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  1. [Cerebral ischemia and histamine].

    Science.gov (United States)

    Adachi, Naoto

    2002-10-01

    Cerebral ischemia induces excess release of glutamate and an increase in the intracellular Ca2+ concentration, which provoke catastrophic enzymatic processes leading to irreversible neuronal injury. Histamine plays the role of neurotransmitter in the central nervous system, and histaminergic fibers are widely distributed in the brain. In cerebral ischemia, release of histamine from nerve endings has been shown to be enhanced by facilitation of its activity. An inhibition of the histaminergic activity in ischemia aggravates the histologic outcome. In contrast, intracerebroventricular administration of histamine improves the aggravation, whereas blockade of histamine H2 receptors aggravates ischemic injury. Furthermore, H2 blockade enhances ischemic release of glutamate and dopamine. These findings suggest that central histamine provides beneficial effects against ischemic neuronal damage by suppressing release of excitatory neurotransmitters. However, histaminergic H2 action facilitates the permeability of the blood-brain barrier and shows deleterious effects on cerebral edema.

  2. Clinical Neuroimaging of cerebral ischemia

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

    1999-06-01

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

  3. Neuronal autophagy in cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

  4. Sirt1 in cerebral ischemia

    Science.gov (United States)

    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 several processes within the central nervous system as well as to possess neuroprotective properties in a variety of pathological conditions such as Alzheimer’s Disease, Parkinson’s Disease, and Huntington’s Disease, among others. Recently, Sirt1 in particular has been identified as a mediator of cerebral ischemia, with potential as a possible therapeutic target. To gather studies relevant to this topic, we used PubMed and previous reviews to locate, select, and resynthesize the lines of evidence presented here. In this review, we will first describe some functions of Sirt1 in the brain, mainly neurodevelopment, learning and memory, and metabolic regulation. Second, we will discuss the experimental evidence that has implicated Sirt1 as a key protein in the regulation of cerebral ischemia as well as a potential target for the induction of ischemic tolerance. PMID:26819971

  5. Sirt1 in cerebral ischemia

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    Kevin B Koronowski

    2015-01-01

    Full Text Available 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 several processes within the central nervous system as well as to possess neuroprotective properties in a variety of pathological conditions such as Alzheimer′s Disease, Parkinson′s Disease, and Huntington′s Disease, among others. Recently, Sirt1 in particular has been identified as a mediator of cerebral ischemia, with potential as a possible therapeutic target. To gather studies relevant to this topic, we used PubMed and previous reviews to locate, select, and resynthesize the lines of evidence presented here. In this review, we will first describe some functions of Sirt1 in the brain, mainly neurodevelopment, learning and memory, and metabolic regulation. Second, we will discuss the experimental evidence that has implicated Sirt1 as a key protein in the regulation of cerebral ischemia as well as a potential target for the induction of ischemic tolerance.

  6. Animal models of cerebral ischemia

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    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.

  7. Experimental Focal Cerebral Ischemia

    DEFF Research Database (Denmark)

    Christensen, Thomas

    2007-01-01

    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 ischemic focus...

  8. Mitochondrial Targeted Antioxidant in Cerebral Ischemia.

    Science.gov (United States)

    Ahmed, Ejaz; Donovan, Tucker; Yujiao, Lu; Zhang, Quanguang

    There has been much evidence suggesting that reactive oxygen species (ROS) generated in mitochondria during cerebral ischemia play a major role in programming the senescence of organism. Antioxidants dealing with mitochondria slow down the appearance and progression of symptoms in cerebral ischemia and increase the life span of organisms. The mechanisms of mitochondrial targeted antioxidants, such as SKQ1, Coenzyme Q10, MitoQ, and Methylene blue, include increasing adenosine triphosphate (ATP) production, decreasing production of ROS and increasing antioxidant defenses, providing benefits in neuroprotection following cerebral ischemia. A number of studies have shown the neuroprotective role of these mitochondrial targeted antioxidants in cerebral ischemia. Here in this short review we have compiled the literature supporting consequences of mitochondrial dysfunction, and the protective role of mitochondrial targeted antioxidants.

  9. [Chronic cerebral ischemia associated with Raynaud's syndrome].

    Science.gov (United States)

    Putilina, M V

    2015-01-01

    Over the last years, a number of patients with chronic cerebral ischemia has been increased significantly. Compensatory possibilities of the brain and cerebral circulatory system are so great that even serious disturbances of blood circulation could not cause clinical signs of brain dysfunction for a long time. At the same time, long-term ischemia can lead to peripheral local disturbances of microcirculation that is appears to be a first signal of the problems with homeostasis. Therefore, Raynaud's syndrome may be one of the predictors of standard symptoms of chronic cerebral ischemia (CCI). This phenomenon is explicitly considered as a sign of blood circulation impairment while the pathogenetic mechanism of vascular arterial bed instability is completely ignored. Detailed study of clinical correlations of Raynaud's syndrome in CCI would help to develop a common pharmacotherapeutic approach to its treatment.

  10. Cerebral hypoxia and ischemia in preterm infants

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    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

  11. Purine Metabolism in Acute Cerebral Ischemia

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    Ye. V. Oreshnikov

    2008-01-01

    Full Text Available Objective: to study the specific features of purine metabolism in clinically significant acute cerebral ischemia. Subjects and materials. Three hundred and fifty patients with the acutest cerebral ischemic stroke were examined. The parameters of gas and electrolyte composition, acid-base balance, the levels of malonic dialdehyde, adenine, guanine, hypox-anthine, xanthine, and uric acid, and the activity of xanthine oxidase were determined in arterial and venous bloods and spinal fluid. Results. In ischemic stroke, hyperuricemia reflects the severity of cerebral metabolic disturbances, hemodynamic instability, hypercoagulation susceptiility, and the extent of neurological deficit. In ischemic stroke, hyperuri-corachia is accompanied by the higher spinal fluid levels of adenine, guanine, hypoxanthine, and xanthine and it is an indirect indicator of respiratory disorders of central genesis, systemic acidosis, hypercoagulation susceptibility, free radical oxidation activation, the intensity of a stressor response to cerebral ischemia, cerebral metabolic disturbances, the depth of reduced consciousness, and the severity of neurological deficit. Conclusion. The high venous blood activity of xanthine oxidase in ischemic stroke is associated with the better neurological parameters in all follow-up periods, the better early functional outcome, and lower mortality rates. Key words: hyperuricemia, stroke, xanthine oxidase, uric acid, cerebral ischemia.

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

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

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

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

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    Jun Li

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

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

    Institute of Scientific and Technical Information of China (English)

    Caiwei Qiu; Bo Sheng; Shurong Wang; Jin Liu

    2013-01-01

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

  15. Effect of heat shock protein 70 on cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Wen Yan; Xiulian Chen; Rui Chen; Shiming Xu; Lijuan Zhang; Hongjuan Wang; Chunyue Huo

    2006-01-01

    OBJECTIVE: To summarize the relationship between heat shock protein 70 (HSP70) and cerebral ischemia.DATA SOURCES: An online search of Medline database was undertaken to identify relevant articles published in English from January 1980 to December 2005 by using the keywords of "heat shock protein 70, ischemia". Meanwhile, Chinese relevant articles published from January 2000 to December 2005 were searched in China National Knowledge Infrastructure (CNKI) database and Chinese Journal of Clinical Rehabilitation with the keywords of "heat shock protein 70, cerebral ischemia" in Chinese.STUDY SELECTION: More than 100 related articles were screened, and 29 references mainly about HSP70and cerebral ischemia were selected, including basic and clinical researches. As to the articles with similar content, those published in the authoritative journals in recent 3 years were preferential.DATA EXTRACTION : A total of 29 articles were collected and classified according to the structure, function and clinical application of HSP70. Among them, 1 article is about the structure of HSP70, 27 about the relationship between HSP70 and cerebral ischemia, and 2 about the clinical application of HSP70.DATA SYNTHESTS: HSP70 is one of the most conservative proteins during biological evolution. Experiments in cerebral ischemia revealed that HSP70 expression was time-dependent, also correlated with the injured site and severity. The cerebral ischemia induced HSP70 gene expression in hippocampus of gerbil had protection to tolerance of fatal ischemic injury for neurons. The increase of HSP70 expression may be one of the endogenous protective mechanisms during cerebral ischemia, and can effectively alleviate cerebral ischemia. Thus HSP70 protein and HSP70 mRNA have been taken as important indexes extensively applied in the basic study of cerebral ischemia by some scholars abroad.CONCLUSTON: HSP70 plays a protective role in cerebral ischemia, and a deeper research into the biological function of

  16. Post-Traumatic Late Onset Cerebral Ischemia

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    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.

  17. Mixed models in cerebral ischemia study

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    Matheus Henrique Dal Molin Ribeiro

    2016-06-01

    Full Text Available The data modeling from longitudinal studies stands out in the current scientific scenario, especially in the areas of health and biological sciences, which induces a correlation between measurements for the same observed unit. Thus, the modeling of the intra-individual dependency is required through the choice of a covariance structure that is able to receive and accommodate the sample variability. However, the lack of methodology for correlated data analysis may result in an increased occurrence of type I or type II errors and underestimate/overestimate the standard errors of the model estimates. In the present study, a Gaussian mixed model was adopted for the variable response latency of an experiment investigating the memory deficits in animals subjected to cerebral ischemia when treated with fish oil (FO. The model parameters estimation was based on maximum likelihood methods. Based on the restricted likelihood ratio test and information criteria, the autoregressive covariance matrix was adopted for errors. The diagnostic analyses for the model were satisfactory, since basic assumptions and results obtained corroborate with biological evidence; that is, the effectiveness of the FO treatment to alleviate the cognitive effects caused by cerebral ischemia was found.

  18. Selective gene expression in focal cerebral ischemia.

    Science.gov (United States)

    Jacewicz, M; Kiessling, M; Pulsinelli, W A

    1986-06-01

    Regional patterns of protein synthesis were examined in rat cortex made ischemic by the occlusion of the right common carotid and middle cerebral arteries. At 2 h of ischemia, proteins were pulse labeled with intracortical injections of a mixture of [3H]leucine, [3H]isoleucine, and [3H]proline. Newly synthesized proteins were analyzed by two-dimensional gel fluorography, and the results correlated with local CBF, measured with [14C]iodoantipyrine as tracer. Small blood flow reductions (CBF = 50-80 ml 100 g-1 min-1) were accompanied by a modest inhibition in synthesis of many proteins and a marked increase in one protein (Mr 27,000). With further reduction in blood flow (CBF = 40 ml 100 g-1 min-1), synthesis became limited to a small group of proteins (Mr 27,000, 34,000, 73,000, 79,000, and actin) including two new polypeptides (Mr 55,000 and 70,000). Severe ischemia (CBF = 15-25 ml 100 g-1 min-1) caused the isoelectric modification of several proteins (Mr 44,000, 55,000, and 70,000) and induced synthesis of another protein (Mr 40,000). Two polypeptides (Mr 27,000 and 70,000) dominated residual protein synthesis in severe ischemia. The changes in protein synthesis induced by different grades of ischemia most likely comprise a variation of the so-called "heat shock" or "stress" response found in all eukaryotic cells subjected to adverse conditions. Since heat shock genes are known to confer partial protection against anoxia and a variety of other noxious insults, their induction may be a factor in limiting the extent of ischemic tissue damage.

  19. Cephalea, Horner's syndrome and cerebral ischemia: pathognomonic triad

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    Fulvio Pomero

    2007-06-01

    Full Text Available Dissection of cerebral vessels represents an important cause of stroke in young patients without cardiovascular risk factors. Clinical feature of this pathology is quite peculiar and is described as combination of cephalea, Horner’s syndrome and cerebral ischemia. Clinical suspicion and fast access to ecocolordoppler are the only ways to save vessels’ patency and to restore cerebral blood flow.

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

    Institute of Scientific and Technical Information of China (English)

    Bangyu Ju; Jing Zhang; Guohua Jiang

    2007-01-01

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

  1. Neuroprotection by inhibiting the c-Jun N-terminal kinase pathway after cerebral ischemia occurs independently of interleukin-6 and keratinocyte-derived chemokine (KC/CXCL1 secretion

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    Benakis Corinne

    2012-04-01

    Full Text Available Abstract Background Cerebral ischemia is associated with the activation of glial cells, infiltration of leukocytes and an increase in inflammatory mediators in the ischemic brain and systemic circulation. How this inflammatory response influences lesion size and neurological outcome remains unclear. D-JNKI1, an inhibitor of the c-Jun N-terminal kinase pathway, is strongly neuroprotective in animal models of stroke. Intriguingly, the protection mediated by D-JNKI1 is high even with intravenous administration at very low doses with undetectable drug levels in the brain, pointing to a systemic mode of action, perhaps on inflammation. Findings We evaluated whether D-JNKI1, administered intravenously 3 h after the onset of middle cerebral artery occlusion (MCAO, modulates secretion of the inflammatory mediators interleukin-6 and keratinocyte-derived chemokine in the plasma and from the spleen and brain at several time points after MCAO. We found an early release of both mediators in the systemic circulation followed by an increase in the brain and went on to show a later systemic increase in vehicle-treated mice. Release of interleukin-6 and keratinocyte-derived chemokine from the spleen of mice with MCAO was not significantly different from sham mice. Interestingly, the secretion of these inflammatory mediators was not altered in the systemic circulation or brain after successful neuroprotection with D-JNKI1. Conclusions We demonstrate that neuroprotection with D-JNKI1 after experimental cerebral ischemia is independent of systemic and brain release of interleukin-6 and keratinocyte-derived chemokine. Furthermore, our findings suggest that the early systemic release of interleukin-6 and keratinocyte-derived chemokine may not necessarily predict an unfavorable outcome in this model.

  2. 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.

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

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    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.

  4. Relationship between vasospasm, cerebral perfusion, and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage

    NARCIS (Netherlands)

    Dankbaar, Jan W.; Rijsdijk, Mienke; van der Schaaf, Irene C.; Velthuis, Birgitta K.; Wermer, Marieke J. H.; Rinkel, Gabriel J. E.

    2009-01-01

    Vasospasm after aneurysmal subarachnoid hemorrhage (SAH) is thought to cause ischemia. To evaluate the contribution of vasospasm to delayed cerebral ischemia (DCI), we investigated the effect of vasospasm on cerebral perfusion and the relationship of vasospasm with DCI. We studied 37 consecutive SAH

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

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    Deniz Kamacı Şener

    2012-12-01

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

  6. 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.

  7. 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 (Pneurogenesis in CA1-CA3 fields was increased as compared to the control (P<0.05).

  8. Tenoxicam exerts a neuroprotective action after cerebral ischemia in rats.

    Science.gov (United States)

    Galvão, Rita I M; Diógenes, João P L; Maia, Graziela C L; Filho, Emídio A S; Vasconcelos, Silvânia M M; de Menezes, Dalgimar B; Cunha, Geanne M A; Viana, Glauce S B

    2005-01-01

    In this study we investigated the effects of Tenoxicam, a type 2 cyclooxygenase (COX-2) inhibitor, on brain damage induced by ischemia-reperfusion. Male Wistar rats (18-month old average) were anesthetized and submitted to ischemia occlusion of both common carotid arteries (BCAO) for 45 min. After 24 h of reperfusion, rats were decapitated and hippocampi removed for further assays. Animals were divided into sham-operated, ischemia, ischemia + Tenoxicam 2.5 mg/kg, and ischemia + Tenoxicam 10 mg/kg groups. Tenoxicam was administered intraperitoneally immediately after BCAO. Histological analyses show that ischemia produced significant striatal as well as hippocampal lesions which were reversed by the Tenoxicam treatment. Tenoxicam also significantly reduced, to control levels, the increased myeloperoxidase activity in hippocampus homogenates observed after ischemia. However, nitrite concentrations showed only a tendency to decrease in the ischemia + Tenoxicam groups, as compared to that of ischemia alone. On the other hand, hippocampal glutamate and aspartate levels were not altered by Tenoxicam. In conclusion, we showed that ischemia is certainly related to inflammation and to increased free radical production, and selective COX-2 inhibitors might be neuroprotective agents of potential benefit in the treatment of cerebral brain ischemia.

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

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

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

  10. 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.

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

    Science.gov (United States)

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

    2013-02-01

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

  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. Electroencephalographic Response to Sodium Nitrite May Predict Delayed Cerebral Ischemia After Severe Subarachnoid Hemorrhage

    Science.gov (United States)

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

    2016-01-01

    Objectives: Aneurysmal subarachnoid hemorrhage often leads to death and poor clinical outcome. Injury occurring during the first 72 hours is termed “early brain injury,” with disruption of the nitric oxide pathway playing an important pathophysiologic role in its development. Quantitative electroencephalographic variables, such as α/δ frequency ratio, are surrogate markers of cerebral ischemia. This study assessed the quantitative electroencephalographic response to a cerebral nitric oxide donor (intravenous sodium nitrite) to explore whether this correlates with the eventual development of delayed cerebral ischemia. Design: Unblinded pilot study testing response to drug intervention. Setting: Neuroscience ICU, John Radcliffe Hospital, Oxford, United Kingdom. Patients: Fourteen World Federation of Neurosurgeons grades 3, 4, and 5 patients (mean age, 52.8 yr [range, 41–69 yr]; 11 women). Interventions: IV sodium nitrite (10 μg/kg/min) for 1 hour. Measurements and Main Results: Continuous electroencephalographic recording for 2 hours. The alpha/delta frequency ratio was measured before and during IV sodium nitrite infusion. Seven of 14 patients developed delayed cerebral ischemia. There was a +30% to +118% (range) increase in the alpha/delta frequency ratio in patients who did not develop delayed cerebral ischemia (p < 0.0001) but an overall decrease in the alpha/delta frequency ratio in those patients who did develop delayed cerebral ischemia (range, +11% to –31%) (p = 0.006, multivariate analysis accounting for major confounds). Conclusions: Administration of sodium nitrite after severe subarachnoid hemorrhage differentially influences quantitative electroencephalographic variables depending on the patient’s susceptibility to development of delayed cerebral ischemia. With further validation in a larger sample size, this response may be developed as a tool for risk stratification after aneurysmal subarachnoid hemorrhage. PMID:27441898

  14. Heart rate variability in patients with chronic cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Smyshlaeva О.М.

    2010-12-01

    Full Text Available The purpose of the work is to estimate the status of autonomic nervous system in patients with chronic cerebral ischemia by means of the analysis of heart rate variability at various stages of disease. 120 patients with chronic cerebral ischemia aged from 45 to 65 took part in the research. The comparison group included 30 patients with an arterial hypertension and without chronic cerebral ischemia. Heart rate variability analisis included time-domain and frequency-domain methods of five-minute sequence of the electrocardiographic intervals registered in at rest and in or-thostatic probe. The results of research have shown, that autonomic disorders with prevalence of sympathetic nervous system accompany initial implications of chronic cerebral ischemia. The second stage of disease is characterized by depression of activity of both autonomic, and central regulation. The expressed depression of autonomic maintenance of regulation of heart rhythm of both from sympathetic, and from parasympathetic nervous system was observed at the third stage of chronic cerebral ischemia

  15. Evaluation of murine models of permanent focal cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    席刚明; 汪华侨; 何国厚; 黄朝芬; 魏国耀

    2004-01-01

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

  16. Delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage : the role of coagulation and fibrinolysis

    NARCIS (Netherlands)

    M.D.I. Vergouwen

    2009-01-01

    Patients with aneurysmal subarachnoid hemorrhage (SAH) are at risk to develop complications, especially within the first two weeks after the hemorrhage. Delayed cerebral ischemia (DCI) is a complication which occurs in about 30% of SAH patients, leading to symptoms such as aphasia, hemiparesis, or i

  17. [Antioxidant effects of antihypoxic drugs in cerebral ischemia].

    Science.gov (United States)

    Plotnikov, M B; Kobzeva, E A; Plotnikova, T M

    1992-05-01

    Cerebral ischemia in rats (both carotid arteries occlusion) during 30 min, 3 hours and recirculation (1 hour) after ischemia (30 min) stimulated diene conjugates and fluorescent products accumulation in brain tissue. Intraperitoneal injection of sodium hydroxybutyrate (100 mg/kg), bemitil (50 mg/kg), ethomersol (50 mg/kg) reduced brain lipid peroxidation and did not yield in this respect to emoxypin (5 mg/kg). In contrast to emoxypin, sodium hydroxybutyrate, bemitil and ethomersol had no antiradical activity.

  18. 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.

  19. Endogenous Protease Nexin-1 Protects against Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    Jonathan Thevenet

    2013-08-01

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

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

    Science.gov (United States)

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

    2013-08-14

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

  1. Diffusion and Perfusion MRI in Acute Cerebral Ischemia

    Institute of Scientific and Technical Information of China (English)

    Tchoyoson CC Lim; Chong-Tin Tan

    2001-01-01

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

  2. Endothelin Receptors, Mitochondria and Neurogenesis in Cerebral Ischemia

    Science.gov (United States)

    Gulati, Anil

    2016-01-01

    Background: Neurogenesis is most active during pre-natal development, however, it persists throughout the human lifespan. The putative role of mitochondria in neurogenesis and angiogenesis is gaining importance. Since, ETB receptor mediated neurogenesis and angiogenesis has been identified, the role of these receptors with relevance to mitochondrial functions is of interest. Methods: In addition to work from our laboratory, we undertook an extensive search of bibliographic databases for peer-reviewed research literature. Specific technical terms such as endothelin, mitochondria and neurogenesis were used to seek out and critically evaluate literature that was relevant. Results: The ET family consists of three isopeptides (ET-1, ET-2 and ET-3) that produce biological actions by acting on two types of receptors (ETA and ETB). In the central nervous system (CNS) ETA receptors are potent constrictors of the cerebral vasculature and appear to contribute in the causation of cerebral ischemia. ETA receptor antagonists have been found to be effective in animal model of cerebral ischemia; however, clinical studies have shown no efficacy. Mitochondrial functions are critically important for several neural development processes such as neurogenesis, axonal and dendritic growth, and synaptic formation. ET appears to impair mitochondrial functions through activation of ETA receptors. On the other hand, blocking ETB receptors has been shown to trigger apoptotic processes by activating intrinsic mitochondrial pathway. Mitochondria are important for their role in molecular regulation of neurogenesis and angiogenesis. Stimulation of ETB receptors in the adult ischemic brain has been found to promote angiogenesis and neurogenesis mediated through vascular endothelial growth factor and nerve growth factor. It will be interesting to investigate the effect of ETB receptor stimulation on mitochondrial functions in the CNS following cerebral ischemia. Conclusion: The findings of this

  3. Changes in Cerebral Perfusion around the Time of Delayed Cerebral Ischemia in Subarachnoid Hemorrhage Patients

    NARCIS (Netherlands)

    Dankbaar, J. W.; de Rooij, N. K.; Smit, E. J.; Velthuis, B. K.; Frijns, C. J. M.; Rinkel, G. J. E.; van der Schaaf, I. C.

    2011-01-01

    Background: Because the pathogenesis of delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) is unclear, we studied cerebral perfusion at different time points around the occurrence of DCI. Methods: We prospectively enrolled 53 patients admitted to the University Medical Center Utrech

  4. Alterations in the Cerebral Microvascular Proteome Expression Profile After Transient Global Cerebral Ischemia in Rat

    DEFF Research Database (Denmark)

    Spray, Stine; Johansson, Sara E; Edwards, Alistair V G;

    2016-01-01

    This study aimed at obtaining an in-depth mapping of expressional changes of the cerebral microvasculature after transient global cerebral ischemia (GCI) and the impact on these GCI-induced expressional changes of post-GCI treatment with a mitogen-activated protein kinase kinase (MEK1/2) inhibitor...

  5. Treatment of acute hydrocephalus and cerebral ischemia after subarachnoid hemorrhage

    NARCIS (Netherlands)

    D. Hasan (Djo)

    1990-01-01

    textabstractOnly recently has acute hydrocephalus after subarachnoid hemorrhage been recognized as a clinical important problem. The mortality rate in patients with acute hydrocephalus after subarachnoid hemorrhage is higher than in those without, which is mainly caused by cerebral ischemia. An expl

  6. Cerebrovascular angiotensin AT1 receptor regulation in cerebral ischemia

    DEFF Research Database (Denmark)

    Edvinsson, L.

    2008-01-01

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

  7. [Neuroprotection of herbs promoting EPO on cerebral ischemia].

    Science.gov (United States)

    Li, Xu; Bai, Zhen-ya; Zhang, Fei-yan; Xu, Xiao-yu

    2015-06-01

    Amounts of researches show that EPO is characterized with neurotrophic and neuroprotective manner, especially in brain stroke, which attracts a large numbers of researchers to study it. With the accumulating researches on its neuroprotection, many related mechanisms were revealed, such as antioxidant, anti-apoptosis, angiogenesis, anti-inflammatory, which suggests a multiple targets role of EPO on brain stroke. However, because of the high risk of thromboembolism in clinical administration of rhEPO and its analogs, the herbs are potential to be a replacer for its less side effects. Many researchers suggested that a larger of herbs were founded having the action of increasing the endogenous EPO in the model of anemia and cerebral ischemia. At the same time, there herbs were also proved that they had the action of against cerebral ischemia while some without considering the role of EPO in the reports. Considering of the action of promoting EPO of these herbs and the neural protection of EPO, this essay mainly summarizes the studies of herbs promoting EPO in the cerebral ischemia and discusses the mechanism of regulating the EPO of these herbs, for the aim of finding the potential drugs against cerebral ischemia.

  8. Ligustrazine monomer against cerebral ischemia-reperfusion injury

    Directory of Open Access Journals (Sweden)

    Hai-jun Gao

    2015-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    QiuLi-ying; YuJuan; ChenChong-hong; ZhouYu

    2004-01-01

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

  10. Autoregulation of cerebral blood flow in experimental focal brain ischemia.

    Science.gov (United States)

    Dirnagl, U; Pulsinelli, W

    1990-05-01

    The relationship between systemic arterial pressure (SAP) and neocortical microcirculatory blood-flow (CBF) in areas of focal cerebral ischemia was studied in 15 spontaneously hypertensive rats (SHRs) anesthetized with halothane (0.5%). Ischemia was induced by ipsilateral middle cerebral artery/common carotid artery occlusion and CBF was monitored continuously in the ischemic territory using laser-Doppler flowmetry during manipulation of SAP with I-norepinephrine (hypertension) or nitroprusside (hypotension). In eight SHRs not subjected to focal ischemia, we demonstrated that 0.5% halothane and the surgical manipulations did not impair autoregulation. Autoregulation was partly preserved in ischemic brain tissue with a CBF of greater than 30% of preocclusion values. In areas where ischemic CBF was less than 30% of preocclusion values, autoregulation was completely lost. Changes in SAP had a greater influence on CBF in tissue areas where CBF ranged from 15 to 30% of baseline (9% change in CBF with each 10% change in SAP) than in areas where CBF was less than 15% of baseline (6% change in CBF with each 10% change in SAP). These findings demonstrate that the relationship between CBF and SAP in areas of focal ischemia is highly dependent on the severity of ischemia. Autoregulation is lost in a gradual manner until CBF falls below 30% of normal. In areas without autoregulation, the slope of the CBF/SAP relationship is inversely related to the degree of ischemia.

