arterial and venous brain ischemia. Experts' recommendations: stroke management in the intensive care unit].

    Science.gov (United States)

    Calvet, D; Bracard, S; Mas, J-L

    2012-06-01

    With thrombolysis, intravenous alteplase (0.9 mg/kg body weight, maximum 90 mg), with 10% of the dose given as a bolus followed by a 60-minute infusion, is recommended within 4.5 hours of onset of ischemic stroke. When indicated, intravenous thrombolysis must be initiated as soon as possible. It is possible to use intravenous alteplase in patients with seizures at stroke onset, if the neurological deficit is related to acute cerebral ischemia. Intravenous alteplase can be discussed for use on a case-by-case basis, according to risk of bleeding, in selected patients under 18 years and over 80 years of age, although for the current European recommendations this would be an off-label use. In hospitals with a stroke unit, intravenous thrombolysis is prescribed by a neurologist (current French labelling) or a physician having the French certification for neurovascular diseases (outside the current French labelling). The patient must be monitored in the stroke unit or in case of multiple organ failure in an intensive and critical care unit. In hospitals without a stroke unit, thrombolysis must be decided by the neurologist from the corresponding stroke unit via telemedicine. It is recommended to perform brain imaging 24 hours after thromboysis. Intra-arterial thrombolysis can be contemplated on a case-by-case basis after multidisciplinary discussion within a 6-hour time window for patients with acute middle cerebral artery or carotid occlusions, and within a larger time window for patients with basilar artery occlusion, because of their very poor spontaneous prognosis. Mechanical thrombectomy can also be contemplated in the same situations. With antiplatelet agents, it is recommended that patients receive aspirin (160 mg-325 mg) within 48 hours of ischemic stroke onset. When thrombolysis is performed or contemplated, it is recommended to delay the initiation of aspirin or other antithrombotic drugs for 24 hours. The use of antiplatelet agents that inhibit the

  13. Neuroprotective effects of the free radical scavenger Edaravone (MCI-186) in mice permanent focal brain ischemia.

    Science.gov (United States)

    Shichinohe, Hideo; Kuroda, Satoshi; Yasuda, Hiroshi; Ishikawa, Tatsuya; Iwai, Masaru; Horiuchi, Masatsugu; Iwasaki, Yoshinobu

    2004-12-17

    The present study was aimed to evaluate the effect of the free radical scavenger Edaravone on infarct volume due to permanent MCA occlusion in mice and, if so, to elucidate the mechanism of its neuroprotective effects. Male Balb/c mice were subjected to permanent middle cerebral artery occlusion and were treated with 3.0 mg/kg of Edaravone or vehicle 30 min before ischemia. Infarct volume was assessed by 2,3,5-triphenyltetrazolium chloride (TTC) method after 24 h. Furthermore, in situ detection of superoxide in the ipsilateral neocortex was carried out using the superoxide-sensitive dye dihydroethidium (DHE) staining technique. Pretreatment with 3.0 mg/kg of Edaravone ameliorated the tissue damage in the infarct rim and significantly reduced infarct volume to about 77% of the control (pscavenging reactive oxygen species especially in the neurons during permanent focal cerebral ischemia. PMID:15542075

  14. Vasopressin impairs brain, heart and kidney perfusion: an experimental study in pigs after transient myocardial ischemia

    OpenAIRE

    Müller, Stig; How, Ole-Jakob; Hermansen, Stig Eggen; Stenberg, Thor Allan; Sager, Georg; Myrmel, Truls

    2008-01-01

    Introduction: Arginine vasopressin (AVP) is increasingly used to restore mean arterial pressure (MAP) in low-pressure shock states unresponsive to conventional inotropes. This is potentially deleterious since AVP is also known to reduce cardiac output by increasing vascular resistance. The effects of AVP on blood flow to vital organs and cardiac performance in a circulation altered by cardiac ischemia are still not sufficiently clarified. We hypothesised that restoring MAP by low dose, th...

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

    Directory of Open Access Journals (Sweden)

    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.

  16. Insulin Receptor Substrate-1 Activation Mediated p53 Downregulation Protects Against Hypoxic-Ischemia in the Neonatal Brain.

    Science.gov (United States)

    Tu, Yi-Fang; Jiang, Si-Tse; Chow, Yen-Hung; Huang, Chao-Ching; Ho, Chien-Jung; Chou, Ya-Ping

    2016-08-01

    This study determined if dietary restriction (DR) protects against hypoxic-ischemia (HI) in the neonatal brain via insulin receptor substrate-1 (IRS-1)/Akt pathway-mediated downregulation of p53 in the neurovascular unit. On postnatal (P) day 7, HI was induced in rat pups grouped from P1 into normal litter size (NL, 12 pups/dam) and increased litter size (DR, 18 pups/dam). In vivo IRS-1 anti-sense oligonucleotide and IRS-1 overexpressed recombinant adenovirus were given, and neurovascular damage was assessed. In vitro models of oxygen-glucose deprivation (OGD) examined the inhibition and overexpression of IRS-1 on p53 and cell death in neurons and endothelial cells. Compared to NL pups, DR pups had significantly higher IRS-1, p-IRS-1, and pAkt levels, decreased p53, more tight junction proteins, reduced blood-brain barrier (BBB) damage after HI, and less infarct volumes at P21. Immunofluorescence revealed that IRS-1 was upregulated in the endothelial cells and neurons of DR pups. IRS-1 downregulation in DR pups reduced p-Akt, increased p53, worsened BBB damage, and increased brain injury, whereas IRS-1 overexpression in NL pups upregulated p-Akt, decreased p53, attenuated BBB damage, and decreased brain injury. In vitro, IRS-1 downregulation aggravated cell death in neurons and endothelial cells and is associated with decreased p-Akt and increased p53. In contrast, IRS-1 overexpression reduced cell death in endothelial cells with increased p-Akt and decreased p53. In conclusion, DR reduces neurovascular damage after HI in the neonatal brain through an IRS-1/Akt-mediated p53 downregulation, suggesting that IRS-1 signaling is a therapeutic target for hypoxic brain injury in neonates. PMID:26111627

  17. Treadmill exercise ameliorates ischemia-induced brain edema while suppressing Na⁺/H⁺ exchanger 1 expression.

    Science.gov (United States)

    Nishioka, Ryutaro; Sugimoto, Kana; Aono, Hitomi; Mise, Ayano; Choudhury, Mohammed E; Miyanishi, Kazuya; Islam, Afsana; Fujita, Takahiro; Takeda, Haruna; Takahashi, Hisaaki; Yano, Hajime; Tanaka, Junya

    2016-03-01

    Exercise may be one of the most effective and sound therapies for stroke; however, the mechanisms underlying the curative effects remain unclear. In this study, the effects of forced treadmill exercise with electric shock on ischemic brain edema were investigated. Wistar rats were subjected to transient (90 min) middle cerebral artery occlusion (tMCAO). Eighty nine rats with substantially large ischemic lesions were evaluated using magnetic resonance imaging (MRI) and were randomly assigned to exercise and non-exercise groups. The rats were forced to run at 4-6m/s for 10 min/day on days 2, 3 and 4. Brain edema was measured on day 5 by MRI, histochemical staining of brain sections and tissue water content determination (n=7, each experiment). Motor function in some rats was examined on day 30 (n=6). Exercise reduced brain edema (Pexercise. Exercise prevented the ischemia-induced expression of mRNA encoding aquaporin 4 (AQP4) and Na(+)/H(+) exchangers (NHEs) (n=5 or 7, Prat brains and also in mixed glial cultures. Corticosterone at ~10nM reduced NHE1 and AQP4 expression in mixed glial and pure microglial cultures. Dexamethasone and aldosterone at 10nM did not significantly alter NHE1 and AQP4 expression. Exposure to a NHE inhibitor caused shrinkage of microglial cells. These results suggest that the stressful short-period and slow-paced treadmill exercise suppressed NHE1 and AQP4 expression resulting in the amelioration of brain edema at least partly via the moderate increase in plasma corticosterone levels. PMID:26724742

  18. nNOS expression of hippocampal neurons in aged rats after brain ischemia/reperfusion and its role in DND development

    Institute of Scientific and Technical Information of China (English)

    杨传红; 赖晃文; 詹纯列; 肖育华; 郑文岭

    2002-01-01

    To study the role of neuronal nitric oxide synthase (nNOS) in aged rats' hippocampal delayed neuronal death (DND) following brain ischemia. Methods: Models of incomplete brain ischemia were induced by clipping common carotid artery. A total of 46 aged SD rats were divided into 8 groups: normal control group ( Group A, n = 5 ), sham-operation group ( Group B, n = 5), reperfusion 1, 6, 12, 24, 48, and 96 hours groups after brain ischemia for 30 minutes ( Group C, D,E, F, G, and H, n = 6/group). The expression of nNOS was examined by immunohistochemistry and neuronal ultrastructural changes were observed by the transmission electron microscopy (TEM) at different time points after reperfusion. Results: Immunohistochemistry showed that nNOS expression in the hippocampal neurons was high in Group E, iow expression in Group D, moderate expression in Group F and G. There was nearly no expression of nNOS in Group A, B, C, and H. UItrastructure of hippocampal neurons was damaged more severely in reperfusion over 24 hours groups. Conclusions: Nitric oxide (NO) may be one of the important factors in inducing DND after ischemia/reperfusion.

  19. Early environmental enrichment affects neurobehavioral development and prevents brain damage in rats submitted to neonatal hypoxia-ischemia.

    Science.gov (United States)

    Schuch, Clarissa Pedrini; Diaz, Ramiro; Deckmann, Iohanna; Rojas, Joseane Jiménez; Deniz, Bruna Ferrary; Pereira, Lenir Orlandi

    2016-03-23

    Our previous results demonstrated improved cognition in adolescent rats housed in environmental enrichment (EE) that underwent neonatal hypoxia-ischemia (HI). The aim of this study was to investigate the effects of early EE on neurobehavioral development and brain damage in rats submitted to neonatal HI. Wistar rats were submitted to the HI procedure on the 7th postnatal day (PND) and housed in an enriched environment (8th-20th PND). The maturation of physical characteristics and the neurological reflexes were evaluated and the volume of striatum, corpus callosum and neocortex was measured. Data analysis demonstrated a clear effect of EE on neurobehavioral development; also, daily performance was improved in enriched rats on righting, negative geotaxis and cliff aversion reflex. HI caused a transient motor deficit on gait latency. Brain atrophy was found in HI animals and this damage was partially prevented by the EE. In conclusion, early EE stimulated neurobehavioral development in neonate rats and also protects the neocortex and the corpus callosum from atrophy following HI. These findings reinforce the potential of EE as a strategy for rehabilitation following neonatal HI and provide scientific support to the use of this therapeutic strategy in the treatment of neonatal brain injuries in humans.

  20. Helium preconditioning protects the brain against hypoxia/ischemia injury via improving the neurovascular niche in a neonatal rat model.

    Science.gov (United States)

    Li, Yi; Zhang, Peixi; Liu, Ying; Liu, Wenwu; Yin, Na

    2016-11-01

    This study aimed to investigate whether helium preconditioning (He-PC) is able to exert neuroprotective effects via improving focal neurovascular niche in a neonatal rat hypoxia/ischemia (HI) brain injury model. Seven day old rat pups were divided into control group, HI group and He-PC group. HI was induced by exposure to 8% oxygen for 90min one day after preconditioning with 70% helium-30% oxygen for three 5-min periods. At 3 and 7 days, the brain was collected for the detection of inflammation related factors (tumor necrosis factor α [TNF-α], interleukin-1β [IL-1β], IL-10) and growth/neurotrophic factors (brain-derived neurotrophic factor [BDNF], basic fibroblast growth factor [bFGF] and nerve growth factor [NGF]); at 7 days, neurobehaviors were evaluated, and the brain was collected for the detection of mRNA expression of vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1) by PCR, protein expression of angiogenesis related molecules (VEGF, Ang-1, Tie-2 and Flt-1) by Western blotting and microvessel density (MCD) by immunohistochemistry for vWF. Results showed He-PC was able to reduce TNF-α and IL-1β, further increase IL-10, BDNF, bFGF and NGF, elevate the mRNA expression of VEGF and Ang-1, increase the protein expression of VEGF, Ang-1, Tie-2 and Flt-1, promote angiogenesis and improve neurobehaviors as compared to HI group. These findings suggest that He-PC may improve the post-stroke neurovascular niche to exert neuroprotective effects on neonatal HI brain injury. PMID:27515290

  1. Detection of hypoxic cells with the 2-nitroimidazole, EF5, correlates with early redox changes in rat brain after perinatal hypoxia-ischemia.

    Science.gov (United States)

    Bergeron, M; Evans, S M; Sharp, F R; Koch, C J; Lord, E M; Ferriero, D M

    1999-01-01

    The hypoxia-dependent activation of nitroheterocyclic drugs by cellular nitroreductases leads to the formation of intracellular adducts between the drugs and cellular macromolecules. Because this covalent binding is maximal in the absence of oxygen, detection of bound adducts provides an assay for estimating the degree of cellular hypoxia in vivo. Using a pentafluorintated derivative of etanidazole called EF5, we studied the distribution of EF5 adducts in seven-day-old rats subjected to different treatments which decrease the level of oxygen in the brain. EF5 solution was administered intraperitoneally 30 min prior to each treatment. The effect of acute and chronic hypoxia on EF5 adduct formation (binding) was studied in the brain of newborn rats exposed to global hypoxia (8% O2 for 30, 90 or 150 min) and in the brain of chronically hypoxic rat pups with congenital cardiac defects (Wistar Kyoto). The effect of combined hypoxia-ischemia was investigated in rat pups subjected to right carotid coagulation and concurrent exposure to 8% O2 for 30, 90 or 150 min. Brains were frozen immediately at the end of each treatment. Using a Cy3-conjugated monoclonal mouse antibody (ELK3-51) raised against EF5 adducts, hypoxic cells within brain regions were visualized by fluorescence immunocytochemistry. Brains from controls or vehicle-injected animals showed no EF5 binding. Notably, brains from animals which were chronically hypoxemic as a result of congenital cardiac defects also showed no EF5 binding. A short exposure (30 min) to hypoxia or to combined hypoxia-ischemia resulted in increased background stain and few scattered cells with low-intensity immunostaining. Acute hypoxia exposure of at least 90-150 min, which in this age animal does not result in frank cellular damage, produced patchy areas of low- to moderate-intensity fluorescence scattered throughout the brain. In contrast, 90-150 min of hypoxia-ischemia was associated with intense immunofluorescence in the

  2. Role of hydrogen sulfide in early blood-brain barrier disruption following transient focal cerebral ischemia.

    Directory of Open Access Journals (Sweden)

    Zheng Jiang

    Full Text Available We determined the role of endogenous hydrogen sulfide (H2S in cerebral vasodilation/hyperemia and early BBB disruption following ischemic stroke. A cranial window was prepared over the left frontal, parietal and temporal cortex in mice. Transient focal cerebral Ischemia was induced by directly ligating the middle cerebral artery (MCA for two hours. Regional vascular response and cerebral blood flow (CBF during ischemia and reperfusion were measured in real time. Early BBB disruption was assessed by Evans Blue (EB and sodium fluorescein (Na-F extravasation at 3 hours of reperfusion. Topical treatment with DL-propargylglycine (PAG, an inhibitor for cystathionine γ-lyase (CSE and aspartate (ASP, inhibitor for cysteine aminotransferase/3-mercaptopyruvate sulfurtransferase (CAT/3-MST, but not O-(Carboxymethylhydroxylamine hemihydrochloride (CHH, an inhibitor for cystathionine β-synthase (CBS, abolished postischemic cerebral vasodilation/hyperemia and prevented EB and Na-F extravasation. CSE knockout (CSE-/- reduced postischemic cerebral vasodilation/hyperemia but only inhibited Na-F extravasation. An upregulated CBS was found in cerebral cortex of CSE-/- mice. Topical treatment with CHH didn't further alter postischemic cerebral vasodilation/hyperemia, but prevented EB extravasation in CSE-/- mice. In addition, L-cysteine-induced hydrogen sulfide (H2S production similarly increased in ischemic side cerebral cortex of control and CSE-/- mice. Our findings suggest that endogenous production of H2S by CSE and CAT/3-MST during reperfusion may be involved in postischemic cerebral vasodilation/hyperemia and play an important role in early BBB disruption following transient focal cerebral ischemia.

  3. 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.

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

    Institute of Scientific and Technical Information of China (English)

    Haiyan Xu; Chengwei Zhang; Chunxiao Zhang

    2011-01-01

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

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

    OpenAIRE

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

    2013-01-01

    Brain-derived neurotrophic factor is associated with the insulin signaling pathway and glucose tabolism. We hypothesized that expression of brain-derived neurotrophic factor and its receptor may be involved in glucose intolerance following ischemic stress. To verify this hypothesis, this study aimed to observe the changes in brain-derived neurotrophic factor and tyrosine kinase B receptor expression in glucose metabolism-associated regions following cerebral ischemic stress in mice. At day 1 ...

  6. Potential application of hydrogen in traumatic and surgical brain injury, stroke and neonatal hypoxia-ischemia

    OpenAIRE

    Eckermann Jan M; Krafft Paul R; Shoemaker Lorelei; Lieberson Robert E; Chang Steven D; Colohan Austin

    2012-01-01

    Abstract This article summarized findings of current preclinical studies that implemented hydrogen administration, either in the gas or liquid form, as treatment application for neurological disorders including traumatic brain injury (TBI), surgically induced brain injury (SBI), stroke, and neonatal hypoxic-ischemic brain insult (HI). Most reviewed studies demonstrated neuroprotective effects of hydrogen administration. Even though anti-oxidative potentials have been reported in several studi...

  7. Bilobalide inhibits the expression of aquaporin 1, 4 and glial fibrillary acidic protein in rat brain tissue after permanent focal cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Haiming Qin; Fulin Song; Hongguang Han; Hong Qu; Xingwen Zhai; Bin Qin; Song You

    2011-01-01

    The present results demonstrated that in an adult rat model of permanent middle cerebral artery occlusion (pMCAO), pretreatment with bilobalide reduced brain water content and infarct area, down-regulated aquaporin 1, 4 mRNA expression in brain edema tissue, then inhibited their synthesis in the striatum, in particular at the early stage of ischemia (at 8 hours after pMCAO), inhibited glial fibrillary acidic protein expression, and lightened reactive gliosis. These data sug-gest that bilobalide attenuates brain edema formation due to reduced expression of aquaporins.

  8. Mesenchymal stem cells induce T-cell tolerance and protect the preterm brain after global hypoxia-ischemia.

    Directory of Open Access Journals (Sweden)

    Reint K Jellema

    Full Text Available Hypoxic-ischemic encephalopathy (HIE in preterm infants is a severe disease for which no curative treatment is available. Cerebral inflammation and invasion of activated peripheral immune cells have been shown to play a pivotal role in the etiology of white matter injury, which is the clinical hallmark of HIE in preterm infants. The objective of this study was to assess the neuroprotective and anti-inflammatory effects of intravenously delivered mesenchymal stem cells (MSC in an ovine model of HIE. In this translational animal model, global hypoxia-ischemia (HI was induced in instrumented preterm sheep by transient umbilical cord occlusion, which closely mimics the clinical insult. Intravenous administration of 2 x 10(6 MSC/kg reduced microglial proliferation, diminished loss of oligodendrocytes and reduced demyelination, as determined by histology and Diffusion Tensor Imaging (DTI, in the preterm brain after global HI. These anti-inflammatory and neuroprotective effects of MSC were paralleled by reduced electrographic seizure activity in the ischemic preterm brain. Furthermore, we showed that MSC induced persistent peripheral T-cell tolerance in vivo and reduced invasion of T-cells into the preterm brain following global HI. These findings show in a preclinical animal model that intravenously administered MSC reduced cerebral inflammation, protected against white matter injury and established functional improvement in the preterm brain following global HI. Moreover, we provide evidence that induction of T-cell tolerance by MSC might play an important role in the neuroprotective effects of MSC in HIE. This is the first study to describe a marked neuroprotective effect of MSC in a translational animal model of HIE.

  9. BLOCKADE OF BRAIN ANGIOTENSIN II AT1 RECEPTORS AMELIORATES STRESS, ANXIETY, BRAIN INFLAMMATION AND ISCHEMIA: THERAPEUTIC IMPLICATIONS

    OpenAIRE

    Saavedra, Juan M.; Sánchez-Lemus, Enrique; BENICKY, Julius

    2010-01-01

    Poor adaptation to stress, alterations in cerebrovascular function and excessive brain inflammation play critical roles in the pathophysiology of many psychiatric and neurological disorders such as major depression, schizophrenia, post traumatic stress disorder, Parkinson's and Alzheimer's diseases and traumatic brain injury. Treatment for these highly prevalent and devastating conditions is at present very limited and many times inefficient, and the search for novel therapeutic options is of...

  10. Vasodilation by in vivo activation of astrocyte endfeet via two-photon calcium uncaging as a strategy to prevent brain ischemia

    Science.gov (United States)

    Chen, Yuanxin; Mancuso, James; Zhao, Zhen; Li, Xuping; Cheng, Jie; Roman, Gustavo; Wong, Stephen T. C.

    2013-12-01

    Decreased cerebral blood flow causes brain ischemia and plays an important role in the pathophysiology of many neurodegenerative diseases, including Alzheimer's disease and vascular dementia. In this study, we photomodulated astrocytes in the live animal by a combination of two-photon calcium uncaging in the astrocyte endfoot and in vivo imaging of neurovasculature and astrocytes by intravital two-photon microscopy after labeling with cell type specific fluorescent dyes. Our study demonstrates that photomodulation at the endfoot of a single astrocyte led to a 25% increase in the diameter of a neighboring arteriole, which is a crucial factor regulating cerebral microcirculation in downstream capillaries. Two-photon uncaging in the astrocyte soma or endfoot near veins does not show the same effect on microcirculation. These experimental results suggest that infrared photomodulation on astrocyte endfeet may be a strategy to increase cerebral local microcirculation and thus prevent brain ischemia.

  11. Moderately delayed post-insult treatment with normobaric hyperoxia reduces excitotoxin-induced neuronal degeneration but increases ischemia-induced brain damage

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    Haelewyn Benoit

    2011-04-01

    Full Text Available Abstract Background The use and benefits of normobaric oxygen (NBO in patients suffering acute ischemic stroke is still controversial. Results Here we show for the first time to the best of our knowledge that NBO reduces both NMDA-induced calcium influxes in vitro and NMDA-induced neuronal degeneration in vivo, but increases oxygen and glucose deprivation-induced cell injury in vitro and ischemia-induced brain damage produced by middle cerebral artery occlusion in vivo. Conclusions Taken together, these results indicate that NBO reduces excitotoxin-induced calcium influx and subsequent neuronal degeneration but favors ischemia-induced brain damage and neuronal death. These findings highlight the complexity of the mechanisms involved by the use of NBO in patients suffering acute ischemic stroke.

  12. The effects of voluntary, involuntary, and forced exercises on brain-derived neurotrophic factor and motor function recovery: a rat brain ischemia model.

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    Zheng Ke

    Full Text Available BACKGROUND: Stroke rehabilitation with different exercise paradigms has been investigated, but which one is more effective in facilitating motor recovery and up-regulating brain neurotrophic factor (BDNF after brain ischemia would be interesting to clinicians and patients. Voluntary exercise, forced exercise, and involuntary muscle movement caused by functional electrical stimulation (FES have been individually demonstrated effective as stroke rehabilitation intervention. The aim of this study was to investigate the effects of these three common interventions on brain BDNF changes and motor recovery levels using a rat ischemic stroke model. METHODOLOGY/PRINCIPAL FINDINGS: One hundred and seventeen Sprague-Dawley rats were randomly distributed into four groups: Control (Con, Voluntary exercise of wheel running (V-Ex, Forced exercise of treadmill running (F-Ex, and Involuntary exercise of FES (I-Ex with implanted electrodes placed in two hind limb muscles on the affected side to mimic gait-like walking pattern during stimulation. Ischemic stroke was induced in all rats with the middle cerebral artery occlusion/reperfusion model and fifty-seven rats had motor deficits after stroke. Twenty-four hours after reperfusion, rats were arranged to their intervention programs. De Ryck's behavioral test was conducted daily during the 7-day intervention as an evaluation tool of motor recovery. Serum corticosterone concentration and BDNF levels in the hippocampus, striatum, and cortex were measured after the rats were sacrificed. V-Ex had significantly better motor recovery in the behavioral test. V-Ex also had significantly higher hippocampal BDNF concentration than F-Ex and Con. F-Ex had significantly higher serum corticosterone level than other groups. CONCLUSION/SIGNIFICANCE: Voluntary exercise is the most effective intervention in upregulating the hippocampal BDNF level, and facilitating motor recovery. Rats that exercised voluntarily also showed less

  13. Hypoxia-ischemia or excitotoxin-induced tissue plasminogen activator- dependent gelatinase activation in mice neonate brain microvessels.

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    Priscilla L Omouendze

    Full Text Available Hypoxia-ischemia (HI and excitotoxicity are validated causes of neonatal brain injuries and tissue plasminogen activator (t-PA participates in the processes through proteolytic and receptor-mediated pathways. Brain microvascular endothelial cells from neonates in culture, contain and release more t-PA and gelatinases upon glutamate challenge than adult cells. We have studied t-PA to gelatinase (MMP-2 and MMP-9 activity links in HI and excitotoxicity lesion models in 5 day-old pups in wild type and in t-PA or its inhibitor (PAI-1 genes inactivated mice. Gelatinolytic activities were detected in SDS-PAGE zymograms and by in situ fluorescent DQ-gelatin microscopic zymographies. HI was achieved by unilateral carotid ligature followed by a 40 min hypoxia (8%O₂. Excitotoxic lesions were produced by intra parenchymal cortical (i.c. injections of 10 µg ibotenate (Ibo. Gel zymograms in WT cortex revealed progressive extinction of MMP-2 and MMP-9 activities near day 15 or day 8 respectively. MMP-2 expression was the same in all strains while MMP-9 activity was barely detectable in t-PA⁻/⁻ and enhanced in PAI-1⁻/⁻ mice. HI or Ibo produced activation of MMP-2 activities 6 hours post-insult, in cortices of WT mice but not in t-PA⁻/⁻ mice. In PAI-1⁻/⁻ mice, HI or vehicle i.c. injection increased MMP-2 and MMP-9 activities. In situ zymograms using DQ-gelatin revealed vessel associated gelatinolytic activity in lesioned areas in PAI-1⁻/⁻ and in WT mice. In WT brain slices incubated ex vivo, glutamate (200 µM induced DQ-gelatin activation in vessels. The effect was not detected in t-PA⁻/⁻ mice, but was restored by concomitant exposure to recombinant t-PA (20 µg/mL. In summary, neonatal brain lesion paradigms and ex vivo excitotoxic glutamate evoked t-PA-dependent gelatinases activation in vessels. Both MMP-2 and MMP-9 activities appeared t-PA-dependent. The data suggest that vascular directed protease inhibition may have

  14. Influence of mild hypothermia on vascular endothelial growth factor and infarct volume in brain tissues after cerebral ischemia in rats

    Institute of Scientific and Technical Information of China (English)

    Fei Ye; Gangming Xi; Biyong Qin; Shifeng Wang; Chengyan Li

    2006-01-01

    BACKGROUND: It has been demonstrated that mild hypothermia has obvious protective effect on both whole and local cerebral ischemia. However, the definite mechanism is still unclear for the brain protection of mild hypothermia on cerebral edema, inhibiting inflammatory reaction, stabilizing blood brain barrier, etc.OBJECTIVE: To investigate the effect of mild hypothermia on the expression of vascular endothelial growth factor and the infarct volume after cerebral ischemia in rats, and analyze the brain protective mechanism of mild hypothermia.DESIGN: A randomized grouping and controlled animal trial.SETTING: Department of Neurology, People's Hospital of Yunyang Medical College.MATERIALS: Twenty adult male SD rats of clean degree, weighing (250±30) g, were provided by the animal experimental center, School of Medicine, Wuhan University. The kits for SP immunohistochemistry were purchased from Beijing Zhongshan Golden Bridge Biotechnology Co., Ltd.METHODS: The experiments were carried out in the laboratory of Department of Neurology, Renmen Hospital of Wuhan University from May to July 2005. ① The 20 rats were divided randomly into normal temperature group (n =10) and mild hypothermia group (n =10). Models of permanent middle cerebral artery occlusion were established with modified nylon suture embolization. The rats were assessed with the Longa standards: O point for without nerve dysfunction; 1 for mild neurological deficit (fore claws could no extend completely); 2 for moderate neurological deficit (circling towards the affected side); 3 for severe neurological deficit (tilting towards the affected side); 4 for coma and unconscious; 1 -3 points represented that models were successfully established. The rats of the normal temperature group were fed at room temperature, and those in the mild hypothermia group were induced by hypothermia from 2 hours postoperatively, and the rectal temperature was kept at 34-35 ℃ for 72 hours. ② Measurement of infarct volume

  15. Osthole, a natural coumarin improves cognitive impairments and BBB dysfunction after transient global brain ischemia in C57 BL/6J mice: involvement of Nrf2 pathway.

    Science.gov (United States)

    Chen, ZiWei; Mao, XueXuan; Liu, AnMin; Gao, XiaoYun; Chen, XiaoHong; Ye, MinZhong; Ye, JianTao; Liu, PeiQing; Xu, SuoWen; Liu, JianXin; He, Wei; Lian, QiShen; Pi, RongBiao

    2015-01-01

    Oxidative stress and blood-brain barrier (BBB) disruption play important roles in cerebral ischemic pathogenesis and may represent targets for treatment. Earlier studies have shown that osthole, a main active constituent isolated from Cnidium monnieri (L.) Cusson, could be considered as an attractive therapeutic agent in the treatment of ischemic stroke. However, the mechanism underlying the protective effect remains vague. In this study we aimed to investigate the effect of osthole on transient cerebral ischemia as well as its mechanism(s) in C57 BL/6 J mice. Mice were subjected to transient global cerebral ischemia induced by bilateral common carotid artery occlusion for 25 min. Behavioral test was performed at 4 days after ischemia, followed by assessment of neuronal loss in hippocampal CA1 region. Osthole significantly improved the cognitive ability and enhanced the survival of pyramidal neurons in the CA1 region of mice after lesion. Further studies showed that osthole attenuated the permeation of BBB, which may contribute to antioxidative effect by increasing the superoxide dismutase activity and decreasing the malondialdehyde level in model mice. Further studies revealed that osthole obviously up-regulated the protein levels of nuclear factor erythroid 2-related factor 2/heme oxygenase 1 in HT22 cells. In conclusion, our findings indicated that osthole exerts neuroprotective effects against global cerebral ischemia injury by reducing oxidative stress injury and reserving the disruption of BBB, which may be attributed to elevating the protein levels of Nrf2 and HO-1. PMID:25424966

  16. Manganese-enhanced magnetic resonance imaging (MEMRI) of brain activity and applications to early detection of brain ischemia.

    Science.gov (United States)

    Aoki, Ichio; Naruse, Shoji; Tanaka, Chuzo

    2004-12-01

    Divalent manganese ion (Mn2+) has been reported to be a useful contrast agent for functional MRI, through a technique named activity-induced manganese-dependent MRI (AIM). In AIM, signal enhancement is related to functional increases in calcium influx, and therefore AIM is, thus far, the only MRI method able to map brain activation in vivo independently of the surrogate hemodynamic changes used in functional MRI. Because of its high signal-to-noise ratio (SNR) and high sensitivity, AIM allows the use of multi-slice or three-dimensional MRI techniques to map functional activity at high spatial resolution. In the present review, we define AIM as a functional MRI tool based on the administration of divalent ionized manganese through an open or disrupted blood-brain barrier (BBB). The adequacy and efficacy of AIM in detecting neural activation is described in light of supporting experiments on inhibition of calcium channels, FOS expression, and on direct comparison to BOLD- and perfusion-based functional MRI. Two main applications of AIM, mapping brain activation in rat somatosensory cortex, as well stroke research based on the well-established middle cerebral artery occlusion model, are described in detail. Methodological problems associated with a strong dependence on anesthetic conditions, potential corruption due to disruption of the BBB, and unspecific increase of the baseline signal due to acoustical noise are discussed. Finally, recommended preparation methods and experimental protocols for AIM are introduced.

  17. Neuropharmacology – Special Issue on Cerebral Ischemia Mechanisms of Ischemic Brain Damage – Review Article

    OpenAIRE

    Doyle, Kristian P.; Simon, Roger P.; Stenzel-Poore, Mary P

    2008-01-01

    Each year in the United States approximately 700,000 individuals are afflicted with a stroke and currently there are almost 2 million survivors of stroke living in the US with prolonged disability. In China 1.5 million people die from stroke each year and in developed nations stroke is the third leading cause of death, only surpassed by heart disease and cancer. Brain injury following stroke results from the complex interplay of multiple pathways including excitotoxicity, acidotoxicity, ionic...

  18. MAPK and pro-inflammatory mediators in the walls of brain blood vessels following cerebral ischemia

    OpenAIRE

    Maddahi, Aida

    2012-01-01

    INTRODUCTION Stroke is a serious neurological disease which may lead to death and severe disability [1, 2]. There are two major types of stroke: ischemic and hemorrhagic stroke. Both are associated with disruption of blood flow to a part of the brain with rapid depletion of cellular energy and oxygen, resulting in ionic disturbances and eventually neuronal cell death [3]. The pathologic process that develops after stroke is divided into acute (within hours), sub-acute (hours to days), ...

  19. Protective effect of ultrashortwave versus radix salviae miltiorrhizae on brains of rats with cerebral ischemia-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Lixin Zhang; Zhiqiang Wang; Zhiqiang Zhang; Xiuhua Yuan; Xiaojie Tong

    2006-01-01

    intraperitoneally injected with 0.01 mL/g RSM parenteral solution at 30 minutes before reperfusion and given small dosage of USW on head for 10 minutes once at 6 hours after reperfusion; sixteen rats in sham operation group did not receive any treatment. All 80 rats were taken brains at 24 hours after reperfusion to measure wet and dry weights to calculate water content: Cerebral water content (%) = (1-dry/wet weight) × 100%. Superoxide dismutase (SOD) activity was measured by hydroxylamine method and malondialdehyde (MDA) content was measured by TBA photometric method.MAIN OUTCOME MEASURES: Cerebral water content, SOD activity and MDA content.RESULTS: All 160 rats except 80 failing in modeling were involved in the final analysis. ① The cerebral water content of left hemisphere made no significant difference (P > 0.05). The cerebral water content of right hemisphere in the control group and the three treatment groups was obviously higher than that of the sham operation group [(81.26±0.77)%, (79.74±0.68)%, (79.76±0.81)%, (79.61 ±0.79)%, (77.43±0.61)%, P < 0.05].The cerebral water content of right hemisphere in the three treatment groups was obviously lower than that of the control group (P < 0.05). There was no significant difference among the three treatment groups (P > 0.05).② Compared with the control group, SOD activity (right) of the control group decreased obviously (P < 0.05),while MDA content increased obviously (P < 0.05). SOD activity in the three therapeutic groups increased obviously, while MDA content decreased obviously (P < 0.05); there was no significant difference among the three treatment groups (P > 0.05).CONCLUSION: ① USW and RSM therapy have neuroprotective effects against focal cerebral ischemia-reperfusion injuries by means of decreasing cerebral water content and MDA and increasing the activity of SOD. ② Synergistic action was not observed between these two therapeutic methods.

  20. Dapsone improves functional deficit and diminishes brain damage evaluated by 3-Tesla magnetic resonance image after transient cerebral ischemia and reperfusion in rats.

    Science.gov (United States)

    Diaz-Ruiz, Araceli; Roldan-Valadez, Ernesto; Ortiz-Plata, Alma; Mondragón-Lozano, Rodrigo; Heras-Romero, Yessica; Mendez-Armenta, Marisela; Osorio-Rico, Laura; Nava-Ruiz, Concepción; Ríos, Camilo

    2016-09-01

    Stroke is a frequent cause of death and the first of disability in the world population. We have shown that dapsone acts as an antioxidant, antiinflammatory and antiapoptotic agent after brain Ischemia reperfusion (I/R) in rats; however, its therapeutic efficacy, measured by imaging has not been characterized. In this context, the aim of this study was to evaluate the neuroprotective effect of dapsone by magnetic resonance imaging (MRI) and to correlate imaging markers with motor function and oxidative stress after transient cerebral ischemia and reperfusion (I/R). We used male rats throughout the experiment. Functional deficit after I/R was assessed by using Longa scale. The area of brain tissue damage was measured by histology. The nuclear factor erythroid 2-related factor 2 (Nrf-2) and the amount of reactive oxygen species (ROS) were measured as biomarkers of oxidative stress. Finally, difussion tensor MRI was employed to measure the fractional anisotropy (FA), as a MRI marker of the pathophysiologic brain status. Results showed a better functional recovery and less damaged tissue in animals treated with dapsone vs control group. The values of FA were higher in animals receiving treatment, indicating a better preservation of brain structure. At early stages of the damage, dapsone was able to reduce both oxidative markers (Nrf-2 and ROS). Our findings provide new evidence for the efficacy of dapsone when administered during the acute phase after I/R and that quantitative sequences of MRI are useful for characterizing its potential therapeutic benefits after stroke. PMID:27321157

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

  2. Willed-movement training reduces brain damage and enhances synaptic plasticity related proteins synthesis after focal ischemia.

    Science.gov (United States)

    Nie, Jingjing; Yang, Xiaosu; Tang, Qingping; Shen, Qin; Li, Simin

    2016-01-01

    It has been wildly accepted that willed movement(WM) training promotes neurological rehabilitation in patients with stroke. However, it was not clear whether the effect of WM is better than other forms of exercise. The purpose of this study is to assess different effects of WM and other forms of exercise on rats with focal ischemia. The subjects are all had right middle cerebral artery occlusion (MCAO) surgery and randomly allocated to three groups of training and one control group with no training. Infarct volume by 2,3,5-triphenyltetrazolium chloride (TTC) dye, expression of PICK1 and synaptophysin in cerebral cortex and striatum of injured side by western blotting and immunofluorescence performed are analyzed. Exercise has done respectively on rats in each group for 15 days and 30 days. Compared with the control group, the brain damage is reduced in other groups after 15 days exercise. The protein expressions levels of synaptophysin and PICK1 are upregulated after exercise. Concentration of PICK1 protein in WM is greater than other exercise groups, and the expression of synaptophysin in WM and SM groups are higher than EM groups. The number of PICK1 positive cells, synaptophysin and PICK1 co-positive cells are increased by exercise. Synaptophysin is widely distributed in cortex surrounding the injury area in WM and EM. It is indicated in our result that willed-movement training is the most effective intervention in enhancing the PICK1-mediated synaptic plasticity in the area adjacent to the damage region of ischemic rats. PMID:26556240

  3. Neuroprotective profile of enoxaparin, a low molecular weight heparin, in in vivo models of cerebral ischemia or traumatic brain injury in rats: a review.

    Science.gov (United States)

    Stutzmann, Jean-Marie; Mary, Veronique; Wahl, Florence; Grosjean-Piot, Odile; Uzan, André; Pratt, Jeremy

    2002-01-01

    The development of treatments for acute neurodegenerative diseases (stroke and brain trauma) has focused on (i) reestablishing blood flow to ischemic areas as quickly as possible (i.e. mainly antithrombotics or thrombolytics for stroke therapy) and (ii) on protecting neurons from cytotoxic events (i.e. neuroprotective therapies such as anti-excitotoxic or anti-inflammatory agents for stroke and neurotrauma therapies). This paper reviews the preclinical data for enoxaparin in in vivo models of ischemia and brain trauma in rats. Following a photothrombotic lesion in the rat, enoxaparin significantly reduced edema at 24 h after lesion when the treatment was started up to 18 h after insult. Enoxaparin was also tested after an ischemic insult using the transient middle cerebral artery occlusion (tMCAO) model in the rat. Enoxaparin, 2 x 1.5 mg/kg i.v., significantly reduced the lesion size and improved the neuroscore when the treatment was started up to 5 h after ischemia. Enoxaparin, administered at 5 h after insult, reduced cortical lesion size in a dose-dependent manner. In permanent MCAO, enoxaparin (5 and 24 h after insult) significantly reduced lesion size and improved neuroscore. A slight and reversible elevation of activated partial thromboplastin time (APTT) suggests that enoxaparin is neuroprotective at a non-hemorrhagic dose. Traumatic brain injury (TBI) is often accompanied by secondary ischemia due in part to edema-induced compression of blood vessels. When enoxaparin, at 0.5 mg/kg i.v. + 4 x 1 mg/kg s.c., was administered later than 30 h after TBI, it significantly reduced edema in hippocampus and parietal cortex. At one week after TBI the lesion size was significantly reduced and the neurological deficit significantly improved in enoxaparin treated animals. Finally, the cognitive impairment was significantly improved by enoxaparin at 48 h to 2 weeks after TBI. The anticoagulant properties of unfractionated heparin and specifically enoxaparin can explain

  4. Mild hypothermia effects on intercellular adhesion molecule-1 and serum interleukin-6 expression in brain tissues of a rat focal ischemia model

    Institute of Scientific and Technical Information of China (English)

    Shengqi Fu; Lei Yang; Shuling Zhang; Shilong Sun; Xingai Mao

    2008-01-01

    BACKGROUND: Previous studies have confirmed the neuroprotective effect of mild hypothermia on ischemic brain injury.OBJECTIVE: To investigate the effects of mild hypothermia on intercellular adhesion molecule-1 expression and serum interleukin-6 levels in ischemic brain tissues of focal brain ischemia rats, and to explore the neuroprotective effects of mild hypothermia on ischemic brain injury.DESIGN, TIME AND SETTING: A randomized, controlled, neurobiological experiment was performed at the Central Laboratory, First Affiliated Hospital, Xinxiang Medical College, China from February to July 2006.MATERIALS: Thirty healthy, adult, Sprague Dawley rats were used to establish middle cerebral artery occlusion models using the suture method. The immunohistochemistry (streptavidin-biotin-peroxidase complex method) kit was purchased from Boster, China. Interleukin-6 radioimmunoassay was supplied by Institute of Radioimmunity, Technology Development Center, General Hospital of Chinese PLA. METHODS: The rats were equally and randomly assigned into mild hypothermia and control groups, and middle cerebral artery occlusion models were established. The rectal temperature was maintained at (37 ± 0.5)℃ in the control group. In the mild hypothermia group, the rectal temperature was maintained at (33±1)℃.MAIN OUTCOME MEASURES: At 12 hours after model establishment, the ischemic brain hemispheres were coronally sliced at the level of the optic chiasm. The number of intercellular adhesion molecule- 1 -positive vessels per high-power field was observed with an optical microscope. Serum interleukin-6 levels were measured by radioimmunoassay.RESULTS: Compared with the control group, intercellular adhesion molecule-I and serum interleukin-6 expressions were significantly decreased in ischemic brain tissues of the mild hypothermia group (P < 0.01).CONCLUSION: Mild hypothermia exhibits a neuroprotective effect by reducing serum interleukin-6 and intercellular adhesion molecule- 1

  5. Effect of Ligustrazine and Shenmai Injection on ATPase and free radical metabolism in the aged rats with myocardial injury after brain ischemia/reperfusion

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    AIM: To study the protecitve mechanism of Ligustrazine (LT), Shenmai Parenteral Injection (SPI), combination of Ligustrazine and Shenmai Parenteral Injection (LSP) to myocardial injury after brain ischemia-reperfusion in aged rats from the change in ATPase and free radical in order to provide theoretical basic for prevention and cure of cerebral infarction. METHODS: Aged rats (more than 20 months) were divided into model group, control group, Nimotop group, LT group, SPI group and LSP group. We measured the following items in aged rats with 60 min of reperfusion after 30 min of brain ischemia: the content of MDA, the activities of superoxide dismutase (SOD), lactic dehydrrogenase (LDH), creatine phosphokinase (CPK), ATPase. RESUTLS: The CPK and LDH activities in the model rats increased obviously. The serum CPK activity in the LSP group, the LT group, nimotop group was lower than those in the model group obviously. The serum LDH activities in LT group and SPI group were obviously lower compared with those in the model group. The activity of Na+-K+-ATPase and Ca2+-ATPase in model group was decreased. Contrast to the model group, the activity of Na+-K+-ATPase in LSP group, Nimotop group, LT group and the activities of Ca2+-ATPase in the LSP group were higher. The serum MDA/SOD ratio was larger than that in the control group. The decrease in myocardial SOD activity and the increase in the MDA level, MDA/SOD ratio in the model group showed significant difference compared with that in the control. The MDA level in the LSP group was lower than that in the model group. The increase in myocardial SOD activity and decrease in MDA, MDA/SOD ratio were obvious in the LSP group compared with the model group. CONCLUSION: The myocardial injury after brain ischemia-reperfusion in aged rats was related to the decrease in the activity of Na+-K+-ATPase and injury of free radical. LT, SPI, LSP and Nimotop could prevent this inury. Nimotop and LT could enhanced the

  6. Effects of Chuanxiongqin hydrochloride on increasing the fluidity of brain cell membrane and scavenging free radicals in model rats with ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Chenxu Li

    2006-01-01

    BACKGROUND: The fluidity of cell membrane can be affected by various factors. Many experiments have confirmed that the ischemia/reperfusion of organic tissue can increase the contents of free radicals, which lead to high rigidity and Iow fluidity of cell membrane, and the conditions can be changed by Chuanxiongqin.OBJECTIVE: To observe the effect and mechanism of Chuanxiongqin hydrochloride on the fluidity of brain cell membrane in rat models of ischemia/reperfusion.DESIGN: A completely randomized controlled animal trial.SETTINGS: Institute of Brain Sciences; Department of Physiology, Medical College, Datong University.MATERIALS: Twenty male grade I Wistar rats of 170-220 g were randomly divided into model group (n =10)and control group (n =10). Chuanxiongqin hydrochloride (molecular mass was 172.2) was purchased from the National Institute for the Control of Pharmaceutical and Biological Products (batch number; 0817-9803); Spin labelers: 5-cfoxyl-stearlic acid methylester (5DS), 16-doxyl-stearlic acid methylester (16DS), xanthine, xanthine oxidase (XOD) and 5,5-dimeth-1-pyrroline- N-oxide (DMPO) from Sigma Company; Bruker ESP 300 electron paramagnetic resonance (EPR) spectrometer by Bruker Company (Germany).METHODS: The experiments were carried out in the State Key Laboratory of Natural and Biomimetic Drugs,Peking University from June 2001 to July 2002. In the model group, rats were made into models of cerebral ischemia by 30-minute ligation and 2-hour reperfusion of common carotid arteries; The rats in the control group were not made into models. The order parameter (S) and rotational correlation time (тc) were detected with the ESR spectrometer by means of spin labeling. The greater the S and тc, the smaller the fluidity. Meanwhile, the clearance rate of free radicals was detected with ESR spin trapping. The measurement data were compared using the ttest.MAIN OUTCOME MEASURES: The S, тc and clearance rates of O2 and OH free radicals were compared between the

  7. 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.

