WorldWideScience

Sample records for brain ischemia

  1. Endoplasmic reticulum stress in brain ischemia.

    Science.gov (United States)

    Su, Yingchao; Li, Feng

    2016-08-01

    Endoplasmic reticulum (ER) stress is an intricate mechanism that mediates numerous responses during brain ischemia, thus being essential to determine the fate of neurons. In recent years, studies of the mechanisms of brain ischemic injury have centered on ER stress, glutamate excitotoxicity, dysfunction of mitochondria, inflammatory reactions, calcium overload and death receptor pathways. The role of ER stress is highly important. In addition to resulting in neuronal cell death through calcium toxicity and apoptotic pathways, ER stress also triggers a series of adaptive responses including unfolded protein response (UPR), autophagy, the expression of pro-survival proteins and the enhancement of ER self-repair ability, leading to less ischemic brain damage. This paper provides an overview of recent advances in understanding of the relations between ER stress and brain ischemia. PMID:26289799

  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. 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.

  4. Hyperbaric oxygen modalities are differentially effective in distinct brain ischemia models

    OpenAIRE

    Ostrowski, Robert P.; Katarzyna Stepien; Emanuela Pucko; Ewa Matyja

    2016-01-01

    The effectiveness and efficacy of hyperbaric oxygen (HBO) preconditioning and post-treatment modalities have been demonstrated in experimental models of ischemic cerebrovascular diseases, including global brain ischemia, transient focal and permanent focal cerebral ischemia, and experimental neonatal hypoxia-ischemia encephalopathy. In general, early and repetitive post-treatment of HBO appears to create enhanced protection against brain ischemia whereas delayed HBO treatment after transient ...

  5. 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...

  6. Brain polyphosphoinositide metabolism during focal ischemia in rat cortex

    International Nuclear Information System (INIS)

    Using a rat model of stroke, we examined the effects of focal cerebral ischemia on the metabolism of polyphosphoinositides by injecting 32Pi into both the left and right cortices. After equilibration of the label for 2-3 hours, ischemia induced a significant decrease (p less than 0.001) in the concentrations of labeled phosphatidyl 4,5-bisphosphates (66-78%) and phosphatidylinositol 4-phosphate (64-67%) in the right middle cerebral artery cortex of four rats. The phospholipid labeling pattern in the left middle cerebral artery cortex, which sustained only mild ischemia and no permanent tissue damage, was not different from that of two sham-operated controls. However, when 32Pi was injected 1 hour after the ischemic insult, there was a significant decrease (p less than 0.01) in the incorporation of label into the phospholipids in both cortices of four ischemic rats compared with four sham-operated controls. Furthermore, differences in the phospholipid labeling pattern were observed in the left cortex compared with the sham-operated controls. The change in labeling pattern was attributed to the partial reduction in blood flow following ligation of the common carotid arteries. We provide a sensitive procedure for probing the effects of focal cerebral ischemia on the polyphosphoinositide signaling pathway in the brain, which may play an important role in the pathogenesis of tissue injury

  7. 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...

  8. 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

  9. 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.

  10. Neuroprotective effects of crocin on the histopathological alterations following brain ischemia-reperfusion injury in rat

    OpenAIRE

    Javad Raouf Sarshoori; Mohammad Hossien Asadi; Mohammad Taghi Mohammadi

    2014-01-01

    Objective(s): Some histopathological alterations take place in the ischemic regions following brain ischemia. Recent studies have demonstrated some neuroprotective roles of crocin in different models of experimental cerebral ischemia. Here, we investigated the probable neuroprotective effects of crocin on the brain infarction and histopathological changes after transient model of focal cerebral ischemia. Materials and Methods: Experiment was performed in four groups of rats (each group; n=8),...

  11. Nonlinear Dynamic Theory of Acute Cell Injuries and Brain Ischemia

    Science.gov (United States)

    Taha, Doaa; Anggraini, Fika; Degracia, Donald; Huang, Zhi-Feng

    2015-03-01

    Cerebral ischemia in the form of stroke and cardiac arrest brain damage affect over 1 million people per year in the USA alone. In spite of close to 200 clinical trials and decades of research, there are no treatments to stop post-ischemic neuron death. We have argued that a major weakness of current brain ischemia research is lack of a deductive theoretical framework of acute cell injury to guide empirical studies. A previously published autonomous model based on the concept of nonlinear dynamic network was shown to capture important facets of cell injury, linking the concept of therapeutic to bistable dynamics. Here we present an improved, non-autonomous formulation of the nonlinear dynamic model of cell injury that allows multiple acute injuries over time, thereby allowing simulations of both therapeutic treatment and preconditioning. Our results are connected to the experimental data of gene expression and proteomics of neuron cells. Importantly, this new model may be construed as a novel approach to pharmacodynamics of acute cell injury. The model makes explicit that any pro-survival therapy is always a form of sub-lethal injury. This insight is expected to widely influence treatment of acute injury conditions that have defied successful treatment to date. This work is supported by NIH NINDS (NS081347) and Wayne State University President's Research Enhancement Award.

  12. Dexmedetomidine Postconditioning Reduces Brain Injury after Brain Hypoxia-Ischemia in Neonatal Rats.

    Science.gov (United States)

    Ren, Xiaoyan; Ma, Hong; Zuo, Zhiyi

    2016-06-01

    Perinatal asphyxia can lead to death and severe disability. Brain hypoxia-ischemia (HI) injury is the major pathophysiology contributing to death and severe disability after perinatal asphyxia. Here, seven-day old Sprague-Dawley rats were subjected to left brain HI. Dexmedetomidine was given intraperitoneally after the brain HI. Yohimbine or atipamezole, two α2 adrenergic receptor antagonists, were given 10 min before the dexmedetomidine injection. Neurological outcome was evaluated 7 or 28 days after the brain HI. Frontal cerebral cortex was harvested 6 h after the brain HI. Left brain HI reduced the left cerebral hemisphere weight assessed 7 days after the brain HI. This brain tissue loss was dose-dependently attenuated by dexmedetomidine. Dexmedetomidine applied within 1 h after the brain HI produced this effect. Dexmedetomidine attenuated the brain HI-induced brain tissue and cell loss as well as neurological and cognitive dysfunction assessed from 28 days after the brain HI. Dexmedetomidine postconditioning-induced neuroprotection was abolished by yohimbine or atipamezole. Brain HI increased tumor necrosis factor α and interleukin 1β in the brain tissues. This increase was attenuated by dexmedetomidine. Atipamezole inhibited this dexmedetomidine effect. Our results suggest that dexmedetomidine postconditioning reduces HI-induced brain injury in the neonatal rats. This effect may be mediated by α2 adrenergic receptor activation that inhibits inflammation in the ischemic brain tissues. PMID:26932203

  13. Application of laser therapy in the treatment of brain ischemia

    Science.gov (United States)

    Zalesskaya, G. A.; Nechipurenko, N. I.; Musienko, J. I.; Kuchinsky, A. V.

    2007-06-01

    Intravenous laser irradiation of blood (ILIB) by helium-neon laser (HNL) with λ=632.8 nm, 2.5-4.5 mW at the light guide outlet was employed to investigate ILIB influence on blood oxygen transport (BOT), hydro-ion balance for normal rabbits and after modeling of local ischemia of brain (LIB). Marked improvement of disturbances typical for ischemia was revealed for both hydro-ion balance characteristics and BOT parameters such as oxygen tension (p vO II), oxygen hemoglobin saturation (s vO II), p vO II of blood under its 50% saturation by O II (p50) and tendency was found to their normalization. To identify the molecular photoacceptors and the mechanisms of primary photoreactions the spectral data were used both in visible and infrared regions. On the basis of spectral analysis hemoglobin was discussed as a possible photoacceptor when blood is irradiated with HNL radiation. Variations in the redox properties of respiratory chain components were considered as primary mechanisms of light action on photoacceptor molecules that initiated a cascade of secondary reactions controlling cellular homeostasis parameters.

  14. 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 ...

  15. Hyperbaric oxygen modalities are differentially effective in distinct brain ischemia models

    Directory of Open Access Journals (Sweden)

    Robert P Ostrowski

    2016-01-01

    Full Text Available The effectiveness and efficacy of hyperbaric oxygen (HBO preconditioning and post-treatment modalities have been demonstrated in experimental models of ischemic cerebrovascular diseases, including global brain ischemia, transient focal and permanent focal cerebral ischemia, and experimental neonatal hypoxia-ischemia encephalopathy. In general, early and repetitive post-treatment of HBO appears to create enhanced protection against brain ischemia whereas delayed HBO treatment after transient focal ischemia may even aggravate brain injury. This review advocates the level of injury reduction upon HBO as an important component for translational evaluation of HBO based treatment modalities. The combined preconditioning and HBO post-treatment that would provide synergistic effects is also worth considering.

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    Theresa Ann Lusardi

    2014-02-01

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

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. 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

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

    DEFF Research Database (Denmark)

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

    2005-01-01

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

  6. Preconditioning with a novel metallopharmaceutical NO donor in anesthetized rats subjected to brain ischemia/reperfusion.

    Science.gov (United States)

    Campelo, Marcio Wilker Soares; Oriá, Reinaldo Barreto; Lopes, Luiz Gonzaga de França; Brito, Gerly Anne de Castro; Santos, Armenio Aguiar dos; Vasconcelos, Raquel Cavalcante de; Silva, Francisco Ordelei Nascimento da; Nobrega, Beatrice Nuto; Bento-Silva, Moisés Tolentino; Vasconcelos, Paulo Roberto Leitão de

    2012-04-01

    Rut-bpy is a novel nitrosyl-ruthenium complex releasing NO into the vascular system. We evaluated the effect of Rut-bpy (100 mg/kg) on a rat model of brain stroke. Forty rats were assigned to four groups (Saline solution [SS], Rut-bpy, SS+ischemia-reperfusion [SS+I/R] and Rut-bpy+ischemia-reperfusion [Rut-bpy+I/R]) with their mean arterial pressure (MAP) continuously monitored. The groups were submitted (SS+I/R and Rut-bpy+I/R) or not (SS and Rut-bpy) to incomplete global brain ischemia by occlusion of the common bilateral carotid arteries during 30 min followed by reperfusion for further 60 min. Thirty minutes before ischemia, rats were treated pairwise by intraperitoneal injection of saline solution or Rut-bpy. At the end of experiments, brain was removed for triphenyltetrazolium chloride staining in order to quantify the total ischemic area. In a subset of rats, hippocampus was obtained for histopathology scoring, nitrate and nitrite measurements, immunostaining and western blotting of the nuclear factor- κB (NF-κB). Rut-bpy pre-treatment decreased MAP variations during the transition from brain ischemia to reperfusion and decreased the fractional injury area. Rut-bpy pre-treatment reduced NF-κB hippocampal immunostaining and protein expression with improved histopathology scoring as compared to the untreated operated control. In conclusion, Rut-bpy improved the total brain infarction area and hippocampal neuronal viability in part by inhibiting NF-κB signaling and helped to stabilize the blood pressure during the transition from ischemia to reperfusion. PMID:22160748

  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. Ischemia Alters the Expression of Connexins in the Aged Human Brain

    OpenAIRE

    Taizen Nakase; Tetsuya Maeda; Yasuji Yoshida; Ken Nagata

    2009-01-01

    Although the function of astrocytic gap junctions under ischemia is still under debate, increased expression of connexin 43 (Cx43) has been observed in ischemic brain lesions, suggesting that astrocytic gap junctions could provide neuronal protection against ischemic insult. Moreover, different connexin subtypes may play different roles in pathological conditions. We used immunohistochemical analysis to investigate alterations in the expression of connexin subtypes in human stroke brains. Sev...

  12. 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.

  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. Brain targeted solid lipid nanoparticles for brain ischemia: preparation and in vitro characterization.

    Science.gov (United States)

    Morsi, Nadia M; Ghorab, Dalia M; Badie, Hany A

    2013-01-01

    This study aims at formulating solid lipid nanoparticles (SLNs) of Vinpocetine (VIN) to be used as a brain targeted sustained drug-delivery system. VIN is a derivative of vincamine alkaloid, used for chronic cerebral vascular ischemia. However, it suffers from low bioavailability and short half-life. Its oral bioavailability is recorded to be between 7 and 55%. Its elimination half-life is 1-2 h so it would be a good candidate for a sustained drug-delivery system. VIN SLNs were prepared using modified high shear homogenization followed by ultrasonication technique. The effect of incorporating different lipids at different concentrations of various surfactants was investigated. The VIN SLNs were characterized by entrapment efficiency percent (EE%), particle size distribution, zeta-potential, and cumulative released percent after 96 h. The EE% ranged between 83.34% ± 0.95-94.56% ± 0.11 due to the lipophilic character of VIN. The mean particle size measured ranged from 123 nm-464 nm. The cumulative released percent after 96 h ranged from 23.55% to 75.67% showing a controlled release profile. Formula (F32) composed of 5% glyceryl monostearate (GMS) and stabilized by 2% surfactant mixture [Tween 80, Pluronic F 68 (1:1)] was the most appropriate formula for brain delivery having EE% of 89.09% ± 1.49, zero-order release kinetics with cumulative released percent of 72.12% after 96 h, zeta-potential of -11.3 ± 0.97 mV. It showed a unimodal size distribution with particle size ≈ 90 nm and polydispersity index of 0.121. The formula of choice in this study exhibited a zero-order sustained release profile and met the requirement for a brain targeted SLN so it could be a promising formula to deliver VIN to the brain. PMID:23477526

  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. The NMDA receptor changes during reperfusion after local ischemia in the rat brain

    International Nuclear Information System (INIS)

    Objective: To study the changes of N-methyl-D-aspartate(NMDA) receptor in the rat brain during reperfusion after local ischemia. Methods: The rat cerebral focal ischemia/reperfusion model after middle cerebral artery occlusion (MCAO) was made by the intraluminal suture method. After ischemia and reperfusion models were completed, the rat brain was removed immediately and dissected under the frozen state. After incubation with 3H-MK-801 which was used as a radioactive ligand, the samples were exposed on the hypersensitive film at the room temperature. Regions of interest (ROIs) were set bilaterally in each autoradiographic brain image. LEICAQ-550IWL imaging analysis system was used to detect the density of NMDA receptor. The ratios of the receptor density between affected and unaffected side in the same ROI were compared. Before receptor binding assay, the middle section of the ischemic cortex was separated, homogenized and centrifugated. After binding with the radioligand, radioactivity was measured by liquid scintillation counter. Scatchard plot was made from the liquid scintillation counter and affinity (Kd) and maximal binding (Bmax) changes of NMDA receptor were calculated. The results of Kd and Bmax were compared between groups. Results: NMDA receptor density in the corresponding ROI increased significantly during 2 h ischemia and 2 h reperfusion in comparison with the result of the sham group, which showed that the NMDA receptor channel was opened abundantly. The opening of the channel was mainly caused by the increase of the excitatory amino acids. There was significant decrease in the degree of channel opening in the 24 h and 72 h reperfusion groups in corresponding ROIs and no difference was found between two groups. The value of Kd in ischemia and reperfusion groups did not change. Bmax of NMDA receptor increased obviously during 2 h reperfusion and decreased obviously during 24 h and 72 h reperfusion. Conclusions: During the ischemia reperfusion, the

  17. Inhaled nitric oxide protects males but not females from neonatal mouse hypoxia-ischemia brain injury.

    Science.gov (United States)

    Zhu, Changlian; Sun, Yanyan; Gao, Jianfeng; Wang, Xiaoyang; Plesnila, Nikolaus; Blomgren, Klas

    2013-04-01

    It was recently discovered that while under normal conditions inhaled nitric oxide (iNO) does not affect cerebral blood flow, it selectively dilates arterioles in the ischemic penumbra during experimental cerebral ischemia, thereby increasing collateral blood flow and reducing ischemic brain damage. The mechanism was verified in multiple models, but only in male animals. Our aim was to evaluate the effects of iNO on brain injury in neonatal males and females. Nine-day-old mice were subjected to unilateral hypoxia-ischemia (HI), using 10% oxygen balanced with nitrogen, with or without 50 ppm NO. Brain injury 72 h after HI was reduced by iNO as judged by percentage of injury (-21.7%), atrophy (-23.7%), and total pathological score (-29%). The injury was significantly reduced in males (-32.4%, pbrain injury in a gender-related manner. PMID:24323275

  18. 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.

  19. Changes in astrocyte morphology and extracellular space volume fraction in brain slices after ischemia

    Czech Academy of Sciences Publication Activity Database

    Anděrová, Miroslava; Hock, Miroslav; Antonova, Tatiana; Chvátal, Alexandr; Syková, Eva

    Lisabon, 2004. s. 495. [Forum of European Neuroscience /4./. 10.07.2004-14.07.2004, Lisabon] R&D Projects: GA ČR GA305/02/1528; GA ČR GA305/03/1172; GA ČR GA305/04/1293; GA MŠk LN00A065 Keywords : extracellular space * brain ischemia Subject RIV: FH - Neurology

  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. 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.

  3. 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

  4. Brain ischemia with Alzheimer phenotype dysregulates Alzheimer's disease-related proteins.

    Science.gov (United States)

    Ułamek-Kozioł, Marzena; Pluta, Ryszard; Bogucka-Kocka, Anna; Januszewski, Sławomir; Kocki, Janusz; Czuczwar, Stanisław J

    2016-06-01

    There are evidences for the influence of Alzheimer's proteins on postischemic brain injury. We present here an overview of the published evidence underpinning the relationships between β-amyloid peptide, hyperphosphorylated tau protein, presenilins, apolipoproteins, secretases and neuronal survival/death decisions after ischemia and development of postischemic dementia. The interactions of above molecules and their influence and contribution to final ischemic brain degeneration resulting in dementia of Alzheimer phenotype are reviewed. Generation and deposition of β-amyloid peptide and tau protein pathology are essential factors involved in Alzheimer's disease development as well as in postischemic brain dementia. Postischemic injuries demonstrate that ischemia may stimulate pathological amyloid precursor protein processing by upregulation of β- and γ-secretases and therefore are capable of establishing a vicious cycle. Functional postischemic brain recovery is always delayed and incomplete by an injury-related increase in the amount of the neurotoxic C-terminal of amyloid precursor protein and β-amyloid peptide. Finally, we present here the concept that Alzheimer's proteins can contribute to and/or precipitate postischemic brain neurodegeneration including dementia with Alzheimer's phenotype. PMID:26940197

  5. 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

  6. 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.

  7. 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.

  8. 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. 

  9. Ischemia Alters the Expression of Connexins in the Aged Human Brain

    Directory of Open Access Journals (Sweden)

    Taizen Nakase

    2009-01-01

    Full Text Available Although the function of astrocytic gap junctions under ischemia is still under debate, increased expression of connexin 43 (Cx43 has been observed in ischemic brain lesions, suggesting that astrocytic gap junctions could provide neuronal protection against ischemic insult. Moreover, different connexin subtypes may play different roles in pathological conditions. We used immunohistochemical analysis to investigate alterations in the expression of connexin subtypes in human stroke brains. Seven samples, sectioned after brain embolic stroke, were used for the analysis. Data, evaluated semiquantitatively by computer-assisted densitometry, was compared between the intact hemisphere and ischemic lesions. The results showed that the coexpression of Cx32 and Cx45 with neuronal markers was significantly increased in ischemic lesions. Cx43 expression was significantly increased in the colocalization with astrocytes and relatively increased in the colocalization with neuronal marker in ischemic lesions. Therefore, Cx32, Cx43, and Cx45 may respond differently to ischemic insult in terms of neuroprotection.

  10. 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

  11. 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.

  12. 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.

  13. 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...

  14. 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

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

    Directory of Open Access Journals (Sweden)

    Jinatta Jittiwat

    2009-01-01

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

  16. 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

  17. 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...... NMR spectra at 0.18 and 0.22 ppm (relative to the chemical shift of 1,2-diacyl-sn-glycero-3-phosphocholine (PCD(DIACYL)) at -0.84 ppm). These signals were identified as originating from 1,2-diacyl- sn-glycero-3-phospho-(N-acyl)-ethanolamine (NAPED(DIACYL)) and 1-(1'- alkenyl)-2-acyl-sn-glycero-3......-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-EDTA in the...

  18. 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

  19. 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

  20. 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

  1. Effect of hypoosmotic stress and ischemia on astrocyte membrane currents and morphology in brain slices in situ

    Czech Academy of Sciences Publication Activity Database

    Chvátal, Alexandr; Anděrová, Miroslava; Vargová, Lýdia; Hock, Miroslav; Syková, Eva

    San Diego, 2004. s. -. [Society for Neuroscience, Annual Meeting /34./. 23.10.2004-27.10.2004, San Diego] R&D Projects: GA ČR GA305/02/1528; GA ČR GA305/03/1172; GA ČR GA305/04/1293 Keywords : hypoosmotic stress * ischemia * brain slices Subject RIV: FH - Neurology

  2. 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.