  11. Neuroprotective effects of female sex steroids in cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Drača Sanja

    2013-03-01

    Full Text Available The central and peripheral nervous system are important targets of sex steroids. Sex steroids affect the brain development and differentiation, and influence neuronal functions. Recent evidence emphasizes a striking sex-linked difference in brain damage after experimental stroke, as well as the efficacy of hormones in treating cerebral stroke injury. Several different models of cerebral ischemia have been utilized for hormone neuroprotection studies, including transient or permanent middle cerebral artery occlusion, transient global ischemia, and transient forebrain ischemia. Extensive experimental studies have shown that female sex steroids such as progesterone and 176-estradiol exert neuroprotective effects in the experimental models of stroke, although deleterious effects have also been reported. Also, a significance of numerous factors, including gender and age of experimental animals, localization of brain lesion, duration of ischemia and precise dose of steroids has been pointed out. There are multiple potential mechanisms that might be invoked to explain the beneficial effects of female sex steroids in brain injury, involving neuroprotection, anti-inflammatory properties, effects on vasculature and altered transcriptional regulation. A several clinical trials on the effects of sex hormones to traumatic brain injury have been performed, suggesting that hormone therapy may represent a new therapeutic tool to combat certain diseases, such as traumatic brain injury. Further basic science studies and randomized clinical trials are necessary to reveal a potential application of these molecules as a new therapeutic strategy.

  12. 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.

  13. The clinical relevance of cerebral microbleeds in patients with cerebral ischemia and atrial fibrillation.

    Science.gov (United States)

    Haji, Shamir; Planchard, Ryan; Zubair, Adeel; Graff-Radford, Jonathan; Rydberg, Charlotte; Brown, Robert D; Flemming, Kelly D

    2016-02-01

    The clinical significance of cerebral microbleeds (CMB) in patients hospitalized with atrial fibrillation (AF) and cerebral ischemia is unclear. We aimed to determine the prevalence of CMB in this population and determine the future risk of intracerebral hemorrhage (ICH) and cerebral infarction (CI). The medical records and brain imaging of patients hospitalized with cerebral ischemia due to AF between 2008 and 2011 were reviewed. Followup was obtained through medical record review, mailed survey, and acquisition of death certificates. Prevalence was calculated from those patients with a hemosiderin-sensitive MRI sequence. Recurrent CI and ICH were calculated using Kaplan-Meier curves censored at 3 years. Among 426 patients hospitalized with cerebral ischemia due to AF, 134 had an MRI with hemosiderin-sensitive sequences. The prevalence of CMB was 27.6%. At 3 years, 90.6% of CMB-negative patients were overall stroke free (ICH and CI) compared to 78.6% CMB-positive patients (p = 0.0591). Only one patient in the CMB-positive group had an ICH distant to the CMB. There was a nonsignificant trend toward higher recurrent CI, recurrent overall stroke rate, and mortality in patients with 5 or more CMB compared to 0-4 CMB. The rate of prospective CI in patients with prior cerebral ischemia due to AF is higher than the rate of ICH in patients with CMB. Further study is warranted to assess larger numbers of patients to determine appropriate antithrombotic use in this high-risk population.

  14. Effect of Buyang Huanwu decoction and its disassembled recipes on rats’ neurogenesis after focal cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    曲铁兵

    2014-01-01

    Objective To explore the effect of Buyang Huanwu Decoction(BYHWD)and its disassembled recipes on rats’neurogenesis after focal cerebral ischemia and to investigate its underlying molecular mechanisms.Methods Focal cerebral ischemia model was induced by occlusion of the right middle cerebral artery for 90 min using the

  15. P2X7 receptors in cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Hui-Yu Bai; Ai-Ping Li

    2013-01-01

    Cerebral ischemia is one of the most common diseases resulting in death and disability in aged people.It leads immediately to rapid energy failure,ATP depletion,and ionic imbalance,which increase extracellular ATP levels and accordingly activate P2X7 receptors.These receptors are ATP-gated cation channels and widely distributed in nerve cells,especially in the immunocompetent cells of the brain.Currently,interest in the roles of P2X7 receptors in ischemic brain injury is growing.In this review,we discuss recent research progress on the actions of P2X7 receptors,their possible mechanisms in cerebral ischemia,and the potential therapeutic value of P2X7 receptor antagonists which may provide a new target both for clinical and for research purposes.

  16. Effects of rapamycin on cerebral oxygen supply and consumption during reperfusion after cerebral ischemia.

    Science.gov (United States)

    Chi, O Z; Barsoum, S; Vega-Cotto, N M; Jacinto, E; Liu, X; Mellender, S J; Weiss, H R

    2016-03-01

    Activation of the mammalian target of rapamycin (mTOR) leads to cell growth and survival. We tested the hypothesis that inhibition of mTOR would increase infarct size and decrease microregional O2 supply/consumption balance after cerebral ischemia-reperfusion. This was tested in isoflurane-anesthetized rats with middle cerebral artery blockade for 1h and reperfusion for 2h with and without rapamycin (20mg/kg once daily for two days prior to ischemia). Regional cerebral blood flow was determined using a C(14)-iodoantipyrine autoradiographic technique. Regional small-vessel arterial and venous oxygen saturations were determined microspectrophotometrically. The control ischemic-reperfused cortex had a similar blood flow and O2 consumption to the contralateral cortex. However, microregional O2 supply/consumption balance was significantly reduced in the ischemic-reperfused cortex. Rapamycin significantly increased cerebral O2 consumption and further reduced O2 supply/consumption balance in the reperfused area. This was associated with an increased cortical infarct size (13.5±0.8% control vs. 21.5±0.9% rapamycin). We also found that ischemia-reperfusion increased AKT and S6K1 phosphorylation, while rapamycin decreased this phosphorylation in both the control and ischemic-reperfused cortex. This suggests that mTOR is important for not only cell survival, but also for the control of oxygen balance after cerebral ischemia-reperfusion.

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

  18. Effect of Morphine Withdrawal Syndrome on Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    Mohammad Allahtavakoli

    2011-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

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

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

    Science.gov (United States)

    Yamazaki, Yui; Harada, Shinichi; Tokuyama, Shogo

    2015-09-14

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

  1. Role of unphosphorylated transcription factor STAT3 in late cerebral ischemia after subarachnoid hemorrhage

    DEFF Research Database (Denmark)

    Samraj, Ajoy K; Müller, Anne H; Grell, Anne-Sofie;

    2014-01-01

    Molecular mechanisms behind increased cerebral vasospasm and local inflammation in late cerebral ischemia after subarachnoid hemorrhage (SAH) are poorly elucidated. Using system biology tools and experimental SAH models, we have identified signal transducer and activator of transcription 3 (STAT3...

  2. 12 hours after cerebral ischemia is the optimal time for bone marrow mesenchymal stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Seyed Mojtaba Hosseini

    2015-01-01

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

  3. 12 hours after cerebral ischemia is the optimal time for bone marrow mesenchymal stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

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

  4. Protective Effects and Mechanism of Puerarin on Learning-Memory Disorder after Global Cerebral Ischemia-Reperfusion Injury in Rats

    Institute of Scientific and Technical Information of China (English)

    WU Hai-qin; GUO He-na; WANG Hu-qing; CHANG Ming-ze; ZHANG Gui-lian; ZHAO Ying-xian

    2009-01-01

    Objective: To observe the effect of puerarin on the learning-memory disorder after global cerebral ischemia-reperfusion injury in rats, and to explore its mechanism of action. Methods: The global cerebral ischemia-reperfusion injury model was established using the modified Pulsinelli four-vessel occlusion in Sprague-Dawley rats. Rats were intraperitoneally injected with puerarin (100 mg/kg) 1 h before ischemia and once every 6 h afterwards. The learning-memory ability was evaluated by the passive avoidance test. The dynamic changes of the cell counts of apoptosis and positive expression of Bcl-2 in the hippocampus CA1 region were determined by the TUNEL and immunohistochemical methods, respectively. Results: (1) Compared with the reperfusion group, the step through latency (STL) in the passive avoidance test in the puerarin group was prolonged significantly (P<0.01). (2) The apoptotic neurons were injured most severely on the 3rd day in the hippocampal CA1 region after global ischemia and reperfusion. In the pueradn group, the number of apoptotic cells decreased at respective time points after ischemia-reperfusion (P<0.01). (3) The level of positive expression of Bcl-2 varied according to the duration of reperfusion and the peak level occurred on day 1 in the hippocampal CA1 region after global cerebral ischemia. Compared with the reperfusion group, the expression of Bcl-2 in the pueradn group was up-regulated at the respective time points after ischemia raperfusion (P<0.01), reaching the peak on day 1. Conclusions: Puerarin could improve the learning-memory ability after global cerebral ischemia and reperfusion in rats. The protective mechanism might be related to the effect of inhibiting or delaying the cell apoptosis through up-regulating the expression of Bcl-2 after ischemia and reperfusion.

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

    DEFF Research Database (Denmark)

    Vikman, P; Edvinsson, L

    2006-01-01

    MCA samples distributing to the ischemic area, 7-10 days post-stroke. The gene expression was examined with real-time polymerase chain reaction (PCR) and microarray, proteins were studied with immunohistochemistry. We investigated genes previously shown to be upregulated in animal models of cerebral...... with microarray and seven genes chosen for further investigation with real-time PCR; ELK3, LY64, Metallothionin IG, POU3F4, Actin alpha2, RhoA and smoothelin. Six of these were regulated the same way when confirming array expression with real-time PCR. Gene expression studies in the human MCA leading......We have investigated the gene expression in human middle cerebral artery (MCA) after ischemia. Ischemic stroke affects the perfusion in the affected area and experimental cerebral ischemia results in upregulation of vasopressor receptors in the MCA leading to the ischemic area. We obtained human...

  6. Cerebrovascular endothelin receptor upregulation in cerebral ischemia

    DEFF Research Database (Denmark)

    Edvinsson, Lars

    2009-01-01

    leading to the enhanced expression of vascular endothelin receptors show that both protein kinase C (PKC) and mitogen activating protein kinase (MAPK) play important roles. The results from this work provide new perspectives on the pathophysiology of ischemic stroke, and give a possible explanation......Stroke is a serious neurological disease and the third leading cause of death in the western world. In roughly 15 % of the cases, the cause is due to an intracranial haemorrhage, and the remaining 85 % represent ischemic strokes. Ischemic stroke is caused by the occlusion of a cerebral artery...... either by an embolus or by local thrombosis. Several studies have shown an involvement of the endothelin system in ischemic stroke. This review aims to examine the alterations of vascular endothelin receptor expression in ischemic stroke. Furthermore, studies of the intracellular signalling pathways...

  7. 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.

  8. Cognitive Status in Patients with Chronic Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    Yokudhon N. Madjidova

    2013-12-01

    Full Text Available The aim of our study was to examine the cognitive functions in patients with chronic cerebral ischemia (stages I- II of discirculatory encephalopathy of various origins. Systematization of the patients was performed according to EV Schmidt’s classification of the vascular lesions of the brain. All the subjects were categorized into two groups. Group 1 consisted of 115 patients (42 men and 73 women with chronic cerebral ischemia (CCI that had developed, mainly, against the background of arterial hypertension (AH. Group 2 consisted of 122 patients (33 men and 89 women with CCI, which developed, mainly, against the backdrop of atherosclerosis of the cerebral vessels. The mean age was 54.2±0.7 years in Group 1 and 56.8±0.8 years Group 2, respectively. Control group included 30 healthy subjects (mean age: 52.2±0.9 years without any objective manifestations of CCI. The stage of cognitive deficit was determined by employing the MMSE test and the Bourdon test. The “Schulte Tables” technique was used for estimating the stability of attention and rate of sensorimotor reactions. Luria’s Memory Ten-Word Retrieval Test (LMTWRT was applied for estimating attention and memory. The present study indicates that the cognitive deficits detected in patients with CIC were characterized by the greatest severity against the background of AH. AH predominantly damages the subcortical structures, resulting in subcortical angioencephalopathy, which ultimately leads to a deterioration of the intellectual-mental processes.

  9. Pharmacologicalmodification of thegabaergicsystem as a potentialvariant of cerebral protection in acute cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Олександр Володимирович Тихоновський

    2015-10-01

    Full Text Available The aim is to study the possible impact of some derivatives of gamma-aminobutyric acid (GABA, piracetam, picamilon and Krebs cycle intermediates - succinate (as sodium salt on the pathobiochemical changes in the central nervous system, that occur under experimental playing of acute ischemic tissue damage of the cerebrum.Research methods: The study was conducted in 96 rats Wistar, who were on a standardized vivarium diet. Cerebral ischemia was caused by bond of the unilateral common carotid artery. All drugs were administered intraperitoneally once daily for 4 days after modeling of an acute cerebral ischemia after which animals were withdrawn from experiment. In the brain tissues concentrations of pyruvic, izocitric, dairy and apple acids were determined. The activity of antioxidant enzymes: catalase and superoxide dysmutaza. In addition, the brain tissues the contents of lipid peroxidation products were evaluated – diene conjugates and malonic dialdehyde. Level of brain energy production was judged by the content of the adenylic nucleotide and also phosphocreatine . The degree of destruction of the brain cells was assessed by activity of the enzyme lactate dehydrogenase in the blood and brain fraction of the creatine phosphokinase.Research results: As a result of studies, on the 4th day of ischemia a significant carbohydrate metabolism is detected, which is reflected in the sharp strengthening of anaerobic glycolysis and reduced activity of the Krebs cycle reactions, as evidenced by a significant increase in quantity of lactate and decrease in quantity of malate, isocitrate and pyruvate.A sharp strengthening of anaerobic glycolysis results in the accumulation of oxidized products and intermediates especially the latter product – lactic acid. Metabolic acidosis develops against the background of energy failure, which leads to activation of lipid peroxidation reactions. Courses appointment of the cyclic derivatives of GABA piracetam

  10. 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.)

  11. Propofol inhibits inflammation and lipid peroxidation following cerebral ischemia/ reperfusion in rabbits

    Institute of Scientific and Technical Information of China (English)

    Xiaodong Wei; Xing Wan; Bo Zhao; Jiabao Hou; Min Liu; Bangchang Cheng

    2012-01-01

    The present study established a rabbit model of global cerebral ischemia using the ‘six-vessel' method, which was reperfused after 30 minutes of ischemia. Rabbits received intravenous injection of propofol at 5 mg/kg prior to ischemia and 20 mg/kg per hour after ischemia until samples were prepared. Results revealed that propofol inhibited serum interleukin-8, endothelin-1 and malondialdehyde increases and promoted plasma superoxide dismutase activity after cerebral ischemia/reperfusion. In addition, cerebral cortex edema was attenuated with little neuronal nuclear degeneration and pyknosis with propofol treatment. The cross-sectional area of neuronal nuclei was, however, increased following propofol treatment. These findings suggested that propofol could improve anti-oxidant activity and inhibit synthesis of inflammatory factors to exert a protective effect on cerebral ischemia/reperfusion injury.

  12. A comparative study of EEG suppressions induced by global cerebral ischemia and anoxia.

    Science.gov (United States)

    Zagrean, L; Vatasescu, R; Oprica, M; Nutiu, O; Ferechide, D

    1995-01-01

    Cerebral ischemia and anoxia induce sequential changes that include ionic redistribution, alteration of enzimatic reactions governing metabolism and intracellular signaling. Despite high technology instrumentation including positron emission, tomography and magnetic resonance imaging used to unravel the intricacies of cerebral blood flow and metabolism, the electroencephalography (EEG) retains a useful place in the evaluation of processes induced by cerebral ischemia, especially in experimental conditions. We have investigated in this study EEG suppression and recovery following global cerebral ischemia, obtained by "four vessel occlusion model", reperfusion and anoxia. Both cerebral ischemia and anoxia have produced a sudden diminution of electrical brain activity and flat line was recorded after 8-10 sec. in the ischemic rats, but after 35-40 sec. in the anoxic rats. After same period of time (2 min) of ischemia and anoxia EEG recovery has been faster in the ischemic rat.

  13. Effect of Salvianolic Acid B on Mitochondrial Function of Cerebral Ischemia in Mice

    Institute of Scientific and Technical Information of China (English)

    JIANG Yufeng; LUO Xuechun; WANG Ximei; FANG Lei; HUANG Qifu

    2009-01-01

    The effects of salvianolic acid B (SalB) on the mitochondrial membrane potential (MMP), calcium, and apoptosis of neurons with cerebral ischemia in mice were investigated using an acute cerebral ischemia model established by ligating the bilateral common carotid arteries in mica. The MMP, the intracellular cal-cium concentration, and the apoptosis rate of cortical neurons were measured at 6 min, 12 min, 18 min, 24 min, and 30 min after cerebral ischemia by a flow cytometer. The experiments show that SalB increases the MMP and reduces the intracellular calcium and the apoptosis rate at different stages of the cerebral ischemia in mice. The results show that the protective mechanism of SalB on cerebral ischemia enhances the MMP and maintains intracellular calcium homeostasis.

  14. Cerebral ischemia produces laddered DNA fragments distinct from cardiac ischemia and archetypal apoptosis.

    Science.gov (United States)

    MacManus, J P; Fliss, H; Preston, E; Rasquinha, I; Tuor, U

    1999-05-01

    The electrophoretic pattern of laddered DNA fragments which has been observed after cerebral ischemia is considered to indicate that neurons are dying by apoptosis. Herein the authors directly demonstrate using ligation-mediated polymerase chain reaction methods that 99% of the DNA fragments produced after either global or focal ischemia in adult rats, or produced after hypoxia-ischemia in neonatal rats, have staggered ends with a 3' recess of approximately 8 to 10 nucleotides. This is in contrast to archetypal apoptosis in which the DNA fragments are blunt ended as seen during developmental programmed cell death in dying cortical neurons, neuroblastoma, or thymic lymphocytes. It is not simply ischemia that results in staggered ends in DNA fragments because ischemic myocardium is similar to archetypal apoptosis with a vast majority of blunt-ended fragments. It is concluded that the endonucleases that produce this staggered fragmentation of the DNA backbone in ischemic brain must be different than those of classic or type I apoptosis.

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

    Institute of Scientific and Technical Information of China (English)

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

    2016-01-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    drug targets to restore normal cerebral artery contractile function as part of successful neuroprotective therapy. METHODS: We have employed in vitro methods on human and rat cerebral arteries to study the regulatory mechanisms and the efficacy of target selective inhibitor, Mithramycin A (MitA...... arteries. RESULTS: Increased expression of specificity protein (Sp1) was observed in human and rat cerebral arteries after organ culture, strongly correlating with the ETBR upregulation. Similar observations were made in MCAO rats. Treatment with MitA, a Sp1 specific inhibitor, significantly downregulated...... vasoconstriction in focal cerebral ischemia via MEK-ERK signaling, which is also conserved in humans. The results show that MitA can effectively be used to block ETBR mediated vasoconstriction as a supplement to an existing ischemic stroke therapy....

  17. 3-N-butylphthalide improves neuronal morphology after chronic cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

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

  18. Effect of retinoic acid on expression of LINGO-1 and neural regeneration after cerebral ischemia.

    Science.gov (United States)

    Xing, Hong-yi; Meng, Er-yan; Xia, Yuan-peng; Peng, Hai

    2015-02-01

    The purpose of this study was to observe the expression of LINGO-1 after cerebral ischemia, investigate the effects of retinoic acid (RA) on the expression of LINGO-1 and GAP-43, and the number of synapses, and to emplore the repressive effect of LINGO-1 on neural regeneration after cerebral ischemia. The model of permanent focal cerebral ischemia was established by the modified suture method of middle cerebral artery occlusion (MCAO) in Sprague-Dawley (SD) rats. The expression of LINGO-1 was detected by Western blotting and that of GAP-43 by immunohistochemistry. The number of synapses was observed by transmission electron microscopy. The SD rats were divided into three groups: sham operation (sham) group, cerebral ischemia (CI) group and RA treatment (RA) group. The results showed that the expression level of LINGO-1 at 7th day after MCAO in sham, CI and RA groups was 0.266 ± 0.019, 1.215 ± 0.063 and 0.702 ± 0.081, respectively (PLINGO-1 expression is up-regulated after cerebral ischemia, and RA inhibits the expression of LINGO-1, promotes the expression of GAP-43 and increases the number of synapses. It suggests that LINGO-1 may be involved in the pathogenesis of cerebral ischemia, which may provide an experimenal basis for LINGO-1 antogonist, RA, for the treatment of cerebral ischemia.

  19. 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.

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

    Science.gov (United States)

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

    1993-05-01

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

  1. 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.

  2. 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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

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

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    Tang Huiling

    2010-10-01

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

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

    Science.gov (United States)

    2010-01-01

    Background Ischemic hypoxic brain injury often causes irreversible brain damage. The lack of effective and widely applicable pharmacological treatments for ischemic stroke patients may explain a growing interest in traditional medicines. From the point of view of "self-medication" or "preventive medicine," Cordyceps sinensis was used in the prevention of cerebral ischemia in this paper. Methods The right middle cerebral artery occlusion model was used in the study. The effects of Cordyceps sinensis (Caterpillar fungus) extract on mortality rate, neurobehavior, grip strength, lactate dehydrogenase, glutathione content, Lipid Peroxidation, glutathione peroxidase activity, glutathione reductase activity, catalase activity, Na+K+ATPase activity and glutathione S transferase activity in a rat model were studied respectively. Results Cordyceps sinensis extract significantly improved the outcome in rats after cerebral ischemia and reperfusion in terms of neurobehavioral function. At the same time, supplementation of Cordyceps sinensis extract significantly boosted the defense mechanism against cerebral ischemia by increasing antioxidants activity related to lesion pathogenesis. Restoration of the antioxidant homeostasis in the brain after reperfusion may have helped the brain recover from ischemic injury. Conclusions These experimental results suggest that complement Cordyceps sinensis extract is protective after cerebral ischemia in specific way. The administration of Cordyceps sinensis extract significantly reduced focal cerebral ischemic/reperfusion injury. The defense mechanism against cerebral ischemia was by increasing antioxidants activity related to lesion pathogenesis. PMID:20955613

  6. Homocysteine Aggravates Cortical Neural Cell Injury through Neuronal Autophagy Overactivation following Rat Cerebral Ischemia-Reperfusion

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    Yaqian Zhao

    2016-07-01

    Full Text Available Elevated homocysteine (Hcy levels have been reported to be involved in neurotoxicity after ischemic stroke. However, the underlying mechanisms remain incompletely understood to date. In the current study, we hypothesized that neuronal autophagy activation may be involved in the toxic effect of Hcy on cortical neurons following cerebral ischemia. Brain cell injury was determined by hematoxylin-eosin (HE staining and TdT-mediated dUTP Nick-End Labeling (TUNEL staining. The level and localization of autophagy were detected by transmission electron microscopy, western blot and immunofluorescence double labeling. The oxidative DNA damage was revealed by immunofluorescence of 8-Hydroxy-2′-deoxyguanosine (8-OHdG. Hcy treatment aggravated neuronal cell death, significantly increased the formation of autophagosomes and the expression of LC3B and Beclin-1 in the brain cortex after middle cerebral artery occlusion-reperfusion (MCAO. Immunofluorescence analysis of LC3B and Beclin-1 distribution indicated that their expression occurred mainly in neurons (NeuN-positive and hardly in astrocytes (GFAP-positive. 8-OHdG expression was also increased in the ischemic cortex of Hcy-treated animals. Conversely, LC3B and Beclin-1 overexpression and autophagosome accumulation caused by Hcy were partially blocked by the autophagy inhibitor 3-methyladenine (3-MA. Hcy administration enhanced neuronal autophagy, which contributes to cell death following cerebral ischemia. The oxidative damage-mediated autophagy may be a molecular mechanism underlying neuronal cell toxicity of elevated Hcy level.

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    Xin-juan Li

    2015-01-01

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

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

    Science.gov (United States)

    Li, Xin-Juan; Li, Chao-Kun; Wei, Lin-Yu; Lu, Na; Wang, Guo-Hong; Zhao, Hong-Gang; Li, Dong-Liang

    2015-06-01

    The present study aimed to explore the mechanism underlying the protective effects of hydrogen sulfide against neuronal damage caused by cerebral ischemia/reperfusion. We established the middle cerebral artery occlusion model in rats via the suture method. Ten minutes after middle cerebral artery occlusion, the animals were intraperitoneally injected with hydrogen sulfide donor compound sodium hydrosulfide. Immunofluorescence revealed that the immunoreactivity of P2X7 in the cerebral cortex and hippocampal CA1 region in rats with cerebral ischemia/reperfusion injury decreased with hydrogen sulfide treatment. Furthermore, treatment of these rats with hydrogen sulfide significantly lowered mortality, the Longa neurological deficit scores, and infarct volume. These results indicate that hydrogen sulfide may be protective in rats with local cerebral ischemia/reperfusion injury by down-regulating the expression of P2X7 receptors.

  10. Hydrogen sulifde intervention in focal cerebral ischemia/reperfusion injur y in rats

    Institute of Scientific and Technical Information of China (English)

    Xin-juan Li; Chao-kun Li; Lin-yu Wei; Na Lu; Guo-hong Wang; Hong-gang Zhao; Dong-liang Li

    2015-01-01

    The present study aimed to explore the mechanism underlying the protective effects of hydro-gen sulifde against neuronal damage caused by cerebral ischemia/reperfusion. We established the middle cerebral artery occlusion model in rats via the suture method. Ten minutes after middle cerebral artery occlusion, the animals were intraperitoneally injected with hydrogen sulifde donor compound sodium hydrosulifde. Immunolfuorescence revealed that the immu-noreactivity of P2X7 in the cerebral cortex and hippocampal CA1 region in rats with cerebral ischemia/reperfusion injury decreased with hydrogen sulfide treatment. Furthermore, treat-ment of these rats with hydrogen sulifde signiifcantly lowered mortality, the Longa neurological deifcit scores, and infarct volume. These results indicate that hydrogen sulifde may be protec-tive in rats with local cerebral ischemia/reperfusion injury by down-regulating the expression of P2X7 receptors.

  11. Pyruvate dehydrogenase complex in cerebral ischemia-reperfusion injury

    Directory of Open Access Journals (Sweden)

    Alexa Thibodeau

    2016-01-01

    Full Text Available Pyruvate dehydrogenase (PDH complex is a mitochondrial matrix enzyme that serves a critical role in the conversion of anaerobic to aerobic cerebral energy. The regulatory complexity of PDH, coupled with its significant influence in brain metabolism, underscores its susceptibility to, and significance in, ischemia-reperfusion injury. Here, we evaluate proposed mechanisms of PDH-mediated neurodysfunction in stroke, including oxidative stress, altered regulatory enzymatic control, and loss of PDH activity. We also describe the neuroprotective influence of antioxidants, dichloroacetate, acetyl-L-carnitine, and combined therapy with ethanol and normobaric oxygen, explained in relation to PDH modulation. Our review highlights the significance of PDH impairment in stroke injury through an understanding of the mechanisms by which it is modulated, as well as an exploration of neuroprotective strategies available to limit its impairment.