  8. Inhibition of Brain Swelling after Ischemia-Reperfusion by β-Adrenergic Antagonists: Correlation with Increased K+ and Decreased Ca2+ Concentrations in Extracellular Fluid

    Directory of Open Access Journals (Sweden)

    Dan Song

    2014-01-01

    Full Text Available Infarct size and brain edema following ischemia/reperfusion are reduced by inhibitors of the Na+, K+, 2Cl−, and water cotransporter NKCC1 and by β1-adrenoceptor antagonists. NKCC1 is a secondary active transporter, mainly localized in astrocytes, driven by transmembrane Na+/K+ gradients generated by the Na+,K+-ATPase. The astrocytic Na+,K+-ATPase is stimulated by small increases in extracellular K+ concentration and by the β-adrenergic agonist isoproterenol. Larger K+ increases, as occurring during ischemia, also stimulate NKCC1, creating cell swelling. This study showed no edema after 3 hr medial cerebral artery occlusion but pronounced edema after 8 hr reperfusion. The edema was abolished by inhibitors of specifically β1-adrenergic pathways, indicating failure of K+-mediated, but not β1-adrenoceptor-mediated, stimulation of Na+,K+-ATPase/NKCC1 transport during reoxygenation. Ninety percent reduction of extracellular Ca2+ concentration occurs in ischemia. Ca2+ omission abolished K+ uptake in normoxic cultures of astrocytes after addition of 5 mM KCl. A large decrease in ouabain potency on K+ uptake in cultured astrocytes was also demonstrated in Ca2+-depleted media, and endogenous ouabains are needed for astrocytic K+ uptake. Thus, among the ionic changes induced by ischemia, the decrease in extracellular Ca2+ causes failure of the high-K+-stimulated Na+,K+-ATPase/NKCC1 ion/water uptake, making β1-adrenergic activation the only stimulus and its inhibition effective against edema.

  9. Erythropoietin delivered via intra-arterial infusion reduces endoplasmic reticulum stress in brain microvessels of rats following cerebral ischemia and reperfusion.

    Science.gov (United States)

    Zhao, Haiping; Wang, Rongliang; Wu, Xiaoning; Liang, Jia; Qi, Zhifeng; Liu, Xiangrong; Min, Lianqiu; Ji, Xunming; Luo, Yumin

    2015-03-01

    Local infusion of low dose erythropoietin (EPO) alleviates cerebral ischemia and reperfusion (I/R) injury in rats; however, the underlying molecular mechanisms are still unclear. The present study investigated the effect of low dose EPO treatment on I/R-induced endoplasmic reticulum (ER) stress in brain tissue and isolated microvessels in rodents. Sprague-Dawley rats were subjected to 2 h ischemia/24 h reperfusion by middle cerebral artery (MCA) occlusion, then administered fluorescein isothiocyanate-labeled EPO via MCA infusion (MCAI) or subcutaneous injection (SI) to compare the efficiency of two modes of delivery. Neurobehavioral deficits and infarct volume, and the expression of ER stress-associated proteins and apoptosis in brain tissue or isolated microvessels, as well as the transcriptional activity of 16 factors involved in ER stress and the unfolded protein response in brain tissue was asscessed. A higher EPO level in cerebrospinal fluid and brain tissue was observed in rats treated with EPO by MCAI (800 IU/kg) than by SI (5000 IU/kg). Moreover, neurobehavioral deficits and infarct volume were reduced in rats treated with EPO by MCAI and salubrinal. EPO suppressed the expression of ER stress signals glucose-regulated protein 78, activating transcription factor (ATF) 6α, and CCAAT enhancer-binding protein homologous protein (CHOP), as well as that of the pro-apoptotic protein caspase-3 in brain microvessels, and decreased the number of CHOP-positive, apoptotic neurons. EPO treatment also reduced the transcriptional activities of CHOP, forkhead box protein O1, and ATF4. These results provide evidence that low dose EPO treatment via MCAI provides neuroprotection following acute ischemic stroke by inhibiting the ER stress response. PMID:25626440

  10. Metallothionein-II Inhibits Lipid Peroxidation and Improves Functional Recovery after Transient Brain Ischemia and Reperfusion in Rats

    Directory of Open Access Journals (Sweden)

    Araceli Diaz-Ruiz

    2014-01-01

    Full Text Available After transient cerebral ischemia and reperfusion (I/R, damaging mechanisms, such as excitotoxicity and oxidative stress, lead to irreversible neurological deficits. The induction of metallothionein-II (MT-II protein is an endogenous mechanism after I/R. Our aim was to evaluate the neuroprotective effect of MT-II after I/R in rats. Male Wistar rats were transiently occluded at the middle cerebral artery for 2 h, followed by reperfusion. Rats received either MT (10 μg per rat i.p. or vehicle after ischemia. Lipid peroxidation (LP was measured 22 h after reperfusion in frontal cortex and hippocampus; also, neurological deficit was evaluated after ischemia, using the Longa scoring scale. Infarction area was analyzed 72 hours after ischemia. Results showed increased LP in frontal cortex (30.7% and hippocampus (26.4%, as compared to control group; this effect was fully reversed by MT treatment. Likewise, we also observed a diminished neurological deficit assessed by the Longa scale in those animals treated with MT compared to control group values. The MT-treated group showed a significant (P<0.05 reduction of 39.9% in the infarction area, only at the level of hippocampus, as compared to control group. Results suggest that MT-II may be a novel neuroprotective treatment to prevent ischemia injury.

  11. Delayed administration of a matrix metalloproteinase inhibitor limits progressive brain injury after hypoxia-ischemia in the neonatal rat

    Directory of Open Access Journals (Sweden)

    Pennypacker Keith R

    2008-08-01

    Full Text Available Abstract Background Hypoxia-ischemia (H-I can produce widespread neurodegeneration and deep cerebral white matter injury in the neonate. Resident microglia and invading leukocytes promote lesion progression by releasing reactive oxygen species, proteases and other pro-inflammatory mediators. After injury, expression of the gelatin-degrading matrix metalloproteinases (MMPs, MMP-2 and MMP-9, are thought to result in the proteolysis of extracellular matrix (ECM, activation of cytokines/chemokines, and the loss of vascular integrity. Thus, therapies targeting ECM degradation and progressive neuroinflammation may be beneficial in reducing H-I – induced neuropathy. Minocycline has MMP-inhibitory properties and is both anti-inflammatory and neuroprotective. AG3340 (prinomastat is an MMP inhibitor with high selectivity for the gelatinases. The purpose of this study was to determine whether these compounds could limit H-I – induced injury when administered at a delayed time point. Methods Sprague-Dawley rats were exposed to H-I at postnatal day 7 (P7, consisting of unilateral carotid artery ligation followed by 90 min exposure to 8% O2. Minocycline, AG3340, or vehicle were administered once daily for 6 days, beginning 24 hours after insult. Animals were sacrificed at P14 for neurohistological assessments. Immunohistochemistry was performed to determine the degree of reactive astrogliosis and immune cell activation/recruitment. Neural injury was detected using the Fluoro-Jade stain, a marker that identifies degenerating cells. Results CD11b and glial fibrillary acidic protein (GFAP immunopositive cells increased in ipsilateral cortex after treatment with vehicle alone, demonstrating microglia/macrophage recruitment and reactive astrogliosis, respectively. Fluoro-Jade staining was markedly increased throughout the fronto-parietal cortex, striatum and hippocampus. Treatment with minocycline or AG3340 inhibited microglia/macrophage recruitment

  12. Nursing experience of newborn hypoxia-ischemia brain%新生儿缺氧缺血性脑病的护理体会

    Institute of Scientific and Technical Information of China (English)

    徐军

    2015-01-01

    目的:探讨新生儿缺氧缺血性脑病的有效护理方法。方法:收治缺氧缺血性脑病患儿72例,分别采用呼吸道护理、氧气护理、惊厥护理、颅高压护理和饮食护理等护理方法。结果:痊愈68例(95%),并发吸入性肺炎3例(4%),死亡1例(1%)。结论:早期积极地观察病情、合理的护理措施对促进患儿的早日康复有着重要的意义。%Objective:To explore the effective nursing method of newborn hypoxia-ischemia brain.Methods:72 cases of children with hypoxia-ischemia brain were given the nursing methods including the nursing of respiratory tract,the oxygen nursing, convulsions nursing,intracranial hypertension nursing and diet nursing.Results:68 cases of patients were cured(95%);3 cases of patients had aspiration pneumonia(4%);1 cases died(1%).Conclusion:Early active observation and reasonable nursing measures had great significance to promote the early recovery of children.

  13. The Effects of Xanthine Oxidoreductase Inhibitors on Oxidative Stress Markers following Global Brain Ischemia Reperfusion Injury in C57BL/6 Mice.

    Directory of Open Access Journals (Sweden)

    Masahiro Yamaguchi

    Full Text Available We demonstrated that 3-nitrotyrosine and 4-hydroxy-2-nonenal levels in mouse brain were elevated from 1 h until 8 h after global brain ischemia for 14 min induced with the 3-vessel occlusion model; this result indicates that ischemia reperfusion injury generated oxidative stress. Reactive oxygen species production was observed not only in the hippocampal region, but also in the cortical region. We further evaluated the neuroprotective effect of xanthine oxidoreductase inhibitors in the mouse 3-vessel occlusion model by analyzing changes in the expression of genes regulated by the transcription factor nuclear factor-kappa B (including pro-inflammatory cytokines interleukin-1β (IL-1β and tumor necrosis factor-α (TNF-α, matrix metalloproteinase-9 and intercellular adhesion molecules-1. Administration of allopurinol resulted in a statistically significant decrease in IL-1β and TNF-α mRNA expression, whereas febuxostat had no significant effect on expression of these genes; nevertheless, both inhibitors effectively reduced serum uric acid concentration. It is suggested that the neuroprotective effect of allopurinol is derived not from inhibition of reactive oxygen species production by xanthine oxidoreductase, but rather from a direct free-radical-scavenging effect.

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

    Science.gov (United States)

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

    2006-01-01

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

  15. Changes in brain levels of N-acylethanolamines and 2-arachidonoylglycerol in focal cerebral ischemia in mice

    DEFF Research Database (Denmark)

    Degn, Matilda; Lambertsen, Kate L.; Petersen, Gitte;

    2007-01-01

    The N-acylethanolamines (NAEs) and 2-arachidonoylglycerol (2-AG) are bioactive lipids that can modulate inflammatory responses and protect neurons against glutamatergic excitotoxicity. We have used a model of focal cerebral ischemia in young adult mice to investigate the relationship between foca...

  16. Gene expression profile induced by oral administration of baicalin and gardenin after focal brain ischemia in rats

    Institute of Scientific and Technical Information of China (English)

    Zhan-jun ZHANG; Zhong WANG; Xiao-yan ZHANG; Kang YING; Jian-xun LIU; Yong-yan WANG

    2005-01-01

    Aim: To investigate differential gene expression and the pharmacological mechanism of baicalin and gardenin in focal cerebral ischemia in rats with high-density cDNA microarray. Methods: Rat left middle cerebral arteries were occluded and treated with either baicalin or gardenin. The pharmacological effects were investigated using the difference in infarction areas before and after treatment, which were determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Gene expression was demonstrated using a "Biostar40S" gene microarray. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to verify the result of the selected genes. Results: Both baicalin and gardenin reduced the infarction areas in focal cerebral ischemia rats (P<0.05). The differential genes were 211,177, and 70 (upregulated or downregulated) in the model group, baicalin,and gardenin treatment groups compared with the sham-operated group,respectively. Gene expression of RpL19 and Csnk2 underwent an approximately 1.9 and 2.1-fold increase, respectively, verified by semiquantitative RT-PCR, which was the same trend as the cDNA microarray. Conclusion: Differential gene expression with respect to the pharmacological effects of baicalin and gardenin on focal cerebral ischemia by cDNA microarray revealed a number of clues with respect to the therapeutic mechanisms of Chinese traditional medicine. In addition,the present study provided theoretical and experimental evidence that will aid future studies examining cerebral ischemia.

  17. Kolaviron, a Garcinia kola biflavonoid complex, protects against ischemia/reperfusion injury: pertinent mechanistic insights from biochemical and physical evaluations in rat brain.

    Science.gov (United States)

    Akinmoladun, Afolabi C; Akinrinola, Bolanle L; Olaleye, M Tolulope; Farombi, Ebenezer O

    2015-04-01

    The pathophysiology of stroke is characterized by biochemical and physical alterations in the brain. Modulation of such aberrations by therapeutic agents affords insights into their mechanism of action. Incontrovertible evidences that oxidative stress is involved in the pathophysiology of neurologic disorders have brought antioxidative compounds, especially plant phytochemicals, under increasing focus as potential remedies for the prevention and management of neurodegenerative diseases. Kolaviron, a biflavonoid complex isolated from Garcinia kola Heckel (Guttiferae) was evaluated for neuroprotectivity in brains of male Wistar rats submitted to bilateral common carotid artery occlusion-induced global ischemia/reperfusion injury (I/R). Animals were divided into six groups: sham treated, vehicle (I/R), 50 mg/kg kolaviron + I/R, 100 mg/kg kolaviron + I/R, 200 mg/kg kolaviron + I/R and quercetin (20 mg/kg i.p.) + I/R. The common carotid arteries were occluded for 30 min followed by 2 h of reperfusion. Relative brain weight and brain water content were determined and oxidative stress and neurochemical markers were also evaluated. I/R caused significant decreases in glutathione level and the activities of enzymic antioxidants, the sodium pump and acetylcholinesterase while significant increases were recorded in relative brain weight, brain water content, lipid peroxidation and the activities of glutamine synthetase and myeloperoxidase. There was a remarkable ablation of I/R induced oxidative stress, neurochemical aberrations and brain edema in animals pretreated with kolaviron. The results suggested that the protection afforded by kolaviron probably involved regulation of redox and electrolyte homeostasis as well as anti-inflammatory and antiexcitotoxic mechanisms. PMID:25638229

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

    DEFF Research Database (Denmark)

    Henriksson, Marie; Stenman, Emelie; Vikman, Petter;

    2007-01-01

    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...... 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........ 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...

  19. Color-coded perfused blood volume imaging using multidetector CT: initial results of whole-brain perfusion analysis in acute cerebral ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Kloska, Stephan P.; Fischer, Tobias; Fischbach, Roman; Heindel, Walter [University of Muenster, Department of Clinical Radiology, Muenster (Germany); Nabavi, Darius G.; Dittrich, Ralf; Ringelstein, E.B. [University of Muenster, Department of Neurology, Muenster (Germany); Ditt, Hendrik; Klotz, Ernst [Siemens AG, Medical Solutions, Forchheim (Germany)

    2007-09-15

    Computed tomography (CT) is still the primary imaging modality following acute stroke. To evaluate a prototype of software for the calculation of color-coded whole-brain perfused blood volume (PBV) images from CT angiography (CTA) and nonenhanced CT (NECT) scans, we studied 14 patients with suspected acute ischemia of the anterior cerebral circulation. PBV calculations were performed retrospectively. The detection rate of ischemic changes in the PBV images was compared with NECT. The volume of ischemic changes in PBV was correlated with the infarct volume on follow-up examination taking potential vessel recanalization into account. PBV demonstrated ischemic changes in 12/12 patients with proven infarction and was superior to NECT (8/12) in the detection of early ischemia. Moreover, PBV demonstrated the best correlation coefficient with the follow-up infarct volume (Pearson's R = 0.957; P = 0.003) for patients with proven recanalization of initially occluded cerebral arteries. In summary, PBV appears to be more accurate in the detection of early infarction compared to NECT and mainly visualizes the irreversibly damaged ischemic tissue. (orig.)

  20. Crosstalk between complement and Toll-like receptor activation in relation to donor brain death and renal ischemia-reperfusion injury.

    Science.gov (United States)

    Damman, Jeffrey; Daha, Mohamed R; van Son, Willem J; Leuvenink, Henri G; Ploeg, Rutger J; Seelen, Marc A

    2011-04-01

    Two central pathways of innate immunity, complement and Toll-like receptors (TLRs), play an important role in the pathogenesis of renal injury inherent to kidney transplantation. Recent findings indicate close crosstalk between complement and TLR signaling pathways. It is suggested that mitogen activated protein kinases (MAPKs) might be the key molecules linking both the complement and TLR pathways together. Complement and TLRs are important mediators of renal ischemia-reperfusion injury (IRI). Besides IRI, complement C3 can also be upregulated and activated in the kidney before transplantation as a direct result of brain death (BD) in the donor. This local upregulation and activation of complement in the donor kidney has been proven to be detrimental for renal allograft outcome. Also TLR4 and several of its major ligands are upregulated by donor BD compared to living donors. Important and in line with the observations above, kidney transplant recipients have a benefit when receiving a kidney from a TLR4 Asp299Gly/Thr399Ile genotypic donor. The role of complement and TLRs and crosstalk between these two innate immune systems in relation to renal injury during donor BD and ischemia-reperfusion are focus of this review. Future strategies to target complement and TLR activation in kidney transplantation are considered.

  1. PET Imaging with [(18)F]FSPG Evidences the Role of System xc(-) on Brain Inflammation Following Cerebral Ischemia in Rats.

    Science.gov (United States)

    Domercq, Maria; Szczupak, Boguslaw; Gejo, Jon; Gómez-Vallejo, Vanessa; Padro, Daniel; Gona, Kiran Babu; Dollé, Frédéric; Higuchi, Makoto; Matute, Carlos; Llop, Jordi; Martín, Abraham

    2016-01-01

    In vivo Positron Emission Tomography (PET) imaging of the cystine-glutamate antiporter (system xc(-)) activity with [(18)F]FSPG is meant to be an attractive tool for the diagnosis and therapy evaluation of brain diseases. However, the role of system xc(-) in cerebral ischemia and its involvement in inflammatory reaction has been scarcely explored. In this work, we report the longitudinal investigation of the neuroinflammatory process following transient middle cerebral artery occlusion (MCAO) in rats using PET with [(18)F]FSPG and the translocator protein (TSPO) ligand [(18)F]DPA-714. In the ischemic territory, [(18)F]FSPG showed a progressive binding increase that peaked at days 3 to 7 and was followed by a progressive decrease from days 14 to 28 after reperfusion. In contrast, [(18)F]DPA-714 evidenced maximum binding uptake values over day 7 after reperfusion. Ex vivo immnunohistochemistry confirmed the up-regulation of system xc(-) in microglial cells and marginally in astrocytes. Inhibition of system xc(-) with sulfasalazine and S-4-CPG resulted in increased arginase (anti-inflammatory M2 marker) expression at day 7 after ischemia, together with a decrease in TSPO and microglial M1 proinflammatory markers (CCL2, TNF and iNOS) expression. Taken together, these results suggest that system xc(-) plays a key role in the inflammatory reaction underlying experimental stroke.

  2. Sirt1 in cerebral ischemia

    OpenAIRE

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

    2015-01-01

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

  3. Depressed glucose consumption at reperfusion following brain ischemia does not correlate with mitochondrial dysfunction and development of infarction: an in vivo positron emission tomography study.

    Science.gov (United States)

    Martín, Abraham; Rojas, Santiago; Pareto, Deborah; Santalucia, Tomàs; Millán, Olga; Abasolo, Ibane; Gómez, Vanessa; Llop, Jordi; Gispert, Joan D; Falcon, Carles; Bargalló, Núria; Planas, Anna M

    2009-05-01

    Glucose consumption is severely depressed in the ischemic core, whereas it is maintained or even increased in penumbral regions during ischemia. Conversely, glucose utilization is severely reduced early after reperfusion in spite that glucose and oxygen are available. Experimental studies suggest that glucose hypometabolism might be an early predictor of brain infarction. However, the relationship between early glucose hypometabolism with later development of infarction remains to be further studied in the same subjects. Here, glucose consumption was assessed in vivo by positron emission tomography (PET) with (18)F-fluorodeoxyglucose ((18)F-FDG) in a rat model of ischemia/reperfusion. Perfusion was evaluated by PET with (13)NH(3) during and after 2-hour (h) middle cerebral artery occlusion, and (18)F-FDG was given after 2h of reperfusion. Brain infarction was evaluated at 24h. Mitochondrial oxygen consumption was examined ex vivo using a biochemical method. Cortical (18)F-FDG uptake was reduced by 45% and 25% in the ischemic core and periphery, respectively. However, substantial alteration of mitochondrial respiration was not apparent until 24h, suggesting that mitochondria retained the ability to consume oxygen early after reperfusion. These results show reduced glucose use at early reperfusion in regions that will later develop infarction and, to a lesser extent, in adjacent regions. Depressed glucose metabolism in the ischemic core might be attributable to reduced metabolic requirement due to irreversible cellular injury. However, reduced glucose metabolism in peripheral regions suggests either an impairment of glycolysis or reduced glucose demand. Thus, our study supports that glycolytic depression early after reperfusion is not always related to subsequent development of infarction.

  4. Effects of repetitive transcranial magnetic stimulation on adenosine triphosphate content and microtubule associated protein-2 expression after cerebral ischemia-reperfusion injury in rat brain

    Institute of Scientific and Technical Information of China (English)

    FENG Hong-lin; YAN Li; CUI Li-ying

    2008-01-01

    Background Repetitive transcranial magnetic stimulation (rTMS) research has mainly been focused on the therapeutic effect of psychiatric disorders and Parkinson's disease. A few studies have shown that rTMS might protect against delayed neuronal death induced by transient ischemia, enhance long-term potentiation in ischemic conditions and affect regional brain blood flow and metabolism. The aim of this study was to determine the effects of repetitive transcranial magnetic stimulation (rTMS) on adenosine triphosphate (ATP) content and microtubule associated protein-2 (MAP-2) expression in rat brain after middle cerebral artery occlusion (MCAO)/reperfusion.Methods To study the effects of different timecourses of rTMS on ATP content and MAP-2 expression, 90 rats were randomly divided into three groups (30 rats in each group). To study the effects of multiple rTMS parameters on ATP content and MAP-2 expression, the rats in each group were further divided into six subgroups (five rats each). The rats were sacrificr, 24-hour and 48-hour intervals after reperfusion, and the brain tissues were collected for the detection of ATP and MAP-2.Results rTMS could significantly increase ATP content and MAP-2 expression in the left brain following ischemic insult (P<0.01) and different rTMS parameters had different effects on the ATP level and the MAP-2 expression in the left striatum. A high-frequency rTMS played an important role in MAP-2 expression and ATP preservation.Conclusions This study revealed that rTMS induced significant increase of ATP content and MAP-2 expression in the injured area of the brain, suggesting that the regulation of both ATP and MAP-2 may be involved in the biological mechanism of the effect of rTMS on neural recovery. Therefore, rTMS may become a potential adjunctive therapy for ischemic cerebrovascular disease.

  5. The effect of hyperglycemia on blood brain barrier of rats with focal cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Objective: To determine whether hyperglycemia could aggravate the microvascular damage in ischemic stroke.Methods: Hyperglycemia model was made by injection of streptozocin through subcutaneous injection in wistar rats. Using the suture model, the rats were subjected to 3 h of focal ischemia and different times of reperfusion,including 6,12,24,48,96 h and 7 d. TTC dyeing was used to show the infarction area of rats. The infarctive volume of rats were calculated by computer imaging analysis system;Matrix metalloproteinase (MMP-2) and (MMP-9)were detected by immunohistochemistry and in situ hybridization histochemistry in Wistar rats.Results: The infarctive volume was siginificantly larger in hyperglycemic rats than that of nonhyperglycemic rats. The level of MMP-2,MMP-9 expression in the group of hyperglycemic rats was higher than that of nonhyperglycemic rats. Conclusion: Hyperglycemia aggravated the injury of focal ischmia-reperfusion in wistar rats and the higher expression of MMP-2, MMP-9 might be one of the mechanism in aggravation of focal ischemia/reperfusion injury.

  6. Reperfusion of the rat brain tissues following acute ischemia: the correlation among diffusion-weighted imaging, histopathology,and aquaporin-4 expression

    Institute of Scientific and Technical Information of China (English)

    LU Hong; HU Hui; HE Zhan-ping

    2011-01-01

    Background Although some studies have reported that aquaporin-4 (AQP4) plays a role in the post-ischemic edema formation and diffusion-weighted imaging (DWI), little is known about the AQP4 expression in stage of the reperfusion following acute cerebral ischemia, as well as the correlation between histopathology and DWl. The aim of the study was to investigate the correlation among DWl, histopathology and the AQP4 expression in the reperfused rat brain tissues following acute ischemia.Methods Seventy Wistar rats were randomly divided into a control group (group A), and several occluded and reperfusion groups. They had their middle cerebral artery unilaterally occluded (MCAO) for 30 minutes (group B) followed by 30 minutes (group D) or 60 minutes (group E) of reperfusion, or 60 minutes of MCAO (group C) followed by 30 minutes (group F), or 60 minutes (group G) of reperfusion (n=10 for each group). All rats underwent DWl scanning.The relative apparent diffusion coefficient (rADC) value of each rat was calculated. All the rats were sacrificed and the cerebral ischemic tissues were examined for histopathology. Real-time fluro-quantitative polymerase chain reaction (RT-PCR) and Western-blotting were performed. The amount of AQP4 mRNA (Ex △△Ct) and AQP4 protein (Q) was statistically analyzed. The correlation between rADC values and AQP4 mRNA expression was analyzed with the Pearson correlation test.Results In all the reperfusion groups, the areas of hyper-intensity signal in DWl were decreased, and the rADC value increased and the AQP4 expression decreased significantly compared with the occluded group (t=26.89, t=18.26, P<0.01). There was a negative correlation between AQP4 mRNA expression and rADC values (r=-0.72, P<0.01). A mixed edema, composed of cerebral intracelluar edema and vasogenic brain edema, was observed in all the reperfusion groups.It was more prevalent in groups D and F than in the groups E and G. With the reperfusion time postponed, the cerebral

  7. Magnetic resonance imaging tracing of transplanted bone marrow mesenchymal stem cells in a rat model of cardiac arrest-induced global brain ischemia

    Institute of Scientific and Technical Information of China (English)

    Yue Fu; Xiangshao Fang; Tong Wang; Jiwen Wang; Jun Jiang; Zhigang Luo; Xiaohui Duan; Jun Shen; Zitong Huang

    2009-01-01

    BACKGROUND: Numerous studies have shown that magnetic resonance imaging (MRI) can detect survival and migration of super paramagnetic iron oxide-labeled stem cells in models of focal cerebral infarction. OBJECTIVE: To observe distribution of bone marrow mesenchymal stem cells (BMSCs) in a rat model of global brain ischemia following cardiac arrest and resuscitation, and to investigate the feasibility of tracing iron oxide-labeled BMSCs using non-invasive MRI. DESIGN, TIME AND SETTING: The randomized, controlled, molecular imaging study was performed at the Linbaixin Medical Research Center, Second Affiliated Hospital, Sun Yat-sen University, and the Institute of Cardiopulmonary Cerebral Resuscitation, Sun Yat-sen University, China from October 2006 to February 2009.MATERIALS: A total of 40 clean, Sprague Dawley rats, aged 6 weeks and of either gender, were supplied by the Experimental Animal Center, Sun Yat-sen University, China, for isolation of BMSCs. Feridex (iron oxide), Gyroscan Inetra 1.5T MRI system, and cardiopulmonary resuscitation device were used in this study. METHODS: A total of 30 healthy, male Sprague Dawley rats, aged 6 months, were used to induce ventricular fibrillation using alternating current. After 8 minutes, the rats underwent 6-minute chest compression and mechanical ventilation, followed by electric defibrillation, to establish rat models of global brain ischemia due to cardiac arrest and resuscitation. A total of 24 successful models were randomly assigned to Feridex-labeled and non-labeled groups (n=12 for each group). At 2 hours after resuscitation, 5 x 10 6 Feddex-labeled BMSCs, with protamine sulfate as a carrier, and 5 × 10 6 non-labeled BMSCs were respectively transplanted into both groups of rats through the right carotid artery (cells were harvested in 1 mL phosphate buffered saline). MAIN OUTCOME MEASURES: Feridex-labeled BMSCs were observed by Prussian blue staining and electron microscopy. Signal intensity, celluar viability

  8. Neural stem cell transplantation in the hippocampus of rats with cerebral ischemia/reperfusion injury Activation of the phosphatidylinositol-3 kinase/Akt pathway and increased brain-derived neurotrophic factor expression

    Institute of Scientific and Technical Information of China (English)

    Yu Zhao; Shengtao Yao; Shijun Wang

    2010-01-01

    The phosphatidylinositol-3 kinase (PI3K)/Akt pathway and brain-derived neurotrophic factor (BDNF) are involved in neurological functional recovery following cerebral ischemia. Therefore, we hypothesized that mechanisms of neuroprotection by transplantation of neural stem cells (NSCs) on cerebral ischemia contributed to activation of the PI3K/Akt pathway and enhanced BDNF expression. In the present study, Wortmannin (a specific, covalent inhibitor of PI3K) was administered adjacent to ischemic hippocampus by stereotactic transplantation to further confirm the neuroprotective mechanisms of NSC transplantation following cerebral ischemia. Results showed that focal infarct volume was significantly smaller in the NSCs group, but the neurological behavior score in the NSC group was significantly greater than the middle cerebral artery occlusion model group, Wortmannin treatment group, and NSCs + Wortmannin treatment group. Protein expression of RDNF was significantly greater in the NSC group compared with the Wortmannin treatment group and NSCs + Wortmannin treatment group. These results suggest that the neuroprotective role of NSC transplantation in the cerebral ischemia activated the PI3K/Akt pathway and upregulated BDNF expression in lesioned brains.

  9. 脑缺血合并高脂血症模型大鼠脑组织的病理改变**☆%Pathological changes of brain tissue in a rat model with coexistence of hyperlipidemia and cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    张振强; 宋军营; 贾亚泉; 李澎涛; 潘彦舒

    2013-01-01

    BACKGROUND:Cerebral ischemia often occurs in underlying pathological conditions, such as hypertension, hyperlipidemia and diabetes. Therefore, it is of great significance to construct a cerebral ischemia rat model with hyperlipidemia and to study the effect of basic pathological changes on the cerebral ischemia. OBJECTIVE:To observe the brain tissue pathological changes of rat models with coexistence of hyperlipidemia and cerebral ischemia, and the effect of hyperlipidmia on cerebral ischemia. METHODS:The rats were fed with high-fat diet to establish the hyperlipidmia models, and then focal cerebral ischemia models were prepared with suture method. At 3 and 7 days after modeling, the 2,3,5-triphenyltetrazolium chloride staining was used to observe the volume of brain tissue ischemia, and hematoxylin-eosin staining was performed to observe pathological change of the margin of the brain tissue ischemia zone. RESULTS AND CONCLUSION:2,3,5-Triphenyltetrazolium chloride staining staining results showed that the volume of cerebral ischemia was significantly reduced in the hyperlipidemia+cerebral ischemia 7 day group. Hematoxylin-eosin staining results showed there was typical ischemic changes in al the cerebral ischemia models, and the number of microglial cel s after cerebral ischemia for 7 days was significantly smal er than that after cerebral ischemia for 3 days, and the changes were more obvious in the hyperlipidemia+7-day cerebral ischemia group when compared with the hyperlipidemia+3-day cerebral ischemia group. Ultrastructure showed there were neuronal and glial nuclear membrane shrinkage in al the cerebral ischemia models, mitochondria cristae was disappeared completely, endothelial cel mitochondria was decreased, most of the synaptic vesicles of nerve synapse were dissolved;the damages above were improved after ischemia for 7 days, especial y hyperlipidemia+cerebral ischemia for 7 days, the neuronal degeneration and necrosis were reduced, the mitochondrial

  10. Animal models of cerebral ischemia

    Science.gov (United States)

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

    2015-11-01

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

  11. The roles of cold-inducible RNA binding protein in the brain ischemia%冷诱导RNA结合蛋白在脑缺血中的作用

    Institute of Scientific and Technical Information of China (English)

    吴淋; 段满林

    2015-01-01

    Background Cold-inducible RNA binding protein (CIRP) is one of the cold-shock proteins induced by hypothermia and widely expressed in the brain,Recent studies have shown that CIRP plays an important role in ischemic brain injury.Objective To review the roles of CIRP in the brain ischemia and the related research advances.Content We briefly introduced the structure of CIRP and its expression distribution in the brain,and then elucidated its roles in brain ischemia.Trend The neuroprotective mechanism of CIRP is still unclear,but it provides a new therapeutic strategy for brain ischemia.%背景 冷诱导RNA结合蛋白(cold-inducible RNA binding protein,CIRP)是一种低温诱导的,在脑组织广泛表达的冷休克蛋白.新近研究表明CIRP在缺血诱发的脑损伤中发挥重要的作用. 目的 对CIRP在脑缺血中的作用及相关研究进展进行综述. 内容 概述了CIRP的结构特征及其在脑部的表达情况,阐述了其在脑缺血中的作用. 趋向 CIRP的具体作用机制尚不明确,但对其机制的研究为治疗脑缺血提供了新的方向.

  12. 脑缺血肺损伤大鼠肺组织中脑源性神经营养因子的表达变化%Expression Changes of BDNF in Lung of Rats Subjected to Brain Ischemia

    Institute of Scientific and Technical Information of China (English)

    但齐琴; 戴萍; 王盛兰; 李劲涛; 张云辉

    2012-01-01

    目的 研究脑缺血肺损伤大鼠肺组织中脑源性神经营养因子(BDNF)基因的表达变化,探讨BDNF的生物学作用.方法 成年SD大鼠46只,随机分为假手术组和脑缺血肺损伤组,每组23只,其中5只用于神经行为评价和肺水肿测定,用HE染色观察肺病理学炎症反应;每组8只动物用于RT-PCR检测肺组织BDNFmRNA含量变化;5只用ELISA检测肺组织BDNF蛋白含量变化;5只动物取肺组织进行免疫组化染色观察BDNF在肺的分布.结果 脑缺血后3d大鼠神经功能明显受损,肺组织明显充血,水肿,大量炎性细胞浸润.BDNF mRNA表达较假手术组高(P<0.05),BDNF蛋白水平亦高于假手术组(P<0.05).BDNF免疫阳性产物定位于肺上皮和平滑肌细胞.结论 脑缺血大鼠有明显肺水肿,肺组织BDNF表达上调,提示BDNF与脑缺血肺水肿有关.%Objective To investigate the expression of brain-derived neurotrophic factor (BDNF) in lung injury induced by brain ischemia in rats. Methods 46 adult SD rats were assigned randomly to sham operation group and brain ischemia lung injury group (BILI,n= 23 in each group). Rats were subjected brain ischemia and allowed to survived 3 d. After performed neurological functional severe deficit evaluation, lung edema was observed (n = 5). The BDNF expression for its mRNA and protein in lung tissues was determined by using ELISA (77 = 5) and RT-PCR technique (n = 8). The localization of BDNF was also determined by immunohistochemistry (n = 5). Results After brain ischemia for 3 days, the severe neurological functional deficit and edema in lung were seen. BDNF was located in cytoplasma of smooth muscle and epithial cells in the lung. The level of BDNF mRNA (indicated by RT-PCR) and the protein level (indicated by ELISA) were all upregulated at 3 days after brain ischemia (P<0. 05). Conclusion Lung edema occurred after brain ischemia in rats is concomitant with BDNF expression, which consists of the mechanism involved

  13. FoxP3 T cells and the pathophysiologic effects of brain death and warm ischemia in donor kidneys

    NARCIS (Netherlands)

    C.C. Baan (Carla); A. Peeters (Anna); M.W.H.J. Demmers (Martijn); W.M. Mol (Wendy); K. Boer (Karin); J.N. Samsom (Janneke); A.T. Rowshani (Ajda); J.N.M. IJzermans (Jan); W. Weimar (Willem)

    2012-01-01

    textabstractBackground and objectives Forkhead box P3 regulatory T cells control inflammatory responses, but it remains unclear whether they inhibit brain death-initiated inflammation and tissue injury in deceased kidney donors. Design, setting, participants, & measurement To study the actions of re

  14. Imaging brain inflammation with [(11)C]PK11195 by PET and induction of the peripheral-type benzodiazepine receptor after transient focal ischemia in rats.

    Science.gov (United States)

    Rojas, Santiago; Martín, Abraham; Arranz, Maria J; Pareto, Deborah; Purroy, Jesús; Verdaguer, Esther; Llop, Jordi; Gómez, Vanessa; Gispert, Joan D; Millán, Olga; Chamorro, Angel; Planas, Anna M

    2007-12-01

    [(11)C]PK11195 is used in positron emission tomography (PET) studies for imaging brain inflammation in vivo as it binds to the peripheral-type benzodiazepine receptor (PBR) expressed by reactive glia and macrophages. However, features of the cellular reaction required to induce a positive [(11)C]PK11195 signal are not well characterized. We performed [(11)C]PK11195 PET and autoradiography in rats after transient focal cerebral ischemia. We determined [(3)H]PK11195 binding and PBR expression in brain tissue and examined the lesion with several markers. [(11)C]PK11195 standard uptake value increased at day 4 and grew further at day 7 within the ischemic core. Accordingly, ex vivo [(3)H]PK11195 binding increased at day 4, and increases further at day 7. The PET signal also augmented in peripheral regions, but to a lesser extent than in the core. Binding in the region surrounding infarction was supported by [(11)C]PK11195 autoradiography at day 7 showing that the radioactive signal extended beyond the infarcted core. Enhanced binding was preceded by increases in PBR mRNA expression in the ipsilateral hemisphere, and a 18-kDa band corresponding to PBR protein was detected. Peripheral-type benzodiazepine receptor immunohistochemistry showed subsets of ameboid microglia/macrophages within the infarcted core showing a distinctive strong PBR expression from day 4. These cells were often located surrounding microhemorrhages. Reactive astrocytes forming a rim surrounding infarction at day 7 also showed some PBR immunostaining. These results show cellular heterogeneity in the level of PBR expression, supporting that PBR is not a simple marker of inflammation, and that the extent of [(11)C]PK11195 binding depends on intrinsic features of the inflammatory cells.

  15. Delayed hyperoxic ventilation attenuates oxygen-induced free radical accumulation during early reperfusion after global brain ischemia.

    Science.gov (United States)

    Wang, Yan; Yuan, Li; Liu, Ping; Zhao, Min

    2015-02-11

    To compare the effect of immediate and delayed administration of oxygen on the accumulation of free radicals in ischemia-reperfusion animal models. Thirty-two adult male Mongolian gerbils with microdialysis probes implanted in the right hippocampal CA1 were divided randomly into four groups (eight each). One group was sham-operated (Sham group) whereas the other three groups were subjected to 10 min bilateral carotid artery occlusion (BCAO). BCAO-treated animals were then subjected to the following: (a) immediate 30% O2 (near normoxia, NO group), (b) immediate 100% O2 (hyperoxia, HO group), and (c) 30% O2 for 60 min, followed by 100% O2 for 60 min (delayed hyperoxia, DHO group). Hippocampal accumulation of hydroxyl radicals (•OH) during reperfusion was estimated by measuring 2,3-dihydroxybenzoic acid (DHBA) and 2,5-DHBA in microdialysis perfusate. Hippocampi were removed 2 h after perfusion to measure malondialdehyde, pyruvate dehydrogenase activity, indices of lipid peroxidation, and cellular respiration. At 24 h after BCAO, the histology of hippocampi was analyzed to rate the injury. Immediately after the onset of reperfusion, all groups showed markedly elevated DHBA, which returned to baseline over 1-2 h. Compared with the NO group, the HO group showed significantly higher peak DHBA and slower recovery. In contrast, the DHO group was not significantly different from the NO group in terms of the DHBA level. DHO animals also showed significantly lower hippocampal malondialdehyde accumulation and higher pyruvate dehydrogenase activity at 2 h after reperfusion versus the HO group. Histology analysis also showed animals in the DHO group with ameliorated injury compared with the HO group. Hydroxyl radical accumulation was more sensitive to O2 during early reperfusion. Delayed hyperoxia may re-establish oxidative metabolism while minimizing oxidative stress after CA.

  16. Avaliação da isquemia cerebral pela respiração mitocondrial: modelo experimental Study of brain ischemia by mitochondrial respiration: experimental model

    Directory of Open Access Journals (Sweden)

    Carlos Gilberto Carlotti Junior

    2001-06-01

    Full Text Available A isquemia cerebral acontece em várias doenças. Um dos fatores críticos para a recuperação de um paciente é a duração do processo isquêmico. A atividade cerebral depende do suprimento de energia, isto sugere que o estudo da função mitocondrial pode ser utilizado para a avaliação do dano neuronal. O objetivo deste trabalho foi o de estudar a respiração mitocondrial pela oclusão da artéria cerebral média esquerda pela técnica do fio intraluminal. Ratos da raça Wistar foram subdivididos em 4 grupos: controle e 15, 30 e 60 minutos de oclusão. Os resultados mostraram que não há diferença estatisticamente significativa entre o grupo de 15 minutos e o grupo controle. O grupo de 30 minutos teve diminuição do estado III da respiração mitocondrial comparado com o grupo controle. O grupo de 60 minutos teve diminuição dos estados III e IV comparados com o grupo controle. A respiração mitocondrial permitiu uma avaliação efetiva e precoce do processo isquêmico focal no cérebro do rato.Brain ischemia occurs in several diseases. One of the critical factors for recovery of patients is the duration of the ischemic process. Brain activity depends on the energetic supply, it suggests that the study of mitochondrial function can be useful for evaluation of neuronal damage. The purpose of the present research was to study the mitochondrial respiration by occlusion of the left middle cerebral artery by intraluminal suture technique. Adults Wistar rats were subdivided in 4 groups: control, 15, 30 and 60 minutes of occlusion. Results showed that there was no significant difference between the group of 15 minutes and the control group. The group of 30 minutes had significant decrease of state III of mitochondrial respiration compared with control group. The group of 60 minutes had significant decrease in state III and IV of mitochondrial respiration compared with control group. Mitochondrial respiration allowed an early and effective

  17. Plasminogen Activator Inhibitor-1 Mitigates Brain Injury in a Rat Model of Infection-Sensitized Neonatal Hypoxia–Ischemia

    OpenAIRE

    Yang, Dianer; Sun, Yu-Yo; Nemkul, Niza; Baumann, Jessica M.; Shereen, Ahmed; Dunn, R. Scott; Wills-Karp, Marsha; Lawrence, Daniel A.; Lindquist, Diana M.; Kuan, Chia-Yi

    2012-01-01

    Intrauterine infection exacerbates neonatal hypoxic–ischemic (HI) brain injury and impairs the development of cerebral cortex. Here we used low-dose lipopolysaccharide (LPS) pre-exposure followed by unilateral cerebral HI insult in 7-day-old rats to study the pathogenic mechanisms. We found that LPS pre-exposure blocked the HI-induced proteolytic activity of tissue-type plasminogen activator (tPA), but significantly enhanced NF-κB signaling, microglia activation, and the production of pro-inf...

  18. Evaluation of Porin Interaction with Adenine Nucleotide Translocase and Cyclophilin-D Proteins after Brain Ischemia and Reperfusion

    Directory of Open Access Journals (Sweden)

    Mohammad Ali Atlasi

    2011-01-01

    Full Text Available Objective (s Porin is a mitochondrial outer membrane channel, which usually functions as the pathway for the movement of various substances in and out of the mitochondria and is considered to be a component of the permeability transition (PT pore complex that plays a role in the PT. We addressed the hypothesis that porin interacts with other mitochondrial proteins after ischemic injury.Materials and MethodsFor this purpose, we used in vivo 4-vessel occlusion model of rat brain and porin purification method by hydroxyapatite column. After SDS gel electrophoresis and silver nitrate staining, Western blotting was done for porin, adenine nucleotide translocase and cyclophilin-D proteins.Results Porin was purified from mitochondrial mixture in ischemic brain and control groups. Investigation of interaction of adenine nucleotide transposes (ANT and cyclophilin-D with porin by Western blotting showed no proteins co-purified with porin from injured tissues.Conclusion The present study implies that there may not be interaction between porin, and ANT or cyclophilin-D, and if there is any, it is not maintained during the purification procedure.

  19. Early whole-brain CT perfusion for detection of patients at risk for delayed cerebral ischemia after subarachnoid hemorrhage.

    Science.gov (United States)

    Malinova, Vesna; Dolatowski, Karoline; Schramm, Peter; Moerer, Onnen; Rohde, Veit; Mielke, Dorothee

    2016-07-01

    OBJECT This prospective study investigated the role of whole-brain CT perfusion (CTP) studies in the identification of patients at risk for delayed ischemic neurological deficits (DIND) and of tissue at risk for delayed cerebral infarction (DCI). METHODS Forty-three patients with aneurysmal subarachnoid hemorrhage (aSAH) were included in this study. A CTP study was routinely performed in the early phase (Day 3). The CTP study was repeated in cases of transcranial Doppler sonography (TCD)-measured blood flow velocity (BFV) increase of > 50 cm/sec within 24 hours and/or on Day 7 in patients who were intubated/sedated. RESULTS Early CTP studies revealed perfusion deficits in 14 patients, of whom 10 patients (72%) developed DIND, and 6 of these 10 patients (60%) had DCI. Three of the 14 patients (21%) with early perfusion deficits developed DCI without having had DIND, and the remaining patient (7%) had neither DIND nor DCI. There was a statistically significant correlation between early perfusion deficits and occurrence of DIND and DCI (p 50 cm/sec within 24 hours, revealing a perfusion deficit in 3 of them (38%). Two of the 3 patients (67%) developed DCI without preceding DIND and 1 patient (33%) had DIND without DCI. In 4 of the 7 patients (57%) who were sedated and/or comatose, additional CTP studies on Day 7 showed perfusion deficits. All 4 patients developed DCI. CONCLUSIONS Whole-brain CTP on Day 3 after aSAH allows early and reliable identification of patients at risk for DIND and tissue at risk for DCI. Additional CTP investigations, guided by TCD-measured BFV increase or persisting coma, do not contribute to information gain.