  3. Ionizing radiation can induce tolerance of rat brain neurons against transient ischemia tissue

    International Nuclear Information System (INIS)

    In experiments authors used irradiation of experimental animals (male rats Wistar) of the head by doses 10, 20, 30, rep. 50 Gy gamma-ray, two days before application of lethal ischemic action (for-C), induced by 8 minutes lasting closing blood supply of the brain by carotids. Irradiation before ischemia caused a noticeable increase in the proportion of surviving neurons. This effect was increased with radiation dose. A statistically significant decrease in neuronal degeneration was recorded after doses of 30 Gy (23.10%) and 50 Gy (8.99%) compared with 49.9% in animals without exposure. Functionality of rescued neurons were determined by testing spatial memory of rats in the Morris swimming pool. Animals irradiated with 50 Gy needed less time than non-irradiated animals to find a platform hidden below the water surface in repeated test. Differences in smaller doses were not statistically significant. (authors)

  4. 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.

  5. 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

  6. 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.

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

    International Nuclear Information System (INIS)

    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.)

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  9. 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

  10. Changes in cerebral blood flow and psychometric indicators in veterans with early forms of chronic brain ischemia

    Directory of Open Access Journals (Sweden)

    Vasilenko Т.М.

    2015-09-01

    Full Text Available The goal is to study the cerebral blood flow and psychometric characteristics in veterans of Afghanistan with early forms of chronic brain ischemia. Material and Methods. The study included 74 veterans of the Afghan war aged from 45 to 55 years: group 1, 28 people with NPNKM; Group 2-28 patients with circulatory encephalopathy stage 1; group 3-18 healthy persons. Doppler examination of cerebral vessels was carried out on the unit «Smart-lite». Reactive and personal anxiety of patients was assessed using the scale of Spielberger, evaluation of the quality of life through the test SAN. Determining the level of neuroticism and psychoticism was conducted by the scale of neuroticism and psy-choticism. Results: The study of cerebral blood flow in the Afghan war veterans showed signs of insolvency of carotid and carotid-basilar anastomoses, hypoperfusion phenomenon with the depletion of autoregulation, violation of the outflow of venous blood at the level of the microvasculature, accompanied by cerebral arteries spasm. More than 40% of patients with early forms of chronic brain ischemia had high personal anxiety, low levels of well-being and activity, with maximum expression of dyscirculatory hypoxia. Conclusion. Readaptation of veterans of Afghanistan is accompanied by the changes in psychometric performance and the formation of the earliest forms of brain chronic ischemia associated with inadequate hemodynamics providing increased functional activity of the brain and the inefficiency of compensatory-adaptive reactions.

  11. 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.

  12. 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.

  13. Neurotrophic Signaling Factors in Brain Ischemia/Reperfusion Rats: Differential Modulation Pattern between Single-Time and Multiple Electroacupuncture Stimulation

    OpenAIRE

    Changpeng Wang; Fan Yang; Xiaoyan Liu; Ming Liu; Yun Zheng; Jingchun Guo

    2014-01-01

    Electroacupuncture (EA) treatment has been widely used for stroke-like disorders in traditional Chinese medicine. However, the underlying mechanisms remain unclear. Our previous studies showed that single-time EA stimulation at “Baihui” (GV 20) and “Shuigou” (GV 26) after the onset of ischemia can protect the brain against ischemic injury in rats with middle cerebral artery occlusion (MCAO). Here, we further investigated the differential effects between multiple EA and single-time EA stimulat...

  14. Estrogen stimulates microglia and brain recovery from hypoxia-ischemia in normoglycemic but not diabetic female mice

    OpenAIRE

    Zhang, Liqun; Nair, Aji; Krady, Kyle; Corpe, Christopher; Bonneau, Robert H.; Simpson, Ian A.; Vannucci, Susan J

    2004-01-01

    Diabetic hyperglycemia increases ischemic brain damage in experimental animals and humans. The mechanisms are unclear but may involve enhanced apoptosis in penumbral regions. Estrogen is an established neuroprotectant in experimental stroke. Our previous study demonstrated that female diabetic db/db mice suffered less damage following cerebral hypoxia-ischemia (H/I) than male db/db mice. Here we investigated the effects of diabetes and estrogen apoptotic gene expression following H/I. Female ...

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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. PMID:25355958

  20. 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

  1. Human microglia transplanted in rat focal ischemia brain induce neuroprotection and behavioral improvement.

    Directory of Open Access Journals (Sweden)

    Dashdemberel Narantuya

    Full Text Available BACKGROUND AND PURPOSE: Microglia are resident immunocompetent and phagocytic cells of central nervous system (CNS, which produce various cytokines and growth factors in response to injury and thereby regulate disease pathology. The purpose of this study is to investigate the effects of microglial transplantation on focal cerebral ischemia model in rat. METHODS: Transient middle cerebral artery occlusion (MCAO in rats was induced by the intraluminal filament technique. HMO6 cells, human microglial cell line, were transplanted intravenously at 48 hours after MCAO. Functional tests were performed and the infarct volume was measured at 7 and 14 days after MCAO. Migration and cell survival of transplanted microglial cells and host glial reaction in the brain were studied by immunohistochemistry. Gene expression of neurotrophic factors, cytokines and chemokines in transplanted cells and host rat glial cells was determined by laser capture microdissection (LCM and quantitative real time-PCR. RESULTS: HMO6 human microglial cells transplantation group demonstrated significant functional recovery compared with control group. At 7 and 14 days after MCAO, infarct volume was significantly reduced in the HMO group. In the HMO6 group, number of apoptotic cells was time-dependently reduced in the infarct core and penumbra. In addition, number of host rat microglia/macrophages and reactive astrocytes was significantly decreased at 7 and 14 days after MCAO in the penumbra. Gene expression of various neurotrophic factors (GDNF, BDNF, VEGF and BMP7 and anti-inflammatory cytokines (IL4 and IL5 was up-regulated in transplanted HMO6 cells of brain tissue compared with those in culture. The expression of GDNF and VEGF in astrocytes in penumbra was significantly up-regulated in the HMO6 group. CONCLUSIONS: Our results indicate that transplantation of HMO6 human microglial cells reduces ischemic deficits and apoptotic events in stroke animals. The results were mediated

  2. 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.

  3. Inhibition of central angiotensin-converting enzyme with enalapril protects the brain from ischemia/reperfusion injury in normotensive rat

    Directory of Open Access Journals (Sweden)

    H Panahpour

    2010-03-01

    Full Text Available "n  Background and the Purpose of the study: Central Angiotensin Converting Enzyme (ACE has an important role on cerebral microcirculation and metabolism. However, its role in terms of protecting the brain from ischemic/reperfusion (I/R injury are debatable. This study evaluated the role of ACE, using enalapril as ACE inhibitor, in protection of the brain from I/R injury during transient focal cerebral ischemia (TFCI in normotensive rat. Method: Male Sprague Dawley rats (280-320g randomly assigned to control ischemic and enalapril pre-treated ischemic groups. Enalapril was injected intraperitoneally 1 h before middle cerebral artery occlusion (MCAO at the dose of 0.03 or 0.1 mg/kg. Cerebral ischemia was induced by 60 min MCAO followed by 24 hrs reperfusion. After evaluation of neurological deficit scores (NDS the animal was sacrificed for assessment of cerebral infarction and edema. Results: TFCI induced cerebral infarctions (283±18 mm3, brain edema (4.1±0.4% and swelling (9.8±1.5% with NDS of 3.11±0.36. Non-hypotensive dose of enalapril (0.03 mg/kg improved NDS (1.37±0.26, reduced cerebral infarction (45%, brain edema (54% and swelling of the lesioned hemispheres (34% significantly. However, hypotensive dose of enalapril (0.1 mg/kg could improve neurological activity (1.67±0.31 and failed to reduce cerebral infarction (276±39mm3 and swelling (10.4±1.4%. Conclusion: In the rat model of transient focal cerebral ischemia, inhibition of angiotensin converting enzyme with non-hypotensive doses of enalapril has the benefit of improving neurological activity, reducing cerebral infarction, brain swelling and edema of acute ischemic stroke. Therefore, it is reasonable to conclude that central renin-angiotensin system may participate in ischemic/reperfusion injury of the cerebral cortex.

  4. Platelet activating factor receptor blockade enhances recovery after multifocal brain ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Kochanek, P.M.; Dutka, A.J.; Kumaroo, K.K.; Hallenbech, J.M.

    1987-12-14

    The authors treated four anesthetized dogs with the platelet activating factor (PAF) receptor antagonist kadsurenone prior to 60 min of multifocal ischemia induced by air embolism, and measured neuronal recovery, blood flow and autologous /sup 111/In-labeled platelet accumulation for 4 h after ischemia. Four anesthetized animals with identical ischemia served as controls. Kadsurenone administered 5 min prior to ischemia and continuously throughout ischemia and recovery significantly enhanced recovery of cortical somatosensory evoked response (CSER) amplitude when compared to controls. They estimated platelet accumulation as /sup 111/In activity (cmp/g tissue) in the injured hemisphere minus that in the non-injured hemisphere. Kadsurenone treated animals did not exhibit significantly altered /sup 111/In labeled platelet accumulation when compared to controls. Beneficial effects of PAF receptor blockade other than those on platelet accumulation may be involved. 20 references, 1 figure.

  5. Platelet activating factor receptor blockade enhances recovery after multifocal brain ischemia

    International Nuclear Information System (INIS)

    The authors treated four anesthetized dogs with the platelet activating factor (PAF) receptor antagonist kadsurenone prior to 60 min of multifocal ischemia induced by air embolism, and measured neuronal recovery, blood flow and autologous 111In-labeled platelet accumulation for 4 h after ischemia. Four anesthetized animals with identical ischemia served as controls. Kadsurenone administered 5 min prior to ischemia and continuously throughout ischemia and recovery significantly enhanced recovery of cortical somatosensory evoked response (CSER) amplitude when compared to controls. They estimated platelet accumulation as 111In activity (cmp/g tissue) in the injured hemisphere minus that in the non-injured hemisphere. Kadsurenone treated animals did not exhibit significantly altered 111In labeled platelet accumulation when compared to controls. Beneficial effects of PAF receptor blockade other than those on platelet accumulation may be involved. 20 references, 1 figure

  6. 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.

  7. EAAC1 Gene Deletion Increases Neuronal Death and Blood Brain Barrier Disruption after Transient Cerebral Ischemia in Female Mice

    Directory of Open Access Journals (Sweden)

    Bo Young Choi

    2014-10-01

    Full Text Available EAAC1 is important in modulating brain ischemic tolerance. Mice lacking EAAC1 exhibit increased susceptibility to neuronal oxidative stress in mice after transient cerebral ischemia. EAAC1 was first described as a glutamate transporter but later recognized to also function as a cysteine transporter in neurons. EAAC1-mediated transport of cysteine into neurons contributes to neuronal antioxidant function by providing cysteine substrates for glutathione synthesis. Here we evaluated the effects of EAAC1 gene deletion on hippocampal blood vessel disorganization after transient cerebral ischemia. EAAC1−/− female mice subjected to transient cerebral ischemia by common carotid artery occlusion for 30 min exhibited twice as much hippocampal neuronal death compared to wild-type female mice as well as increased reduction of neuronal glutathione, blood–brain barrier (BBB disruption and vessel disorganization. Pre-treatment of N-acetyl cysteine, a membrane-permeant cysteine prodrug, increased basal glutathione levels in the EAAC1−/− female mice and reduced ischemic neuronal death, BBB disruption and vessel disorganization. These findings suggest that cysteine uptake by EAAC1 is important for neuronal antioxidant function under ischemic conditions.

  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. 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

  10. 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.

  11. 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...

  12. Application of EPI diffusion-weighted and Gd-DTPA T2* perfusion imaging in the diagnosis of brain ischemia

    International Nuclear Information System (INIS)

    Purpose: To study the MR and CT appearances of brain ischemia on diffusion-weighted imaging (DWI) and evaluate the role of EPI ADC-map, DWI and T2* perfusion imaging in acute stroke. Methods: DWI or ADC-map and routine T1WI and T2WI were performed in 36 patients with stroke (the time after onset of stroke: 2 hours - 2 months). Among them, 12 cases had perfusion imaging simultaneously. Results: Gd-DTPA T2* perfusion imaging demonstrated decrease of rrCBV and rrCBF in 10 cases; identical in 1 case and increase in 1 case. The mean transit time in the diseased area was longer than that of the contralateral corresponding region (paired t test: P2* perfusion imaging can demonstrate the decrease and restoration of CBF in the brain ischemic regions. DWI and ADC-map are highly valuable in the early diagnosis and monitoring the development of brain ischemic disease

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

    Science.gov (United States)

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

    2010-12-29

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

  15. 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

  16. 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

  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. 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)

  19. 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.

  20. Cortical evoked potential and extracellular K+ and H+ at critical levels of brain ischemia

    DEFF Research Database (Denmark)

    Astrup, J; Symon, L; Branston, N M; Lassen, N A

    1977-01-01

    evoked response. This study tests the hypothesis that electrical failure in ischemia may be directly associated with a massive release of intracellular K+ or with a critical degree of extracellular acidosis. By microelectrode techniques, measurements of blood flow, extracellular activity of K+ and H+ as...... occurred at 18 greater than 6 greater than 2 ml/100 gm per minute (median with 5% confidence limits). Thus a dual threshold in ischemia for neuronal function is described, the threshold for release of K+ being clearly lower than the threshold for complete electrical failure. Further, the findings support...

  1. Does Neonatal Brain Ischemia Induce Schizophrenia-Like Behavior in Young Adult Rats?

    Czech Academy of Sciences Publication Activity Database

    Tejkalová, H.; Kaiser, M.; Klaschka, Jan; Šťastný, František

    2007-01-01

    Roč. 56, č. 6 (2007), s. 815-823. ISSN 0862-8408 R&D Projects: GA MZd(CZ) NR8797 Institutional research plan: CEZ:AV0Z10300504; CEZ:AV0Z50110509 Keywords : neonatal ischemia * schizophrenia * rat * prepulse inhibition Subject RIV: FL - Psychiatry, Sexuology Impact factor: 1.505, year: 2007

  2. 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

  3. 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

  4. 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. ...

  5. β-Dystroglycan cleavage by matrix metalloproteinase-2/-9 disturbs aquaporin-4 polarization and influences brain edema in acute cerebral ischemia.

    Science.gov (United States)

    Yan, W; Zhao, X; Chen, H; Zhong, D; Jin, J; Qin, Q; Zhang, H; Ma, S; Li, G

    2016-06-21

    Dystroglycan (DG) is widely expressed in various tissues, and throughout the cerebral microvasculature. It consists of two subunits, α-DG and β-DG, and the cleavage of the latter by matrix metalloproteinase (MMP)-2 and -9 underlies a number of physiological and pathological processes. However, the involvement of MMP-2/-9-mediated β-DG cleavage in cerebral ischemia remains uncertain. In astrocytes, DG is crucial for maintaining the polarization of aquaporin-4 (AQP4), which plays a role in the regulation of cytotoxic and vasogenic edema. The present study aimed to explore the effects of MMP-2/-9-mediated β-DG cleavage on AQP4 polarization and brain edema in acute cerebral ischemia. A model of cerebral ischemia was established via permanent middle cerebral artery occlusion (pMCAO) in male C57BL/6 mice. Western blotting, real-time polymerase chain reaction (PCR), immunohistochemical staining, immunofluorescent staining, electron microscopy, and light microscopy were used. Captopril was applied as a selective MMP-2/-9 inhibitor. Recombinant mouse MMP (rmMMP)-2 and -9 were used in an in vitro cleavage experiment. The present study demonstrated evidence of β-DG cleavage by MMP-2/-9 in pMCAO mouse brains; this cleavage was implicated in AQP4 redistribution and brain edema in cerebral ischemia. In addition, captopril exacerbated cytotoxic edema and ameliorated vasogenic edema at 24h after pMCAO, and alleviated brain edema and neurological deficit at 48h and 72h. In conclusion, this study provides novel insight into the effects of MMP-2/-9-mediated β-DG cleavage in acute cerebral ischemia. Such findings might facilitate the development of a therapeutic strategy for the optimization of MMP-2/-9 targeted treatment in cerebral ischemia. PMID:27038751

  6. 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.

  7. 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.

  8. 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

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

    OpenAIRE

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

    2010-01-01

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

  10. 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...

  11. 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

  12. 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

  13. The Noncompetitive AMPAR Antagonist Perampanel Abrogates Brain Endothelial Cell Permeability in Response to Ischemia: Involvement of Claudin-5.

    Science.gov (United States)

    Lv, Jian-Meng; Guo, Xiao-Min; Chen, Bo; Lei, Qi; Pan, Ya-Juan; Yang, Qian

    2016-07-01

    The blood-brain barrier (BBB) is formed by brain endothelial cells, and decreased BBB integrity contributes to vasogenic cerebral edema and increased mortality after stroke. In the present study, we investigated the protective effect of perampanel, an orally active noncompetitive AMPA receptor antagonist, on BBB permeability in an in vitro ischemia model in murine brain endothelial cells (mBECs). The results showed that perampanel significantly attenuated oxygen glucose deprivation (OGD)-induced loss of cell viability, release of lactate dehydrogenase, and apoptotic cell death in a dose-dependent manner. Perampanel treatment did not alter the expression and surface distribution of various glutamate receptors. Furthermore, the results of calcium imaging showed that perampanel had no effect on OGD-induced increase in intracellular Ca(2+) concentrations. Treatment with perampanel markedly reduced the paracellular permeability of mBECs after OGD in different time points, as measured by transepithelial electrical resistance assay. In addition, the expression of claudin-5 at protein level, but not at mRNA level, was increased by perampanel treatment after OGD. Knockdown of claudin-5 partially prevented perampanel-induced protection in cell viability and BBB integrity in OGD-injured mBECs. These data show that the noncompetitive AMPA receptor antagonist perampanel affords protection against ischemic stroke through caludin-5 mediated regulation of BBB permeability. PMID:26306919

  14. 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

  15. 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

  16. 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.

  17. 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 ...

  18. 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...

  19. Stress-responsive heme oxygenase-1 isoenzyme participates in Toll-like receptor 4-induced inflammation during brain ischemia.

    Science.gov (United States)

    Wang, Rui; Wang, Shu-Ting; Wang, Yu-Di; Wu, Gang; Du, Yan; Qian, Man-Qing; Liang, Xing-Guang; Elbatreek, Mahmoud H; Yang, Hong-Yu; Liu, Zhi-Rong; Fukunaga, Kohji; Liu, Jian-Xiang; Lu, Ying-Mei

    2016-04-13

    Toll-like receptors (TLRs) are involved in the progression of ischemic brain injury and hence vascular dementia; however, the underlying mechanisms are largely unknown. Here, we have investigated the interrelationship between stress-responsive heme oxygenase (HO)-1 isoenzyme and TLR4 during chronic brain hypoperfusion. The right unilateral common carotid artery occlusion was performed by ligation of the right common carotid artery in C57BL/6J mice. The brain cortex or hippocampus was removed for western blotting and confocal immunofluorescence analysis. The link between HO-1 and TLR4 was further examined by silencing TLR4 and pharmacological inhibition of HO-1 in primary cultured cortical neurons. Cognitive dysfunction and decrease in cerebral blood flow in mice were observed 4 weeks after the occlusion. Our data further show that common carotid artery occlusion induced an increase in TLR4 and HO-1 protein levels. Although the administration of CoPP (10 mg/kg), HO-1 agonist, improved the cognitive dysfunction in a mice model of occlusion, western blot analysis in primary cultured cortical neurons showed that HO-1 was upregulated after lipopolysaccharide treatment; this was partially abolished by the TLR4 siRNA interference. The flow cytometry analysis showed that pharmacological inhibition of HO-1 by ZnPP (100 μM) further exaggerated lipopolysaccharide-induced neuronal cell death. Hence, stress-responsive HO-1 isoenzyme participates in TLR4-induced inflammation during chronic brain ischemia. The pharmacological manipulation of TLR4 or the HO-1 antioxidant defense pathway may represent a novel treatment strategy for neuronal protection in vascular dementia. PMID:26966782

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    Eckermann Jan M

    2012-04-01

    Full Text Available 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 studies, further neuroprotective mechanisms of hydrogen therapy remain to be elucidated. Hydrogen may serve as an adjunct treatment for neurological disorders.

  2. 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...

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

    Directory of Open Access Journals (Sweden)

    Haelewyn Benoit

    2011-04-01

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

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  8. Hyperbaric oxygen preconditioning ameliorates hypoxia-ischemia brain damage by activating Nrf2 expression in vivo and in vitro.