  12. 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

    cerebral ischemia reperfusion was detected with TUNEL technique. SOD expression was detected with immunohistochemical technique. ③ The intergroup difference was compared with the t test.MAIN OUTCOME MEASURES: The apoptosis of the nerve cells and SOD expression were mainly observed in each group.RESULTS: Finally, 52 rats were involved in the analysis of results. ① Number of apoptotic cells: In the sham-operated group, a few apoptotic cells could be observed in brain tissue. The apoptotic cells at each time point in the control group and treatment group were obviously more than those in the sham-operated group (P < 0.05). In the treatment group, the numbers of apoptotic cells at 12 hours, 1 and 3 days after reperfusion were significantly fewer than those in the control group, and those at 6 hours, 7 and 14 days were similar to those in the control group. ② Number of SOD positive cells: In the sham-operated group, there was weak expression of SOD in brain tissue, and the positive cells were extremely few, the positive cells at each time point were significantly more in the control group and treatment group than in the sham-operated group (P< 0.05). In the treatment group, the numbers of positive cells at 6 and 12 hours, 1 and 3 days after reperfusion were significantly fewer than those in the control group, and those at 7-14 days were similar to those in the control group. ③ Cellular forms: In the control group, the karyopyknosis occurred in the nerve cells,which were irregularly distributed, nucleolus disappeared, and some scattered cell fragments were observed.The forms of the nerve cells in the treatment group were generally normal.CONCLUSION: Phycocyanin plays a neuroprotective role in cerebral ischemia reperfusion injury by activating the SOD expression and inhibiting apoptosis.

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

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    Mai Sakai

    2014-11-01

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

  14. Polydendrocytes display large lineage plasticity following focal cerebral ischemia.

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    Pavel Honsa

    Full Text Available Polydendrocytes (also known as NG2 glial cells constitute a fourth major glial cell type in the adult mammalian central nervous system (CNS that is distinct from other cell types. Although much evidence suggests that these cells are multipotent in vitro, their differentiation potential in vivo under physiological or pathophysiological conditions is still controversial.To follow the fate of polydendrocytes after CNS pathology, permanent middle cerebral artery occlusion (MCAo, a commonly used model of focal cerebral ischemia, was carried out on adult NG2creBAC:ZEG double transgenic mice, in which enhanced green fluorescent protein (EGFP is expressed in polydendrocytes and their progeny. The phenotype of the EGFP(+ cells was analyzed using immunohistochemistry and the patch-clamp technique 3, 7 and 14 days after MCAo. In sham-operated mice (control, EGFP(+ cells in the cortex expressed protein markers and displayed electrophysiological properties of polydendrocytes and oligodendrocytes. We did not detect any co-labeling of EGFP with neuronal, microglial or astroglial markers in this region, thus proving polydendrocyte unipotent differentiation potential under physiological conditions. Three days after MCAo the number of EGFP(+ cells in the gliotic tissue dramatically increased when compared to control animals, and these cells displayed properties of proliferating cells. However, in later phases after MCAo a large subpopulation of EGFP(+ cells expressed protein markers and electrophysiological properties of astrocytes that contribute to the formation of glial scar. Importantly, some EGFP(+ cells displayed membrane properties typical for neural precursor cells, and moreover these cells expressed doublecortin (DCX--a marker of newly-derived neuronal cells. Taken together, our data indicate that polydendrocytes in the dorsal cortex display multipotent differentiation potential after focal ischemia.

  15. Transesophageal echocardiography in patients with cryptogenic cerebral ischemia

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    Dreger Henryk

    2009-03-01

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

  16. Amyloid beta-peptide worsens cognitive impairment following cerebral ischemia-reperfusion injury*****

    Institute of Scientific and Technical Information of China (English)

    Bo Song; Qiang Ao; Ying Niu; Qin Shen; Huancong Zuo; Xiufang Zhang; Yandao Gong

    2013-01-01

    Amyloid β-peptide, a major component of senile plaques in Alzheimer’s disease, has been impli-cated in neuronal cel death and cognitive impairment. Recently, studies have shown that the pathogenesis of cerebral ischemia is closely linked with Alzheimer’s disease. In this study, a rat model of global cerebral ischemia-reperfusion injury was established via occlusion of four arteries;meanwhile, fibril ar amyloid β-peptide was injected into the rat lateral ventricle. The Morris water maze test and histological staining revealed that administration of amyloid β-peptide could further aggravate impairments to learning and memory and neuronal cel death in the hippocampus of rats subjected to cerebral ischemia-reperfusion injury. Western blot showed that phosphorylation of tau protein and the activity of glycogen synthase kinase 3β were significantly stronger in cerebral is-chemia-reperfusion injury rats subjected to amyloidβ-peptide administration than those undergoing cerebral ischemia-reperfusion or amyloidβ-peptide administration alone. Conversely, the activity of protein phosphatase 2A was remarkably reduced in rats with cerebral ischemia-reperfusion injury fol owing amyloidβ-peptide administration. These findings suggest that amyloidβ-peptide can po-tentiate tau phosphorylation induced by cerebral ischemia-reperfusion and thereby aggravate cog-nitive impairment.

  17. Effectiveness of diagnostic strategies in suspected delayed cerebral ischemia : A decision analysis

    NARCIS (Netherlands)

    Rawal, Sapna; Barnett, Carolina; John-Baptiste, Ava; Thein, Hla Hla; Krings, Timo; Rinkel, Gabriel J E

    2015-01-01

    Background and Purpose-Delayed cerebral ischemia (DCI) is a serious complication after aneurysmal subarachnoid hemorrhage. If DCI is suspected clinically, imaging Methods designed to detect angiographic vasospasm or regional hypoperfusion are often used before instituting therapy. Uncertainty in the

  18. Hemostasis and fibrinolysis in delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage : a systematic review

    NARCIS (Netherlands)

    Boluijt, Jacoline; Meijers, Joost C. M.; Rinkel, Gabriel J. E.; Vergouwen, Mervyn D. I.

    2015-01-01

    Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) has been associated with microthrombosis, which can result from activated hemostasis, inhibited fibrinolysis, or both. We systematically searched the PUBMED and EMBASE databases to identify hemostatic or fibrinolytic par

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

    DEFF Research Database (Denmark)

    Ilie, Andrei; Spulber, Stefan; Avramescu, Sinziana;

    2006-01-01

    Global cerebral ischemia induces, within seconds, suppression of spontaneous electrocortical activity, partly due to alterations in synaptic transmission. In vitro studies have found that repeated brief hypoxic episodes prolong the persistence of synaptic transmission due to weakened adenosine re...

  20. Cerebroprotective activity of Pentapetes phoenicea on global cerebral ischemia in rats

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    Koneru Naga Sravanthi

    2016-01-01

    Conclusion: The result of the study indicates that the treatment with P. phoenicea enhances the antioxidant defense against BCAO-induced global cerebral ischemia/reperfusion and exerts cerebroprotection.

  1. A role for interferon-gamma in focal cerebral ischemia in mice

    DEFF Research Database (Denmark)

    Lambertsen, Kate Lykke; Gregersen, Rikke; Meldgaard, Michael;

    2004-01-01

    The pro-inflammatory cytokine interferon-gamma (IFNgamma) has traditionally been associated with inflammatory CNS disease and more recently with ischemia-induced pathology. Using a murine model of focal cerebral ischemia, we found no evidence for induction of IFNgamma mRNA after permanent middle...

  2. 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, ...

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

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

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

  4. Pharmacological manipulation of brain glycogenolysis as a therapeutic approach to cerebral ischemia.

    Science.gov (United States)

    Xu, Li; Sun, Hongbin

    2010-10-01

    Brain ischemia resulting from multiple disease states including cardiac arrest, stroke and traumatic brain injury, is a leading cause of death and disability. Despite significant resources dedicated to developing pharmacological interventions, few effective therapeutic options are currently available. The basic consequence of cerebral ischemia, characterized by energy failure and subsequent brain metabolic abnormalities, enables the protective effects by pharmacological manipulation of brain metabolism. We present here the important roles of brain glycogen metabolism and propose inhibition of glycogenolysis as a therapeutic approach to cerebral ischemia.

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

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    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.

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

    Science.gov (United States)

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

    1982-07-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  9. Selective estrogen receptor modulators (SERMs) enhance neurogenesis and spine density following focal cerebral ischemia.

    Science.gov (United States)

    Khan, Mohammad M; Wakade, Chandramohan; de Sevilla, Liesl; Brann, Darrell W

    2015-02-01

    Selective estrogen receptor modulators (SERMs) have been reported to enhance synaptic plasticity and improve cognitive performance in adult rats. SERMs have also been shown to induce neuroprotection against cerebral ischemia and other CNS insults. In this study, we sought to determine whether acute regulation of neurogenesis and spine remodeling could be a novel mechanism associated with neuroprotection induced by SERMs following cerebral ischemia. Toward this end, ovariectomized adult female rats were either implanted with pellets of 17β-estradiol (estrogen) or tamoxifen, or injected with raloxifene. After one week, cerebral ischemia was induced by the transient middle-cerebral artery occlusion (MCAO) method. Bromodeoxyuridine (BrdU) was injected to label dividing cells in brain. We analyzed neurogenesis and spine density at day-1 and day-5 post MCAO. In agreement with earlier findings, we observed a robust induction of neurogenesis in the ipsilateral subventricular zone (SVZ) of both the intact as well as ovariectomized female rats following MCAO. Interestingly, neurogenesis in the ipsilateral SVZ following ischemia was significantly higher in estrogen and raloxifene-treated animals compared to placebo-treated rats. In contrast, this enhancing effect on neurogenesis was not observed in tamoxifen-treated rats. Finally, both SERMs, as well as estrogen significantly reversed the spine density loss observed in the ischemic cortex at day-5 post ischemia. Taken, together these results reveal a profound structural remodeling potential of SERMs in the brain following cerebral ischemia. This article is part of a Special Issue entitled "Sex steroids and brain disorders".

  10. Comparative assessment of the effectiveness of modern neuroprotectors in conditions of experimental chronic cerebral ischemia

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    A. V. Demchenko

    2015-04-01

    Full Text Available Modern pharmacological influence on the pathological changes in cerebral ischemia is actual task of the modern neurology. Aim. To make a comparative assessment of the effectiveness of modern neuroprotectors in conditions of experimental chronic cerebral ischemia. Methods and results. Experimental study of the neuroprotective effects of the citicoline, cortexin and tiocetam on the cognitive functions on the model of the chronic cerebral ischemia was conducted on 75 white rats. Biochemical, immunoassay, pharmacological, statistical methods were used. Conclusion. Obtained results showed citicoline, cortexin and tiocetam ability to positively influence on the molecular-biochemical changes in the brain cortex with ischemia. This resulted in the glutathione-dependent enzymes activity increase, recover of the thiol-disulfide system balance, nitrotyrosine concentration decrease, improvement of the cognitive function in the experimental animals.

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

  12. Alterations of interneurons of the gerbil hippocampus after transient cerebral ischemia: effect of pitavastatin.

    Science.gov (United States)

    Himeda, Toshiki; Hayakawa, Natsumi; Tounai, Hiroko; Sakuma, Mio; Kato, Hiroyuki; Araki, Tsutomu

    2005-11-01

    We investigated the immunohistochemical alterations of parvalbumin (PV)-expressing interneurons in the hippocampus after transient cerebral ischemia in gerbils in comparison with neuronal nitric oxide synthase (nNOS)-expressing interneurons. We also examined the effect of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor pitavastatin against the damage of neurons and interneurons in the hippocampus after cerebral ischemia. Severe neuronal damage was observed in the hippocampal CA1 pyramidal neurons 5 and 14 days after ischemia. The PV immunoreactivity was unchanged up to 2 days after ischemia. At 5 and 14 days after ischemia, in contrast, a conspicuous reduction of PV immunoreactivity was observed in interneurons of the hippocampal CA1 sector. Furthermore, a significant decrease of PV immunoreactivity was found in interneurons of the hippocampal CA3 sector. No damage of nNOS-immunopositive interneurons was detected in the gerbil hippocampus up to 1 day after ischemia. Thereafter, a decrease of nNOS immunoreactive interneurons was found in the hippocampal CA1 sector up to 14 days after ischemia. Pitavastatin significantly prevented the neuronal cell loss in the hippocampal CA1 sector 5 days after ischemia. Our immunohistochemical study also showed that pitavastatin prevented significant decrease of PV- and nNOS-positive interneurons in the hippocampus after ischemia. Double-labeled immunostainings showed that PV immunoreactivity was not found in nNOS-immunopositive interneurons of the brain. The present study demonstrates that cerebral ischemia can cause a loss of both PV- and nNOS-immunoreactive interneurons in the hippocampal CA1 sector. Our findings also show that the damage to nNOS-immunopositive interneurons may precede the neuronal cell loss in the hippocampal CA1 sector after ischemia and nNOS-positive interneurons may play some role in the pathogenesis of cerebral ischemic diseases. Furthermore, our present study indicates that pitavastatin can

  13. bcl-xl over-expression in transgenic mice reduces cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Furong Wang; Yongsheng Jiang; Yan Liu; Wenwu Xiao; Suming Zhang

    2008-01-01

    reperfusion, cerebral infarct volume was reduced by 30% in bcl-xl transgenic mice compared with wild-type mice. Simultaneously, the number of apoptotic cells in the ischemic cerebral cortex was significantly less in the transgenic mice compared with the wild-type mice. Overall, the number of apoptotic cells in the transgenic mice remained at a relatively low level. Prior to and subsequent to cerebral ischemia/reperfusion, transgenic mice exhibited markedly higher Bcl-xl protein levels compared with wild-type mice. In addition, after reperfusion, the level of Bcl-xl protein was increased in both transgenic and wild-type mice, but there was no significant difference (P > 0.05) between the two groups. The level of cytochrome C in the transgenic mice was low in the first 24 hours after reperfusion and increased thereafter but was still lower compared with wild-type mice. Neurological function scores demonstrated that transgenic mice exhibited milder neurological function impairment compared with wild-type mice. CONCLUSION: bcl-xl over-expression can inhibit cytochrome C release and result in an inhibitory effect on neural cell apoptosis, thereby alleviating neural cell injury. This is likely to occur due to exogenous over-expression of bcl-xl rather than endogenous production of bcl-xl.

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

    Directory of Open Access Journals (Sweden)

    Xiao-ge Yan

    2015-01-01

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

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

    DEFF Research Database (Denmark)

    Stenman, Emelie; Malmsjö, Malin; Uddman, Erik;

    2002-01-01

    BACKGROUND AND PURPOSE: Elevated levels of endothelin-1 (ET-1) have been reported in cerebral ischemia. A role for ET may prove more important if the vascular receptors were changed. We addressed whether there is any change in ET receptor expression in cerebral ischemia. METHODS: The right middle...... receptors in the pathogenesis of a vascular component after cerebral ischemia....... cerebral artery (MCA) was occluded in male Wistar rats for 2 hours with the intraluminal filament method. The basilar artery and both MCAs were removed after 46 hours of recirculation. The contractile responses to ET-1, a combined ET(A) and ET(B) receptor agonist, and sarafotoxin 6c (S6c), a selective ET...

  16. Effect of morphine preconditioning on neuronal apoptosis following cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    He Dong; Xiangyu Ji; Dong Wang; Yueyi Ren; Shiduan Wang; Jianfang Song

    2010-01-01

    Apoptosis,a form of neuronal damage,takes place following cerebral ischemia/reperfusion injury,and caspase-3 plays an important role in apoptosis.Studies have shown that morphine preconditioning influences neuronal apoptosis and related protein expression following cerebral ischemia/reperfusion injury.In the present study,neuronal degeneration was attenuated,and the number of apoptotic cells and caspase-3 expression decreased following morphine preconditioning in a rat model of cerebral ischemia/reperfusion injury.Moreover,pathological changes were attenuated with increasing morphine doses,as well as the number of apoptotic cells and caspase-3 expression.Results from the present study revealed that morphine preconditioning reduced ischemic brain injury and improved cerebral ischemic tolerance in a dose-dependent manner.The anti-apoptotic mechanism of morphine is closely related to Caspase-3.

  17. Lateral intracerebroventricular injection of Apelin-13 inhibits apoptosis after cerebral ischemia/reperfusion injur y

    Institute of Scientific and Technical Information of China (English)

    Xiao-ge Yan; Bao-hua Cheng; Xin Wang; Liang-cai Ding; Hai-qing Liu; Jing Chen; Bo Bai

    2015-01-01

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

  18. The role of carotid artery stenting for recent cerebral ischemia.

    Science.gov (United States)

    Bosiers, M; Callaert, J; Deloose, K; Verbist, J; Keirse, K; Peeters, P

    2010-06-01

    Patients with cerebral ischemia as a result of acute cervical internal carotid artery occlusion are generally considered to have a poor prognosis. Despite maximal medical treatment, a better treatment for patients with acute ischemic stroke who present with serious neurologic symptoms on admission or continue to deteriorate neurologically due to a total occlusion, a dissection or a high-grade stenosis of the internal carotid artery is required. An effective intervention to improve their neurologic symptoms and clinical outcome has not yet been established and represents a challenging and complex problem. Treatment of acute symptomatic occlusion of the cervical internal carotid artery includes intravenous administration of thrombolytic agent, carotid endarterectomy and an interventional approach (intra-arterial administration of thrombolytic agent, transluminal angioplasty with or without stenting). The endovascular interventional approach is becoming a part of the stroke therapy armamentarium for intracranial occlusion. It may also now be considered in select patients with acute internal carotid artery occlusion. Stenting and angioplasty for acute internal carotid artery occlusion appears to be feasible, safe and may be associated with early neurological improvement. The encouraging preliminary results await confirmation from prospective, randomized studies.

  19. Clinical and etiological associations in chronic cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Yu. V. Zhitkova

    2015-01-01

    Full Text Available Objective: to study the clinical features of chronic cerebral ischemia (CCI in relation to the leading etiological factor.Patients and methods. Examinations were made in 515 non-stroke CCI patients: 306 men and 209 women aged 58 to 75 years with hypertension and no obvious atherosclerosis of head and neck vessels (n=197; with obvious atherosclerosis of head and neck vessels and no hypertension (n=157; with obvious atherosclerosis of head and neck vessels and hypertension (n=161. In all cases, the investigators performed standard neurological examination and evaluated cognitive, affective symptoms with a set of neuropsychological scales and equilibrium and gait abnormalities with the Tinetti scale.Results and discussion. The development of extrapyramidal syndrome was more related to hypertension or its concurrence with the atherosclerotic process. The patients with atherosclerosis and no hypertension showed a more distinct differentiation of clinical syndromes, which was associated with stenosis in the specific vascular bed; this was probably due to decreased local perfusion. A relationship was established between hypertension and the development of severe cognitive impairments (CIs that had predominantly a dysregulation neuropsychological profile. In the patients with atherosclerosis and no hypertension, emotional disorders were more common than CI and the latter resembled Alzheimer’s disease. A differentiated prophylactic and therapeutic strategy accounting for the leading etiological factor will be able to prevent or significantly reduce functional limitations in patients with CCI.

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

    Science.gov (United States)

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

    2016-01-01

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

  1. 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

  2. Dragon's blood dropping pills have protective effects on focal cerebral ischemia rats model.

    Science.gov (United States)

    Xin, Nian; Yang, Fang-Ju; Li, Yan; Li, Yu-Juan; Dai, Rong-Ji; Meng, Wei-Wei; Chen, Yan; Deng, Yu-Lin

    2013-12-15

    Dragon's blood is a bright red resin obtained from Dracaena cochinchinensis (Lour.) S.C.Chen (Yunnan, China). As a traditional Chinese medicinal herb, it has great traditional medicinal value and is used for wound healing and to stop bleeding. Its main biological activity comes from phenolic compounds. In this study, phenolic compounds were made into dropping pills and their protective effects were examined by establishing focal cerebral ischemia rats model used method of Middle Cerebral Artery Occlusion (MCAO), and by investigating indexes of neurological scores, infarct volume, cerebral index, cerebral water content and oxidation stress. Compared to model group, high, middle and low groups of Dragon's blood dropping pills could improve the neurological function significantly (pDragon's blood dropping pills had protective effects on focal cerebral ischemia rats.

  3. An immunohistochemical study of parvalbumin containing interneurons in the gerbil hippocampus after cerebral ischemia.

    Science.gov (United States)

    Araki, T; Kato, H; Liu, X H; Kogure, K; Kato, K; Itoyama, Y

    1994-09-01

    We investigated postischemic changes of non-pyramidal neurons in the gerbil hippocampus 1 h - 7 days after 10 min of cerebral ischemia, with parvalbumin and microtubule-associated protein 2 (MAP2)-immunohistochemistry. Parvalbumin-immunoreactive interneurons in the hippocampus were unaffected up to 24 h after ischemia. A slight reduction of the immunoreactivity in neuronal processes was seen in the hippocampal CA1 sector 48 h after ischemia. Seven days after ischemia, a marked loss of parvalbumin-immunoreactive interneurons was observed in the hippocampal CA1 and CA3 sectors. Furthermore, reduced staining in the dentate granular and molecular layers was observed. MAP2-immunoreactive pyramidal neurons in the hippocampus were unchanged up to 48 h after ischemia. Seven days after ischemia, a severe loss of MAP2 immunoreactivity was found in the hippocampal CA1 and CA3 neurons and dentate hilar neurons. However, scattered CA1 neurons, most likely interneurons, preserved MAP2 immunoreactivity. The results demonstrate that transient cerebral ischemia can cause a loss of parvalbumin-immunoreactive interneurons in the hippocampus. Furthermore, some interneurons seem to lose parvalbumin synthesis. Although dentate granule cells are resistant to ischemia, considerable reductions of afferent input was suggested by parvalbumin staining.

  4. 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.

  5. Intercellular adhesion molecule-1 expression in the hippocampal CA1 region of hyperlipidemic rats with chronic cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Yingying Cheng; Ying Zhang; Hongmei Song; Jiachun Feng

    2012-01-01

    Chronic cerebral ischemia is a pathological process in many cerebrovascular diseases and it is induced by long-term hyperlipidemia, hypertension and diabetes mellitus. After being fed a high-fat diet for 4 weeks, rats were subjected to permanent occlusion of bilateral common carotid arteries to establish rat models of chronic cerebral ischemia with hyperlipidemia. Intercellular adhesion molecule-1 expression in rat hippocampal CA1 region was determined to better understand the mechanism underlying the effects of hyperlipidemia on chronic cerebral ischemia. Water maze test results showed that the cognitive function of rats with hyperlipidemia or chronic cerebral ischemia, particularly in rats with hyperlipidemia combined with chronic cerebral ischemia, gradually decreased between 1 and 4 months after occlusion of the bilateral common carotid arteries. This correlated with pathological changes in the hippocampal CA1 region as detected by hematoxylin-eosin staining. Immunohistochemical staining showed that intercellular adhesion molecule-1 expression in the hippocampal CA1 region was noticeably increased in rats with hyperlipidemia or chronic cerebral ischemia, in particular in rats with hyperlipidemia combined with chronic cerebral ischemia. These findings suggest that hyperlipidemia aggravates chronic cerebral ischemia-induced neurological damage and cognitive impairment in the rat hippocampal CA1 region, which may be mediated, at least in part, by up-regulated expression of intercellular adhesion molecule-1.

  6. Nimodipine Prevents Early Loss of Hippocampal CA1 Parvalbumin Immunoreactivity After Focal Cerebral Ischemia in the Rat

    NARCIS (Netherlands)

    Benyó, Zoltán; de Jong, Giena; Luiten, Paul G.M.

    1995-01-01

    The effect of focal cerebral ischemia induced by middle cerebral artery occlusion on hippocampal interneurons containing the calcium-binding protein parvalbumin (PV) was studied in rats. Four hours after the onset of ischemia, a reduced number of PV-immunoreactive (-ir) neurons was observed in the l

  7. Effects of Focal Cerebral Ischemia on Exosomal Versus Serum miR126.

    Science.gov (United States)

    Chen, Fan; Du, Yang; Esposito, Elga; Liu, Yi; Guo, Shuzhen; Wang, Xiaoying; Lo, Eng H; Xing, Changhong; Ji, Xunming

    2015-12-01

    Emerging data suggest that exosomal microRNA (miRNA) may provide potential biomarkers in acute ischemic stroke. However, the effects of ischemia-reperfusion on total versus exosomal miRNA responses in circulating blood remain to be fully defined. Here, we quantified levels of miR-126 in whole serum versus exosomes extracted from serum and compared these temporal profiles against reperfusion and outcomes in a rat model of acute focal cerebral ischemia. First, in vitro experiments confirmed the vascular origin and changes in miR-126 in brain endothelial cultures subjected to oxygen-glucose deprivation. Then in vivo experiments were performed by inducing permanent or transient focal cerebral ischemia in rats, and total serum and exosomal miR-126 levels were quantified, along with measurements of infarction and neurological outcomes. Exosomal levels of miR-126 showed a transient reduction at 3 h post-ischemia that appeared to normalize back close to pre-ischemic baselines after 24 h. There were no detectable differences in exosomal miR-126 responses in permanent or transient ischemia. Serum miR-126 levels appeared to differ in permanent versus transient ischemia. Significant reductions in serum miR-126 were detected at 3 h after permanent ischemia but not transient ischemia. By 24 h, serum miR-126 levels were back close to baseline in both permanent and transient ischemia. Overall, there were no correlations between serum miR-126 and exosomal miR-126. This proof-of-concept study suggests that changes in serum miR-126 may be able to distinguish severe permanent ischemia from milder injury after transient ischemia.

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

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

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

  9. Effect of total flavonoids of Radix Ilicis pubescentis on cerebral ischemia reperfusion model

    Directory of Open Access Journals (Sweden)

    Xiaoli Yan

    2017-03-01

    Full Text Available This paper aims to observe the effects of total flavonoids of Radix Ilicis pubescentis on mouse model of cerebral ischemia reperfusion. Mice were orally given different doses of total flavonoids of Radix Ilicis pubescentis 10 d, and were administered once daily. On the tenth day after the administration of 1 h in mice after anesthesia, we used needle to hook the bilateral common carotid artery (CCA for 10 min, with 10 min ischemia reperfusion, 10 min ischemia. Then we restored their blood supply, copy the model of cerebral ischemia reperfusion; We then had all mice reperfused for 24 h, and then took their orbital blood samples and measured blood rheology. We quickly removed the brain, with half of the brain having sagittal incision. Then we fixed the brains and sectioned them to observe the pathological changes of brain cells in the hippocampus and cortex. We also measured the other half sample which was made of brain homogenate of NO, NOS, Na+-K+-, ATP enzyme Mg2+-ATPase and Ca2+-ATPase. Acupuncture needle hook occlusion of bilateral common carotid arteries can successfully establish the model of cerebral ischemia reperfusion. After comparing with the model mice, we concluded that Ilex pubescens flavonoids not only reduce damage to the brain nerve cells in the hippocampus and cortex, but also significantly reduce the content of NO in brain homogenate, the activity of nitric oxide synthase (NOS and increases ATP enzyme activity (P < 0.05, P < 0.01. In this way, cerebral ischemia reperfusion injury is improved. Different dosages of Ilex pubescens flavonoids on mouse cerebral ischemia reperfusion model have good effects.