  20. Neuronal autophagy in cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Feng Xu; Jin-Hua Gu; Zheng-Hong Qin

    2012-01-01

    Autophagy has evolved as a conserved process for the bulk degradation and recycling of cytosolic components,such as long-lived proteins and organelles.In neurons,autophagy is important for homeostasis and protein quality control and is maintained at relatively low levels under normal conditions,while it is upregulated in response to pathophysiological conditions,such as cerebral ischemic injury.However,the role of autophagy is more complex.It depends on age or brain maturity,region,severity of insult,and the stage of ischemia.Whether autophagy plays a beneficial or a detrimental role in cerebral ischemia depends on various pathological conditions.In this review,we elucidate the role of neuronal autophagy in cerebral ischemia.

  1. Interaction of ARC and Daxx: a novel endogenous target to preserve motor function and cell loss after focal brain ischemia in mice

    OpenAIRE

    Donath, Stefan; An, Junfeng; Lee, Sabrina Lin Lin; Gertz, Karen; Datwyler, Anna Lena; Harms, Ulrike; Müller, Susanne; Farr, Tracy D; Füchtemeier, Martina; Lättig-Tünnemann, Gisela; Lips, Janet; Foddis, Marco; Mosch, Larissa; Bernard, Rene; Grittner, Ulrike

    2016-01-01

    The aim of this study was to explore the signaling and neuroprotective effect of transactivator of transcription (TAT) protein transduction of the apoptosis repressor with CARD (ARC) in in vitro and in vivo models of cerebral ischemia in mice. In mice, transient focal cerebral ischemia reduced endogenousARCprotein in neurons in the ischemic striatum at early reperfusion time points, and in primary neuronal cultures, RNA interference resulted in greater neuronal susceptibility to oxygen glucos...

  2. Interaction of ARC and Daxx: a novel endogenous target to preserve motor function and cell loss after focal brain ischemia in mice

    OpenAIRE

    DONATH, S.; J. An; Lee, S.L.L.; Gertz, K; Datwyler, A.L.; Harms, U.; Mueller, S.; Farr, T.D.; Fuechtemeier, M.; Laettig-Tuennemann, G.; Lips, J.; Foddis, M.; Mosch, L.; Bernard, R.; Grittner, U.

    2016-01-01

    The aim of this study was to explore the signaling and neuroprotective effect of transactivator of transcription (TAT) protein transduction of the apoptosis repressor with CARD (ARC) in in vitro and in vivo models of cerebral ischemia in mice. In mice, transient focal cerebral ischemia reduced endogenous ARC protein in neurons in the ischemic striatum at early reperfusion time points, and in primary neuronal cultures, RNA interference resulted in greater neuronal susceptibility to oxygen gluc...

  3. Silencing CHOP Gene gene Reduced reduced The the Acute acute Brain brain Injury injury in Cerebral cerebral Ischemia ischemia Reperfusion reperfusion in rRats%沉默CHOP基因减轻脑缺血再灌注大鼠的急性脑损伤

    Institute of Scientific and Technical Information of China (English)

    郑胜哲; 谷月; 何春珂; 王婷婷; 贾丽君

    2013-01-01

    目的 研究大鼠脑缺血再灌注后急性脑损伤中CHOP蛋白的作用.方法 将36只SD大鼠随机分为对照组、vector组和LV-shRNA组,经微型注射泵向control组左脑室中注射PBS,vector组注射入LV-CMV-control 质粒,向LV-shRNA组注射入LV-CMV-CHOP shRNA质粒.线栓法制作大鼠缺血再灌注模型后,TTC染色检测各组大鼠脑梗死体积,Western Blot检测所有大鼠脑内CHOP、Bcl-2和Caspase 3的表达,TUNEL染色检测梗死区细胞凋亡.结果 LV-shRNA组大鼠脑梗死体积明显小于对照组和vector组(P<0.01);Western Blot结果显示LV-shRNA组大鼠脑内CHOP和Caspase3含量明显低于对照组和vector组(P<0.01),而Bcl-2高于对照组和vector组(P>0.05);TUNEL染色显示LV-shRNA组大鼠脑梗死区域内凋亡细胞明显少于对照组和vector组(P<0.01).结论 CHOP在脑缺血后具有促进急性脑损伤的作用,沉默CHOP可通过减轻细胞凋亡反应发挥神经保护作用.%Objective ive To investigate the role of CHOP in the acute cerebral injury in rats with focal cerebral ischemia/reperfusion. Methods 36 rats were randomly divided into control group, vector group and LV-shRNA group. PBS was injected into the left ventricle of rats in control group via micro-injection pump,whereas LV-CMV-control plasmid and LV-CMV-CHOP shRNA plasmid were injected into the rats brain of vector group and LV-CMV-control group respectively. The animal model of the left MCA ischemia/reperfusion was established by suture method. Cerebral infarct volume was measured by TTC staining and the expression of CHOP, Bcl-2 and Caspase 3 in rats brain were detected by Western Blot-blot. In addition,TUNEL staining was utilized to examine cell apoptosis in infarct zone. Results The infarction volume of rats in LV-shRNA group was obviously less than control group and vector group (P 0.05). TUNEL staining showed that the apoptosis cells in LV-shRNA group rats' infarction area was markedly less than those in control

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

    OpenAIRE

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

    2011-01-01

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

  5. Xenon and sevoflurane provide analgesia during labor and fetal brain protection in a perinatal rat model of hypoxia-ischemia.

    Directory of Open Access Journals (Sweden)

    Ting Yang

    Full Text Available It is not possible to identify all pregnancies at risk of neonatal hypoxic-ischemic encephalopathy (HIE. Many women use some form of analgesia during childbirth and some anesthetic agents have been shown to be neuroprotective when used as analgesics at subanesthetic concentrations. In this study we sought to understand the effects of two anesthetic agents with presumptive analgesic activity and known preconditioning-neuroprotective properties (sevoflurane or xenon, in reducing hypoxia-induced brain damage in a model of intrauterine perinatal asphyxia. The analgesic and neuroprotective effects at subanesthetic levels of sevoflurane (0.35% or xenon (35% were tested in a rat model of intrauterine perinatal asphyxia. Analgesic effects were measured by assessing maternal behavior and spinal cord dorsal horn neuronal activation using c-Fos. In separate experiments, intrauterine fetal asphyxia was induced four hours after gas exposure; on post-insult day 3 apoptotic cell death was measured by caspase-3 immunostaining in hippocampal neurons and correlated with the number of viable neurons on postnatal day (PND 7. A separate cohort of pups was nurtured by a surrogate mother for 50 days when cognitive testing with Morris water maze was performed. Both anesthetic agents provided analgesia as reflected by a reduction in the number of stretching movements and decreased c-Fos expression in the dorsal horn of the spinal cord. Both agents also reduced the number of caspase-3 positive (apoptotic neurons and increased cell viability in the hippocampus at PND7. These acute histological changes were mirrored by improved cognitive function measured remotely after birth on PND 50 compared to control group. Subanesthetic doses of sevoflurane or xenon provided both analgesia and neuroprotection in this model of intrauterine perinatal asphyxia. These data suggest that anesthetic agents with neuroprotective properties may be effective in preventing HIE and should be

  6. Cardiac Arrest-Induced Global Brain Hypoxia-Ischemia during Development Affects Spontaneous Activity Organization in Rat Sensory and Motor Thalamocortical Circuits during Adulthood.

    Science.gov (United States)

    Shoykhet, Michael; Middleton, Jason W

    2016-01-01

    Normal maturation of sensory information processing in the cortex requires patterned synaptic activity during developmentally regulated critical periods. During early development, spontaneous synaptic activity establishes required patterns of synaptic input, and during later development it influences patterns of sensory experience-dependent neuronal firing. Thalamocortical neurons occupy a critical position in regulating the flow of patterned sensory information from the periphery to the cortex. Abnormal thalamocortical inputs may permanently affect the organization and function of cortical neuronal circuits, especially if they occur during a critical developmental window. We examined the effect of cardiac arrest (CA)-associated global brain hypoxia-ischemia in developing rats on spontaneous and evoked firing of somatosensory thalamocortical neurons and on large-scale correlations in the motor thalamocortical circuit. The mean spontaneous and sensory-evoked firing rate activity and variability were higher in CA injured rats. Furthermore, spontaneous and sensory-evoked activity and variability were correlated in uninjured rats, but not correlated in neurons from CA rats. Abnormal activity patterns of ventroposterior medial nucleus (VPm) neurons persisted into adulthood. Additionally, we found that neurons in the entopeduncular nucleus (EPN) in the basal ganglia had lower firing rates yet had higher variability and higher levels of burst firing after injury. Correlated levels of power in local field potentials (LFPs) between the EPN and the motor cortex (MCx) were also disrupted by injury. Our findings indicate that hypoxic-ischemic injury during development leads to abnormal spontaneous and sensory stimulus-evoked input patterns from thalamus to cortex. Abnormal thalamic inputs likely permanently and detrimentally affect the organization of cortical circuitry and processing of sensory information. Hypoxic-ischemic injury also leads to abnormal single neuron and

  7. Early MEK1/2 Inhibition after Global Cerebral Ischemia in Rats Reduces Brain Damage and Improves Outcome by Preventing Delayed Vasoconstrictor Receptor Upregulation

    DEFF Research Database (Denmark)

    Johansson, Sara Ellinor; Larsen, Stine Schmidt; Povlsen, Gro Klitgaard;

    2014-01-01

    neuronal cell death after global cerebral ischemia. The aim was to characterize the time-course of receptor upregulation and associated neuronal damage after global ischemia and investigate whether treatment with the MEK1/2 inhibitor U0126 can prevent cerebrovascular receptor upregulation and thereby...... with U0126 normalised cerebrovascular ETB and 5-HT1B receptor expression and contractile function, reduced hippocampal cell death and improved survival rate compared to vehicle treated animals.CONCLUSIONS: Excessive cerebrovascular expression of contractile ETB and 5-HT1B receptors is a delayed response...... to global cerebral ischemia peaking 3 days after the insult, which likely contributes to the development of delayed neuronal damage. The enhanced cerebrovascular contractility can be prevented by treatment with the MEK1/2 inhibitor U0126, diminishes neuronal damage and improves survival rate, suggesting MEK...

  8. Protective Effect effect of Flavonoids flavonoids from Polygala Polygala Hongkongensis on the Blood blood Brain brain Barrier barrier in Rats rats with Focal focal Cerebral cerebral Ischemia ischemia Reperfusion reperfusion%香港远志黄酮苷对局灶性脑缺血再灌注大鼠血脑屏障的保护及作用机制

    Institute of Scientific and Technical Information of China (English)

    詹海涛; 吴剑峰; 李海燕; 孟红旗; 曾煦欣

    2012-01-01

    Objective To investigate the influence of flavonoids from Polygala Hongkongensis( FPH) on the permeability of Blood blood Brain brain Barrierbarrier ( BBB) , brain water content and expression of matrix metalloproleinase-9 ( MMP-9) 、and aquaporin 4( AQP4) in rats with focal cerebral ischemia reperfusion(IR). Methods SD rats were randomly divided into sham operated group ", model group and treatment groups (the treatment groups were divided into Kaempferol-3-O-rutinoside( PHN-08 ) 、and kaempferol-3-0-glucoside( PHN-11) and combined formula group. Treatment groups received drug respectively according to grouping protocol, the sham operated and model groups received infusions of normal saline. The method of middle cerebral artery occlusion ( MCAO) by thread approach was used to establish the model of focal brain ischemia reperfusion(IR) IR. At the IR 24h and 48h,the mount of Evan' s blue( EB) exudation of the brain tissue、brain water content and expression of MMP-9 、and AQP4 were observed. Results At the IR 24h and 48h,compared with that of the sham operated group,the mount of EB exudationNbrain water content and expression of MMP-9 and、AQP4 were significantly increased in both of the model and treatment groups(P <0. 05). Compared with that of the model group,the mount of EB exudatioexudation, n, brain water content and expression of MMP-9 and 、 AQP4 were significantly decreased in the treatment groups( P <0. 05). Conclusion The FPH given prior to the rats with focal cerebral IR plays a protective role on the BBB,which may be achieved by decreasing the expression of MMP-9 and AQP4.%目的 探讨香港远志黄酮苷预处理,对局灶性脑缺血再灌注大鼠血脑屏障(BBB)通透性、脑含水量、基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)及水通道蛋白4(aquaporin 4,AQP4)表达的影响.方法 线栓法制备SD大鼠大脑中动脉闭塞(MCAO)局灶性脑缺血再灌注模型,随机分假手术组、模型组、山柰酚-3-O

  9. The corticosterone synthesis inhibitor metyrapone prevents hypoxia/ischemia-induced loss of synaptic function in the rat hippocampus

    NARCIS (Netherlands)

    Krugers, HJ; Maslam, S; Korf, J; Joels, M

    2000-01-01

    Background and Purpose-Ischemia is accompanied by abundant corticosterone secretion, which could potentially exacerbate brain damage via activation of glucocorticoid receptors. We addressed whether manipulating steroid levels during ischemia affects hippocampal synaptic function along with neuronal

  10. [Imaging of intestinal ischemia].

    Science.gov (United States)

    Van Beers, B E; Danse, E; Hammer, F; Goffette, P

    2004-04-01

    Ischemic bowel disease includes acute and chronic mesenteric ischemia, and colon ischemia. Cross-sectional imaging, and more particularly computed tomography, has an increasing role in the detection of acute and chronic mesenteric ischemia. Vascular obstructions or stenoses and changes in the bowel wall can be observed. Functional information can be added with MRI by using sequences that are sensitive to oxygen saturation in the superior mesenteric vein. Arteriography remains the reference examination in patients with acute mesenteric ischemia. PMID:15184799

  11. Clinical Neuroimaging of cerebral ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Nakagawara, Jyoji [Nakamura Memorial Hospital, Sapporo (Japan)

    1999-06-01

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

  12. Acute Spinal Cord Ischemia during Aortography Treated with Intravenous Thrombolytic Therapy

    OpenAIRE

    Restrepo, Lucas; Guttin, Jorge F.

    2006-01-01

    Acute anterior spinal cord ischemia is a rare but disastrous complication of endovascular aortic procedures. Although intravenous thrombolysis with recombinant tissue plasminogen activator is an effective treatment for acute brain ischemia, its use for the treatment of spinal cord ischemia has not previously been reported. We report the case of a patient who developed anterior spinal cord ischemia during diagnostic aortography. He was treated with intravenous recombinant tissue plasminogen ac...

  13. Post-conditioning exacerbates the MnSOD immune-reactivity after experimental cerebral global ischemia and reperfusion in the rat brain hippocampus.

    Science.gov (United States)

    Nemethova, Miroslava; Danielisova, Viera; Gottlieb, Miroslav; Burda, Jozef

    2008-01-01

    This study monitored the effects of sub-lethal ischemia (post-conditioning) applied after a previous ischemic attack by way of the MnSOD immune-reactivity examined in CA1 and dentate gyrus of the rat hippocampus. The experimental 10 min transient cerebral ischemia was followed by 2 days of reperfusion, the rats then underwent a second ischemia (4 or 6 min post-conditioning). MnSOD immune-reactivity was evaluated after 5 h, 1 and 2 days. Results obtained by computer microdensitometric image analysis indicated that 4 min of ischemic post-conditioning caused higher MnSOD immune-reactivity than 6 min. However, higher viability of CA1 neurons after stronger (6 min) post-conditioning when production of MnSOD is lower, as well as differences between MnSOD in CA1 and dentate gyrus indicates another mechanism switching pro-apoptotic destination of CA1 neurons to anti-apoptotic. PMID:17936646

  14. Infrared laser hemotherapy in cerebral ischemia modeling

    Science.gov (United States)

    Musienko, Julia I.; Nechipurenko, Natalia I.

    2003-10-01

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

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

    Science.gov (United States)

    Miao, Mingsan; Cheng, Bolin; Li, Min

    2015-01-01

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

  16. Effects of brain focal ischemia or chronic stress on the hippocampus-dependent learning and memory function%脑缺血与慢性应激对依赖海马的学习记忆的影响

    Institute of Scientific and Technical Information of China (English)

    毛琳; 李德强; 罗本燕

    2011-01-01

    目的 对比脑缺血与慢性应激所致认知损害及海马病变的强弱,为临床改善脑卒中后认知障碍(poststroke cognitive impairment,PSCI)提供参考.方法 40只成年雄性SD大鼠平均分为4组:对照组、应激组、缺血组与缺血加应激组,缺血手术采用改良的选择性大脑中动脉栓塞术;应激处理采用连续3周的慢性不可预见性温和应激;Moms水迷宫实验评价依赖海马的学习记忆功能;免疫组织化学染色及半定量RT-PCR观察海马CA3区脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)的表达变化.结果 应激或缺血均可使大鼠学习功能明显下降,表现为与同时点对照组比较,逃避潜伏期显著延长,二者的综合作用更明显.慢性应激对学习功能的影响强于脑缺血损伤.应激或缺血均减弱记忆功能,但二者的作用差异无统计学意义.与对照相比,缺血显著增加海马CA3区BDNF的表达(27.0±2.5与20.1±2.1),应激降低BDNF的表达(15.2±1.8与20.1±2.1),二者综合作用仍显著降低BDNF的表达(8.2±1.5),差异均具有统计学意义(F=52.87,P<0.05).结论 缺血与应激均降低大鼠学习记忆功能,应激对认知功能的损害高于缺血,而缺血与应激的综合作用对认知功能损害与抑制BDNF表达作用更明显,提示进行PSCI的综合治疗时,要重视心理社会应激干预和抑郁状态的改善.%Objective To compare the intensity of cognitive impairment and the level of pathological lesion in hippocampus induced by ischemia or chronic stress for a more valuable guidance in the treatment of post-stroke cognitive impairment(PSCI).Methods Forty male adult SD rats were divided medially into 4 groups:control,stress,ischemia and ischemia plus stress.Animals in 3 treatment groups were subjected respectively to an operation of modified selective middle cerebral artery occlusion or a procedure of continuous 3-week chronic unpredictable mild stress or a combined program of

  17. Brain

    Science.gov (United States)

    ... will return after updating. Resources Archived Modules Updates Brain Cerebrum The cerebrum is the part of the ... the outside of the brain and spinal cord. Brain Stem The brain stem is the part of ...

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

    Science.gov (United States)

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

  19. Simultaneous near-IR spectroscopy and magnetic resonance imaging to assess cerebral oxygenation and brain water during hypoxia-ischemia in two-week-old rats

    Science.gov (United States)

    Shaw, R. A.; Tuor, U. I.; Foniok, T.; Bascaramurty, S.; Ringland, K.; McKenzie, E.; Qiao, M.; Tomanek, B.; Mantsch, Henry H.

    2001-10-01

    Cerebral near-infrared spectroscopy can potentially probe several parameters related to the onset of stroke and the ensuing tissue damage. One obvious marker of ischemia is cerebral oxygenation, which can be lowered sharply in stroke-affected tissue. Also commonly assessed, though less straightforward to recover, is the redox state of the cytochrome aa3 copper center. Finally, parameters that are in principle available but seldom recovered from in vivo near-IR spectra are changes in water concentration and scattering properties of the tissue. We have evaluated the potential for near-IR spectroscopy to detect relevant changes in cerebral oxygenation, blood volume, water content, and scattering properties in an infant rat stroke model that is well characterized by magnetic resonance imaging methods. The specific aim was to acquire near-IR spectra simultaneously with MR images and to correlate stroke-associated changes detected via these two modalities prior to, during and after a hypoxia-ischemia episode within this stroke model. Presented here are results from the design and testing of a near-IR illumination/detection system that is compatible with an MR imaging system, and the recovery of trends in the near-IR spectra that complement the hypoxic-ischemic changes observed in the MR images. Unexpectedly large intensity changes observed for the in vivo near-IR water absorptions are ascribed to hypoxia-induced variations in effective optical pathlength, suggesting that the water absorptions may prove generally useful as a means to track such changes.

  20. Neuroprotective effect of melatonin on preterm rat after hypoxia-ischemia brain damage%褪黑素对新生大鼠缺血缺氧后脑损伤的保护作用

    Institute of Scientific and Technical Information of China (English)

    乔丽丽; 沈伟勤; 陈国宏

    2012-01-01

    目的 探讨褪黑素对新生大鼠缺氧缺血性脑损伤 (HIBD) 的保护作用.方法 Wistar大鼠 48 只,5日龄时结扎左侧颈总动脉,吸入氧氮混合气体 50 min 制作成HIBD模型,随机分成生理盐水组,褪黑素组,缺血缺氧 (HI)+生理盐水组,HI+褪黑素组.褪黑素腹腔注射共 3 次,每次 5 mg/kg,第 1 次在结扎动脉前,第 2 次在吸入氧氮混合气体前给予,第 3 次在HIBD模型制作 24 h 后给予.大鼠在HIBD模型制作后 72 h 被处死,取脑作免疫组化染色,判断脑灰质 (microtubule-associatedprotein-2,MAP-2)、脑白质 (myelin basic protein,MBP) 损伤;HIBD模型制作后 7 周作Y迷宫记忆功能测试.结果 褪黑素能明显减轻HIBD大鼠脑灰质MAP-2和脑白质MBP损伤,还可提高大鼠的长期记忆能力和运动协调能力.结论 褪黑素对HIBD大鼠大脑损伤有明显的短期和长期保护作用.%Objective To investigate neuroprotective effect of melatonin on newborn rat brain after hypoxia-ischemia brain damage (HIBD). Methods Forty-eight 5-day-old Wistar rats were randomly divided into physiological saline group, melatonin group, hypoxia-ischemia (HI) + saline group and HI + melatonin group. The HIBD rat models were induced by unilateral ligation of the left common carotid artery followed by 50 min inhalation of mixed oxygen and nitrogen. Melatonin was intraperitoneally injected three times with a dose of 5mg/kg before artery ligation, before ischemia and after 24h HI immediately. The rats were sacrified after 72h HI and the immunohistochemical staining was applied to brain tissue. Microtubule-associated protein-2 (MAP-2) and myelin basic protein (MBP) were evaluated as indicators for damages in grey matter and white matter, respectively. The memory abilities of the rats were measured through Y maze test at 7 weeks after HI. Results Melatonin treatment reduced the injury of grey matter and white matter significantly, and improved the long-term memory ability and motor

  1. Migraine and ischemia

    NARCIS (Netherlands)

    van der Wammes-van der Heijden, E.A.

    2009-01-01

    An association between migraine and ischemic events, especially ischemic stroke, has been debated for many years. Whether migraine is a risk factor for ischemic events or ischemia triggers migraine, or both, is still unclear. This thesis explores different relationships between migraine and ischemia

  2. 脑缺血发生后 IP-10趋化 NK 细胞通过血脑屏障%Chemotactic effect of IP-10 to natural killer cells getting through blood brain barrier after cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    张瑶; 冯涛; 祝鸿雁; 王广友; 王丹丹; 李呼伦

    2014-01-01

    Objective To research the chemotactic effect of IP-10 on natural killer cells after cerebral ischemia .Methods Experiments in vivo: NK infiltration and IP-10 and CXCR3 ex-pression in pMCAO mouse brain were detected by immunofluorescence;NK infiltration in pM-CAO brains was detected by flowcytometry;IP-10 total expression level in brain were investiga-ted by RT-PCR.Experiments in vitro:Established blood brain barrier ( B.B.B.) in vitro;IP-10 expression of the supernatant from brain microvascular endothclial cell ( BMVEC ) and neu-ral cells after oxygen-gluoose depriuation ( OGD) were detected by ELISA; B.B.B.in vitro were separated into NK , NK+IP-10 blockade two groups , after OGD 6 h, NK cells migration counts were detected by flowcytometry;NK cells were cultured together with IP -10 ( 10 ng/mL), IP-10 (50 ng/mL), IP-10(100 ng/mL), then CXCR3 geomean.MFI value were de-tected by flowcytometry .Results Experiments in vivo:NK cells were found in pMCAO brain section and expressing CXCR 3 and IP-10; NK cells infiltration were higher in ischemia-hemi-sphere , and got a peak at 12 h ( P<0.05 );NK cells had anobviously increase by 12 h at in-filtration frequency (P<0.01 );IP-10 had a highest level at 12 h ( P<0.001 ) .Experiments in vitro:Neural cell had higher expression of IP-10 after OGD than BMVEC ( P <0.001 );Compared with group NK , group NK+IP-10 blockade had lower NK cells migration counts ( P<0.05 ) and permeability ( P<0.001 ) .Conclusion ①NK cells plays an important role dur-ing cerebral ischemia;②IP-10 can absorb NK cells across B .B.B.when ischemia happens by combined with its receptor CXCR 3 and has dose dependent .%目的:探讨脑缺血发生后 IP-10对NK细胞的趋化作用。方法体内实验:免疫荧光染色观察永久性大脑中动脉栓塞小鼠模型( pMCAO)脑组织中NK细胞浸润情况以及IP-10、CXCR3表达情况;流式细胞术检测pMCAO小鼠模型脑中NK细胞浸润数目;RT-PCR

  3. 太冲、合谷穴对脑缺血作用机制的研究进展%Mechanisms of Action of Taichong and Hegu Point on Brain Ischemia

    Institute of Scientific and Technical Information of China (English)

    沈俊明; 詹宇豪

    2016-01-01

    With the improvement of living standards and the speedup of social aging,ischemic cerebro-vascular disease has become one of the diseases severely impairing the human health .Treatments of cerebral ischemia are increasingly explored.Taichong and Hegu,as a crucial pair of acupoints,can treat and improve ischemic cerebral vascular disease symptoms throug various ways ,and improve brain blood circulation and pro-mote blood vessel regeneration;improve memory and post-stroke depression.In recent years, the traditional medicine and modern medicine research with regards to the two acupoints,has made significant progress, which provides a strong basis for the further treatment and improve prognosis of cerebral ischemia disease , making the standard more objective and the result more reliable .The current studies are mainly focusing on middle cerebral blood flow,related brain regions and the influence and mechanism of depression after stroke , but further clinical mechanisms are still under exploration .%随着生活水平的提高、社会老龄化的不断加快,缺血性脑血管病逐渐成为危害人类健康的疾病之一. 人们不断寻求治疗脑缺血疾病的方法,太冲、合谷穴作为临床针灸常用的重要穴位,从多种途径治疗和改善缺血性脑血管病的病症,改善脑血流循环,促进血管再生;改善记忆及卒中后抑郁等症状. 近年来太冲、合谷穴在传统医学和现代医学两方面的相关研究有了显著进展,为进一步治疗脑缺血疾病及改善预后提供了有力依据,使标准更加客观,结果更加可靠. 重点对脑缺血疾病中脑血流、相关脑功能区以及脑卒中后抑郁症的影响和作用机制显现出越来越大的优势,但其更深入的临床机制仍处于探索阶段,需进一步研究和阐明.

  4. Minocycline upregulates cyclic AMP response element binding protein and brain-derived neurotrophic factor in the hippocampus of cerebral ischemia rats and improves behavioral deficits

    Directory of Open Access Journals (Sweden)

    Zhao Y

    2015-02-01

    Full Text Available Yu Zhao,1 Ming Xiao,2 Wenbo He,3 Zhiyou Cai3 1Department of Neurology, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China; 2Department of Anatomy, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 3Department of Neurology, Renmin Hospital, Hubei University of Medicine, Shiyan Renmin Hospital, Shiyan, Hubei Province, People’s Republic of China Background and purpose: The cAMP response element binding protein (CREB plays an important role in the mechanism of cognitive impairment and is also pivotal in the switch from short-term to long-term memory. Brain-derived neurotrophic factor (BDNF seems a promising avenue in the treatment of cerebral ischemia injury since this neurotrophin could stimulate structural plasticity and repair cognitive impairment. Several findings have displayed that the dysregulation of the CREB–BDNF cascade has been involved in cognitive impairment. The aim of this study was to investigate the effect of cerebral ischemia on learning and memory as well as on the levels of CREB, phosphorylated CREB (pCREB, and BDNF, and to determine the effect of minocycline on CREB, pCREB, BDNF, and behavioral functional recovery after cerebral ischemia. Methods: The animal model was established by permanent bilateral occlusion of both common carotid arteries. Behavior was evaluated 5 days before decapitation with Morris water maze and open-field task. Four days after permanent bilateral occlusion of both common carotid arteries, minocycline was administered by douche via the stomach for 4 weeks. CREB and pCREB were examined by Western blotting, reverse transcription polymerase chain reaction, and immunohistochemistry. BDNF was measured by immunohistochemistry and Western blotting. Results: The model rats after minocycline treatment swam shorter distances than control rats before finding the platform (P=0.0007. The number of times the

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

    OpenAIRE

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

    2013-01-01

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

  6. The oxygen free radicals originating from mitochondrial complex I contribute to oxidative brain injury following hypoxia-ischemia in neonatal mice

    Science.gov (United States)

    Niatsetskaya, Zoya V.; Sosunov, Sergei A.; Matsiukevich, Dzmitry; Utkina-Sosunova, Irina V.; Ratner, Veniamin I.; Starkov, Anatoly A.; Ten, Vadim S.

    2012-01-01

    Oxidative stress and Ca++ toxicity are mechanisms of hypoxic-ischemic (HI) brain injury. This work investigates if partial inhibition of mitochondrial respiratory chain protects HI-brain by limiting generation of oxidative radicals during reperfusion. HI-insult was produced in p10 mice treated with complex-I (C-I) inhibitor, pyridaben (P), or vehicle. Administration of P significantly decreased extent of HI injury. Mitochondria isolated from the ischemic hemisphere in P-treated animals showed reduced H2O2 emission, less oxidative damage to the mitochondrial matrix, and increased tolerance to Ca++ triggered opening of permeability transition pore. Protective effect of P administration was also observed when the reperfusion-driven oxidative stress was augmented by the exposure to 100% O2 which exacerbated brain injury only in V-treated mice. In vitro, intact brain mitochondria dramatically increased H2O2 emission in response to hyperoxia, resulting in substantial loss of Ca++ buffering capacity. However, in the presence of C-I inhibitor, rotenone, or antioxidant, catalase, these effects of hyperoxia were abolished. Our data suggest that the reperfusion-driven recovery of C-I dependent mitochondrial respiration contributes not only to the cellular survival, but also causes an oxidative damage to the mitochondria, potentiating a loss of Ca++ buffering capacity. This highlights a novel neuroprotective strategy against HI-brain injury where the major therapeutic principle is a pharmacological attenuation, rather than an enhancement of mitochondrial oxidative metabolism during early reperfusion. PMID:22378894

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

    Directory of Open Access Journals (Sweden)

    Milovanović Aleksandar

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Meiyan Xuan

    2015-01-01

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

  9. Decrease in brain choline-containing compounds following a short period of global ischemia in gerbils as detected by 1H NMR spectroscopy in vivo.

    Science.gov (United States)

    Kuhmonen, J; Sivenius, J; Riekkinen, P J; Kauppinen, R A

    1994-08-01

    Cerebral metabolism was studied in the postischaemic gerbil brain using surface coil 31P and 1H NMR spectroscopy. The ratio of choline-containing compounds (Cho) to total creatine (Cr) in the brain decreased from 0.46 +/- 0.02 to 0.32 +/- 0.02 by the fifth day following exposure to 5 min of global ischaemia and it remained at this low level for at least 19 days. The amounts of cerebral Cho as quantified by 1H NMR in vivo were 1.70 +/- 0.15 and 1.09 +/- 0.22 mmol/kg in control and postischaemic animals, respectively. The T2 of Cho was longer in the postischaemic cerebral cortex than in the control one. N-acetyl aspartate (NAA) as determined by 1H NMR in vivo did not differ in the two animal groups. High-resolution 1H NMR of acid-extracted brain cortices showed a decrease in total Cho (glycerophosphocholine, phosphocholine and choline) by 31%, but no changes in NAA, total creatine, taurine and myo-inositol, in the brain cortex seven days postischaemia relative to control animals. The decrease in acid extractable Cho was mainly due to the drop in glycerophosphocholine concentration. 31P NMR indicated normal energy state and phosphomonoester/phosphocreatine (PCr) and phosphodiester/PCr ratios in the in vivo brain 7 days postischaemia. Silver impregnation did not reveal neuronal degeneration but immunohistochemical staining showed a number of glial fibrillary acidic protein expressing astrocytes as indicators of reactive gliosis in the postischaemic cerebral cortex. These data show, for the first time, that a 1H NMR decrease in Cho metabolites takes place as a consequence of brief ischaemic episode even in the absence of obvious neuronal degeneration. PMID:7848813

  10. Effect of Alcoholic Extraction of Cuscutae Semen on Brain Ischemia-Reperfusion in Mice%菟丝子醇提液对小鼠脑缺血再灌注损伤的保护作用

    Institute of Scientific and Technical Information of China (English)

    王嘉毅; 杨柳; 郑维兵; 张毅

    2013-01-01

    Objective To study the improvement of alcoholic extraction of cuscutae semen (AECS) on learning and memory impairment induced by cerebral ischemia- reperfusion (I/R) in mice, as well as its effect and mechanism on the the activities of relative enzymes in the liver and brain tissues. Methods AECS was obtained by ultrasonic extraction. Cerebral I/R injury was produced in conscious mice by temporarily obstructing bilateral common carotid arteries. The protective effects of three different doses of AECS on learning and memory impairment in I/R mice were observed using the passive avoidance test and biochemical methods of observing the glutathione peroxidase (GSH-Px) activities in liver and brain. Results The medium and high doses of AECS could decrease the number of error and prolong the latent time in passive avoidance test and increase the activity of GSH-Px in brain and liver tissues. Conclusion AECS shows protective effects on learning and memory impairment of mice induced by cerebral I/R injury. The possible mechanism was argued that AECS can increase the activity of GSH-Px in brain and liver tissues.%  目的探讨菟丝子醇提液(AECS)对脑缺血再灌注(I/R)小鼠学习记忆障碍的改善作用,对肝脑组织中相关酶的作用及其作用机制。方法利用超声提取法制备AECS;采用暂时性阻断两侧颈总动脉的方法制备小鼠脑I/R损伤的模型,进行避暗实验,观察AECS对小鼠学习记忆功能的保护作用;生化方法测定肝脑组织中谷胱甘肽过氧化物酶(GSH-Px)活性。结果AECS中、高剂量可明显减少脑I/R小鼠避暗实验中错误次数,延长潜伏期;AECS中、高剂量能不同程度地提高肝、脑组织中GSH-Px活性。结论AECS对脑I/R所致小鼠记忆功能障碍具有保护作用,其作用机制可能为增强肝、脑组织中GSH-Px活性。

  11. 菟丝子醇提液对小鼠脑缺血再灌注损伤的保护作用%Effect of Alcoholic Extraction of Cuscutae Semen on Brain Ischemia-Reperfusion in Mice

    Institute of Scientific and Technical Information of China (English)

    王嘉毅; 杨柳; 郑维兵; 张毅

    2013-01-01

    Objective To study the improvement of alcoholic extraction of cuscutae semen (AECS) on learning and memory impairment induced by cerebral ischemia- reperfusion (I/R) in mice, as well as its effect and mechanism on the the activities of relative enzymes in the liver and brain tissues. Methods AECS was obtained by ultrasonic extraction. Cerebral I/R injury was produced in conscious mice by temporarily obstructing bilateral common carotid arteries. The protective effects of three different doses of AECS on learning and memory impairment in I/R mice were observed using the passive avoidance test and biochemical methods of observing the glutathione peroxidase (GSH-Px) activities in liver and brain. Results The medium and high doses of AECS could decrease the number of error and prolong the latent time in passive avoidance test and increase the activity of GSH-Px in brain and liver tissues. Conclusion AECS shows protective effects on learning and memory impairment of mice induced by cerebral I/R injury. The possible mechanism was argued that AECS can increase the activity of GSH-Px in brain and liver tissues.%  目的探讨菟丝子醇提液(AECS)对脑缺血再灌注(I/R)小鼠学习记忆障碍的改善作用,对肝脑组织中相关酶的作用及其作用机制。方法利用超声提取法制备AECS;采用暂时性阻断两侧颈总动脉的方法制备小鼠脑I/R损伤的模型,进行避暗实验,观察AECS对小鼠学习记忆功能的保护作用;生化方法测定肝脑组织中谷胱甘肽过氧化物酶(GSH-Px)活性。结果AECS中、高剂量可明显减少脑I/R小鼠避暗实验中错误次数,延长潜伏期;AECS中、高剂量能不同程度地提高肝、脑组织中GSH-Px活性。结论AECS对脑I/R所致小鼠记忆功能障碍具有保护作用,其作用机制可能为增强肝、脑组织中GSH-Px活性。

  12. A novel nuclear factor erythroid 2-related factor 2 (Nrf2) activator RS9 attenuates brain injury after ischemia reperfusion in mice.

    Science.gov (United States)

    Yamauchi, Keita; Nakano, Yusuke; Imai, Takahiko; Takagi, Toshinori; Tsuruma, Kazuhiro; Shimazawa, Masamitsu; Iwama, Toru; Hara, Hideaki

    2016-10-01

    Recanalization of occluded vessels leads to ischemia-reperfusion injury (IRI), with oxidative stress as one of the main causes of injury, despite the fact that recanalization therapy is the most effective treatment for ischemic stroke. The nuclear factor erythroid 2-related factor 2 (Nrf2) is one of the transcription factors which has an essential role in protection against oxidative stress. RS9 is a novel Nrf2 activator obtained from bardoxolone methyl (BARD), an Nrf2 activator that has already been tested in a clinical trial, using a biotransformation technique. RS9 has been reported to lead to higher Nrf2 activation and less cytotoxicity than BARD. In this study, we investigated the effects of RS9 on IRI. Mice were intraperitoneally treated immediately after 2h of transient middle cerebral artery occlusion (MCAO) with a vehicle solution or 0.2mg/kg of RS9. Post-onset treatment of RS9 attenuated the infarct volume and improved neurological deficits 22h after reperfusion. RS9 activated Nrf2 2 and 6h after reperfusion and activated heme oxygenase-1 at 6 and 22h after reperfusion. RS9 also attenuated the phosphorylation of NF-κB p65 2 and 6h after reperfusion. Finally, RS9 improved the survival rate and neurological deficits 7days after MCAO. Our results suggest that the activation of Nrf2 by RS9 has a neuroprotective effect, mediated by attenuating both oxidative stress and neuroinflammation, and that RS9 is an effective therapeutic candidate for the treatment of IRI. PMID:27474227

  13. 脑缺血对新生大鼠脑室下区神经新生的影响%Neurogenesis in the SVZ of the neonatal rats with brain ischemia injury

    Institute of Scientific and Technical Information of China (English)

    崔曙东; 周文浩; 孙金峤; 陈超; 曹云; 杨毅; 邵肖梅

    2008-01-01

    Objective To investigate the differentiation of neural stem cells in the subventrieular zone(SVZ)of the 3-day-old neonatal rats with ischemic brain injury and to provide the experimental evidences on endogenous repair mechanism of premature brain injury after ischemia. Methods Thirty-two 3-day-old rats were divided into experimental group and the control group.Rats in the experimental group were subjected to bilateral common arteries occlusion.while those in control group were not.All rats were administrated 5-bromodeoxyuridine(BrdU)50 mg/kg by intraperitoneal injection twice daily during 5 to 7 days after the operation.At 14 days and 28 days after operation,rats were sacrificed and their brains were collected.The changes of newborn cells in the SVZ of brain were observed by marking the BrdU,neuronal class Ⅲ β-tubulin(TuJ1),oligodendrocyte O antigen-4 (O4)and glial fibrillary acidic protein(GFAP)with immunofluorescence. Results Compared with the control group,the number(7800±800 vs 4200±700,10 700±1400 vs 4600±600)of newborn neuron(BrdU+/TuJl+)and the number(6100±1000 vs 2600±500,7300±1400 vs 2800±800)of newborn oligodendrocytes(BrdU+/O4+)per field increased significantly at 14 days and 28 days after operation in the experimental group,so did the number of newborn astrocytes per field(4500±700 vs 2700±500,6700±1100 vs 3000±600)respectively(P<0.01). Conclusions The number of neurons,oligodendroeytes and atrocytes in the SVZ increased after brain ischemia,which suggested that SVZ might have the function of repair after brain ischemia injury.%目的 观察3日龄新生大鼠缺血性脑损伤后脑室下区(subventricular zone,SVZ)新生细胞的变化,探讨未成熟脑缺血性损伤后的内源性修复机制. 方法 3日龄新生SD大鼠32只随机分为实验组和对照组,每组16只.实验组结扎双侧颈总动脉,对照组不结扎.两组大鼠均于术后5~7 d给予5-溴脱氧尿嘧啶(5-bromodeoxyuridine,BrdU),每次50 mg

  14. Silent myocardial ischemia.

    Science.gov (United States)

    Gutterman, David D

    2009-05-01

    Although much progress has been made in reducing mortality from ischemic cardiovascular disease, this condition remains the leading cause of death throughout the world. This might in part be due to the fact that over half of patients have a catastrophic event (heart attack or sudden death) as their initial manifestation of coronary disease. Contributing to this statistic is the observation that the majority of myocardial ischemic episodes are silent, indicating an inability or failure to sense ischemic damage or stress on the heart. This review examines the clinical characteristics of silent myocardial ischemia, and explores mechanisms involved in the generation of angina pectoris. Possible mechanisms for the more common manifestation of injurious reductions in coronary flow; namely, silent ischemia, are also explored. A new theory for the mechanism of silent ischemia is proposed. Finally, the prognostic importance of silent ischemia and potential future directions for research are discussed.

  15. Differential Neuroprotective Effects of Carnosine, Anserine, and N-Acetyl Carnosine against Permanent Focal Ischemia

    OpenAIRE

    Min, Jiangyong; Senut, Marie-Claude; Rajanikant, Krishnamurthy; Greenberg, Eric; Bandagi, Ram; Zemke, Daniel; Mousa, Ahmad; Kassab, Mounzer; Farooq, Muhammad U.; Gupta, Rishi; Majid, Arshad

    2008-01-01

    Carnosine (β-alanyl-L-histidine) has been shown to exhibit neuroprotection in rodent models of cerebral ischemia. In the present study, we further characterized the effects of carnosine treatment in a mouse model of permanent focal cerebral ischemia and compared them with its related peptides anserine and N-acetylated carnosine. We also evaluated the efficacy of bestatin, a carnosinase inhibitor, in ameliorating ischemic brain damage. Permanent focal cerebral ischemia was induced by occlusion...

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

    OpenAIRE

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

    2015-01-01

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

  17. Migraine and ischemia

    OpenAIRE

    van der Wammes-van der Heijden, E.A.

    2009-01-01

    An association between migraine and ischemic events, especially ischemic stroke, has been debated for many years. Whether migraine is a risk factor for ischemic events or ischemia triggers migraine, or both, is still unclear. This thesis explores different relationships between migraine and ischemia: the effect of anticoagulants on migraine, the possible relationship between cardiac right-to-left shunts (RLS) and migraine, and antimigraine drug use in relation to ischemic complications and ca...

  18. Imaging mass spectrometry detection of gangliosides species in the mouse brain following transient focal cerebral ischemia and long-term recovery.

    Directory of Open Access Journals (Sweden)

    Shawn N Whitehead

    Full Text Available Gangliosides, a member of the glycosphingolipid family, are heterogeneously expressed in biological membranes and are particularly enriched within the central nervous system. Gangliosides consist of mono- or poly-sialylated oligosaccharide chains of variable lengths attached to a ceramide unit and are found to be intimately involved in brain disease development. The purpose of this study is to examine the spatial profile of ganglioside species using matrix-assisted laser desorption/ionization (MALDI imaging (IMS following middle cerebral artery occlusion (MCAO reperfusion injury in the mouse. IMS is a powerful method to not only discriminate gangliosides by their oligosaccharide components, but also by their carbon length within their sphingosine base. Mice were subjected to a 30 min unilateral MCAO followed by long-term survival (up to 28 days of reperfusion. Brain sections were sprayed with the matrix 5-Chloro-2-mercaptobenzothiazole, scanned and analyzed for a series of ganglioside molecules using an Applied Biosystems 4800 MALDI TOF/TOF. Traditional histological and immunofluorescence techniques were performed to assess brain tissue damage and verification of the expression of gangliosides of interest. Results revealed a unique anatomical profile of GM1, GD1 and GT1b (d18:1, d20:1 as well as other members of the glycosphingolipid family. There was marked variability in the ratio of expression between ipsilateral and contralateral cortices for the various detected ganglioside species following MCAO-reperfusion injury. Most interestingly, MCAO resulted in the transient induction of both GM2 and GM3 signals within the ipsilateral hemisphere; at the border of the infarcted tissue. Taken together, the data suggest that brain region specific expression of gangliosides, particularly with respect to hydrocarbon length, may play a role in neuronal responses to injury.

  19. Hydrogen-rich saline mediates neuroprotection through the regulation of endoplasmic reticulum stress and autophagy under hypoxia-ischemia neonatal brain injury in mice.

    Science.gov (United States)

    Bai, Xuemei; Liu, Song; Yuan, Lin; Xie, Yunkai; Li, Tong; Wang, Lingxiao; Wang, Xueer; Zhang, Tiantian; Qin, Shucun; Song, Guohau; Ge, Li; Wang, Zhen

    2016-09-01

    Hydrogen as a new medical gas exerts organ-protective effects through regulating oxidative stress, inflammation and apoptosis. Multiple lines of evidence reveal the protective effects of hydrogen in various models of brain injury. However, the exact mechanism underlying this protective effect of hydrogen against hypoxic-ischemic brain damage (HIBD) is not fully understood. The present study was designed to investigate whether hydrogen-rich saline (HS) attenuates HIBD in neonatal mice and whether the observed protection is associated with reduced endoplasmic reticulum (ER) stress and regulated autophagy. The results showed that HS treatment significantly improved brain edema and decreased infarct volume. Furthermore, HS significantly attenuated HIBD-induced ER stress responses, including the decreased expression of glucose-regulated protein 78, C/EBP homologous protein, and down-regulated transcription factor. Additionally, we demonstrated that HS induced autophagy, including increased LC3B and Beclin-1 expression and decreased phosphorylation of mTOR and Stat3, as well as phosphorylation of ERK. Taken together, HS exerts neuroprotection against HIBD in neonatal mouse, mediated in part by reducing ER stress and increasing autophagy machinery. PMID:27317636

  20. 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.

  1. Effect of compound preparation Tongqiao Jiannao capsules on neural cell apoptosis and Bcl-2 and Bax protein levels in a rat model of brain ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Rui Wang; Guanglai Li; Wei Wang; Huanying Li

    2008-01-01

    Bcl-2-positive cells were slightly decreased compared with the sham-operated group. Bcl-2- and Bax-pnsitive cells and apoptotic cells were primarily distributed in the ischemic penumbra. In the Tongqiao Jiannao capsule-treated group, neuronal apoptosis was inhibited, and the number of Bcl-2-positive cells was significantly increased (P < 0.01), while the number of Bax-positive cells was significantly decreased (P < 0.01), compared with the MCAO group.CONCLUSION: Tongqiao Jiannao capsules elevated Bcl-2 expression, lowered Bax expression, and inhibited cellular apoptosis during the process of cerebral ischemia/reperfusion injury.