    Science.gov (United States)

    Zhai, Xiao; Lin, Han; Chen, Yu; Chen, Xiao; Shi, Jiazi; Chen, Ouyang; Li, Jiasi; Sun, Xuejun

    2016-01-01

    The present study aimed to investigate whether hyperbaric oxygen preconditioning (HBO-PC) could ameliorate hypoxia-ischemia brain damage (HIBD) by an increase of Nrf2 expression. P7 Sprague-Dawley rats (aged 7 d, n = 195) were used in two in vivo experiments, including BO-PC exposure experiments in non-HIBD models and treatment experiments in HIBD models. 2,3,5-triphenyltetrazolium chloride (TTC) staining, Nissl Staining, and TUNEL staining were performed. And expressions of Nrf2, HO-1, and GSTs were measured. For in vitro studies, oxygen-glucose deprivation cells were established. Morphological and apoptotic staining and gene silencing of Nrf2 by siRNA transfection were investigated. For exposure experiments, HBO-PC for longer time increased the expression of Nrf2 significantly. And for treatment experiments, HBO-PC treatment significantly decreased infarction area, lessened neuronal injury, reduced apoptosis, and increased both the expression of Nrf2 and activities of its downstream proteins. Cytology tests confirmed effects of HBO-PC treatments. Besides, Nrf2 siRNA significantly reduced protective effects of HBO-PC. These observations demonstrated that an up-regulation of Nrf2 by HBO-PC might play an important role in the generation of tolerance against HIBD. PMID:26729624

  9. 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

  10. Overweight worsens apoptosis, neuroinflammation and blood-brain barrier damage after hypoxic ischemia in neonatal brain through JNK hyperactivation

    Directory of Open Access Journals (Sweden)

    Wu Hsin-Chieh

    2011-04-01

    Full Text Available Abstract Background Apoptosis, neuroinflammation and blood-brain barrier (BBB damage affect the susceptibility of the developing brain to hypoxic-ischemic (HI insults. c-Jun N-terminal kinase (JNK is an important mediator of insulin resistance in obesity. We hypothesized that neonatal overweight aggravates HI brain damage through JNK hyperactivation-mediated upregulation of neuronal apoptosis, neuroinflammation and BBB leakage in rat pups. Methods Overweight (OF pups were established by reducing the litter size to 6, and control (NF pups by keeping the litter size at 12 from postnatal (P day 1 before HI on P7. Immunohistochemistry and immunoblotting were used to determine the TUNEL-(+ cells and BBB damage, cleaved caspase-3 and poly (ADP-ribose polymerase (PARP, and phospho-JNK and phospho-BimEL levels. Immunofluorescence was performed to determine the cellular distribution of phospho-JNK. Results Compared with NF pups, OF pups had a significantly heavier body-weight and greater fat deposition on P7. Compared with the NF-HI group, the OF-HI group showed significant increases of TUNEL-(+ cells, cleaved levels of caspase-3 and PARP, and ED1-(+ activated microglia and BBB damage in the cortex 24 hours post-HI. Immunofluorescence of the OF-HI pups showed that activated-caspase 3 expression was found mainly in NeuN-(+ neurons and RECA1-(+ vascular endothelial cells 24 hours post-HI. The OF-HI group also had prolonged escape latency in the Morris water maze test and greater brain-volume loss compared with the NF-HI group when assessed at adulthood. Phospho-JNK and phospho-BimEL levels were higher in OF-HI pups than in NF-HI pups immediately post-HI. JNK activation in OF-HI pups was mainly expressed in neurons, microglia and vascular endothelial cells. Inhibiting JNK activity by AS601245 caused more attenuation of cleaved caspase-3 and PARP, a greater reduction of microglial activation and BBB damage post-HI, and significantly reduced brain damage in

  11. The protection conferred against ischemia-reperfusion injury in the diabetic brain by N-acetylcysteine is associated with decreased dicarbonyl stress.

    Science.gov (United States)

    Wang, Bin; Aw, Tak Yee; Stokes, Karen Y

    2016-07-01

    Diabetes, a risk factor for stroke, leads to elevated blood methylglyoxal (MG) levels. This is due to increased MG generation from the high glucose levels, and because diabetes impairs the glutathione (GSH)-glyoxalase system for MG elimination. MG glycates proteins and causes dicarbonyl stress. We investigated the contribution of MG and GSH to stroke outcome. Cerebral ischemia/reperfusion was performed in chemical-induced (streptozotocin) and genetic Akita mouse models of Type 1 diabetes. Brain infarction and functions of the GSH-dependent MG elimination pathway were determined. Diabetes increased post-ischemia-reperfusion cerebral infarct area in association with elevated MG and diminished GSH levels. Infarct size correlated with brain MG-to-GSH ratio. Expression of glutamate-cysteine ligase catalytic subunit (GCLc) was increased in diabetic brain. GCL activity was unchanged. MG-adducts were elevated in the diabetic brain and, using immunoprecipitation, we identified one of the bands as glycated occludin. This was accompanied by increased blood-brain barrier permeability. Total protein carbonyls were elevated, indicative of oxidative/carbonyl stress. N-acetylcysteine (NAC) corrected MG-to-GSH ratio, and reduced diabetic brain infarct area, occludin glycation and permeability. In addition, protein carbonyls were decreased by NAC. We showed that the diabetic brain exhibited a lower GSH-dependent potential for MG elimination, which contributed to increased protein glycation, and oxidative/carbonyl stress. The consequence of these changes was aggravated post-stroke brain injury. NAC administration protected against the exacerbated brain damage via restored GSH generation and normalization of the MG-to-GSH ratio and possibly by attenuating oxidative/carbonyl stress. This treatment could contribute to the successful management of stroke risk/outcome in diabetes. PMID:27083477

  12. Perfusion measurements of the brain: using dynamic CT for the quantitative assessment of cerebral ischemia in acute stroke

    International Nuclear Information System (INIS)

    Objective: Perfusion CT has been successfully used as a functional imaging technique for the differential diagnosis of patients with hyperacute stroke. We investigated to what extent this technique can also be used for the quantitative assessment of cerebral ischemia. Methods and material: We studied linearity, spatial resolution and noise behaviour of cerebral blood flow (CBF) determination with computer simulations and phantom measurements. Statistical ROI based analysis of CBF images of a subset of 38 patients from a controlled clinical stroke study with currently more than 75 patients was done to check the power of relative cerebral blood flow (rCBF) values to predict definite infarction and ischemic penumbra. Classification was performed using follow-up CT and MR data. Results: Absolute CBF values were systematically underestimated, the degree depended on the cardiac output of the patients. Phantom measurements and simulations indicated very good linearity allowing reliable calculation of rCBF values. Infarct and penumbra areas in 19 patients receiving standard heparin therapy had mean rCBF values of 0.19 and 0.62, respectively. The corresponding values for 19 patients receiving local intraarterial fibrinolysis were 0.18 and 0.57. The difference between infarct and penumbra values was highly significant (P<0.0001) in both groups. No penumbra area was found with an rCBF value of less than 0.20. While in the heparin group only 25% of all areas with an rCBF between 0.20 and 0.35 survived, in the fibrinolytic group 61% of these areas could be saved (P<0.05). Conclusion: Perfusion CT is a fast and practical technique for routine clinical application. It provides substantial and important additional information for the selection of the optimal treatment strategy for patients with hyperacute stroke. Relative values of cerebral blood flow discriminate very well between areas of reversible and irreversible ischemia; an rCBF value of 0.20 appears to be a definite lower

  13. 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...

  14. Microglial Involvement in Neuroplastic Changes Following Focal Brain Ischemia in Rats

    OpenAIRE

    Madinier, Alexandre; Bertrand, Nathalie; Mossiat, Claude; Prigent-Tessier, Anne; Beley, Alain; Marie, Christine; Garnier, Philippe

    2009-01-01

    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 ...

  15. 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), ...

  16. Protective Effect of Angiopoietin-1 on the Blood Brain Barrier after Focal Cerebral IschemiaReperfusion Injury in Rats

    Directory of Open Access Journals (Sweden)

    Xuan GAO

    2015-03-01

    Full Text Available Objective: To observe the protective effect of angiopoietin-1 (Ang-1 on the blood brain barrier (BBB after focal cerebral ischemia-reperfusion injury (CIRI in rats. Methods: Forty male healthy Wister rats were selected. The focal CIRI models were established using middle cerebral artery occlusion and 30 rats were divided into sham-operation group (n=10, normal saline group (NS group (n=10 and Ang-1 treatment group (n=10. The rats were killed 48 h after reperfusion, and brain water content, BBB permeability, cerebral infarction volume and neurological severity scores in rats were detected respectively. Results: 48 h after reperfusion, both the brain water content and Evans blue (EB content in Ang-1 treatment group were significantly lower than in NS control [(68.69±4.46 % vs. (79.08±4.12 %, P<0.001; (98.60±10.56 μg/g vs. (379.90±21.64 μg/g, P<0.001], and there was no statistical significance by comparison to those in sham-operation group [(65.37±3.28 %; (89.62±8.65 μg/g, P>0.05]. The cerebral infarction volume in Ang-1 treatment group was markedly smaller than in NS group [(0.119±0.022 cm3 vs. (0.407±0.036 cm3, P<0.001], and no significant difference was presented when compared with sham-operation group [(0.104±0.011 cm3, P>0.05]. Besides, the neurological severity scores in Ang-1 treatment group were notably lower than in NS group [(1.83±0.29 points vs. (2.87±0.34 points, P<0.001], but higher than in sham-operation group [(0.79±0.11 points, P<0.001]. Conclusion: Ang-1 can decrease BBB permeability after focal CIRI in rats, so it has a protective effect on CIRI.

  17. 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.

  18. 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

  19. 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

  20. Stimulation of the subthalamic vasodilator area and fastigial nucleus independently protects the brain against focal ischemia.

    Science.gov (United States)

    Glickstein, S B; Ilch, C P; Reis, D J; Golanov, E V

    2001-08-31

    We investigated whether stimulation of the functionally discrete subthalamic region, subthalamic cerebrovasodilator area (SVA), which increases cerebral blood flow (CBF) when excited, would, like stimulation of cerebellar fastigial nucleus (FN), produce central neurogenic neuroprotection. A 1-h electrical stimulation of SVA or FN reduced infarctions triggered by permanent occlusion of middle cerebral artery (MCA) by 48-55% in Sprague-Dawley rats and by 59% in Fisher rats. The salvaging effect of SVA stimulation, similar to FN, was long lasting and reduced the volume of infarctions placed 72 h or 10 days later by 58 and 26%, respectively, in Fisher rats. Bilateral lesioning of FN neurons by the microinjection of ibotenic acid 5 days before SVA stimulation did not affect SVA-evoked neuroprotection. Bilateral lesions of SVA neurons administered 5 days before FN stimulation had no effect on FN-induced neuroprotection but reversed the stimulus-locked increase in CBF accompanying FN stimulation. This study demonstrates that (1) excitation of neurons and/or fibers projecting through the SVA reduces ischemic infarctions as substantially as excitation of FN neurons; (2) the effects are long-lasting and not attributable to increases in cerebral blood flow, changes in blood gases or brain temperature, or rat strain; (3) the neuroprotective effects of SVA and FN stimulation are mutually independent and (4) FN-evoked cerebrovasodilation is mediated by SVA neurons. The SVA and FN are part of a neuronal system in CNS, which is distributed and, when excited, acts to protect the brain from ischemic injury. PMID:11520492

  1. 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

  2. Hepatic ischemia

    Science.gov (United States)

    Hepatic ischemia is a condition in which the liver does not get enough blood or oxygen, causing injury to ... pressure from any condition can lead to hepatic ischemia. Such conditions may include: Abnormal heart rhythms Dehydration ...

  3. 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

  4. Clinical significance of changes of serum IL-6 and TNF-α levels in rat models of hypoxic-ischemia brain injury

    International Nuclear Information System (INIS)

    Objective: To explore the clinical significance of changes of serum interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels in rat models of hypoxic-ischemia (HI) brain injury. Methods: Seventy five rat HI brain injury nodels were prepared with bilateral occlusion of common carotid artery for 24rs followed 2hrs later by hypoxia (breathing 8% oxygen) for 2hrs. One fifth of the animals were sacrificed at 4h, 8h, 12h, 24h and 48h later respectively, the serum and brain homogenate concentrations of IL-6 and TNF-α were determined with RIA and brain tissues were pathologically examined. Results: The concentrations of IL-6 and TNF-α were dynamically changed within 48h in serum and brain homogenate. Peak values occurred at 24h with serum and at 12h with brain homogenate. Meanwhile, levels of both cytokines were significantly higher in the models than those in controls (P<0.01 or P<0.05). Conclusion: The concentrations of IL-6 and TNF-α were dynamically(sham operation only, 15 animals) changed and might be regarded as the clinical markers of degree of HI brain injury. (authors)

  5. 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.

  6. Synchrotron radiation x-ray fluorescence (SRXRF) elemental distribution analysis of brain tissue in a rat model of transient focal ischemia

    International Nuclear Information System (INIS)

    It is shown recently that transient focal ischemia with a duration of 15 minutes in rat leads to delayed neurodegeneration in striatum, as evidenced by shortened T1 relaxation time in this brain region. The mechanism underlying such T1 change has been proposed to be deposition of paramagnetic metal ions, such as manganese, in the ischemic brain tissue. To further investigate the characteristics of metal ion deposition in the ischemic brain tissue, elemental (i.e., Ca, Mn, Fe and Zn) distribution was measured in rat brain sections 2 weeks after a 15-min middle cerebral artery occlusion (MCAO) using synchrotron radiation X-Ray fluorescence analysis (SRXRF). The right middle cerebral arteries of 4 Wistar rats weighting 200-250 g were occluded under mild anesthesia (1-1.5% isoflurane) for 15 minutes by inserting a silicon-coated nylon thread from the external carotid artery into the internal carotid artery. Two weeks later the rats were decapitated and the brain was immediately removed, frozen in liquid nitrogen, cut into 100 m sections at the level of striatum with a microtome, and put onto polycarbonate films specially designed for SRXRF examination. All SRXRF spectra obtained with a beam spot size of 100 m x 100 m were normalized to the acquisition time and the counting of the ion chambers, and the contribution from the supporting polycarbonate film was subtracted. The X-ray peak area for each element (A) and the Compton scattering intensity (B) for the whole brain section were obtained. The relative content for each element was taken as the ratio of A to B. The results show that, compared to those in the contralateral striatum (i.e., left hemisphere), the relative contents of Ca and Mn in the ipsilateral striatum (i.e., right hemisphere) increased 1300.3±500.3% and 39±23%, respectively. The relative contents of Fe and Zn in the ischemic striatum showed no obvious changes as compared to control, contrasted to the results reported by Danielisova et al who showed

  7. 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.

  8. [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

  9. 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.

  10. 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

    induction of ischemia. Accumulation of NAEs did not depend on regulation of N-acylphosphatidylethanolamine-hydrolyzing phospholipase D or fatty acid amide hydrolase. Treatment with the fatty acid amide hydrolase inhibitor URB597 (cyclohexyl carbamic acid 3'-carbamoyl-biphenyl-3-yl ester; 1 mg/kg; i.p.) 1...

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

    Science.gov (United States)

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

    2016-04-01

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

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

    International Nuclear Information System (INIS)

    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.)

  13. The dose-response effect of acute intravenous transplantation of human umbilical cord blood cells on brain damage and spatial memory deficits in neonatal hypoxia-ischemia.

    Science.gov (United States)

    de Paula, S; Greggio, S; Marinowic, D R; Machado, D C; DaCosta, J Costa

    2012-05-17

    Despite the beneficial effects of cell-based therapies on brain repair shown in most studies, there has not been a consensus regarding the optimal dose of human umbilical cord blood cells (HUCBC) for neonatal hypoxia-ischemia (HI). In this study, we compared the long-term effects of intravenous administration of HUCBC at three different doses on spatial memory and brain morphological changes after HI in newborn Wistar rats. In addition, we tested whether the transplanted HUCBC migrate to the injured brain after transplantation. Seven-day-old animals underwent right carotid artery occlusion and were exposed to 8% O(2) inhalation for 2 h. After 24 h, randomly selected animals were assigned to four different experimental groups: HI rats administered with vehicle (HI+vehicle), HI rats treated with 1×10(6) (HI+low-dose), 1×10(7) (HI+medium-dose), and 1×10(8) (HI+high-dose) HUCBC into the jugular vein. A control group (sham-operated) was also included in this study. After 8 weeks of transplantation, spatial memory performance was assessed using the Morris water maze (MWM), and subsequently, the animals were euthanized for brain morphological analysis using stereological methods. In addition, we performed immunofluorescence and polymerase chain reaction (PCR) analyses to identify HUCBC in the rat brain 7 days after transplantation. The MWM test showed a significant spatial memory recovery at the highest HUCBC dose compared with HI+vehicle rats (Pbrain atrophy was also significantly lower in the HI+medium- and high-dose groups compared with the HI+vehicle animals (Pbrains by immunohistochemistry and PCR analyses 7 days after intravenous administration. These results revealed that HUCBC transplantation has the dose-dependent potential to promote robust tissue repair and stable cognitive improvement after HI brain injury. PMID:22441035

  14. The early diagnostic value of oral acetazolamide load combined with SPECT rCBF imaging in patients with transient ischemia attack in brain

    International Nuclear Information System (INIS)

    Objective: In order to assess the diagnostic value of acetazolamide (ACZ) combined with rCBF-SPECT imaging in patients with transient ischemia attack (TIA). Methods: SPECT imaging was performed before and after oral ACZ with visual and semiquantitative analysis of the images. Blood gas analysis was done before and after ACZ administration either. Results: After ACZ loading, in normal group, 99Tcm-ECD was distributed symmetrically on correspondent parts of the brain and rCBF was generally increased. The blood pH was decreased and blood PCO2 was increased, respectively in TIA group, the positive rate of hypoperfusion foci on SPECT images were increased from 5/6 to 6/6 in symptomatic patients and from 60% to 92% in asymptomatic patients. The total positive rate was 93%. Conclusion: Oral ACZ before SPECT imaging is a simple, reliable way for early diagnosis in patients with TIA

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

    DEFF Research Database (Denmark)

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

    2001-01-01

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

  16. Sirt1 in cerebral ischemia

    OpenAIRE

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

    2015-01-01

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

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. The Differences in the Cellular and Plasma Antioxidative Capacity Between Transient and Defined Focal Brain Ischemia: Does it Suggest Supporting Time-Dependent Neuroprotection Therapy?

    Science.gov (United States)

    Ljubisavljevic, Srdjan; Cvetkovic, Tatjana; Zvezdanovic, Lilika; Stojanovic, Svetlana; Stojanovic, Ivana; Kocic, Gordana; Zivkovic, Miroslava; Paunovic, Lidija; Milenkovic, Ljiljana; Lukic, Dragisa; Stamenovic, Jelena; Pavlovic, Dusica

    2016-07-01

    There are many opened questions about the precocious role of oxidative stress in the physiopathology of the early stage of transitory ischemic attack (TIA) and defined focal brain ischemia, as well as about its correlation with clinical severity, short-lasting and clinical outcome prediction in these conditions. The study evaluates the values of glutathione (GSH), glutathione peroxidase, and superoxide dismutase (SOD) in hemolysates and total thiol content (-SH), advanced oxidation protein products (AOPP), SOD, and malondialdehyde (MDA) in plasma, in TIA and stroke patients in the early stage of their neurological onset. The results are interpreted in view of the potential relationship between tested parameters and clinical severity and clinical outcome prediction. Better hemolysates' and total antioxidant profile with higher values of AOPP were observed in TIA compared to stroke patients (p outcome in stroke patients (p measurement of oxidative stress in TIA and stroke patients would be important for identifying patients' subgroups which might receive supporting therapy providing better neurological recovery and clinical outcome. That approach might give us an additional view of a short-lasting risk of stroke occurrence after TIA, and its clinical outcome and prognosis. PMID:26335597

  4. Effects of acute versus post-acute systemic delivery of neural progenitor cells on neurological recovery and brain remodeling after focal cerebral ischemia in mice.

    Science.gov (United States)

    Doeppner, T R; Kaltwasser, B; Teli, M K; Bretschneider, E; Bähr, M; Hermann, D M

    2014-01-01

    Intravenous transplantation of neural progenitor cells (NPCs) induces functional recovery after stroke, albeit grafted cells are not integrated into residing neural networks. However, a systematic analysis of intravenous NPC delivery at acute and post-acute time points and their long-term consequences does not exist. Male C57BL6 mice were exposed to cerebral ischemia, and NPCs were intravenously grafted on day 0, on day 1 or on day 28. Animals were allowed to survive for up to 84 days. Mice and tissues were used for immunohistochemical analysis, flow cytometry, ELISA and behavioral tests. Density of grafted NPCs within the ischemic hemisphere was increased when cells were transplanted on day 28 as compared with transplantation on days 0 or 1. Likewise, transplantation on day 28 yielded enhanced neuronal differentiation rates of grafted cells. Post-ischemic brain injury, however, was only reduced when NPCs were grafted at acute time points. On the contrary, reduced post-ischemic functional deficits due to NPC delivery were independent of transplantation paradigms. NPC-induced neuroprotection after acute cell delivery was due to stabilization of the blood-brain barrier (BBB), reduction in microglial activation and modulation of both peripheral and central immune responses. On the other hand, post-acute NPC transplantation stimulated post-ischemic regeneration via enhanced angioneurogenesis and increased axonal plasticity. Acute NPC delivery yields long-term neuroprotection via enhanced BBB integrity and modulation of post-ischemic immune responses, whereas post-acute NPC delivery increases post-ischemic angioneurogenesis and axonal plasticity. Post-ischemic functional recovery, however, is independent of NPC delivery timing, which offers a broad therapeutic time window for stroke treatment. PMID:25144721

  5. 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...