  10. Early events triggering delayed vasoconstrictor receptor upregulation and cerebral ischemia after subarachnoid hemorrhage

    DEFF Research Database (Denmark)

    Povlsen, Gro Klitgaard; Johansson, Sara Ellinor; Larsen, Carl Christian

    2013-01-01

    that the drop in cerebral blood flow (CBF) and wall tension experienced by cerebral arteries in acute SAH is a key triggering event. We here investigate the importance of the duration of this acute CBF drop in a rat SAH model in which a fixed amount of blood is injected into the prechiasmatic cistern either......Upregulation of vasoconstrictor receptors in cerebral arteries, including endothelin B (ETB) and 5-hydroxytryptamine 1B (5-HT(1B)) receptors, has been suggested to contribute to delayed cerebral ischemia, a feared complication after subarachnoid hemorrhage (SAH). This receptor upregulation has been...

  11. Focal Cerebral Ischemia Induces Alzheimer s Disease-like Pathological Change in Rats

    Institute of Scientific and Technical Information of China (English)

    王海均; 赵洪洋; 叶佑范; 熊南翔; 黄俊红; 姚东晓; 沈寅; 赵心同

    2010-01-01

    The changes in the tau protein phosphorylation and expression of bcl-2,and bax in rat parietal cortex neurons after focal cerebral ischemia-reperfusion(I/R)were explored,and the relationship between the tau protein phosphorylation and the expression of bax or apoptosis was clarified in order to elucidate the relationship between cerebral infarction and Alzheimer's disease.The rat focal cerebral I/R model was induced by occlusion of the right middle cerebral artery using the intraluminal suture method.The le...

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

    Science.gov (United States)

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

    1991-08-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Zheng Jiang

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

  15. 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.

  16. 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.

  17. 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.

  18. Rapamycin alleviates brain edema after focal cerebral ischemia reperfusion in rats.

    Science.gov (United States)

    Guo, Wei; Feng, Guoying; Miao, Yanying; Liu, Guixiang; Xu, Chunsheng

    2014-06-01

    Brain edema is a major consequence of cerebral ischemia reperfusion. However, few effective therapeutic options are available for retarding the brain edema progression after cerebral ischemia. Recently, rapamycin has been shown to produce neuroprotective effects in rats after cerebral ischemia reperfusion. Whether rapamycin could alleviate this brain edema injury is still unclear. In this study, the rat stroke model was induced by a 1-h left transient middle cerebral artery occlusion using an intraluminal filament, followed by 48 h of reperfusion. The effects of rapamycin (250 μg/kg body weight, intraperitoneal; i.p.) on brain edema progression were evaluated. The results showed that rapamycin treatment significantly reduced the infarct volume, the water content of the brain tissue and the Evans blue extravasation through the blood-brain barrier (BBB). Rapamycin treatment could improve histological appearance of the brain tissue, increased the capillary lumen space and maintain the integrity of BBB. Rapamycin also inhibited matrix metalloproteinase 9 (MMP9) and aquaporin 4 (AQP4) expression. These data imply that rapamycin could improve brain edema progression after reperfusion injury through maintaining BBB integrity and inhibiting MMP9 and AQP4 expression. The data of this study provide a new possible approach for improving brain edema after cerebral ischemia reperfusion by administration of rapamycin.

  19. Anti-inlfammatory properties of lipoxin A4 protect against diabetes mellitus complicated by focal cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Jiang-quan Han; Cheng-ling Liu; Zheng-yuan Wang; Ling Liu; Ling Cheng; Ya-dan Fan

    2016-01-01

    Lipoxin A4 can alleviate cerebral ischemia/reperfusion injury by reducing the inlfammatory reaction, but it is currently unclear whether it has a protective effect on diabetes mellitus complicated by focal cerebral ischemia/reperfusion injury. In this study, we established rat models of diabetes mellitus using an intraperitoneal injection of streptozotocin. We then induced focal cerebral ischemia/reperfusion injury by occlusion of the middle cerebral artery for 2 hours and reperfusion for 24 hours. After administration of lipoxin A4via the lateral ventricle, infarction volume was reduced, the expression levels of pro-inlfammatory factors tumor necrosis factor alpha and nuclear fac-tor-kappa B in the cerebral cortex were decreased, and neurological functioning was improved. These ifndings suggest that lipoxin A4 has strong neuroprotective effects in diabetes mellitus complicated by focal cerebral ischemia/reperfusion injury and that the underlying mech-anism is related to the anti-inlfammatory action of lipoxin A4.

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

    Institute of Scientific and Technical Information of China (English)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Nian-Guang Li

    2012-09-01

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

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

    Institute of Scientific and Technical Information of China (English)

    Santhrani Thakur; Pradeepthi Chilikuri; Bindu Pulugurtha; Lavanya Yaidikar

    2015-01-01

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

  3. 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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

  5. 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.

  6. Effect of propofol post-treatment on blood-brain barrier integrity and cerebral edema after transient cerebral ischemia in rats.

    Science.gov (United States)

    Lee, Jae Hoon; Cui, Hui Song; Shin, Seo Kyung; Kim, Jeong Min; Kim, So Yeon; Lee, Jong Eun; Koo, Bon-Nyeo

    2013-11-01

    Although propofol has been reported to offer neuroprotection against cerebral ischemia injury, its impact on cerebral edema following ischemia is not clear. The objective of this investigation is to evaluate the effects of propofol post-treatment on blood-brain barrier (BBB) integrity and cerebral edema after transient cerebral ischemia and its mechanism of action, focusing on modulation of aquaporins (AQPs), matrix metalloproteinases (MMPs), and hypoxia inducible factor (HIF)-1α. Cerebral ischemia was induced in male Sprague-Dawley rats (n = 78) by occlusion of the right middle cerebral artery for 1 h. For post-treatment with propofol, 1 mg kg(-1) min(-1) of propofol was administered for 1 h from the start of reperfusion. Nineteen rats undergoing sham surgery were also included in the investigation. Edema and BBB integrity were assessed by quantification of cerebral water content and extravasation of Evans blue, respectively, following 24 h of reperfusion. In addition, the expression of AQP-1, AQP-4, MMP-2, and MMP-9 was determined 24 h after reperfusion and the expression of HIF-1α was determined 8 h after reperfusion. Propofol post-treatment significantly reduced cerebral edema (P cerebral edema after transient cerebral ischemia, in association with reduced expression of AQP-1, AQP-4, MMP-2, and MMP-9. The decreased expression of AQPs and MMPs after propofol post-treatment might result from suppression of HIF-1α expression.

  7. 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.

  8. Hyperexpressed Netrin-1 Promoted Neural Stem Cells Migration in Mice after Focal Cerebral Ischemia

    Science.gov (United States)

    Lu, Haiyan; Song, Xiaoyan; Wang, Feng; Wang, Guodong; Wu, Yuncheng; Wang, Qiaoshu; Wang, Yongting; Yang, Guo-Yuan; Zhang, Zhijun

    2016-01-01

    Endogenous Netrin-1 (NT-1) protein was significantly increased after cerebral ischemia, which may participate in the repair after transient cerebral ischemic injury. In this work, we explored whether NT-1 can be steadily overexpressed by adeno-associated virus (AAV) and the exogenous NT-1 can promote neural stem cells migration from the subventricular zone (SVZ) region after cerebral ischemia. Adult CD-1 mice were injected stereotacticly with AAV carrying NT-1 gene (AAV-NT-1). Mice underwent 60 min of middle cerebral artery (MCA) occlusion 1 week after injection. We found that NT-1 mainly expressed in neuron and astrocyte, and the expression level of NT-1 significantly increased 1 week after AAV-NT-1 gene transfer and lasted for 28 days, even after transient middle cerebral artery occlusion (tMCAO) as well (p < 0.05). Immunohistochemistry results showed that the number of neural stem cells was greatly increased in the SVZ region of AAV-NT-1-transduced mice compared with control mice. Our study showed that overexpressed NT-1 promoted neural stem cells migration from SVZ. This result suggested that NT-1 is a promising factor for repairing and remodeling after focal cerebral ischemia.

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

  10. Eupatilin exerts neuroprotective effects in mice with transient focal cerebral ischemia by reducing microglial activation

    Science.gov (United States)

    Cho, Kyu Suk; Jeon, Se Jin; Kwon, Oh Wook; Jang, Dae Sik; Kim, Sun Yeou; Ryu, Jong Hoon; Choi, Ji Woong

    2017-01-01

    Microglial activation and its-driven neuroinflammation are characteristic pathogenetic features of neurodiseases, including focal cerebral ischemia. The Artemisia asiatica (Asteraceae) extract and its active component, eupatilin, are well-known to reduce inflammatory responses. But the therapeutic potential of eupatilin against focal cerebral ischemia is not known, along with its anti-inflammatory activities on activated microglia. In this study, we investigated the neuroprotective effect of eupatilin on focal cerebral ischemia through its anti-inflammation, particularly on activated microglia, employing a transient middle cerebral artery occlusion/reperfusion (tMCAO), combined with lipopolysaccharide-stimulated BV2 microglia. Eupatilin exerted anti-inflammatory responses in activated BV2 microglia, in which it reduced secretion of well-known inflammatory markers, including nitrite, IL-6, TNF-α, and PGE2, in a concentration-dependent manner. These observed in vitro effects of eupatilin led to in vivo neuroprotection against focal cerebral ischemia. Oral administration of eupatilin (10 mg/kg) in a therapeutic paradigm significantly reduced brain infarction and improved neurological functions in tMCAO-challenged mice. The same benefit was also observed when eupatilin was given even within 5 hours after MCAO induction. In addition, the neuroprotective effects of a single administration of eupatilin (10 mg/kg) immediately after tMCAO challenge persisted up to 3 days after tMCAO. Eupatilin administration reduced the number of Iba1-immunopositive cells across ischemic brain and induced their morphological changes from amoeboid into ramified in the ischemic core, which was accompanied with reduced microglial proliferation in ischemic brain. Eupatilin suppressed NF-κB signaling activities in ischemic brain by reducing IKKα/β phosphorylation, IκBα phosphorylation, and IκBα degradation. Overall, these data indicate that eupatilin is a neuroprotective agent against

  11. 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.

  12. 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.

  13. Danhong injection A modulator for Golgi structural stability after cerebral ischemia-reperfusion injury*

    Institute of Scientific and Technical Information of China (English)

    Yan Wang; Zhiping Hu; Wei Lu

    2013-01-01

    The cerebral ischemia-reperfusion model was established using the suture occlusion method, and rats were intraperitoneal y given 8 mL/kg Danhong injection once a day prior to model establishment. Rat brain tissues were harvested at 6, 24, 48, 72 hours after reperfusion. Immunohistochemical staining showed that transforming growth factor-β1 expression increased, while Golgi matrix protein GM130 expression decreased after cerebral ischemia-reperfusion. Danhong injection was shown to significantly up-regulate the expression of transforming growth factor-β1 and GM130, and expres-sion levels peaked at 7 days after reperfusion. At 7 days after cerebral ischemia-reperfusion, Golgi morphology was damaged in untreated rats, while Golgi morphology breakage was not observed after intervention with Danhong injection. These experimental findings indicate that Danhong injec-tion can up-regulate the expression of transforming growth factor-β1 and GM130, and maintain Golgi stability, thus playing a neuroprotective role in rats after cerebral ischemia-reperfusion.

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

    DEFF Research Database (Denmark)

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

    2005-01-01

    A key pathological event during cerebral ischemia is the excitotoxic release of glutamate. We have shown previously that alpha-melanocyte-stimulating hormone (alpha-MSH) enhances the hypothermia induced by kainic acid. We have investigated the effects of systemic administration of alpha-MSH on four...

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

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

  16. Glutamic acid and cerebral ischemia%谷氨酸与脑缺血

    Institute of Scientific and Technical Information of China (English)

    李学忠; 包仕尧

    2002-01-01

    @@ Half century ago, the relationship between some amino acids and neurological function has been researched, and especially when the micro dialysis technology in vivo was improved, the relationship was researched by new methods. In the paper, the relationship of glutamic acid (Glu) and cerebral ischemia will be reviewed.

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

    DEFF Research Database (Denmark)

    Moldovan, M; Zagrean, Ana-Maria; Avramescu, S;

    2004-01-01

    During recovery after a transient global cerebral ischemia (TGCI), rat electrocorticogram (ECoG) shows epochs of synchronized activity (SA) alternating with epochs of low amplitude background activity (BA). The aim of this study was to compare the changes in these electrical activities during a 3...

  18. Autophagy:a double-edged sword for neuronal survival after cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Wenqi Chen; Yinyi Sun; Kangyong Liu; Xiaojiang Sun

    2014-01-01

    Evidence suggests that autophagy may be a new therapeutic target for stroke, but whether acti-vation of autophagy increases or decreases the rate of neuronal death is still under debate. This review summarizes the potential role and possible signaling pathway of autophagy in neuronal survival after cerebral ischemia and proposes that autophagy has dual effects.

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

    Science.gov (United States)

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

    2015-01-01

    The formation of glial scar impedes the neurogenesis and neural functional recovery following cerebral ischemia. Histamine showed neuroprotection at early stage after cerebral ischemia, however, its long-term effect, especially on glial scar formation, hasn’t been characterized. With various administration regimens constructed for histidine, a precursor of histamine, we found that histidine treatment at a high dose at early stage and a low dose at late stage demonstrated the most remarkable long-term neuroprotection with decreased infarct volume and improved neurological function. Notably, this treatment regimen also robustly reduced the glial scar area and facilitated the astrocyte migration towards the infarct core. In wound-healing assay and transwell test, histamine significantly promoted astrocyte migration. H2 receptor antagonists reversed the promotion of astrocyte migration and the neuroprotection provided by histidine. Moreover, histamine upregulated the GTP-bound small GTPase Rac1, while a Rac1 inhibitor, NSC23766, abrogated the neuroprotection of histidine and its promotion of astrocyte migration. Our data indicated that a dose/stage-dependent histidine treatment, mediated by H2 receptor, promoted astrocyte migration towards the infarct core, which benefited long-term post-cerebral ischemia neurological recovery. Therefore, targeting histaminergic system may be an effective therapeutic strategy for long-term cerebral ischemia injury through its actions on astrocytes. PMID:26481857

  20. Clinical Observation on 30 Cases of Transient Cerebral Ischemia Attack Treated with Acupuncture and Medication

    Institute of Scientific and Technical Information of China (English)

    Feng Lingmei; Zhang Jun; Cai Wei; Sun Yah

    2007-01-01

    Objective: To probe the curative effect of acupuncture and medication on transient cerebral ischemia attack. Method: 30 patients with transient cerebral ischemia attack in the treatment group were acupunctured at Fengchi (GB 20), Wangu (GB 12) and Tianzhu (BL 10) and given orally leech capsules and centipede capsules. 30 patients with transient cerebral ischemia attack in the control group were given intravenous drip of compound Danshen injection and orally aspirin. At the end of two treatment courses, the curative effects were evaluated and the changes in blood rheology and in 3 indexes of blood coagulation were observed before and after treatment in the 2 groups. Results: The total effective rate in the treatment group was 86.7% with obvious difference as compared to the control group (P<0.05).There were remarkable differences in blood rheology and 3 indexes of blood coagulation before and after treatment in the treatment group (P<0.05, P<0.01). There were remarkable differences after treatment between the 2 groups (P<0.05). Conclusion: Acupuncture at Fengchi (GB 20), Wangu (GB 12) and Tianzhu (BL 10) and medication with leech capsules and centipede capsules are effective methods in treating transient cerebral ischemia attack.

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

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    Dong-shu Zhang

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-10-20

    The formation of glial scar impedes the neurogenesis and neural functional recovery following cerebral ischemia. Histamine showed neuroprotection at early stage after cerebral ischemia, however, its long-term effect, especially on glial scar formation, hasn't been characterized. With various administration regimens constructed for histidine, a precursor of histamine, we found that histidine treatment at a high dose at early stage and a low dose at late stage demonstrated the most remarkable long-term neuroprotection with decreased infarct volume and improved neurological function. Notably, this treatment regimen also robustly reduced the glial scar area and facilitated the astrocyte migration towards the infarct core. In wound-healing assay and transwell test, histamine significantly promoted astrocyte migration. H2 receptor antagonists reversed the promotion of astrocyte migration and the neuroprotection provided by histidine. Moreover, histamine upregulated the GTP-bound small GTPase Rac1, while a Rac1 inhibitor, NSC23766, abrogated the neuroprotection of histidine and its promotion of astrocyte migration. Our data indicated that a dose/stage-dependent histidine treatment, mediated by H2 receptor, promoted astrocyte migration towards the infarct core, which benefited long-term post-cerebral ischemia neurological recovery. Therefore, targeting histaminergic system may be an effective therapeutic strategy for long-term cerebral ischemia injury through its actions on astrocytes.

  3. CD38 exacerbates focal cytokine production, postischemic inflammation and brain injury after focal cerebral ischemia.

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    Chi-un Choe

    Full Text Available BACKGROUND: Converging evidence suggests that inflammatory processes significantly influence brain injury and clinical impairment in ischemic stroke. Although early studies suggested a key role of lymphocytes, recent data has emphasized the orchestrating function of innate immunity, i.e., macrophages and microglia. The bifunctional receptor and ectoenzyme CD38 synthesizes calcium-mobilizing second messengers (e.g., cyclic ADP-ribose, which have been shown to be necessary for activation and migration of myeloid immune cells. Therefore, we investigated the dynamics of CD38 in stroke and the impact of CD38-deficiency on cytokine production, inflammation and cerebral damage in a mouse model of cerebral ischemia-reperfusion. METHODOLOGY/PRINCIPAL FINDINGS: We show that the local expression of the chemokine MCP-1 was attenuated in CD38-deficient mice compared with wildtype mice after focal cerebral ischemia and reperfusion. In contrast, no significant induction of MCP-1 expression was observed in peripheral blood after 6 hours. Flow cytometry analysis revealed less infiltrating macrophages and lymphocytes in the ischemic hemisphere of CD38-deficient mice, whereas the amount of resident microglia was unaltered. An up-regulation of CD38 expression was observed in macrophages and CD8(+ cells after focal cerebral ischemia in wildtype mice, whereas CD38 expression was unchanged in microglia. Finally, we demonstrate that CD38-deficiency decreases the cerebral ischemic injury and the persistent neurological deficit after three days of reperfusion in this murine temporary middle cerebral artery occlusion (tMCAO model. CONCLUSION/SIGNIFICANCE: CD38 is differentially regulated following stroke and its deficiency attenuates the postischemic chemokine production, the immune cell infiltration and the cerebral injury after temporary ischemia and reperfusion. Therefore CD38 might prove a therapeutic target in ischemic stroke.

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

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    Adem Bozkurt Aras

    2015-01-01

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

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

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    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.

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

    Science.gov (United States)

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

    2006-08-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  9. Immunohistochemical Detection of Apoptosis-Related Proteins in Gerbil Hippocampus Transient Cerebral Ischemia: Neuroprotective Effect of Pitavastatin

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    Toshiki Himeda

    2005-01-01

    Full Text Available Delayed and selective neuronal damage was caused in the CA1 sector of hippocampus following 5 min of transient cerebral ischemia in gerbils. We investigated the immunohistochemical alterations of apoptosis-related proteins such as bcl-2α, bcl-xs/l, bax, cytochrome c, and active caspase 3 and TUNEL staining in the hippocampus at 1 and 5 hr and 1, 2, 5 and 14 days after transient cerebral ischemia in gerbils. We also examined the effect of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor pitavastatin against the alterations of apoptosis-related proteins and TUNEL staining in the hippocampus after cerebral ischemia. The alterations of apoptosis-related proteins in the hippocampal CA1 sector were more pronounced than the changes of hippocampal CA3 sector and dentate gyrus after cerebral ischemia. The alterations of apoptosis-related proteins in the hippocampal CA1 sector after cerebral ischemia preceded the neuronal damage in this region. Furthermore, the study with TUNEL staining showed that a marked increase of TUNEL-positive nuclei was evident only in the hippocampal CA1 sector 5 days after cerebral ischemia. Our immunohistochemical study also showed that pitavastatin prevented the alterations of apoptosis-related proteins and the increase of TUNEL-positive nuclei in the hippocampal CA1 sector 5 days after cerebral ischemia. The present study indicates that transient cerebral ischemia in gerbils causes the mitochondrial-dependent apoptosis in the hippocampal CA1 sector. Furthermore, our present study demonstrates that pitavastatin can prevent the alterations of apoptosis-related proteins and the increase of TUNEL-positive nuclei in the hippocampal CA1 sector after cerebral ischemia. Thus our study provides novel therapeutic strategies in clinical stroke.

  10. 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.

  11. Regional cerebral blood flow and glucose metabolism following transient forebrain ischemia.

    Science.gov (United States)

    Pulsinelli, W A; Levy, D E; Duffy, T E

    1982-05-01

    Progressive brain damage after transient cerebral ischemia may be related to changes in postischemic cerebral blood flow and metabolism. Regional cerebral blood flow (rCBF) and cerebral glucose utilization (rCGU) were measured in adult rats prior to, during (only rCBF), and serially after transient forebrain ischemia. Animals were subjected to 30 minutes of forebrain ischemia by occluding both common carotid arteries 24 hours after cauterizing the vertebral arteries. Regional CBF was measured by the indicator-fractionation technique using 4-iodo-[14C]-antipyrine. Regional CGU was measured by the 2-[14C]deoxyglucose method. The results were correlated with the distribution and progression of ischemic neuronal damage in animals subjected to an identical ischemic insult. Cerebral blood flow to forebrain after 30 minutes of moderate to severe ischemia (less than 10% control CBF) was characterized by 5 to 15 minutes of hyperemia; rCBF then fell below normal and remained low for as long as 24 hours. Post-ischemic glucose utilization in the forebrain, except in the hippocampus, was depressed below control values at 1 hour and either remained low (neocortex, striatum) or gradually rose to normal (white matter) by 48 hours. In the hippocampus, glucose utilization equaled the control value at 1 hour and fell below control between 24 and 48 hours. The appearance of moderate to severe morphological damage in striatum and hippocampus coincided with a late rise of rCBF above normal and with a fall of rCGU; the late depression of rCGU was usually preceded by a period during which metabolism was increased relative to adjacent tissue. Further refinement of these studies may help identify salvageable brain after ischemia and define ways to manipulate CBF and metabolism in the treatment of stroke.

  12. [Consensus review. Pharmacological neuroprotection in cerebral ischemia: is it still a therapeutic option?].

    Science.gov (United States)

    Castillo, J; Alvarez-Sabin, J; Dávalos, A; Diez-Tejedor, E; Lizasoain, I; Martínez-Vila, E; Vivancos, J; Zarranz, J J

    2003-09-01

    Our increasing knowledge concerning the pathophysiology of cerebral ischemia is leading to a considerable development of drugs that at various levels block or modify the chain of biochemical processes set off as a consequence of hypoperfusion of cerebral parenchyma. In this zone of ischemic penumbra, the interaction between the neuronal ischemia cascade, the response of the glia and changes in the microcirculation, determine the evolution towards either functional recovery of the ischemic fabric or it necrosis. In various types of animal models, the majority of neuroprotective drugs have been shown to have considerable efficacy. However, this has not been translated into human clinical practice. The identification of persistence of recoverable cerebral tissue, together with the development of new designs of clinical trails better adapted to preclinical experiences and to the features of the drugs concerned, may contribute to an improved applicability of the new drugs in human clinical practice.

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

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

    1999-08-01

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

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

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    Shi-Dong Zhang

    2011-12-01

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

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

    Science.gov (United States)

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

    1990-11-01

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

  16. Effects of crocin on reperfusion-induced oxidative/nitrative injury to cerebral microvessels after global cerebral ischemia.

    Science.gov (United States)

    Zheng, Yong-Qiu; Liu, Jian-Xun; Wang, Jan-Nong; Xu, Li

    2007-03-23

    This paper studied the effects of crocin, a pharmacologically active component of Crocus sativus L., on ischemia/reperfusion (I/R) injury in mice cerebral microvessels. Transient global cerebral ischemia (20 min), followed by 24 h of reperfusion, significantly promoted the generation of nitric oxide (NO) and malondialdehyde (MDA) in cortical microvascular homogenates, as well as markedly reduced the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) and promoted the activity of nitric oxide synthase (NOs). Reperfusion for 24 h led to serous edema with substantial microvilli loss, vacuolation, membrane damage and mitochondrial injuries in cortical microvascular endothelial cells (CMEC). Furthermore, enhanced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and decreased expression of matrix metalloproteinase-9 (MMP-9) were detected in cortical microvessels after I (20 min)/R (24 h). Reperfusion for 24 h also induced membrane (functional) G protein-coupled receptor kinase 2 (GRK2) expression, while it reduced cytosol GRK2 expression. Pretreatment with crocin markedly inhibited oxidizing reactions and modulated the ultrastructure of CMEC in mice with 20 min of bilateral common carotid artery occlusion (BCCAO) followed by 24 h of reperfusion in vivo. Furthermore, crocin inhibited GRK2 translocation from the cytosol to the membrane and reduced ERK1/2 phosphorylation and MMP-9 expression in cortical microvessels. We propose that crocin protects the brain against excessive oxidative stress and constitutes a potential therapeutic candidate in transient global cerebral ischemia.

  17. Monocarboxylate transporter 4 plays a significant role in the neuroprotective mechanism of ischemic preconditioning in transient cerebral ischemia

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    Seongkweon Hong

    2015-01-01

    Full Text Available Monocarboxylate transporters (MCTs, which carry monocarboxylates such as lactate across biological membranes, have been associated with cerebral ischemia/reperfusion process. In this study, we studied the effect of ischemic preconditioning (IPC on MCT4 immunoreactivity after 5 minutes of transient cerebral ischemia in the gerbil. Animals were randomly designated to four groups (sham-operated group, ischemia only group, IPC + sham-operated group and IPC + ischemia group. A serious loss of neuron was found in the stratum pyramidale of the hippocampal CA1 region (CA1, not CA2/3, of the ischemia-only group at 5 days post-ischemia; however, in the IPC + ischemia groups, neurons in the stratum pyramidale of the CA1 were well protected. Weak MCT4 immunoreactivity was found in the stratum pyramidale of the CA1 in the sham-operated group. MCT4 immunoreactivity in the stratum pyramidale began to decrease at 2 days post-ischemia and was hardly detected at 5 days post-ischemia; at this time point, MCT4 immunoreactivity was newly expressed in astrocytes. In the IPC + sham-operated group, MCT4 immunoreactivity in the stratum pyramidale of the CA1 was increased compared with the sham-operated group, and, in the IPC + ischemia group, MCT4 immunoreactivity was also increased in the stratum pyramidale compared with the ischemia only group. Briefly, present findings show that IPC apparently protected CA1 pyramidal neurons and increased or maintained MCT4 expression in the stratum pyramidale of the CA1 after transient cerebral ischemia. Our findings suggest that MCT4 appears to play a significant role in the neuroprotective mechanism of IPC in the gerbil with transient cerebral ischemia.