  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

    Directory of Open Access Journals (Sweden)

    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. 果糖二磷酸钠镁对鼠脑缺血-再灌注损伤的保护作用%Protective Effects of Sodium Magnesium Fructose Diphosphate on Brain Damage of Rats Subjected to Focal Cerebral Ischemia and Reperfusion

    Institute of Scientific and Technical Information of China (English)

    董志; 曾凡新; 周岐新; 傅洁民; 薛春生

    2002-01-01

    目的:三究果糖二磷酸钠镜头(FDPM)对大鼠脑缺备一再灌注引起脑损伤的保护作用.方法:自大鼠颈总动脉插入尼龙线栓栓塞大脑中动脉,造成大脑缺血,拔出线栓实线灌注.脑缺血10 min后给予400 mg·kg-1FDPM,400 mg·kg-1FDP及30mg·kg-1MgSO4,分别于脑缺血1h再灌注2h,5h和23h分别进行神经病学评分,并于脑缺血1h再灌注23h时测定脑梗塞面积及脑组织MDA含量,观察大脑组织病理学变化.结果:FDPM降低脑血一再灌注大鼠神经病学评分,缩小脑梗塞面积,降低脑组织MDA含量,减轻光镜下脑组织的病理改变.其作用强于FDP或MgSO4.结论:FDPM可显著保护大脑缺血再灌注引起的脑损伤,其作用单用FDP或MgSO4.%Objective: To study the effects of sodium magnesiusm fructose diphesphate(FDPM) on brain dsmage of rais after ischemia-reperfusion. Methods: Rats were subjected to cerebral ischemia-reperfusion induced by inserting a nylon thread into internal carotid artery to block the origin of middle cerebral artery and removing the thread later.FDPM (400 mg·kg-1)fructose-l,6-diphosphate(FDP, 400 mg·kg- 1)and magnesium sulfate (MgSO4, 30 mg·kg-1) were administrated 10 min af ter the onset of ischemia. Neurological scale, brain infarct area, Malondialdehyde(MDA) content and histopathological chang es of brain tissue were studied. Results: FDPM decreased neurological scale, diminished brain infarct area, reduced MDA content and relieved histopathologial change of rat brain tissue subjJected to ischemia-repefusion. These effecis were more powerful than that of FDP or MgSO4.Conclusions:It is suggested that FDPM markedly preventad rats against brain damage after cerebral ischmia-reperfusion,and its effect was better than that of FDP or MgSO4.

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

    Science.gov (United States)

    Bousser, Marie-Germaine

    2013-02-01

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

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

    Science.gov (United States)

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

    2015-11-01

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

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

    DEFF Research Database (Denmark)

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

    2001-01-01

    , in peri-infarct areas in adult rat brain after transient middle cerebral artery occlusion (MCAO) and correlated it to the expression of the growth-associated protein-43 (GAP-43), a marker for axonal regeneration and sprouting, using non-radioactive in situ hybridization techniques. Within the infarct, MBP......, corresponding to the appearance of process-bearing MBP and occasional MOG-immunoreactive oligodendrocytes in parallel sections. Quantitative analysis revealed significant increases in the density of oligodendrocytes (up to 7.6-fold) and in the level of MBP mRNA expressed by individual cells. Parallel sections...... showed that increased expression of GAP-43 mRNA in neurons was concomitant to MBP mRNA upregulation in oligodendrocytes. While the mechanisms regulating oligodendrocyte survival and myelination signals are not clear at this point, axonal sprouting could putatively serve as a stimulus for the upregulation...

  7. Neuroprotective Effects of Pregabalin on Cerebral Ischemia and Reperfusion

    Science.gov (United States)

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

    2016-01-01

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

  8. 陷窝蛋白在脑缺血后血脑屏障破坏中的作用%Role of caveolins in the blood-brain barrier disruption after cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    王昭君; 王刘敏; 林颖; 刘亚红

    2016-01-01

    陷窝蛋白是陷窝的主要组成蛋白,也是实现其生理功能的重要蛋白。陷窝蛋白表达于平滑肌细胞、内皮细胞和脂肪细胞。陷窝既参与了细胞的脂肪摄取、胞吞和胞饮等基本生理过程,也对细胞的信号转导以及大分子物质的转运和通透起着非常重要的作用。随着对陷窝蛋白的分子构成和生物化学功能研究的深入,越来越多的研究表明陷窝及其主要成分陷窝蛋白在脑血管病的病理生理学过程起着重要作用。文章就陷窝蛋白在脑缺血后血脑屏障破坏中的作用进行了综述。%Caveolins are the major component proteins of the caveolae, and they are also the essential proteins to carry out the physiological functions of caveolae. Caveolins are expressed in smooth muscle cels, endothelial cels, and adipocytes. Caveolae are not only involved in the basic physiological processes, such as celular fat intake, endocytosis, and pinocytosis, but also play a very important role in cel signal transduction and transport and permeability of macromolecular substance. With the in-depth research on the molecular structure and biochemical function of caveolins, increasing studies have shown that caveolae and their main component caveolins play an important role in the pathophysiological process of cerebrovascular diseases. This article reviews the roles of caveolins in the blood-brain barrier destruction after cerebral ischemia.

  9. 和厚朴酚通过抑制脑MPTP开放和调节PARP-1活性保护全脑缺血的作用研究%Honokiol protects brain against global brain ischemia in mice through inhibiting MPTP opening and PARP-1 activity

    Institute of Scientific and Technical Information of China (English)

    杨爽; 刘晓岩; 胡振宇; 陈世忠; 王银叶

    2012-01-01

    目的 研究和厚朴酚微乳剂对全脑缺血的影响,探讨其可能的作用机制.方法 用断头法制备小鼠急性全脑缺血模型;用分光光度法观察脑线粒体通透性转换孔(MPTP)开放程度;用荧光法测定聚腺苷二磷酸核糖聚合酶-1(PARP-1)活性;用MTT法侧细胞活力.结果 和厚朴酚(7~70 μg*kg-1)单次静注可剂量依赖地增加小鼠断头后喘息次数、降低小鼠脑匀浆液中乳酸的含量,升高脑匀浆液中ATP的含量.和厚朴酚(2.5 μmol*L-1~10 μmol*L-1)可浓度依赖地降低脑组织MPTP的开放,它可浓度依赖地抑制聚腺苷二磷酸核糖聚合酶(PARP-1)活性,其IC50=76.82 μmol*L-1,和厚朴酚可明显提高缺氧损伤的PC12细胞存活率.结论 和厚朴酚对全脑缺血有保护作用,该作用与其可能减轻缺血状态、抑制能量耗竭和乳酸堆积有关,可能与抑制神经细胞MPTP开放、抑制PARP-1的活性、从而保护神经细胞有关.这些结果为其治疗全脑缺血提供了实验依据.%Aim To investigate the influence of hono-kiol microemulsion on global ischemia in mice, and explore its potential action mechanism. Methods Global ischemia model in mice was prepared by decapitation, the opening of mitochondria permeability transition pore ( MPTP ) was detected by spectrophotometry, and the activity of poly-ADP ribose polymerase-1 ( PARP-1 ) was determined by fluorometric method. Results Honokiol ( 7 ~ 70 μg · kg -1 bolus iv ) significantly increased the breath times of mice, and decreased lactic acid contents and augmented ATP level in brain ho-mogenate in this model. Honokiol ( 2. 5 μmol · L -1 ~ 10 μmol ·L-1 ) concentration dependently reduced ΔA520 of mitochondria suspension and inhibited PARP-1 activity. In addition, honokiol enhanced the viability of PC 12 cells injured by anoxia. Conclusions This study first discovers the protection of honokiol on global ischemia. The mechanism of its action may be correlated with its

  10. Multiple molecular penumbras after focal cerebral ischemia.

    Science.gov (United States)

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

    2000-07-01

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

  11. Post-Traumatic Late Onset Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    Gencer Genc

    2014-03-01

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

  12. Experimental Focal Cerebral Ischemia

    DEFF Research Database (Denmark)

    Christensen, Thomas

    2007-01-01

    Focal cerebral ischemia due to occlusion of a major cerebral artery is the cause of ischemic stroke which is a major reason of mortality, morbidity and disability in the populations of the developed countries. In the seven studies summarized in the thesis focal ischemia in rats induced by occlusion......-PBN on the periinfarct depolarizations and infarct volume was investigated. In study number six, the activity of the mitochondrial electron transport complexes I, II and IV was evaluated histochemically during reperfusion after MCAO in order to assess the possible role of mitochondrial dysfunction in focal ischemic...

  13. Brain glycogen

    DEFF Research Database (Denmark)

    Obel, Linea Lykke Frimodt; Müller, Margit S; Walls, Anne B;

    2012-01-01

    Glycogen is a complex glucose polymer found in a variety of tissues, including brain, where it is localized primarily in astrocytes. The small quantity found in brain compared to e.g., liver has led to the understanding that brain glycogen is merely used during hypoglycemia or ischemia....... In this review evidence is brought forward highlighting what has been an emerging understanding in brain energy metabolism: that glycogen is more than just a convenient way to store energy for use in emergencies-it is a highly dynamic molecule with versatile implications in brain function, i.e., synaptic...... activity and memory formation. In line with the great spatiotemporal complexity of the brain and thereof derived focus on the basis for ensuring the availability of the right amount of energy at the right time and place, we here encourage a closer look into the molecular and subcellular mechanisms...

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

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

  15. 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-

  16. Free Radicals and Matrix Metalloproteinases in Blood-Brain Barrier Disruption after Cerebral Ischemia%自由基和基质金属蛋白酶介导脑缺血血脑屏障损伤的研究进展

    Institute of Scientific and Technical Information of China (English)

    戚智锋; 罗玉敏; 刘克建

    2012-01-01

    血脑屏障的破坏是引起脑缺血损伤及继发水肿、出血、炎症的微观原因.缺血缺氧和再灌注过程产生的自由基,以及后续基质金属蛋白酶的激活,是破坏血脑屏障结构和功能的重要分子机制.因而,在脑缺血早期及时抑制自由基产生并清除自由基,抑制基质金属蛋白酶的活性,是降低脑缺血血脑屏障损伤及其并发症的关键环节.本文将从血脑屏障损伤的角度,概述自由基与基质金属蛋白酶在脑缺血损伤过程中的作用.%Cerebral ischemia results in the compromise of blood-brain barrier (BBB) integrity, leading to neurovascular complications, including cerebral hemorrhage, edema, and inflammation. Free radicals and matrix metalloproteinases (MMPs) are critically involved in the mechanism of BBB breakdown following cerebral ischemia and reperfusion. Scavenging free radicals and inhibiting activation of MMPs are potential strategies to protect BBB integrity and reduce ischemia complications. In this review, we will focus on the the role of free radicals and MMPs activation in BBB damages in cerebral ischemia.

  17. 脑缺血后大脑皮质神经生长因子和脑源性神经营养因子的改变%The Change of Nerve Growth Factor and Brain Derived Neurotrophic Factor in Neurons of Cerebral Cortex of Adult Rat Following Local Ischemia

    Institute of Scientific and Technical Information of China (English)

    曾兢; 王廷华; 张晓; 米兰兰; 高礼

    2001-01-01

    【内容摘要】目的探讨脑缺血后大脑皮质神经生长因子(NGF)、脑源性神经营养因子(BDNF)的变化。方法采用免疫组织化学ABC法观察NGF和BDNF的改变。结果 NGF、BDNF样免疫阳性反应物主要分布于大脑皮质第3、5层的神经元。脑缺血1小时后,NGF、BDNF在皮质神经元的表达明显增加。结论 NGF、BDNF与脑缺血后大脑皮质神经细胞的损伤修复有关。%Objective To acquire knowledge about the change of nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) in neurons of cerebral cortex of adult rat following local ischemia. Methods Using specific antiserums of NGF and BDNF by immunohistochemical ABC method. Results NGF-like and BDNF-like immunoreactions distributed mainly in the neurons of the third and fifth layers in cerebral cortex. After local ischemia, the average gray degrees of NGF and BDNF in neurons of cerebral cortex both decreased on the operated side more than on the un-operated side. Conclusion This experiment demonstrated that the levels of NGF and BDNF in neurons of cerebral cortex following ischemia were upregulated apparently, suggesting that NGF and BDNF may play an important role in the process of neurons' reaction after ischemia.

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

  19. Effects of cerebral perfusion pressure on acute cerebral ischemia after traumatic brain injury%脑灌注压对创伤性脑损伤后急性脑缺血的影响

    Institute of Scientific and Technical Information of China (English)

    刘胜; 王诚; 刘远新; 吴涛; 郝建忠; 郭强

    2010-01-01

    目的 观察不同脑灌注压(CPP)对创伤性脑损伤后急性脑缺血的影响.方法 实验家兔60只,随机分为正常对照组(无损伤组)、高CPP组(90~110)mm Hg、中CPP组(70~80)mm Hg、低CPP组(50~60)mm Hg、极低CPP组(35~45)mm Hg.采用Feeney's自由落体撞击法建立急性局灶性脑挫裂伤模型,伤后80 min静脉给予升压和降压药物调控血压使CPP达到设计要求,同步进行脑血流、CPP测定,并进行图像分析,且观察不同CPP下颅脑损伤后急性脑缺血动物脑含水量及神经组织超微结构改变.结果 对照组局部脑血流量(rCBF)为156.18±6.22;高CPP组实验组rCBF为140.03±17.32,中CPP组rCBF为100.46±21.37,低CPP组rCBF为86.46±10.30,极低CPP组rCBF为60.36±8.32.对照组脑含水量为(78.21±0.26)%;高CPP组实验组脑含水量为(80.15±0.52)%,中CPP组脑含水量为(80.27±0.36)%,低CPP组脑含水量为(81.18±0.62)%,极低CPP组脑含水量为(81.34±0.83)%.实验组脑组织含水量高于对照组(P0.05).低CPP组及极低CPP组脑含水量、超微结构较对照组差异有统计学意义(P0.05). The changes in water content in brain and ultra-microstructures in nervous tissue in the low CPP group and the lower group were more significant than the control group (P<0.01). Conclusion To improve cerebral circulation availably is the important link to prevent the acute cerebral ischemia making the irreversible damage of brain after traumatic brain injury.

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

    Directory of Open Access Journals (Sweden)

    Hasan Hüseyin Özdemir

    2013-09-01

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

  1. Radiological Evaluation of Bowel Ischemia.

    Science.gov (United States)

    Dhatt, Harpreet S; Behr, Spencer C; Miracle, Aaron; Wang, Zhen Jane; Yeh, Benjamin M

    2015-11-01

    Intestinal ischemia, which refers to insufficient blood flow to the bowel, is a potentially catastrophic entity that may require emergent intervention or surgery in the acute setting. Although the clinical signs and symptoms of intestinal ischemia are nonspecific, computed tomography (CT) findings can be highly suggestive in the correct clinical setting. In our article, we review the CT diagnosis of arterial, venous, and nonocclusive intestinal ischemia. We discuss the vascular anatomy, pathophysiology of intestinal ischemia, CT techniques for optimal imaging, key and ancillary radiological findings, and differential diagnosis. PMID:26526436

  2. Animal models of focal brain ischemia

    OpenAIRE

    Sicard Kenneth M; Fisher Marc

    2009-01-01

    Abstract Stroke is a leading cause of disability and death in many countries. Understanding the pathophysiology of ischemic injury and developing therapies is an important endeavor that requires much additional research. Animal stroke models provide an important mechanism for these activities. A large number of stroke models have been developed and are currently used in laboratories around the world. These models are overviewed as are approaches for measuring infarct size and functional outcome.

  3. The Effect of Pentoxifylline on bcl-2 Gene Expression Changes in Hippocampus after Ischemia-Reperfusion in Wistar Rats by a Quatitative RT-PCR Method

    OpenAIRE

    Sari, Soyar; Hashemi, Mehrdad; Mahdian, Reza; Parivar, Kazem; Rezayat, Mehdi

    2013-01-01

    Ischemia-reperfusion injury is the tissue damage caused when blood supply returns to the tissue after a period of ischemia or lack of oxygen. Ischemia-reperfusion brain injury initiates an inflammatory response involving the expression of adhesion molecules and cytokines. Twenty–four male Wistar rats (250-300 g body wt) were used in this study. The animals were divided into four groups of 6 rats each: I: Control group that was subjected to ischemia-reperfusion, II: Ischemia-reperfusion group ...

  4. Endogenous protease nexin-1 protects against cerebral ischemia.

    Science.gov (United States)

    Mirante, Osvaldo; Price, Melanie; Puentes, Wilfredo; Castillo, Ximena; Benakis, Corinne; Thevenet, Jonathan; Monard, Denis; Hirt, Lorenz

    2013-01-01

    The serine protease thrombin plays a role in signalling ischemic neuronal death in the brain. Paradoxically, endogenous neuroprotective mechanisms can be triggered by preconditioning with thrombin (thrombin preconditioning, TPC), leading to tolerance to cerebral ischemia. Here we studied the role of thrombin's endogenous potent inhibitor, protease nexin-1 (PN-1), in ischemia and in tolerance to cerebral ischemia induced by TPC. Cerebral ischemia was modelled in vitro in organotypic hippocampal slice cultures from rats or genetically engineered mice lacking PN-1 or with the reporter gene lacZ knocked into the PN-1 locus PN-1HAPN-1-lacZ/HAPN-1-lacZ (PN-1 KI) exposed to oxygen and glucose deprivation (OGD). We observed increased thrombin enzyme activity in culture homogenates 24 h after OGD. Lack of PN-1 increased neuronal death in the CA1, suggesting that endogenous PN-1 inhibits thrombin-induced neuronal damage after ischemia. OGD enhanced β-galactosidase activity, reflecting PN-1 expression, at one and 24 h, most strikingly in the stratum radiatum, a glial cell layer adjacent to the CA1 layer of ischemia sensitive neurons. TPC, 24 h before OGD, additionally increased PN-1 expression 1 h after OGD, compared to OGD alone. TPC failed to induce tolerance in cultures from PN-1(-/-) mice confirming PN-1 as an important TPC target. PN-1 upregulation after TPC was blocked by the c-Jun N-terminal kinase (JNK) inhibitor, L-JNKI1, known to block TPC. This work suggests that PN-1 is an endogenous neuroprotectant in cerebral ischemia and a potential target for neuroprotection. PMID:23949634

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

    OpenAIRE

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

    1992-01-01

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

  6. Evaluation of murine models of permanent focal cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    席刚明; 汪华侨; 何国厚; 黄朝芬; 魏国耀

    2004-01-01

    Background To date murine models of permanent focal cerebral ischemia have not been well characterized. The purposes of this paper were to compare three different permanent middle cerebral artery occlusion (MCAo) models with or without craniectomy, and to identify an ideal mouse model of permanent focal cerebral ischemia.Methods Experiments were performed on 45 healthy adult male Kunming mice, weighing 28 to 42 g. The animals were randomly assigned to three groups (n=15 in every group) based on surgical procedure: MCAo via the external carotid artery (ECA), MCAo via the common carotid artery (CCA), and direct ligation of the middle cerebral artery (MCA). Each day post-ischemia, the animals were scored using an eight-grade neurological function scale, and mortality was also recorded. Seven days post-ischemia, the brains were removed for lesion size determination using triphenyltetrazolium chloride staining. Correlation analysis of lesion volume and neurological score was carried out. Results Mortality in the group receiving direct MCA ligation was lowest among the three groups, and there was a significant difference between the direct MCA ligation group and the two intraluminal occlusion groups (P0.7, P<0.05), suggesting good reproducibility of lesion volume in the three groups, but the infarct volume was more constant in the direct MCA ligation group. Conclusion The direct ligation model of MCAo provides an optimal means of studying permanent focal cerebral ischemia, and is preferable to the models using intraluminal sutures.

  7. Effect of baicalin on the autophagy and Beclin-1 expression in rats with cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Xiang-Long Hong; Yue-Feng Chen; Ping-Xuan Ma

    2016-01-01

    Objective:To explore the effect of baicalin on the autophagy and Beclin-1 expression in rats with cerebral ischemia, and the role of autophagy in the cerebral ischemia injury. Methods:The healthy male SD rats were randomized into the sham operation group, the ischemia model group, baicalin treatment group (100 mg/kg), and 3MA group (15 mg/kg), with 10 rats in each group. Transient focal cerebral ischemia injury model in rats was induced by occlusion of middle cerebral artery (MCA) for 180 min. The rats were given the corresponding drugs through the tail veins 30 min before molding. Half of the specimens were used for TTC staining to analyze the cerebral infarction volume. The others were used to determine the expression of Beclin-1 in the brain tissues by Western-blot. Results:When compared with the ischemia model group, the cerebral infarction volume in 3MA group was significantly increased, while that in baicalin treatment group was significantly reduced, and the comparison among the groups was statistically significant. When compared with the ischemia model group, Beclin-1 expression level in baicalin treatment group was significantly elevated, while Beclin-1 expression level in 3MA group was significantly higher than that in the sham-operation group but lower than that in the ischemia model group. Conclusions:The autophagy level of brain tissues in normal rats is low. The cerebral ischemia can activate autophagy. The activated autophagy is probably involved in the neuroprotection of cerebral ischemia injury. Application of 3MA to inhibit the occurrence of autophagy can aggravate the cerebral injury. Baicalin can significantly improve the cerebral ischemia injury and promote the occurrence of autophagy, whose mechanism is probably associated with the up-regulation of Beclin-1 expression to promote the activation of type III PI3K signal transduction pathway.

  8. Triptolide for cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

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

    2007-01-01

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

  9. 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.

  10. 64 row CT cerebral perfusion applied research of brain ischemia%64排CT脑灌注对脑组织缺血程度的应用研究

    Institute of Scientific and Technical Information of China (English)

    刘贯清; 肖新兰; 李晓; 黄小宁; 李五根

    2015-01-01

    Objective Application of 64 row CT cerebral perfusion brain tissue ischemia. Methods 40 cases of clinical diag-nosis of acute cerebral infarction,patients with unilateral lobe brain perfusion CT perfusion showed abnormal,in combination with MRI to determine infarct,according to the cerebral blood flow group,group A (low perfusion group) and group B (infarction group), respectively,evaluation of two groups of cerebral blood flow perfusion parameters and comparison analysis. Results Of 40 cases, 18 cases of group A,CTP anomaly low perfusion of figure is determined by MTT extend approximately 1.28 (R),decreased CBF mild,CBV basic no change Or moderately reduced,only determined by MTT extension was statistically significant (P<0.01);Infarc-tion group,22 cases of group B,infarction area surrounding IP abnormal perfusion is determined by MTT extend approximately 1. 48(R),CBF significantly decreased approximately 0.45(R),CBV moderately reduced,which extended determined by MTT was sta-tistically significant (P<0.001),decrease CBF was statistically significant (P<0.01);Infarction district performance is determined by MTT extend approximately 1.64(R),CBF significantly decreased approximately 0.36(R),significantly lower CBV (approximately 0. 37)R. Which determined by MTT extension was statistically significant (P<0.001),CBF decline was statistically significant(P<0.01). Conclusion Brain tissue hypoperfusion area with the infarction in central and peripheral IP area the perfusion parameters have significant differences,according to the variation of perfusion parameters characteristics can make the image on the degree of is-chemic infarction assessment,when rCBF<0.5,suggesting infarction risk is extremely high,the clinical guidance for early interven-tion treatment.%目的:探讨应用64排CT脑灌注评价脑组织缺血程度。方法40例临床诊断急性脑梗塞,CT灌注显示单侧脑叶灌注异常患者,结合MRI判断梗塞,根据脑血流量进行分组,A

  11. Effect of Morphine Withdrawal Syndrome on Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    Mohammad Allahtavakoli

    2011-01-01

    Full Text Available Objective(sOpioid abuse is still remained a major mental health problem, a criminal legal issue and may cause ischemic brain changes including stroke and brain edema. In the present study, we investigated whether spontaneously withdrawal syndrome might affect stroke outcomes.Materials and MethodsAddiction was induced by progressive incremental doses of morphine over 7 days. Behavioral signs of withdrawal were observed 24, 48 and 72 hr after morphine deprivation and total withdrawal score was determined. Cerebral ischemia was induced 18-22 hr after the last morphine injection by placing a natural clot into the middle cerebral artery (MCA. Neurological deficits were evaluated at 2, 24 and 48 hr after ischemia induction, and infarct size and brain edema were determined at 48 hr after stroke.ResultsMorphine withdrawal animals showed a significant increase in total withdrawal score and decrease of weight gain during the 72 hr after the last morphine injection. Compared to the addicted and control animals, infarct volume and brain edema were significantly increased in the morphine deprived animals (P< 0.05 at 48 hr after cerebral ischemia. Also, neurological deficits were higher in the morphine-withdrawn rats at 48 hr after stroke (P< 0.05. ConclusionOur data indicates that spontaneous withdrawal syndrome may worsen stroke outcomes. Further investigations are necessary to elucidate mechanisms of opiate withdrawal syndrome on stroke.

  12. Effects of aromatic resuscitation drugs on blood brain barrier in cerebral ischemia-reperfusion injury model rats%芳香开窍药对脑缺血再灌注损伤大鼠血脑屏障影响的实验研究

    Institute of Scientific and Technical Information of China (English)

    倪彩霞; 曾南; 许福会; 苟玲; 刘金伟; 王建; 夏厚林

    2011-01-01

    Objective: To research the effects of moschus, boraeol, styrax and benzoinum on the structure and function of blood brain barrier in cerebral ischemia-reperfusion injury model rats. Method; Focal middle cerebral artery occlusion ( MCAO) was introduced as an in vivo ischemic model in rats. After 2 h MCAO, nylon suture was pulled up 1 cm to give blood reperfusion. After 22 h reperfusion, all animals were decapitated. The ultramicrostructure of blood brain barrier of ischemia hemisphere side in fronto-pa-rietal cortex region by transmission electron microscope, and the content of VEGF and MMP-9 in ischemia side brain tissue were measured by ELISA. Result: In model and solvent group rats, the capillary endothelium cells, astro-glial cells and nerve cells in ischemia hemisphere side in fronto-parietal region were emerged in different degree compared with sham-operated groups, which exhibited tight junction between endothelial cells being opened, basal lamina being dissolved, and permeability increasing, and cellularedema. In bor-neol(0.2 g · kg-1)group rats, the structure of three kinds of cells were nearly normal, which tight junction structure was clear, rough endoplasmic reticulum and polyribosome could be found in cytoplasm. In moschus(66. 6 mg· kg-1 )group rats, the structure of capillary endothelium cells and astrocytes were nearly normal as well as the basal lamina, but the electrons in neurons was maldistribution. In styrax(1. 332 g· kg-1)group rats, astrocytes were nearly normal, while capillary endothelial cells and neurons exhibited oedema in different degrees. And the basal lamina was discontinuous, augmentation of cell spaces in endothelial cells increased the permeability, some endoplasmic reticulum broadened and ribosome ablated. In benzoinum( 1.0 g· kg-1)group rats, oedema of capillary endothelial cells and astrocytes was significant, basal lamina broke. Meanwhile endoplasmic reticulum broadened as vacuole, the number of ribosome in rough endoplasmic

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

    Science.gov (United States)

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

    2016-04-01

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

  14. 不同剂量脑醒喷鼻剂对再灌注损伤脑组织自由基及一氧化氮合酶变化的干预%Changes of free radicals and nitric oxide synthase in rat brain following ischemia-reperfusion injury due to different dosage brain-awakening nasal sprayer intervention

    Institute of Scientific and Technical Information of China (English)

    李荣; 吴伟; 陈宏珪; 黄衍寿; 刘煜德; 杨开清

    2005-01-01

    BACKGROUND: Brain-awakening nasal sprayer is composed of many herbs,such as Chuanxiong and Shichangpu, which were regarded by "Shennong Bencaojing" as having the function of "preventing stroke in the brain".OBJECTIVE: To observe the changes of free radicals and nitric oxide synthase in rat brain following focal ischemic-reperfusional injury due to brain-awakening nasal sprayer intervention and compare with that due to classical nimodipine.DESIGN: A randomized controlled study.SETTING: Department of internal medicine of a hospital affiliated to a traditional Chinese medical university.MATERIALS: Seventy adult male Wistar rats of clean grade, were randomly divided into seven groups: brain-awakening nasal sprayer of higher dosage group, moderate dosage group, lower dosage group, nimodipine intraperitoneal injection group, physical saline nasal sprayer group, menstruum nasal sprayer group, and sham operation group with 10 rats in each.METHODS: Focal brain ischemia-reperfusion model was established by blocking the left cerebral middle artery in rats of all the groups except sham operation group. Three days before model establishment and during reperfusion, rats were given different dosages of brain-awakening nasal sprayer composed of Chuanxiongqin and Shichangpu of 5.4, 2.7, 1.08 mg/(kg · d) and 1.35, 0. 54, 0.27 g/(kg· d), respectively, three times a day; which was replaced by physical saline and menstruum nasal sprayer of 0. 18 mL/ (kg · d),three times a day in physical saline nasal sprayer group and menstruum nasal sprayer group; rats in nimodipine intraperitoneal injection group received intraperitoneal injection of nimodipine by 0. 8 mg/(kg · d) twice a day. Rats in sham operation group were routinely raised. The content of prodialdehyde, superoxide dismutase and nitric oxide synthase were measured with colorimetric method.MAIN OUTCOME MEASURES: ① The changes of prodialdehyde content, superoxide dismutase and nitric oxide synthase activity in rat brain

  15. Notch1 Signaling Modulates Neuronal Progenitor Activity in the Subventricular Zone in Response to Aging and Focal Ischemia

    OpenAIRE

    Sun, Fen; Mao, XiaoOu; Xie, Lin; Ding, Meiping; Shao, Bei; Jin, Kunlin

    2013-01-01

    Neurogenesis diminishes with aging and ischemia-induced neurogenesis also occurs, but reduced in aged brain. Currently, the cellular and molecular pathways mediating these effects remain largely unknown. Our previous study has shown that Notch1 signaling regulates neurogenesis in subventricular zone (SVZ) of young-adult brain after focal ischemia, but whether a similar effect occurs in aged normal and ischemic animals is unknown. Here, we used normal and ischemic aged rat br...

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

    Science.gov (United States)

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

    2006-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Feng Zhang

    2010-10-01

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

  18. APE/Ref-1蛋白与脑缺血/再灌注神经元损伤%APE/Ref-1 protein and ischemia/reperfusion injury of neurons in the brain

    Institute of Scientific and Technical Information of China (English)

    汪效松; 李智文

    2003-01-01

    Cerebral ischemia and the aftermath of reperfusion form a hypoxic/hyperoxic sequence of events that can trigger DNA damage in neurons of central nervous system.Neuronal apoptosis will happen without immediate DNA repair.APE/Ref-1 is a multifunctional protein involoved in DNA base excision repair pathway and in redox reguiation of DNA-binding activity of AP-1 family members.which may play an important role in protection of postischemic neuronal damage.

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

    Science.gov (United States)

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

    2016-06-01

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

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

    Institute of Scientific and Technical Information of China (English)

    张蓬勃; 刘勇; 李捷; 王莹

    2003-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-09-15

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

  2. Effect of propofol on brain injury induced by intestinal ischemia-reperfusion in rats%异丙酚对肠缺血再灌注大鼠脑损伤的影响

    Institute of Scientific and Technical Information of China (English)

    冼东锋; 周军; 张涛; 郭俊英; 李偲; 黄文起

    2016-01-01

    Objective To investigate the effects of propofol on brain injury induced by intestinal ischemia-reperfusion (I/R) in rats.Methods Forty-eight adult male Sprague-Dawley rats,weighing 250-300 g,were randomly allocated to one of 3 groups (n =16 each) using a random number table:sham operation group (group Sham),I/R group,and propofol group (group P).Intestinal I/R was produced by occlusion of the superior mesenteric artery for 90 min followed by reperfusion.In group P,propofol 50 mg/kg was injected intraperitoneally at 30 min before reperfusion,and the equal volume of fat emulsion was given in the other two groups.Blood samples were collected at 24 h of reperfusion for determination of serum tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) concentrations.The cerebral cortex and hippocampus were isolated for measurement of TNF-α and IL-1β mRNA expression (by real-time reverse transcriptase-polymerase chain reaction) and myeloperoxidase (MPO) activity (using colorimetric method).Morris water maze test was carried out at 1,3 and 5 days of reperfusion.Results Compared with group Sham,the serum TNF-α and IL-1β concentrations were significantly increased,the expression of TNF-o and IL-1β mRNA in the cerebral cortex and hippocampus was up-regulated,the MPO activity was increased,and the escape latency was prolonged,and the frequency of crossing the original platform was decreased during reperfusion in group I/R (P<0.05).In group I/R,the concentrations of serum TNF-αand IL-1β were significantly decreased,thc cxpression of TNF-α and IL-1β mRNA in the cerebral cortex and hippocampus was down-regulated,and the escape latency was shortened,and the frequency of crossing the original platform was increased during reperfusion (P<0.05),and no significant change was found in MPO activity in group P (P>0.05).Conclusion Propofol reduces brain injury induced by intestinal I/R through inhibiting systemic and local inflammatory responses in rats.%目的

  3. 浸入式金属自显影技术检测游离锌离子在人脑外伤、急性脑缺血、癫痫后神经元中的异常聚集%Abnormal accumulation of free zinc ions in neurons of patients after traumatic brain injury/acute ischemia/epilepsy by immersion autometallography

    Institute of Scientific and Technical Information of China (English)

    朱林; 纪祥军; 王汉东

    2013-01-01

    目的 研究游离锌离子在脑外伤、急性脑缺血和癫痫患者神经元中的分布,为探讨锌离子是否参与上述疾病的神经元损伤提供形态学证据. 方法 于南京军区南京总医院神经外科手术台上直接采集3例脑缺血标本、3例癫痫标本、5例脑外伤标本和5例相对正常新鲜皮层标本,应用浸入式金属自显影方法检测标本中的锌离子分布,应用HE染色观察神经元形态学变化.结果 脑外伤、急性脑缺血和癫痫患者皮层神经元内聚集了大量的锌离子,阳性反应产物主要位于含锌神经元的胞体和轴突终末,胶质细胞中未见明显着色.在正常皮层未见阳性反应产物沉积.进一步的HE染色提示这些富含锌的神经元呈明显损伤样外观. 结论 锌离子可能在脑外伤、急性脑缺血和癫痫的神经元损伤中起重要作用,参与这些疾病的病理生理过程.%Objective To study the distributions of free zinc ions in the neurons of patients after traumatic brain injury/acute ischemia/epilepsy and to provide morphological evidence of involvement of zinc ions in the neuronal injury.Methods Fresh cortex specimens from patients suffered from brain trauma (n=5),acute ischemia (n=3) and epilepsy(n=3) were collected during the surgeries.Immersion autometallography was used to detect the free zinc ions in the neurons,and HE staining was employed to observe the morphological changes of the neurons.Results Pathological zinc accumulation was extensively presented in the neurons of patients after ischemia,epilepsy and mechanical head trauma.Zinc-positive products were predominantly located in the neural bodies and the axon terminals,and could not be seen in the glial cells and the neurons of normal cortex.HE staining indicated that apparently damaged neurons were observed in all of the brain regions with zinc ions labeled neuronal somata.Conclusion zinc ions might play important roles in the neurons of patients after brain

  4. Progesterone is neuroprotective by inhibiting cerebral edema after ischemia

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

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

  5. Mapping tissue chromophore changes in cerebral ischemia: a pilot study

    Science.gov (United States)

    Abookasis, David; Mathews, Marlon S.; Lay, Christopher; Cuccia, David J.; Frostig, Ron D.; Linskey, Mark E.; Tromberg, Bruce J.

    2007-02-01

    We describe the projection of spatially modulated light for quantitatively mapping changes in oxyhemoglobin, deoxyhemoglobin, and oxygen saturation in two pilot studies in the rat barrel cortex during both permanent and temporary cerebral ischemia. The approach is based on the projection of spatial modulation of white light onto the brain. The reflected light is captured on a CCD camera, which is then processed to obtain the concentration and distribution of chromophores over a wide field. Preliminary results confirm a measurable and quantifiable increase in tissue molecular concentration of deoxy-hemoglobin and decrease in hemoglobin oxygen concentration in both experimental settings. Our preliminary data from our pilot studies demonstrate that spatial modulation of light can provide quantitative chromophore mapping of the brain and has a potential role in monitoring the course and severity of cerebral ischemia in cerebrovascular disease patients.

  6. 低声压级次声对缺血再灌注损伤大鼠脑组织胰岛素样生长因子-1的影响%Effects of infrasound with low sound pressure level on the content of IGF-1 in brain of rats with focal cerebral ischemia-refusion injury

    Institute of Scientific and Technical Information of China (English)

    李川; 范建中; 吴红瑛; 魏轶

    2008-01-01

    目的 观察低声压级次声对局灶性脑缺血再灌注损伤的影响及其作用机制.方法 用线栓法制备右侧大脑中动脉栓塞-再灌注大鼠模型,以Infrasound 8TM次声治疗仪产生的次声作为处理因素.将32只大鼠随机假手术组(n=8)、造模组(n=8)、次声组(n=16),次声组按每天作用时间分为20 min组及120 min组.每组8只.动态观察(2 h、1 d、3 d和7 d)各组神经功能状态.7 d后大鼠断头取脑,采用免疫组化技术观察缺血侧大脑皮层胰岛素样生长因子-1(IGF-1)变化.结果 与模型组相比,次声120 min组神经症状改善明显(P<0.05).次声120 min组缺血侧大脑皮质IGF-1表达明显增加,与模型组比较差异有统计学意义(P<0.01).结论 低声压级次声(120 min/d,7 d)对大鼠局灶性脑缺血再灌注损伤具有保护作用,其机制与增加IGF-1表达有关.%Objective To study the effects and mechanisms of infrasound with low sound pressure level on focal cerebral ischemia-refusion injury. Methods Focal cerebral ischemia was produced by 2 hours of occlusion of the middle cerebral artery in rats. lnfrasound generated by infrasound 8TM device was used as treatment factor. Thirty-two Sprague-Dawley rats were divided into three groups: sham group (n=8), model group (n=8) and in-frasound group (n=16) , and the infrasound group was subdivided into 20- and 120-min infrasound groups, with 8 rats in each group. Neurological symptoms was assessed at 2 h, 1 d, 3 d and 7 d, respectively. These rats were sacrificed after 7 days of infrasound treatment and their brains were harvested. The number of IGF-1 posive cells of ischemia cortex was counted by using immunohistochemical technique. Results Compared with model group, neurological symptoms of rats in 120-min infrasound group was significantly improved (P<0.05); the number of IGF-1 positive cells of ischemia cortex in 120-min infrasound group increased significantly as compared with that in model group (P<0

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

    OpenAIRE

    Bacigaluppi, Marco; Comi, Giancarlo; Dirk M Hermann

    2010-01-01

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

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

    Science.gov (United States)

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

    2011-02-01

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

  9. Effect of minocycline on cerebral ischemia- reperfusion injury

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

  10. In vivo Dynamic Studies of Brain Metabolism

    Institute of Scientific and Technical Information of China (English)

    LUO Xuechun; JIANG Yufeng; ZHANG Riqing

    2005-01-01

    Nuclear magnetic resonance (NMR) can noninvasively monitor intracellular concentrations and kinetic properties of numerous inorganic and organic compounds. A 31P NMR surface coil was used in vivo to dynamically measure phosphocreatine (PCr), adenosine triphosphate (ATP), and intracellular inorganic phosphate (Pi) levels in mouse brain during ischemia-reperfusion to study the damage of cerebral tissues caused by ischemia and effects of herbs on cerebral energy metabolism during ischemia-reperfusion. The study provides dynamic brain energy metabolism data during different periods. The data show that some herbs more rapidly increase the PCr level during the recovery phase than in the control group.

  11. Metabolic crisis in severely head-injured patients: is ischemia just the tip of the iceberg?

    Science.gov (United States)

    Carre, Emilie; Ogier, Michael; Boret, Henry; Montcriol, Ambroise; Bourdon, Lionel; Jean-Jacques, Risso

    2013-10-11

    Ischemia and metabolic crisis are frequent post-traumatic secondary brain insults that negatively influence outcome. Clinicians commonly mix up these two types of insults, mainly because high lactate/pyruvate ratio (LPR) is the common marker for both ischemia and metabolic crisis. However, LPR elevations during ischemia and metabolic crisis reflect two different energetic imbalances: ischemia (Type 1 LPR elevations with low oxygenation) is characterized by a drastic deprivation of energetic substrates, whereas metabolic crisis (Type 2 LPR elevations with normal or high oxygenation) is associated with profound mitochondrial dysfunction but normal supply of energetic substrates. The discrimination between ischemia and metabolic crisis is crucial because conventional recommendations against ischemia may be detrimental for patients with metabolic crisis. Multimodal monitoring, including microdialysis and brain tissue oxygen monitoring, allows such discrimination, but these techniques are not easily accessible to all head-injured patients. Thus, a new "gold standard" and adapted medical education are required to optimize the management of patients with metabolic crisis.

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

    Science.gov (United States)

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

    2010-10-30

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

  13. Comprehensive regional and temporal gene expression profiling of the rat brain during the first 24 h after experimental stroke identifies dynamic ischemia-induced gene expression patterns, and reveals a biphasic activation of genes in surviving tissue

    DEFF Research Database (Denmark)

    Rickhag, Karl Mattias; Wieloch, Tadeusz; Gidö, Gunilla;

    2006-01-01

    In order to identify biological processes relevant for cell death and survival in the brain following stroke, the postischemic brain transcriptome was studied by a large-scale cDNA array analysis of three peri-infarct brain regions at eight time points during the first 24 h of reperfusion following......-dehydrogenase1, and Choline kinase) or cell death-regulating genes such as mitochondrial CLIC. We conclude that a biphasic transcriptional up-regulation of the brain-derived neurotrophic factor (BDNF)-G-protein coupled receptor (GPCR)-mitogen-activated protein (MAP) kinase signaling pathways occurs in surviving...... tissue, concomitant with a progressive and persistent activation of cell proliferation signifying tissue regeneration, which provide the means for cell survival and postischemic brain plasticity....