  6. 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.

  7. Detection of regional cerebral ischemia in the rat brain with susceptibility-enhanced echo-planar MR imaging

    International Nuclear Information System (INIS)

    This paper reports on an ultrafast imaging technique with a magnetic susceptibility contrast medium in order to monitor the relative perfusion of normal and compromised rat brain tissue. Unilateral (right) middle cerebral artery (MCA) occlusion (n = 4) was performed in Sprague-Dawley rats. Control (n = 4) and sham-operated (n = 3) rats were also studied. MR imaging was performed with a General Electric 2.0-T CSI system (equipped with Acustar S-150 self-shielded gradients). Coronal gradient refocused echo-planar images were acquired in 65.6 msec (section thickness 2 mm; sweep width, 62.5 kHz; 64 x 64 image matrix; field of view, 40 x 40 mm) in sets of 12 or 16, before and during bolus administration of MR contrast material 0.05 mmol of iron per kilogram as AMI-25 superparamagnetic iron oxide particles

  8. 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...

  9. 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...

  10. 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 ...

  11. 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

  12. 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; Edvinsson, Lars

    2014-01-01

    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...

  13. 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

  14. Mesenteric artery ischemia

    Science.gov (United States)

    Mesenteric artery ischemia occurs when there is a narrowing or blockage of one or more of the three major arteries that ... that supply blood to the intestine causes mesenteric ischemia. The arteries that supply blood to the intestines ...

  15. [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

  16. Clinical Neuroimaging of cerebral ischemia

    International Nuclear Information System (INIS)

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

  17. 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...

  18. Complex pattern of interaction between in utero hypoxia-ischemia and intra-amniotic inflammation disrupts brain development and motor function

    OpenAIRE

    Jantzie, Lauren L.; Corbett, Christopher J; Berglass, Jacqueline; Firl, Daniel J.; Flores, Julian; Mannix, Rebekah; Robinson, Shenandoah

    2014-01-01

    Background Infants born preterm commonly suffer from a combination of hypoxia-ischemia (HI) and infectious perinatal inflammatory insults that lead to cerebral palsy, cognitive delay, behavioral issues and epilepsy. Using a novel rat model of combined late gestation HI and lipopolysaccharide (LPS)-induced inflammation, we tested our hypothesis that inflammation from HI and LPS differentially affects gliosis, white matter development and motor impairment during the first postnatal month. Metho...

  19. Complex pattern of interaction between in utero hypoxia-ischemia and intra-amniotic inflammation disrupts brain development and motor function

    OpenAIRE

    Jantzie, Lauren L.; Corbett, Christopher J; Berglass, Jacqueline; Firl, Daniel J.; Flores, Julian; Mannix, Rebekah; Robinson, Shenandoah

    2014-01-01

    Background: Infants born preterm commonly suffer from a combination of hypoxia-ischemia (HI) and infectious perinatal inflammatory insults that lead to cerebral palsy, cognitive delay, behavioral issues and epilepsy. Using a novel rat model of combined late gestation HI and lipopolysaccharide (LPS)-induced inflammation, we tested our hypothesis that inflammation from HI and LPS differentially affects gliosis, white matter development and motor impairment during the first postnatal month. Meth...

  20. 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

  1. Infrared laser hemotherapy in cerebral ischemia modeling

    Science.gov (United States)

    Musienko, Julia I.; Nechipurenko, Natalia I.

    2003-10-01

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

  2. Effect of 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

  3. 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

  4. 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 ...

  5. 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, ...

  6. Improvement in Memory and Brain Long-term Potentiation Deficits Due to Permanent Hypoperfusion/Ischemia by Grape Seed Extract in Rats

    Directory of Open Access Journals (Sweden)

    Alireza Sarkaki

    2013-09-01

    Full Text Available   Objective(s: Cerebral hypoperfusion/ischemia (CHI is a neurological disease where impaired hippocampus electrical activity and cognition caused by a serial pathophysiological events. This study aimed to evaluate the effects of chronic oral administration of grape seed extract (GSE on passive avoidance memory and long-term potentiation (LTP after permanent bilateral common carotid arteries occlusion (2CCAO in male adult rats.   Materials and Methods: Thirty-two adult male Wistar rats were randomly divided into: 1 Sham+Veh, 2 Isch+Veh, 3 Sham+GSE, 4 Isch+GSE. In order to make 2CCAO as an animal model of CHI, carotid arteries were ligatured and then cut bilaterally. To evaluation of passive avoidance memory, step-down latency (STL was measured and LTP was recorded from hippocampal dentate gyrus (DG after high frequency stimulation (HFS in all rats. Results: We found that memory was significantly impaired in rats after CHI (P

  7. 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

  8. Ischemia-Reperfusion Damage

    OpenAIRE

    Yapca, Omer E.; Borekci, Bunyamin; Suleyman, Halis

    2013-01-01

    Ischemia-reperfusion damage is a complex pathological process that begins with tissue anoxia and continues with the production of free oxygen radicals, expanding with the inflammatory response. The literature suggests the importance of antioxidant and anti-inflammatory treatment to treat ischemia-reperfusion-related tissue damage.

  9. 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

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

    OpenAIRE

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

    2013-01-01

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

  11. Prodigiosin inhibits gp91phox and iNOS expression to protect mice against the oxidative/nitrosative brain injury induced by hypoxia–ischemia

    International Nuclear Information System (INIS)

    This study aimed to explore the mechanisms by which prodigiosin protects against hypoxia-induced oxidative/nitrosative brain injury induced by middle cerebral artery occlusion/reperfusion (MCAo/r) injury in mice. Hypoxia in vitro was modeled using oxygen–glucose deprivation (OGD) followed by reoxygenation of BV-2 microglial cells. Our results showed that treatment of mice that have undergone MCAo/r injury with prodigiosin (10 and 100 μg/kg, i.v.) at 1 h after hypoxia ameliorated MCAo/r-induced oxidative/nitrosative stress, brain infarction, and neurological deficits in the mice, and enhanced their survival rate. MCAo/r induced a remarkable production in the mouse brains of reactive oxygen species (ROS) and a significant increase in protein nitrosylation; this primarily resulted from enhanced expression of NADPH oxidase 2 (gp91phox), inducible nitric oxide synthase (iNOS), and the infiltration of CD11b leukocytes due to breakdown of blood–brain barrier (BBB) by activation of nuclear factor-kappa B (NF-κB). All these changes were significantly diminished by prodigiosin. In BV-2 cells, OGD induced ROS and nitric oxide production by up-regulating gp91phox and iNOS via activation of the NF-κB pathway, and these changes were suppressed by prodigiosin. In conclusion, our results indicate that prodigiosin reduces gp91phox and iNOS expression possibly by impairing NF-κB activation. This compromises the activation of microglial and/or inflammatory cells, which then, in turn, mediates prodigiosin's protective effect in the MCAo/r mice. -- Highlights: ► Prodigiosin ameliorated brain infarction and deficits. ► Prodigiosin protected against hypoxia/reperfusion-induced brain injury. ► Prodigiosin diminished oxidative/nitrosativestress and leukocytes infiltration. ► Prodigiosin reduced BBB breakdown. ► Prodigiosin down-regulated gp91phox and iNOS by inhibiting NF-κB activation.

  12. 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

  13. Blood-brain barrier permeability to manganese and to Gd-DOTA in a rat model of transient cerebral ischaemia. : BBB permeability after transient cerebral ischemia

    OpenAIRE

    Grillon, Emmanuelle; Provent, Peggy; Montigon, Olivier; Segebarth, Christoph; Rémy, Chantal; Barbier, Emmanuel

    2008-01-01

    Loss of integrity of the blood-brain barrier (BBB) and brain swelling is a potentially lethal complication of reperfusion in human stroke. To assess the time course of BBB modifications, we performed angiography, diffusion-weighted imaging, T1-weighted (T1 W) imaging and T1 mapping, and monitored acute changes after middle cerebral artery occlusion and recanalization in rats (n = 27). The animals were grouped according to the duration of occlusion: 30 min (group A, n = 8), 1 h 30 min (group B...

  14. 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.

  15. 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.

    Science.gov (United States)

    Xuan, Meiyan; Okazaki, Mari; Iwata, Naohiro; Asano, Satoshi; Kamiuchi, Shinya; Matsuzaki, Hirokazu; Sakamoto, Takeshi; Miyano, Yoshiyuki; Iizuka, Hiroshi; Hibino, Yasuhide

    2015-01-01

    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. PMID:25945116

  16. 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。

  17. 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

  18. 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

  19. 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 ...

  20. 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...

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

    International Nuclear Information System (INIS)

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

  2. Acute Mesenteric Ischemia

    Science.gov (United States)

    ... 2 Diabetes, Heart Disease a Dangerous Combo Are 'Workaholics' Prone to OCD, Anxiety? ALL NEWS > Resources First ... surgery is needed. Acute mesenteric ischemia has multiple causes. The most common are Arterial embolism Arterial thrombus ...

  3. 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...

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. [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

  10. mRNA redistribution during permanent focal cerebral ischemia.

    Science.gov (United States)

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

    2013-12-01

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

  11. 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).

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. A Novel Ligustrazine Derivative T-VA Prevents Neurotoxicity in Differentiated PC12 Cells and Protects the Brain against Ischemia Injury in MCAO Rats

    Directory of Open Access Journals (Sweden)

    Guoling Li

    2015-09-01

    Full Text Available Broad-spectrum drugs appear to be more promising for the treatment of acute ischemic stroke. In our previous work, a new ligustrazine derivative (3,5,6-trimethylpyrazin-2-yl methyl 3-methoxy-4-[(3,5,6-trimethylpyrazin-2-ylmethoxy]benzoate (T-VA showed neuroprotective effect on injured PC12 cells (EC50 = 4.249 µM. In the current study, we show that this beneficial effect was due to the modulation of nuclear transcription factor-κB/p65 (NF-κB/p65 and cyclooxygenase-2 (COX-2 expressions. We also show that T-VA exhibited neuroprotective effect in a rat model of ischemic stroke with concomitant improvement of motor functions. We propose that the protective effect observed in vivo is owing to increased vascular endothelial growth factor (VEGF expression, decreased oxidative stress, and up-regulation of Ca2+–Mg2+ ATP enzyme activity. Altogether, our results warrant further studies on the utility of T-VA for the potential treatment of ischemic brain injuries, such as stroke.

  18. 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...

  19. Magnetic resonance imaging of experimental cerebral ischemia

    International Nuclear Information System (INIS)

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

  20. Brain imaging and brain function

    International Nuclear Information System (INIS)

    This book is a survey of the applications of imaging studies of regional cerebral blood flow and metabolism to the investigation of neurological and psychiatric disorders. Contributors review imaging techniques and strategies for measuring regional cerebral blood flow and metabolism, for mapping functional neural systems, and for imaging normal brain functions. They then examine the applications of brain imaging techniques to the study of such neurological and psychiatric disorders as: cerebral ischemia; convulsive disorders; cerebral tumors; Huntington's disease; Alzheimer's disease; depression and other mood disorders. A state-of-the-art report on magnetic resonance imaging of the brain and central nervous system rounds out the book's coverage

  1. 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.

  2. Microglia protect neurons against ischemia by synthesis of tumor necrosis factor

    DEFF Research Database (Denmark)

    Lambertsen, Kate Lykke; Clausen, Bettina Hjelm; Babcock, Alicia Anne;

    2009-01-01

    Microglia and infiltrating leukocytes are considered major producers of tumor necrosis factor (TNF), which is a crucial player in cerebral ischemia and brain inflammation. We have identified a neuroprotective role for microglial-derived TNF in cerebral ischemia in mice. We show that cortical infa......-like receptor 2 expression in unmanipulated brain, which might also influence the neuronal response to injury. Our results identify microglia and microglial-derived TNF as playing a key role in determining the survival of endangered neurons in cerebral ischemia....

  3. 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-

  4. 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.

  5. 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.

  6. The evolving concept of physiological ischemia training vs. ischemia preconditioning.

    Science.gov (United States)

    Ni, Jun; Lu, Hongjian; Lu, Xiao; Jiang, Minghui; Peng, Qingyun; Ren, Caili; Xiang, Jie; Mei, Chengyao; Li, Jianan

    2015-11-01

    Ischemic heart diseases are the leading cause of death with increasing numbers of patients worldwide. Despite advances in revascularization techniques, angiogenic therapies remain highly attractive. Physiological ischemia training, which is first proposed in our laboratory, refers to reversible ischemia training of normal skeletal muscles by using a tourniquet or isometric contraction to cause physiologic ischemia for about 4 weeks for the sake of triggering molecular and cellular mechanisms to promote angiogenesis and formation of collateral vessels and protect remote ischemia areas. Physiological ischemia training therapy augments angiogenesis in the ischemic myocardium by inducing differential expression of proteins involved in energy metabolism, cell migration, protein folding, and generation. It upregulates the expressions of vascular endothelial growth factor, and induces angiogenesis, protects the myocardium when infarction occurs by increasing circulating endothelial progenitor cells and enhancing their migration, which is in accordance with physical training in heart disease rehabilitation. These findings may lead to a new approach of therapeutic angiogenesis for patients with ischemic heart diseases. On the basis of the promising results in animal studies, studies were also conducted in patients with coronary artery disease without any adverse effect in vivo, indicating that physiological ischemia training therapy is a safe, effective and non-invasive angiogenic approach for cardiovascular rehabilitation. Preconditioning is considered to be the most protective intervention against myocardial ischemia-reperfusion injury to date. Physiological ischemia training is different from preconditioning. This review summarizes the preclinical and clinical data of physiological ischemia training and its difference from preconditioning. PMID:26664354

  7. Experimental Focal Cerebral Ischemia

    DEFF Research Database (Denmark)

    Christensen, Thomas

    2007-01-01

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

  8. 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.

  9. 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

  10. 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.

  11. 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 ...

  12. Increased cardiac BNP expression associated with myocardial ischemia

    DEFF Research Database (Denmark)

    Goetze, J P; Christoffersen, Christina; Perko, M; Arendrup, H; Rehfeld, J F; Kastrup, J; Nielsen, L B

    2003-01-01

    Congestive heart failure is accompanied by increased cardiac brain natriuretic peptide (BNP) gene expression with elevated plasma concentrations of BNP and its precursor, proBNP. We investigated if myocardial ischemia in the absence of overt heart failure may be another mechanism for increased...... and proBNP concentrations to ventricular, but not atrial, BNP mRNA levels. Plasma BNP and proBNP concentrations were markedly increased in patients with coronary artery disease but without concomitant left ventricular dysfunction. These results are compatible with the notion that myocardial ischemia......, even in the absence of left ventricular dysfunction, augments cardiac BNP gene expression and increases plasma BNP and proBNP concentrations. Thus, elevated BNP and proBNP concentrations do not necessarily reflect heart failure but may also result from cardiac ischemia....

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

    OpenAIRE

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

    1992-01-01

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

  14. Ischemia causes muscle fatigue

    Science.gov (United States)

    Murthy, G.; Hargens, A. R.; Lehman, S.; Rempel, D. M.

    2001-01-01

    The purpose of this investigation was to determine whether ischemia, which reduces oxygenation in the extensor carpi radialis (ECR) muscle, causes a reduction in muscle force production. In eight subjects, muscle oxygenation (TO2) of the right ECR was measured noninvasively and continuously using near infrared spectroscopy (NIRS) while muscle twitch force was elicited by transcutaneous electrical stimulation (1 Hz, 0.1 ms). Baseline measurements of blood volume, muscle oxygenation and twitch force were recorded continuously, then a tourniquet on the upper arm was inflated to one of five different pressure levels: 20, 40, 60 mm Hg (randomized order) and diastolic (69 +/- 9.8 mm Hg) and systolic (106 +/- 12.8 mm Hg) blood pressures. Each pressure level was maintained for 3-5 min, and was followed by a recovery period sufficient to allow measurements to return to baseline. For each respective tourniquet pressure level, mean TO2 decreased from resting baseline (100% TO2) to 99 +/- 1.2% (SEM), 96 +/- 1.9%, 93 +/- 2.8%, 90 +/- 2.5%, and 86 +/- 2.7%, and mean twitch force decreased from resting baseline (100% force) to 99 +/- 0.7% (SEM), 96 +/- 2.7%, 93 +/- 3.1%, 88 +/- 3.2%, and 86 +/- 2.6%. Muscle oxygenation and twitch force at 60 mm Hg tourniquet compression and above were significantly lower (P ischemia leading to a 7% or greater reduction in muscle oxygenation causes decreased muscle force production in the forearm extensor muscle. Thus, ischemia associated with a modest decline in TO2 causes muscle fatigue.

  15. 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

  16. 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

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

    Science.gov (United States)

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

    2016-01-01

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

  18. 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

  19. Ischemia causes muscle fatigue

    Science.gov (United States)

    Murthy, G.; Hargens, A. R.; Lehman, S.; Rempel, D. M.

    2001-01-01

    The purpose of this investigation was to determine whether ischemia, which reduces oxygenation in the extensor carpi radialis (ECR) muscle, causes a reduction in muscle force production. In eight subjects, muscle oxygenation (TO2) of the right ECR was measured noninvasively and continuously using near infrared spectroscopy (NIRS) while muscle twitch force was elicited by transcutaneous electrical stimulation (1 Hz, 0.1 ms). Baseline measurements of blood volume, muscle oxygenation and twitch force were recorded continuously, then a tourniquet on the upper arm was inflated to one of five different pressure levels: 20, 40, 60 mm Hg (randomized order) and diastolic (69 +/- 9.8 mm Hg) and systolic (106 +/- 12.8 mm Hg) blood pressures. Each pressure level was maintained for 3-5 min, and was followed by a recovery period sufficient to allow measurements to return to baseline. For each respective tourniquet pressure level, mean TO2 decreased from resting baseline (100% TO2) to 99 +/- 1.2% (SEM), 96 +/- 1.9%, 93 +/- 2.8%, 90 +/- 2.5%, and 86 +/- 2.7%, and mean twitch force decreased from resting baseline (100% force) to 99 +/- 0.7% (SEM), 96 +/- 2.7%, 93 +/- 3.1%, 88 +/- 3.2%, and 86 +/- 2.6%. Muscle oxygenation and twitch force at 60 mm Hg tourniquet compression and above were significantly lower (P forearm extensor muscle. Thus, ischemia associated with a modest decline in TO2 causes muscle fatigue.

  20. 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...

  1. [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

  2. 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.

  3. 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

  4. 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.

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

    International Nuclear Information System (INIS)

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

  6. 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.)

  7. 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

  8. 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.

  9. 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

  10. 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 followi...

  11. 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,...

  12. Myocardial ischemia in hypertrophic cardiomyopathy

    International Nuclear Information System (INIS)

    Myocardial ischemia in hypertrophic cardiomyopathy is multifactorial and explains the occurrence of angina, in about 50% of patients. The pathophysiology of myocardial ischemia may be explained by the increase of the ventricular mass and relative paucity of the coronary microcirculation; the elevated ventricular filling pressures and myocardial stiffness causing a compression of the coronary microvessels; the impaired coronary vasodilator flow reserve caused by anatomic and functional abnormalities; and the systolic compression of epicardial vessel (myocardial bridges). Myocardial ischemia must be investigated by perfusion scintigraphic methods since its presence influences the prognosis and has relevant clinical implications for management of patients. Patients with hypertrophic cardiomyopathy and documented myocardial ischemia usually need to undergo invasive coronary angiography to exclude the presence of concomitant atherosclerotic coronary disease. (author)

  13. [Cerebral ischemia in young adults].

    Science.gov (United States)

    Berlit, P; Endemann, B; Vetter, P

    1991-08-01

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

  14. 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

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

    Directory of Open Access Journals (Sweden)

    Yong-gang YAO

    2014-08-01

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

  16. 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.

  17. 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.

  18. 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

  19. 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.

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

    Directory of Open Access Journals (Sweden)

    Fang-fang Liu

    2015-01-01

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

  1. 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.

  2. 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.