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

    Institute of Scientific and Technical Information of China (English)

    Jianji Pei; Liqiang Liu; Jinping Pang; Xiaohong Tian

    2008-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    Ke Liu; Jiansheng Li

    2006-01-01

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

  20. Granulocyte colony-stimulating factor regulates JNK pathway to alleviate damage after cerebral ischemia reperfusion

    Institute of Scientific and Technical Information of China (English)

    LI Ya-guo; LIU Xiao-li; ZHENG Chao-bo

    2013-01-01

    Background Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a potent hematopoietic growth factor that both enhances the survival and drives the differentiation and proliferation of myeloid lineage cells.Recent studies have suggested that GM-CSF has a neuroprotective effect against cerebral ischemia injury,but the molecular mechanisms have been unclear.This study aimed to investigate the influences of a short-acting (half-life 3.5 hours) G-CSF and a long-acting (half-life 40 hours) pegylated G-CSF on the JNK signaling pathway after cerebral ischemia reperfusion.Methods A total of 52 Sprague-Dawley rats were randomly divided into four groups:a sham group (n=4),a vehicle with saline (n=16),a short-acting G-CSF treatment group (n=16) and a long-acting G-CSF treatment group (n=16).The cerebral ischemia reperfusion model was established for the sham group and G-CSF treatment groups by middle cerebral artery occlusion (MCAO).Five days post reperfusion,rats were sacrificed and the brains were removed.Changes in neurological function after cerebral ischemia reperfusion was evaluated according to Neurological Severity Score (NSS) and the lesion volume and infarct size were measured by 2,3,5-triphenyltetrazolium chloride staining.The numbers of apoptotic neurons in these ischemic areas:left cerebral cortex,striatum and hippocampus were calculated by TUNEL assay,and expression of JNK/P-JNK,c-jun/P-c-jun in these areas was detected by Western blotting.Results Compared with the saline vehicle group ((249.68±23.36) mm3,(19.27±3.37)%),G-CSF-treated rats revealed a significant reduction in lesion volume (long-acting:(10.89±1.90)%,P <0.01; short-acting G-CSF:(11.69±1.41)%,P <0.01)and infarct size (long-acting:(170.53±18.47) mm3,P <0.01; short-acting G-CSF:(180.74±16.93) mm3,P <0.01) as well as less neuron functional damage (P <0.01) and a smaller number of apoptotic neurons in ischemic areas (P <0.01).The activity of P-JNK and P-c-jun in the

  1. Effects of electroacupuncture on astrocytes in the marginal zone of focal cerebral ischemia in rats

    Institute of Scientific and Technical Information of China (English)

    Yan Luo; Nenggui Xu; Wei Yi; Yong Zi; Yixu Du

    2009-01-01

    BACKGROUND: Astrocytes react sensitively to cerebral ischemia, causing reactive proliferation and activation, which may contribute to their effect in protecting or injuring neuronal regeneration. Whether acupuncture, as a treatment for cerebral ischemia, regulates the activated state of astrocytes has become a focus of recent investigations.OBJECTIVE: To observe the effects of electroacupuncture (EA) on ultrastructure changes and reactive proliferation of astrocytes in the marginal zone of focal cerebral ischemia in rats. DESIGN, TIME AND SETTING: Randomized, controlled animal study. This study was performed at the Experimental Animal Center of Guangzhou University of Traditional Chinese Medicine between December 2007 and July 2008.MATERIALS: A total of 90 male Wistar rats were randomly divided into sham operated, model and EA groups. Each group was subdivided into 1 hour, 1, 3, 7, and 21 days post-cerebral ischemia groups, with six animals for each time point. Rabbit anti-rat glial fibrillary acidic protein (GFAP) and goat anti-rabbit IgG/tetramethylrhodamine isothiocyanate were provided by Beijing Biosynthesis Biotechnology. The G-6805 electric acupuncture apparatus was provided by Shanghai Huayi.METHODS: Heat-coagulation-induced occlusion of the middle cerebral artery was performed to establish a model of focal cerebral ischemia, in the model and EA groups. Middle cerebral arteries were exposed without occlusion in sham operated group. EA was applied immediately after surgery in the EA group, 4/20 Hz, 2.0-3.0 V, 1-3 mA, to Baihui (GV 20) and Dazhui (GV 14), for 30 minutes. The treatment was performed once a day. The sham operated and model groups did not receive acupuncture.MAIN OUTCOME MEASURES: In the marginal zone of focal cerebral ischemia in rats at different time points after intervention, the ultrastructure changes of astrocytes were observed by using transmission electronic microscopy. GFAP expression in astrocytes was also measured by laser confocal

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

    Institute of Scientific and Technical Information of China (English)

    补娟

    2013-01-01

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

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

    OpenAIRE

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

    2000-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-08-01

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

  5. Flurbiprofen axetil promotes neuroprotection by activation of cerebral peroxisome proliferator-activated receptor gamma after focal cerebral ischemia in rats

    Institute of Scientific and Technical Information of China (English)

    LIU Jun-le; JIN Jian-wen; PEI Shu-jun; WANG Chen

    2012-01-01

    Background Our previous papers indicate that flurbiprofen axetil (FA),a cyclooxygenase inhibitor,is a promising therapeutic strategy for cerebral ischemia in rats.This study aimed to investigate whether FA could promote a neuroprotective effect by activation of peroxisome proliferator-activated receptor-γ (PPAR-γ) after focal cerebral ischemia in rats.Methods Totally 48 male Sprague-Dawley (SD) rats were randomly assigned into six groups (n=8 in each group):animals in group ischemia/reperfusion (I/R) only received 120-minute transient middle cerebral artery occlusion (tMCAO);animals in group I/R +FA were administered FA (10 mg/kg) by caudal vein just after 120-minute tMCAO; animals in group I/R +FA+GW9662 were administered GW9662 (a PPAR-γ inhibitor,1 mg/kg) intraperitoneally 30 minutes before cerebral ischemia onset and FA (10 mg/kg) by caudal vein just after 120-minute tMCAO; animals in group I/R +GW9662 were administered GW9662 (1 mg/kg) intraperitoneally 30 minutes before cerebral ischemia onset; animals in group I/R +DMSO were administered 3% DMSO (vehicle of GW9662,1 ml/kg) intraperitoneally 30 minutes before cerebral ischemia onset; animals in sham group experienced the identical surgery apart from the insertion of the nylon filament.The neurologic deficit score (NDS) were performed at 72 hours after reperfusion,and then mean brain infarct volume percentage (MBIVP) was determined with 2,3,5-triphenyltetrazolium chloride (TTC) 10(g)/L staining.Results NDS was significantly increased in group I/R+FA (12.0 (10.0-15.0)),group I/R+FA+GW9662 (10.0 (8.0-12.0)),and in group I/R+FA+DMSO (12.0 (9.0-14.0)) at 72 hours after reperfusion compared with those in group I/R (7.5(6.0-10.0)) NDS was conspicuously different between group I/R+FA (12.0 (10.0-15.0)) and group I/R+FA+GW9662 (10.0 (8.0-12.0)).MBIVP in group I/R ((45.82±8.83)%) was significantly greater than that in group I/R+FA((23.52±9.90)%),group I/R+FA+GW9662 ((33.17±7.15)%); MBIVP in group

  6. Autoradiographic localization of N-type VGCCs in gerbil hippocampus and failure of omega-conotoxin MVIIA to attenuate neuronal injury after transient cerebral ischemia.

    Science.gov (United States)

    Azimi-Zonooz, A; Kawa, C B; Dowell, C D; Olivera, B M

    2001-07-13

    In the mammalian central nervous system, transient global ischemia of specific duration causes selective degeneration of CA1 pyramidal neurons in hippocampus. Many of the ischemia-induced pathophysiologic cascades that destroy the neurons are triggered by pre- and postsynaptic calcium entry. Consistent with this, many calcium channel blockers have been shown to be neuroprotective in global models of ischemia. omega-Conotoxin MVIIA, a selective N-type VGCC blocker isolated from the venom of Conus magus, protects CA1 neurons in the rat model of global ischemia, albeit transiently. The mechanism by which this peptide renders neuroprotection is unknown. We performed high-resolution receptor autoradiography with the radiolabeled peptide and observed highest binding in stratum lucidum of CA3 subfield, known to contain inhibitory neurons potentially important in the pathogenesis of delayed neuronal death. This finding suggested that the survival of stratum lucidum inhibitory neurons might be the primary event, leading to CA1 neuroprotection after ischemia. Testing of this hypothesis required the reproduction of its neuroprotective effects in the gerbil model of global ischemia. Surprisingly, we found that omega-MVIIA did not attenuate CA1 hippocampal injury after 5 min of cerebral ischemia in gerbil. Possible reasons are discussed. Lastly, we show that the peptide can be used as a synaptic marker in assessing short and long-term changes that occur in hippocampus after ischemic injury.

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

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

    OpenAIRE

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

    2012-01-01

    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 ani...

  9. 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

  10. Neuroprotective Effect of Phosphocreatine on Focal Cerebral Ischemia-Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Tiegang Li

    2012-01-01

    Full Text Available Phosphocreatine (PCr is a natural compound, which can donate high-energy phosphate group to ADP to synthesize ATP, even in the absence of oxygen and glucose. At present, it is widely used in cardiac and renal ischemia-reperfusion (IR disease. In this study, to examine the protective efficacy of PCr against cerebral IR, disodium creatine phosphate was injected intravenously into rats before focal cerebral IR. Intracranial pressure (ICP, neurological score, cerebral infarction volume, and apoptotic neurons were observed. Expression of caspase-3 and aquaporin-4 (AQP4 was analyzed. Compared with IR group, rats pretreated with PCr had better neurologic score, less infarction volume, fewer ultrastructural histopathologic changes, reduced apoptosis, and lower aquaporin-4 level. In conclusion, PCr is neuroprotective after transient focal cerebral IR injury. Such a protection might be associated with apoptosis regulating proteins.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1988-02-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    BACKGROUND: Interferon (IFN)-β exerts anti-inflammatory effects, coupled to remarkable neurological improvements in multiple sclerosis, a neuroinflammatory condition of the central nervous system. Analogously, it has been hypothesized that IFN-β, by limiting inflammation, decreases neuronal death...... strength tests, and cerebral infarct volumes were given by lack of neuronal nuclei immunoreactivity. RESULTS: Here, we report alterations in local and systemic inflammation in IFN-β knockout (IFN-βKO) mice over 8 days after induction of focal cerebral ischemia. Notably, IFN-βKO mice showed a higher number...

  13. [Cardioprotective effect of drugs with antioxidant activity in acute cerebral ischemia].

    Science.gov (United States)

    Stoliarova, V V

    2001-01-01

    The bioelectric cardiac activity was studied in the experiments on white mice with an acute cerebral blood circulation disorder. It was found that he resulting EEG changes possess a specific character, with the sympathoadrenal system stimulation playing an important role in the acute cerebrocardiac syndrome development. The antioxidant-type agents such as emoxypine (50 mg/kg), mexidol (50 mg/kg), and cytochrome C (10 mg/kg) produce a significant cardioprotective effect in the test animals with experimental cerebral ischemia, which was comparable with the effect of propranolol (obsidane) (0.1 mg/kg).

  14. Repeated doses of melatonin protects against focal cerebral ischemia in the rat

    OpenAIRE

    Pei, Z; Pang, SF; Cheung, RTF

    2000-01-01

    We studied the time window of neuroprotection against focal ischemia by a single dose or repeated doses of melatonin (MT) at 5 mg/kg. Adult male Sprague-Dawley rats (280 to 360 g) were anesthetized with sodium pentobarbital (60 mg/kg, I.P.) to undergo reversible right-sided endovascular middle cerebral artery occlusion (MCAO) for 3 hours. Arterial blood pressure, heart rate and cerebral blood flow were monitored, and rectal temperature was kept between 36.5 and 37.5 ºC throughout anesthesia. ...

  15. 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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Chen Hua-De

    2001-02-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  19. Protective effect of ginkgo proanthocyanidins against cerebral ischemia/reperfusion injury associated with its antioxidant effects

    Science.gov (United States)

    Cao, Wang-li; Huang, Hai-bo; Fang, Ling; Hu, Jiang-ning; Jin, Zhu-ming; Wang, Ru-wei

    2016-01-01

    Proanthocyanidins have been shown to effectively protect ischemic neurons, but its mechanism remains poorly understood. Ginkgo proanthocyanidins (20, 40, 80 mg/kg) were intraperitoneally administered 1, 24, 48 and 72 hours before reperfusion. Results showed that ginkgo proanthocyanidins could effectively mitigate neurological disorders, shorten infarct volume, increase superoxide dismutase activity, and decrease malondialdehyde and nitric oxide contents. Simultaneously, the study on grape seed proanthocyanidins (40 mg/kg) confirmed that different sources of proanthocyanidins have a similar effect. The neurological outcomes of ginkgo proanthocyanidins were similar to that of nimodipine in the treatment of cerebral ischemia/reperfusion injury. Our results suggest that ginkgo proanthocyanidins can effectively lessen cerebral ischemia/reperfusion injury and protect ischemic brain tissue and these effects are associated with antioxidant properties. PMID:28123420

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

    Science.gov (United States)

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

    2014-08-01

    Ganoderma lucidum is a traditional Chinese medicine, which has been shown to have both anti-oxidative and anti-inflammatory effects, and noticeably decreases both the infarct area and neuronal apoptosis of the ischemic cortex. This study aimed to investigate the protective effects and mechanisms of pretreatment with ganoderma lucidum (by intragastric administration) in cerebral ischemia/reperfusion injury in rats. Our results showed that pretreatment with ganoderma lucidum for 3 and 7 days reduced neuronal loss in the hippocampus, diminished the content of malondialdehyde in the hippocampus and serum, decreased the levels of tumor necrosis factor-α and interleukin-8 in the hippocampus, and increased the activity of superoxide dismutase in the hippocampus and serum. These results suggest that pretreatment with ganoderma lucidum was protective against cerebral ischemia/reperfusion injury through its anti-oxidative and anti-inflammatory actions.

  1. TRPM7 in cerebral ischemia and potential target for drug development in stroke

    Institute of Scientific and Technical Information of China (English)

    Christine You-Jin BAE; Hong-shuo Sun

    2011-01-01

    Searching for effective pharmacological agents for stroke treatment has largely been unsuccessful. Despite initial excitement, antagonists for glutamate receptors, the most studied receptor channels in ischemic stroke, have shown insufficient neuroprotective effects in clinical trials. Outside the traditional glutamate-mediated excitotoxicity, recent evidence suggests few non-glutamate mechanisms,which may also cause ionic imbalance and cell death in cerebral ischemia. Transient receptor potential melastatin 7 (TRPM7) is a Ca2+permeable, non-selective cation channel that has recently gained attention as a potential cation influx pathway involved in ischemic events. Compelling new evidence from an in vivo study demonstrated that suppression of TRPM7 channels in adult rat brain in vivo using virally mediated gene silencing approach reduced delayed neuronal cell death and preserved neuronal functions in global cerebral ischemia. In this review, we will discuss the current understanding of the role of TRPM7 channels in physiology and pathophysiology as well as its therapeutic potential in stroke.

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

    Institute of Scientific and Technical Information of China (English)

    Chenxu Li

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Li Gao

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

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

    OpenAIRE

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

    2013-01-01

    Bone marrow cells for the treatment of ischemic brain injury may depend on the secretion of a large number of neurotrophic factors. Bone marrow regenerative cells are capable of increasing the secretion of neurotrophic factors. In this study, after tail vein injection of 5-fluorouracil for 7 days, bone marrow cells and bone marrow regenerative cells were isolated from the tibias and femurs of rats, and then administered intravenously via the tail vein after focal cerebral ischemia. Immunohist...

  5. Neuroprotective Effects of Sesamin and Sesamolin on Gerbil Brain in Cerebral Ischemia

    OpenAIRE

    Cheng, Fu-Chou; Jinn, Tzyy-Rong; Hou, Rolis C. W.; Tzen, Jason T. C.

    2006-01-01

    Sesamin and sesamolin, abundant lignans found in sesame oil, have been demonstrated to possess several bioactivities beneficial for human health. Excess generation of nitric oxide in lipopolysaccharide-stimulated rat primary microglia cells was significantly attenuated when they were pretreated with sesamin or sesamolin. The neuroprotective effect of sesamin and sesamolin was also observed in vivo using gerbils subjected to a focal cerebral ischemia induced by occlusion of the right common ca...

  6. [Acute cerebral ischemia: an unusual clinical presentation of isolated left ventricular noncompaction in an adult patient].

    Science.gov (United States)

    Fiorencis, Andrea; Quadretti, Laura; Bacich, Daniela; Chiodi, Elisabetta; Mele, Donato; Fiorencis, Roberto

    2013-01-01

    Isolated left ventricular noncompaction in adults is uncommon. The most frequent clinical manifestations are heart failure due to left ventricular systolic dysfunction and supraventricular and ventricular arrhythmias, which may be sustained and associated with sudden death. Thromboembolic complications are also possible. We report the case of an adult patient with isolated left ventricular noncompaction who came to our observation because of acute cerebral ischemia, an initial presentation of the disease only rarely described.

  7. Effects of vagus nerve stimulation on cognitive functioning in rats with cerebral ischemia reperfusion

    OpenAIRE

    Liu, Ai-Fen; Zhao, Feng-bo; Wang, Jing; Lu, Yi-Fan; Tian, Jian; Zhao, Yin; Gao, Yan; Hu, Xia-jun; LIU, XIAO-YAN; Tan, Jie; Tian, Yun-li; Shi, Jing

    2016-01-01

    Background Vagus nerve stimulation (VNS) has become the most common non-pharmacological treatment for intractable drug-resistant epilepsy. However, the contribution of VNS to neurological rehabilitation following stroke has not been thoroughly examined. Therefore, we investigated the specific role of acute VNS in the recovery of cognitive functioning and the possible mechanisms involved using a cerebral ischemia/reperfusion (I/R) injury model in rats. Methods The I/R-related injury was modele...

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

    DEFF Research Database (Denmark)

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

    2000-01-01

    and metabolism. The objective of this study was to investigate the effects of preventive treatment with Ginkgo biloba extract (EGb 761--Tebonin) in cerebral global ischemia and reperfusion in rats using computerized EEG analysis. Ginkgo biloba extract, known to be, in vitro, a free radicals scavanger and a PAF.......0015). Computerized spectral analysis of EEG has shown that the percentage of slow waves at 10 minutes after reperfusion was 117% higher in control group than in Ginkgo biloba group (p

  9. Neonatal Cerebral Ischemia: A Risk Factor for ADHD

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2004-03-01

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

  10. 坏死性凋亡与脑缺血%Necroptosis and Cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    朱新永; 卢志伟; 徐恩

    2015-01-01

    坏死性凋亡是新近发现的一种细胞死亡方式,与感染、肿瘤、心脏疾病、神经变性疾病以及脑血管病等多种疾病相关。坏死性凋亡参与了脑缺血再灌注损伤的发生和发展。因此,深入研究脑缺血时坏死性凋亡的诱导、调节和阻断机制,不仅有利于加深对脑细胞死亡方式的理解,也有利于针对脑缺血治疗的新靶点研发新的药物。%Necroptosisisanewlydiscoveredwayofceldeath.Itisassociatedwithinfection, tumor, heart disease, neurodegenerative disease, cerebrovascular disease, and other diseases. Necroptosis involves in the occurrence and development of cerebral ischemia-reperfusion injury. Therefore, w hen the cerebral ischemia is studied in depth, the induction, regulation and blocking mechanisms of necroptosis are not only conducive to deepen the understanding of the death mode of brain cel s, but also conducive to develop new drugs for the new targets in the treatment of cerebral ischemia.

  11. Salvianolate increases heat shock protein expression in a cerebral ischemia-reperfusion injury model

    Institute of Scientific and Technical Information of China (English)

    Jinnan Zhang; Wei Lu; Qiang Lei; Xi Tao; Hong You; Pinghui Xie

    2013-01-01

    Stroke remains a worldwide health problem. Salvianolate exerts a protective effect in various mi-crocirculatory disturbance-related diseases, but studies of the mechanisms underlying its protective action have mainly focused on the myocardium, whereas little research has been carried out in brain tissue fol owing ischemia-reperfusion. We assessed the neuroprotective effects of salvianolate in a rat model of cerebral ischemia-reperfusion injury induced using the suture method. At onset and 24 and 48 hours after reperfusion, rats were intraperitoneal y injected with salvianolate (18 mg/kg) or saline. Neurological deficit scores at 72 hours showed that the neurological functions of rats that had received salvianolate were significantly better than those of the rats that had received saline. 2,3,5-Triphenyltetrazolium chloride was used to stain cerebral tissue to determine the extent of the infarct area. A significantly smal er infarct area and a significantly lower number of apoptotic cel s were observed after treatment with salvianolate compared with the saline treatment. Expression of heat shock protein 22 and phosphorylated protein kinase B in ischemic brain tissue was significantly greater in rats treated with salvianolate compared with rats treated with saline. Our findings suggest that salvianolate provides neuroprotective effects against cerebral ischemia-reperfusion injury by upregulating heat shock protein 22 and phosphorylated protein kinase B expression.

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

    Science.gov (United States)

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

    1990-01-01

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

  13. The effect of ASK1 on vascular permeability and edema formation in cerebral ischemia.

    Science.gov (United States)

    Song, Juhyun; Cheon, So Yeong; Lee, Won Taek; Park, Kyung Ah; Lee, Jong Eun

    2015-01-21

    Apoptosis signal-regulating kinase-1 (ASK1) is the mitogen-activated protein kinase kinase kinase (MAPKKK) and participates in the various central nervous system (CNS) signaling pathways. In cerebral ischemia, vascular permeability in the brain is an important issue because regulation failure of it results in edema formation and blood-brain barrier (BBB) disruption. To determine the role of ASK1 on vascular permeability and edema formation following cerebral ischemia, we first investigated ASK1-related gene expression using microarray analyses of ischemic brain tissue. We then measured protein levels of ASK1 and vascular endothelial growth factor (VEGF) in brain endothelial cells after hypoxia injury. We also examined protein expression of ASK1 and VEGF, edema formation, and morphological alteration through cresyl violet staining in ischemic brain tissue using ASK1-small interference RNA (ASK1-siRNA). Finally, immunohistochemistry was performed to examine VEGF and aquaporin-1 (AQP-1) expression in ischemic brain injury. Based on our findings, we propose that ASK1 is a regulating factor of vascular permeability and edema formation in cerebral ischemia.

  14. Effect of Rosiglitazone Maleate on Inflammation Following Cerebral Ischemia/Reperfusion in Rats

    Institute of Scientific and Technical Information of China (English)

    XIONG Nanxiang; SUN Fan; ZHAO Hongyang; XIANG Jizhou

    2007-01-01

    In order to evaluate the neuroprotective effect of Rosiglitazone Maleate (RSG) against brain ischemic injury, the effects of Rosiglitazone Maleate on the inflammation following cerebral ischemia/reperfusion were investigated. Focal cerebral ischemia was induced by the intraluminal thread for cerebral middle artery (MCA) occlusion. Rosiglitazone Maleate at concentrations of 0.5,2 and 5 mg/kg was infused by intragastric gavage twice immediately and 2 h after MCA occlusion,respectively. The effects of Rosiglitazone Maleate on brain swelling, myeloperoxidase and interleukin-6 mRNA level in brain tissue after MCA occlusion and reperfusion were evaluated. The results showed that as compared with the model control group, RSG (0.5 mg/kg) had no significant influence on brain swelling (P>0.05), but 2 mg/kg and 5 mg/kg RSG could significantly alleviate brain swelling (P<0.05). All different doses of RSG could obviously reduce MPO activity in brain tissue after MCA occlusion and reperfusion in a dose-dependent manner. RSG (0.5 and 2 mg/kg) could decrease the expression levels of IL-6 mRNA in brain tissue after MCA occlusion and reperfusion to varying degrees (P<0.05) with the difference being significant between them. It was concluded that RSG could effectively ameliorate brain ischemic injury after 24 h MCA occlusion and inhibit the inflammatory response after ischemia-reperfusion in this model.

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

    Directory of Open Access Journals (Sweden)

    Jin-Young Chung

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

  16. The study of protective effects and mechanisms of rofecoxib on focal cerebral ischemia- reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    YUJuan; ZHOUYu; QIULi-Ying; CHENBai-Ling; CHENChong-Hong

    2004-01-01

    AIM : To study the protective effects and the mechanisms of rofecoxib as a specific type 2 cyclooxygenase (COX- 2 inhibitor on focal cerebral ischemia reperfusion injury ( CIRI in rats. METHODS : The model of focal CIRI was induced by reversible middle cerebral artery occlusion ( MCAO with inserting a thread through internal carotid artery, 2 h occlusion followed

  17. Ischemia Induces Release of Endogenous Amino Acids from the Cerebral Cortex and Cerebellum of Developing and Adult Mice

    Directory of Open Access Journals (Sweden)

    Simo S. Oja

    2013-01-01

    Full Text Available Ischemia enhanced release of endogenous neuroactive amino acids from cerebellar and cerebral cortical slices. More glutamate was released in adult than developing mice. Taurine release enhanced by K+ stimulation and ischemia was more than one magnitude greater than that of GABA or glutamate in the developing cerebral cortex and cerebellum, while in adults the releases were almost comparable. Aspartate release was prominently enhanced by both ischemia and K+ stimulation in the adult cerebral cortex. In the cerebellum K+ stimulation and ischemia evoked almost 10-fold greater GABA release in 3-month olds than in 7-day olds. The release of taurine increased severalfold in the cerebellum of 7-day-old mice in high-K+ media, whereas the K+-evoked effect was rather small in adults. In 3-month-old mice no effects of K+ stimulation or ischemia were seen in the release of aspartate, glycine, glutamine, alanine, serine, or threonine. The releases from the cerebral cortex and cerebellum were markedly different and also differed between developing and adult mice. In developing mice only the release of inhibitory taurine may be large enough to counteract the harmful effects of excitatory amino acids in ischemia in both cerebral cortex and cerebellum, in particular since at that age the release of glutamate and aspartate cannot be described as massive.