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

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

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

  15. 高血糖加重全脑缺血再灌注后缺血不敏感区神经元损伤%Hyperglycemia increases neuron injury in the invulnerable regions under global brain ischemia/reperfusion in rats*

    Institute of Scientific and Technical Information of China (English)

    景丽; 张建忠; 马轶; 郭风英; 王一理

    2011-01-01

    目的:探讨高血糖条件下脑缺血再灌注损伤加重的机制.方法:通过双侧颈总动脉结扎及放血法制备大鼠全脑缺血/再灌注模型,采用组织病理学、组织化学显色和末端脱氧核苷酸转移酶介导的dUTP原位切口末端标记(TUNEL)染色,对比观察注射性高血糖和糖尿病性高血糖大鼠神经元变性以及凋亡.结果:缺血敏感区额叶皮质和海马CA1区可见,各实验组在缺血15 min,再灌注1、3、6h各时间点变性和凋亡神经元数量均多于假手术组(P<0.01).但高血糖组、糖尿病组在缺血15 min,再灌注1、3、6h各时间点,变性和凋亡神经元的数目与正常血糖组接近.在缺血耐受区扣带皮质和海马CA3区,高血糖组和糖尿病组在缺血15 min,再灌注1、3、6h各时间点,变性和凋亡神经元的数目多于正常血糖组(P<0.05).在糖尿病组和高血糖组之间,各时间点变性和凋亡神经元数量无差异.结论:不论是急性高血糖还是糖尿病性高血糖,均可加重暂时性全脑缺血再灌注所引起的神经元损伤,特别是在高血糖条件下,大鼠脑缺血不敏感区扣带皮质和海马CA3区变性及凋亡神经元增加.%Objective:To explore the mechanism by which increases brain injury induced by ischemia/reperfusion under hyperglycemia. Methods: Rats with hyperglycemia injected glucose (hyperglycemia group), hyperglycemia with experimental diabetes mellitus (diabetes group) were subjected to 15 min of global brain ischemia, and then reperfused for 1, 3 and 6 hours. Global brain ischemia and reperfusion was induced with the 2-common carotid arteries occlusion model with exsangui-nation and reinfusing the shed blood. The degeneration and apoptosis of neurons in the experimental rats were detected by means of histopathology, histochemistry and TdT-mediated-dUTP nick end labeling (TUNED techniques. Results: In the vulnerable regions of frontal cortex and CA1 sector of hippocampus, the degeneration

  16. 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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

  19. Effects of recombinant human erythropoietin on expression of Bid mRNA and caspase-3 activity in the brain of newborn rats subjected to cerebral hypoxia-ischemia%重组人促红细胞生成素对新生大鼠缺氧缺血时脑组织Bid mRNA表达及caspase-3活性的影响

    Institute of Scientific and Technical Information of China (English)

    崔德荣; 许涛; 江伟

    2008-01-01

    目的 研究重组人促红细胞生成素(rhEPO)对新生大鼠缺氧缺血时脑组织Bid mRNA表达及半胱氨酸天冬氨酸蛋白酶-3(caspase-3)活性的影响,以探讨其神经保护作用机制.方法 7日龄雄性SD大鼠90只,体重12~18 g,随机分为3组(n=30):假手术组(S组)、缺氧缺血组(HIBD组)和rhEPO组.HIBD组和rhEPO组建立HIBD模型后,分别腹腔注射生理盐水和rhEPO 3 000 IU/ks.于腹腔注射后6、12、24、48和72 h(T1~5)时每组各处死6只大鼠,取左侧大脑组织100 mg,采用RT-PCR法检测Bid mRNA表达,比色法测定caspase-3活性.结果 与S组相比,HIBD组和rhEPO组大鼠T1-5时脑组织Bid mRNA表达上调,caspase-3活性升高(P<0.01);与HIBD组相比,rhEPO组T1-5时脑组织BidmRNA表达下调(P<0.01),T2-4时caspase-3活性降低(P<0.01).脑组织Bid mRNA表达与caspase-3活性呈正相关(r=0.911,P<0.01).结论 外源性rhEPO可通过下调Bid mRNA表达和降低caspase-3活性从而对HIBD后脑组织产生保护作用.%Objective To investigate the effects of recombinant human erythropeietin(rh-EPO)on Bid mRNA and caspase-3 activity in the brain after hypoxic-ischemic brain damage(HIBD)in neonatal rats and the possible mechanism of the neuroprotective effect of rh-EPO.Methods Ninety 7 day old male SD rats weighing 12-18 g were randomly divided into 3 groups(n=30 each):group Ⅰ sham operation(S);group Ⅱ hypoxia-ischemia group(HI)and group Ⅲ rh-EPO.The animals were anesthetized with ether.Left common carotid artery was ligated with 4-0 silk and 3 days later the animals were placed in a 2 L airtisht vessel filled with 8%O2-92%N2 at 2-3 L/min for 2 h in group Ⅱ and Ⅲ.rh-EPO 3 000 IU/kg in 4 ml/kg normal saline(NS)was administered intraperitoneally after induction of hypoxia-ischemia(HI)in group Ⅲ while in group Ⅱ NS 4 ml/kg was given IP instead.Six animals in each group were killed at 6,12,24,48 and 72 h(T1-5)respectively after IP NS or rh-EPO.Their brains were removed for

  20. Effects of hypoxic pretreatment on changes in cerebral ultrastructure and free radical content induced by brain hypoxia and ischemia%缺氧预处理对缺血缺氧脑组织超微结构与自由基的影响

    Institute of Scientific and Technical Information of China (English)

    孟凌新; 董有靖; 崔健君; 王忠成

    2001-01-01

    目的观察缺氧预处理对缺血缺氧脑组织超微结构及脑组织自由基的影响.方法将40只小鼠随机分为4组.A组为盐水对照组,B组为缺氧预处理组,IH组为缺血缺氧组,BIH组为缺氧预处理后缺血缺氧组.各组有6只小鼠分别采用黄嘌呤氧化酶法和硫代巴比妥酸法检测脑组织的超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量,另4只小鼠用于透射电镜下脑组织超微结构的观察.结果与A组比较,B组SOD活性增加,IH组MDA含量明显增加,而BIH组SOD活性明显增加的同时,MDA含量较比IH组明显降低.电镜显示B组除部分神经元轻度肿胀外,脑组织超微结构基本同A组,IH组细胞核变形,细胞浆成空泡,严重者满视野几乎找不到正常细胞,无损害的神经元<10%,BIH组细胞结构基本恢复正常,无损伤神经元达63%.结论缺氧预处理对再缺血缺氧引起的神经元损伤有保护作用,内源性抗氧化物质的增加与其有直接关系.%Objective To investigate whether hypoxic pretreatment could ameliorate the cerebral injuries induced by brain hypoxia and ischemia. Methods Forty mice weighting 18-25g were randomly allocated to 4 groups of ten mice each. Group A served as control. In group B animals received hypoxic pretreatment. Mouse was put in a 150ml bottle, then the mouth of the bottle was closed. The mouse was taken out breathing fresh air whenever it developed dyspnea. When it recovered, it was put in the closed bottle again. The process was repeated four times. In group IH animals received ischemia/hypoxia induced by ligation of left common carotid artery and breathing 8% O2 . In group BIH animals received hypoxic pretreatment first and then ischemia/hypoxia. All animals were decapitated at the end of experiment and brain was removed for ultrastrcture examination and determination of superoxide dismutase (SOD) activity and malondialdehyde (MDA) content. Results In group B SOD activity incrreased significantly as

  1. Changes of monoamine nervous transmitter and free radical met abolism in aged rats with gastrointestinal injury after brain ischemia reper fusion%脑缺血再灌注胃肠损伤老龄大鼠单胺类神经递质 和自由基代谢的变化

    Institute of Scientific and Technical Information of China (English)

    李建生; 赵君玫; 郭盛典; 李建国

    2001-01-01

    Objective: To study the mechanism of gastrointestinal injury after brain ischemia reperfusi on in aged rats from the changes of dopamine(DA),noradrenalin(NE),epinephrine(E) and the injury of free radical.Methods:Young(5months) and aged (20 months or more) rats were divided into young model group (YMG),young control group(YCG),aged model group (AMG),aged control group(ACG).The following items were measured in rats with 60 minute reperfusion after 30 minute brain ischemia:the pathological change of ga strointestinal tract:the activities of super-oxide dismutase(SOD),the contents of MDA,DA,NE,E. Results:The pathological change of gastrointestinal tract was found in the YMG and the AMG.The excitability of sympathetic-adrenal system was enhanced in the YMG and the AMG,this change in the AMG was serious compared w ith that in the YMG.The gastrointestinal MDA/SOD ratio was larger in the ACG and the YMG than that in the YCG.The stomach MDA/SOD ratio was larger in the AMG th an that in the ACG and the YMG.Conclusion: The gastrointestinal injury after brain ischemia rep erfusion in aged rats was correlated with the change of the enhanced excitabilit y of sympathetic-adrenal system and free radical injury.With aging these pathol ogical change were obvious and distinctive compared with that in the young rats.%目的:从多巴胺(DA)、去甲肾上腺素(NE)、肾上腺素(E)变化和自由基损伤方面揭示脑缺血再灌注胃肠损伤的机制。方法:青年(5月龄)和老龄(20月龄以上)大鼠均分为模型组和正常对照组,观察大鼠全脑缺血30 min再灌注60 min后胃肠损伤的病理改变和超氧化物岐化酶(SOD)的活性及丙二醛(MDA)、DA、NE、E含量。结果:青年和老龄模型组胃肠出现明显的病理改变。青年和老龄模型组交感-肾上腺系统兴奋性增强,其中老龄模型组较青年模型组大鼠严重。老龄对照组和青年模型组胃肠组织MDA/SOD比值高于青年对照组,

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

    Science.gov (United States)

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

    2016-04-01

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

  3. 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

  4. Cerebral hypoxia and ischemia in preterm infants

    Directory of Open Access Journals (Sweden)

    Alberto Ravarino

    2014-06-01

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

  5. A basic study on molecular hydrogen (H2) inhalation in acute cerebral ischemia patients for safety check with physiological parameters and measurement of blood H2 level

    OpenAIRE

    Ono Hirohisa; Nishijima Yoji; Adachi Naoto; Sakamoto Masaki; Kudo Yohei; Kaneko Kumi; Nakao Atsunori; Imaoka Takashi

    2012-01-01

    Abstract Background In animal experiments, use of molecular hydrogen ( H2) has been regarded as quite safe and effective, showing benefits in multiple pathological conditions such as ischemia-reperfusion injury of the brain, heart, kidney and transplanted tissues, traumatic and surgical injury of the brain and spinal cord, inflammation of intestine and lung , degenerative striatonigral tissue and also in many other situations. However, since cerebral ischemia patients are in old age group, th...

  6. Effects of Exercise Pre-Conditioning on Hippocampus Expression of Bcl-2 and Bax Protein and Apoptosis Following Ischemia/Reperfusion Injury in Male Rats

    OpenAIRE

    Nabi Shamsaei; Hamid Rajabi; Nahid Aboutaleb; Farnaz Nikbakht; Pezhman Motamedi; Mehdi Khaksari; Sohaila Erfani

    2015-01-01

    Introduction: Cerebral ischemia/reperfusion leads to loss of vulnerable neurons by apoptosis in specific brain regions specially in the hippocampus. There is some evidence indicating that the neuroprotective effects of physical activity on the brain. Therefore,the main purpose of this study was to investigate the effect of exercise pre-conditioning on apoptosis-related proteins expression in hippocampal CA1 neurons after induction of ischemia. Methods: 21 Male rats weighing 260-300g were ...

  7. Crocus sativus L. (Saffron) Extract and its Active Constituents (Crocin and Safranal) on Ischemia-Reperfusion in Rat Skeletal Muscle

    OpenAIRE

    Hossein Hosseinzadeh; Mohammad Hadi Modaghegh; Zahra Saffari

    2009-01-01

    Saffron and its constituents have been shown to decrease ischemia-reperfusion (I/R) injury in kidney or brain tissues. In this study, the effects of saffron ethanolic extract and its constituents, crocin and safranal, were evaluated in skeletal muscle during I/R injury. Hind limb ischemia was induced using clamping the common femoral artery and vein. After 2 h ischemia, the clamp of the femoral vessels of animals was taken off and the animal underwent 1h reperfusion. Muscle injuries were eval...

  8. Ischemic postconditioning protects against ischemic brain injury by up-regulation of acid-sensing ion channel 2a

    Institute of Scientific and Technical Information of China (English)

    Wang-sheng Duanmu; Liu Cao; Jing-yu Chen; Hong-fei Ge; Rong Hu; Hua Feng

    2016-01-01

    Ischemic postconditioning renders brain tissue tolerant to brain ischemia, thereby alleviating ischemic brain injury. However, the exact mechanism of action is still unclear. In this study, a rat model of global brain ischemia was subjected to ischemic postconditioning treat-ment using the vessel occlusion method. After 2 hours of ischemia, the bilateral common carotid arteries were blocked immediately for 10 seconds and then perfused for 10 seconds. This procedure was repeated six times. Ischemic postconditioning was found to mitigate hippocampal CA1 neuronal damage in rats with brain ischemia, and up-regulate acid-sensing ion channel 2a expression at the mRNA and protein level. These ifndings suggest that ischemic postconditioning up-regulates acid-sensing ion channel 2a expression in the rat hippo-campus after global brain ischemia, which promotes neuronal tolerance to ischemic brain injury.

  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. Arachidonic Acid and Cerebral Ischemia Risk: A Systematic Review of Observational Studies

    Directory of Open Access Journals (Sweden)

    Mai Sakai

    2014-11-01

    Full Text Available Background: Arachidonic acid (ARA is a precursor of various lipid mediators. ARA metabolites such as thromboxane A2 cause platelet aggregation and vasoconstriction, thus may lead to atherosclerotic disease. It is unclear whether dietary ARA influences the ARA-derived lipid mediator balance and the risk for atherosclerotic diseases, such as cerebral ischemia. Considering the function of ARA in atherosclerosis, it is reasonable to focus on the atherothrombotic type of cerebral ischemia risk. However, no systematic reviews or meta-analyses have been conducted to evaluate the effect of habitual ARA exposure on cerebral ischemia risk. We aimed to systematically evaluate observational studies available on the relationship between ARA exposure and the atherothrombotic type of cerebral ischemia risk in free-living populations. Summary: The PubMed database was searched for articles registered up to June 24, 2014. We designed a PubMed search formula as follows: key words for humans AND brain ischemia AND study designs AND ARA exposure. Thirty-three articles were reviewed against predefined criteria. There were 695 bibliographies assessed from the articles that included both ARA and cerebral ischemia descriptions. Finally, we identified 11 eligible articles and categorized them according to their reporting and methodological quality. We used the Strengthening the Reporting of Observational Studies in Epidemiology Statement (STROBE checklist to score the reporting quality. The methodological quality was qualitatively assessed based on the following aspects: subject selection, ARA exposure assessment, outcome diagnosis, methods for controlling confounders, and statistical analysis. We did not conduct a meta-analysis due to the heterogeneity among the studies. All eligible studies measured blood ARA levels as an indicator of exposure. Our literature search did not identify any articles that evaluated dietary ARA intake and tissue ARA as assessments of

  11. Thrombolysis and neuroprotection in cerebral ischemia.

    Science.gov (United States)

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

    2006-01-01

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

  12. 核因子-кB与窒息新生鼠缺氧缺血性脑损伤相关性研究%THE CORRELATIONAL RESEARCH OF NF-KB AND HYPOXIA ISCHEMIA REPERFUSION BRAIN INJURY OF NEWBORN RATS WITH ASPHYXIA

    Institute of Scientific and Technical Information of China (English)

    张海鸿; 王宝宏; 赵国英

    2011-01-01

    [目的]观察新生鼠窒息后不同时间段脑组织NF-кB动态变化,以探讨NF-кB信号途径在新生鼠窒息后缺氧缺血性脑损伤中的作用.[方法]出生7 d新生鼠随机分为对照组(A组)和窒息组(B组);制备新生鼠窒息模型,并于窒息后1、3、5和7 d取脑组织行石蜡切片.采用免疫组织化学方法检测窒息新生鼠脑组织NF-KB p65活性表达水平.[结果]窒息组各组脑组织NF-кB的表达均较A组显著增强(P<0.05),以5 d时升高最明显,并伴有神经细胞坏死及凋亡现象.[结论]NF-кB可能通过炎症反应机制介导窒息后脑损伤过程.%[Objectjve]To observe the activation of NF-κB in hypoxia ischemia reperfusion brain injury of newborn rats with asphyxia. To explore the effect of NF-κB signal pathway on brain injury of newborn with asphyxia .[Methods]The new born rats(7days old)were randomly dividen into control group (A) and asphyxia grup(B). The model of asphyxia was induced in B group ,immunohisto-chemical method was used to detect the activity of NF-κB P65 in the brain of the newborn rats,and hematoxylin- eosin staining was per -formed to observe the histological evidence of asphyxia in the brain, [Results]The activity of NF- κB P65 was higher in group B than that jn group A(p< 0.05) , increased to the highest peak at 5th day, with newe cell death and apaptosia in group B. [Conclusion] The NF-κB may play an important role in brain injury ,with asphyxia.

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

    DEFF Research Database (Denmark)

    Reinstrup, Peter; Nordström, Carl-Henrik

    2011-01-01

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

  14. Localization and spatiotemporal expression of IDO following transient forebrain ischemia in gerbils.

    Science.gov (United States)

    Taguchi, Ayako; Hara, Akira; Saito, Kuniaki; Hoshi, Masato; Niwa, Masayuki; Seishima, Mitsuru; Mori, Hideki

    2008-06-27

    Indoleamine 2,3-dioxygenase (IDO) is the rate-limiting enzyme in the kynurenine pathway that converts L-tryptophan to L-kynurenine. Transient forebrain ischemia initiates a series of cellular events that lead to the delayed neuronal degeneration of several brain regions. The goal of this study was to determine the localization of IDO in gerbil brain, and analyze the spatiotemporal expression of IDO in a transient forebrain ischemic model. Expression of IDO in the normal gerbil brain was observed by using immunohistochemistry. Time-course of the expression of IDO following transient forebrain ischemic gerbils was examined by immunohistochemistry, combined with hematoxylin and eosin staining for morphological analysis, and in situ terminal dUTP-biotin nick end labeling of DNA fragments (TUNEL) method. In normal gerbils, IDO immunostaining was observed in thalamus, hypothalamus and amygdaloid nucleus. IDO expression was negative in the cingulate cortex, hippocampal CA1 region and parietal cortex. Following transient ischemia, we observed a time-dependent increase of IDO expression in CA1, cingulate cortex and hypothalamus. The peak of IDO expression in CA1 and cingulate cortex occurred at 48 h after ischemic insult and diminished by 2 weeks. TUNEL staining was observed only in the CA1 region at 72 and 96 h after transient ischemia. Thus, IDO protein is present in specific regions in gerbil brain, and dynamic changes of IDO expression was observed in some neurons following transient ischemia. PMID:18501338

  15. Ischemia-induced endothelial cell swelling and mitochondrial dysfunction are attenuated by dietary polyphenols in vitro

    Science.gov (United States)

    Polyphenols possess anti-oxidant and anti-inflammatory properties. Oxidative stress (OS) and inflammation have been implicated in the pathogenesis of cytotoxic brain edema in cerebral ischemia. In addition, OS and pro-inflammatory cytokines also damage the endothelial cells and the neurovascular uni...

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

    (n =15): ischemia 15 minutes and reperfusion 180 minutes. ② Preparation of the model of global cerebral ischemia: Four-vessel occlusion- induced global cerebral ischemia rat models were modified, I.e. Bilateral vertebral arteries could be electrocauterized and blocked, and bilateral common carotid arteries were enclosed with 10-0 suture loosely. On the second day, keeping the animal awake, the suture was tightened and kept tense to block the blood flow of bilateral common carotid artery. After certain duration of ischemia, the suture was cut off and drawn out, thus the reperfusion of bilateral common carotid artery was resumed. ③Observation of physiological indexes: VSM hemodynamic monitor and temperature monitor (Thermal ert TH-5,U.S.A) were used to record and measure the changes of blood pressure, rectal temperature, brain temperature ,arterial blood gas and other physiological indexes of the rats in the control group before, 5 and 15 minutes after ischemia and 10,30,60,120 and 180 minutes after reperfusion. ④Preparation of brain tissue pathological samples: Except for ischemia control group, rats of other groups were anesthetized and their brain tissues were harvested and subjected to haematoxylin and eosin staining at 72 hours after reperfusion. ⑤ Evaluation of pathological change of brain tissue: The coronal plane of anterior commissure of cerebrum was used to evaluate corpora striatum, and the coronal plane of anterior hippocampus was used to evaluate hippocampal CA1/2 region, CA3 region and CA4 region, subiculum, superior pyramidal lobe and inferior pyramidal lobe of dentate gyrus as well as neocortex. Irreversible neuronal damage included pyknotic cells with eosinophilic cytoplasm and trachychromatic nucleus, homogenous cytoplasm and naked nucleus. Neurons without the above changes were considered to be normal. The number of normal neurons in the above-mentioned brain regions was counted under the microscope. MAIN OUTCOME MEASURES: ① The changes of

  17. 可卡因-苯丙胺调节转录肽在脑缺血中的神经保护机制%Neuroprotective mechanisms of cocaine-and amphetamine-regulated transcript peptides in brain ischemia

    Institute of Scientific and Technical Information of China (English)

    王路娜; 沙杜鹃; 张均

    2013-01-01

    可卡因-苯丙胺调节转录肽(cocaine-and amphetamine-regulated transcript peptides,CART)是一种存在于人和动物的内源性神经肽,参与调节体内多种生理和病理学过程.多项研究提示,CART在中枢神经系统中广泛分布,具有一定的中枢神经保护作用.文章对CART在脑缺血中的神经保护机制进行了综述.%Cocaine-and amphetamine-regulated transcript(CART) peptides are endogenous neurotransmitters with important roles in a number of physiological and pathological processes in vivo.Many studies suggested that CART is widely distributed in the central nervous system,and it has some central protective effects.This article reviews the recent progress in research on the protective effect of CART on cerebral ischemia and its mechanisms.

  18. An optimal dose of tea polyphenols protects against global cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Jianrui Lv; Junbin Tian; Rongliang Xue; Jing Zhao; Xin Wei; Hui Gao; Rongguo Fu; Gang Wu; Wei Li; Xiaoming Lei

    2013-01-01

    Previous studies addressing the protection of tea polyphenols against cerebral ischemia/ reperfusion injury often use focal cerebral ischemia models, and the optimal dose is not unified. In this experiment, a cerebral ischemia/reperfusion injury rat model was established using a modified four-vessel occlusion method. Rats were treated with different doses of tea polyphenols (25, 50, 100, 150, 200 mg/kg) via intraperitoneal injection. Results showed that after 2, 6, 12, 24, 48 and 72 hours of reperfusion, peroxide dismutase activity and total antioxidant capacity in brain tissue gradually increased, while malondialdehyde content gradually decreased after tea polyphenol intervention. Tea polyphenols at 200 mg/kg resulted in the most apparent changes. Terminal deoxynucleotidyl transferase-mediated nick end labeling and flow cytometry showed that 200 mg/kg tea polyphenols significantly reduced the number and percentage of apoptotic cells in the hippocampal CA1 region of rats after cerebral ischemia/reperfusion injury. The open field test and elevated plus maze experiments showed that tea polyphenols at 200 mg/kg strengthened exploratory behavior and reduced anxiety of cerebral ischemia/reperfusion injured rats. Experimental findings indicate that tea polyphenols protected rats against cerebral ischemia/ reperfusion injury and 200 mg/kg is regarded as the optimal dose.

  19. Isolation and Characterization of Ischemia-Derived Astrocytes (IDAs) with Ability to Transactivate Quiescent Astrocytes

    OpenAIRE

    Villarreal, Alejandro; Rosciszewski, Gerardo; Murta, Veronica; Cadena, Vanesa; Usach, Vanina; Dodes-Traian, Martin M.; Setton-Avruj, Patricia; Barbeito, Luis H.; Ramos, Alberto J.

    2016-01-01

    Reactive gliosis involving activation and proliferation of astrocytes and microglia, is a widespread but largely complex and graded glial response to brain injury. Astroglial population has a previously underestimated high heterogeneity with cells differing in their morphology, gene expression profile, and response to injury. Here, we identified a subset of reactive astrocytes isolated from brain focal ischemic lesions that show several atypical characteristics. Ischemia-derived astrocytes (I...

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

    OpenAIRE

    Milovanović Aleksandar; Milovanović J.; Milovanović Anđela; Konstatinović Ljubica; Petrović M.; Kekuš Divna; Petronijević-Vrzić Svetlana; Artiko Vera

    2012-01-01

    Dopamine, norepinephrine and serotonin are biogenic amines which are transmitters of the central nervous system. The effects of ischemia on the brain parenchyma depends on many factors, such is the mechanism of blood flow interruption, velocity of the occurring blood flow interruption, duration of an ischemic episode, organization of anatomical structures of the brain blood vessels etc., which all influence the final outcome. During interruption of the brai...

  1. Long Lasting Local and Systemic Inflammation after Cerebral Hypoxic ischemia in Newborn Mice

    OpenAIRE

    Max Winerdal; Malin Elisabeth Winerdal; Johan Kinn; Vijay Urmaliya; Ola Winqvist; Ulrika Adén

    2012-01-01

    BACKGROUND: Hypoxic ischemia (HI) is an important cause of neonatal brain injury and subsequent inflammation affects neurological outcome. In this study we performed investigations of systemic and local activation states of inflammatory cells from innate and adaptive immunity at different time points after neonatal HI brain injury in mice. METHODOLOGY/PRINCIPAL FINDINGS: We developed a multiplex flow cytometry based method combined with immunohistochemistry to investigate cellular immune resp...

  2. Systematic investigation of transcription factors critical in the protection against cerebral ischemia by Danhong injection

    Science.gov (United States)

    Wei, Junying; Zhang, Yanqiong; Jia, Qiang; Liu, Mingwei; Li, Defeng; Zhang, Yi; Song, Lei; Hu, Yanzhen; Xian, Minghua; Yang, Hongjun; Ding, Chen; Huang, Luqi

    2016-01-01

    Systematic investigations of complex pathological cascades during ischemic brain injury help to elucidate novel therapeutic targets against cerebral ischemia. Although some transcription factors (TFs) involved in cerebral ischemia, systematic surveys of their changes during ischemic brain injury have not been reported. Moreover, some multi-target agents effectively protected against ischemic stroke, but their mechanisms, especially the targets of TFs, are still unclear. Therefore, a comprehensive approach by integrating network pharmacology strategy and a new concatenated tandem array of consensus transcription factor response elements method to systematically investigate the target TFs critical in the protection against cerebral ischemia by a medication was first reported, and then applied to a multi-target drug, Danhong injection (DHI). High-throughput nature and depth of coverage, as well as high quantitative accuracy of the developed approach, make it more suitable for analyzing such multi-target agents. Results indicated that pre-B-cell leukemia transcription factor 1 and cyclic AMP-dependent transcription factor 1, along with six other TFs, are putative target TFs for DHI-mediated protection against cerebral ischemia. This study provides, for the first time, a systematic investigation of the target TFs critical to DHI-mediated protection against cerebral ischemia, as well as reveals more potential therapeutic targets for ischemic stroke. PMID:27431009

  3. Neuroprotective effect of olive oil in the hippocampus CA1 neurons following ischemia: Reperfusion in mice

    Directory of Open Access Journals (Sweden)

    M Zamani

    2013-01-01

    Full Text Available Introduction: Transient global ischemia induces selective, delayed neuronal death of pyramidal neurons in the hippocampal CA1. Oxidative Stress is considered to be involved in a number of human diseases including ischemia. Preliminary studies confirmed reduction of cell death in brain following treatment with antioxidants. Aim: According to this finding, we study the relationship between consumption of olive oil on cell death and memory disorder in brain ischemia. We studied the protective effect of olive oil against ischemia-reperfusion. Material and Methods: Experimental design includes three groups: Intact (n = 8, ischemic control (n = 8 and treatment groups with olive oil (n = 8. The mice treated with olive oil as pre-treatment for a week. Then, ischemia induced by common carotid artery ligation and following the reduction of inflammation [a week after ischemia], the mice post-treated with olive oil. Nissl staining applied for counting necrotic cells in hippocampus CA1. Tunnel kit was used to quantify apoptotic cell death while to short term memory scale, we apply y-maze and shuttle box tests and for detection the rate of apoptotic and treated cell, we used western blotting test for bax and bcl2 proteins. Results: High rate of apoptosis was seen in ischemic group that significantly associated with short-term memory loss. Cell death was significantly lower when mice treated with olive oil. The memory test results were adjusted with cell death results and bax and bcl2 expression in all groups′ comparison. Ischemia for 15 min induced cell death in hippocampus with more potent effect on CA1. Conclusion: Olive oil intake significantly reduced cell death and decreased memory loss.

  4. Glucose metabolism and neurogenesis in the gerbil hippocampus after transient forebrain ischemia.

    Science.gov (United States)

    Yoo, Dae Young; Lee, Kwon Young; Park, Joon Ha; Jung, Hyo Young; Kim, Jong Whi; Yoon, Yeo Sung; Won, Moo-Ho; Choi, Jung Hoon; Hwang, In Koo

    2016-08-01

    Recent evidence exists that glucose transporter 3 (GLUT3) plays an important role in the energy metabolism in the brain. Most previous studies have been conducted using focal or hypoxic ischemia models and have focused on changes in GLUT3 expression based on protein and mRNA levels rather than tissue levels. In the present study, we observed change in GLUT3 immunoreactivity in the adult gerbil hippocampus at various time points after 5 minutes of transient forebrain ischemia. In the sham-operated group, GLUT3 immunoreactivity in the hippocampal CA1 region was weak, in the pyramidal cells of the CA1 region increased in a time-dependent fashion 24 hours after ischemia, and in the hippocampal CA1 region decreased significantly between 2 and 5 days after ischemia, with high level of GLUT3 immunoreactivity observed in the CA1 region 10 days after ischemia. In a double immunofluorescence study using GLUT3 and glial-fibrillary acidic protein (GFAP), we observed strong GLUT3 immunoreactivity in the astrocytes. GLUT3 immunoreactivity increased after ischemia and peaked 7 days in the dentate gyrus after ischemia/reperfusion. In a double immunofluorescence study using GLUT3 and doublecortin (DCX), we observed low level of GLUT3 immunoreactivity in the differentiated neuroblasts of the subgranular zone of the dentate gyrus after ischemia. GLUT3 immunoreactivity in the sham-operated group was mainly detected in the subgranular zone of the dentate gyrus. These results suggest that the increase in GLUT3 immunoreactivity may be a compensatory mechanism to modulate glucose level in the hippocampal CA1 region and to promote adult neurogenesis in the dentate gyrus. PMID:27651772

  5. Effects of treadmill training after cerebral ischemia on expression in the brain of axonal guidance factor Netrin-4 and its receptor protein%跑台运动训练对脑缺血大鼠轴突导向因子Netrin-4及其受体DCC蛋白表达的影响

    Institute of Scientific and Technical Information of China (English)

    黄欢; 刘楠

    2015-01-01

    目的 观察跑台运动训练对脑缺血大鼠脑组织中轴突导向因子Netrin-4及其受体结直肠癌缺失(DCC)蛋白表达的影响,旨在探讨运动训练促进脑缺血后神经功能恢复的相关机制.方法 取成年雄性SD大鼠63只,按随机数字表法分为假手术组(n=9)、模型组(n=27)和运动组(n=27).模型组和运动组大鼠采用改良的Longa线栓法制备大脑中动脉闭塞(MCAO)脑缺血模型,假手术组大鼠手术方法同模型组和运动组,但是不插入线栓.运动组于造模成功后24 h采用跑台训练器进行运动训练,其余2组则不进行运动训练.采用修正的神经行为学评分方法(mNSS)评价模型组和运动组大鼠造模后第3、7、14天的神经功能,并断头取脑,采用Western blot法以及免疫荧光法检测脑缺血区组织中Netrin-4、DCC蛋白的表达情况.结果 造模后第3、7、14天,运动组和模型组的mNSS评分与假手术组比较,差异均有统计学意义(P<0.01);造模后第7、14天,运动组的mNSS评分分别为(6.89±1.27)分和(5.22±1.09)分,低于模型组同时间点,差异均有统计学意义(P<0.05);造模后第7、14天,运动组的Netrin-4、DCC蛋白表达均较模型组增强(P<0.05);造模后第14天,经免疫荧光法检测发现,Netrin-4主要在脑缺血区的血管和星形胶质细胞中表达,而DCC蛋白主要在脑缺血区的神经元轴突和星形胶质细胞中表达.结论 跑台运动训练可促进脑缺血大鼠神经功能恢复,其机制可能与上调脑缺血区组织中Netrin-4、DCC蛋白的表达,进而增强了神经、血管的再生和重建有关.%Objective To observe the effects of treadmill training on the expression of axonal guidance factor Netrin-4 and its receptor deleted in colorectal cancer (DCC) protein in the brains of rats with cerebral ischemia.Also to explore how training promotes the recovery of neurological function after cerebral ischemia.Methods Sixty-three adult, male Sprague

  6. Effects of ketamine,midazolam,thiopental,and propofol on brain ischemia injury in rat cerebral cortical slices%氯胺酮,咪唑安定,硫喷妥钠和异丙酚对大鼠皮层脑片缺血性损伤的作用

    Institute of Scientific and Technical Information of China (English)

    薛庆生; 于布为; 王泽剑; 陈红专

    2004-01-01

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

  7. Dynamic changes in the distribution and time course of blood-brain barrier-permeative nitroxides in the mouse head with EPR imaging: visualization of blood flow in a mouse model of ischemia.

    Science.gov (United States)

    Emoto, Miho C; Sato-Akaba, Hideo; Hirata, Hiroshi; Fujii, Hirotada G

    2014-09-01

    Electron paramagnetic resonance (EPR) imaging using nitroxides as redox-sensitive probes is a powerful, noninvasive method that can be used under various physiological conditions to visualize changes in redox status that result from oxidative damage. Two blood-brain barrier-permeative nitroxides, 3-hydroxymethyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (HMP) and 3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-yloxy (MCP), have been widely used as redox-sensitive probes in the brains of small animals, but their in vivo distribution and properties have not yet been analyzed in detail. In this study, a custom-made continuous-wave three-dimensional (3D) EPR imager was used to obtain 3D EPR images of mouse heads using MCP or HMP. This EPR imager made it possible to take 3D EPR images reconstructed from data from 181 projections acquired every 60s. Using this improved EPR imager and magnetic resonance imaging, the distribution and reduction time courses of HMP and MCP were examined in mouse heads. EPR images of living mice revealed that HMP and MCP have different distributions and different time courses for entering the brain. Based on the pharmacokinetics of the reduction reactions of HMP and MCP in the mouse head, the half-lives of HMP and MCP were clearly and accurately mapped pixel by pixel. An ischemic mouse model was prepared, and the half-life of MCP was mapped in the mouse head. Compared to the half-life in control mice, the half-life of MCP in the ischemic model mouse brain was significantly increased, suggesting a shift in the redox balance. This in vivo EPR imaging method using BBB-permeative MCP is a useful noninvasive method for assessing changes in the redox status in mouse brains under oxidative stress.

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

    International Nuclear Information System (INIS)

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

  9. Enhanced cerebrovascular expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 via the MEK/ERK pathway during cerebral ischemia in the rat

    DEFF Research Database (Denmark)

    Maddahi, Aida; Chen, Qingwen; Edvinsson, Lars

    2009-01-01

    BACKGROUND: Cerebral ischemia is usually characterized by a reduction in local blood flow and metabolism and by disruption of the blood-brain barrier in the infarct region. The formation of oedema and opening of the blood-brain barrier in stroke is associated with enhanced expression of metallopr......BACKGROUND: Cerebral ischemia is usually characterized by a reduction in local blood flow and metabolism and by disruption of the blood-brain barrier in the infarct region. The formation of oedema and opening of the blood-brain barrier in stroke is associated with enhanced expression...

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

    Science.gov (United States)

    Gupta, Y K; Briyal, Seema

    2004-10-01

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

  11. Experimental myocardial ischemia. Pt. 2

    International Nuclear Information System (INIS)

    The comparative effects of meglumine sodium diatrizoate (MSD), sodium meglumine calcium metrizoate (SMCM), and metrizamide (M) were studied in an isolated canine heart preparation. The parameters observed were coronary blood flow (CBF), myocardial contractile force (MCF), positive and negative dF/dt, and perfusion pressure during normal and ischemic perfusion conditions. MSD had an initial negative inotropic effect but baseline MCF returned in 1 min during normal perfusion and 2 min under ischemic conditions. SMCM and M had only a positive inotropic effect under normal perfusion. However, during ischemia, the positive effect of SMCM was followed by a decrease in contractile force. M showed only a positive effect on force during ischemia. Our results indicate that calcium additive may increase the risk of coronary arteriography in patients with severe coronary artery disease. (orig.)

  12. Non-Specific Inhibition of Ischemia- and Acidosis-Induced Intracellular Calcium Elevations and Membrane Currents by α-Phenyl-N-tert-butylnitrone, Butylated Hydroxytoluene and Trolox

    Directory of Open Access Journals (Sweden)

    Christopher Katnik

    2014-02-01

    Full Text Available Ischemia, and subsequent acidosis, induces neuronal death following brain injury. Oxidative stress is believed to be a key component of this neuronal degeneration. Acute chemical ischemia (azide in the absence of external glucose and acidosis (external media buffered to pH 6.0 produce increases in intracellular calcium concentration ([Ca2+]i and inward membrane currents in cultured rat cortical neurons. Two α-tocopherol analogues, trolox and butylated hydroxytoluene (BHT, and the spin trapping molecule α-Phenyl-N-tert-butylnitrone (PBN were used to determine the role of free radicals in these responses. PBN and BHT inhibited the initial transient increases in [Ca2+]i, produced by ischemia, acidosis and acidic ischemia and increased steady state levels in response to acidosis and the acidic ischemia. BHT and PBN also potentiated the rate at which [Ca2+]i increased after the initial transients during acidic ischemia. Trolox inhibited peak and sustained increases in [Ca2+]i during ischemia. BHT inhibited ischemia induced initial inward currents and trolox inhibited initial inward currents activated by acidosis and acidic ischemia. Given the inconsistent results obtained using these antioxidants, it is unlikely their effects were due to elimination of free radicals. Instead, it appears these compounds have non-specific effects on the ion channels and exchangers responsible for these responses.

  13. Isolated trochlear nerve paralysis due to brainstem ischemia: a case report

    Directory of Open Access Journals (Sweden)

    Halit Yaşar

    2013-08-01

    Full Text Available Trochlear neuropathy is the most common isolated cranial nerve palsy which affects the ocular movements. Patients complain of double vision especially during descending stairs or bending. Only 5 % of trochlear nerve palsy is isolated. The most common cause of trochlear nerve palsy is congenital causes. Trauma is the most common reason among acquired causes and ischemia-induced causes are extremely rare. In this article we present a 61-year-old female patient who has an isolated trochlear nerve palsy after a brain stem ischemia.

  14. Effects on Mongolian Warm Acupuncture on VEGF Levels and Cerebral Edema of Brain Tissue in Early Focal Cerebral Ischemia%蒙医温针对局灶性脑缺血早期脑组织 VEGF含量和脑水肿的影响

    Institute of Scientific and Technical Information of China (English)

    李玉棠; 萨仁图雅; 乌云格日勒; 王月红; 阿日嘎太; 水灵; 乌力吉木仁; 斯楞格; 萨其拉

    2014-01-01

    目的:探讨蒙医温针对大鼠局灶性脑缺血再灌注后脑组织 VEGF 水平、脑梗死体积,脑含水量的影响。方法:将雄性 SD大鼠随机分为蒙医温针组、针刺组、尼莫地平组、假手术组、模型组5组。采用改良线栓法建立大鼠中动脉阻塞再灌注模型,各组在造模成功1 h 时进行治疗,1次/d,假手术组和模型组不给于治疗。各组大鼠在术后24 h 进行神经功能评分及测脑组织VEGF 水平和脑梗死体积及脑含水量。结果:假手术组无神经功能缺损症状,蒙医温针组与各组比较脑组织 VEGF 含量有统计学意义,各组脑梗死体积、脑含水量与假手术组比较均有统计学意义,蒙医温针组脑梗死体积、脑含水量与模型组比较有统计学意义。结论:蒙医温针有改善大鼠局灶性脑梗死后的神经功能和减轻脑水肿、降低脑梗死体积作用。蒙医温针治疗缺血性脑卒中进行早期干预具有十分重要的临床意义。%Objective:To explore the effect of the Mongolian warm acupuncture on VEGF levels in brain tissue,infarct volume,brain water content in rats with cerebral ischemia after reperfusion.Methods:Male SD rats were randomly divided into Mongolian warm acu-puncture group,acupuncture group,nimodipine group,sham operation group,and model group.Modified suture method was used to set up artery occlusion in rats occlusion and reperfusion model.Rats in each group except sham group and model group were treated for one hour once a day after being successfully modelled.The nerve function,VEGF levels in brain tissue,infarct volume and brain water con-tent after 24 hours of surgery were measured.Results:The sham operation group had no nerve functional defect symptoms,and Mongoli-an warm acupuncture group showed significantly different outcomes in VEGF levels in the brain tissue compared with other groups;in-farct volume and brain water content in each group were significantly

  15. 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).

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  17. 跑台训练对大鼠脑缺血再灌注损伤后胶质纤维酸性蛋白和脑源性神经营养因子表达的影响%Effects of Treadmill Training on Expression of Glial Fibrillary Acidic Protein and Brain-derived Neurotrophic Factor in Rats with Cerebral Ischemia-reperfusion

    Institute of Scientific and Technical Information of China (English)

    谢宏文; 谢旭光

    2016-01-01

    目的:观察跑台训练对大鼠脑缺血再灌注损伤后胶质纤维酸性蛋白(GFAP)和脑源性神经营养因子(BDNF)表达的影响。方法成年雄性Wistar大鼠30只随机分为假手术组、模型组和跑台训练组,每组10只。采用线栓法制备大脑中动脉阻塞2 h再灌注模型。假手术组插线10 mm后即刻退出。跑台训练组在造模成功后第3天进行跑台训练12 d,在造模后第4、8、15天采用改良神经功能缺损评分(mNSS)对各组大鼠评分,造模后第15天HE染色观察脑组织病理学变化,Western blotting检测BDNF和GFAP表达。结果造模后15 d,与模型组比较,跑台训练组mNSS评分明显降低(F=9.931, P<0.01),缺血侧皮质脑组织病理损伤减轻,GFAP(t=6.73)和BDNF(t=3.78)表达明显升高(P<0.01)。结论跑台训练可促进大鼠脑缺血再灌注损伤后GFAP和BDNF的表达,促进神经功能的恢复。%Objective To explore the effect of treadmill training on expression of glial fibrillary acidic protein (GFAP) and brain-derived neurotrophic factor (BDNF) after cerebral ischemia-reperfusion in rats. Methods 30 male Wistar rats were randomly divided into sham group, model group and treadmill training group, with 10 rats in each group. The latter 2 groups were modeled with middle cerebral artery occlusion for 2 hours and reperfusion. The treadmill training group underwent treadmill exercise on the 3rd day after modeling for 12 days. Neurological function was evaluated with modified Neurological Severity Scores (mNSS). The neuronal pathological change in ischemic cortex was observed with HE staining. The expressions of GFAP and BDNF in cortex were determined by Western blotting. Results Com-pared with the model group, the mNSS scores decreased in the treadmill training group (F=9.931, P<0.01), the pathological damage in the ischemia cortex significantly lessened, and the expressions of GFAP (t=6.73) and BDNF (t=3.78) increased (P<0.05). Conclusion

  18. Quantitative evaluation of the changes of brain metabolits in rats with focal cerebral ischemia by using 1H magnetic resonance spectrum%1H磁共振波谱对局灶性脑缺血大鼠脑内代谢物变化的定量评估

    Institute of Scientific and Technical Information of China (English)

    周仁兰; 谢鹏; 罗天友; 吕发金; 牟君; 王运良

    2005-01-01

    BACKGROUND: Brain metabolic abnormality can be observed after cerebral ischemia.OBJECTIVE: To observe the changes of biochemical metabolism of rats with focal cerebral ischemia with 1H magnetic resonance spectroscopy (MRS) in order to reflect the metabolite abnormalities of rats during cerebral ischemic recovery phase.DESIGN: Randomized controlled study.SETTING: Departments of Neurology and department of Radiology of First Affiliated Hospital of Chongqing Medical University.MATERIALS: The experiment was conducted at the Radiological Department of First Affiliated Hospital of Chongqing Medical University from April to July 2004. Totally 24 adult Wistar rats with clean grade were randomly divided into three groups, namely: control group, sham operation group and cerebral ischemia group, with 8 rats in each group.METHODS: The focal cerebral ischemic model was established by occluding the right internal carotid artery in cerebral ischemia group and the filament were just inserted into the internal carotid artery not into the middle cerebral artery in sham operation group, nothing was done except for anesthetizing in the control group. 1H MRS was performed within the area of cerebral infarction and the homologous area of the contralateral hemisphere using 1.5T GE signa Highspeed MRI spectrometer in cerebral ischemic and shamed operation group at the following time point of 30 minutes, 1, 3, 6, 12, 24 hours, 3, 7, 15 days, 1 and 2 months after cerebral ischemia, and in the control group at the same time point.MAIN OUTCOME MEASURES: Changes of lactate, N-acetyl-aspartate (NAA), choline and creatine in infarct hemisphere and contralateral hemisphere.RESULTS: Totally 24 rats were selected in the study, but two died of anesthesia in sham operation group and four of serious brain edema in cerebral ischemia group, only 18 rats entered the final analysis with 8 in normal control group, 6 in sham operation group and 4 in cerebral isThe marked increase in NAA, choline and

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

    Science.gov (United States)

    Panickar, Kiran S; Jang, Saebyeol

    2013-08-01

    Cerebral ischemia is caused by an interruption of blood flow to the brain which generally leads to irreversible brain damage. Ischemic injury is associated with vascular leakage, inflammation, tissue injury, and cell death. Cellular changes associated with ischemia include impairment of metabolism, energy failure, free radical production, excitotoxicity, altered calcium homeostasis, and activation of proteases all of which affect brain functioning and also contribute to longterm disabilities including cognitive decline. Inflammation, mitochondrial dysfunction, increased oxidative/nitrosative stress, and intracellular calcium overload contribute to brain injury including cell death and brain edema. However, there is a paucity of agents that can effectively reduce cerebral damage and hence considerable attention has focused on developing newer agents with more efficacy and fewer side-effects. Polyphenols are natural compounds with variable phenolic structures and are rich in vegetables, fruits, grains, bark, roots, tea, and wine. Most polyphenols have antioxidant, anti-inflammatory, and anti-apoptotic properties and their protective effects on mitochondrial functioning, glutamate uptake, and regulating intracellular calcium levels in ischemic injury in vitro have been demonstrated. This review will assess the current status of the potential effects of polyphenols in reducing cerebral injury and improving cognitive function in ischemia in animal and human studies. In addition, the review will also examine available patents in nutrition and agriculture that relates to cerebral ischemic injury with an emphasis on plant polyphenols.

  20. 结扎孕鼠双侧子宫动脉复制围产期缺氧缺血性脑损伤动物模型%Reconstructing new animal model of peri-delivery hypoxia-ischemia brain damage by ligaturing bilateral uterine arteries of pregnant mouse

    Institute of Scientific and Technical Information of China (English)

    薄涛; 李巍; 严超英; 霍淑芳

    2001-01-01

    Objective Hypoxia-ischemia brain injury (HIBD) in infants is one of the important factors which induce intelligent defect,cerebral palasy in human beings. Therefore, we produced a new animal model to study HIBD. Method We assigned twenty 19.5-pregnancy-day mice to four groups randomly and had ligated their bilateral uteral arteries for 0,10,20, and 30 minutes respectively before the cesarean sections. Of each group,we observed the mortality,the growth and the brain's pathological changes. Result The longer the uteral arteries were ligated,the higher the mortality was. The slowlier the body weight increased, the more serious the spastic paralysis was .We also found the mice is similar in the brain pathological change to the human beings such as the edema regions,spotted hemorrhage,and local malacosis in the cortex. Conclusion This is a simple and useful model to study HIBD in newborn.%目的 制作一种新型围产期缺氧缺血性脑损伤(HIBD)的动物模型,为进一步深入研究其病理生理机制及治疗方法提供条件。方法 结扎足月妊娠待产(妊娠19.5d)昆明母鼠双侧子宫动脉,不同时间行剖宫产娩出胎鼠,与正常剖宫产娩出的胎鼠相比较,观察实验胎鼠的生长发育及脑部病理改变。结果 随着结扎子宫动脉阻断血供时间的延长,胎鼠的死亡率迅速增高,两者具有直线正相关关系(P<0.05),实验组胎鼠体重增长明显减慢,运动发育迟滞,脑部的病理改变与人类HIBD的改变相一致。结论 通过结扎孕鼠双侧子宫动脉,胎鼠所产生的一系列变化符合人类HIBD的改变,这是一种较理想的、操作较简便的复制HIBD动物模型的方法。

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    Yongshan Hu

    2012-02-01

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

  3. Temporal and topographic profiles of tissue hypoxia following transient focal cerebral ischemia in rats.

    Science.gov (United States)

    Noto, Takahisa; Furuichi, Yasuhisa; Ishiye, Masayuki; Matsuoka, Nobuya; Aramori, Ichiro; Mutoh, Seitaro; Yanagihara, Takehiko; Manabe, Noboru

    2006-08-01

    Intravascular accumulation of blood cells after brain ischemia-reperfusion can cause obstruction of cerebral blood flow and tissue hypoxia/ischemia as a consequence. In the present study, we examined temporal and topographic changes of tissue hypoxia/ischemia after occlusion of the middle cerebral artery (MCA) for 60 min in rats with immunohistochemical staining for hypoxia (2-nitroimidazole hypoxia marker: hypoxyprobe-1 adducts). Our results showed that tissue hypoxia expressed as positive staining for hypoxyprobe-1 adducts preceded neuronal degeneration. Platelets and granulocytes were detected close to the hypoxyprobe-1 adducts positive area. These results suggested that the hypoxic environment could persist even after reperfusion of MCA, because of vascular obstruction with accumulation of platelets and granulocytes.

  4. Buyang Huanwu decoction enhances cell membrane fluidity in rats with cerebral ischemia/reperfusion

    Institute of Scientific and Technical Information of China (English)

    Chenxu Li

    2012-01-01

    After bilateral carotid artery occlusion for 30 minutes and reperfusion for 2 hours, distinct patho-logical changes presented in the cerebral cortex and cerebellum of rats. Compared with normal rats, nerve cell membrane fluidity significantly decreased in ischemia/reperfusion rats as detected by spin-labeling electron spin resonance, consistent with order parameter S and rotational correlation time TC measurements. Brain nerve cells from rats with ischemia/reperfusion injury were cultured with 1-100 mg/mL Buyang Huanwu decoction. Results showed that Buyang Huanwu decoction gradually increased membrane fluidity dose-dependently to normal levels, and eliminated hydroxide (OH·) and superoxide (O2·) free radicals dose-dependently. These findings suggest that Buyang Huanwu decoction can protect against cell membrane fluidity changes in rats with ischemia/ reper-fusion injury by scavenging free radicals.