  3. Magnesium chloride alone or in combination with diazepam fails to prevent hippocampal damage following transient forebrain ischemia

    Directory of Open Access Journals (Sweden)

    H. Milani

    1999-10-01

    Full Text Available In the central nervous system, magnesium ion (Mg2+ acts as an endogenous modulator of N-methyl-D-aspartate (NMDA-coupled calcium channels, and may play a major role in the pathomechanisms of ischemic brain damage. In the present study, we investigated the effects of magnesium chloride (MgCl2, 2.5, 5.0 or 7.5 mmol/kg, either alone or in combination with diazepam (DZ, on ischemia-induced hippocampal cell death. Male Wistar rats (250-300 g were subjected to transient forebrain ischemia for 15 min using the 4-vessel occlusion model. MgCl2 was applied systemically (sc in single (1x, 2 h post-ischemia or multiple doses (4x, 1, 2, 24 and 48 h post-ischemia. DZ was always given twice, at 1 and 2 h post-ischemia. Thus, ischemia-subjected rats were assigned to one of the following treatments: vehicle (0.1 ml/kg, N = 34, DZ (10 mg/kg, N = 24, MgCl2 (2.5 mmol/kg, N = 10, MgCl2 (5.0 mmol/kg, N = 17, MgCl2 (7.5 mmol/kg, N = 9 or MgCl2 (5 mmol/kg + DZ (10 mg/kg, N = 14. Seven days after ischemia the brains were analyzed histologically. Fifteen minutes of ischemia caused massive pyramidal cell loss in the subiculum (90.3% and CA1 (88.4% sectors of the hippocampus (P0.05. Both DZ alone and DZ + MgCl2 reduced rectal temperature significantly (P<0.05. No animal death was observed after drug treatment. These data indicate that exogenous magnesium, when administered systemically post-ischemia even in different multiple dose schedules, alone or with diazepam, is not useful against the histopathological effects of transient global cerebral ischemia in rats.

  4. Placental ischemia increases seizure susceptibility and cerebrospinal fluid cytokines.

    Science.gov (United States)

    Warrington, Junie P

    2015-11-01

    Eclampsia is diagnosed in preeclamptic patients who develop unexplained seizures and/or coma during pregnancy or postpartum. Eclampsia is one of the leading causes of maternal and infant morbidity and mortality, accounting for ~13% of maternal deaths worldwide. Little is known about the mechanisms contributing to the pathophysiology of eclampsia, partly due to the lack of suitable animal models. This study tested the hypothesis that placental ischemia, induced by reducing utero-placental perfusion, increases susceptibility to seizures, cerebrospinal fluid (CSF) inflammation, and neurokinin B (NKB) expression in brain and plasma. Pentylenetetrazol (PTZ), a pro-convulsive drug, was injected into pregnant and placental ischemic rats (40 mg/kg, i.p.) on gestational day 19 followed by video monitoring for 30 min. Seizure scoring was blindly conducted. Placental ischemia hastened the onset of seizures compared to pregnant controls but had no effect on seizure duration. Placental ischemia increased CSF levels of IL-2, IL-17, IL-18 and eotaxin (CCL11), had no effect on plasma NKB; however, PTZ increased plasma NKB in both pregnant and placental ischemic rats. NKB was strongly correlated with latency to seizure in normal pregnant rats (R(2) = 0.88 vs. 0.02 in placental ischemic rats). Lastly, NKB decreased in the anterior cerebrum in response to placental ischemia and PTZ treatment but was unchanged in the posterior cerebrum. These data demonstrate that placental ischemia is associated with increased susceptibility to seizures and CSF inflammation; thus provides an excellent model for elucidating mechanisms of eclampsia-like symptoms. Further studies are required to determine the role of CSF cytokines/chemokines in mediating increased seizure susceptibility. PMID:26603461

  5. 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.

  6. Brain SPECT

    International Nuclear Information System (INIS)

    Brain SPECT investigations have gained broad acceptance since the introduction of the lipophilic tracer Tc-99m-HMPAO. Depending on equipment and objectives in different departments, the examinations can be divided into three groups: 1. Under normal conditions and standardised patient preparation the 'rest' SPECT can be performed in every department with a tomographic camera. In cerebrovascular disease there is a demand for determination of either the perfusion reserve in reversible ischemia or prognostic values in completed stroke. In cases of dementia, SPECT may yield useful results according to differential diagnosis. Central cerebral system involvement in immunologic disease may be estimated with higher sensitivity than in conventional brain imaging procedures. In psychiatric diseases there is only a relative indication for brain SPECT, since results during recent years have been contradictory and may be derived only in interventional manner. In brain tumor diagnostics SPECT with Tl-201 possibly permits grading. In inflammatory disease, especially in viral encephalitis, SPECT may be used to obtain early diagnosis. Normal pressure hydrocephalus can be distinguished from other forms of dementia and, consequently, the necessity for shunting surgery can be recognised. 2. In departments equipped for emergency cases an 'acute' SPECT can be performed in illnesses with rapid changing symptoms such as different forms of migraine, transient global amnesia, epileptic seizures (so-called 'ictal SPECT') or urgent forms like trauma. 3. In cooperation with several departments brain SPECT can be practised as an interventional procedure in clinical and in scientific studies. (orig./MG)

  7. 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

  8. 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

  9. 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...

  10. 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 ...

  11. Neuroprotective Effect against Cerebral Ischemia of Passiflora foetida

    Directory of Open Access Journals (Sweden)

    Jintanaporn Wattanathorn

    2012-01-01

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

  12. 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...

  13. 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.

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

    Science.gov (United States)

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

    2016-01-15

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

  15. 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

  16. 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....

  17. 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...

  18. 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

  19. 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...

  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. 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...

  2. 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.

  3. 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.

  4. 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

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

    Directory of Open Access Journals (Sweden)

    Kyungjin Lee

    2015-06-01

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

  6. 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

  7. 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...

  8. 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

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

    Directory of Open Access Journals (Sweden)

    Tang Huiling

    2010-10-01

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

  10. 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.)

  11. Myocardial ischemia in Kawasaki disease

    International Nuclear Information System (INIS)

    The detection of myocardial ischemia is essential for evaluation of patients with Kawasaki disease, especially who have had coronary artery lesions. To evaluate the clinical efficacy of Tl-201 single photon emission computed tomography (SPECT) after dipyridamole infusion (maximum dose 0.70 mg/kg) for detecting myocardial ischemia, 44 patients with Kawasaki disease aged 7.7±4.8 years at the study and 10 age matched controls were observed. In the Kawasaki disease group, significant coronary artery stenosis was observed in 14, coronary aneurysm without stenosis in 18, the regression of the coronary aneurysms in 2 and without coronary lesions in 10 patients. In 24 of 44 patients, treadmill exercise stress test was also performed at the same period. Myocardial ischemic changes were observed in 11 patients, all combined with significant coronary artery stenosis. The sensitivity of SPECT for detection of overall coronary stenosis was 79%, coronary that of treadmill exercise test was only 33% (p<0.001). Furthermore, among the patients having significant coronary stenosis, the severity score was significantly elevated in patients who had electrocardiographic abnormal Q wave compared to those without abnormal Q wave (51.0±38.8 versus 20.0±12.1, p<0.05). These data suggest that the pharmacological stress scintigraphy using dipyridamole injection provides not only the accurate detection but quantitative evaluation of myocardial ischemia in these patients. This noninvasive technique may become one of the most useful index for detection and follow-up of myocardial ischemia in Kawasaki disease. (author)

  12. 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.

  13. 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.

  14. 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).

  15. 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.

  16. 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

  17. 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...

  18. 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.

  19. 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.

  20. 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.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    International Nuclear Information System (INIS)

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

  3. 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.

  4. 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.

  5. 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

  6. Chick embryo partial ischemia model: a new approach to study ischemia ex vivo.

    Directory of Open Access Journals (Sweden)

    Syamantak Majumder

    Full Text Available BACKGROUND: Ischemia is a pathophysiological condition due to blockade in blood supply to a specific tissue thus damaging the physiological activity of the tissue. Different in vivo models are presently available to study ischemia in heart and other tissues. However, no ex vivo ischemia model has been available to date for routine ischemia research and for faster screening of anti-ischemia drugs. In the present study, we took the opportunity to develop an ex vivo model of partial ischemia using the vascular bed of 4(th day incubated chick embryo. METHODOLOGY/PRINCIPAL FINDINGS: Ischemia was created in chick embryo by ligating the right vitelline artery using sterile surgical suture. Hypoxia inducible factor- 1 alpha (HIF-1alpha, creatine phospho kinase-MB and reactive oxygen species in animal tissues and cells were measured to confirm ischemia in chick embryo. Additionally, ranolazine, N-acetyl cysteine and trimetazidine were administered as an anti-ischemic drug to validate the present model. Results from the present study depicted that blocking blood flow elevates HIF-1alpha, lipid peroxidation, peroxynitrite level in ischemic vessels while ranolazine administration partially attenuates ischemia driven HIF-1alpha expression. Endothelial cell incubated on ischemic blood vessels elucidated a higher level of HIF-1alpha expression with time while ranolazine treatment reduced HIF-1alpha in ischemic cells. Incubation of caprine heart strip on chick embryo ischemia model depicted an elevated creatine phospho kinase-MB activity under ischemic condition while histology of the treated heart sections evoked edema and disruption of myofibril structures. CONCLUSIONS/SIGNIFICANCE: The present study concluded that chick embryo partial ischemia model can be used as a novel ex vivo model of ischemia. Therefore, the present model can be used parallel with the known in vivo ischemia models in understanding the mechanistic insight of ischemia development and in

  7. 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)

  8. 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.

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

    Science.gov (United States)

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

    2016-07-15

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

  10. 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.

  11. 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

  12. 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.

  13. Perioperative brain damage after cardiovascular surgery

    International Nuclear Information System (INIS)

    We examined 39 cases (1.6%) of post-operative brain damages out of 2,445 sequential cases of cardiovascular surgery in NCVC during past three years. In this study, we investigated clinical course and CT findings of each patient in details and analyzed the causes of the post operative brain damages. Of 39 cases, 23 (59%) were complicated with cerebral ischemia, 8 (21%) with subdural hematoma (SDH), 2 (5%) with intracranial hemorrhage (ICH) and 1 (2%) with subarachnoid hemorrhage (SAH), respectively. 5 cases (13%) had unclassified brain damages. In 23 cases of cerebral ischemia there were 5 cases of hypotension-induced ischemia, 4 cases of hypoxic encephalopathy, 3 cases of ischemia induced by intra-operative maneuvers, 3 cases of embolism after operation and a single case of 'microembolism'. Seven cases could not be classified into any of these categories. Duration of ECC was 169.9±48.5 min on the average in patients with such brain damages as SDH, ICH, SAH and cardiogenic embolism, which were thought not to be related with ECC. On the other hand, that of the patients hypotensive ischemia or 'microembolism' gave an average value of 254.5±96.8 min. And these patients were thought to have occurred during ECC. There was a statistically significant difference between these two mean values. (J.P.N.)

  14. 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 in the...

  15. Brain atrophy during aging

    International Nuclear Information System (INIS)

    Age-related brain atrophy was investigated in thousands of persons with no neurologic disturbances using X-CT and NMR-CT. Brain atrophy was minimal in 34-35 years old in both sexes, increased exponentially to the increasing age after 34-35 years, and probably resulted in dementia, such as vascular or multi-infarct dementia. Brain atrophy was significantly greater in men than in women at all ages. Brain volumes were maximal in 34-35 years old in both sexes with minimal individual differences which increased proportionally to the increasing age. Remarkable individual differences in the extent of brain atrophy (20 - 30 %) existed among aged subjects. Progression of brain atrophy was closely related to loss of mental activities independently of their ages. Our longitudinal study has revealed that the most important factors promoting brain atrophy during aging was the decrease in the cerebral blood flow. We have classified brain atrophy into sulcal and cisternal enlargement type (type I), ventricular enlargement type (type II) and mixed type (type III) according to the clinical study using NMR-CT. Brain atrophy of type I progresses significantly in almost all of the geriatric disorders. This type of brain atrophy progresses significantly in heavy smokers and drinkers. Therefore this type of brain atrophy might be caused by the decline in the blood flow in anterior and middle cerebral arteries. Brain atrophy of type II was caused by the disturbance of cerebrospinal fluid circulation after cerebral bleeding and subarachnoid bleeding. Brain atrophy of type III was seen in vascular dementia or multi-infarct dementia which was caused by loss of brain matter after multiple infarction, and was seen also in dementia of Alzheimer type in which degeneration of nerve cells results in brain atrophy. NMR-CT can easily detect small infarction (lacunae) and edematous lesions resulting from ischemia and hypertensive encephalopathy. (J.P.N.)

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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...

  3. 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

  4. 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.

  5. Endovascular interventional therapy for acute limb ischemia

    International Nuclear Information System (INIS)

    Acute limb ischemia is an urgent and common clinical condition which occurs when the blood flow to a certain extremity is suddenly blocked b either embolic agent or thrombotic vascular lesion. Prompt restoration of perfusion through early intervention can significantly decrease the incidence of amputation and mortality. The main therapeutic methods include surgical operation and endovascular interventional technique. For recent years, considerable progress in treating acute limb ischemia with endovascular interventional technique has been achieved. This article aims to make a comprehensive review in respect of the endovascular intervention therapy for acute limb ischemia. (authors)

  6. 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.

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    Yamamoto T

    2001-10-01

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

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

    OpenAIRE

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

    2010-01-01

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

  10. 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...

  11. Preconditioned hyperbaric oxygenation protects skin flap grafts in rats against ischemia/reperfusion injury

    OpenAIRE

    Kang, Nan; Hai, Yong; Liang, Fang; GAO, CHUN-JIN; LIU, XUE-HUA

    2014-01-01

    Hyperbaric oxygen (HBO) therapy is an effective therapy for ischemia/reperfusion (I/R) injury of the brain, small intestine, testes and liver. However, the detailed molecular mechanisms underlying the effect of HBO therapy remain undetermined. In the current study, the hypothesis that preconditioning rats with HBO protects grafted skin flaps against subsequent I/R injury was investigated. In addition, the molecular mechanisms underlying HBO therapy were characterized by analyzing the roles of...

  12. 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...

  13. 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 ...

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

    OpenAIRE

    Heydenreich, Nadine

    2013-01-01

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

  15. 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...

  16. Effect of policosanol on cerebral ischemia in Mongolian gerbils

    Directory of Open Access Journals (Sweden)

    V. Molina

    1999-10-01

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

  17. 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.

  18. The Neuroprotective Effects of Intramuscular Insulin-Like Growth Factor-I Treatment in Brain Ischemic Rats

    OpenAIRE

    Chang, Heng-Chih; Yang, Yea-Ru; Wang, Paulus S; Kuo, Chia-Hua; Wang, Ray-Yau

    2013-01-01

    Brain ischemia leads to muscle inactivity-induced atrophy and may exacerbate motor function deficits. Intramuscular insulin-like growth factor I (IGF-I) injection has been shown to alleviate the brain ischemia-induced muscle atrophy and thus improve the motor function. Motor function is normally gauged by the integrity and coordination of the central nervous system and peripheral muscles. Whether brain ischemic regions are adaptively changed by the intramuscular IGF-I injection is not well un...

  19. 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.)

  20. 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.)

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

    Science.gov (United States)

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

    2014-01-01

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

  2. 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...

  3. 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.

  4. 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…

  5. 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

  6. 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

  7. Cerebral Ischemia Mediates the Effect of Serum Uric Acid on Cognitive Function

    Science.gov (United States)

    Vannorsdall, Tracy D.; Jinnah, H.A.; Gordon, Barry; Kraut, Michael; Schretlen, David J.

    2016-01-01

    Background and Purpose High normal concentrations of serum uric acid (UA) are associated with mild cognitive dysfunction and increased cerebral ischemia as indexed by white matter hyperintensity volumes. We hypothesized that individual differences in white matter hyperintensities mediate the association between UA and mild cognitive dysfunction. Methods One hundred eighty community-dwelling adults aged 20 to 96 years completed neuropsychological testing, laboratory blood studies, and a brain MRI scan. Results Serum UA was associated (Pischemia might mediate the association between UA and cognitive dysfunction. Even mild elevations in UA appear to contribute to structural and functional brain changes. PMID:18772442

  8. 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

  9. 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.

  10. [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

  11. Reversal of apparent diffusion coefficient (ADC) following transient focal cerebral ischemia in cats

    International Nuclear Information System (INIS)

    To determine the minimal threshold ADC ratio suggesting reversible ischemia in a temporary model of MCAO. Seven Korean cats weighing 3-3.5 kg were used as a temporary model of MCAO. The MCA was occluded for 1 hour, and diffusion-weighted images (DWI), and ADC and regional cerebral blood volume (rCBV) maps, were obtained at 1, 3, 6 and 24 hours after reperfusion using a 1.5T MR unit. The Cats were sacrificed 24 hours after imaging. Triphenyl tetrazolium chloride (TTC) staining of brain slices was performed, and DWI images and TTC-stained brain slices were compared with the naked eye. Reversible ischemia was defined as the area of high signal intensity at 1-hour DWI that normalized at follow-up DWI and in which TTC staining was normal. Using the ADC image obtained at 1 hour after reperfusion, 60 ADC ratios were obtained in the periphery of the infarct and reversible ischemia. Tissue survival showing normal TTC staining was used for final determination. The sensitivity and specificity of each ADC ratio was obtained and an ROC curve was plotted. Five of seven cats showed the reversible ischemia. An area of high signal intensity was seen on DWI images obtained 1 hours after reperfusion, and this improved at follow-up imaging. The distribution of the ADC ratio in the periphery of the infarct core was 0.71-0.81, and in the periphery of reversible ischemia it was 0.79-0.93. The ADC ratio of 0.80 obtained 1 hr after reperfusion predicted the survival of the ischemic tissure with 93% sensitivity and 90% specificity. The ADC ratio of the reversible ischemia was 0.82 ±0.03 at 1 hour after reperfusion, and this was higher than that of the infarct, which was 0.74±0.03. The minimal threshold ADC ratio suggesting reversible ischemia in this temporary model of MCAO was 0.80

  12. Expression of somatostatin mRNA and peptide in rat hippocampus after cerebral ischemia

    DEFF Research Database (Denmark)

    Bering, Robert; Johansen, Flemming Fryd

    Somatostatin, ischemia, hippocampus, rat, in situ hybridisation, immunocytochemistry, neuropathology......Somatostatin, ischemia, hippocampus, rat, in situ hybridisation, immunocytochemistry, neuropathology...

  13. 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

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

    International Nuclear Information System (INIS)

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

  15. 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.

  16. Hyperbaric oxygen therapy for the treatment of radiation-induced macular ischemia

    Directory of Open Access Journals (Sweden)

    Shamim A Haji

    2010-05-01

    Full Text Available Shamim A Haji1,2, Ronald EP Frenkel1,2,31Eye Research Foundation, Stuart, FL, USA; 2East Florida Eye Institute, Stuart, FL, USA; 3Bascom Palmer Eye Institute, Miami, FL, USAPurpose: To report a case of radiation-induced macular ischemia where vision and macular perfusion improved after hyperbaric oxygen (HBO therapy.Methods: A 62-year-old male patient developed radiation-induced macular ischemia after he was treated with radiation for brain glioma. The patient presented with best spectacle-corrected visual acuity (BSCVA acuity of 20/400 in his right eye. Optical coherence tomography (OCT showed central macular thickness of 468 μm. The patient received focal laser, intravitreal triamcinolone, and HBO therapy.Results: The patient’s vision improved from 20/400 to 20/100 after focal laser and intravitreal triamcinolone. His central macular thickness improved from 468 μm to 132 μm. After receiving HBO therapy, his VA improved to 20/50 and fluorescein angiography showed improvement in macular perfusion.Conclusion: HBO therapy improves macular perfusion in patients with radiation-induced macular ischemia.Keywords: macular ischemia, visual acuity, hyperbaric oxygen therapy, macular perfusion

  17. The effect of mitochondrial calcium uniporter on mitochondrial fission in hippocampus cells ischemia/reperfusion injury

    International Nuclear Information System (INIS)

    The mitochondrial calcium uniporter (MCU) transports free Ca2+ into the mitochondrial matrix, maintaining Ca2+ 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 Ca2+ 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 Ca2+ 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

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. 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

  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

    . 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......, we observed novel TTR distribution throughout the infarct, localized to disintegrated β-tubulin III(+) neurons and cell debris. Specific elimination of TTR synthesis in the liver by RNAi had no effect on TTR distribution in the infarct, indicating that the observed TTR infiltration derived from CSF...... and not from the serum. This finding is corroborated by results from 'in situ' hybridization and real time PCR that excluded the presence of transthyretin mRNA in the infarct and peri-infarct areas. Our data suggest that in conditions of a compromised heat-shock response, CSF TTR contributes to control...

  4. 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.