  18. Total flavonoid of Litsea coreana leve exerts anti-oxidative effects and alleviates focal cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Shuying Dong; Xuhui Tong; Jun Li; Cheng Huang; Chengmu Hu; Hao Jiao; Yuchen Gu

    2013-01-01

    In this study, we hypothesized that total flavonoid of Litsea coreana leve (TFLC) protects against focal cerebral ischemia/reperfusion injury. TFLC (25, 50, 100 mg/kg) was administered oral y to a rat model of focal ischemia/reperfusion injury, while the free radical scavenging agent, edaravone, was used as a positive control drug. Results of neurological deficit scoring, 2,3,5-triphenyl tetrazolium chloride staining, hematoxylin-eosin staining and biochemical tests showed that TFLC at different doses significantly al eviated cerebral ischemia-induced neurological deficits and histopathological changes, and reduced infarct volume. Moreover, it suppressed the increase in the levels of nitrates plus nitrites, malondialdehyde and lactate dehydrogenase, and it diminished the reduction in gluta-thione, superoxide dismutase and catalase activities induced by cerebral ischemia/reperfusion in-jury. Compared with edaravone, the protective effects of TFLC at low and medium doses (25, 50 mg/kg) against cerebral ischemia/reperfusion injury were weaker, while the protective effects at high dose (100 mg/kg) were similar. Our experimental findings suggest that TFLC exerts neuroprotective effects against focal cerebral ischemia/reperfusion injury in rats, and that the effects may be asso-ciated with its antioxidant activities.

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

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

  20. Nimodipine prevents early loss of hippocampal CA1 parvalbumin immunoreactivity after focal cerebral ischemia in the rat.

    Science.gov (United States)

    Benyó, Z; De Jong, G I; Luiten, P G

    1995-01-01

    The effect of focal cerebral ischemia induced by middle cerebral artery occlusion on hippocampal interneurons containing the calcium-binding protein parvalbumin (PV) was studied in rats. Four hours after the onset of ischemia, a reduced number of PV-immunoreactive (-ir) neurons was observed in the lateral part of the CA1 region, while PV-ir was not altered in the CA2 and CA3 areas. Pretreatment with the L-type Ca2+ channel blocker nimodipine prevented the ischemia-induced loss of PV-ir in the CA1, suggesting a role for L-type voltage sensitive calcium channels in the mechanism of early neuronal alterations in the hippocampus CA1 region after focal cerebral ischemia.

  1. 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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

  4. [Comparative evaluation of the neuroprotective activity of phenotropil and piracetam in laboratory animals with experimental cerebral ischemia].

    Science.gov (United States)

    Tiurenkov, I N; Bagmetov, M N; Epishina, V V

    2007-01-01

    The neuroprotective properties of phenotropil and piracetam were studied in Wistar rats with low and high sensitivity with respect to 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 the brain cortex under ischemic injury conditions were studied. Phenotropil and (to a lower extent) piracetam reduced the extent of neuralgic deficiency manifestations, retained the locomotor, research, and memory functions in animals with gravitational cerebral ischemia, increased the survival of experimental animals, and favored the restoration of local cerebral flow upon the occlusion of carotid arteries.

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

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

  6. Neuroprotective effect of Cerebralcare Granule after cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Xiao-xiao Zhang; Fen-fen He; Gui-lin Yan; Ha-ni Li; Dan Li; Yan-ling Ma; Fang Wang; Nan Xu; Fei Cao

    2016-01-01

    Cerebralcare Granule (CG) improves cerebral microcirculation and relieves vasospasm, but studies investigating its therapeutic effect on cerebral ischemia/reperfusion injury are lacking. In the present study, we administered CG (0.3, 0.1 and 0.03 g/mL intragastrically) to rats for 7 consecutive days. We then performed transient occlusion of the middle cerebral artery, followed by reperfusion, and administered CG daily for a further 3 or 7 days. Compared with no treatment, high-dose CG markedly improved neurological function assessed using the Bederson and Garcia scales. At 3 days, animals in the high-dose CG group had smaller infarct volumes, greater interleukin-10 expression, and fewer interleukin-1β-immunoreactive cells than those in the untreated model group. Furthermore, at 7 days, high-dose CG-treated rats had more vascular endothelial growth factor-immunoreactive cells, elevated angiopoietin-1 and vascular endothelial growth factor ex-pression, and improved blood coagulation and lfow indices compared with untreated model animals. These results suggest that CG exerts speciifc neuroprotective effects against cerebral ischemia/reperfusion injury.

  7. Reduced brain edema and infarct volume in aquaporin-4 deficient mice after transient focal cerebral ischemia.

    Science.gov (United States)

    Yao, Xiaoming; Derugin, Nikita; Manley, Geoffrey T; Verkman, A S

    2015-01-01

    Aquaporin-4 (AQP4) is a water channel expressed in astrocyte end-feet lining the blood-brain barrier. AQP4 deletion in mice is associated with improved outcomes in global cerebral ischemia produced by transient carotid artery occlusion, and focal cerebral ischemia produced by permanent middle cerebral artery occlusion (MCAO). Here, we investigated the consequences of 1-h transient MCAO produced by intraluminal suture blockade followed by 23 h of reperfusion. In nine AQP4(+/+) and nine AQP4(-/-) mice, infarct volume was significantly reduced by an average of 39 ± 4% at 24h in AQP4(-/-) mice, cerebral hemispheric edema was reduced by 23 ± 3%, and Evans Blue extravasation was reduced by 31 ± 2% (mean ± SEM). Diffusion-weighted magnetic resonance imaging showed greatest reduction in apparent diffusion coefficient around the occlusion site after reperfusion, with remarkably lesser reduction in AQP4(-/-) mice. The reduced infarct volume in AQP4(-/-) mice following transient MCAO supports the potential utility of therapeutic AQP4 inhibition in stroke.

  8. Electroacupuncture Ameliorates Cerebral Ischemia-Reperfusion Injury by Regulation of Autophagy and Apoptosis

    Science.gov (United States)

    Shu, Shi; Li, Chun-Ming; You, Yan-Li; Qian, Xiao-Lu

    2016-01-01

    Background. The therapeutic mechanisms of cerebral ischemia treatment by acupuncture are yet not well addressed. Objective. We investigated the effects of electroacupuncture (EA) at GV26 observing the expression of autophagy-related proteins Beclin-1 and LC3B and proportion of apoptotic cells and Bcl-2 positive cells in MCAO/R model rats. Methods. Sprague-Dawley (SD) male rats were randomly assigned to 7 groups: model groups (M6h, M24h, and M72h), EA treatment groups (T6h, T24h, and T72h), and sham operation group (S). Neurological deficit and cerebral infarction volume were measured to assess the improvement effect, while the expression of Beclin-1 and LC3B and proportion of Tunel-positive and Bcl-2 positive cells were examined to explore EA effect on autophagy and apoptosis. Results. EA significantly decreased neurological deficit scores and the volume of cerebral infarction. Beclin-1 was significantly decreased in T24h, while LC3B-II/LC3B-I ratio markedly reduced in 6th hour. EA groups markedly reduced the number of Tunel positive cells, especially in T24h. Meanwhile, the number of Bcl-2 positive cells obviously increased after EA treatment, especially in T6h and T24h. Conclusions. The alleviation of inadequate autophagy and apoptosis may be a key mechanism involved in the reflex regulation of EA at GV26 to treat cerebral ischemia.

  9. Ginger pharmacopuncture improves cognitive impairment and oxidative stress following cerebral ischemia.

    Science.gov (United States)

    Jittiwat, Jinatta; Wattanathorn, Jintanaporn

    2012-12-01

    Recent findings have demonstrated that acupuncture and ginger can each improve memory impairment following cerebral ischemia. We hypothesized that ginger pharmacopuncture, a combination of these two treatments, could increase the beneficial effects. Due to the limitation of supporting evidence, we aimed to determine whether ginger pharmacopuncture could improve cognitive function and oxidative stress following cerebral ischemia. Male Wistar rats were induced by right middle cerebral artery occlusion (Rt. MCAO) and subjected to either acupuncture or ginger pharmacopuncture once daily over a period of 14 days after Rt. MCAO. Cognitive function was determined every 7 days, using escape latency and retention time as indices, and the oxidative stress status of the rats was determined at the end of the study. Rats subjected either to acupuncture or to ginger pharmacopuncture at GV20 demonstrated enhanced spatial memory, and the activities of catalase and glutathione peroxidase in both cerebral cortex and hippocampus were improved. Elevation of superoxide dismutase activity was observed only in the hippocampus. Cognitive enhancement was observed sooner with ginger pharmacopuncture than with acupuncture. The cognitive enhancing effect of acupuncture and ginger pharmacopuncture is likely to be at least partially attributable to decreased oxidative stress. However, other mechanisms may also be involved, and this requires further study.

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Ning-qun Wang

    2015-01-01

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

  12. 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.

  13. 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.

  14. Establishment of a rhesus monkey model of middle cerebral artery ischemia and reperfusion using a microcatheter embolization method

    Institute of Scientific and Technical Information of China (English)

    Jie Yang; Xiaoqi Huang; Hongxia Li; Li Wang; Jingqiu Cheng; Jian Guo; Hongbo Zheng; Muke Zhou; Li He; Wenying Cao; Li Xiao; Jiachuan Duan; Qiyong Gong

    2010-01-01

    Nonhuman primates are closest to humans in terms of lineage,and middle cerebral artery ischemia/reperfusion responses of nonhuman primates are most similar to ischemic stroke in humans.Therefore,nonhuman primates could be utilized to simulate the process of ischemic stroke in the human.Few studies,however,have reported the use of endovascular technology to establish a rhesus monkey stroke model.In the present study,seven adult,male,rhesus monkeys were selected and,following anesthesia,a microcatheter was inserted into one side of the middle cerebral artery via the femoral artery to block blood flow,thereby resulting in middle cerebral artery occlusion.After 2 hours,the microcatheter was withdrawn to restore the middle cerebral artery blood flow and to establish ischemia/reperfusion.Results from angiography and magnetic resonance angiography confirmed occlusion and reopening of the middle cerebral artery.Magnetic resonance imaging revealed the existence of ischemic brain lesions,and neurological examination showed sustained functional deficits following surgery.The rhesus monkey middle cerebral artery ischemia/reperfusion models established by microcatheter embolization had the advantage of non—craniotomy invasion and reproducibility.The scope and degree of ischemic damage using this model was controllable.Therefore,this nonhuman primate model is an ideal model for cerebral ischemia and reperfusion.

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

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    Linlin Li; Shilei Wang; Haihong Luan

    2011-01-01

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

  16. Neuronal differentiation of adipose-derived stem cells and their transplantation for cerebral ischemia

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    Guoping Tian; Xiaoguang Luo; Jin Zhou; Jinge Wang; Bing Xu; Li Li; Feng Zhu; Jian Han; Jianping Li; Siyang Zhang

    2012-01-01

    OBJECTIVE: To review published data on the biological characteristics, differentiation and applications of adipose-derived stem cells in ischemic diseases.DATA RETRIEVAL: A computer-based online search of reports published from January 2005 to June 2012 related to the development of adipose-derived stem cells and their transplantation for treatment of cerebral ischemia was performed in Web of Science using the key words"adipose-derived stem cells", "neural-like cells", "transplantation", "stroke", and "cerebral ischemia". SELECTION CRITERIA: The documents associated with the development of adipose-derived stem cells and their transplantation for treatment of cerebral ischemia were selected, and those published in the last 3-5 years or in authoritative journals were preferred in the same field. Totally 89 articles were obtained in the initial retrieval, of which 53 were chosen based on the inclusion criteria. MAIN OUTCOME MEASURES: Biological characteristics and induced differentiation ofadipose-derived stem cells and cell transplantation for disease treatment as well as the underlying mechanism of clinical application. RESULTS: The advantages of adipose-derived stem cells include their ease of procurement, wide availability, rapid expansion, low tumorigenesis, low immunogenicity, and absence of ethical constraints. Preclinical experiments have demonstrated that transplanted adipose-derived stem cells can improve neurological functions, reduce small regions of cerebral infarction, promote angiogenesis, and express neuron-specific markers. The improvement of neurological functions was demonstrated in experiments using different methods and time courses of adipose-derived stem cell transplantation, but the mechanisms remain unclear.CONCLUSION: Further research into the treatment of ischemic disease by adipose-derived stem cell transplantation is needed to determine their mechanism of action.

  17. [Clinico-epidemiological characteristics of transient cerebral ischemia in the region of the Ukrainian Carpathian Mountains].

    Science.gov (United States)

    Buletsa, B A; Lupich, P P; Litvinova, L A

    1991-01-01

    Altogether 225 patients with transitory derangements of cerebral circulation (TDCC) underwent clinico-laboratory examinations. Arterial hypertension and cerebral atherosclerosis turned out to be among most frequently occurring factors of TDCC. The provoking factors included psychoemotional stress and drops of barometric pressure. The course and outcome of TDCC were greatly affected by an increase in blood concentration of catecholamines and thyroid hormones. The high concentration of triiodothyronine in the blood contributed to the development of cerebral stroke.

  18. 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.

  19. 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.

  20. Neuroprotective effects of Schisandrin B against transient focal cerebral ischemia in Sprague-Dawley rats.

    Science.gov (United States)

    Lee, Tae Hwa; Jung, Chang Hwa; Lee, Dae-Hee

    2012-12-01

    Fruits of Schisandra have been traditionally used in East Asia for the treatment of dyspnea, cough, dysentery, insomnia, tonic-clonic seizures, and amnesia. Schisandrin B, a dibenzocyclooctadiene derivative isolated from Fructus Schisandrae, has been shown to produce antioxidant effect on rodent liver and heart. In the present study, we investigated the neuroprotective effects of Schisandrin B, a constituent drug of the fruit of Schisandra, against focal cerebral ischemia in rats. Schisandrin B (10, 30 mg/kg, i.p.) was twice administered 30 min before the onset of ischemia and 2h after reperfusion. Schisandrin B 10 and 30 mg/kg treated groups showed infarct volumes reduced by 25.7% and 53.4%, respectively, 2h after occlusion. Also, Schisandrin B treated animal treatment abrogated protein expression of TNF-α and IL-1β and degradation of MMP-2 and MMP-9 in ischemic hemispheres. These results suggest that Schisandrin B treatment provides a neuroprotective effect to rats after transient focal cerebral ischemia by inhibiting inflammation and by protecting against metalloproteinase degradation.

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

    Institute of Scientific and Technical Information of China (English)

    刘新峰; 金泳清; 陈光辉

    1996-01-01

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

  2. 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.

  3. Protective Effect Of Bosentan In Experimental Cerebral Ischemia-Reperfusion Injury

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    Eser Ataş

    2013-02-01

    Full Text Available OBJECTIVE: In cerebral ischemia, there are many factors that start the events leading to cell death. These factors contain free radical production, excitotoxicity, sodium and calcium flow disruption, enzymatic changes, stimulation of the inflamatuar process, the activation of platelets and leukocytes, delayed coagulation, endothelial dysfunction and endothelin (ET release. Bosentan is the competitive antagonist of endothelin receptors; ETA and ETB. The aim of this study is to determine whether the protective effects of bosentan in experimental cerebral ischemia reperfusion injury. MATERIAL and METHODS: In this study, after ischemia-reperfusion procedure, bosentan molecule was regularly given to rats for 5 days. The brain tissues of decapitated rats were histopathologically examined. The levels of oxidant and antioxidant were determined in these brain tissues. RESULTS: It was observed that antioxidant levels and histopathological examinations were in rats given bosentan better than control group rats. CONCLUSION: In conclusion, this study has showed that bosentan may be an agent which could reduce negative effects resulting from neuronal death associated with ischemic stroke.

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

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    Awooda Hiba A

    2013-01-01

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

  5. Progress in the Study of Acupuncture in Regulating Post-Cerebral Ischemia/Reperfusion Cell-Apoptosis Related Gene Expression

    Institute of Scientific and Technical Information of China (English)

    卜渊; 耿德勤; 曾因明

    2003-01-01

    @@ Cerebralvascular disease has already become one of the serious illnesses that threatens human health. Along with the development of medicine, although the therapeutic method harvested huge progress, currently ideal therapeutic methods are lacking. The conventional acupuncture has definite therapeutic effect on cerebropathy. Clinical practice and various animal experiments confirmed that acupuncture could alleviate the pathologic damage after cerebral ischemic injury and promote the nerve function recovery. Past studies showed that the role of acupuncture in treating cerebral ischemia is realized through alleviating post-ischemic neuron necrosis, while recent study discovered that acupuncture has inhibitory effect on post-ischemia induced neuronal necrosis(1), which brought the mechanism of acupuncture in treating cerebral ischemia from the biochemical and metabolical level to the molecular biologic level. The studies revealed that after cerebral ischemia, many genes were induced to express themselves, protein product they coded directly or indirectly participated in the regulation of post-cerebral ischemia apoptosis of neuron, some promoting the apoptosis, while others inhibiting apoptosis with some of the function still unclear. The anti-apoptotic effect of acupuncture is accomplished through regulating the relevant apoptotic gene expression(2), and now it is reviewed as follows:

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

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    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.

  7. PUMA is invovled in ischemia/reperfusion-induced apoptosis of mouse cerebral astrocytes.

    Science.gov (United States)

    Chen, H; Tian, M; Jin, L; Jia, H; Jin, Y

    2015-01-22

    PUMA (p53-upregulated modulator of apoptosis), a BH3-only member of the Bcl-2 protein family, is required for p53-dependent and p53-independent forms of apoptosis. PUMA has been invovled in the onset and progress of several diseases, including cancer, acquired immunodeficiency syndrome, and ischemic brain disease. Although many studies have shown that ischemia and reperfusion (I/R) can induce the apoptosis of astrocytes, the role of PUMA in I/R-mediated apoptosis of cerebral astrocyte apoptosis remains unclear. To mimic in vivo I/R conditions, primary mouse cerebral astrocytes were incubated in a combinational cultural condition of oxygen, glucose, and serum deprivation (OSGD) for 1 h followed by reperfusion (OSGD/R). Cell death determination assays and cell viability assays indicated that OSGD and OSGD/R induce the apoptosis of primary cerebral astrocytes. The expression of PUMA was significantly elevated in primary cerebral astrocytes during OSGD/R. Moreover, targeted down-regulation of PUMA by siRNA transfection significantly decreased the OSGD/R-induced apoptosis of primary cerebral astrocytes. We also found that OSGD and OSGD/R triggered the release of cytochrome c in astrocytes, indicating the dependence on a mitochondrial apoptotic pathway. Reactive oxygen species (ROS) was extremely generated during OSGD and OSGD/R, and the elimination of ROS by treated with N-acetyl-L-cysteine (NAC) remarkably inhibited the expression of PUMA and the apoptosis of primary cerebral astrocytes. The activation of Caspase 3 and Caspase 9 was extremely elevated in primary cerebral astrocytes during OSGD. In addition, we found that knockdown of PUMA led to the depressed expression of Bax, cleaved caspase-9 and caspase-3 during OSGD/R. These results indicate that PUMA is invovled in the apoptosis of cerebral astrocytes upon I/R injury.

  8. AQP4 expression and its correlation with the Lac and NAA using proton magnetic resonance spectroscopy after rat cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    ZHOU Ren-lan; XIE Peng

    2006-01-01

    Objective: To determine whether AQP4 expression is associated with lactate (Lac) and Nacetyl aspartate (NAA) and with apparent diffusion coefficient (ADC) abnormality after rat cerebral ischemia. Methods: The time courses of ADC and lactate and NAA assessed by proton magnetic resonance spectroscopy (1HMRS) were investigated at the time point of 6 h, and 1, 3, 7 d after rat cerebral ischemia induced by middle cerebral artery occlusion. Expression of AQP4 mRNA and protein were measured using RT-PCR and Western blot analysis respectively. Results: Significant reductions of NAA concentration and increases of lactate concentration were found after rat cerebral ischemia. The expressions of AQP4 mRNA and protein were increased at 6 h, and reached the peak at 1-3 d, then began to decrease at 7 d after rat cerebral ischemia. The expression of AQP4 was significantly correlated with NAA (rRT =-0.856, rw =-0. 927, P<0. 01), and with lactate (rW=0. 473, rRT=0. 413, P<0. 05), and with ADC values during the period of 1-7 d after rat cerebral ischemia (rW=0. 984, rRT= -0. 925, P<0.05). In addition, correlations between Lac and the ADC values(r=-0. 677, P<0. 05)and between NAA and ADC values during the period of 1-7 d after rat cerebral ischemia (r= 0. 909, P<0.05) were also observed. Conclusion: The data suggest that AQP4 is involved in the transport of water when brain edema is formed and cell membrane integrity is lost.

  9. Preconditioning of intravenous parecoxib attenuates focal cerebral ischemia/reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    WANG Na; GUO Qu-lian; YE Zhi; XIA Ping-ping; WANG E; YUAN Ya-jing

    2011-01-01

    Background Several studies suggest that oyclooxygenase-2 (COX-2) contributes to the delayed progression of ischemic brain damage. This study was designed to investigate whether COX-2 inhibition with parecoxib reduces focal cerebral ischemia/reperfusion injury in rats.Methods Ninety male Sprague-Dawley rats were randomly assigned to three groups: the sham group, ischemia/reperfusion (I/R) group and parecoxib group. The parecoxib group received 4 mg/kg of parecoxib intravenously via the vena dorsalis penis 15 minutes before ischemia and again at 12 hours after ischemia. The neurological deficit scores (NDSs) were evaluated at 24 and 72 hours after reperfusion. The rats then were euthanized. Brains were removed and processed for hematoxylin and eosin staining, Nissl staining, and measurements of high mobility group Box 1 protein (HMGB1) and tumor necrosis factor-a (TNF-α) levels. Infarct volume was assessed with 2,3,5-triphenyltetrazolium chloride (TTC) staining.Results The rats in the I/R group had lower NDSs (P <0.05), larger infarct volume (P <0.05), lower HMGB1 levels (P<0.05), and higher TNF-α levels (P<0.05) compared with those in the sham group. Parecoxib administration significantly improved NDSs, reduced infarct volume, and decreased HMGB1 and TNF-α levels (P <0.05).Conclusions Pretreatment with intravenous parecoxib was neuroprotective. Its effects may be associated with the attenuation of inflammatory reaction and the inhibition of inflammatory mediators.

  10. Membrane attack complex inhibitor CD59a protects against focal cerebral ischemia in mice

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    Nietfeld Wilfried

    2010-03-01

    Full Text Available Abstract Background The complement system is a crucial mediator of inflammation and cell lysis after cerebral ischemia. However, there is little information about the exact contribution of the membrane attack complex (MAC and its inhibitor-protein CD59. Methods Transient focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO in young male and female CD59a knockout and wild-type mice. Two models of MCAO were applied: 60 min MCAO and 48 h reperfusion, as well as 30 min MCAO and 72 h reperfusion. CD59a knockout animals were compared to wild-type animals in terms of infarct size, edema, neurological deficit, and cell death. Results and Discussion CD59a-deficiency in male mice caused significantly increased infarct volumes and brain swelling when compared to wild-type mice at 72 h after 30 min-occlusion time, whereas no significant difference was observed after 1 h-MCAO. Moreover, CD59a-deficient mice had impaired neurological function when compared to wild-type mice after 30 min MCAO. Conclusion We conclude that CD59a protects against ischemic brain damage, but depending on the gender and the stroke model used.

  11. Cerebral ischemia is exacerbated by extracellular nicotinamide phosphoribosyltransferase via a non-enzymatic mechanism.

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    Bing Zhao

    Full Text Available Intracellular nicotinamide phosphoribosyltransferase (iNAMPT in neuron has been known as a protective factor against cerebral ischemia through its enzymatic activity, but the role of central extracellular NAMPT (eNAMPT is not clear. Here we show that eNAMPT protein level was elevated in the ischemic rat brain after middle-cerebral-artery occlusion (MCAO and reperfusion, which can be traced to at least in part from blood circulation. Administration of recombinant NAMPT protein exacerbated MCAO-induced neuronal injury in rat brain, while exacerbated oxygen-glucose-deprivation (OGD induced neuronal injury only in neuron-glial mixed culture, but not in neuron culture. In the mixed culture, NAMPT protein promoted TNF-α release in a time- and concentration-dependent fashion, while TNF-α neutralizing antibody protected OGD-induced, NAMPT-enhanced neuronal injury. Importantly, H247A mutant of NAMPT with essentially no enzymatic activity exerted similar effects on ischemic neuronal injury and TNF-α release as the wild type protein. Thus, eNAMPT is an injurious and inflammatory factor in cerebral ischemia and aggravates ischemic neuronal injury by triggering TNF-α release from glia cells, via a mechanism not related to NAMPT enzymatic activity.

  12. Clinical features of development of chronic cerebral ischemia against background of pronounced decrease of cognitive functions

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    Zalisna Yu.D.

    2013-12-01

    Full Text Available The paper presents the results of analyses of cognitive failure in chronic cerebral ischemia (CCI with lesion of deep divisions of the brain white matter and basal ganglia, leading to disruption of communication of frontal and subcortical brain structures (the phenomenon of separation. Mechanism of separation primarily is associated with hypertension, which leads to secondary changes of the vascular wall microvasculature. For cerebral vascular insufficiency and for diseases, primarily involving basal ganglia, intellectual inertia, bradyphreniya and decreased concentration are more common. According to studies, chronic cerebral ischemia (CCI is recorded in 20-30% of people of working age. The main etiological forms of CCI are considered to be hypertensive, atherosclerotic and mixed. For CCI of the second stage formation of neurological syndromes (pseu¬dobulbar, pyramidal, extrapyramidal, atactic, increased cognitive disorder that causes temporary or permanent disa¬bility of patients, reduction of their quality of life are characteristic. The aim of the study was to determine the cha¬racteristics of cognitive impairment in patients with CCI (hypertonic and mixed origin and their relationship to clinical and neurological manifestations of the disease. Based on the data obtained through clinical examination and neu¬ropsychological testing, marked processes of attention exhaustion and a higher risk of progression of cognitive impairment in the group with a mixed form (hypertension and atherosclerotic were revealed.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-07-18

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

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

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    Anand Kumar Pandey

    2015-01-01

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

  15. Therapeutic time window for the neuroprotective effects of NGF when administered after focal cerebral ischemia.

    Science.gov (United States)

    Yang, Ji-Ping; Liu, Huai-Jun; Yang, Hua; Feng, Ping-Yong

    2011-06-01

    In the present study, we evaluated the neuroprotection time window for nerve growth factor (NGF) after ischemia/reperfusion brain injury in rabbits as related to this anti-apoptosis mechanism. Male New Zealand rabbits were subjected to 2 h of middle cerebral artery occlusion (MCAO), followed by 70 h of reperfusion. NGF was administered after injury to evaluate the time window. Neurological deficits, infarct volume, neural cell apoptosis and expressions of caspase-3 and Bcl-2 were measured. Compared to saline-treated control, NGF treatment at 2, 3 and 5 h after MCAO significantly reduced infarct volume, neural cell apoptosis and expression of caspase-3 (P NGF provides an extended time window of up to 5 h after ischemia/reperfusion brain injury, in part by attenuating the apoptosis.