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

    Directory of Open Access Journals (Sweden)

    Majid Asadi-Shekaari

    2009-01-01

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

  6. Role of brain glutamic acid metabolism changes in neurodegenerative pathologies

    OpenAIRE

    Nina Pavlovna Kanunnikova

    2012-01-01

    Glutamic acid is an essential participant of brain metabolism. It is known that the glutamate is a neurotransmitter in a numerous part of the brain synapses and acts through various ionotropic or metabotropic receptors. Multiple alterations of the brain glutamate system are observed in both acute and chronic brain injures. Glutamate metabolism changes take place in many neurodegenerative pathologies, such as brain ischemia, Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, amyot...

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

    Directory of Open Access Journals (Sweden)

    Wang-shu Xu

    2016-01-01

    Full Text Available Bumetanide has been shown to lessen cerebral edema and reduce the infarct area in the acute stage of cerebral ischemia. Few studies focus on the effects of bumetanide on neuroprotection and neurogenesis in the chronic stage of cerebral ischemia. We established a rat model of cerebral ischemia by injecting endothelin-1 in the left cortical motor area and left corpus striatum. Seven days later, bumetanide 200 µg/kg/day was injected into the lateral ventricle for 21 consecutive days with a mini-osmotic pump. Results demonstrated that the number of neuroblasts cells and the total length of dendrites increased, escape latency reduced, and the number of platform crossings increased in the rat hippocampal dentate gyrus in the chronic stage of cerebral ischemia. These findings suggest that bumetanide promoted neural precursor cell regeneration, dendritic development and the recovery of cognitive function, and protected brain tissue in the chronic stage of ischemia.

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

    Institute of Scientific and Technical Information of China (English)

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

    2016-01-01

    Bumetanide has been shown to lessen cerebral edema and reduce the infarct area in the acute stage of cerebral ischemia. Few studies focus on the effects of bumetanide on neuroprotection and neurogenesis in the chronic stage of cerebral ischemia. We established a rat model of cerebral ischemia by injecting endothelin-1 in the left cortical motor area and left corpus striatum. Seven days later, bumeta-nide 200 µg/kg/day was injected into the lateral ventricle for 21 consecutive days with a mini-osmotic pump. Results demonstrated that the number of neuroblasts cells and the total length of dendrites increased, escape latency reduced, and the number of platform crossings increased in the rat hippocampal dentate gyrus in the chronic stage of cerebral ischemia. These ifndings suggest that bumetanide promoted neural precursor cell regeneration, dendritic development and the recovery of cognitive function, and protected brain tissue in the chronic stage of ischemia.

  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. Pretreatment with Bone Morphogenetic Protein-7 (BMP-7) Mimics Ischemia Preconditioning Following Intestinal Ischemia/Reperfusion Injury in The Intestine and Liver

    OpenAIRE

    Radhakrishnan, Ravi S.; Radhakrishnan, Geetha L.; Radhakrishnan, Hari R.; Xue, Hasen; Adams, Sasha D.; Moore-Olufemi, Stacey D.; Harting, Matthew T.; Cox, Charles S.; Kone, Bruce C.

    2008-01-01

    Intestinal ischemia/reperfusion (I/R) injury has been shown to cause intestinal mucosal injury and adversely affect function. Ischemic preconditioning (IPC) has been shown to protect against intestinal I/R injury by reducing polymorphonuclear leukocyte infiltration, intestinal mucosal injury, and liver injury, and preserve intestinal transit. Bone morphogenetic protein 7 (BMP-7) has been shown to protect against I/R injury in the kidney and brain. Recently, microarray analysis has been used t...

  11. Reparative neurogenesis after cerebral ischemia: Clinical application prospects

    International Nuclear Information System (INIS)

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

  12. Reparative neurogenesis after cerebral ischemia: Clinical application prospects

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-11-17

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

  13. Reparative neurogenesis after cerebral ischemia: Clinical application prospects

    Science.gov (United States)

    Khodanovich, M. Yu.

    2015-11-01

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

  14. Retinal ischemia and embolism. Causes and outcomes

    NARCIS (Netherlands)

    Wijman, C.A.C.

    2007-01-01

    The ocular fundus allows direct visualization of the retinal vasculature, blood vessels that are part of the cerebral circulation. Unraveling the causes of retinal ischemia may provide further insight in the pathophysiological processes that underlie cerebral ischemia. The primary aim of the studies

  15. Role of mito-KATP channel in isoflurane preconditioning lightening brain ischemia-reperfusion injury in gerbils%mito-KATP通道在异氟醚预处理减轻沙土鼠脑缺血-再灌注损伤中的作用

    Institute of Scientific and Technical Information of China (English)

    章放香; 张伟晶; 王世平; 安裕文; 邱冰

    2011-01-01

    目的 观察mito-KATP通道在异氟醚(ISO)预处理脑保护中的作用.方法 健康沙土鼠60只随机均分为六组:对照组(A组)、缺血-再灌注组(B组)、1.5%ISO预处理组(C组)、1.5%ISO预处理+5-羟葵酸(5-HD)5 mg/kg组(D组)、1.5%ISO预处理+5-HD 10 mg/kg组(E组)、1.50% ISO预处理+5-HD 15 mg/kg组(F组).预处理方法为连续5d吸入1.5% ISO1 h/d;末次预处理24 h后行缺血-再灌注,D、E、F组缺血前30 min分别腹腔注射5、10、15 mg/kg 5-HD.48 h后HE染色观察脑组织形态学变化,TUNEL法检测海马神经元凋亡,免疫组化检测Bd-2及Bax在海马神经元的表达.结果 与A组比较,B、C、D、E、F组脑损伤评分、神经细胞凋亡率、Bax表达均明显升高(P<0.05);而C、D、E、F组Bcl-2阳性表达明显升高(P<0.05).与C组比较,E、F组脑损伤评分、神经细胞凋亡率及Bax表达明显升高(P<0.05),而Bcl-2阳性表达降低(P<0.05).结论 mito-KATP通道在ISO预处理脑保护效应中起重要作用.%Objective To investigate the effect of mito-KATP channel in isoflurane preconditioning induced brain protection in gerbils. Methods Sixty healthy Mongolian gerbils were randomly divided into 6 groups: group A was normal control; group B was the reperfusion; group C was 1. 5% isofulurance preconditioning; group D was 1.5% isofulurance preconditioning+5-HD 5 mg/kg; group E was 1.5% isofulurance preconditioning + 5-HD 10 mg/kg; group F was 1.5% isofulurance preconditioning +5-HD 15 mg/kg group. Once daily of 1. 5% isoflurane was given for five days. Ischemia-reperfusion injury was occurred 24 h after the last preconditioning day. Groups of D, E and F were injected with 5-HD 5, 10, 15 mg/kg 30 min before ischemia-reperfusion injury. HE staining was used to observe the injury of cerebrum, and the expressions of Bcl-2 and Bax were detected with immunohistochemistry, and TUNEL was used to analyze the neuronal apoptosis. Results Compared with group A, other five groups

  16. Myocardial ischemia and angina pectoris

    International Nuclear Information System (INIS)

    Ambulatory monitoring of ST segment changes was performed in 60 patients presenting with angina, positive ECG stress tests and coronary artery disease, 85% of ischemic ECG events were asymptomatic, 37% occurred with no increase in heart rate and 15% of episodes either lasted 20 minutes or more or fluctuated in severity. A controlled pilot study in ten patients showed depression. Radionuclide studies in 50 patients with angina and coronary artery disease have shown that stress (i.e., atrial pacing) produced different patterns of disturbed regional myocardial perfusion related to the patient's exercise capacity and eventually leading to a decrease in regional myocardial perfusion during the ischemic episode. ST segment depression appeared only after the decrease in regional myocardial perfusion. These findings combined with past research suggest that patients with angina and coronary artery disease can suffer frequent asymptomatic disturbances of the regional myocardial perfusion. The frequency of these episodes and the time course for the recovery of the metabolic consequences mean that segments of ventricular myocardium may be constantly abnormal. The relative importance of changes in coronary tone and malfunction of platelets in the diseased coronary tree needs to be examined in clinical research. Pilot studies of antiplatelet agents have shown a significant beneficial effect on episodes of ischemia occurring at night and those occurring without any increase in heart rate. The techniques and observations in these patients with coronary artery disease all suggest that acute transient regional myocardial ischemia is caused by a variety of mechnisms. Further research using objective methods is required to discover the causes of ischemia and to rationalize treatment. (orig./MG)

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Zhao Yu

    2012-09-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2013-03-15

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

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

    Institute of Scientific and Technical Information of China (English)

    易黎; 张苏明; 张新江

    2002-01-01

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

  2. Transient myocardial ischemia after myocardial infarction

    DEFF Research Database (Denmark)

    Mickley, H

    1995-01-01

    Ambulatory ST-segment monitoring is a relatively new device in the evaluation of myocardial ischemia. The method is unique in allowing us to continuously examine the patient over an extended period of time in a changing environmental milieu. In survivors of acute myocardial infarction...... the prevalence of ambulatory or transient myocardial ischemia is lower than in patients with chronic, stable coronary artery disease. A greater proportion of ischemic episodes, however, are silent than in other subgroups with ischemic heart disease. Early after the infarction, transient myocardial ischemia...... exhibits a circadian variation with a peak activity occurring in the late evening hours. Patients with non-Q wave infarction have more transient myocardial ischemia, whereas thrombolytic therapy seems to result in less residual ischemia. Exercise testing is more sensitive than ambulatory monitoring...

  3. Hypothermia protects somatostatinergic neurons in rat dentate hilus from zinc accumulation and cell death after cerebral ischemia

    DEFF Research Database (Denmark)

    Johansen, Flemming Fryd; Tønder, N.; Berg, Michael;

    1993-01-01

    Neuropathology, dentate hilus, cerebral ischemia, ischemia, rat, hippocampus, somatostatin, zinc, hyperthermia......Neuropathology, dentate hilus, cerebral ischemia, ischemia, rat, hippocampus, somatostatin, zinc, hyperthermia...

  4. Effect of Exogenous Erythropoietin on Caspase-9 and Caspase-3 Expression in Newborn Rats after Hypoxia-ischemia Brain Damage%EPO对新生大鼠缺氧缺血性脑损伤时脑组织Caspase-9和Caspase-3的影响

    Institute of Scientific and Technical Information of China (English)

    白丹; 阴怀清; 阴崇娟; 武师润

    2011-01-01

    目的 观察新生大鼠缺氧缺血性脑损伤(HIBD)时脑组织Caspase-9和Caspase-3的表达变化及促红细胞细胞生成素(EPO)对其表达的影响,从而探讨EPO发挥脑保护作用的可能机制.方法 将新生7 d SD大鼠120只随机分成3组,假手术组、HIBD组、rhEPO治疗组,每组根据不同时间点又分为5个亚组:6 h组、12 h组、24 h组、48 h组、72 h组,每组8只,用免疫组化的方法观察各组脑组织Caspase-9和Caspase-3的表达.结果 Caspase-9的表达在缺氧缺血6 h即增强,12 h时逐渐升高,24 h~72 h维持在高峰水平(P<0.01);Caspase-3的表达也在缺氧缺血6 h即增强,12 h时逐渐升高,24 h~48 h达高峰,72 h稍有降低(P<0.01);rhEPO治疗组各时间点Caspase-9和Caspase-3的表达水平较HIBD组均明显降低(P<0.01).结论 Caspase-9和Caspase-3参与了新生大鼠脑组织HIBD的发生发展过程,EPO可能通过降低新生大鼠缺氧缺血性脑损伤时脑组织Caspase-9和Caspase-3的表达发挥其脑保护作用.%Objective To observe the expression of caspase - 9 and caspase - 3 in brain tissue of neonatal rats after hypoxia - ischemia brain damage (HIBD) and the effects of exogenous erythropoietin (EPO) on the expression of caspase- 9 and caspase- 3. Methods One hundred and twenty seven - day - old neonatal Sprague - Dawley rats were randomly divided into three groups: Sham - operated group, HIBD group and rhEPO treatment group. Each group was further divided into five sub-groups(n= 8) based on different time points after H IBD(6 h, 12 h, 24 h, 48 h, 72 h), respectively. Immunohistochemical technique was used to determine the expression of caspase - 9 and caspase - 3 in brain tissues. Results The expression of caspase - 9 in HIBD group was increased at 6 h after HIBD,increased gradually at 12 h,and maintained the peak level 24 h to 72 h (P<0.01). The expression of caspase-3 in HIBD group was increased at 6 h after HIBD,increased gradually at 12 h,reached the peak at 24 h

  5. Improvement of oxygen supply by an artificial carrier in combination with normobaric oxygenation decreases the volume of tissue hypoxia and tissue damage from transient focal cerebral ischemia

    NARCIS (Netherlands)

    Seiffge, David J.; Lapina, Natalia E.; Tsagogiorgas, Charalambos; Theisinger, Bastian; Henning, Robert H.; Schilling, Lothar

    2012-01-01

    Tissue hypoxia may play an important role in the development of ischemic brain damage. In the present study we investigated in a rat model of transient focal brain ischemia the neuroprotective effects of increasing the blood oxygen transport capacity by applying a semifluorinated alkane (SFA)-contai

  6. Delayed minocycline inhibits ischemia-activated matrix metalloproteinases 2 and 9 after experimental stroke

    Directory of Open Access Journals (Sweden)

    Hess David C

    2006-07-01

    Full Text Available Abstract Background Matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9 are increased in the brain after experimental ischemic stroke in rats. These two proteases are involved with the degradation of the basal lamina and loss of stability of the blood brain barrier that occurs after ischemia and that is associated with thrombolytic therapy in ischemic stroke. Minocycline is a lipophilic tetracycline and is neuroprotective in several models of brain injury. Minocycline inhibits inflammation, apoptosis and extracellular matrix degradation. In this study we investigated whether delayed minocycline inhibits brain MMPs activated by ischemia in a model of temporary occlusion in Wistar rats. Results Both MMP-2 and MMP-9 were elevated in the ischemic tissue as compared to the contra-lateral hemisphere after 3 hours occlusion and 21 hours survival (p In vitro incubation of minocycline in concentrations as low as 0.1 μg/ml with recombinant MMP-2 and MMP-9 impaired enzymatic activity and MMP-9 was more sensitive at lower minocycline concentrations (p Conclusion Minocycline inhibits enzymatic activity of gelatin proteases activated by ischemia after experimental stroke and is likely to be selective for MMP-9 at low doses. Minocycline is a potential new therapeutic agent to acute treatment of ischemic stroke.

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

    Directory of Open Access Journals (Sweden)

    Ying-min Cai

    2016-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

  9. 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.

  10. Rodent Hypoxia Ischemia Models for Cerebral Palsy Research: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Prakasham eRumajogee

    2016-04-01

    Full Text Available Cerebral Palsy (CP is a complex multifactorial disorder, affecting approximately 2.5-3 per 1000 live term births, and up to 22 per 1000 prematurely born babies. CP results from injury to the developing brain incurred before, during or after birth. The most common form of this condition, spastic CP, is primarily associated with injury to the cerebral cortex and sub-cortical white matter as well as the deep gray matter. The major etiological factors of spastic CP are hypoxia/ischemia, occurring during the last third of pregnancy and around the birth age. In addition, inflammation has been found to be an important factor contributing to brain injury, especially in term infants. Other factors, including genetics, are gaining importance. The classic Rice-Vannucci hypoxia-ischemia model (in which 7-day-old rat pups undergo unilateral ligation of the common carotid artery followed by exposure to 8% oxygen hypoxic air is a model of neonatal stroke which has greatly contributed to cerebral palsy research. In this model brain damage resembles that observed in severe CP cases. This model, and its numerous adaptations, allows one to finely tune the injury parameters to mimic, and therefore study, many of the pathophysiological processes and conditions observed in human patients. Investigators can recreate the hypoxia/ischemia and inflammation, which cause brain damage and subsequent motor and cognitive deficits. This model further enables the examination of potential approaches to achieve neural repair and regeneration. In the present review, we compare and discuss the advantages, limitations, and the translational value for cerebral palsy research of hypoxia-ischemia models of perinatal brain injury.

  11. Metabolic Adaptation to Muscle Ischemia

    Science.gov (United States)

    Cabrera, Marco E.; Coon, Jennifer E.; Kalhan, Satish C.; Radhakrishnan, Krishnan; Saidel, Gerald M.; Stanley, William C.

    2000-01-01

    Although all tissues in the body can adapt to varying physiological/pathological conditions, muscle is the most adaptable. To understand the significance of cellular events and their role in controlling metabolic adaptations in complex physiological systems, it is necessary to link cellular and system levels by means of mechanistic computational models. The main objective of this work is to improve understanding of the regulation of energy metabolism during skeletal/cardiac muscle ischemia by combining in vivo experiments and quantitative models of metabolism. Our main focus is to investigate factors affecting lactate metabolism (e.g., NADH/NAD) and the inter-regulation between carbohydrate and fatty acid metabolism during a reduction in regional blood flow. A mechanistic mathematical model of energy metabolism has been developed to link cellular metabolic processes and their control mechanisms to tissue (skeletal muscle) and organ (heart) physiological responses. We applied this model to simulate the relationship between tissue oxygenation, redox state, and lactate metabolism in skeletal muscle. The model was validated using human data from published occlusion studies. Currently, we are investigating the difference in the responses to sudden vs. gradual onset ischemia in swine by combining in vivo experimental studies with computational models of myocardial energy metabolism during normal and ischemic conditions.

  12. 胰岛素对大鼠局灶性脑缺血后脑水肿及水通道蛋白9的影响%Effects of Insulin on Expression of Aquaporin -9 and Brain Edema after Focal Cerebral Is-chemia in Rats

    Institute of Scientific and Technical Information of China (English)

    李珊珊; 陈忠云; 李婧; 徐志伟; 杨旭

    2015-01-01

    Objective: To observe the effects of insulin on expression of Aquaporin-9 (AQP-9) and brain edema after middle cerebral artery occlusion (MCAO) in rats. Methods: One hundred and eighty SD rats were randomly divided into groups of sham, MCAO and insulin treatment, with 30 rats in each group. Six rats in each group were observed at 6 h, 12 h, 24 h, 48 h, 72 h after MCAO. The MCAO models were estabilish by suture method, and the sham group without suture. The insulin treatment group was given insulin by intraperitoneal injection. The nerve function, blood-brain barrier permeability, brain water content and AQP-9 mRNA expression were evaluated. Results: The brain water content, blood-brain barrier permeability and AQP-9 mRNA expression of groups MCAO and insulin began to increase at 6 h and reached peak at 48 h and gradually decreased at 72 h, which were signifi-cantly higher than those in sham group (P<0.05). Compared with the MCAO group, the brain water content, blood-brain barrier permeability and AQP-9 mRNA expression in insulin treatment group were obviously decreased (P<0.05). There were a significantly passive correlation between AQP-9 mRNA expression and brain water contents, blood-brain barrier permeability(r=0.905, P<0.01; r=0.923, P<0.01). Conclusion: Insulin can reduce brain edema through suppressing expression of AQP-9 in cerebral ischemia in rats.%目的:观察胰岛素对大脑中动脉栓塞(MCAO)大鼠模型脑水肿形成及水通道蛋白-9(AQP-9)表达的影响。方法:SD 大鼠180只,随机分为假手术组、模型组、胰岛素组各30只,分别在栓塞后6、12、24、48、72 h 观察6只。线栓法制备 MCAO 模型,假手术组不插入线栓,胰岛素组 MCAO 后立即给予腹腔注射胰岛素干预。各组进行神经功能评分,检测血脑屏障通透性、脑含水量和脑组织 AQP-9 mRNA 表达。结果:模型组和胰岛素组于缺血6 h 后,脑含水量、血脑屏障通透性及 AQP-9 mRNA

  13. Lettuce glycoside B ameliorates cerebral ischemia reperfusion injury by increasing nerve growth factor and neurotrophin-3 expression of cerebral cortex in rats

    Directory of Open Access Journals (Sweden)

    Heqin Zhan

    2014-01-01

    Full Text Available Aims: The aim of the study was to investigate the effects of LGB on cerebral ischemia-reperfusion (I/R injury in rats and the mechanisms of action of LGB. Materials and Methods: The study involved extracting LGB from P. laciniata, exploring affects of LGB on brain ischemia and action mechanism at the molecular level. The cerebral ischemia reperfusion injury of middle cerebral artery occlusion was established. We measured brain histopathology and brain infarct rate to evaluate the effects of LGB on brain ischemia injury. The expressions of nerve growth factor (NGF and neurotrophin-3 (NT-3 were also measured to investigate the mechanisms of action by the real-time polymerase chain reaction and immunohistochemistry. Statistical analysis: All results were mentioned as mean ± standard deviation. One-way analysis of variance was used to determine statistically significant differences among the groups. Values of P < 0.05 were considered to be statistically significant. Results: Intraperitoneal injection of LGB at the dose of 12, 24, and 48 mg/kg after brain ischemia injury remarkably ameliorated the morphology of neurons and brain infarct rate (P < 0.05 , P < 0.01. LGB significantly increased NGF and NT-3 mRNA (messenger RNA and both protein expression in cerebral cortex at the 24 and 72 h after drug administration (P < 0.05, P < 0.01. Conclusions: LGB has a neuroprotective effect in cerebral I/R injury and this effect might be attributed to its upregulation of NGF and NT-3 expression ability in the brain cortex during the latter phase of brain ischemia.

  14. Non-Specific Inhibition of Ischemia- and Acidosis-Induced Intracellular Calcium Elevations and Membrane Currents by α-Phenyl-N-tert-butylnitrone, Butylated Hydroxytoluene and Trolox

    OpenAIRE

    Christopher Katnik; Javier Cuevas

    2014-01-01

    Ischemia, and subsequent acidosis, induces neuronal death following brain injury. Oxidative stress is believed to be a key component of this neuronal degeneration. Acute chemical ischemia (azide in the absence of external glucose) and acidosis (external media buffered to pH 6.0) produce increases in intracellular calcium concentration ([Ca2+] i ) and inward membrane currents in cultured rat cortical neurons. Two α-tocopherol analogues, trolox and butylated hydroxytoluene (BHT), and the spin t...

  15. Short-term treadmill exercise preserves sensory-motor function through inhibiting apoptosis in the hippocampus of hypoxic ischemia injury rat pups.

    Science.gov (United States)

    Choi, Jun-Ho; Kim, Tae-Soo; Park, Joon-Ki; Sim, Young-Je; Kim, Kijeong; Lee, Sam-Jun

    2013-01-01

    Perinatal hypoxic ischemia injury is a common cause of morbidity and mortality in neonates. Physical exercise may ameliorate neurological impairment by impeding neuronal loss following various brain insults. In the present study, the effect of treadmill exercise on sensory-motor function in relation with hippocampal apoptosis following hypoxic ischemia brain injury was investigated. Sensory-motor function was determined by walking initiation test and apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining and caspase-3 immunohistochemistry. On postnatal 7 day, left common carotid artery of the neonatal rats was ligated for two hours and then the neonatal rats were exposed to hypoxia conditions for one hour. The rat pups in the exercise groups were forced to run on a motorized treadmill for 30 min once a day for 10 days, starting 22 days after induction of hypoxic ischemia brain injury. Hypoxic ischemia caused sensory-motor disturbance with enhancement of apoptosis in the hippocampus. Short-term treadmill exercise suppressed hypoxic ischemia injury-induced apoptosis in the hippocampus, and preserved sensory-motor function of hypoxic ischemia injury rat pups. PMID:24282805

  16. Protective effects of Echium amoenum Fisch. and C.A. Mey. against cerebral ischemia in the rats

    Directory of Open Access Journals (Sweden)

    Leila Safaeian

    2015-01-01

    Conclusion: The anthocyanin rich fraction from E. amoenum was found to have protective effects against some brain damages postischemic reperfusion . However, further researches are required for investigating the exact mechanisms of the effect of this plant in the prevention of cerebral ischemia in human.

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

    Institute of Scientific and Technical Information of China (English)

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

    2007-01-01

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

  18. An Early Continuous Experimental Study on Magnetic Resonance Diffusion-weighted Image of Focal Cerebral Ischemia and Reperfusion in Rats

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    The chronological and spatial rules of changes during focal cerebral ischemia and reperfusion in different brain regions with magnetic resonance diffusion-weighted imaging (DWI) in a model of occlusion of middle cerebral artery (MCAO) and the development of cytotoxic edema in acute phase were explored. Fifteen healthy S-D rats with MCA occluded by thread-emboli were randomly divided into three groups. 15 min after the operation, the serial imaging was scanned on DWI for the three groups. The relative mean signal intensity (RMSI) of the frontal lobe, parietal lobe, lateral cauda-putamen, medial cauda-putamen and the volume of regions of hyperintense signal on DWI were calculated. After the last DWI scanning, T2 WI was performed for the three groups. After 15min ischemia, the rats was presented hyperintense signals on DWI. The regions of hyperintense signal were enlarged with prolonging ischemia time. The regions of hyperintense signal were back to normal after 60 min reperfusion with a small part remaining to show hyperintense signal. The RMSIs of parietal lobe and lateral cauda-putamen were higher than that of the frontal lobe and medial cauda-putamen both in ischemia phase and recanalization phase. The three groups werenormal on T2WI imaging. DWI had good sensitivity to acute cerebral ischemia, which was used to study the chronological and spatial rules of development of early cell edema in ischemia regions.

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

    OpenAIRE

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

    2013-01-01

    Long-term exercise prior to brain ischemia enhances the activities of antioxidant enzymes and leads to a significant reduction in brain damage and neurological deficits in rats subjected to transient middle cerebral artery occlusion. However, it has not been established whether relatively short-term exercise generates similar results following middle cerebral artery occlusion. We aimed to determine whether short-term exercise could reduce oxidative damage and prevent sensori-motor dysfunction...

  20. Neuroprotective effects of atorvastatin against cerebral ischemia/reperfusion injury through the inhibition of endoplasmic reticulum stress.

    Science.gov (United States)

    Yang, Jian-Wen; Hu, Zhi-Ping

    2015-08-01

    Cerebral ischemia triggers secondary ischemia/reperfusion injury and endoplasmic reticulum stress initiates cell apoptosis. However, the regulatory mechanism of the signaling pathway remains unclear. We hypothesize that the regulatory mechanisms are mediated by the protein kinase-like endoplasmic reticulum kinase/eukaryotic initiation factor 2α in the endoplasmic reticulum stress signaling pathway. To verify this hypothesis, we occluded the middle cerebral artery in rats to establish focal cerebral ischemia/reperfusion model. Results showed that the expression levels of protein kinase-like endoplasmic reticulum kinase and caspase-3, as well as the phosphorylation of eukaryotic initiation factor 2α, were increased after ischemia/reperfusion. Administration of atorvastatin decreased the expression of protein kinase-like endoplasmic reticulum kinase, caspase-3 and phosphorylated eukaryotic initiation factor 2α, reduced the infarct volume and improved ultrastructure in the rat brain. After salubrinal, the specific inhibitor of phosphorylated eukaryotic initiation factor 2α was given into the rats intragastrically, the expression levels of caspase-3 and phosphorylated eukaryotic initiation factor 2α in the were decreased, a reduction of the infarct volume and less ultrastructural damage were observed than the untreated, ischemic brain. However, salubrinal had no impact on the expression of protein kinase-like endoplasmic reticulum kinase. Experimental findings indicate that atorvastatin inhibits endoplasmic reticulum stress and exerts neuroprotective effects. The underlying mechanisms of attenuating ischemia/reperfusion injury are associated with the protein kinase-like endoplasmic reticulum kinase/eukaryotic initiation factor 2α/caspase-3 pathway. PMID:26487850

  1. Role of Nitric Oxide and Nitric Oxide Synthases in Ischemia-reperfusion Injury in Rat Organotypic Hippocampus Slice

    Institute of Scientific and Technical Information of China (English)

    MENG Xianfang; SHI Jing; LIU Xiaochun; ZHANG Jing; SUN Ning

    2005-01-01

    To investigate the effects of ischemia-reperfusion on the levels of nitric oxide and nitric oxide synthase isoforms (nNOS and iNOS), rat organotypic hippocampus slice were cultured in vitro and subjected to ischemia by oxygen glucose deprivation (OGD) for 30 min and then placed in the normal culture condition. The ischemia-reperfusion produced a time-dependent increase in nitrite levels in the culture medium. Reverse transcriptional-polymerase chain reaction showed augmented levels of mRNA for both nNOS and iNOS when compared with control at 12 h and remained increase at 36 h after OGD (P<0.05). The protein levels of both nitric oxide synthase isoforms increased significantly as determined by Western Blot. OGD also caused neurotoxicity in this model as revealed by the elevated lactate dehydrogenase (LDH) efflux into the incubation solution. The results suggest that organotypic hippocampus slice is a useful model in studying ischemia-reperfusion brain injury. NO and NOS may play a critical role in the ischemia-reperfusion brain damage in vitro.

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

    OpenAIRE

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

    2013-01-01

    Bone marrow cells for the treatment of ischemic brain injury may depend on the secretion of a large number of neurotrophic factors. Bone marrow regenerative cells are capable of increasing the secretion of neurotrophic factors. In this study, after tail vein injection of 5-fluorouracil for 7 days, bone marrow cells and bone marrow regenerative cells were isolated from the tibias and femurs of rats, and then administered intravenously via the tail vein after focal cerebral ischemia. Immunohist...

  3. Therapeutic potential of the novel hybrid molecule JM-20 against focal cortical ischemia in rats

    OpenAIRE

    Yanier Núñez Figueredo; Jeney Ramírez-Sanchez; Gisele Hansel; Gilberto L. Pardo-Andreu; Nelson Merino; Guillermo Aparicio; Rene Delgado-Hernández; Laura García-Pupo; Estael Ochoa-Rodríguez; Yamila Verdecia-Reyes; Souza, Diogo O

    2016-01-01

    Context: Despite the great mortality and morbidity of stroke, treatment options remain limited. We previously showed that JM-20, a novel synthetic molecule, possessed a strong neuroprotective effect in rats subjected to transient middle cerebral artery occlusion. However, to verify the robustness of the pre-clinical neuroprotective effects of JM-20 to get good prognosis in the translation to the clinic, it is necessary to use other experimental models of brain ischemia. Aims: To evaluate ...

  4. Hydrogen sulphide and mild hypothermia activate the CREB signaling pathway and prevent ischemia-reperfusion injury

    OpenAIRE

    Dai, Hai-bin; Ji, Xiangjun; Zhu, Si-Hai; Hu, Yi-min; Zhang, Li-dong; Miao, Xiao-lei; Ma, Ru-Meng; Duan, Man-lin; Li, Wei-Yan

    2015-01-01

    Background Both hydrogen sulphide (H2S) and mild hypothermia have been reported to prevent brain damage caused by reperfusion assault through regulating the N-methyl-D-aspartate receptor (NMDAR). However, the relationship between the two treatments and how they exert neuro-protective effects through NMDARs remain to be elucidated. Methods Transient cerebral ischemia was induced using the Pulsinelli four-vessel occlusion method. We used sodium hydrosulphide (NaHS) as the H2S donor. We randomly...

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

    OpenAIRE

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

    2016-01-01

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

  6. Electroencephalographic Response to Sodium Nitrite May Predict Delayed Cerebral Ischemia After Severe Subarachnoid Hemorrhage

    Science.gov (United States)

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

    2016-01-01

    Objectives: Aneurysmal subarachnoid hemorrhage often leads to death and poor clinical outcome. Injury occurring during the first 72 hours is termed “early brain injury,” with disruption of the nitric oxide pathway playing an important pathophysiologic role in its development. Quantitative electroencephalographic variables, such as α/δ frequency ratio, are surrogate markers of cerebral ischemia. This study assessed the quantitative electroencephalographic response to a cerebral nitric oxide donor (intravenous sodium nitrite) to explore whether this correlates with the eventual development of delayed cerebral ischemia. Design: Unblinded pilot study testing response to drug intervention. Setting: Neuroscience ICU, John Radcliffe Hospital, Oxford, United Kingdom. Patients: Fourteen World Federation of Neurosurgeons grades 3, 4, and 5 patients (mean age, 52.8 yr [range, 41–69 yr]; 11 women). Interventions: IV sodium nitrite (10 μg/kg/min) for 1 hour. Measurements and Main Results: Continuous electroencephalographic recording for 2 hours. The alpha/delta frequency ratio was measured before and during IV sodium nitrite infusion. Seven of 14 patients developed delayed cerebral ischemia. There was a +30% to +118% (range) increase in the alpha/delta frequency ratio in patients who did not develop delayed cerebral ischemia (p < 0.0001) but an overall decrease in the alpha/delta frequency ratio in those patients who did develop delayed cerebral ischemia (range, +11% to –31%) (p = 0.006, multivariate analysis accounting for major confounds). Conclusions: Administration of sodium nitrite after severe subarachnoid hemorrhage differentially influences quantitative electroencephalographic variables depending on the patient’s susceptibility to development of delayed cerebral ischemia. With further validation in a larger sample size, this response may be developed as a tool for risk stratification after aneurysmal subarachnoid hemorrhage. PMID:27441898

  7. Effect of policosanol on cerebral ischemia in Mongolian gerbils

    Directory of Open Access Journals (Sweden)

    Molina V.

    1999-01-01

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

  8. Nitro-Oxidative Stress after Neuronal Ischemia Induces Protein Nitrotyrosination and Cell Death

    Directory of Open Access Journals (Sweden)

    Marta Tajes

    2013-01-01

    Full Text Available Ischemic stroke is an acute vascular event that obstructs blood supply to the brain, producing irreversible damage that affects neurons but also glial and brain vessel cells. Immediately after the stroke, the ischemic tissue produces nitric oxide (NO to recover blood perfusion but also produces superoxide anion. These compounds interact, producing peroxynitrite, which irreversibly nitrates protein tyrosines. The present study measured NO production in a human neuroblastoma (SH-SY5Y, a murine glial (BV2, a human endothelial cell line (HUVEC, and in primary cultures of human cerebral myocytes (HC-VSMCs after experimental ischemia in vitro. Neuronal, endothelial, and inducible NO synthase (NOS expression was also studied up to 24 h after ischemia, showing a different time course depending on the NOS type and the cells studied. Finally, we carried out cell viability experiments on SH-SY5Y cells with H2O2, a prooxidant agent, and with a NO donor to mimic ischemic conditions. We found that both compounds were highly toxic when they interacted, producing peroxynitrite. We obtained similar results when all cells were challenged with peroxynitrite. Our data suggest that peroxynitrite induces cell death and is a very harmful agent in brain ischemia.

  9. Diffusion-weighted MR imaging (DWI) in spinal cord ischemia

    International Nuclear Information System (INIS)

    Spinal cord infarction is a rare clinical diagnosis characterized by a sudden onset of paralysis, bowel and bladder dysfunction, and loss of pain and temperature perception, with preservation of proprioception and vibration sense. Magnetic resonance imaging (MRI) usually demonstrates intramedullary hyperintensity on T2-weighted MR images with cord enlargement. However, in approximately 45% of patients, MR shows no abnormality. Diffusion-weighted MR imaging (DWI) has been widely used for the evaluation of a variety of brain disorders, especially for acute stroke. Preliminary data suggest that DWI has the potential to be useful in the early detection of spinal infarction. We performed DWI, using navigated, interleaved, multishot echo planar imaging (IEPI), in a series of six patients with a clinical suspicion of acute spinal cord ischemia. In all patients, high signal was observed on isotropic DWI images with low ADC values (0.23 and 0.86 x 10-3 cm2/s), indicative of restricted diffusion. We analyzed the imaging findings from conventional MR sequences and diffusion-weighted MR sequences in six patients with spinal cord infarction, compared the findings with those in published series, and discuss the value of DWI in spinal cord ischemia based on current experience. Although the number of patients with described DWI findings totals only 23, the results of previously published studies and those of our study suggest that DWI has the potential to be a useful and feasible technique for the detection of spinal infarction. (orig.)

  10. Diffusion-weighted MR imaging (DWI) in spinal cord ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Thurnher, Majda M. [Medical University of Vienna, Department of Radiology, Neuroradiology Section, Vienna (Austria); Bammer, Roland [Stanford University, Lucas MRS/I Center, Department of Radiology, Stanford, CA (United States)

    2006-11-15

    Spinal cord infarction is a rare clinical diagnosis characterized by a sudden onset of paralysis, bowel and bladder dysfunction, and loss of pain and temperature perception, with preservation of proprioception and vibration sense. Magnetic resonance imaging (MRI) usually demonstrates intramedullary hyperintensity on T2-weighted MR images with cord enlargement. However, in approximately 45% of patients, MR shows no abnormality. Diffusion-weighted MR imaging (DWI) has been widely used for the evaluation of a variety of brain disorders, especially for acute stroke. Preliminary data suggest that DWI has the potential to be useful in the early detection of spinal infarction. We performed DWI, using navigated, interleaved, multishot echo planar imaging (IEPI), in a series of six patients with a clinical suspicion of acute spinal cord ischemia. In all patients, high signal was observed on isotropic DWI images with low ADC values (0.23 and 0.86 x 10{sup -3} cm{sup 2}/s), indicative of restricted diffusion. We analyzed the imaging findings from conventional MR sequences and diffusion-weighted MR sequences in six patients with spinal cord infarction, compared the findings with those in published series, and discuss the value of DWI in spinal cord ischemia based on current experience. Although the number of patients with described DWI findings totals only 23, the results of previously published studies and those of our study suggest that DWI has the potential to be a useful and feasible technique for the detection of spinal infarction. (orig.)

  11. Tacrolimus (FK506 reduces ischemia-induced hippocampal damage in rats: a 7- and 30-day study

    Directory of Open Access Journals (Sweden)

    F. Giordani

    2003-04-01

    Full Text Available The neuroprotective effect of the immunosuppressant agent FK506 was evaluated in rats after brain ischemia induced for 15 min in the 4-vessel occlusion model. In the first experimental series, single doses of 1.0, 3.0 or 6.0 mg FK506/kg were given intravenously (iv immediately after ischemia. In the second series, FK506 (1.0 mg/kg was given iv at the beginning of reperfusion, followed by doses applied intraperitoneally (ip 6, 24, 48, and 72 h post-ischemia. The same protocol was used in the third series except that all 5 doses were given iv. Damage to the hippocampal field CA1 was assessed 7 or 30 days post-ischemia on three different stereotaxic planes along the septotemporal axis of the hippocampus. Ischemia caused marked neurodegeneration on all planes (P<0.001. FK506 failed to provide neuroprotection to CA1 both when applied iv as a single dose of 1.0, 3.0 or 6.0 mg/kg (experiment 1, and after five iv injections of 1.0 mg/kg (experiment 3. In contrast, the repeated administration of FK506 combining iv plus ip administration reduced CA1 cell death on all stereotaxic planes both 7 and 30 days post-ischemia (experiment 2; P<=0.01. Compared to vehicle alone, FK506 reduced rectal temperature in a dose-dependent manner (P<=0.05; however, this effect did not alter normothermia (37ºC. FK506 reduced ischemic brain damage, an effect sustained over time and apparently dependent on repeated doses and on delivery route. The present data extend previous findings on the rat 4-vessel occlusion model, further supporting the possible use of FK506 in the treatment of ischemic brain damage.

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

    OpenAIRE

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

    2007-01-01

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

  13. Effects of immediate and delayed mild hypothermia on endogenous antioxidant enzymes and energy metabolites following global cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hong; ZHANG Jun-jian; MEI Yuan-wu; SUN Sheng-gang; TONG E-tang

    2011-01-01

    Background The optimal time window for the administration of hypothermia following cerebral ischemia has been studied for decades,with disparity outcomes.In this study,the efficacy of mild brain hypothermia beginning at different time intervals on brain endogenous antioxidant enzyme and energy metabolites was investigated in a model of global cerebral ischemia.Methods Forty-eight male Sprague-Dawley rats were divided into a sham-operated group,a normothermia (37℃-38℃) ischemic group and a mild hypothermic (31℃-32℃) ischemia groups.Rats in the last group were subdivided into four groups:240 minutes of hypothermia,30 minutes of normothermia plus 210 minutes of hypothermia,60 minutes of normothermia plus 180 minutes of hypothermia and 90 minutes of normothermia plus 150 minutes of hypothermia (n=8).Global cerebral ischemia was established using the Pulsinelli four-vessel occlusion model for 20minutes and mild hypothermia was applied after 20 minutes of ischemia.Brain.tissue was collected following 20 minutes of cerebral ischemia and 240 minutes of reperfusion,and used to measure the levels of superoxide dismutase (SOD),glutathione peroxidase (GSH-Px),reduced glutathione (GSH) and adenosine triphosphate (ATP).Results Mild hypothermia that was started within 0 to 60 minutes delayed the consumption of SOD,GSH-Px,GSH,and ATP (P <0.05 or P <0.01) in ischemic tissue,as compared to a normothermic ischemia group.In contrast,mild hypothermia beginning at 90 minutes had little effect on the levels of SOD,GSH-Px,GSH,and ATP (P>0.05).Conclusions Postischemic mild brain hypothermia can significantly delay the consumption of endogenous antioxidant enzymes and energy metabolites,which are critical to the process of cerebral protection by mild hypothermia.These results show that mild hypothermia limits ischemic injury if started within 60 minutes,but loses its protective effects when delayed until 90 minutes following cerebral ischemia.

  14. Expression of somatostatin mRNA and peptide in rat hippocampus after cerebral ischemia

    DEFF Research Database (Denmark)

    Bering, Robert; Johansen, Flemming Fryd

    1993-01-01

    Somatostatin, ischemia, hippocampus, rat, in situ hybridisation, immunocytochemistry, neuropathology......Somatostatin, ischemia, hippocampus, rat, in situ hybridisation, immunocytochemistry, neuropathology...

  15. Pharmacological Neuroprotection after Perinatal Hypoxic-Ischemic Brain Injury

    NARCIS (Netherlands)

    Fan, Xiyong; Kavelaars, Annemieke; Heijnen, Cobi J.; Groenendaal, Floris; van Bel, Frank

    2010-01-01

    Perinatal hypoxia-ischemia (HI) is an important cause of neonatal brain injury. Recent progress in the search for neuroprotective compounds has provided us with several promising drugs to reduce perinatal HI-induced brain injury. In the early stage (first 6 hours after birth) therapies are concentra

  16. Insults to the Developing Brain and Impact on Neurodevelopmental Outcome

    Science.gov (United States)

    Adams-Chapman, Ira

    2009-01-01

    Premature infants have a disproportionately increased risk for brain injury based on several mechanisms including intraventricular hemorrhage, ischemia and the vulnerability of developing neuronal progenitor cells. Injury to the developing brain often results in neurologic abnormalities that can be correlated with a structural lesion; however more…

  17. 宫内亚临床感染对缺氧缺血性脑损伤新生大鼠的增敏作用及其与表观遗传的关系%Intrauterine subclinical inflammation sensitive to hypoxic-ischemia brain damage in newborn rats and the epigenetic relationship

    Institute of Scientific and Technical Information of China (English)

    徐发林; 王彩红; 张彦华; 段佳佳; 郭佳佳; 邢秋景; 董慧芳; 李文丽

    2015-01-01

    目的 探讨宫内亚临床感染、出生后缺氧缺血(HI)单独及联合作用对未成熟脑发育的影响,未成熟脑损伤后组蛋白去乙酰化酶(HDACs)及HDAC1 mRNA的表达及其意义,促红细胞生产素(EPO)对未成熟大鼠脑白质损伤的保护作用.方法 孕鼠分为脂多糖(LPS)组和9g/L盐水(NS)组,于孕15 d分别腹腔注射LPS 0.3 mg/kg或等剂量NS,继续饲养至分娩,称取出生体质量.待新生大鼠5日龄时随机数字表法分为对照组、LPS组、HI组、LPS+ HI组,干预组分LPS+ HI+ NS组和LPS+ HI+ EPO组,分别于HI后6h、24 h及7d灌注取脑.酶联免疫吸附法检测脑组织中肿瘤坏死因子(TNF-α)及HDACs水平;免疫组织化学法检测微管相关蛋白-2(MAP-2)染色情况及HI后7d脑组织碱性髓鞘蛋白(MBP)的表达;实时荧光定量PCR方法检测MAP-2 mRNA及HDAC1 mRNA表达.结果 LPS+ HI组TNF-α、HDACs及HDAC1 mRNA表达水平最高,MBP表达水平最低,与其他组比较差异有统计学意义(F =60.20,P<0.05),另3组之间差异无统计学意义(P>0.05);LPS+ HI+ EPO组MBP水平[积分光密度(IOD)值:131.59 ±2.24]明显高于LPS+ HI+ NS组(IOD值:103.36±3.62),差异有统计学意义(=16.24,P<0.05).LPS+ HI组MAP-2免疫组织化学染色在HI后24 h显示散在坏死灶,余3组均未出现坏死灶.LPS+ HI组MAP-2 mRNA损伤后6h表达降低,后逐渐升高,与其他组相比差异均有统计学意义(P均<0.05).结论 宫内亚临床感染对出生后HI具有增敏作用;二者联合作用所导致的未成熟脑神经损伤可致表观遗传学改变.EPO对未成熟脑损伤的脑白质具有保护作用.%Objective To investigate the effects of subclinical intrauterine infection,postnatal hypoxia-ischemia(HI) alone or in combination on the immature brain development,the changes and significance of histone deacetylases(HDACs) and HDAC1 mRNA after brain injury,and the protective effect of erythropoietin (EPO) on white matter injury.Methods Pregnant SD rats were

  18. 右美托咪定对全脑缺血再灌注大鼠血脑屏障通透性的影响%Effect of dexmedetomidine on permeability of blood-brain barrier in rats subjected to global cerbral ischemia-reperfusion

    Institute of Scientific and Technical Information of China (English)

    郭培培; 严虹; 陈璟莉; 吴会生; 袁世荧

    2013-01-01

    Objective To evaluate the effects of dexmedetomidine on the permeability of blood-brain barrier in rats subjected to global cerebral ischemia-reperfusion (I/R).Methods Thirty-six male Sprague-Dawley rats,weighing 250-300 g,were randomly divided into 3 groups (n =12 each):sham operation group (group S),global cerebral I/R group (group I/R) and dexmedetomidine group (group D).Global cerebral I/R was induced by occlusion of bilateral common carotid arteries combined with hypotension (MAP was maintained at 35-45 mm Hg) in anesthetized rats.In group D,dexmedetomidine was infused at a rate of 3μg· kg-1 · h-1 until 2 h of reperfusion after a loading dose of dexmedetomidine 3 μg/kg was injected intravenously immediately after onset of I/R.The rats were sacrificed at 24 h of reperfusion and their brains were immediately removed for microscopic examination of hippocampal CA1 region and for determination of the cell apoptosis,brain water content,Evans blue content and aquaporin 4 (AQP4) expression.Results The number of apoptotic cells was significantly larger,and brain water content,Evans blue content and AQP4 expression were higher in groups I/R and D than in group S (P < 0.05 or 0.01).The number of apoptotic cells was significantly smaller,and brain water content,and Evans blue content and AQP4 expression were lower in group D than in group I/R (P < 0.05 or 0.01).Global cerebral I/R-induced pathological changes were significantly attenuated in group D.Conclusion Dexmedetomidine can decrease the permeability of blood-brain barrier and attenuate global cerebral I/R injury in rats,and down-regulation of AQP4 expression may be involved in the mechanism.%目的 评价右美托咪定对全脑缺血再灌注大鼠血脑屏障通透性的影响.方法 成年雄性SD大鼠36只,体重250 ~ 300 g,采用随机数字表法,将其分为3组(n=12):假手术组(S组)、全脑缺血再灌注组(I/R组)和右美托咪定组(D组).采用夹闭双侧颈总动脉联合低血压法

  19. 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.