  5. 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.

  6. Mesenteric ischemia in acute aortic dissection.

    Science.gov (United States)

    Orihashi, Kazumasa

    2016-05-01

    Mesenteric ischemia complicated by acute aortic dissection (AAD) is uncommon, but serious, as there is no established treatment strategy and it can progress rapidly to multi-organ failure. Diagnosing mesenteric ischemia before necrotic change is difficult, not only for primary care physicians, but even for gastrointestinal or cardiovascular surgeons as it can occur at any time during surgery. Thus, measures need to be in place at the bedside to enable us to obtain information on visceral perfusion. It is often difficult to decide which of laparotomy or aortic repair should be performed first, especially when there is associated shock or malperfusion of other vital organs. The standard surgical procedures for mesenteric ischemia are prompt revascularization of the mesenteric artery and, if needed, resection of necrotic intestine. However, the development of endovascular treatment and the introduction of hybrid ORs have improved the treatment strategies for mesenteric ischemia. This article reviews the issues of "diagnosis" in relation to the mechanism of mesenteric ischemia, and discusses the current "treatment strategies". PMID:26024781

  7. 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.

  8. 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…

  9. 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.

  10. Magnetic resonance spectroscopy and imaging in cerebral ischemia

    International Nuclear Information System (INIS)

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

  11. 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

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. Helical CT findings in mesenteric ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seung Hoon; Lim, Hyo Keun; Lee, Won Jae; Choi, Sang Hee; Lee, Soon Jin; Cho, Jae Min; Kim, Kyung Ah; Lee, Yon Ok [Sungkyunkwan Univ. College of Medicine. Samsung Medical Center, Seoul (Korea, Republic of)

    1998-08-01

    Ischemic bowel disease is one of the common causes of acute abdomen, which results from insufficient blood flow to the small bowel and colon caused by arterial or venous occlusion or mesenteric vasoconstriction. Early diagnosis by clinical, laboratory, and radiologic findings is often difficult and delay in adequate therapy results in substantial morbidity and mortality. CT is known to be useful for the evaluation of patients with suspected bowel ischemia or infarction. This study describes the spectrum of helical CT findings in acute and chronic mesenteric ischemia due to various causes, and explains the value of CT findings for specific diagnosis.

  17. 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.

  18. 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...

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

    DEFF Research Database (Denmark)

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

    1992-01-01

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

  20. 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.

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

    Science.gov (United States)

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

    2015-04-15

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

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. K+ channel openers prevent global ischemia-induced expression of c-fos, c-jun, heat shock protein, and amyloid beta-protein precursor genes and neuronal death in rat hippocampus.

    OpenAIRE

    Heurteaux, C; Bertaina, V; Widmann, C; Lazdunski, M

    1993-01-01

    Transient global forebrain ischemia induces in rat brain a large increase of expression of the immediate early genes c-fos and c-jun and of the mRNAs for the 70-kDa heat-shock protein and for the form of the amyloid beta-protein precursor including the Kunitz-type protease-inhibitor domain. At 24 hr after ischemia, this increased expression is particularly observed in regions that are vulnerable to the deleterious effects of ischemia, such as pyramidal cells of the CA1 field in the hippocampu...

  7. 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.

  8. 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.

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

    OpenAIRE

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

    2010-01-01

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

  10. 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 ...

  11. 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 ...

  12. 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 ...

  13. In vivo imaging of activated microglia in a mouse model of focal cerebral ischemia by two-photon microscopy

    OpenAIRE

    Bok, Seoyeon; Wang, Taejun; Lee, Chan-Ju; Jeon, Seong-Uk; Kim, Young-eun; Kim, Jeongwoo; Hong, Beom-Ju; Yoon, Calvin Jinse; Kim, Sungjee; Lee, Seung-Hoon; KIM, HAK JAE; Kim, Il Han; Kim, Ki Hean; Ahn, G-One

    2015-01-01

    Microglia are brain resident macrophages rapidly responding to various stimuli to exert appropriate inflammatory responses. Although they have recently been exploited as an attractive candidate for imaging neuroinflammation, it is still difficult to visualize them at the cellular and molecular levels. Here we imaged activated microglia by establishing intracranial window chamber (ICW) in a mouse model of focal cerebral ischemia by using two-photon microscopy (TPM), in vivo. Intravenous inject...

  14. 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...

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

    Directory of Open Access Journals (Sweden)

    Yang Tsai-Hsiu

    2010-10-01

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

  16. 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.

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

    International Nuclear Information System (INIS)

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

  18. 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.

  19. 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.

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

    Science.gov (United States)

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

    2015-12-01

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

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

    Science.gov (United States)

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

    2008-02-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  3. 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

  4. 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

  5. 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

  6. 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.

  7. Inhibition of microRNA-181 reduces forebrain ischemia-induced neuronal loss

    OpenAIRE

    Moon, Jeong-mi; Xu, Lijun; Rona G Giffard

    2013-01-01

    MicroRNA (miRNA), miR-181a, is enriched in the brain, and inhibition of miR-181a reduced astrocyte death in vitro and infarct volume after stroke in vivo. This study investigated the role of miR-181a in neuronal injury in vitro and hippocampal neuronal loss in vivo after forebrain ischemia. miR-181a levels were altered by transfection with mimic or antagomir. N2a cells subjected to serum deprivation and oxidative stress showed less cell death when miR-181a was reduced and increased death when...

  8. 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...

  9. 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

  10. Caffeine reduces dipyridamole-induced myocardial ischemia

    International Nuclear Information System (INIS)

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

  11. 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

  12. Diagnosis of brain death

    Directory of Open Access Journals (Sweden)

    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.

  13. 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...

  14. 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.

  15. Cardiac tolerance to ischemia in neonatal SHR

    Czech Academy of Sciences Publication Activity Database

    Chvojková, Zuzana; Ošťádalová, Ivana; Kuneš, Jaroslav; Zicha, Josef; Ošťádal, Bohuslav

    Antalya: NATO Security Through Science, 2005. s. P9-P9. [NATO Advanced research workshop "Stress induced biochanges in the heart:From genes to bedside".. 02.02.2005-07.02.2005, Antalya] R&D Projects: GA MŠk(CZ) 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : cardiac tolerance to ischemia * neonatal SHR * ischemic preconditioning Subject RIV: ED - Physiology

  16. 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.

  17. 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

  18. Critical Limb Ischemia: Advanced Medical Therapy

    OpenAIRE

    Davies, Mark G.

    2012-01-01

    Systemic atherosclerosis and its risk factors are present in the majority of patients with critical limb ischemia. Aggressive medical therapy is an immediate and necessary part of the work-up and management of these patients and will involve a multidisciplinary approach. Risk stratification based on a patient’s current clinical cardiovascular condition is important in determining the most appropriate and safe intervention and will allow both the patient and physician to make an informed decis...

  19. Colonic urticaria pattern due to early ischemia

    International Nuclear Information System (INIS)

    The unusual radiographic pattern of bleb-like mounds on the surface of the colon mucosa, previously described as colonic urticaria, was seen in 3 patients in whom no allergic state was present. This urticaria-like pattern was due to colonic distention in all 3, and represented only submucosal edema on the gross and microscopic specimens. We hypothesize that this pattern is due to early changes of ischemia caused by colon distention. (orig.)

  20. 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

  1. 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...

  2. Modulation of cardiac metabolism during myocardial ischemia.

    Science.gov (United States)

    Chagas, Antonio C P; Dourado, Paulo M M; Galvão, Tatiana de Fátima Gonçalves

    2008-01-01

    Metabolic modulation during myocardial ischemia is possible by the use of specific drugs, which may induce a shift from free fatty acid towards predominantly glucose utilization by the myocardium to increase ATP generation per unit oxygen consumption. Three agents (trimetazidine, ranolazine, and perhexiline) have well-documented anti-ischaemic effects. However, perhexiline, the most potent agent currently available, requires plasma-level monitoring to avoid hepato-neuro-toxicity. Besides, the long-term safety of trimetazidine and ranolazine has yet to be established. In addition to their effect in ischemia, the potential use of these drugs in chronic heart failure is gaining recognition as clinical and experimental data are showing the improvement of myocardial function following treatment with several of them, even in the absence of ischemia. Future applications for this line of treatment is promising and deserves additional research. In particular, large, randomised, controlled trials investigating the effects of these agents on mortality and hospitalization rates due to coronary artery disease are needed. PMID:18991673

  3. 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 ...

  4. Orexigenic hormone ghrelin attenuates local and remote organ injury after intestinal ischemia-reperfusion.

    Directory of Open Access Journals (Sweden)

    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

  5. 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

  6. 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.

  7. A model of ischemia-induced neuroblast activation in the adult subventricular zone.

    Directory of Open Access Journals (Sweden)

    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.

  8. Transforming Growth Factor -α Improves Memory Impairment and Neurogenesis Following Ischemia Reperfusion

    Directory of Open Access Journals (Sweden)

    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.

  9. 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

  10. 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

  11. Relaxation along a fictitious field (RAFF and Z-spectroscopy using alternating-phase irradiation (ZAPI in permanent focal cerebral ischemia in rat.

    Directory of Open Access Journals (Sweden)

    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.

  12. Transplantation of mesenchymal stem cells promotes the functional recovery of the central nervous system following cerebral ischemia by inhibiting myelin-associated inhibitor expression and neural apoptosis

    Science.gov (United States)

    FENG, NIANPING; HAO, GUANG; YANG, FENGGANG; QU, FUJUN; ZHENG, HAIHONG; LIANG, SONGLAN; JIN, YONGHUA

    2016-01-01

    Cerebral ischemia, which may lead to cerebral hypoxia and damage of the brain tissue, is a leading cause of human mortality and adult disability. Mesenchymal stem cells (MSCs) are a class of adult progenitor cells with the ability to differentiate into multiple cell types. The transplantation of bone marrow-derived MSCs is a potential therapeutic strategy for cerebral ischemia. However, the underlying mechanism has yet to be elucidated. In the present study, primary MSCs were isolated from healthy rats, labeled and transplanted into the brains of middle cerebral artery occlusion rat models. The location of the labeled MSCs in the rat brains were determined by fluorescent microscopy, and the neurological functions of the rats were scored. Immunohistochemical analyses demonstrated that the protein expression levels of myelin-associated inhibitors of regeneration, including Nogo-A, oligodendrocyte myelin glycoprotein and myelin-associated glycoprotein, were decreased following transplantation of the bone marrow-derived MSCs. Furthermore, the mRNA expression levels of Capase-3 and B-cell lymphoma 2, as determined by reverse transcription-quantitative polymerase chain reactions, were downregulated and upregulated, respectively, in the MSC-transplanted rats; thus suggesting that neural apoptosis was inhibited. The results of the present study suggested that the transplantation of bone marrow-derived MSCs was able to promote the functional recovery of the central nervous system following cerebral ischemia. Accordingly, inhibitors targeting myelin-associated inhibitors and apoptosis may be of clinical significance for cerebral ischemia in the future.

  13. 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...

  14. Adult midgut malrotation presented with acute bowel obstruction and ischemia

    Directory of Open Access Journals (Sweden)

    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.

  15. Brain Multimodality Monitoring: Updated Perspectives

    Science.gov (United States)

    Roh, David

    2016-01-01

    The challenges posed by acute brain injury (ABI) involve the management of the initial insult in addition to downstream inflammation, edema, and ischemia that can result in secondary brain injury (SBI). SBI is often subclinical, but can be detected through physiologic changes. These changes serve as a surrogate for tissue injury/cell death and are captured by parameters measured by various monitors that measure intracranial pressure (ICP), cerebral blood flow (CBF), brain tissue oxygenation (PbtO2), cerebral metabolism, and electrocortical activity. In the ideal setting, multimodality monitoring (MMM) integrates these neurological monitoring parameters with traditional hemodynamic monitoring and the physical exam, presenting the information needed to clinicians who can intervene before irreversible damage occurs. There are now consensus guidelines on the utilization of MMM, and there continue to be new advances and questions regarding its use. In this review, we examine these recommendations, recent evidence for MMM, and future directions for MMM. PMID:27095434

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

    Directory of Open Access Journals (Sweden)

    Anand Kumar Pandey

    2015-01-01

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

  17. [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

  18. Brain Basics

    Medline Plus

    Full Text Available ... Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses magnetic fields to take pictures of the brain's structure, studies show that brain growth in children with autism ...

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

    Directory of Open Access Journals (Sweden)

    Bolanle Famakin

    2012-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Yuanjun Zhu

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

  1. Magnolol protects neurons against ischemia injury via the downregulation of p38/MAPK, CHOP and nitrotyrosine

    International Nuclear Information System (INIS)

    Magnolol is isolated from the herb Magnolia officinalis, which has been demonstrated to exert pharmacological effects. Our aim was to investigate whether magnolol is able to act as an anti-inflammatory agent that brings about neuroprotection using a global ischemic stroke model and to determine the mechanisms involved. Rats were treated with and without magnolol after ischemia reperfusion brain injury by occlusion of the two common carotid arteries. The inflammatory cytokine production in serum and the volume of infarction in the brain were measured. The proteins present in the brains obtained from the stroke animal model (SAM) and control animal groups with and without magnolol treatment were compared. Magnolol reduces the total infarcted volume by 15% and 30% at dosages of 10 and 30 mg/kg, respectively, compared to the untreated SAM group. The levels of acute inflammatory cytokines, including interleukin-1 beta, tumor necrosis factor alpha, and interleukin-6 were attenuated by magnolol. Magnolol was also able to suppress the production of nitrotyrosine, 4-hydroxy-2-nonenal (4-HNE), inducible NO synthase (iNOS), various phosphorylated p38 mitogen-activated protein kinases and various C/EBP homologues. Furthermore, this modulation of ischemia injury factors in the SAM model group treated with magnolol seems to result from a suppression of reactive oxygen species production and the upregulation of p-Akt and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). These findings confirm the anti-oxidative properties of magnolol, including the inhibition of ischemic injury to neurons; this protective effect seems to involve changes in the in vivo activity of Akt, GSK3β and NF-κB. - Graphical abstract: Schematic presentation of the signaling pathways involved in magnolol inhibited transient global ischemia brain apoptosis and inflammation in rats. The effect of magnolol on the scavenger of ROS, which inhibits p38 MAPK and CHOP protein inactivation

  2. Magnolol protects neurons against ischemia injury via the downregulation of p38/MAPK, CHOP and nitrotyrosine

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Jiann-Hwa [Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); School of Medicine, Fu-Jen Catholic University, Taipei, Taiwan (China); Department of Emergency Medicine, Cathay General Hospital, Taipei, Taiwan (China); Kuo, Hsing-Chun [Institute of Nursing and Department of Nursing, Chang Gung University of Science and Technology, Taiwan (China); Chronic Diseases and Health Promotion Research Center, CGUST, Taiwan (China); Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan (China); Lee, Kam-Fai [Department of Pathology, Chang Gung Memorial Hospital at Chiayi, Taiwan (China); Tsai, Tung-Hu, E-mail: thtsai@ym.edu.tw [Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Graduate Institute of Acupuncture Science, China Medical University, Taichung, Taiwan (China); Department of Education and Research, Taipei City Hospital, Taipei, Taiwan (China)

    2014-09-15

    Magnolol is isolated from the herb Magnolia officinalis, which has been demonstrated to exert pharmacological effects. Our aim was to investigate whether magnolol is able to act as an anti-inflammatory agent that brings about neuroprotection using a global ischemic stroke model and to determine the mechanisms involved. Rats were treated with and without magnolol after ischemia reperfusion brain injury by occlusion of the two common carotid arteries. The inflammatory cytokine production in serum and the volume of infarction in the brain were measured. The proteins present in the brains obtained from the stroke animal model (SAM) and control animal groups with and without magnolol treatment were compared. Magnolol reduces the total infarcted volume by 15% and 30% at dosages of 10 and 30 mg/kg, respectively, compared to the untreated SAM group. The levels of acute inflammatory cytokines, including interleukin-1 beta, tumor necrosis factor alpha, and interleukin-6 were attenuated by magnolol. Magnolol was also able to suppress the production of nitrotyrosine, 4-hydroxy-2-nonenal (4-HNE), inducible NO synthase (iNOS), various phosphorylated p38 mitogen-activated protein kinases and various C/EBP homologues. Furthermore, this modulation of ischemia injury factors in the SAM model group treated with magnolol seems to result from a suppression of reactive oxygen species production and the upregulation of p-Akt and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). These findings confirm the anti-oxidative properties of magnolol, including the inhibition of ischemic injury to neurons; this protective effect seems to involve changes in the in vivo activity of Akt, GSK3β and NF-κB. - Graphical abstract: Schematic presentation of the signaling pathways involved in magnolol inhibited transient global ischemia brain apoptosis and inflammation in rats. The effect of magnolol on the scavenger of ROS, which inhibits p38 MAPK and CHOP protein inactivation

  3. Detection of vascular cell adhesion molecule-1 expression with USPIO-enhanced molecular MRI in a mouse model of cerebral ischemia

    International Nuclear Information System (INIS)

    Vascular damage plays a critical role after stroke, leading notably to edema, hemorrhages and stroke recurrence. Tools to characterize the vascular lesion are thus a real medical need. In this context, the specific nano-particular contrast agent P03011, an USPIO (ultra-small superparamagnetic iron oxide) conjugated to a peptide that targets VCAM-1 (vascular cell adhesion molecule-1), was developed to detect this major component of the vascular inflammatory response. This study aimed to make the proof of concept of the capacity of this targeted USPIO to detect VCAM-1 with MRI after cerebral ischemia in mouse. The time course of VCAM-1 expression was first examined by immunohistochemistry in our model of cerebral ischemia-reperfusion. Secondly, P03011 or non-targeted USPIO P03007 were injected 5 h after ischemia (100 mmol iron kg-1; i.v.) and in vivo and ex vivo MRI were performed 24 h after ischemia onset. Double labeling immunofluorescence was then performed on brain slices in order to detect both USPIO and VCAM-1. VCAM-1 expression was significantly up-regulated 24 h after ischemia in our model. In animals receiving P03011, both in vivo and ex vivo MRI performed 24 h after ischemia onset showed hypointense foci which could correspond to iron particles. Histological analysis showed a co-localization of the targeted USPIO and VCAM-1. This study demonstrates that VCAM-1 detection is possible with the USPIO P03011 in a model of cerebral ischemia. This kind of contrast agent could be an interesting clinical tool to characterize ischemic lesions in terms of vascular damage. (authors)

  4. Difference in transient ischemia-induced neuronal damage and glucose transporter-1 immunoreactivity in the hippocampus between adult and young gerbils

    Directory of Open Access Journals (Sweden)

    Seung Min Park

    2016-05-01

    Full Text Available Objective(s: The alteration of glucose transporters is closely related with the pathogenesis of brain edema. We compared neuronal damage/death in the hippocampus between adult and young gerbils following transient cerebral ischemia/reperfusion and changes of glucose transporter-1(GLUT-1-immunoreactive microvessels in their ischemic hippocampal CA1 region. Materials and Methods: Transient cerebral ischemia was developed by 5-min occlusion of both common carotid arteries. Neuronal damage was examined by cresyl violet staining, NeuN immunohistochemistry and Fluoro-Jade B histofluorescence staining and changes in GLUT-1 expression was carried out by immunohistochemistry. Results: About 90% of pyramidal neurons only in the adult CA1 region were damaged after ischemia/reperfusion; in the young, about 53 % of pyramidal neurons were damaged from 7 days after ischemia/reperfusion. The density of GLUT-1-immunoreactive microvessels was significantly higher in the young sham-group than that in the adult sham-group. In the ischemia-operated-groups, the density of GLUT-1-immunoreactive microvessels was significantly decreased in the adult and young at 1 and 4 days post-ischemia, respectively, thereafter, the density of GLUT-1-immunoreactive microvessels was gradually increased in both groups after ischemia/reperfusion. Conclusion: CA1 pyramidal neurons of the young gerbil were damaged much later than that in the adult and that GLUT-1-immunoreactive microvessels were significantly decreased later in the young. These data indicate that GLUT-1 might differently contribute to neuronal damage according to age after ischemic insults.