  16. E2-25K SUMOylation inhibits proteasome for cell death during cerebral ischemia/reperfusion

    Science.gov (United States)

    Jeong, Eun Il; Chung, Hae Won; Lee, Won Jea; Kim, Seo-Hyun; Kim, Hyunjoo; Choi, Seon-Guk; Jung, Yong-Keun

    2016-01-01

    Cerebral ischemia/reperfusion (I/R) causes brain damage accompanied by ubiquitin accumulation and impairment of proteasome activity. In this study, we report that E2-25K, an E2-conjugating enzyme, is SUMOylated during oxidative stress and regulates cerebral I/R-induced damage. Knockdown of E2-25K expression protects against oxygen/glucose deprivation and reoxygenation (OGD/R)-induced neuronal cell death, whereas ectopic expression of E2-25K stimulates it. Compared with the control mice, cerebral infarction lesions and behavioral/neurological disorders are ameliorated in E2-25K knockout mice during middle cerebral artery occlusion and reperfusion. In particular, E2-25K is SUMOylated at Lys14 under oxidative stress, OGD/R and I/R to prompt cell death. Further, E2-25K downregulates the proteasome subunit S5a to impair proteasome complex and thus restrain proteasome activity under oxidative stress. This proteasome inhibitory activity of E2-25K is dependent on its SUMOylation. These results suggest that E2-25K has a crucial role in oxidative stress and cerebral I/R-induced damage through inhibiting proteasome via its SUMOylation. PMID:28032866

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

    Directory of Open Access Journals (Sweden)

    Alexander G. Kruglov, PhD, ScD

    2012-06-01

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

  18. Application of Mathematical Modelling as a Tool to Analyze the EEG Signals in Rat Model of Focal Cerebral Ischemia

    Science.gov (United States)

    Paul, S.; Bhattacharya, P.; Pandey, A. K.; Patnaik, R.

    2014-01-01

    The present paper envisages the application of mathematical modelling with the autoregressive (AR) model method as a tool to analyze electroencephalogram data in rat subjects of transient focal cerebral ischemia. This modelling method was used to determine the frequencies and characteristic changes in brain waveforms which occur as a result of disorders or fluctuating physiological states. This method of analysis was utilized to ensure actual correlation of the different mathematical paradigms. The EEG data was obtained from different regions of the rat brain and was modelled by AR method in a MATLAB platform. AR modelling was utilized to study the long-term functional outcomes of a stroke and also is preferable for EEG signal analysis because the signals consist of discrete frequency intervals. Modern spectral analysis, namely AR spectrum analysis, was used to correlate the conditional and prevalent changes in brain function in response to a stroke.

  19. Dynamics of cerebral tissue injury and perfusion after temporary hypoxia-ischemia in the rat - Evidence for region-specific sensitivity and delayed damage

    NARCIS (Netherlands)

    Dijkhuizen, RM; Knollema, S; van der Worp, H. Bart; Ter Horst, GJ; De Wildt, DJ; van der Sprenkel, JWB; Tulleken, KAF; Nicolay, K

    1998-01-01

    Background and Purpose-Selective regional sensitivity and delayed damage in cerebral ischemia provide opportunities for directed and late therapy for stroke. Our aim was to characterize the spatial and temporal profile of ischemia-induced changes in cerebral perfusion and tissue status, with the use

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

    DEFF Research Database (Denmark)

    Lassen, N A

    1978-01-01

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

  1. Ultrastructural changes of rat cortical neurons following ligustrazine intervention for cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Hui Zhang; Jianfeng Dong; Qiuzhen Zhao; Wen Song; Aihua Bo

    2008-01-01

    BACKGROUND: Ligustrazine can reduce the production of free radicals and the content of malonaldehyde, and improve the enzymatic activity of adenosine-triphosphate in cerebral anoxia. It also can increase the expression of heat shock protein-70 and Bcl-2, thus alleviating brain tissue injury caused by cerebral ischemia/reperfusion. This study aimed to address the question of whether ligustrazine can protect the membrane structure of neurons.OBJECTIVE: To establish rat models of cerebral ischemia/reperfusion, observe the membrane structure and main organelles of neurons with electron microscope after ligustrazine intervention, and to analyze the dose-dependent effects of ligustrazine on neuronal changes.DESIGN: Arandomized controlled study.SETTING: Department of Anatomy Research and Electron Microscopy, Hebei North University. MATERIALS: Forty Wistar rats of SPS grade, weighing 180–250 g and equal proportion of female and male, were provided by Hebei Medical University Animal Center (No. 060126). The ligustrazine injection (40 g/L, No. 05012) was produced by Beijing Yongkang Yaoye. LKB4 Ultramicrotome was purchased from LKB Company in Sweden. JEM100CXII electron microscope was purchased from JEOL in Japan.METHODS: The experiment was performed in the Laboratory of the Department of Anatomy and Electron Microscopy, Hebei North University from June to August 2006. ① Wistar rats were allowed to adapt for 3 days, and were then randomly divided into four groups, according to the numeration table method: normal group, model group, low-dose ligustrazine group, and high-dose ligustrazine group. There were 10 rats in each group. ②Rats in the model group, low-dose ligustrazine group, and high-dose ligustrazine group un-derwent cerebral ischemia/reperfusion model, according to Bannister's method. The carotid artery was opened for reperfusion after 90 minutes of cerebral ischemia. Samples were collected from the cerebral cor-tex after 24 hours. Animals from the ligustrazine

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

  3. Insulin Reduces Cerebral Ischemia/Reperfusion Injury in the Hippocampus of Diabetic Rats

    OpenAIRE

    Collino, Massimo; Aragno, Manuela; Castiglia, Sara; Tomasinelli, Chiara; Thiemermann, Christoph; Boccuzzi, Giuseppe; Fantozzi, Roberto

    2009-01-01

    OBJECTIVE—There is evidence that insulin reduces brain injury evoked by ischemia/reperfusion (I/R). However, the molecular mechanisms underlying the protective effects of insulin remain unknown. Insulin is a well-known inhibitor of glycogen synthase kinase-3β (GSK-3β). Here, we investigate the role of GSK-3β inhibition on I/R-induced cerebral injury in a rat model of insulinopenic diabetes. RESEARCH DESIGN AND METHODS—Rats with streptozotocin-induced diabetes were subjected to 30-min occlusio...

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

    Institute of Scientific and Technical Information of China (English)

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

    2016-01-01

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

  5. 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.

  6. 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

  7. Does Piroxicam really protect ischemic neurons and influence neuronal firing in cerebral ischemia? An exploration towards therapeutics.

    Science.gov (United States)

    Bhattacharya, Pallab; Pandey, Anand Kumar; Paul, Sudip; Patnaik, Ranjana

    2013-09-01

    Cerebral ischemia is still one of the most confusing and enigmatic neurological disorders with least understood injuries. The EEG measures have been traditionally used to detect residual neural dysfunctions after cerebral ischemia although having several shortcomings, yielding controversial and inconsistent results. It is feasible to hypothesize that advanced EEG research can overcome these shortcomings and provide more clear information regarding the long lasting neural impairment in the subjects suffered from brain stroke. To our understanding, EEG power spectrum density measures can significantly contribute towards intervening drug administered diseased model and give us correct status of neuronal firing after an insult. On the basis of our findings we hypothesize that Piroxicam, a non-steroidal anti-inflammatory drug (NSAID) can protect neurons and improves neuronal firing after ischemia/reperfusion injury in animal model of focal cerebral ischemia. This is the first ever finding which advocates the role of Piroxicam, a NSAID in neuronal firing apart from its other neuroprotective roles. Thus, we consider the possibility of modulation of neuronal firing as a therapeutic strategy to help prevent neuronal dysfunctions in cerebral ischemia.

  8. [Cerebrospinal fluid sorption in the system of complex treatment of chronic cerebral ischemia].

    Science.gov (United States)

    Shulëv, Iu A; Starchenko, A A; Bikmullin, V N; Dorosh, K V; Martynov, B V

    1997-01-01

    The cerebrospinal fluid was investigated in 16 patients with chronic cerebral ischemia. Reactions of the local immune system of the liquor was shown to change by the autoimmune type. Medical efficiency of cerebrospinal fluid sorption was proved and it can be considered a method of detoxication aimed at breaking the pathogenetic chain: formation of abundance of the autoantibodies--increased amount of the circulating immunocomplexes--damage of the cell membranes--discharge of deep antigens--appearance of a new generation of autoantibodies. Using cerebrospinal fluid sorption as a test for the detection of latent functional reserves of the neurons not changed irreversibly in the zone of reduced perfusion of the cerebral tissue is thought to be a perspective method.

  9. Repeated episodes of focal cerebral ischemia in a patient with mitral valve prolapse and migraine headache

    Directory of Open Access Journals (Sweden)

    Raičević Ranko

    2002-01-01

    Full Text Available Migraine is episodic, paroxysmal disorder where the headache represents the central symptom and is followed with different combinations of neurological gastrointestinal and vegetative changes. Not until the diagnostic procedures were developed, ischemic lesions were verified even in the patients with ordinary migraine. This is a report of a patient with migraine headache followed twice by verified episodes of temporary ischemic attacks and verified focal ischemic lesion of cerebral parenchyma. The mitral valve prolapse was also detected. This all imposed the administration of combined prophylactic antimigrainous and anticoagulant therapy as an imperative because of the risk of the development of repeated ischemia of cerebral tissue. This association also confirmed an opinion that migraine is a wider disorder with the dominant dysfunction of limbic system.

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

    DEFF Research Database (Denmark)

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

    2002-01-01

    We aimed at investigating a new model of mild focal cerebral ischemia in rats with repeated, noninvasive magnetic resonance scanning combined with histology. Magnetic resonance imaging yielded information about infarct development enabling us to test the putative growth of the infarct over time....... The effect of local temperature at the occlusion site in this model was furthermore tested. Thirty-three Wistar rats were subjected to 30 min of simultaneous common carotid artery and distal middle cerebral artery occlusion or sham treatment. Animals were magnetic resonance-scanned repeatedly between day one...... and day 14 after surgery, then sacrificed, and paraffin brain sections stained. All animals scanned 24 h after reperfusion showed an area of edema in the affected cortex, which later was identified as an infarct. Animals with a temperature of 33.9 +/- 1.5 degrees C at the MCA site (hypothermic) showed...

  11. 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.

  12. Changes in corticocerebral morphology in a rat model of focal cerebral ischemia/reperfusion injury following"Xingnao Kaiqiao" acupuncture

    Institute of Scientific and Technical Information of China (English)

    Shu Wang; Zhankui Wang; Guangxia Ni

    2008-01-01

    BACKGROUND: Cerebral ischemia/reperfusion injury has been shown to induce inflammatory reactions,including white blood cell activation and adhesion molecule expression. These reactions often lead to aggravated neuronal injury.OBJECTIVE: To observe corticocerebral pathology, as well as ultrastructural changes, in a rat model of focal cerebral ischemia/reperfusion injury through optical and electron microscopy, and to investigate interventional effects of "Xingnao Kaiqiao" acupuncture (a brain-activating and orifice-opening acupuncture method).DESIGN, TIME AND SETTING: A randomized, controlled, neuropathology, animal experiment was performed at the Laboratory of Molecular Biology, First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine between April and June 2004.MATERIALS: A total of 50 healthy, male, Wistar rats were randomized into 5 groups, with 10 rats per group: control, sham-operated, model, non-acupoint, and "Xingnao Kaiqiao". Transmission electron microscope (TEM 400ST) was provided by Philips, Netherlands. Electro-acupuncture treatment apparatus (KWD-8082) was provided by Changzhou Wujin Great Wall Medical Instrument, China.METHODS: Focal cerebral ischemia/reperfusion injury was induced by occlusion of the middle cerebral artery in the model, non-acupoint, and "Xingnao Kaiqiao" groups. Rats from the control group did not undergo any treatment. The sham-operated group received identical experimental procedures as the model group, except that the nylon suture was not inserted into the right internal carotid artery. At 1, 3, 6, and 12 hours following focal cerebral ischemia/dreperfusion injury induction, rats from the Xingnao Kaiqiao group underwent l-minute acupuncture at the bilateral "Neiguan" (PC 6) acupoint, using a reducing method of lifting-thrusting and twirling-rotating. Subsequently, the rats were subjected to acupuncture at the "Renzhong" (DU26) acupoint 10 times by a heavy bird-pecking method. The non-acupoint group received

  13. 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.

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

    Science.gov (United States)

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

    2016-05-01

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

  15. Effects of transection of cervical sympathetic trunk on cerebral infarct volume and oxygen free radical levels in rats with focal cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Liangzhi Xiong; Yongxia Shi; Feng Xiao; Qingxiu Wang

    2008-01-01

    BACKGROUND: Stellate ganglion block (SGB) plays a protective role on the brain, but the precise mechanism of action is not clear.OBJECTIVE: To simulate SGB by transection of the cervical sympathetic trunk (TCST) and to investigate the TCST effects on changes in cerebral infarct volume and oxygen free radical levels in rats with focal cerebral ischemia/reperfusion injury.DESIGN, TIME AND SETTING: A complete randomized control animal experiment was performed at the Institute of Neurological Diseases of Taihe Hospital, Yunyang Medical College from February to December 2005.MATERIALS: A total of 101 healthy Wistar rats, weighing 280-320g, of both genders, aged 17-18 weeks, were used in this study. 2,3,5-triphenyltetrazolium chloride (TTC) was purchased from Changsha Hongyuan Biological Company. Superoxide dismutase (SOD), malondialdehyde (MDA) and nitric oxide (NO) assay kits were provided by Nanjing Jiancheng Bioengineering Institute.METHODS: Rats were randomly divided into a TCST group, a model group and a sham operation group. Successful models were included in the final analysis, with at least 20 rats in each group. After TCST, rat models of focal cerebral ischemia/reperfusion injury were established in the TCST group by receiving middle cerebral artery occlusion (MCAO) by the intraluminal suture method for 2 hours, followed by 24 hours of reperfusion. Rat models of focal cerebral ischemia/reperfusion injury were made in the model group. Rats in the sham operation group underwent experimental procedures as for the model group, threading depth of 10mm, and middle cerebral artery was not ligated.MAIN OUTCOME MEASURES: Brain tissue sections of ten rats from each group were used to measure cerebral infarct volume by TTC staining. Brain tissue homogenate of another ten rats from each group was used to detect SOD activities, MDA contents and NO levels. Rat neurological function was assessed by neurobehavioral measures.RESULTS: Cerebral infarct volume was bigger in the

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    BACKGROUND: Global cerebral ischemia following cardiac arrest is associated with increased cerebral vasoconstriction and decreased cerebral blood flow, contributing to delayed neuronal cell death and neurological detriments in affected patients. We hypothesize that upregulation of contractile ETB...... and 5-HT1B receptors, previously demonstrated in cerebral arteries after experimental global ischemia, are a key mechanism behind insufficient perfusion of the post-ischemic brain, proposing blockade of this receptor upregulation as a novel target for prevention of cerebral hypoperfusion and delayed...... neuronal cell death after global cerebral ischemia. The aim was to characterize the time-course of receptor upregulation and associated neuronal damage after global ischemia and investigate whether treatment with the MEK1/2 inhibitor U0126 can prevent cerebrovascular receptor upregulation and thereby...

  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. Optical coherence tomography reveals in vivo cortical structures of adult rats in response to cerebral ischemia injury

    Science.gov (United States)

    Ni, Yi-rong; Guo, Zhou-yi; Shu, So-yun; Bao, Xin-min

    2008-12-01

    Optical coherence tomography(OCT) is a high resolution imaging technique which uses light to directly image living tissue. we investigate the potential use of OCT for structural imaging of the ischemia injury mammalian cerebral cortex. And we examine models of middle cerebral artery occlusion (MCAO) in rats in vivo using OCT. In particular, we show that OCT can perform in vivo detection of cortex and differentiate normal and abnormal cortical anatomy. This OCT system in this study provided an axial resolution of 10~15μ m, the transverse resolution of the system is about 25 μm. OCT can provide cross-sectional images of cortical of adult rats in response to cerebral ischemia injury.We conclude that OCT represents an exciting new approach to visualize, in real-time, pathological changes in the cerebral cortex structures and may offer a new tool for Possible neuroscience clinical applications.

  19. Early immature neuronal death initiates cerebral ischemia-induced neurogenesis in the dentate gyrus.

    Science.gov (United States)

    Kim, D H; Lee, H E; Kwon, K J; Park, S J; Heo, H; Lee, Y; Choi, J W; Shin, C Y; Ryu, J H

    2015-01-22

    Throughout adulthood, neurons are continuously replaced by new cells in the dentate gyrus (DG) of the hippocampus, and this neurogenesis is increased by various neuronal injuries including ischemic stroke and seizure. While several mechanisms of this injury-induced neurogenesis have been elucidated, the initiation factor remains unclear. Here, we investigated which signal(s) trigger(s) ischemia-induced cell proliferation and neurogenesis in the hippocampal DG region. We found that early apoptotic cell death of the immature neurons occurred in the DG region following transient forebrain ischemia/reperfusion in mice. Moreover, early immature neuronal death in the DG initiated transient forebrain ischemia/reperfusion-induced neurogenesis through glycogen synthase kinase-3β/β-catenin signaling, which was mediated by microglia-derived insulin-like growth factor-1 (IGF-1). Additionally, we observed that the blockade of immature neuronal cell death, early microglial activation, or IGF-1 signaling attenuated ischemia-induced neurogenesis. These results suggest that early immature neuronal cell death initiates ischemia-induced neurogenesis through microglial IGF-1 in mice.

  20. Neurogenesis after cerebral ischemia%脑缺血后神经发生

    Institute of Scientific and Technical Information of China (English)

    刘晓冬; 邓丽; 张拥波; 王得新

    2010-01-01

    脑缺血后神经发生是神经科学领域的研究热点之一.文章主要从脑缺血后神经发生的主要过程、调节因子、信号通路、微环境以及如何促进脑缺血后神经发生等方面阐述神经发生的研究进展,旨在为卒中后神经功能恢复提供新的治疗思路.%The neurogenesis after cerebral ischemia is one of the research hotspots in the field of neuroscience.This article mainly expounds the advances in research on neurogenesis from the main processes,regulatory factors,signal pathways and microenvironment as well as how to promote neurogenesis following cerebral ischemia.Our purpose is to provide new treatment ideas for the recovery of neurological function following stoke.

  1. Sequential development of reversible and irreversible neuronal damage following cerebral ischemia.

    Science.gov (United States)

    Petito, C K; Pulsinelli, W A

    1984-03-01

    The ultrastructure of reversibly injured cortical neurons and irreversibly injured striatal neurons was studied at 3, 15, 30, and 120 minutes (min) and 24 hours (h) following severe cerebral ischemia produced in rats by permanent occlusion of the vertebral arteries and 30 min occlusion of the carotid arteries. Animals meeting the established criterion of unresponsiveness had widespread neuronal death in the dorsolateral striatum, but no permanent damage in the paramedian cortex. Reversible mitochondrial swelling at three min was followed by dissociation of polyribosomes, decrease in rough endoplasmic reticulum (RER) profiles, and transformation of Golgi apparatus into large clusters of small vesicles without cisterns in both cortical and striatal neurons. Reaccumulation of RER was seen in cortical neurons by 30-120 min and all cortical neurons appeared normal at 24 h. In contrast, most striatal neurons developed dilatation of the Golgi vesicles by 120 min after reperfusion, followed by progressive cell shrinkage and ischemic cell change. Approximately 10-15% of striatal neurons contained cytoplasmic membranous whorls, some continuous with the plasma membrane. The results suggest that structural abnormalities in the Golgi apparatus and in plasma membranes may participate in functional changes critical to irreversible neuronal injury following cerebral ischemia.

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

  3. Pharmacological evaluation of glutamate transporter 1 (GLT-1) mediated neuroprotection following cerebral ischemia/reperfusion injury.

    Science.gov (United States)

    Verma, Rajkumar; Mishra, Vikas; Sasmal, Dinakar; Raghubir, Ram

    2010-07-25

    Recently glutamate transporters have emerged as a potential therapeutic target in a wide range of acute and chronic neurological disorders, owing to their novel mode of action. The modulation of GLT-1, a major glutamate transporter has been shown to exert neuroprotection in various models of ischemic injury and motoneuron degeneration. Therefore, an attempt was made to explore its neuroprotective potential in cerebral ischemia/reperfusion injury using ceftriaxone, a GLT-1 modulator. Pre-treatment with ceftriaxone (100mg/kg. i.v) for five days resulted in a significant reduction (Pceftriaxone-mediated increased glutamine synthetase activity by dihydrokainate (DHK), a GLT-1 specific inhibitor, confirms the specific effect of ceftriaxone on GLT-1 activity. In addition, ceftriaxone also induced a significant (P<0.01) increase in [(3)H]-glutamate uptake, mediated by GLT-1 in glial enriched preparation, as evidenced by use of DHK and DL-threo-beta-benzyloxyaspartate (DL-TBOA). Thus, the present study provides overwhelming evidence that modulation of GLT-1 protein expression and activity confers neuroprotection in cerebral ischemia/reperfusion injury.

  4. Evidence that Patent Foramen Ovale is not a Risk Factor for Cerebral Ischemia in the Elderly

    Science.gov (United States)

    Jones, Elizabeth F.; Calafiore, Paul; Donnan, Geoffrey A.; Tonkin, Andrew M.

    1994-01-01

    Patent foramen ovale (PFO) may be a risk factor for ischemic stroke in young patients. The aim of this study was to assess the importance of PFO in subjects with a wider age range using patient-control methodology. Transesophageal contrast echocardiography and carotid imaging were performed in 220 consecutive patients with cerebral ischemia (mean age 66 +/- 13 years) and in 202 community-based control subjects (mean age 64 +/- 11 years). Of patients with stroke, 35 (16%) had PFO compared with 31 control subjects (15%) (p = 0.98). Analysis of PFO prevalence by age did not show a significant difference between patients and control subjects in the age groups or equal to 70 years (12% vs 17%; p = 0.43). However, the group aged 450 years was relatively small (26 cases, 19 controls). No significant difference in PFO prevalence was detected between patients with cryptogenic stroke (20%), noncryptogenic stroke (14%), and control subjects (15%). These results suggest that PFO is not a risk factor for cerebral ischemia in subjects aged >50 years, which would have major implications for the investigation and management of stroke patients in this age group. Longitudinal studies are now required to assess the incidence of stroke in symptom free patients with PFO.

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  6. Suppression of inflammatory response by flurbiprofen following focal cerebral ischemia involves the NF-κB signaling pathway.

    Science.gov (United States)

    Sun, Bao-Zhu; Chen, Lin; Wu, Qi; Wang, Huan-Liang; Wei, Xin-Bing; Xiang, Yan-Xiao; Zhang, Xiu-Mei

    2014-01-01

    Some studies of animal models of middle cerebral artery occlusion indicate that inflammation plays a key role in the pathogenesis of cerebral ischemia and secondary damage. Flurbiprofen has been suggested to alleviate cerebral ischemia/reperfusion injury in both focal and global cerebral ischemia models, but the mechanisms underlying the protective action are still incompletely understood. In this study we want to investigate the protective effect of flurbiprofen after transient middle cerebral artery occlusion (MCAO) in rats and the role of the NF-κB signaling pathway on this neuroprotective effect. Male Wistar rats were subjected to transient middle cerebral artery occlusion for 2 h, followed by 24 h reperfusion. Flurbiprofen was administrated via tail-vein injection at the onset of reperfusion. HE staining and Immunohistochemistry were carried out to detect the morphological changes in ischemic penumbra cortex. The expression of inflammatory cytokines genes (IL-1β, IL-6 and TNF-α) and the levels of p-NF-κB (p65) in ischemic penumbra cortex were measured by RT-PCR and western blot. Administration of flurbiprofen at the doses of 5 mg/kg and 10 mg/kg significantly attenuated cerebral ischemia/reperfusion injury, as shown by a reduction in the morphological changes and inhibition of pro-inflammatory cytokine expression in ischemic penumbra cortex. Moreover, our findings further demonstrated that the inhibition of NF-κB activity was involved in the neuroprotective effect of flurbiprofen on inflammatory responses. Flurbiprofen protects against cerebral injury by reducing expression of inflammatory cytokines genes and this effect may be partly due to the inhibition of NF-κB signaling pathway.

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

    OpenAIRE

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

    2012-01-01

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

  8. Loss of endoplasmic reticulum Ca homeostasis:contribution to neuronal cell death during cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Ankur BODALIA; Hongbin LI; Michael F JACKSON

    2013-01-01

    The loss of Ca2+ homeostasis during cerebral ischemia is a hallmark of impending neuronal demise.Accordingly,considerable cellular resources are expended in maintaining low resting cytosolic levels of Ca2+.These include contributions by a host of proteins involved in the sequestration and transport of Ca2+,many of which are expressed within intracellular organelles,including lysosomes,mitochondria as well as the endoplasmic reticulum (ER).Ca2+ sequestration by the ER contributes to cytosolic Ca2+ dynamics and homeostasis.Furthermore,within the ER Ca2+ plays a central role in regulating a host of physiological processes.Conversely,impaired ER Ca2+ homeostasis is an important trigger of pathological processes.Here we review a growing body of evidence suggesting that ER dysfunction is an important factor contributing to neuronal injury and loss post-ischemia.Specifically,the contribution of the ER to cytosolic Ca2+ elevations during ischemia will be considered,as will the signalling cascades recruited as a consequence of disrupting ER homeostasis and function.

  9. 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.

  10. 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

    1992-01-01

    ," 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...... constant arterial carbon dioxide tension. In contrast, static exercise with a higher rate of perceived exertion [18 (13-20) vs. 15 (12-18) units; P less than 0.01] was associated with no significant change in Vmean. Muscle ischemia after exercise was not associated with an elevation in Vmean, and it did...

  11. The nitroxide antioxidant tempol is cerebroprotective against focal cerebral ischemia in spontaneously hypertensive rats.

    Science.gov (United States)

    Leker, R R; Teichner, A; Lavie, G; Shohami, E; Lamensdorf, I; Ovadia, H

    2002-08-01

    Free radicals appear to participate in the final common pathway of neuronal death in ischemia and may therefore be an adequate target for therapy. Tempol is a nitroxide antioxidant with proven protective efficacy in several animal models, including myocardial ischemia, that has not been previously tested in models of permanent cerebral ischemia. Spontaneously hypertensive rats underwent permanent middle cerebral artery occlusion (PMCAO). Following dose-response and time-window-finding experiments rats were given vehicle or tempol (50 mg/kg) subcutaneously 1 h after PMCAO (n = 10/group). Five animals in each group were evaluated with a motor scale 24 h after the infarct and were then sacrificed and the injury volume was measured. The remaining animals were examined daily with the motor scale and also with a Morris water maze test on days 26-30 after PMCAO and sacrificed on day 30. Motor scores at all time points examined were significantly better in the tempol-treated animals (P performance in the water maze test for performance on days 26-30 was noted in the tempol group compared with the vehicle-treated group (P volumes at days 1 and 30 were significantly reduced in the tempol group (9.83 +/- 1.05 vs 19.94 +/- 1.43% hemispheric volume, P = 0.0009, and 13.2 +/- 2.97 vs 24.4 +/- 2.38% hemispheric volume, P = 0.02, respectively). In conclusion, treatment with tempol led to significant motor and behavioral improvement and reduced injured tissue volumes both in the short and in the long term after stroke.