  20. Promoting neurogenesis via Wnt/β-catenin signaling pathway accounts for the neurorestorative effects of morroniside against cerebral ischemia injury.

    Science.gov (United States)

    Sun, Fang-Ling; Wang, Wen; Zuo, Wei; Xue, Jin-Long; Xu, Jing-dong; Ai, Hou-Xi; Zhang, Li; Wang, Xiao-Min; Ji, Xun-Ming

    2014-09-01

    Ischemic stroke is a leading cause of mortality and permanent disability in adults worldwide. Neurogenesis triggered by ischemia in the adult mammalian brain may provide insights into stroke treatment. Morroniside is an active component of sarcocarp of C. officinalis that have shown neuroprotective effects. The aim of the present study is to test whether morroniside promotes neurogenesis via Wnt/β-catenin signaling pathway for brain recovery in a rat model of focal cerebral ischemia. Morroniside was administered intragastrically once daily at the concentrations of 30, 90 and 270 mg/kg for 7 days post-ischemia. Neurological functions were detected by Ludmila Belayev score tests. Endogenous neural stem cells responses were investigated with immunofluorescence staining of Ki-67 and Nestin to identify the neurogenesis in the subventricular zone (SVZ). The expression of proteins involved in and related to Wnt/β-catenin signaling pathway was detected by western blotting analysis. Morroniside significantly promoted neurogenesis for brain recovery 7 days post-ischemia. Increased expression of Wnt 3a, β-catenin and T-cell transcription factor-4 (Tcf-4), along with activation of downstream transcription factors Pax6 and neurogenin2 (Ngn2), indicated that the neurorestorative effects of morroniside may be associated with Wnt/β-catenin signaling pathway. These data provide support for understanding the mechanisms of morroniside in neurorestorative effects and suggest a potential new strategy for ischemic stroke treatment. PMID:24876057

  1. [Programmed necrosis: a new target for
ischemia reperfusion injury].

    Science.gov (United States)

    Li, Xiaojing; Ming, Yingzi; Niu, Ying; Liu, Qianwen; Ye, Qifa

    2016-07-01

    Recent years, the researchers have found a new type of cell death, referred to programmed necrosis or necroptosis, which involves the death receptor and the ligand binds and is initiated under the inhibition of apoptosis pathway. Programmed necrosis possesses the morphological features of typical necrosis accompanied by inflammation. The receptor interacting protein kinase 1/3(RIPK1/3) can be inhibited by the specific inhibitors, such as necrostatin-1. RIPK1/3 could regulate programmed necrosis and play a key role in the process. The significance of programmed necrosis in ischemia-reperfusion injury (IRI) has been attracted great attention at present. Simultaneously, a series of studies have found it also involves in the IRI of heart, kidney, brain and retina. PMID:27592584

  2. Diagnosis of acute cardiac ischemia.

    Science.gov (United States)

    Pope, J Hector; Selker, Harry P

    2003-02-01

    A better understanding of coronary syndromes allow physicians to appreciate UAP and AMI as part of a continuum of ACI. ACI is a life-threatening condition whose identification can have major economic and therapeutic importance as far as threatening dysrhythmias and preventing or limiting myocardial infarction size. The identification of ACI continues to challenge the skill of even experienced clinicians, yet physicians continue (appropriately) to admit the overwhelming majority of patients with ACI; in the process, they admit many patients without acute ischemia [2], overestimating the likelihood of ischemia in low-risk patients because of magnified concern for this diagnosis for prognostic and therapeutic reasons. Studies of admitting practices from a decade ago have yielded useful clinical information but have shown that neither clinical symptoms nor the ECG could reliably distinguish most patients with ACI from those with other conditions. Most studies have evaluated the accuracy of various technologies for diagnosing ACI, yet only a few have evaluated the clinical impact of routine use. The prehospital 12-lead ECG has moderate sensitivity and specificity for the diagnosis of ACI. It has demonstrated a reduction of the mean time to thrombolysis by 33 minutes and short-term overall mortality in randomized trials. In the general ED setting, only the ACI-TIPI has demonstrated, in a large-scale multicenter clinical trial, a reduction in unnecessary hospitalizations without decreasing the rate of appropriate admission for patients with ACI. The Goldman chest pain protocol has good sensitivity for AMI but was not shown to result in any differences in hospitalization rate, length of stay, or estimated costs in the single clinical impact study performed. The protocol's applicability to patients with UAP has not been evaluated. Single measurement of biomarkers at presentation to the ED has poor sensitivity for AMI, although most biomarkers have high specificity. Serial

  3. The effect of mitochondrial calcium uniporter on mitochondrial fission in hippocampus cells ischemia/reperfusion injury

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Lantao; Li, Shuhong; Wang, Shilei, E-mail: wshlei@aliyun.com; Yu, Ning; Liu, Jia

    2015-06-05

    The mitochondrial calcium uniporter (MCU) transports free Ca{sup 2+} into the mitochondrial matrix, maintaining Ca{sup 2+} homeostasis, thus regulates the mitochondrial morphology. Previous studies have indicated that there was closely crosstalk between MCU and mitochondrial fission during the process of ischemia/reperfusion injury. This study constructed a hypoxia reoxygenation model using primary hippocampus neurons to mimic the cerebral ischemia/reperfusion injury and aims to explore the exactly effect of MCU on the mitochondrial fission during the process of ischemia/reperfusion injury and so as the mechanisms. Our results found that the inhibitor of the MCU, Ru360, decreased mitochondrial Ca{sup 2+} concentration, suppressed the expression of mitochondrial fission protein Drp1, MIEF1 and Fis1, and thus improved mitochondrial morphology significantly. Whereas spermine, the agonist of the MCU, had no significant impact compared to the I/R group. This study demonstrated that the MCU regulates the process of mitochondrial fission by controlling the Ca{sup 2+} transport, directly upregulating mitochondrial fission proteins Drp1, Fis1 and indirectly reversing the MIEF1-induced mitochondrial fusion. It also provides new targets for brain protection during ischemia/reperfusion injury. - Highlights: • We study MCU with primary neuron culture. • MCU induces mitochondrial fission. • MCU reverses MIEF1 effect.

  4. The clinical relevance of cerebral microbleeds in patients with cerebral ischemia and atrial fibrillation.

    Science.gov (United States)

    Haji, Shamir; Planchard, Ryan; Zubair, Adeel; Graff-Radford, Jonathan; Rydberg, Charlotte; Brown, Robert D; Flemming, Kelly D

    2016-02-01

    The clinical significance of cerebral microbleeds (CMB) in patients hospitalized with atrial fibrillation (AF) and cerebral ischemia is unclear. We aimed to determine the prevalence of CMB in this population and determine the future risk of intracerebral hemorrhage (ICH) and cerebral infarction (CI). The medical records and brain imaging of patients hospitalized with cerebral ischemia due to AF between 2008 and 2011 were reviewed. Followup was obtained through medical record review, mailed survey, and acquisition of death certificates. Prevalence was calculated from those patients with a hemosiderin-sensitive MRI sequence. Recurrent CI and ICH were calculated using Kaplan-Meier curves censored at 3 years. Among 426 patients hospitalized with cerebral ischemia due to AF, 134 had an MRI with hemosiderin-sensitive sequences. The prevalence of CMB was 27.6%. At 3 years, 90.6% of CMB-negative patients were overall stroke free (ICH and CI) compared to 78.6% CMB-positive patients (p = 0.0591). Only one patient in the CMB-positive group had an ICH distant to the CMB. There was a nonsignificant trend toward higher recurrent CI, recurrent overall stroke rate, and mortality in patients with 5 or more CMB compared to 0-4 CMB. The rate of prospective CI in patients with prior cerebral ischemia due to AF is higher than the rate of ICH in patients with CMB. Further study is warranted to assess larger numbers of patients to determine appropriate antithrombotic use in this high-risk population.

  5. The effect of mitochondrial calcium uniporter on mitochondrial fission in hippocampus cells ischemia/reperfusion injury.

    Science.gov (United States)

    Zhao, Lantao; Li, Shuhong; Wang, Shilei; Yu, Ning; Liu, Jia

    2015-06-01

    The mitochondrial calcium uniporter (MCU) transports free Ca(2+) into the mitochondrial matrix, maintaining Ca(2+) homeostasis, thus regulates the mitochondrial morphology. Previous studies have indicated that there was closely crosstalk between MCU and mitochondrial fission during the process of ischemia/reperfusion injury. This study constructed a hypoxia reoxygenation model using primary hippocampus neurons to mimic the cerebral ischemia/reperfusion injury and aims to explore the exactly effect of MCU on the mitochondrial fission during the process of ischemia/reperfusion injury and so as the mechanisms. Our results found that the inhibitor of the MCU, Ru360, decreased mitochondrial Ca(2+) concentration, suppressed the expression of mitochondrial fission protein Drp1, MIEF1 and Fis1, and thus improved mitochondrial morphology significantly. Whereas spermine, the agonist of the MCU, had no significant impact compared to the I/R group. This study demonstrated that the MCU regulates the process of mitochondrial fission by controlling the Ca(2+) transport, directly upregulating mitochondrial fission proteins Drp1, Fis1 and indirectly reversing the MIEF1-induced mitochondrial fusion. It also provides new targets for brain protection during ischemia/reperfusion injury.

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

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

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

  7. 跑台运动训练对脑缺血损伤大鼠热休克蛋白70及C-MYC表达的影响%Effects of treadmill training on the expression of HSP70 and C-MYC in the brains of rats with focal cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    刘德山; 刘楠; 张逸仙; 杜厚伟; 陈荣华

    2010-01-01

    目的 探讨跑台运动训练对局灶性脑缺血大鼠神经功能恢复和脑缺血组织中热休克蛋白70(HSP70)及C-MYC表达的影响.方法 将42只清洁级成年雄性SD大鼠分为假手术组6只、模型组18只、运动组18只.模型组、运动组大鼠采用改良的Longs线栓法制备大脑中动脉闭塞(MCAO)脑缺血模型,运动组于造模成功后24 h采用跑台训练器进行运动训练,每周6 d,共2周,其余2组则置于普通笼内饲养,期间可自由活动、进食.采用修正的神经行为学评分方法评价模型组和运动组大鼠MCAO脑缺血后第3,7,14天的神经功能,并断头取脑,采用逆转录-多聚酶链反应(RT-PCR)法、免疫组织化学和Western blot法检测脑缺血组织中HSP70、C-MYC的表达.结果 运动组大鼠脑缺血第7,14天神经功能评分均明显优于模型组(P<0.05或0.01);运动组大鼠脑缺血第7,14天HSF70和C-MYC表达较模型组增强(P<0.05或0.01).结论 运动训练可促进脑缺血大鼠神经功能恢复,其机制可能与上调脑缺血组织中HSP70及C-MYC表达有关.%Objective To observe the effects of treadmill training on the recovery of neurological function and the expression of HSP70 and C-MYC in the brains of rats with focal cerebral ischemia. Methods Forty-two male adult Sprague-Dawley rats were randomly divided into a sham group ( n =6), a model group (n =18) and a treadmill exercise group (n=18). Focal cerebral ischemia was induced by right middle cerebral artery occlusion (MCAO) in the model group and exercise group using a modified version of Longa's method. The rats in the treadmill exercise group were given treadmill training 6 d per week for 2 weeks after 24 h of MCAO. By contrast, the rats in the sham group and the model group were reared in standard cages. Before the rats were sacrificed at the 3rd, 7th and 14th d after MCAO, their neurological functions were tested using modified neurological severity scores ( mNSS) , and the mRNA and

  8. Effects of treadmill training on the expression of Insulin-like growth factor-1 and its receptor in the brain of rats with focal cerebral ischemia%跑台运动训练对脑缺血损伤大鼠胰岛素样生长因子-1及其受体表达的影响

    Institute of Scientific and Technical Information of China (English)

    张逸仙; 刘楠; 杜厚伟; 陈荣华; 王杰华; 林克旭

    2009-01-01

    目的 探讨跑台运动训练对局灶性脑缺血大鼠神经功能恢复和脑缺血组织中胰岛素样生长因子-1(IGF-1)及其受体(IGF-1R)表达的影响.方法 42只清洁级成年雄性SD大鼠,随机分为假手术组(n=6)、模型组(n=18)和运动组(n=18).模型组、运动组大鼠采用改良的Longa线栓法制备大脑中动脉闭塞(MCAO)脑缺血模型.运动组于造模成功后24 h采用跑台训练器进行运动训练,每周6 d.共4周;其余2组则置于普通笼内饲养,期间可自由活动、进食.采用修正的神经行为学评分方法评价模型组和运动组大鼠MCAO术后第7,14,28天的神经功能,并断头取脑,采用逆转录多聚酶链式反应(RT-PCR)法和免疫组织化学方法检测脑缺血组织中IGF-1、IGF-1R的表达.结果 运动组大鼠术后14,28 d神经功能评分均明显优于模型组(P<0.01和P<0.05);运动组大鼠术后7,14,28 d,IGF-1、IGF-1R表达较模型组明显增强(P<0.05或P<0.01).结论 运动训练可促进脑缺血大鼠神经功能恢复,其机制可能与上调脑缺血组织中IGF-1、IGF-1R表达有关.%Objective To study the effects of treadmill training on the recovery of neurological function and the expression of IGF-1/IGF-1Rin the brain poat focal cerebral ischemia.Metheods Forty-two male,adult Sprague-Dawley rats were randomly divided into a sham group(n=6),a model group(n=18)and a treadmill exercises group(n=18).Focal cerebral ischemia was induced in the latter two groups by right middle cerebral artery occlusion(MCAO)using a modified Longa's metheod.The rats in the treadmill exercises group were given treadmill training 6 days a week for 4weeks beginning 24 h after the MCAO. Rats in the sham group and model groups were reared in standard cages and could move frddly. Before being sacrificed at the 7th 14th and 28th day after the MCAO,the rats' neurological function were tested giving modified neurological weverity scores (mNSS). The expression of IGF-1/IGF-1R

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

    Directory of Open Access Journals (Sweden)

    Max Winerdal

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

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

    Science.gov (United States)

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

    2011-04-18

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

  11. Assessment of Renal Ischemia By Optical Spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Fitzgerald, J T; Demos, S; Michalopoulou, A; Pierce, J L; Troppmann, C

    2004-01-07

    Introduction: No reliable method currently exists for quantifying the degree of warm ischemia in kidney grafts prior to transplantation. We describe a method for evaluating pretransplant warm ischemia time using optical spectroscopic methods. Methods: Lewis rat kidney vascular pedicles were clamped unilaterally in vivo for 0, 5, 10, 20, 30, 60, 90 or 120 minutes; 8 animals were studied at each time point. Injured and contra-lateral control kidneys were then flushed with Euro-Collins solution, resected and placed on ice. 335 nm excitation autofluorescence as well as cross polarized light scattering images were taken of each injured and control kidney using filters of various wavelengths. The intensity ratio of the injured to normal kidneys was compared to ischemia time. Results: Autofluorescence intensity ratios through a 450 nm filter and light scattering intensity ratios through an 800 nm filter both decreased significantly with increasing ischemia time (p < 0.0001 for each method, one-way ANOVA). All adjacent and non-adjacent time points between 0 and 90 minutes were distinguishable using one of these two modalities by Fisher's PLSD. Conclusions: Optical spectroscopic methods can accurately quantify warm ischemia time in kidneys that have been subsequently hypothermically preserved. Further studies are needed to correlate results with physiological damage and posttransplant performance.

  12. CLINICAL EXPERIENCE WITH METABOLIC THERAPY FOR BRAIN ISCHEMIA

    Directory of Open Access Journals (Sweden)

    M. Kh. Shurdumova

    2013-01-01

    Full Text Available The paper describes clinical experience with metabolic therapy, including neuroprotective drugs and antioxidants, for cerebrovascular diseases.It gives the results of basic Russian and foreign clinical studies of ethylmethylhydroxypyridoxine succinate and choline alfoscerate and discusses their efficacy and routes of administration.

  13. CLINICAL EXPERIENCE WITH METABOLIC THERAPY FOR BRAIN ISCHEMIA

    Directory of Open Access Journals (Sweden)

    M. Kh. Shurdumova

    2014-07-01

    Full Text Available The paper describes clinical experience with metabolic therapy, including neuroprotective drugs and antioxidants, for cerebrovascular diseases.It gives the results of basic Russian and foreign clinical studies of ethylmethylhydroxypyridoxine succinate and choline alfoscerate and discusses their efficacy and routes of administration.

  14. Time-dependent changes of glial fibriliary acidic protein and cytosolic phospholipase A2 in hippocampal area of focal cerebral ischemia/reperfusion in rats

    Institute of Scientific and Technical Information of China (English)

    Qingzhou Cheng; Xingui Ming

    2006-01-01

    /reperfusion.RESULTS: All 28 rats were involved in the final analysis without any loss. ① Animal models successfully showed the effect of focal cerebral ischemia. ② Changes of GFAP and cPLA2 in hippocampal area in various phases: Two hours after ischemia/reperfusion, changes of GFAP and cPLA2 were increased gradually,reached at peak at 24 hours, and decreased gradually.CONCLUSION: Courses of GFAP and cPLA2 are changed at the onset of focal cerebral ischemia, and this suggests that both of them participate in injury or protection of brain tissue of focal cerebral ischemia.

  15. Effects of rhEPO on expression of TNF-α,MMP-9 and Ang-2 in brain tissues of rats with acute cerebral ischemia%重组人促红细胞生成素对大鼠急性脑缺血脑组织中肿瘤坏死因子-α基质金属蛋白酶-9和血管生成素-2表达的影响

    Institute of Scientific and Technical Information of China (English)

    严澎; 郭军红

    2011-01-01

    Objective To explore the neuroprotective effects and mechanism of recombinant human erythropoietin (rhEPO) on acute focal cerebral ischemic injury in Sprague-Dawley rats.Methods Fifty-four healthy male SD rats were randomized into sham-operated group, model group and rhEPO treatment group.Suture method was used to establish permanent middle cerebral artery occlusion (pMCAO) model.rhEPO treatment group underwent intraperitoneal injection of 4000 U/kg rhEPO after ischemia for 2 hours, whereas model group and sham-operated group were given equivalent saline at the same time.All rats were decapitated after ischemia for 24 hours, and water contents in the brain tissues were measured by dry-wet weight method.The size of infarction was measured by TTC staining (2,3,5- triphenyl tetrazolium chloride), and the expression of tumor necrosis factor (TNF-α), matrix metalloproteinase-9 (MMP-9) and angiopoietin-2 (Aug-2) were detected by immunohistochemistry.Results Compared with the model group, rhEPO treatment group showed diminished brain tissue water contents, smaller infarction size and lowered expressions of TNF-α and MMP-9 but elevated expression of Ang-2 (P<O.05).Conclusion Recombinant human EPO may be neuroprotective against acute cerebral ischemia in rats, probably by inhibiting the activities of TNF-α and MMP-9 and enhancing expression of Aug-2.%目的 探讨重组人促红细胞生成素(rhEPO)对大鼠急性局灶性脑缺血损伤的神经保护作用及其机制.方法 健康雄性SD大鼠54只随机分为假手术组、模型组和rhEPO治疗组.采用线栓法制作大鼠永久性局灶性脑缺血(pMCAO)模型.rhEPO治疗组在缺血2 h后腹腔注射rhEPO 4000 U/kg,模型组和假手术组在等时间点给予等量的生理盐水.缺血24 h后断头取脑分别用干湿质量法计算脑组织含水量,2,3,5-氯化二苯基四氮唑(TTC)法测量脑梗死体积,免疫组织化学方法测定肿瘤坏死因子-α(TNF-α)、基质金属蛋白酶-9(MMP-9)

  16. The role of neutrophil in the cerebral injury of ischemia/reperfused diabetic rats%糖尿病大鼠缺血再灌注损伤中性白细胞的作用

    Institute of Scientific and Technical Information of China (English)

    王文安; 任惠民; 吕传真

    2002-01-01

    Objective To explore the role of neutrophil in focal cerebral injury of ischemia/reperfused diabetic rats.Methods The infarction size in diabetic and non diabetic rats with ischemia for 1h/reperfusion for 24 h was evaluated by 2,3,5 triphenyl tetrazolium chloride (TTC) staining.The magnitude of cerebral neutrophil infiltration was quantified by measuring myeloperoxidase (MPO) activity of brain tissue in all rats with ischemia for 1h/ reperfused various periods by the method of enzymology.Results The infarction size in the ipsilateral hemisphere of diabetic rats were more significant than that in the normal rats (P< 0.05).The activity of myeloperoxidase (MPO) in the former was also higher than that in the latter (P< 0.05).Conclusions Diabetes could exacerbate inflammatory response to cerebral ischemia reperfusion and thereby aggravate cerebral injury of ischemia/reperfusion.

  17. Magnetic resonance spectroscopy and imaging in cerebral ischemia

    International Nuclear Information System (INIS)

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

  18. The Effect of Prenatal Hypoxia on Brain Development: Short- and Long-Term Consequences Demonstrated in Rodent Models

    Science.gov (United States)

    Golan, Hava; Huleihel, Mahmoud

    2006-01-01

    Hypoxia (H) and hypoxia-ischemia (HI) are major causes of foetal brain damage with long-lasting behavioral implications. The effect of hypoxia has been widely studied in human and a variety of animal models. In the present review, we summarize the latest studies testing the behavioral outcomes following prenatal hypoxia/hypoxia-ischemia in rodent…

  19. Salvianolate increases heat shock protein expression in a cerebral ischemia-reperfusion injury model

    Institute of Scientific and Technical Information of China (English)

    Jinnan Zhang; Wei Lu; Qiang Lei; Xi Tao; Hong You; Pinghui Xie

    2013-01-01

    Stroke remains a worldwide health problem. Salvianolate exerts a protective effect in various mi-crocirculatory disturbance-related diseases, but studies of the mechanisms underlying its protective action have mainly focused on the myocardium, whereas little research has been carried out in brain tissue fol owing ischemia-reperfusion. We assessed the neuroprotective effects of salvianolate in a rat model of cerebral ischemia-reperfusion injury induced using the suture method. At onset and 24 and 48 hours after reperfusion, rats were intraperitoneal y injected with salvianolate (18 mg/kg) or saline. Neurological deficit scores at 72 hours showed that the neurological functions of rats that had received salvianolate were significantly better than those of the rats that had received saline. 2,3,5-Triphenyltetrazolium chloride was used to stain cerebral tissue to determine the extent of the infarct area. A significantly smal er infarct area and a significantly lower number of apoptotic cel s were observed after treatment with salvianolate compared with the saline treatment. Expression of heat shock protein 22 and phosphorylated protein kinase B in ischemic brain tissue was significantly greater in rats treated with salvianolate compared with rats treated with saline. Our findings suggest that salvianolate provides neuroprotective effects against cerebral ischemia-reperfusion injury by upregulating heat shock protein 22 and phosphorylated protein kinase B expression.

  20. Neuroprotective effect of pentosan polysulphate on ischemia-related neuronal death of the hippocampus.

    Science.gov (United States)

    Sakurai-Yamashita, Yasuko; Kinugawa, Hidekazu; Niwa, Masami

    2006-11-27

    Pentosan polysulphate (PPS) negatively charged sulphated glycosaminoglycan was studied in ischemia-related hippocampal neuronal death and compared with a low molecular weight of heparin, named dalteparin in rats. Transient global ischemia was produced by four vessel-occlusion, the occlusion of the bilateral common carotid arteries following the electrocautherization of the vertebral arteries. 3mg/kg of PPS or 300IU/kg of dalteparin was administered i.v. immediately after 7min-occlusion/reperfusion. Seven days after the operation, the animals were perfused with 4% paraformaldehyde, and paraffinized coronal brain sections measuring 6microm in thickness were stained with hematoxylin and eosin. Neuronal damage was then estimated as a ratio of the number of degenerated neurons to that of both the surviving and degenerated neurons in three distinct area of the CA1 subfield. The ratio of neuronal death increased with the length of the occlusion-time, at 5, 7 and 10min. Both PPS and dalteparin significantly inhibited the neuronal damage induced by 7min-occlusion. These results demonstrated that both PPS and dalteparin could thus protect brain neurons against ischemia/reperfusion-induced damage thus suggesting that they may be potentially useful therapeutic agents for acute ischemic stroke. PMID:17011126

  1. Neuroprotective effect of pentosan polysulphate on ischemia-related neuronal death of the hippocampus.

    Science.gov (United States)

    Sakurai-Yamashita, Yasuko; Kinugawa, Hidekazu; Niwa, Masami

    2006-11-27

    Pentosan polysulphate (PPS) negatively charged sulphated glycosaminoglycan was studied in ischemia-related hippocampal neuronal death and compared with a low molecular weight of heparin, named dalteparin in rats. Transient global ischemia was produced by four vessel-occlusion, the occlusion of the bilateral common carotid arteries following the electrocautherization of the vertebral arteries. 3mg/kg of PPS or 300IU/kg of dalteparin was administered i.v. immediately after 7min-occlusion/reperfusion. Seven days after the operation, the animals were perfused with 4% paraformaldehyde, and paraffinized coronal brain sections measuring 6microm in thickness were stained with hematoxylin and eosin. Neuronal damage was then estimated as a ratio of the number of degenerated neurons to that of both the surviving and degenerated neurons in three distinct area of the CA1 subfield. The ratio of neuronal death increased with the length of the occlusion-time, at 5, 7 and 10min. Both PPS and dalteparin significantly inhibited the neuronal damage induced by 7min-occlusion. These results demonstrated that both PPS and dalteparin could thus protect brain neurons against ischemia/reperfusion-induced damage thus suggesting that they may be potentially useful therapeutic agents for acute ischemic stroke.

  2. Protective Effect Of Bosentan In Experimental Cerebral Ischemia-Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Eser Ataş

    2013-02-01

    Full Text Available OBJECTIVE: In cerebral ischemia, there are many factors that start the events leading to cell death. These factors contain free radical production, excitotoxicity, sodium and calcium flow disruption, enzymatic changes, stimulation of the inflamatuar process, the activation of platelets and leukocytes, delayed coagulation, endothelial dysfunction and endothelin (ET release. Bosentan is the competitive antagonist of endothelin receptors; ETA and ETB. The aim of this study is to determine whether the protective effects of bosentan in experimental cerebral ischemia reperfusion injury. MATERIAL and METHODS: In this study, after ischemia-reperfusion procedure, bosentan molecule was regularly given to rats for 5 days. The brain tissues of decapitated rats were histopathologically examined. The levels of oxidant and antioxidant were determined in these brain tissues. RESULTS: It was observed that antioxidant levels and histopathological examinations were in rats given bosentan better than control group rats. CONCLUSION: In conclusion, this study has showed that bosentan may be an agent which could reduce negative effects resulting from neuronal death associated with ischemic stroke.

  3. 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.

  4. Effects of treadmill training on toll-like receptor 2 and toll-like receptor 4 signaling pathway in brain ischemia-reperfusion area of rats after cerebral infarction%跑台训练对大鼠脑缺血再灌注后脑组织toll样受体2、toll样受体4信号转导通路活性的影响

    Institute of Scientific and Technical Information of China (English)

    马跃文; 何曼; 强琳

    2013-01-01

    To study the effects of treadmill training on the recovery of neurological function and expressions of toll-like receptor 2(TLR2), toll-like receptor 4(TLR4),nuclear factor-KB(NF-KB) and myeloid differentiation fac-tor88(MyD88) in brain ischemia-reperfusion area of rats after cerebral ischemia-reperfusion. Method: The brain ischemia-reperfusion rats model was made by middle cerebral artery occulusion (MCAO) with ZeaLonga thread embolism method. A total of 35 male Wistar rats were randomly divided into sham operation group (SH group), operation+treadmill running group(O+TR group) and the operation control group(OC group) randomly. O+TR group and OC group were divided into three sub-groups respectively by different observation time points: 3rdd, 7thd and 14thd 5 rats in each subgroup. O + TR group was given treadmill training after the 3th d post-operation, Neurological function was measured before the operation, at the 3rd d, 7thd and 14thd after the beginning of exercise respectively. After measurement the rats were sacrificed, RT-PCR and Western-blot techniques were used to detect the expressions of TLR2, TLR4, NF- K B and MyD88 in the ischemic brain at the 3rd d, 7th d and 14th d Result: Compared with those in OC groups, the behavioral outcome in O+TR group was much better at the 3rd d, 7thd and 14thd(P<0.05). O + TR group and OC group had obvious higher expression level of TLR2,TLR4,MyD88 and NF-KB as compared to SH group, especially in 3d subgroup (P<0.05). However, after 3d, 7d and 14d of treadmill training, expression attenuation of messenger RNA of TLR2,TLR4,MyD88 and NF-KB took place significantly in O+TR group compared to OC group(P<0.05).Conclusion: The over--expressions of TLR2、TLR4、NF-κB、MyD88 in brain ischemic area can be lessened through treadmill training. Movement therapy promotes recovery of neurological function maybe by reducing TLR2 and TLR4 related inflammatory reaction after cerebral ischemia injury.%目的:探讨跑台训练对大鼠

  5. 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.

  6. Exogenous Nitric Oxide Protects Human Embryonic Stem Cell-Derived Cardiomyocytes against Ischemia/Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    János Pálóczi

    2016-01-01

    Full Text Available Background and Aims. Human embryonic stem cell- (hESC- derived cardiomyocytes are one of the useful screening platforms of potential cardiocytoprotective molecules. However, little is known about the behavior of these cardiomyocytes in simulated ischemia/reperfusion conditions. In this study, we have tested the cytoprotective effect of an NO donor and the brain type natriuretic peptide (BNP in a screening platform based first on differentiated embryonic bodies (EBs, 6 + 4 days and then on more differentiated cardiomyocytes (6 + 24 days, both derived from hESCs. Methods. Both types of hESC-derived cells were exposed to 150 min simulated ischemia, followed by 120 min reperfusion. Cell viability was assessed by propidium iodide staining. The following treatments were applied during simulated ischemia in differentiated EBs: the NO-donor S-nitroso-N-acetylpenicillamine (SNAP (10−7, 10−6, and 10−5 M, BNP (10−9, 10−8, and 10−7 M, and the nonspecific NO synthase inhibitor Nω-nitro-L-arginine (L-NNA, 10−5 M. Results. SNAP (10−6, 10−5 M significantly attenuated cell death in differentiated EBs. However, simulated ischemia/reperfusion-induced cell death was not affected by BNP or by L-NNA. In separate experiments, SNAP (10−6 M also protected hESC-derived cardiomyocytes. Conclusions. We conclude that SNAP, but not BNP, protects differentiated EBs or cardiomyocytes derived from hESCs against simulated ischemia/reperfusion injury. The present screening platform is a useful tool for discovery of cardiocytoprotective molecules and their cellular mechanisms.

  7. Exogenous Nitric Oxide Protects Human Embryonic Stem Cell-Derived Cardiomyocytes against Ischemia/Reperfusion Injury

    Science.gov (United States)

    Pálóczi, János; Varga, Zoltán V.; Szebényi, Kornélia; Sarkadi, Balázs; Madonna, Rosalinda; De Caterina, Raffaele; Csont, Tamás; Eschenhagen, Thomas; Ferdinandy, Péter; Görbe, Anikó

    2016-01-01

    Background and Aims. Human embryonic stem cell- (hESC-) derived cardiomyocytes are one of the useful screening platforms of potential cardiocytoprotective molecules. However, little is known about the behavior of these cardiomyocytes in simulated ischemia/reperfusion conditions. In this study, we have tested the cytoprotective effect of an NO donor and the brain type natriuretic peptide (BNP) in a screening platform based first on differentiated embryonic bodies (EBs, 6 + 4 days) and then on more differentiated cardiomyocytes (6 + 24 days), both derived from hESCs. Methods. Both types of hESC-derived cells were exposed to 150 min simulated ischemia, followed by 120 min reperfusion. Cell viability was assessed by propidium iodide staining. The following treatments were applied during simulated ischemia in differentiated EBs: the NO-donor S-nitroso-N-acetylpenicillamine (SNAP) (10−7, 10−6, and 10−5 M), BNP (10−9, 10−8, and 10−7 M), and the nonspecific NO synthase inhibitor Nω-nitro-L-arginine (L-NNA, 10−5 M). Results. SNAP (10−6, 10−5 M) significantly attenuated cell death in differentiated EBs. However, simulated ischemia/reperfusion-induced cell death was not affected by BNP or by L-NNA. In separate experiments, SNAP (10−6 M) also protected hESC-derived cardiomyocytes. Conclusions. We conclude that SNAP, but not BNP, protects differentiated EBs or cardiomyocytes derived from hESCs against simulated ischemia/reperfusion injury. The present screening platform is a useful tool for discovery of cardiocytoprotective molecules and their cellular mechanisms. PMID:27403231

  8. TRPM7 in cerebral ischemia and potential target for drug development in stroke

    Institute of Scientific and Technical Information of China (English)

    Christine You-Jin BAE; Hong-shuo Sun

    2011-01-01

    Searching for effective pharmacological agents for stroke treatment has largely been unsuccessful. Despite initial excitement, antagonists for glutamate receptors, the most studied receptor channels in ischemic stroke, have shown insufficient neuroprotective effects in clinical trials. Outside the traditional glutamate-mediated excitotoxicity, recent evidence suggests few non-glutamate mechanisms,which may also cause ionic imbalance and cell death in cerebral ischemia. Transient receptor potential melastatin 7 (TRPM7) is a Ca2+permeable, non-selective cation channel that has recently gained attention as a potential cation influx pathway involved in ischemic events. Compelling new evidence from an in vivo study demonstrated that suppression of TRPM7 channels in adult rat brain in vivo using virally mediated gene silencing approach reduced delayed neuronal cell death and preserved neuronal functions in global cerebral ischemia. In this review, we will discuss the current understanding of the role of TRPM7 channels in physiology and pathophysiology as well as its therapeutic potential in stroke.

  9. Use of confocal microscopy in the study of ischemia-induced hippocampal neuronal damage

    Directory of Open Access Journals (Sweden)

    Radenović Lidija

    2008-01-01

    Full Text Available The present study was undertaken to reveal by means of confocal laser microscopy the cytoarchitecture of hippocampal CA3 neurons in Mongolian gerbils before and after cerebral ischemia of different duration. The common carotid arteries of gerbils were occluded for 5, 10, or 15 min. On the 4th, 14th and 28th day after reperfusion, neuronal damage was examined by laser scanning confocal microscopy in the CA3 region of hippocampus (30 μm slices. Slices were stained with fluorescent Nissl staining and fluorescent membrane tracer DiI. Increased duration of cerebral ischemia resulted in a progressive loss of hippocampal CA3 neurons. Four days after the ischemic insult, neuronal damage in the hippocampal CA3 region was mild but visible. On the 28th day after reperfusion, neuronal damage in the observed brain structure was most severe. These results demonstrate the temporal profile of neuronal damage after an ischemic insult as observed using confocal microscopy.

  10. Neuroimaging of Ischemia and Infarction

    OpenAIRE

    Sá de Camargo, Erica C.; Koroshetz, Walter J.

    2005-01-01

    Summary: Since the introduction of thrombolytic therapy as the foundation of acute stroke treatment, neuroimaging has rapidly advanced to empower therapeutic decision making. Diffusion-weighted imaging is the most sensitive and accurate method for stroke detection, and, allied with perfusion-weighted imaging, provides information on the functional status of the ischemic brain. It can also help to identify a response to thrombolytic and neuroprotective therapies. Additionally, multimodal magne...

  11. Post-traumatic contrast enhancing brain lesion

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dae Jung; Kim, Hyun Sook; Jeong, Min Sun; Kim, Deok Ryeong; Cho, Young Kwon; Choi, Yun Sun [Eulji Hospital, Eulji University College of Medicine, Seoul (Korea, Republic of)

    2014-10-15

    Only a few studies have been reported on the MR contrast enhancement and the apparent diffusion coefficient (ADC) findings of the post-traumatic lesion of the brain. We report a case of the venous ischemia in the left frontal lobe observed in the MRI obtained one day after the incidence of trauma. Considering the presented slight increase in the ADC, the vasogenic edema was thought to be the major mechanism of the venous ischemia and excitotoxic injury. In spite of a slight increase in the ADC, the hyperintensity in the diffusion weighted imaging and contrast-enhanced areas eventually changed into hemorrhagic lesions.

  12. Dose-dependent effects of procyanidin on nerve growth factor expression following cerebral ischemia/ reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    Feng Li; Hai Xie; Ying Gao; Tongxia Zhan

    2008-01-01

    BACKGROUND: Recently, grape seed procyanidin (GSP) has been shown to be exhibit antioxidant effects, effectively reducing ischemia/reperfusion injury and inhibiting brain cell apoptosis.OBJECTIVE: To study the effects of GSP on nerve growth factor (NGF) expression and neurological function following cerebral ischemia/reperfusion injury in rats.DESIGN: Randomized controlled study based on SD rats.SETTING: Weifang Municipal People's Hospital. MATERIALS: Forty-eight healthy adult SD rats weighing 280-330 g and irrespective of gender were provided by the Experimental Animal Center of Shandong University. GSP derived from grape seed was a new high-effective antioxidant provided by Tianjin Jianfeng Natural Product Researching Company (batch number: 20060107). Rabbit-anti-rat NGF monoclonal antibody was provided by Beijing Zhongshan Biotechnology Co., Ltd., and SABC immunohistochemical staining kit by Wuhan Boster Bioengineering Co., Ltd. METHODS: The present study was performed in the Functional Laboratory of Weifang Medical College from April 2006 to January 2007. Forty-eight SD rats were randomly divided into the sham operation group, ischemia/reperfusion group, high-dose GSP (40 mg/kg) group, or low-dose GSP (10 mg/kg) group (n = 12 per group). Ischemia/reperfusion injury was established using the threading embolism method of the middle cerebral artery. Rats in the ischemia/reperfusion model group were given saline injection (2 mL/kg i.p.) once daily for seven days pre-ischemia/reperfusion, and once more at 15 minutes before reperfusion. Rats in the high-dose and low-dose GSP groups were injected with GSP (20 or 5 mg/mL i.p., respectively, 2 mL/kg) with the same regime as the ischemia/reperfusion model group. The surgical procedures in the sham operation group were as the same as those in the ischemia/reperfusion model group, but the thread was approximately 10 mm long, thus, the middle cerebral artery was not blocked. MAIN OUTCOME MEASURES: NGF expression in the

  13. Neuroprotective effect ofShenqi Fuzheng injection pretreatment in aged rats with cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Ying-min Cai; Yong Zhang; Peng-bo Zhang; Lu-ming Zhen; Xiao-ju Sun; Zhi-ling Wang; Ren-yan Xu; Rong-liang Xue

    2016-01-01

    Shenqi Fuzheng injection is extracted from the Chinese herbsRadix Astragali andRadix Codonopsis. The aim of the present study was to investigate the neuroprotective effects of Shenqi Fuzheng injection in cerebral ischemia and reperfusion. Aged rats (20–22 months) were divided into three groups: sham, model, and treatment.Shenqi Fuzheng injection or saline (40 mL/kg) was injected into the tail vein daily for 1 week, after which a cerebral ischemia/reperfusion injury model was established. Compared with model rats that received saline, rats in the treatment group had smaller infarct volumes, lower brain water and malondialdehyde content, lower brain Ca2+levels, lower ac-tivities of serum lactate dehydrogenase and creatine kinase, and higher superoxide dismutase activity. In addition, the treatment group showed less damage to the brain tissue ultrastructure and better neurological function. Our ifndings indicate thatShenqi Fuzheng injec-tion exerts neuroprotective effects in aged rats with cerebral ischemia/reperfusion injury, and that the underlying mechanism relies on oxygen free radical scavenging and inhibition of brain Ca2+ accumulation.

  14. The neuroprotective mechanism of brain ischemic preconditioning

    Institute of Scientific and Technical Information of China (English)

    Xiao-qian LIU; Rui SHENG; Zheng-hong QIN

    2009-01-01

    Brain ischemia is one of the most common causes of death and the leading cause of adult disability in the world. Brain ischemic pre- conditioning (BIP) refers to a transient, sublethal ischemia which results in tolerance to later, otherwise lethal, cerebral ischemia. Many attempts have been made to understand the molecular and cellular mechanisms underlying the neuroprotection offered by ischemic preconditioning. Many studies have shown that neuroprotective mechanisms may involve a series of molecular regulatory pathways including activation of the N-methyI-D-aspartate (NMDA) and adenosine receptors; activation of intracellular signaling pathways such as mitogen activated protein kinases (MAPK) and other protein kinases; upregulation of Bcl-2 and heat shock proteins (HSPs); and activation of the ubiquitin-proteasome pathway and the autophagic-lysosomal pathway. A better understanding of the processes that lead to cell death after stroke as well as of the endogenous neuroprotective mechanisms by which BIP protects against brain ischemic insults could help to develop new therapeutic strategies for this devastating neurological disease. The purpose of the present review is to summarize the neuroprotective mechanisms of BIP and to discuss the possibility of mimicking ischemic preconditioning as a new strategy for preventive treatment of ischemia.

  15. 三七总皂甙对缺氧缺血性脑损伤新生鼠内源性神经干细胞增殖分化的影响%Effect of panax notoginseng saponin on proliferation and differentiation of endogenous neural stem cells in neonatal rats with hypoxic-ischemia brain damage

    Institute of Scientific and Technical Information of China (English)

    雷勋明; 陈全景; 张晓芬; 陈少军

    2013-01-01

    Objective: To observe the effect of panax notoginseng saponin (PNS) on proliferation and differentiation of endogenous neural stem cells in neonatal rats with hypoxic - ischemia brain damage ( HIBD) . Methods: Seventy - two neonatal SD rats aged seven days old were randomly divided into Sham operation group, HIBD group, and PNS group, modified Rice - Vannucci method was used to establish HIBD models. The rats were treated with injection of PNS, 5 - bromodeoxyuridine ( BrdU) was used to label neural stem cells at pro-liferative state, immunohistochemical single staining and double - immunofluorescence technique were used to observe the effect of PNS on BrdU immunoreactivity in hippocampus of HIBD rats and BrdU/neuron specific enolase ( NSE) , BrdU/glial fibrillary acidic protein (GFAP) dual - labeling immunoreactivities, then the results were counted and analyzed. Results: Positive BrdU cells existed in hippocampus of HIBD rats; the numbers of positive BrdU cells and dual - labeling positive cells in hippocampus of HIBD rats treated with PNS increased significantly (P <0. 01 ) . Conclusion: PNS can induce the proliferation and differentiation of endogenous neural stem cells in HIBD rats, which indicates that it may have the ability of promoting neurogenesis.%目的:观察三七总皂甙对缺氧缺血性脑损伤(HIBD)新生鼠内源性神经干细胞增殖分化的影响,探讨其促进神经发生的作用.方法:将72只7日龄新生SD乳鼠随机分为假手术组、HIBD组及HIBD的三七总皂甙治疗组,用改良的Rice-Vannucci法制作HIBD模型.注射三七总皂甙干预治疗,用5-溴脱氧尿苷(BrdU)标记处于增殖状态的神经干细胞,免疫单标及双标免疫荧光技术观察三七总皂甙对HIBD海马区BrdU免疫活性及BrdU/NSE (Neuron specific enolase,NSE)、BrdU/GFAP(Glial fibrillary acidic protein,GFAP)双标免疫活性的影响,并计数分析.结果:HIBD的海马区存在BrdU阳性细胞分布;应用三七总皂甙的HIBD海

  16. Effects of body temperature on serum levels of ischemia-modified albumin and malondialdehyde after surgery for intracranial hematomas in patients with severe traumatic brain injury%体温控制对重型颅脑损伤血肿清除术后的疗效及血清IMA、MDA的影响

    Institute of Scientific and Technical Information of China (English)

    刘军; 袁辉纯; 徐立新

    2016-01-01

    目的:探讨体温控制对重型颅脑损伤(sTBI)血肿清除术后的疗效及血清缺血修饰蛋白(IMA)、丙二醛(MDA)的影响。方法2012年3月到2013年1月收治符合标准的sTBI 45例,均行开颅血肿清除术;术后根据体温控制水平分为观察组(25例)和对照组(20例)。观察组使用亚低温治疗仪联合冬眠药物将肛温控制在36.0~36.4℃,维持7 d后自然复温;对照组采用传统降温措施将肛温控制在36.5~37.7℃。采用ELISA法检测血清IMA、MDA水平。结果观察组颅内压在治疗后3 d开始逐渐下降,7 d明显低于对照组(P0.05)。两组血清IMA及MDA水平均在治疗前最高,治疗后1~7 d逐渐下降,治疗组较对照组下降更明显(P<0.05)。结论肛温控制在36.0~36.4℃对sTBI颅内血肿清除术后患者有脑保护作用,其机制可能与降低血清IMA及MDA水平,减轻缺血再灌注损伤有关。%Objective To investigate the effect of body temperature on the serum levels of ischemia-modified albumin (IMA) and malondialdehyde (MDA) after the surgery for the intracranial hematomas in patients with severe traumatic brain injury (sTBI). Methods Forty-five patients with sTBI after the surgery for intracranial hematomas were divided into observed group (n=25) and control group (n=20). In observed group, mild hypothermia therapy apparatus and hibernation drugs were used to control rectal temperature at 36.0~36.4℃for 7 days. In control group, conventional cooling methods were used to control rectal temperature at 36.5~37.7℃. The serum levels of IMA and MDA were detected by ELISA. Results The intracranial pressure, which began to decline 3 days after the body temperature control, was significantly lower in observed group than control group 7 days after the body temperature control (P<0.05). The prognosis was significantly better in observed group than control group 3 months after the body temperature control (P<0.05). There

  17. 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.