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

    Directory of Open Access Journals (Sweden)

    Chhatwani Chirag M

    2016-06-01

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

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

    Directory of Open Access Journals (Sweden)

    In-Ho Kim

    2013-08-01

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

  7. Batroxobin plus hypothermia for protection of cerebral ischemia/reperfusion injury models in gerbils

    Institute of Scientific and Technical Information of China (English)

    Lin Zhang; Pixing Zhang; Yinming Zeng; Qun Chen

    2006-01-01

    BACKGROUND: Hypothermia plays a protective role in cerebral ischemia/reperfusion injury. Dose combination with batroxobin, an active drug for treating cerebrovascular disease, will enhance its protection? OBJECTIVE: To explore the effects of hypothermia, batroxobin, hypothermia combined with batroxobin on complete cerebral ischemia/reperfusion injury in gerbils.DESIGN: A randomized block comparison observation. SETTING: Jiangsu Key Lab of Anesthesiology. MATERIALS: Experimental animal: Sixty Mongolia gerbils weighing 50-80 g, male or female, were provided by the Animals Center of Xuzhou Medical College. Drugs and agents: Batroxobin was provided by Dongling Phar maceutical Industry Organization (Japan). Superoxide dismutase (SOD) and malondiadehyde (MDA) kits were offered by Nanjing Jiancheng Bioengineering Institute. Other reagents were all import or national analytical pure grade. HITACHI R22A refrigerated high-speed centrifuge, and HARRIS ultra-hypothermia refrigerator were used.METHODS: The experiments were completed in Jiangsu Key Lab of Anesthesiology from May 2004 to January 2005. ① The animals were divided into 6 groups by random member table method: sham-operated group (n =6), ischemia control group (n =6), normothermia group (n =12), hypothermia group (n =12), batroxobin group (n =12) and hypothermia+batroxobin group (n =12). Gerbil rats were abdominally anesthetized with sodium pentobarbital. The neck skin was incised to separate bilateral common carotid arteries. Complete cerebral ischemia models were established by occluding bilateral common carotid arteries with artery clamp for 10 minutes, then the clamp was loosened to perfuse the arteries. Iso-electric level of brain electric wave showed the models were established successfully. The gerbils in the batroxobin group and hypothermia+batroxobin group were abdominally injected with batroxobin (8 BU/kg) while reperfusion, and isovolumetric saline was administered to the gerbils in the other groups

  8. A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window.

    Science.gov (United States)

    Yrjänheikki, J; Tikka, T; Keinänen, R; Goldsteins, G; Chan, P H; Koistinaho, J

    1999-11-01

    The only treatment of patients with acute ischemic stroke is thrombolytic therapy, which benefits only a fraction of stroke patients. Both human and experimental studies indicate that ischemic stroke involves secondary inflammation that significantly contributes to the outcome after ischemic insult. Minocycline is a semisynthetic second-generation tetracycline that exerts antiinflammatory effects that are completely separate from its antimicrobial action. Because tetracycline treatment is clinically well tolerated, we investigated whether minocycline protects against focal brain ischemia with a wide therapeutic window. Using a rat model of transient middle cerebral artery occlusion, we show that daily treatment with minocycline reduces cortical infarction volume by 76 +/- 22% when the treatment is started 12 h before ischemia and by 63 +/- 35% when started even 4 h after the onset of ischemia. The treatment inhibits morphological activation of microglia in the area adjacent to the infarction, inhibits induction of IL-1beta-converting enzyme, and reduces cyclooxygenase-2 expression and prostaglandin E(2) production. Minocycline had no effect on astrogliosis or spreading depression, a wave of ionic transients thought to contribute to enlargement of cortical infarction. Treatment with minocycline may act directly on brain cells, because cultured primary neurons were also salvaged from glutamate toxicity. Minocycline may represent a prototype of an antiinflammatory compound that provides protection against ischemic stroke and has a clinically relevant therapeutic window. PMID:10557349

  9. Hydrogen saline offers neuroprotection by reducing oxidative stress in a focal cerebral ischemia-reperfusion rat model

    Directory of Open Access Journals (Sweden)

    Liu Ying

    2011-07-01

    Full Text Available Abstract Hydrogen gas is neuroprotective in cerebral ischemia animal models. In this study, we tested the neuroprotective effects of hydrogen saline, which is safe and easy to use clinically, in a rat model of middle cerebral artery occlusion (MCAO. Sprague-Dawley male rats weighting 250-280 g were divided into sham, MCAO plus hydrogen saline and MCAO groups, and subjected to 90-min ischemia followed by 24 h of reperfusion. Hydrogen saline was injected intraperitoneally at 1 ml/100 g body weight. Infarct volume and brain water content were evaluated at different time points after reperfusion. Oxidative stress, inflammation, and apoptotic cell death markers were measured. Hydrogen saline significantly reduced the infarct volume and edema and improved the neurological function, when it was administered at 0, 3 and 6 h after reperfusion. Hydrogen saline decreased 8-hydroxyl-2'-deoxyguanosine (8-OHdG, reduced malondidehyde, interleukin-1β, tumor necrosis factor-α, and suppressed caspase 3 activity in the ischemic brain. These findings demonstrated hydrogen saline is neuroprotective when administered within 6 h after ischemia. Because hydrogen saline is safe and easy to use, it has clinical potentials to reduce neurological injuries.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2005-06-15

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

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

    International Nuclear Information System (INIS)

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

  12. Silent myocardial ischemia evaluated by ambulatory left ventricular function monitoring

    Energy Technology Data Exchange (ETDEWEB)

    Imai, Kamon; Yumikura, Sei; Araki, Yasushi; Ando, Tatsuo; Saito, Satoshi; Ozawa, Yukio; Hatano, Michinobu; Kamata, Rikisaburo (Nihon Univ., Tokyo (Japan). School of Medicine)

    1989-12-01

    To determine whether left ventricular function is less disturbed in asymptomatic ischemia than in symptomatic ischemia, exercise-induced left ventricular function was measured in beat-to-beat using an ambulatory left ventricular function monitoring system. The study subjects were 22 patients with coronary artery disease. Supine and sitting ergometer exercise tests were performed. Of 44 exercise tests, 33 showed significant ST depression on electro-cardiograms. Among these 33, 17 were asymptomatic: 16, symptomatic. The left ventricular functions during exercise of these 33 were analyzed and compared with those of five normal controls. The changes in end-diastolic volume were not so significant either in controls or in the asymptomatic and symptomatic groups, but the changes in end-systolic volume were reversed in the diseased group, particularly in the symptomatic group. The changes in ejection fraction (EF), therefore, were significantly negative in the diseased group, particularly in the symptomatic group. The correlation between exercise-induced left ventricular dysfunction and symptoms was evaluated among the 33 patients. Symptoms were present in 35% (6/17) in <10% decrease in EF, 44% (4/9) in 10{approx}15% decrease, and 85% (6/7)in {ge}15% decrease, respectively. Thus, asymptomatic ischemia represents a lesser degree of myocardial ischemia as indicated by mild left ventricular dysfunction, compared with symptomatic ischemia. However, some cases of severe myocardial ischemia did not develop symptoms. We concluded that silent myocardial ischemia is responsible for a lesser degree of myocardial ischemia and decreased pain perception. (author).

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

    OpenAIRE

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

    2005-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2002-07-01

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

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Heng-Chih Chang

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

  17. Studies on the active constituents in radix salviae miltiorrhizae and their protective effects on cerebral ischemia reperfusion injury and its mechanism

    Directory of Open Access Journals (Sweden)

    Yan-hui Li

    2015-01-01

    Full Text Available Background: To extract, purify and identify the active constituents in ethanol extract of Radix Salviae Miltiorrhizae, and to analyze the protective effects of tanshinone IIA on cerebral ischemia-reperfusion injury in rats. Materials and Methods: Radix Salviae Miltiorrhizae was extracted by ultrasonic extraction, effective parts were extracted by extraction method, compounds were isolated by preparative TLC and preparative HPLC, and structures of compounds were identified by 1 H NMR and 13 C NMR; the effects of tanshinone IIA on cerebral ischemia-reperfusion injury in rats were determined by establishing rat model of middle cerebral artery occlusion (MCAO. Results: The experimental data show four compounds were isolated, namely tanshinone IIB, hydroxymethylene tanshinone, salvianolic acid B and 9"′-methyl lithospermate B. Tanshinone IIA could alleviate the symptoms of neurological deficit in rats, the neurological deficit alleviating effect became more obvious with the increase of dose; tanshinone IIA experimental groups could reduce the cerebral infarction size and brain water content in rats, different concentrations of tanshinone IIA could decrease the SOD content and increase the MDA content in the frontal and parietal cortices of ischemic hemisphere in the ischemia reperfusion group, the differences were statistically significant compared with the ischemia reperfusion group. Conclusion: Radix Salviae Miltiorrhizae has the protective effects on cerebral ischemia reperfusion injury in rats.

  18. Effects of total saponins of Panax notoginseng on immature neuroblasts in the adult olfactory bulb following global cerebral ischemia/reperfusion

    Institute of Scientific and Technical Information of China (English)

    Xu He; Feng-jun Deng; Jin-wen Ge; Xiao-xin Yan; Ai-hua Pan; Zhi-yuan Li

    2015-01-01

    The main active components extracted from Panax notoginseng are total saponins. They have been shown to inhibit platelet aggregation, increase cerebral blood lfow, improve neurological behavior, decrease infarct volume and promote proliferation and differentiation of neural stem cells in the hippocampus and lateral ventricles. However, there is a lack of studies on whether total saponins of Panax notoginseng have potential benefits on immature neuroblasts in the olfactory bulb following ischemia and reperfusion. This study established a rat model of global cerebral ischemia and reperfusion using four-vessel occlusion. Rats were administered total sa-ponins of Panax notoginseng at 75 mg/kg intraperitoneally 30 minutes after ischemia then once a day, for either 7 or 14 days. Total saponins of Panax notoginseng enhanced the number of dou-blecortin (DCX)+ neural progenitor cells and increased co-localization of DCX with neuronal nuclei and phosphorylated cAMP response element-binding/DCX+ neural progenitor cells in the olfactory bulb at 7 and 14 days post ischemia. These ifndings indicate that following global brain ischemia/reperfusion, total saponins of Panax notoginseng promote differentiation of DCX+ cells expressing immature neuroblasts in the olfactory bulb and the underlying mechanism is related to the activation of the signaling pathway of cyclic adenosine monophosphate response element binding protein.

  19. Aquaporin 9 in rat brain after severe traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Hui Liu

    2012-03-01

    Full Text Available OBJECTIVE: To reveal the expression and possible roles of aquaporin 9 (AQP9 in rat brain, after severe traumatic brain injury (TBI. METHODS: Brain water content (BWC, tetrazolium chloride staining, Evans blue staining, immunohistochemistry (IHC, immunofluorescence (IF, western blot, and real-time polymerase chain reaction were used. RESULTS: The BWC reached the first and second (highest peaks at 6 and 72 hours, and the blood brain barrier (BBB was severely destroyed at six hours after the TBI. The worst brain ischemia occurred at 72 hours after TBI. Widespread AQP9-positive astrocytes and neurons in the hypothalamus were detected by means of IHC and IF after TBI. The abundance of AQP9 and its mRNA increased after TBI and reached two peaks at 6 and 72 hours, respectively, after TBI. CONCLUSIONS: Increased AQP9 might contribute to clearance of excess water and lactate in the early stage of TBI. Widespread AQP9-positive astrocytes might help lactate move into neurons and result in cellular brain edema in the later stage of TBI. AQP9-positive neurons suggest that AQP9 plays a role in energy balance after TBI.

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

    Science.gov (United States)

    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 (IDAs) were isolated from early ischemic penumbra and core. IDA did not originate from myeloid precursors, but rather from pre-existing local progenitors. Isolated IDA markedly differ from primary astrocytes, as they proliferate in vitro with high cell division rate, show increased migratory ability, have reduced replicative senescence and grow in the presence of macrophages within the limits imposed by the glial scar. Remarkably, IDA produce a conditioned medium that strongly induced activation on quiescent primary astrocytes and potentiated the neuronal death triggered by oxygen-glucose deprivation. When re-implanted into normal rat brains, eGFP-IDA migrated around the injection site and induced focal reactive gliosis. Inhibition of gamma secretases or culture on quiescent primary astrocytes monolayers facilitated IDA differentiation to astrocytes. We propose that IDA represent an undifferentiated, pro-inflammatory, highly replicative and migratory astroglial subtype emerging from the ischemic microenvironment that may contribute to the expansion of reactive gliosis. Main Points: Ischemia-derived astrocytes (IDA) were isolated from brain ischemic tissue IDA show reduced replicative senescence, increased cell division and spontaneous migration IDA potentiate death of oxygen-glucose deprived cortical neurons IDA propagate reactive gliosis on quiescent astrocytes in vitro and in vivo Inhibition of gamma secretases facilitates IDA differentiation to astrocytes PMID:27313509

  1. Transient myocardial ischemia of the newborn infant

    International Nuclear Information System (INIS)

    Ten full-term newborn infants with transient myocardial ischemia developed radiographic evidence of cardiomegaly and pulmonary venous congestion within the first few hours of life. In five patients, radiographic findings returned to normal during the first week of life. In the remaining five patients radiographic findings improved within the second week and eventually became normal. Echocardiography done on six patients demonstrated left ventricular dysfunction in all six patients. Those infants with documented perinatal insults tend to have a protracted clinical course with eventual recovery. Pathophysiology and clinical course are discussed. (orig.)

  2. Cocaine-associated lower limb ischemia.

    LENUS (Irish Health Repository)

    Collins, Chris G

    2011-07-25

    Cocaine-associated thrombosis has been reported in the literature with reports of vascular injuries to cardiac, pulmonary, intestinal, placental, and musculoskeletal vessels; however, injury of the pedal vessels is rare. We report on a 31-year-old man who presented 2 months following a cocaine binge with limb-threatening ischemia without an otherwise identifiable embolic source. Angiography confirmed extensive occlusive disease of the tibioperoneal vessels. The patient improved following therapy with heparin and a prostacyclin analogue. Cocaine-induced thrombosis should be considered in patients presenting with acute arterial insufficiency in the lower limb without any other identifiable cause.

  3. Intracoronary levosimendan during ischemia prevents myocardial apoptosis.

    Directory of Open Access Journals (Sweden)

    MarkusMalmberg

    2012-02-01

    Full Text Available Background. Levosimendan is a calcium-sensitizing inotropic agent that prevents myocardial contractile depression following cardiac surgery. Levosimendan has also anti-apoptotic properties, but the role of this mechanism is not clear. We studied whether levosimendan prevents cardiomyocyte apoptosis and post-operative stunning after either intracoronary administration or intravenous infusion in an experimental model. Methods. Pigs (n=24 were subjected to 40 minutes of global, cardioplegic ischemia under cardiopulmonary bypass and 240 minutes of reperfusion. L-IV group received intravenous infusion of levosimendan (65 μg/kg 40 minutes before ischemia and L-IC group received levosimendan (65 μg/kg during ischemia administered intracoronary. Control group was operated without levosimendan. Echocardiography was performed to all animals. Apoptosis was determined from transmyocardial biopsies taken from left ventricle using TUNEL assay and immunohistochemistry of active caspace-3. Results. Apoptosis was induced after ischemia-reperfusion in all groups (pre L-IV 0.002±0.004 % vs. post L-IV 0.020±0.017 % p=0.02, pre L-IC 0.001±0.004 % vs. post L-IC 0.020±0.017 % p<0.001, pre control 0.007±0.013 % vs. post control 0.062±0.044 % p=0.01. The amount of apoptosis was higher in the controls, compared with the L-IV (p=0.03 and the L-IC (p=0.03 groups. Longitudinal left ventricular contraction was significantly reduced in the L-IC and the control groups when compared to the L-IV group (L-IV 0.75±0.12 mm vs. L-IC 0.53±0.11 mm p=0.003, L-IV vs. control 0.54±0.11 p=0.01. Conclusions. Both intracoronary administration and pre-ischemic intravenous infusion of levosimendan equally prevented apoptosis, but intravenous administration was required for optimal preservation of the post-operative systolic left ventricle function.

  4. Repeated early thrombolysis in cervical spinal cord ischemia.

    Science.gov (United States)

    Etgen, Thorleif; Höcherl, Constanze

    2016-07-01

    Specific therapy of acute spinal ischemia is not established. We report the first case of an MRI-verified cervical spinal ischemia treated by thrombolysis and review the literature. A 72-year old woman with right-sided motor hemiparesis and trunk ataxia was treated by intravenous thrombolysis with full recovery. Three days later she developed again a severe right-sided sensorimotor hemiparesis and a second off-label intravenous thrombolysis was repeated. Magnetic resonance imaging revealed a right-sided posterior-lateral cervical spinal ischemia. Spinal ischemia may clinically present with a cerebral-stroke-like picture challenging diagnostic and therapeutic procedure. Systemic thrombolysis might be a treatment option in acute spinal ischemia. In addition, early repeated systemic thrombolysis may be considered in selected strokes. PMID:26762860

  5. Microdialysis in the assessment of regional intestinal ischemia

    DEFF Research Database (Denmark)

    Sommer, Thorbjørn

     The Ph.D.thesis “Microdialysis in the assessment of regional intestinal ischemia” is based on three scientific papers. The diagnosis of intestinal ischemia remains a diagnostic challenge, since no technique has been able to monitor the intestinal perfusion continuously with a high sensitivity and...... specificity. This thesis aimed to explore the possibility of using the microdialysis technique in the detection of regional, intestinal ischemia. A pig model was chosen and microdialysis performed during regional intestinal ischemia. In study I it was demonstrated that regional, intestinal ischemia could be...... technique. Using a 60 % cut off and excluding catheters in which technical failures were observed, a predictive value of a positive test of 1 was observed for lactate and subsequently lower values for the other metabolites measured. In study III it was demonstrated that intestinal ischemia could be detected...

  6. Correlation between neuronal injury and Caspase-3 after focal ischemia in human hippocampus

    Institute of Scientific and Technical Information of China (English)

    戚基萍; 吴爱萍; 王德生; 王立峰; 李淑霞; 徐凤琳

    2004-01-01

    Background Cerebral ischemia is a significant clinical problem, and cerebral ischemia usually causes neuron injury such as apoptosis in various brain areas, including hippocampus. Cysteinyl aspartate-specific protease (Caspases) are fundamental factors of apoptotic mechanism. Caspase-3 inhibitors show effect in attenuating brain injury after ischemia. But all the results were from animal models in research laboratories. This study aimed at investigating the correlation between the change of ischemic neuronal injury and Caspase-3 post-ischemia in human hippocampus. Methods We selected and systematized 48 post-mortem specimens from 48 patients, who died of cerebral infarction. Morphological change was firstly analyzed by observing hematoxyline/eosin-staining hippocampal sections. The expression of Caspase-3 was investigated using the methods of in situ hybridization and immunohistochemistry. Terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick-end labeling (TUNEL) method was used to clarify the involvement of Caspase-3 in neuron death. The loss of MAP 2 (MAP-2) was applied to judging the damaged area and degree of neuronal injury caused by ischemia.Results In the CA1 sector of hippocampus, Caspase-3 immunostaining modestly increased at 8 hours [8.05/high-power field (hpf)], dramatically increased at 24 hours (24.85/hpf), decreased somewhat after 72 hours. Caspase-3 mRNA was detectable at 4 hours (6.75/hpf), reached a maximum at 16 hours (17.60/hpf), faded at 72 hours. TUNEL-positive cells were detectable at 24 hours (10.76/hpf), markedly increased at 48-72 hours. The loss of MAP-2 was obviously detected at 4 hours, progressed significantly between 24 and 72 hours; MAP-2 immunoreactivity was barely detectable at 72 hours. Before 72 hours, the Caspase-3 evolution was related with the upregulation of TUNEL and the loss of MAP-2. The positive correlation between Caspase-3 mRNA and TUNEL was significant at the 0.05 level (correlation

  7. Mangafodipir Protects against Hepatic Ischemia-Reperfusion Injury in Mice

    Science.gov (United States)

    Coriat, Romain; Leconte, Mahaut; Kavian, Niloufar; Bedda, Sassia; Nicco, Carole; Chereau, Christiane; Goulvestre, Claire; Weill, Bernard

    2011-01-01

    Introduction and Aim Mangafodipir is a contrast agent used in magnetic resonance imaging that concentrates in the liver and displays pleiotropic antioxidant properties. Since reactive oxygen species are involved in ischemia-reperfusion damages, we hypothesized that the use of mangafodipir could prevent liver lesions in a mouse model of hepatic ischemia reperfusion injury. Mangafodipir (MnDPDP) was compared to ischemic preconditioning and intermittent inflow occlusion for the prevention of hepatic ischemia-reperfusion injury in the mouse. Methods Mice were subjected to 70% hepatic ischemia (continuous ischemia) for 90 min. Thirty minutes before the ischemic period, either mangafodipir (10 mg/kg) or saline was injected intraperitoneally. Those experimental groups were compared with one group of mice preconditioned by 10 minutes' ischemia followed by 15 minutes' reperfusion, and one group with intermittent inflow occlusion. Hepatic ischemia-reperfusion injury was evaluated by measurement of serum levels of aspartate aminotransferase (ASAT) activity, histologic analysis of the livers, and determination of hepatocyte apoptosis (cytochrome c release, caspase 3 activity). The effect of mangafodipir on the survival rate of mice was studied in a model of total hepatic ischemia. Results Mangafodipir prevented experimental hepatic ischemia-reperfusion injuries in the mouse as indicated by a reduction in serum ASAT activity (P<0.01), in liver tissue damages, in markers of apoptosis (P<0.01), and by higher rates of survival in treated than in untreated animals (P<0.001). The level of protection by mangafodipir was similar to that observed following intermittent inflow occlusion and higher than after ischemic preconditioning. Conclusions Mangafodipir is a potential new preventive treatment for hepatic ischemia-reperfusion injury. PMID:22073237

  8. Mangafodipir protects against hepatic ischemia-reperfusion injury in mice.

    Directory of Open Access Journals (Sweden)

    Romain Coriat

    Full Text Available INTRODUCTION AND AIM: Mangafodipir is a contrast agent used in magnetic resonance imaging that concentrates in the liver and displays pleiotropic antioxidant properties. Since reactive oxygen species are involved in ischemia-reperfusion damages, we hypothesized that the use of mangafodipir could prevent liver lesions in a mouse model of hepatic ischemia reperfusion injury. Mangafodipir (MnDPDP was compared to ischemic preconditioning and intermittent inflow occlusion for the prevention of hepatic ischemia-reperfusion injury in the mouse. METHODS: Mice were subjected to 70% hepatic ischemia (continuous ischemia for 90 min. Thirty minutes before the ischemic period, either mangafodipir (10 mg/kg or saline was injected intraperitoneally. Those experimental groups were compared with one group of mice preconditioned by 10 minutes' ischemia followed by 15 minutes' reperfusion, and one group with intermittent inflow occlusion. Hepatic ischemia-reperfusion injury was evaluated by measurement of serum levels of aspartate aminotransferase (ASAT activity, histologic analysis of the livers, and determination of hepatocyte apoptosis (cytochrome c release, caspase 3 activity. The effect of mangafodipir on the survival rate of mice was studied in a model of total hepatic ischemia. RESULTS: Mangafodipir prevented experimental hepatic ischemia-reperfusion injuries in the mouse as indicated by a reduction in serum ASAT activity (P<0.01, in liver tissue damages, in markers of apoptosis (P<0.01, and by higher rates of survival in treated than in untreated animals (P<0.001. The level of protection by mangafodipir was similar to that observed following intermittent inflow occlusion and higher than after ischemic preconditioning. CONCLUSIONS: Mangafodipir is a potential new preventive treatment for hepatic ischemia-reperfusion injury.

  9. Interventional effect of flunarizine on the expression of cyclooxygenase-2 and plasminogen activator inhibitor type-1 during experimental Cerebral ischemia/reperfusion in gerbils

    Institute of Scientific and Technical Information of China (English)

    Wensheng Zhou; Zhiping Hu; Yan Hong

    2006-01-01

    BACKGROUND:Some researches suggest that induced cyclooxygenase-2 (COX-2) can cause brain injury through a series of ways at the phase of cerebral ischemia/hypoxia.Plasminogen activator inhibitor type-1(PAI-1)is a kind of inhibitor of serine stretch protein enzyme and is able to protect cell surface and microvascular basement membrane from degradation of protease and also protect contact surface among cells so as to maintain integrality of tissue structure.However,correlation of protective effect of flunarizine on brain with COX-2 and PAI-1 should be studied further.OBJECTIVE:To observe the effect of flunadzine on expressions of COX-2 and PAI-1 protein in forebrain and degree of brain injury among gerbils after cerebral ischemia.DESIGN:A randomized controlled animal study.SEITING:Department of Neurology,the Second Xiangya Hospital of Central South University;Department of Neurology,Mawangdui Hospital of Hunan Province.MATERIALS:A total of 40 healthy gerbils,of both genders,aged 9 months,weighing(90±10)g,were selected in this study.Anti-COX-2 multi-antibody,anti-PAI-1 multi-antibody,SABC immunohistochemical kit and DAB kit were provided by Wuhan Boster Biological Engineering Co.,Ltd.;and flunarizine capsule was provided by Xi'an Yangsen Pharmaceutical Company(batch number:041018726,dosage:5 mg/pill).METHODS:The experiment was Carried out in Laboratory of Mental Disease,Hunan Provincial Gedatdcs Institute affiliated by Hunan Provincial Mawangdui Hospital from January 2004 to March 2005.① All gerbils were randomly divided into cerebral ischemia group,flunarizine intervention group,sham operation group and normal control group with 10 in each group.Gerbils in normal control group were only cut off their heads.Gerbils in sham operation group were only dissected their bilateral common carotid arteries and sacdficad 1 day later.Gerbils in cerebral ischemia group and flunanzine intervention group were anesthetized,centrally cut open skin of neck,bluntly dissected

  10. Obestatin Accelerates the Recovery in the Course of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats.

    Directory of Open Access Journals (Sweden)

    Jakub Bukowczan

    Full Text Available Several previous studies have shown that obestatin exhibits protective and regenerative effects in some organs including the stomach, kidney, and the brain. In the pancreas, pretreatment with obestatin inhibits the development of cerulein-induced acute pancreatitis, and promotes survival of pancreatic beta cells and human islets. However, no studies investigated the effect of obestatin administration following the onset of experimental acute pancreatitis.The aim of this study was to evaluate the impact of obestatin therapy in the course of ischemia/reperfusion-induced pancreatitis. Moreover, we tested the influence of ischemia/reperfusion-induced acute pancreatitis and administration of obestatin on daily food intake and pancreatic exocrine secretion.Acute pancreatitis was induced by pancreatic ischemia followed by reperfusion of the pancreas. Obestatin (8 nmol/kg/dose was administered intraperitoneally twice a day, starting 24 hours after the beginning of reperfusion. The effect of obestatin in the course of necrotizing pancreatitis was assessed between 2 and 14 days, and included histological, functional, and biochemical analyses. Secretory studies were performed on the third day after sham-operation or induction of acute pancreatitis in conscious rats equipped with chronic pancreatic fistula.Treatment with obestatin ameliorated morphological signs of pancreatic damage including edema, vacuolization of acinar cells, hemorrhages, acinar necrosis, and leukocyte infiltration of the gland, and led to earlier pancreatic regeneration. Structural changes were accompanied by biochemical and functional improvements manifested by accelerated normalization of interleukin-1β level and activity of myeloperoxidase and lipase, attenuation of the decrease in pancreatic DNA synthesis, and by an improvement of pancreatic blood flow. Induction of acute pancreatitis by pancreatic ischemia followed by reperfusion significantly decreased daily food intake and

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

    Science.gov (United States)

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

    2013-07-01

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

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

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

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

  13. Amino acid transport after transient global ischemia in rats: Quantitative autoradiographic study using 3-[125I]Iodo-alpha-methyl-l-tyrosine

    International Nuclear Information System (INIS)

    We studied the influence of reperfusion on amino acid transport of the brain after transient global ischemia in rats. The animals were subjected to 30-min four-vessel occlusion according to the procedures developed by Pulsinelli prior to recirculation for 3, 6, 24, 48 and 72 h. We used 3-[125I]iodo-alpha-methyl-l-tyrosine as an autoradiographic tracer for selective cerebral amino acid transport maker. Following 30-min global ischemia, uptakes of 3-[125I]iodo-alpha-methyl-l-tyrosine were significantly (P < 0.05) lower in substantia nigra, striatum and ventral tegmental area (6, 24, 48 and 72 h post-reperfusion), but significantly (P < 0.05) higher in cortex and thalamus (3 and 6 h post-reperfusion). The influence of transient global ischemia on cerebral amino acid transport manifested region-specific three different patterns; namely, suppression, acceleration and no change in amino acid transport. The influence of transient ischemia on catecholamine-synthesizing brain sites is most remarkable

  14. Ischemia detection from morphological QRS angle changes.

    Science.gov (United States)

    Romero, Daniel; Martínez, Juan Pablo; Laguna, Pablo; Pueyo, Esther

    2016-07-01

    In this paper, an ischemia detector is presented based on the analysis of QRS-derived angles. The detector has been developed by modeling ischemic effects on the QRS angles as a gradual change with a certain transition time and assuming a Laplacian additive modeling error contaminating the angle series. Both standard and non-standard leads were used for analysis. Non-standard leads were obtained by applying the PCA technique over specific lead subsets to represent different potential locations of the ischemic zone. The performance of the proposed detector was tested over a population of 79 patients undergoing percutaneous coronary intervention in one of the major coronary arteries (LAD (n  =  25), RCA (n  =  16) and LCX (n  =  38)). The best detection performance, obtained for standard ECG leads, was achieved in the LAD group with values of sensitivity and specificity of [Formula: see text], [Formula: see text], followed by the RCA group with [Formula: see text], Sp  =  94.4 and the LCX group with [Formula: see text], [Formula: see text], notably outperforming detection based on the ST series in all cases, with the same detector structure. The timing of the detected ischemic events ranged from 30 s up to 150 s (mean  =  66.8 s) following the start of occlusion. We conclude that changes in the QRS angles can be used to detect acute myocardial ischemia. PMID:27243441

  15. Sildenafil attenuates placental ischemia-induced hypertension.

    Science.gov (United States)

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

    2013-08-15

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

  16. Autophagy and Liver Ischemia-Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Raffaele Cursio

    2015-01-01

    Full Text Available Liver ischemia-reperfusion (I-R injury occurs during liver resection, liver transplantation, and hemorrhagic shock. The main mode of liver cell death after warm and/or cold liver I-R is necrosis, but other modes of cell death, as apoptosis and autophagy, are also involved. Autophagy is an intracellular self-digesting pathway responsible for removal of long-lived proteins, damaged organelles, and malformed proteins during biosynthesis by lysosomes. Autophagy is found in normal and diseased liver. Although depending on the type of ischemia, warm and/or cold, the dynamic process of liver I-R results mainly in adenosine triphosphate depletion and in production of reactive oxygen species (ROS, leads to both, a local ischemic insult and an acute inflammatory-mediated reperfusion injury, and results finally in cell death. This process can induce liver dysfunction and can increase patient morbidity and mortality after liver surgery and hemorrhagic shock. Whether autophagy protects from or promotes liver injury following warm and/or cold I-R remains to be elucidated. The present review aims to summarize the current knowledge in liver I-R injury focusing on both the beneficial and the detrimental effects of liver autophagy following warm and/or cold liver I-R.

  17. Understanding STAT3 signaling in cardiac ischemia.

    Science.gov (United States)

    O'Sullivan, K E; Breen, E P; Gallagher, H C; Buggy, D J; Hurley, J P

    2016-05-01

    Cardiovascular disease is the leading cause of death worldwide. It remains one of the greatest challenges to global health and will continue to dominate mortality trends in the future. Acute myocardial infarction results in 7.4 million deaths globally per annum. Current management strategies are centered on restoration of coronary blood flow via percutaneous coronary intervention, coronary artery bypass grafting and administration of anti-platelet agents. Such myocardial reperfusion accounts for 40-50 % of the final infarct size in most cases. Signaling transducer and activator of transcription 3 (STAT3) has been shown to have cardioprotective effects via canonical and non-canonical activation and modulation of mitochondrial and transcriptional responses. A significant body of in vitro and in vivo evidence suggests that activation of the STAT3 signal transduction pathway results in a cardio protective response to ischemia and attempts have been made to modulate this with therapeutic effect. Not only is STAT3 important for cardiomyocyte function, but it also modulates the cardiac microenvironment and communicates with cardiac fibroblasts. To this end, we here review the current evidence supporting the manipulation of STAT3 for therapeutic benefit in cardiac ischemia and identify areas for future research. PMID:27017613

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

  19. Calcium-permeable ion channels involved in glutamate receptor-independent ischemic brain injury

    Institute of Scientific and Technical Information of China (English)

    Ming-hua LI; Koichi INOUE; Hong-fang SI; Zhi-gang XIONG

    2011-01-01

    Brain ischemia is a leading cause of death and long-term disabilities worldwide. Unfortunately, current treatment is limited to thrombolysis, which has limited success and a potential side effect of intracerebral hemorrhage. Searching for new cell injury mechanisms and therapeutic interventions has become a major challenge in the field. It has been recognized for many years that intracellular Ca2+overload in neurons is essential for neuronal injury associated with brain ischemia. However, the exact pathway(s) underlying the toxic Ca2+ loading remained elusive. This review discusses the role of two Ca2+-permeable cation channels, TRPM7 and acid-sensing channels, in glutamate-independent Ca2+ toxicity associated with brain ischemia.

  20. Brain Tumors

    Science.gov (United States)

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, or ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are metastatic, ...

  1. Brain Basics

    Medline Plus

    Full Text Available ... Basics will introduce you to some of this science, such as: How the brain develops How genes and the environment affect the brain The basic structure of the brain How different parts of the brain communicate and work with each other How changes in the brain ...

  2. Brain Tumors

    Science.gov (United States)

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

  3. Brain Fingerprinting

    Directory of Open Access Journals (Sweden)

    ravi kumar

    2012-12-01

    Full Text Available Brain Fingerprinting is a scientific technique to determine whether or not specific information is stored in an individual's brain by measuring a electrical brain wave response to Word, phrases, or picture that are presented on computer screen. Brain Fingerprinting is a controversial forensic science technique that uses electroencephalograph y (EEG to determine whether specific information is stored in a subject's brain

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

    Science.gov (United States)

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

    2016-01-01

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

  5. Melatonin Improves Outcomes of Heatstroke in Mice by Reducing Brain Inflammation and Oxidative Damage and Multiple Organ Dysfunction

    Directory of Open Access Journals (Sweden)

    Yu-Feng Tian

    2013-01-01

    Full Text Available We report here that when untreated mice underwent heat stress, they displayed thermoregulatory deficit (e.g., animals display hypothermia during room temperature exposure, brain (or hypothalamic inflammation, ischemia, oxidative damage, hypothalamic-pituitary-adrenal axis impairment (e.g., decreased plasma levels of both adrenocorticotrophic hormone and corticosterone during heat stress, multiple organ dysfunction or failure, and lethality. Melatonin therapy significantly reduced the thermoregulatory deficit, brain inflammation, ischemia, oxidative damage, hypothalamic-pituitary-adrenal axis impairment, multiple organ dysfunction, and lethality caused by heat stroke. Our data indicate that melatonin may improve outcomes of heat stroke by reducing brain inflammation, oxidative damage, and multiple organ dysfunction.

  6. Electrocardiographically and symptomatically silent myocardial ischemia during exercise testing

    International Nuclear Information System (INIS)

    Certain patients with coronary artery disease (CAD) may have neither ST depression nor chest pain during exercise despite the presence of myocardial ischemia. The frequency and characteristics of such electrocardiographically and symptomatically silent ischemia were studied in 171 patients with both angiographically documented CAD and scintigraphically documented ischemia. Fifty-six (33%) of 171 patients had neither ST depression nor chest pain (Group N), and 115 (67%) had ST depression and/or chest pain (Group P). The two groups were similar with respect to age, gender, the prevalence of prior infarction, and peak systolic blood pressure. Group N patients, however, had a higher mean peak heart rate and rate-pressure product, less severe scintigraphic ischemia, a lower lung thallium-201 uptake, and a smaller number of diseased vessels. Stepwise discriminant analysis showed a history of effort angina, lung thallium-201 uptake, and scintigraphic severity of ischemia to be significant discriminators between Groups N and P. In conclusion, electrocardiographically and symptomatically silent ischemia may be common during exercise in patients with CAD, and less severe ischemia may be one of important determinants. (author)

  7. The effects of erythropoietin on STAT1 and STAT3 levels following cerebral ischemia-reperfusion in rats

    International Nuclear Information System (INIS)

    Objective: To explore the effects of erythropoietin (EPO) on the expression of signal transducer and activator of transcription (STAT) 1, phosphorylated STAT1 (P-STAT1), STAT3, P-STAT3 and cell apoptosis in rat models of focal cerebral ischemia-reperfusion. Methods: Eighty male Sprague-Dawley rats were randomly and evenly divided into four groups by completely random design method: sham-operation (group A), cerebral ischemia-reperfusion (group B), cerebral ischemia-reperfusion ± saline (group C) and cerebral ischemia-reperfusion ± EPO (group D). The model of focal cerebral ischemia-reperfusion injury was established by blocking the left middle cerebral artery. All rats underwent MRI for the detection of the changes of infarct area between 2 h post ischemia and 24 h of reperfusion. Western blot was used to observe the expression of STAT1, P-STAT1, STAT3, P-STAT3. Terminal oxynucleotidyl transferase mediated dUTP biotin nick end labeling (TUNEL) was used to evaluate the cell apoptosis including the relative area (ROI area/whole brain area of the same layer × 100%) of abnormal signal region,relative optical density (rOD) and apoptotic index. One-way analysis of variance and q test were used to analyze the data. Results: On T2WI imaging, rats in group B and group C presented large hyperintense areas in the cortex and subcortex of left hemispheric ((28.00±4.60)% and (29.70±4.80)% respectively). Group D presented less hyperintense areas in the cortex and subcortex of left hemispheric compared with group B and group C ((21.10±2.40) %; F=11.285, P<0.01). The expression of STAT1 and STAT3 proteins was not significantly affected by ischemia-reperfusion and EPO intervention compared with normal brain tissue (F=0.806, 1.558, both P>0.05). However, the level of P-STAT1 was low in group A (rOD =0.75±0.13) but increased after cerebral ischemia-reperfusion. Compared with group B and group C, P-STAT1 expression was lower in group D (B-D: 2.08±0.15, 2.05±0.16, 1.92±0.05; F

  8. Brain Basics

    Medline Plus

    Full Text Available ... The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are the basic working unit of the ... distant nerve cells (via axons) to form brain circuits. These circuits control specific body functions such as ...

  9. Brain Basics

    Medline Plus

    Full Text Available ... than ever before. Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses magnetic fields to take pictures of the brain's structure, studies ...

  10. Brain Basics

    Medline Plus

    Full Text Available ... Brain Basics provides information on how the brain works, how mental illnesses are disorders of the brain, ... others live with symptoms of mental illness every day. They can be moderate, or serious and cause ...

  11. Brain Basics

    Medline Plus

    Full Text Available ... helps Sarah to better cope with her feelings. Brain Research Modern research tools and techniques are giving scientists ... the treatment for a person's specific conditions. Such brain research help increase the understanding of how the brain ...

  12. Brain Basics

    Medline Plus

    Full Text Available ... little dopamine or problems using dopamine in the thinking and feeling regions of the brain may play ... than ever before. Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses ...

  13. Brain Basics

    Medline Plus

    Full Text Available ... as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are the basic working unit of the brain ... specialized for the function of conducting messages. A neuron has three basic parts: Cell body which includes ...

  14. Brain Malformations

    Science.gov (United States)

    Most brain malformations begin long before a baby is born. Something damages the developing nervous system or causes it ... medicines, infections, or radiation during pregnancy interferes with brain development. Parts of the brain may be missing, ...

  15. Brain Basics

    Medline Plus

    Full Text Available ... brain's structure, studies show that brain growth in children with autism appears to peak early. And as ... grow there are differences in brain development in children who develop bipolar disorder than children who do ...

  16. Brain Basics

    Medline Plus

    Full Text Available ... Basics will introduce you to some of this science, such as: How the brain develops How genes and the environment affect the brain The basic structure of the brain How different parts of ...

  17. Brain Basics

    Medline Plus

    Full Text Available ... understanding of the brain than ever before. Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses magnetic fields to take pictures ...

  18. Brain Basics

    Medline Plus

    Full Text Available ... science, such as: How the brain develops How genes and the environment affect the brain The basic ... that with brain development in people mental disorders. Genes and environmental cues both help to direct this ...

  19. Brain surgery

    Science.gov (United States)

    Craniotomy; Surgery - brain; Neurosurgery; Craniectomy; Stereotactic craniotomy; Stereotactic brain biopsy; Endoscopic craniotomy ... cut depends on where the problem in the brain is located. The surgeon creates a hole in ...

  20. Delayed effects of sublethal ischemia on the acquisition of tolerance to ischemia.

    Science.gov (United States)

    Kuzuya, T; Hoshida, S; Yamashita, N; Fuji, H; Oe, H; Hori, M; Kamada, T; Tada, M

    1993-06-01

    The infarct-limiting effect of ischemic preconditioning is believed to be a transient phenomenon. We examined the delayed effects of repetitive brief ischemia on limiting infarct size in an open-chest dog model by an occlusion (90 minutes) of the left anterior descending coronary artery (LAD) followed by reperfusion (5 hours). The dogs were preconditioned with four brief repeated ischemic episodes induced by 5-minute LAD occlusions with subsequent reperfusion. The size of infarcts initiated by a sustained occlusion immediately or 24 hours after preconditioning was significantly smaller when compared with infarcts in sham-operated dogs (for the immediate occlusion, 14.4 +/- 2.0% versus 39.0 +/- 3.7%, respectively [p pressure products between the two groups. These results indicate that an infarct-limiting effect of brief repeated ischemia can be observed 24 hours after sublethal preconditioning. PMID:8495557