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

    Directory of Open Access Journals (Sweden)

    Shi-Dong Zhang

    2011-12-01

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

  19. Changes in plasma calcitonin gene-related peptide and serum neuron specific enolase in rats with acute cerebral ischemia after low-frequency electrical stimulation with different waveforms and intensities

    Institute of Scientific and Technical Information of China (English)

    Qiang Gao; Yonghong Yang; Shasha Li; Jing He; Chengqi He

    2011-01-01

    Following acute cerebral ischemia in rats, plasma calcitonin gene-related peptide decreased and the level of serum neuron specific enolase and the volume of the infarction increased. Square-wave and triangular-wave electrical stimulation with low or high intensities could increase the plasma calcitonin gene-related peptide, decrease the serum neuron specific enolase and reduce the infarction volume in the brain in rats with cerebral ischemia. There was no significant difference between different wave forms and intensities. The experimental findings indicate that low-frequency electrical stimulation with varying waveforms and intensities can treat acute cerebral ischemia in rats.

  20. Ischemia-induced spreading depolarization in the retina.

    Science.gov (United States)

    Srienc, Anja I; Biesecker, Kyle R; Shimoda, Angela M; Kur, Joanna; Newman, Eric A

    2016-09-01

    Cortical spreading depolarization is a metabolically costly phenomenon that affects the brain in both health and disease. Following severe stroke, subarachnoid hemorrhage, or traumatic brain injury, cortical spreading depolarization exacerbates tissue damage and enlarges infarct volumes. It is not known, however, whether spreading depolarization also occurs in the retina in vivo. We report now that spreading depolarization episodes are generated in the in vivo rat retina following retinal vessel occlusion produced by photothrombosis. The properties of retinal spreading depolarization are similar to those of cortical spreading depolarization. Retinal spreading depolarization waves propagate at a velocity of 3.0 ± 0.1 mm/min and are associated with a negative shift in direct current potential, a transient cessation of neuronal spiking, arteriole constriction, and a decrease in tissue O2 tension. The frequency of retinal spreading depolarization generation in vivo is reduced by administration of the NMDA antagonist MK-801 and the 5-HT(1D) agonist sumatriptan. Branch retinal vein occlusion is a leading cause of vision loss from vascular disease. Our results suggest that retinal spreading depolarization could contribute to retinal damage in acute retinal ischemia and demonstrate that pharmacological agents can reduce retinal spreading depolarization frequency after retinal vessel occlusion. Blocking retinal spreading depolarization generation may represent a therapeutic strategy for preserving vision in branch retinal vein occlusion patients.

  1. Changes in corticocerebral morphology in a rat model of focal cerebral ischemia/reperfusion injury following"Xingnao Kaiqiao" acupuncture

    Institute of Scientific and Technical Information of China (English)

    Shu Wang; Zhankui Wang; Guangxia Ni

    2008-01-01

    BACKGROUND: Cerebral ischemia/reperfusion injury has been shown to induce inflammatory reactions,including white blood cell activation and adhesion molecule expression. These reactions often lead to aggravated neuronal injury.OBJECTIVE: To observe corticocerebral pathology, as well as ultrastructural changes, in a rat model of focal cerebral ischemia/reperfusion injury through optical and electron microscopy, and to investigate interventional effects of "Xingnao Kaiqiao" acupuncture (a brain-activating and orifice-opening acupuncture method).DESIGN, TIME AND SETTING: A randomized, controlled, neuropathology, animal experiment was performed at the Laboratory of Molecular Biology, First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine between April and June 2004.MATERIALS: A total of 50 healthy, male, Wistar rats were randomized into 5 groups, with 10 rats per group: control, sham-operated, model, non-acupoint, and "Xingnao Kaiqiao". Transmission electron microscope (TEM 400ST) was provided by Philips, Netherlands. Electro-acupuncture treatment apparatus (KWD-8082) was provided by Changzhou Wujin Great Wall Medical Instrument, China.METHODS: Focal cerebral ischemia/reperfusion injury was induced by occlusion of the middle cerebral artery in the model, non-acupoint, and "Xingnao Kaiqiao" groups. Rats from the control group did not undergo any treatment. The sham-operated group received identical experimental procedures as the model group, except that the nylon suture was not inserted into the right internal carotid artery. At 1, 3, 6, and 12 hours following focal cerebral ischemia/dreperfusion injury induction, rats from the Xingnao Kaiqiao group underwent l-minute acupuncture at the bilateral "Neiguan" (PC 6) acupoint, using a reducing method of lifting-thrusting and twirling-rotating. Subsequently, the rats were subjected to acupuncture at the "Renzhong" (DU26) acupoint 10 times by a heavy bird-pecking method. The non-acupoint group received

  2. Diagnosis and management of splanchnic ischemia

    Institute of Scientific and Technical Information of China (English)

    Jeroen J Kolkman; Marloes Bargeman; Ad B Huisman; Robert H Geelkerken

    2008-01-01

    Splanchnic or gastrointestinal ischemia is rare and randomized studies are absent.This review focuses on new developments in clinical presentation,diagnostic approaches,and treatments.Splanchnic ischemia can be caused by occlusions of arteries or veins and by physiological vasoconstriction during low-flow states.The prevalence of significant splanchnic arterial stenoses is high,but it remains mostly asymptomatic due to abundant collateral circulation.This is known as chronic splanchnic disease (CSD).Chronic splanchnic syndrome (CSS) occurs when ischemic symptoms develop.Ischemic symptoms are characterized by postprandial pain,fear of eating and weight loss.CSS is diagnosed by a test for actual ischemia.Recently,gastro-intestinal tonometry has been validated as a diagnostic test to detect splanchnic ischemia and to guide treatment.In singlevessel CSD,the complication rate is very low,but some patients have ischemic complaints,and can be treated successfully.In multi-vessel stenoses,the complication rate is considerable,while most have CSS and treatment should be strongly considered.CT and MR-based angiographic reconstruction techniques have emerged as alternatives for digital subtraction angiography for imaging of splanchnic vessels.Duplex ultrasound is still the first choice for screening purposes.The strengths and weaknesses of each modality will be discussed.CSS may be treated by minimally invasive endoscopic treatment of the celiac axis compression syndrome,endovascular antegrade stenting,or laparotomy-assisted retrograde endovascular recanalization and stenting.The treatment plan is highly individualized and is mainly based on precise vessel anatomy,body weight,comorbidity and severity of ischemia.

  3. Pharmacokinetics of ligustrazine ethosome patch in rats and anti-myocardial ischemia and anti-ischemic reperfusion injury effect

    Directory of Open Access Journals (Sweden)

    Liu X

    2011-07-01

    Full Text Available Xingyan Liu1, Hong Liu1, Zhaowu Zeng2, Weihua Zhou3, Jianqiang Liu2, Zhiwei He11China-America Cancer Research Institute, Guangdong Medical College, 2Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical College, Dongguan, Guangdong, 3Yichun University, Yichun, Jiangxi, People's Republic of ChinaAbstract: The objective of this study was to investigate the pharmacokinetics of the ligustrazine ethosome patch and antimyocardial ischemia and anti-ischemic reperfusion injury effect. Male Sprague Dawley rats were divided randomly into 3 groups: Group A (intragastric ligustrazine, Group B (transdermal ligustrazine ethosome patch, and Group C (conventional transdermal ligustrazine patch. After treatment, samples of blood and of various tissues such as heart, liver, spleen, lung, kidney, brain, and muscle samples were taken at different time points. Drug concentration was measured with HPLC, and the drug concentration–time curve was plotted. Pharmacokinetic software 3p97 was applied to calculate pharmacokinetic parameters and the area under the drug concentration–time curve (AUC in various tissues. The rat model of acute myocardial ischemia was constructed with intravenous injection of pituitrin and the model of myocardial ischemia-perfusion injury was constructed by tying off the left anterior descending coronary artery of rats to observe the effect of ligustrazine ethosome patches on ischemic myocardium and ischemia-reperfusion injury. Results showed that AUC was highest in the transdermal drug delivery group of ligustrazine ethosome patch. There were significant differences in whole blood viscosity, plasma viscosity, hematocrit, red blood cell aggregation index, and deformation index between ligustrazine the ethosome patch group and ischemic control group (P < 0.01. Moreover, ligustrazine ethosome patches could reduce the scope of myocardial infarction induced by long-term ischemia. Ligustrazine ethosome patches

  4. Perinatal iron deficiency predisposes the developing rat hippocampus to greater injury from mild to moderate hypoxia-ischemia

    OpenAIRE

    Rao, Raghavendra; Tkac, Ivan; Townsend, Elise L.; Ennis, Kathleen; Gruetter, Rolf; Georgieff, Michael K.

    2007-01-01

    The hippocampus is injured in both hypoxia-ischemia (HI) and perinatal iron deficiency that are co-morbidities in infants of diabetic mothers and intrauterine growth restricted infants. We hypothesized that preexisting perinatal iron deficiency predisposes the hippocampus to greater injury when exposed to a relatively mild HI injury. Iron-sufficient and iron-deficient rats (hematocrit 40% lower and brain iron concentration 55% lower) were subjected to unilateral HI injury of 15, 30, or 45 min...

  5. Brain Basics

    Medline Plus

    Full Text Available ... News About Us Home > Health & Education > Educational Resources Brain Basics Introduction The Growing Brain The Working Brain ... to mental disorders, such as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are ...

  6. Brain Basics

    Science.gov (United States)

    ... News About Us Home > Health & Education > Educational Resources Brain Basics Introduction The Growing Brain The Working Brain ... to mental disorders, such as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are ...

  7. Brain Basics

    Medline Plus

    Full Text Available ... Brain Basics provides information on how the brain works, how mental illnesses are disorders of the brain, ... learning more about how the brain grows and works in healthy people, and how normal brain development ...

  8. AQP4 expression and its correlation with the Lac and NAA using proton magnetic resonance spectroscopy after rat cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    ZHOU Ren-lan; XIE Peng

    2006-01-01

    Objective: To determine whether AQP4 expression is associated with lactate (Lac) and Nacetyl aspartate (NAA) and with apparent diffusion coefficient (ADC) abnormality after rat cerebral ischemia. Methods: The time courses of ADC and lactate and NAA assessed by proton magnetic resonance spectroscopy (1HMRS) were investigated at the time point of 6 h, and 1, 3, 7 d after rat cerebral ischemia induced by middle cerebral artery occlusion. Expression of AQP4 mRNA and protein were measured using RT-PCR and Western blot analysis respectively. Results: Significant reductions of NAA concentration and increases of lactate concentration were found after rat cerebral ischemia. The expressions of AQP4 mRNA and protein were increased at 6 h, and reached the peak at 1-3 d, then began to decrease at 7 d after rat cerebral ischemia. The expression of AQP4 was significantly correlated with NAA (rRT =-0.856, rw =-0. 927, P<0. 01), and with lactate (rW=0. 473, rRT=0. 413, P<0. 05), and with ADC values during the period of 1-7 d after rat cerebral ischemia (rW=0. 984, rRT= -0. 925, P<0.05). In addition, correlations between Lac and the ADC values(r=-0. 677, P<0. 05)and between NAA and ADC values during the period of 1-7 d after rat cerebral ischemia (r= 0. 909, P<0.05) were also observed. Conclusion: The data suggest that AQP4 is involved in the transport of water when brain edema is formed and cell membrane integrity is lost.

  9. Neuroprotective effects of atorvastatin against cerebral ischemia/reperfusion injury through the inhibition of endoplasmic reticulum stress

    Institute of Scientific and Technical Information of China (English)

    Jian-wen Yang; Zhi-ping Hu

    2015-01-01

    Cerebral ischemia triggers secondary ischemia/reperfusion injury and endoplasmic reticulum stress initiates cell apoptosis. However, the regulatory mechanism of the signaling pathway remains unclear. We hypothesize that the regulatory mechanisms are mediated by the protein kinase-like endoplasmic reticulum kinase/eukaryotic initiation factor 2α in the endoplasmic reticulum stress signaling pathway. To verify this hypothesis, we occluded the middle cere-bral artery in rats to establish focal cerebral ischemia/reperfusion model. Results showed that the expression levels of protein kinase-like endoplasmic reticulum kinase and caspase-3, as well as the phosphorylation of eukaryotic initiation factor 2α, were increased after ischemia/reperfusion. Administration of atorvastatin decreased the expression of protein kinase-like endoplasmic reticulum kinase, caspase-3 and phosphorylated eukaryotic initiation factor 2α, reduced the infarct volume and improved ultrastructure in the rat brain. After salubrinal, the speciifc inhibitor of phosphorylated eukaryotic initiation factor 2α was given into the rats in-tragastrically, the expression levels of caspase-3 and phosphorylated eukaryotic initiation factor 2α in the were decreased, a reduction of the infarct volume and less ultrastructural damage were observed than the untreated, ischemic brain. However, salubrinal had no impact on the expression of protein kinase-like endoplasmic reticulum kinase. Experimental ifndings indi-cate that atorvastatin inhibits endoplasmic reticulum stress and exerts neuroprotective effects. The underlying mechanisms of attenuating ischemia/reperfusion injury are associated with the protein kinase-like endoplasmic reticulum kinase/eukaryotic initiation factor 2α/caspase-3 pathway.

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

  11. Neuroprotective effects of atorvastatin against cerebral ischemia/reperfusion injury through the inhibition of endoplasmic reticulum stress

    Directory of Open Access Journals (Sweden)

    Jian-wen Yang

    2015-01-01

    Full Text Available Cerebral ischemia triggers secondary ischemia/reperfusion injury and endoplasmic reticulum stress initiates cell apoptosis. However, the regulatory mechanism of the signaling pathway remains unclear. We hypothesize that the regulatory mechanisms are mediated by the protein kinase-like endoplasmic reticulum kinase/eukaryotic initiation factor 2α in the endoplasmic reticulum stress signaling pathway. To verify this hypothesis, we occluded the middle cerebral artery in rats to establish focal cerebral ischemia/reperfusion model. Results showed that the expression levels of protein kinase-like endoplasmic reticulum kinase and caspase-3, as well as the phosphorylation of eukaryotic initiation factor 2α, were increased after ischemia/reperfusion. Administration of atorvastatin decreased the expression of protein kinase-like endoplasmic reticulum kinase, caspase-3 and phosphorylated eukaryotic initiation factor 2α, reduced the infarct volume and improved ultrastructure in the rat brain. After salubrinal, the specific inhibitor of phosphorylated eukaryotic initiation factor 2α was given into the rats intragastrically, the expression levels of caspase-3 and phosphorylated eukaryotic initiation factor 2α in the were decreased, a reduction of the infarct volume and less ultrastructural damage were observed than the untreated, ischemic brain. However, salubrinal had no impact on the expression of protein kinase-like endoplasmic reticulum kinase. Experimental findings indicate that atorvastatin inhibits endoplasmic reticulum stress and exerts neuroprotective effects. The underlying mechanisms of attenuating ischemia/reperfusion injury are associated with the protein kinase-like endoplasmic reticulum kinase/eukaryotic initiation factor 2α/caspase-3 pathway.

  12. 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.

  13. Transient focal cerebral ischemia/reperfusion induces early and chronic axonal changes in rats: its importance for the risk of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Qinan Zhang

    Full Text Available The dementia of Alzheimer's type and brain ischemia are known to increase at comparable rates with age. Recent advances suggest that cerebral ischemia may contribute to the pathogenesis of Alzheimer's disease (AD, however, the neuropathological relationship between these two disorders is largely unclear. It has been demonstrated that axonopathy, mainly manifesting as impairment of axonal transport and swelling of the axon and varicosity, is a prominent feature in AD and may play an important role in the neuropathological mechanisms in AD. In this study, we investigated the early and chronic changes of the axons of neurons in the different brain areas (cortex, hippocampus and striatum using in vivo tracing technique and grading analysis method in a rat model of transient focal cerebral ischemia/reperfusion (middle cerebral artery occlusion, MCAO. In addition, the relationship between the changes of axons and the expression of β-amyloid 42 (Aβ42 and hyperphosphorylated Tau, which have been considered as the key neuropathological processes of AD, was analyzed by combining tracing technique with immunohistochemistry or western blotting. Subsequently, we found that transient cerebral ischemia/reperfusion produced obvious swelling of the axons and varicosities, from 6 hours after transient cerebral ischemia/reperfusion even up to 4 weeks. We could not observe Aβ plaques or overexpression of Aβ42 in the ischemic brain areas, however, the site-specific hyperphosphorylated Tau could be detected in the ischemic cortex. These results suggest that transient cerebral ischemia/reperfusion induce early and chronic axonal changes, which may be an important mechanism affecting the clinical outcome and possibly contributing to the development of AD after stroke.

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

    Directory of Open Access Journals (Sweden)

    Qiusheng Zheng

    2012-08-01

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

  15. Neuroprotective effects of neuregulin-1 on B35 neuronal cells following ischemia.

    Science.gov (United States)

    Croslan, DaJoie R; Schoell, Matthew C; Ford, Gregory D; Pulliam, John V; Gates, Alicia; Clement, Ceilessia M; Harris, Adalynn E; Ford, Byron D

    2008-05-19

    We previously showed that neuregulin-1 (NRG-1) protected neurons from death in vivo following focal ischemia. The goal of this study was to develop an in vitro rat ischemia model to examine the cellular and molecular mechanisms involved in the neuroprotective effects of NRG-1 on ischemia-induced neuronal death. Rat B-35 neuroblastoma cells differentiated by serum withdrawal, developed enhanced neuronal characteristics including, neurite extension and upregulation of neuronal markers of differentiation. When B35 neurons were subjected to oxygen glucose deprivation (OGD)/reoxygenation or glutamate, widespread neuronal death was seen after both treatments. Treatment with NRG-1 immediately after OGD significantly increased neuronal survival. NRG-1 administration also resulted in a significant decrease in annexin V, an early marker of apoptosis. However, the neurotoxic actions of glutamate were unaffected by NRG-1. The neuroprotective effects of NRG-1 were prevented by an inhibitor of the phosphatidylinositol-3-kinase/Akt pathway. These results provide a new model to gain insight into the mechanisms employed by NRG-1 to protect neurons from ischemic brain injury. PMID:18410912

  16. Neuroprotective effects of Neuregulin-1 on B35 Neuronal Cells following Ischemia

    Science.gov (United States)

    Croslan, DaJoie R.; Schoell, Matthew C.; Ford, Gregory D.; Pulliam, John V.; Gates, Alicia; Clement, Ceilessia M.; Harris, Adalynn E.; Ford, Byron D.

    2008-01-01

    We previously showed that neuregulin-1 (NRG-1) protected neurons from death in vivo following focal ischemia. The goal of this study was to develop an in vitro rat ischemia model to examine the cellular and molecular mechanisms involved in the neuroprotective effects of NRG-1 on ischemia-induced neuronal death. Rat B-35 neuroblastoma cells differentiated by serum withdrawal, developed enhanced neuronal characteristics including, neurite extension and upregulation of neuronal markers of differentiation. When B35 neurons were subjected to oxygen glucose deprivation (OGD)/reoxygenation or glutamate, widespread neuronal death was seen after both treatments. Treatment with NRG-1 immediately after OGD significantly increased neuronal survival. NRG-1 administration also resulted in a significant decrease in annexin V, an early marker of apoptosis. However, the neurotoxic actions of glutamate were unaffected by NRG-1. The neuroprotective effects of NRG-1 were prevented by an inhibitor of the phosphatidylinositol-3-kinase/Akt pathway. These results provide a new model to gain insight into the mechanisms employed by NRG-1 to protect neurons from ischemic brain injury. PMID:18410912

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

    Institute of Scientific and Technical Information of China (English)

    Li-zhen WANG; Xing-zu ZHU

    2004-01-01

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

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

    Science.gov (United States)

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

    2008-02-01

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

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

    Directory of Open Access Journals (Sweden)

    M. Eskandarlou

    2016-01-01

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

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

    OpenAIRE

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

    2009-01-01

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

  1. Cerebral ischemia induces microvascular pro-inflammatory cytokine expression via the MEK/ERK pathway

    DEFF Research Database (Denmark)

    Maddahi, Aida; Edvinsson, Lars

    2010-01-01

    levels of pro-inflammatory mediators in the infarct region. In this study, we hypothesised that inhibition of the cerebrovascular inflammatory reaction with a specific MEK1/2 inhibitor (U0126) to block transcription or a combined receptor blockade would reduce infarct size and improve neurological score...... and endothelin ETA receptors decreased the volume of brain damaged (12.3 +/- 3; P cytokines CONCLUSION: The present study shows elevated microvascular expression of TNF-alpha, IL-1ss, IL-6 and iNOS following focal ischemia, and shows...

  2. Microvessel changes in the gerbil hippocampus after cerebral ischemia and reperfusion by Buyang Huanwu decoction pretreatment

    Institute of Scientific and Technical Information of China (English)

    Xiaoguang Wu; Yixue Li; Haixia Liu; Yuhua Yin; Shumin Zhao; Yuanyuan Guo

    2011-01-01

    Buyang Huanwu decoction (BYHWD) is a classic recipe for the prevention and treatment of ischemic cerebrovascular disease. Gerbils were pretreated with BYHWD, and then subjected to cerebral ischemia and reperfusion. Microvascular changes were determined with laser Doppler monitoring, tannic acid-ferric chloride mordant, and electron microscopy. Results showed that BYHWD pretreatment could enhance the function of hippocampal microvessels, prevent injury, and increase microvasular density and microvasular area density. Thus, these results suggest that BYHWD pretreatment could prevent microvascular occlusion, enhance the capacity of microvascular reperfusion, increase cerebral blood flow, and inhibit neuronal damage, and may be an effective therapy against brain ischemic injury.

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

    Science.gov (United States)

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

    2013-08-15

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

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

    Institute of Scientific and Technical Information of China (English)

    Caiwei Qiu; Bo Sheng; Shurong Wang; Jin Liu

    2013-01-01

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

  5. Ischemia detection using Isoelectric Energy Function.

    Science.gov (United States)

    Kumar, Amit; Singh, Mandeep

    2016-01-01

    A novel method has been proposed for the detection of ischemia using an isoelectric energy function (IEEF) resulting from ST segment deviations in ECG signals. The method consists of five stages: pre-processing, delineation, measurement of isoelectric energy, a beat characterization algorithm and detection of ischemia. The isoelectric energy threshold is used to differentiate ischemic beats from normal beats for ischemic episode detection. Then, ischemic episodes are classified as transmural or subendocardial. The method is validated for recordings of the annotated European ST-T database (EDB). The results show 98.12% average sensitivity (SE) and 98.16% average specificity (SP). These results are significantly better than those of existing methods cited in the literature. The advantage of the proposed method includes simplicity, ruggedness and automatic discarding of noisy beats. PMID:26623944

  6. Effects of Ischemia on Lung Macrophages

    OpenAIRE

    Aigul Moldobaeva; Nico van Rooijen; Wagner, Elizabeth M.

    2011-01-01

    Angiogenesis after pulmonary ischemia is initiated by reactive O(2) species and is dependent on CXC chemokine growth factors, and its magnitude is correlated with the number of lavaged macrophages. After complete obstruction of the left pulmonary artery in mice, the left lung is isolated from the peripheral circulation until 5-7 days later, when a new systemic vasculature invades the lung parenchyma. Consequently, this model offers a unique opportunity to study the differentiation and/or prol...

  7. Endovascular Management of Acute Limb Ischemia.

    LENUS (Irish Health Repository)

    Hynes, Brian G

    2011-09-14

    Despite major advances in pharmacologic and endovascular therapies, acute limb ischemia (ALI) continues to result in significant morbidity and mortality. The incidence of ALI may be as high as 13-17 cases per 100,000 people per year, with mortality rates approaching 18% in some series. This review will address the contemporary endovascular management of ALI encompassing pharmacologic and percutaneous interventional treatment strategies.

  8. Urticarial Vasculitis-Associated Intestinal Ischemia

    Directory of Open Access Journals (Sweden)

    Uni Wong

    2016-01-01

    Full Text Available Urticarial vasculitis (UV is a rare small vessel vasculitis. UV is often idiopathic but can also present in the context of autoimmune disorders such as systemic lupus erythematosus, drug reactions, infections, or a paraneoplastic syndrome. Extracutaneous complications include intestinal ischemic injuries, in UV patients with nonspecific gastrointestinal symptoms such as abdominal pain and nausea. Prompt recognition and treatment can minimize morbidity and mortality. This paper describes a case of urticarial vasculitis-associated intestinal ischemia.

  9. Urticarial Vasculitis-Associated Intestinal Ischemia.

    Science.gov (United States)

    Wong, Uni; Yfantis, Harris; Xie, Guofeng

    2016-01-01

    Urticarial vasculitis (UV) is a rare small vessel vasculitis. UV is often idiopathic but can also present in the context of autoimmune disorders such as systemic lupus erythematosus, drug reactions, infections, or a paraneoplastic syndrome. Extracutaneous complications include intestinal ischemic injuries, in UV patients with nonspecific gastrointestinal symptoms such as abdominal pain and nausea. Prompt recognition and treatment can minimize morbidity and mortality. This paper describes a case of urticarial vasculitis-associated intestinal ischemia. PMID:27190661

  10. Cromakalin pretreatment affects mitochondrial structure and function in a rat model of ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Shilei Wang; Peng Wang; Qingxian Chang; Yu Li; Yan Jiang; Shiduan Wang

    2008-01-01

    BACKGROUND: Mitochondrial structural changes and energy dysmetabolism frequently occur subsequent to cerebral ischemia. Adenosine triphosphate (ATP)-sensitive potassium channel openers exhibit protective effects on cerebral ischemia/reperfusion injury. OBJECTIVE: To validate the effects of cromakalin on mitochondrial structure and function in ischemic penumbra brain tissue in a rat model of middle cerebral artery occlusion (MCAO). DESIGN, TIME AND SETTING: The present single-factor analysis of variance, randomized, controlled, animal experiment was performed at the Institute of Brain Science, Affiliated Hospital of Qingdao University Medical College between October 2007 and March 2008. MATERIALS: Forty male, Wistar rats were randomly divided into four groups, with 10 rats per group: sham-operated, MCAO, MCAO+ATP-sensitive potassium channel opener (cromakalin), and MCAO+eromakalin+ATP-sensitive potassium channel blocking agent (glibenclamide). METHODS: Focal cerebral ischemia/reperfusion injury was induced by MCAO in all groups except the sham-operated group. The MCAO cromakalin group was administered 10 mg/kg cromakalin (i.p.) prior to MCAO induction. The MCAO+cromakalin+glibenclamide group received an injection of 10 mg/kg cromakalin (i.v.), and subsequently an injection of 10 mg/kg cromakalin (i.p.) prior to MCAO induction. MAIN OUTCOME MEASURES: At 24 hours after cerebral ischemia/reperfusion injury, cellular apoptosis was detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick-end labeling technique. Cytochrome C expression was measured by immunohistochemistry. In addition, mitochondrial swelling, membrane fluidity, membrane phospholipid and malonaldehyde (MDA) contents, as well as Na+-K+-ATPase, Ca2+-ATPase, and superoxide dismutase (SOD) activities were determined. RESULTS: Compared with the sham-operated group, the three ischemia groups exhibited significantly elevated mitochondrial MDA content, reduced membrane

  11. Tribulosin protects rat hearts from ischemia/reperfusion injury

    OpenAIRE

    Zhang, Shuang; Li, Hong; Yang, Shi-Jie

    2010-01-01

    Aim: To investigate the protective effect of tribulosin, a monomer of the gross saponins from Tribulus terrestris, against cardiac ischemia/reperfusion injury and the underlying mechanism in rats. Methods: Isolated rat hearts were subjected to 30 min of ischemia followed by 120 min of reperfusion using Langendorff's technique. The hearts were assigned to seven groups: control, ischemia/reperfusion (I/R), treatment with gross saponins from Tribulus terrestris (GSTT) 100 mg/L, treatment with tr...

  12. Effect of heat shock protein 70 on cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Wen Yan; Xiulian Chen; Rui Chen; Shiming Xu; Lijuan Zhang; Hongjuan Wang; Chunyue Huo

    2006-01-01

    OBJECTIVE: To summarize the relationship between heat shock protein 70 (HSP70) and cerebral ischemia.DATA SOURCES: An online search of Medline database was undertaken to identify relevant articles published in English from January 1980 to December 2005 by using the keywords of "heat shock protein 70, ischemia". Meanwhile, Chinese relevant articles published from January 2000 to December 2005 were searched in China National Knowledge Infrastructure (CNKI) database and Chinese Journal of Clinical Rehabilitation with the keywords of "heat shock protein 70, cerebral ischemia" in Chinese.STUDY SELECTION: More than 100 related articles were screened, and 29 references mainly about HSP70and cerebral ischemia were selected, including basic and clinical researches. As to the articles with similar content, those published in the authoritative journals in recent 3 years were preferential.DATA EXTRACTION : A total of 29 articles were collected and classified according to the structure, function and clinical application of HSP70. Among them, 1 article is about the structure of HSP70, 27 about the relationship between HSP70 and cerebral ischemia, and 2 about the clinical application of HSP70.DATA SYNTHESTS: HSP70 is one of the most conservative proteins during biological evolution. Experiments in cerebral ischemia revealed that HSP70 expression was time-dependent, also correlated with the injured site and severity. The cerebral ischemia induced HSP70 gene expression in hippocampus of gerbil had protection to tolerance of fatal ischemic injury for neurons. The increase of HSP70 expression may be one of the endogenous protective mechanisms during cerebral ischemia, and can effectively alleviate cerebral ischemia. Thus HSP70 protein and HSP70 mRNA have been taken as important indexes extensively applied in the basic study of cerebral ischemia by some scholars abroad.CONCLUSTON: HSP70 plays a protective role in cerebral ischemia, and a deeper research into the biological function of

  13. Diagnosis of brain death

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    Calixto Machado

    2010-06-01

    Full Text Available Brain death (BD should be understood as the ultimate clinical expression of a brain catastrophe characterized by a complete and irreversible neurological stoppage, recognized by irreversible coma, absent brainstem reflexes, and apnea. The most common pattern is manifested by an elevation of intracranial pressure to a point beyond the mean arterial pressure, and hence cerebral perfusion pressure falls and, as a result, no net cerebral blood flow is present, in due course leading to permanent cytotoxic injury of the intracranial neuronal tissue. A second mechanism is an intrinsic injury affecting the nervous tissue at a cellular level which, if extensive and unremitting, can also lead to BD. We review here the methodology of diagnosing death, based on finding any of the signs of death. The irreversible loss of cardio-circulatory and respiratory functions can cause death only when ischemia and anoxia are prolonged enough to produce an irreversible destruction of the brain. The sign of such loss of brain functions, that is to say BD diagnosis, is fully reviewed.

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

    Science.gov (United States)

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

    2014-12-15

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

  15. Orexigenic hormone ghrelin attenuates local and remote organ injury after intestinal ischemia-reperfusion.

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    Rongqian Wu

    Full Text Available BACKGROUND: Gut ischemia/reperfusion (I/R injury is a serious condition in intensive care patients. Activation of immune cells adjacent to the huge endothelial cell surface area of the intestinal microvasculature produces initially local and then systemic inflammatory responses. Stimulation of the vagus nerve can rapidly attenuate systemic inflammatory responses through inhibiting the activation of macrophages and endothelial cells. Ghrelin, a novel orexigenic hormone, is produced predominately in the gastrointestinal system. Ghrelin receptors are expressed at a high density in the dorsal vagal complex of the brain stem. In this study, we investigated the regulation of the cholinergic anti-inflammatory pathway by the novel gastrointestinal hormone, ghrelin, after gut I/R. METHODS AND FINDINGS: Gut ischemia was induced by placing a microvascular clip across the superior mesenteric artery for 90 min in male adult rats. Our results showed that ghrelin levels were significantly reduced after gut I/R and that ghrelin administration inhibited pro-inflammatory cytokine release, reduced neutrophil infiltration, ameliorated intestinal barrier dysfunction, attenuated organ injury, and improved survival after gut I/R. Administration of a specific ghrelin receptor antagonist worsened gut I/R-induced organ injury and mortality. To determine whether ghrelin's beneficial effects after gut I/R require the intact vagus nerve, vagotomy was performed in sham and gut I/R animals immediately prior to the induction of gut ischemia. Our result showed that vagotomy completely eliminated ghrelin's beneficial effect after gut I/R. To further confirm that ghrelin's beneficial effects after gut I/R are mediated through the central nervous system, intracerebroventricular administration of ghrelin was performed at the beginning of reperfusion after 90-min gut ischemia. Our result showed that intracerebroventricular injection of ghrelin also protected the rats from gut I

  16. A Model of Ischemia-Induced Neuroblast Activation in the Adult Subventricular Zone

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    Vergni, Davide; Castiglione, Filippo; Briani, Maya; Middei, Silvia; Alberdi, Elena; Reymann, Klaus G.; Natalini, Roberto; Volonté, Cinzia; Matute, Carlos; Cavaliere, Fabio

    2009-01-01

    We have developed a rat brain organotypic culture model, in which tissue slices contain cortex-subventricular zone-striatum regions, to model neuroblast activity in response to in vitro ischemia. Neuroblast activation has been described in terms of two main parameters, proliferation and migration from the subventricular zone into the injured cortex. We observed distinct phases of neuroblast activation as is known to occur after in vivo ischemia. Thus, immediately after oxygen/glucose deprivation (6–24 hours), neuroblasts reduce their proliferative and migratory activity, whereas, at longer time points after the insult (2 to 5 days), they start to proliferate and migrate into the damaged cortex. Antagonism of ionotropic receptors for extracellular ATP during and after the insult unmasks an early activation of neuroblasts in the subventricular zone, which responded with a rapid and intense migration of neuroblasts into the damaged cortex (within 24 hours). The process is further enhanced by elevating the production of the chemoattractant SDf-1α and may also be boosted by blocking the activation of microglia. This organotypic model which we have developed is an excellent in vitro system to study neurogenesis after ischemia and other neurodegenerative diseases. Its application has revealed a SOS response to oxygen/glucose deprivation, which is inhibited by unfavorable conditions due to the ischemic environment. Finally, experimental quantifications have allowed us to elaborate a mathematical model to describe neuroblast activation and to develop a computer simulation which should have promising applications for the screening of drug candidates for novel therapies of ischemia-related pathologies. PMID:19390597

  17. A model of ischemia-induced neuroblast activation in the adult subventricular zone.

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    Davide Vergni

    Full Text Available We have developed a rat brain organotypic culture model, in which tissue slices contain cortex-subventricular zone-striatum regions, to model neuroblast activity in response to in vitro ischemia. Neuroblast activation has been described in terms of two main parameters, proliferation and migration from the subventricular zone into the injured cortex. We observed distinct phases of neuroblast activation as is known to occur after in vivo ischemia. Thus, immediately after oxygen/glucose deprivation (6-24 hours, neuroblasts reduce their proliferative and migratory activity, whereas, at longer time points after the insult (2 to 5 days, they start to proliferate and migrate into the damaged cortex. Antagonism of ionotropic receptors for extracellular ATP during and after the insult unmasks an early activation of neuroblasts in the subventricular zone, which responded with a rapid and intense migration of neuroblasts into the damaged cortex (within 24 hours. The process is further enhanced by elevating the production of the chemoattractant SDf-1alpha and may also be boosted by blocking the activation of microglia. This organotypic model which we have developed is an excellent in vitro system to study neurogenesis after ischemia and other neurodegenerative diseases. Its application has revealed a SOS response to oxygen/glucose deprivation, which is inhibited by unfavorable conditions due to the ischemic environment. Finally, experimental quantifications have allowed us to elaborate a mathematical model to describe neuroblast activation and to develop a computer simulation which should have promising applications for the screening of drug candidates for novel therapies of ischemia-related pathologies.

  18. Transforming Growth Factor -α Improves Memory Impairment and Neurogenesis Following Ischemia Reperfusion

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    Hassan Alipanahzadeh

    2014-04-01

    Full Text Available Objective: Stroke is most important cause of death and disability in adults. The hippocampal CA1 and sub-ventricular zone neurons are vulnerable to ischemia that can impair memory and learning functions. Although neurogenesis normally occurs in the dentate gyrus (DG of the hippocampus and sub-ventricular zone (SVZ following brain damage, this response is unable to compensate for severely damaged areas. This study aims to assess both neurogenesis and the neuroprotective effects of transforming growth factor-alpha (TGF-α on the hippocampus and SVZ following ischemia-reperfusion. Materials and Methods: In this experimental study, a total of 48 male Wistar rats were divided into the following groups: surgical (n=12, phosphate buffered saline (PBS treated vehicle shams (n=12, ischemia (n=12 and treatment (n=12 groups. Ischemia was induced by common carotid occlusion for 30 minutes followed by reperfusion, and TGF-α was then injected into the right lateral ventricle. Spatial memory was assessed using Morris water maze (MWM. Nestin and Bcl-2 family protein expressions were studied by immunohistochemistry (IHC and Western blot methods, respectively. Finally, data were analyzed using Statistical Package for the Social Sciences (SPSS, SPSS Inc., Chicago, USA version 16 and one-way analysis of variance (ANOVA. Results: TGF-α injection significantly increased nestin expression in both the hippocampal DG and SVZ areas. TGF-α treatment caused a significant decrease in Bax expression and an increase in Bcl-2 anti-apoptotic protein expression in the hippocampus. Our results showed a significant increase in the number of pyramidal neurons. Memory also improved significantly following TGF-α treatment. Conclusion: Our findings proved that TGF-α reduced ischemic injury and played a neuroprotective role in the pathogenesis of ischemic injury.

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

    Institute of Scientific and Technical Information of China (English)

    陈唯唯; 漆剑频; 张进华; 黄文华; 宋金梅

    2004-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    Meizeng Zhang; Lihua Wang; Yunliang Guo

    2006-01-01

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

  1. Relaxation along a fictitious field (RAFF) and Z-spectroscopy using alternating-phase irradiation (ZAPI) in permanent focal cerebral ischemia in rat.

    Science.gov (United States)

    Jokivarsi, Kimmo T; Liimatainen, Timo; Kauppinen, Risto A; Gröhn, Olli H J; Närväinen, Johanna

    2013-01-01

    Cerebral ischemia alters the molecular dynamics and content of water in brain tissue, which is reflected in NMR relaxation, diffusion and magnetization transfer (MT) parameters. In this study, the behavior of two new MRI contrasts, Relaxation Along a Fictitious Field (RAFF) and Z-spectroscopy using Alternating-Phase Irradiation (ZAPI), were quantified together with conventional relaxation parameters (T1, T2 and T1ρ) and MT ratios in acute cerebral ischemia in rat. The right middle cerebral artery was permanently occluded and quantitative MRI data was acquired sequentially for the above parameters for up to 6 hours. The following conclusions were drawn: 1) Time-dependent changes in RAFF and T1ρ relaxation are not coupled to those in MT. 2) RAFF relaxation evolves more like transverse, rather than longitudinal relaxation. 3) MT measured with ZAPI is less sensitive to ischemia than conventional MT. 4) ZAPI data suggest alterations in the T2 distribution of macromolecules in acute cerebral ischemia. It was shown that both RAFF and ZAPI provide complementary MRI information from acute ischemic brain tissue. The presented multiparametric MRI data may aid in the assessment of brain tissue status early in ischemic stroke. PMID:23874898

  2. Relaxation along a fictitious field (RAFF and Z-spectroscopy using alternating-phase irradiation (ZAPI in permanent focal cerebral ischemia in rat.

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    Kimmo T Jokivarsi

    Full Text Available Cerebral ischemia alters the molecular dynamics and content of water in brain tissue, which is reflected in NMR relaxation, diffusion and magnetization transfer (MT parameters. In this study, the behavior of two new MRI contrasts, Relaxation Along a Fictitious Field (RAFF and Z-spectroscopy using Alternating-Phase Irradiation (ZAPI, were quantified together with conventional relaxation parameters (T1, T2 and T1ρ and MT ratios in acute cerebral ischemia in rat. The right middle cerebral artery was permanently occluded and quantitative MRI data was acquired sequentially for the above parameters for up to 6 hours. The following conclusions were drawn: 1 Time-dependent changes in RAFF and T1ρ relaxation are not coupled to those in MT. 2 RAFF relaxation evolves more like transverse, rather than longitudinal relaxation. 3 MT measured with ZAPI is less sensitive to ischemia than conventional MT. 4 ZAPI data suggest alterations in the T2 distribution of macromolecules in acute cerebral ischemia. It was shown that both RAFF and ZAPI provide complementary MRI information from acute ischemic brain tissue. The presented multiparametric MRI data may aid in the assessment of brain tissue status early in ischemic stroke.

  3. Adult midgut malrotation presented with acute bowel obstruction and ischemia

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    Akile Zengin

    2016-01-01

    Conclusion: Malrotation should be considered in differential diagnosis in patients presented with acute abdomen and intestinal ischemia. Surgical intervention should be prompt to limit morbidity and mortality.

  4. Influence of exercise training on ischemic brain injury in type 1 diabetic rats

    OpenAIRE

    Arrick, Denise M.; Sun, Hong; Mayhan, William G.

    2012-01-01

    While exercise training (ExT) appears to influence cerebrovascular function during type 1 diabetes (T1D), it is not clear whether this beneficial effect extends to protecting the brain from ischemia-induced brain injury. Thus our goal was to examine whether modest ExT could influence transient focal ischemia-induced brain injury along with nitric oxide synthase (NOS)-dependent dilation of cerebral (pial) arterioles during T1D. Sprague-Dawley rats were divided into four groups: nondiabetic sed...

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

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    Anand Kumar Pandey

    2015-01-01

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

  6. MRI Dynamically Evaluates the Therapeutic Effect of Recombinant Human MANF on Ischemia/Reperfusion Injury in Rats

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    Xian-Yun Wang

    2016-09-01

    Full Text Available As an endoplasmic reticulum (ER stress-inducible protein, mesencephalic astrocyte-derived neurotrophic factor (MANF has been proven to protect dopaminergic neurons and nondopaminergic cells. Our previous studies had shown that MANF protected against ischemia/reperfusion injury. Here, we developed a magnetic resonance imaging (MRI technology to dynamically evaluate the therapeutic effects of MANF on ischemia/reperfusion injury. We established a rat focal ischemic model by using middle cerebral artery occlusion (MCAO. MRI was performed to investigate the dynamics of lesion formation. MANF protein was injected into the right lateral ventricle at 3 h after reperfusion following MCAO for 90 min, when the obvious lesion firstly appeared according to MRI investigation. T2-weighted imaging for evaluating the therapeutic effects of MANF protein was performed in ischemia/reperfusion injury rats on Days 1, 2, 3, 5, and 7 post-reperfusion combined with histology methods. The results indicated that the administration of MANF protein at the early stage after ischemia/reperfusion injury decreased the mortality, improved the neurological function, reduced the cerebral infarct volume, and alleviated the brain tissue injury. The findings collected from MRI are consistent with the morphological and pathological changes, which suggest that MRI is a useful technology for evaluating the therapeutic effects of drugs.

  7. [In vitro evaluation of metabolic change in forebrain ischemia model of rat using proton magnetic resonance spectroscopy].

    Science.gov (United States)

    Tanaka, N

    1997-05-01

    Metabolic disruption resulted from cerebral ischemia and post-ischemia reperfusion injury was studied using proton magnetic resonance spectroscopy (1H MRS). We also analyzed the effect of 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186) which can scavenge free radicals induced in the brain tissue due to ischemic-reperfusion in this experiment. The ischemic model was produced using rat forebrain ischemic model (Pulsinelli's 4 vessels occlusion model). Post-ischemic reperfusion was also induced by the re-opening of the occluded common carotid arteries. The occluded time was 30 min and reperfusion time 0, 10, 30, 60 min. We obtained the specimens in the cortex under microwave fixation. Choline and acetate increased during ischemia and gradually decreased during reperfusion period. These two signals seen in 1H MRS are supposed to represent cell membrane components (products) and the increase of these signals after reperfusion seems to be related to the post ischemic reperfusion injury due to the explosive increase of free radicals. Lactate, which is induced by anaerobic glycolysis, increased during ischemia and promptly disappeared after reperfusion. The treatment of pre-ischemic administration of MCI-186 significantly suppressed increases of choline and acetate. As far as lactate is concerned, post-ischemic administration of this drug significantly reduced its increase at the point of reperfusion. Our results suggest that MCI-186 alternates changes induced by ischemic-reperfusion injury in membranous metabolism, probably due to its free radical scavenging action. PMID:9226472

  8. Brain herniation

    Science.gov (United States)

    ... herniation; Uncal herniation; Subfalcine herniation; Tonsillar herniation; Herniation - brain ... Brain herniation occurs when something inside the skull produces pressure that moves brain tissues. This is most ...

  9. Influence of tongxinluo on microvascular intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression in rat brain ischemia-reperfusion model%通心络对大鼠脑缺血再灌注模型微血管细胞间黏附分子1和血管细胞黏附分子1表达的影响

    Institute of Scientific and Technical Information of China (English)

    赵忠新; 夏斌; 王春燕; 田国红

    2006-01-01

    property and suppressing platelet congregation capability, tongxinluo preparation has been proved by traditional Chinese medicine to possess certain function for protecting endothelial cells.OBJECTIVE: To observe the influence of Chinese medicinal herb "tongxinluo" compound on adhesion molecule expression in brain ischemia-reperfusion (IR) animal model.DESIGN: Randomized and controlled experiment.SETTING: Department of Neurology, Changzheng Hospital Affiliated to the Second Military Medical University of Chinese PLA.MATERIALS: This experiment was conducted at the laboratory of the Department of Neurology, Shanghai Changzheng Hospital, between October 2002 and January 2003. Totally 25 male SD rats were randomized into sham-operation group of 5 rats, model group of 10 rats and tongxinluo group of 10 rats.METHODS: Middle cerebral artery was occluded using thread-bolt method to induce focal brain IR model in rats. In sham-operation group,nylon thread was placed around the external carotid artery approximating to the branch of internal carotid artery, and the other procedure was the same as that in model group. Rats in tongxinluo group were given tongxininfusion before IR for 1 consecutive week, which was replaced by physiological saline of the same dosage in model group and sham-operation group. Brain tissues were obtained under anesthesia condition and cut into slices; conventional HE staining, immunohistochemical and in situ hybridization staining were conducted.MAIN OUTCOME MEASURES:① The number of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)positive microvessels fo