  12. Neuroprotective mechanisms of curcumin against cerebral ischemia-induced neuronal apoptosis and behavioral deficits.

    Science.gov (United States)

    Wang, Qun; Sun, Albert Y; Simonyi, Agnes; Jensen, Michael D; Shelat, Phullara B; Rottinghaus, George E; MacDonald, Ruth S; Miller, Dennis K; Lubahn, Dennis E; Weisman, Gary A; Sun, Grace Y

    2005-10-01

    Increased oxidative stress has been regarded as an important underlying cause for neuronal damage induced by cerebral ischemia/reperfusion (I/R) injury. In recent years, there has been increasing interest in investigating polyphenols from botanical source for possible neuroprotective effects against neurodegenerative diseases. In this study, we investigated the mechanisms underlying the neuroprotective effects of curcumin, a potent polyphenol antioxidant enriched in tumeric. Global cerebral ischemia was induced in Mongolian gerbils by transient occlusion of the common carotid arteries. Histochemical analysis indicated extensive neuronal death together with increased reactive astrocytes and microglial cells in the hippocampal CA1 area at 4 days after I/R. These ischemic changes were preceded by a rapid increase in lipid peroxidation and followed by decrease in mitochondrial membrane potential, increased cytochrome c release, and subsequently caspase-3 activation and apoptosis. Administration of curcumin by i.p. injections (30 mg/kg body wt) or by supplementation to the AIN76 diet (2.0 g/kg diet) for 2 months significantly attenuated ischemia-induced neuronal death as well as glial activation. Curcumin administration also decreased lipid peroxidation, mitochondrial dysfunction, and the apoptotic indices. The biochemical changes resulting from curcumin also correlated well with its ability to ameliorate the changes in locomotor activity induced by I/R. Bioavailability study indicated a rapid increase in curcumin in plasma and brain within 1 hr after treatment. Together, these findings attribute the neuroprotective effect of curcumin against I/R-induced neuronal damage to its antioxidant capacity in reducing oxidative stress and the signaling cascade leading to apoptotic cell death.

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

    DEFF Research Database (Denmark)

    Bering, Robert; Johansen, Flemming Fryd

    1993-01-01

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

  14. Chinese herbal formula Tongluo Jiunao injection protects against cerebral ischemia by activating neurotrophin 3/tropomyosin-related kinase C pathway

    Directory of Open Access Journals (Sweden)

    Peiman Alesheikh

    2015-01-01

    Full Text Available The Chinese herbal formula Tongluo Jiunao, containing the active components Panax notoginseng and Gardenia jasminoides, has recently been patented and is in use clinically. It is known to be neuroprotective in cerebral ischemia, but the underlying pathway remains poorly understood. In the present study, we established a rat model of cerebral ischemia by occlusion of the middle cerebral artery, and administered Tongluo Jiunao, a positive control (Xuesai Tong, containing Panax notoginseng or saline intraperitoneally to investigate the pathway involved in the action of Tongluo Jiunao injection. 2,3,5-Triphenyltetrazolium chloride (TTC staining showed that the cerebral infarct area was significantly smaller in model rats that received Tongluo Jiunao than in those that received saline. Enzyme-linked immunosorbent assay revealed significantly greater expression of neurotrophin 3 and growth-associated protein 43 in ischemic cerebral tissue, and serum levels of neurotrophin 3, in the Tongluo Jiunao group than in the saline group. The reverse transcription polymerase chain reaction and immunohistochemical staining showed that after treatment with Tongluo Jiunao or Xuesai Tong, tropomyosin-related kinase C gene expression and immunoreactivity were significantly elevated compared with saline, with the greatest expression observed after Tongluo Jiunao treatment. These findings suggest that Tongluo Jiunao injection exerts a neuroprotective effect in rats with cerebral ischemia by activating the neurotrophin 3/tropomyosin-related kinase C pathway.

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

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

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

  16. Time-dependent changes in cerebral blood flow after acetazolamide loading into patients with hemodynamic cerebral ischemia. Relationship to cerebral oxygen metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Masakazu [Iwate Medical Univ., Morioka (Japan). School of Medicine

    2001-10-01

    The aim of this study was to clarify the relationship between time-dependent changes in cerebral blood flow (CBF) after acetazolamide loading and cerebral oxygen metabolism (CMRO{sub 2}). The subjects consisted of 30 patients with severe stenosis or occlusion of either internal carotid, middle cerebral, or vertebro-basilar artery. Regional CBF was measured at the resting state and 6, 16 and 30 minutes after intravenous administration of 1 gram of acetazolamide using the positron emission tomography in combination with the [{sup 15}O] H{sub 2}O bolus-injection method. Prior to CBF study, regional cerebral oxygen extraction fraction (OEF) was measured using the [{sup 15}O] O{sub 2} inhalation method. Regional CMRO{sub 2} was calculated based on CBF and OEF. According to the time-dependent changes in CBF responses to acetazolamide loading, the CBF responses are classified into good response type, paradoxical response type, and poor response type. Good response type (CBF increase rate more than 20% 6 minutes after acetazolamide loading), paradoxical response type (decrease of CBF 6 minutes after acetazolamide loading) and poor response type (CBF increase rate less than 20% 6 minutes after acetazolamide loading) were identified in 39, 11 and 10 areas, respectively. Brain areas with good response type showed normal OEF and normal CMRO{sub 2}. Brain areas with paradoxical response type showed increased OEF and normal CMRO{sub 2}. Brain areas with poor response type showed normal OEF and decreased CMRO{sub 2}. In view of these findings, the writer concludes that sequential measurement of cerebral blood flow (CBF) after acetazolamide loading enables one to know the regional cerebral oxygen metabolic state in patients with hemodynamic ischemia, and CBF should be measured at an early stage after the administration of acetazolamide to accurately detect misery perfusion. (author)

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

    Directory of Open Access Journals (Sweden)

    Vikman Petter

    2007-01-01

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

  18. Scutellarin attenuates microglia-mediated neuroinflammation and promotes astrogliosis in cerebral ischemia - a therapeutic consideration

    Science.gov (United States)

    Wu, Chun-Yun; Fang, Ming; Karthikeyan, Aparna; Yuan, Yun; Ling, Eng-Ang

    2016-11-18

    Neuroinflammation plays an important role in different brain diseases including acute brain injuries such as cerebral ischemic stroke and chronic neurodegenerative diseases e.g. Alzheimer's disease etc. The central player in this is the activated microglia which produce substantial amounts of proinflammatory mediators that may exacerbate the disease. Associated with microglia activation is astrogliosis characterized by hypertrophic astrocytes with increased expression of proinflammatory cytokines, neurotrophic factors, stem cell, neuronal and proliferation markers, all these are crucial for reconstruction of damaged tissue and ultimate restoration of neurological functions. Here, we review the roles of activated microglia and reactive astrocytes in brain diseases with special reference to cerebral ischemia, and the effects of scutellarin, a Chinese herbal extract on both glial cells. We first reviewed the close spatial relation between activated microglia and reactive astrocytes as it suggests that both glial cells work in concert for tissue reconstruction and repair. Secondly, we have identified scutellarin as a putative therapeutic agent as it has been found to not only suppress microglial activation thus ameliorating neuroinflammation, but also enhance astrocytic reaction. In the latter, scutellarin amplified the astrocytic reaction by upregulating the expression of neurotrophic factors among others thus indicating its neuroprotective role. Remarkably, the effects of scutellarin on reactive astrocytes were mediated by activated microglia supporting a functional "cross-talk" between the two glial types. This review highlights some of our recent findings taking into consideration of others demonstrating the beneficial effects of scutellarin on both glial cell types in cerebral ischemia as manifested by improvement of neurological functions.

  19. Long Non-coding RNA H19 Induces Cerebral Ischemia Reperfusion Injury via Activation of Autophagy

    Science.gov (United States)

    Wang, Jue; Cao, Bin; Han, Dong; Sun, Miao; Feng, Juan

    2017-01-01

    Long non-coding RNA H19 (lncRNA H19) was found to be upregulated by hypoxia, its expression and function have never been tested in cerebral ischemia and reperfusion (I/R) injury. This study intended to investigate the role of lncRNA H19 and H19 gene variation in cerebral I/R injury with focusing on its relationship with autophagy activation. Cerebral I/R was induced in rats by middle cerebral artery occlusion followed by reperfusion. SH-SY5Y cells were subjected to oxygen and glucose deprivation and reperfusion (OGD/R) to simulate I/R injury. Real-time PCR, flow cytometry, immunofluorescence and Western blot were used to evaluate the level of lncRNA H19, apoptosis, autophagy and some related proteins. The modified multiple ligase reaction was used to analyze the gene polymorphism of six SNPs in H19, rs217727, rs2067051, rs2251375, rs492994, rs2839698 and rs10732516 in ischemic stroke patients. We found that the expression of lncRNA H19 was upregulated by cerebral I/R in rats, as well as by OGD/R in vitro in the cells. Inhibition of lncRNA H19 and autophagy protected cells from OGD/R-induced death, respectively. Autophagy activation induced by OGD/R was prevented by H19 siRNA. Autophagy inducer, rapamycin, abolished lncRNA H19 effect. Furthermore, we found that lncRNA H19 inhibited autophagy through DUSP5-ERK1/2 axis. The result from blood samples of ischemic patients revealed that the variation of H19 gene increased the risk of ischemic stroke. Taken together, the results of present study suggest that LncRNA H19 could be a new therapeutic target of ischemic stroke. PMID:28203482

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

    Directory of Open Access Journals (Sweden)

    Ying Jiang

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

  1. Protective Role of Fucoidan in Cerebral Ischemia-Reperfusion Injury through Inhibition of MAPK Signaling Pathway.

    Science.gov (United States)

    Che, Nan; Ma, Yijie; Xin, Yinhu

    2016-11-25

    Fucoidan has been reported to exhibit various beneficial activities ranging from to antivirus and anticancer properties. However, little information is available about the effects of fucoidan on cerebral ischemia-reperfusion injury (IRI). Our study aimed to explore the effects of fucoidan on cerebral IRI, as well as the underlying mechanisms. Sprague-Dawley (SD) rats were randomly subjected to four groups: Sham, IRI+saline (IRI+S), IRI+80 mg/kg fucoidan (IRI+F80), and IRI+160 mg/kg fucoidan (IRI+F160). Fucoidan (80 mg/kg or 160 mg/kg) was intraperitoneally injected from 7 days before the rats were induced to cerebral IRI model with middle cerebral artery occlusion (MCAO) method. At 24 h after reperfusion, neurological deficits and the total infarct volume were determined. The levels of inflammation-associated cytokines (interleukin (IL)-1β, IL-6, myeloperoxidase (MPO), and tumor necrosis factor (TNF)-α), oxidative stress-related proteins (malondialdehyde (MDA) and superoxide dismutase (SOD)) in the ischemic brain were measured by enzyme-linked immunosorbent assay (ELISA). Besides, the levels of apoptosis-related proteins (p-53, Bax, and B-cell lymphoma (Bcl)-2) and mitogen-activated protein kinase (MAPK) pathway (phosphorylation-extracellular signalregulated kinase (p-ERK), p-c-Jun N-terminal kinase (JNK), and p-p38) were measured. Results showed that administration of fucoidan significantly reduced the neurological deficits and infarct volume compared to the IRI+S group in a dose-dependent manner. Also, fucoidan statistically decreased the levels of inflammation-associated cytokines, and oxidative stress-related proteins, inhibited apoptosis, and suppressed the MAPK pathway. So, Fucoidan plays a protective role in cerebral IRI might be by inhibition of MAPK pathway.

  2. Increases of Catalase and Glutathione Peroxidase Expressions by Lacosamide Pretreatment Contributes to Neuroprotection Against Experimentally Induced Transient Cerebral Ischemia.

    Science.gov (United States)

    Choi, Hyun Young; Park, Joon Ha; Chen, Bai Hui; Shin, Bich Na; Lee, Yun Lyul; Kim, In Hye; Cho, Jeong-Hwi; Lee, Tae-Kyeong; Lee, Jae-Chul; Won, Moo-Ho; Ahn, Ji Hyeon; Tae, Hyun-Jin; Yan, Bing Chun; Hwang, In Koo; Cho, Jun Hwi; Kim, Young-Myeong; Kim, Sung Koo

    2016-09-01

    Lacosamide is a new antiepileptic drug which is widely used to treat partial-onset seizures. In this study, we examined the neuroprotective effect of lacosamide against transient ischemic damage and expressions of antioxidant enzymes such as Zn-superoxide dismutase (SOD1), Mn-superoxide dismutase (SOD2), catalase (CAT) and glutathione peroxidase (GPX) in the hippocampal cornu ammonis 1 (CA1) region following 5 min of transient global cerebral ischemia in gerbils. We found that pre-treatment with 25 mg/kg lacosamide protected CA1 pyramidal neurons from transient global cerebral ischemic insult using hematoxylin-eosin staining and neuronal nuclear antigen immunohistochemistry. Transient ischemia dramatically changed expressions of SOD1, SOD2 and GPX, not CAT, in the CA1 pyramidal neurons. Lacosamide pre-treatment increased expressions of CAT and GPX, not SOD1 and 2, in the CA1 pyramidal neurons compared with controls, and their expressions induced by lacosamide pre-treatment were maintained after transient cerebral ischemia. In brief, pre-treatment with lacosamide protected hippocampal CA1 pyramidal neurons from ischemic damage induced by transient global cerebral ischemia, and the lacosamide-mediated neuroprotection may be closely related to increases of CAT and GPX expressions by lacosamide pre-treatment.

  3. Asiaticoside attenuates memory impairment induced by transient cerebral ischemia-reperfusion in mice through anti-inflammatory mechanism.

    Science.gov (United States)

    Chen, She; Yin, Zhu-Jun; Jiang, Chen; Ma, Zhan-Qiang; Fu, Qiang; Qu, Rong; Ma, Shi-Ping

    2014-07-01

    Asiaticoside (AS) is isolated from Centella asiatica (L.) which has been using for a long time as a memory enhancing drug in India. This study was to investigate the effects of AS on memory impairment and inflammatory cytokines expression induced by transient cerebral ischemia and reperfusion in mice, as well as the potential signaling pathway. Transient bilateral common carotid artery occlusion (tBCCAO) induced severe memory deficits in mice according to the Morris water maze task and the step-down passive avoidance test. Meanwhile the microglial activation and the gene expression of inflammatory cytokines including interleukin (IL)-1β, interleukin (IL)-6 and tumor necrosis factor (TNF)-α were increased in the hippocampus of the mice with cerebral ischemia and reperfusion. Oral administration of AS (40 and 60 mg/kg, once per day, started the day after surgery and lasted for 7 days) significantly ameliorated the memory impairment and the inflammation. Moreover, AS (20, 40 and 60 mg/kg) markedly reduced the microglial overactivation and the phosphorylation of p38 MAPK in hippocampus compared with the transient cerebral ischemia and reperfusion group. These results suggested that AS showed the neuroprotective effect against transient cerebral ischemia and reperfusion in mice, and this effect might be associated with the anti-inflammation effect of AS via inhibiting overactivation of p38 MAPK pathway.

  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. Lack of association between right-to-left shunt and cerebral ischemia after adjustment for gender and age

    Directory of Open Access Journals (Sweden)

    Heider Peter

    2008-10-01

    Full Text Available Abstract Introduction A number of studies has addressed the possible association between patent foramen ovale (PFO and stroke. However, the role of PFO in the pathogenesis of cerebral ischemia has remained controversial and most studies did not analyze patient subgroups stratified for gender, age and origin of stroke. Methods To address the role of PFO for the occurrence of cerebral ischemia, we investigated the prevalence of right-to-left shunt in a large group of patients with acute stroke or TIA. 763 consecutive patients admitted to our hospital with cerebral ischemia were analyzed. All patients were screened for the presence of PFO by contrast-enhanced transcranial Doppler sonography at rest and during Valsalva maneuver. Subgroup analyses were performed in patients stratified for gender, age and origin of stroke. Results A right-to-left shunt was detected in 140 (28% male and in 114 (42% female patients during Valsalva maneuver, and in 66 (13% and 44 (16% at rest respectively. Patients with right-to-left shunt were younger than those without (P P = 0.001 but not female patients (P > 0.05. After adjusting for age no significant association between PFO and stroke of unknown origin was found in either group. Conclusion Our findings argue against paradoxical embolization as a major cause of cerebral ischemia in patients with right-to-left shunt. Our data demonstrate substantial gender-and age-related differences that should be taken into account in future studies.

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

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

  8. Chronic Cerebral Ischemia and Alzheime Disease%慢性脑缺血与阿尔茨海默病

    Institute of Scientific and Technical Information of China (English)

    徐钧

    2012-01-01

    Currently Alzheimer disease( AD )is the main type of dementia, and is the fourth cause of death in the elders. There are quite a few theories about AD pathogenesis, it's now considered that chronic cerebral ischemia may be the cause of AD. For chronic cerebral ischemia can lead to different degrees of brain pathological damage, the β-amyloid peptide deposition , neurons apoptosis , energy metabolic disorders, and immune oxidative damage caused by chronic cerebral ischemia may be the AD pathogenesis. Here is to make a review' on the role of chronic cerebral ischemia in AD pathogenesis and the ultimate cause of AD.%当前阿尔茨海默病(AD)是痴呆的主要类型,并且是导致老年人死亡的第四大原因.关于AD的病因很多,现在认为慢性脑缺血可能为AD的病因.因为慢性脑缺血能够导致脑组织不同程度的病理损伤,其引起的β淀粉样肽的沉积、神经元的凋亡、能量代谢障碍、免疫氧化损伤可能是AD的发病机制.现对慢性脑缺血在AD发病的作用和其最终导致AD的原因进行综述.

  9. Automation of Classical QEEG Trending Methods for Early Detection of Delayed Cerebral Ischemia: More Work to Do.

    Science.gov (United States)

    Wickering, Ellis; Gaspard, Nicolas; Zafar, Sahar; Moura, Valdery J; Biswal, Siddharth; Bechek, Sophia; OʼConnor, Kathryn; Rosenthal, Eric S; Westover, M Brandon

    2016-06-01

    The purpose of this study is to evaluate automated implementations of continuous EEG monitoring-based detection of delayed cerebral ischemia based on methods used in classical retrospective studies. We studied 95 patients with either Fisher 3 or Hunt Hess 4 to 5 aneurysmal subarachnoid hemorrhage who were admitted to the Neurosciences ICU and underwent continuous EEG monitoring. We implemented several variations of two classical algorithms for automated detection of delayed cerebral ischemia based on decreases in alpha-delta ratio and relative alpha variability. Of 95 patients, 43 (45%) developed delayed cerebral ischemia. Our automated implementation of the classical alpha-delta ratio-based trending method resulted in a sensitivity and specificity (Se,Sp) of (80,27)%, compared with the values of (100,76)% reported in the classic study using similar methods in a nonautomated fashion. Our automated implementation of the classical relative alpha variability-based trending method yielded (Se,Sp) values of (65,43)%, compared with (100,46)% reported in the classic study using nonautomated analysis. Our findings suggest that improved methods to detect decreases in alpha-delta ratio and relative alpha variability are needed before an automated EEG-based early delayed cerebral ischemia detection system is ready for clinical use.

  10. Cerebral ischemia/stroke and small ubiquitin-like modifier (SUMO) conjugation--a new target for therapeutic intervention?

    Science.gov (United States)

    Yang, Wei; Sheng, Huaxin; Homi, H Mayumi; Warner, David S; Paschen, Wulf

    2008-08-01

    Transient cerebral ischemia/stroke activates various post-translational protein modifications such as phosphorylation and ubiquitin conjugation that are believed to play a major role in the pathological process triggered by an interruption of blood supply and culminating in cell death. A new system of post-translational protein modification has been identified, termed as small ubiquitin-like modifier (SUMO) conjugation. Like ubiquitin, SUMO is conjugated to the lysine residue of target proteins in a complex process. This review summarizes observations from recent experiments focusing on the effect of cerebral ischemia on SUMO conjugation. Transient global and focal cerebral ischemia both induced a rapid, dramatic and long-lasting rise in levels of SUMO2/3 conjugation. After transient focal cerebral ischemia, SUMO conjugation was particularly prominent in neurons located at the border of the ischemic territory where SUMO-conjugated proteins translocated to the nucleus. Many SUMO conjugation target proteins are transcription factors and sumoylation has been shown to have a major impact on the activity, stability, and cellular localization of target proteins. The rise in levels of SUMO-conjugated proteins is therefore likely to have a major effect on the fate of post-ischemic neurons. The sumoylation process could provide an exciting new target for therapeutic intervention.

  11. 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.

  12. Reconstruction of cerebral hemodynamics with dynamic contrast-enhanced time-resolved near-infrared measurements before and during ischemia

    Science.gov (United States)

    Elliott, Jonathan T.; Diop, Mamadou; Morrison, Laura B.; Lee, Ting-Yim; St. Lawrence, Keith

    2013-03-01

    We present a dynamic contrast-enhanced near-infrared (DCE-NIR) technique that is capable of non-invasive quantification of cerebral hemodynamics in adults. The challenge of removing extracerebral contamination is overcome through the use of multi-distance time-resolved DCE-NIR combined with the kinetic deconvolution optical reconstruction (KDOR) analytical method. As proof-of-principle, cerebral blood flow, cerebral blood volume and mean transit time recovered with DCE-NIR are compared with CT perfusion values in an adult pig during normocapnia, hypocapnia, and ischemia. Measurements of blood flow acquired with DCE-NIR were compared against concomitant measurements using CT Perfusion.

  13. 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.

  14. Physiological meaning of cerebral oxygen saturation for piglet with hypoxia-ischemia

    Science.gov (United States)

    Ding, Haishu; Huang, Lan; Jen, Chungchien; Hwang, Betau; Lee, Zhiguang; Teng, Yichao; Zheng, Meizhi

    2005-01-01

    The physiological meaning of cerebral oxygen saturation absolute values and the oxygen metabolism of piglet with hypoxia-ischemia (HIE) were researched. The subjects were two piglets. During the total experiment of hypoxia then recovery, the regional cerebral tissue oxygen (rScO2), pulse oxygen saturation (SpO2) were detected non-invasively and the jugular oxygen saturation (SjO2), arterial oxygen saturation (SaO2) were given invasively. The results show that because SjO2 was equal to or larger than rScO2 and SaO2 > ScO2, rScO2 cannot be determined by the weighted sum of SjO2 and SaO2 which had been presented in some papers. According to above-mentioned analysis, the ecchymoma and pathological changes of the vessels due to HIE may be another contribution of rScO2. SjO2 was correlated with SaO2 (R=0.996 and 0.962 for two piglets) and the values of (SaO2-SjO2) are close to constants (29.3+/-8% and 30.3+/-8%).It means that because the subjects were under anesthesia, the oxygen consumption of cerebral tissue kept constants.

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

    Directory of Open Access Journals (Sweden)

    Xumei Wang

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Shuai Hou

    2016-07-01

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

  17. Therapeutic time window of flurbiprofen axetil's neuroprotective effect in a rat model of transient focal cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Background The neuroprotective effect of the cyclooxygenase (COX) inhibitor has been demonstrated in acute and chronic neurodegenerative processes. But its function under cerebral ischemic conditions is unclear. This study was designed to evaluate the neuroprotective efficacy of emulsified flurbiprofen axetil (FA, COX inhibitor) and its therapeutic time window in a model of transient middle cerebral artery occlusion (MCAO) in rats. Methods Forty-eight male SD rats were randomly assigned into six groups (n=8 in each group); three FA groups, vehicle, sham and ischemia/reperfusion (I/R) groups. Three doses of FA (5, 10 or 20 mg/kg, intravenous infusion) were administered just after cerebral ischemia/reperfusion (I/R). The degree of neurological outcome was measured by the neurologic deficit score (NDS) at 24, 48 and 72 hours after I/R. Mean brain infarct volume percentage (MBIVP) was determined with 2,3,5-triphenyltetrazolium chloride (TTC) staining at 72 hours after I/R. In three other groups (n=8 in each group), the selected dosage of 10 mg/kg was administrated intravenously at 6, 12 and 24 hours after I/R. Results The three different doses of FA improved NDS at 24, 48 and 72 hours after I/R and significantly reduced MBIVP. However, the degree of MBIVP in the FA 20 mg/kg group differed from that in FA 10 mg/kg group. Of interest is the finding that the neuroprotective effect conferred by 10 mg/kg of FA was also observed when treatment was delayed until 12-24 hours after ischemia reperfusion. Conclusion COX inhibitor FA is a promising therapeutic strategy for cerebral ischemia and its therapeutic time window could last for 12--24 hours after cerebral ischemia reperfusion, which would help in lessening the initial ischemic brain damage.

  18. Ischemia

    Science.gov (United States)

    Byeon, Suk Ho; Kim, Min; Kwon, Oh Woong

    "Ischemia" implies a tissue damage derived from perfusion insufficiency, not just an inadequate blood supply. Mild thickening and increased reflectivity of inner retina and prominent inner part of synaptic portion of outer plexiform layer are "acute retinal ischemic changes" visible on OCT. Over time, retina becomes thinner, especially in the inner portion. Choroidal perfusion supplies the outer portion of retina; thus, choroidal ischemia causes predominant change in the corresponding tissue.

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

    Directory of Open Access Journals (Sweden)

    Jing Han

    2015-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    Xiaohong Liu; Zhiqiang Zhang; Lixin Zhang

    2006-01-01

    BACKGROUND: It has shown that magnetic field can improve blood circulation, decrease blood viscosity, inhibit free radicals, affect Ca2+ flow in nerve cells, control inflammatory and immunological reaction, and accelerate nerve cell regeneration. In addition, protective effect of magnetic field, which acts as an iatrophysics, on ischemic brain tissues has been understood gradually.OBJECTIVE: To investigate the effects of rotating magnetic field (RMF) on volume of cerebral infarction,cerebral edema and metabolism of free radicals in rats after cerebral ischemia/reperfusion injury.DESIGN: Randomized controlled animal study.SETTING: Rehabilitation Center of disabled children, Liaoniang; Department of Rehabilitation, the Second Affiliated Hospital, China Medical University; Department of Rehabilitation Physiotherapy, the First Affiliated Hospital, China Medical University.MATERIALS: A total of 70 healthy Wistar rats aged 18-20 weeks of both genders were selected and randomly divided into 3 groups: sham operation group with 12 rats, control group with 20 rats and treatment group with 38 rats. The treatment group included 4 time points: immediate reperfusion with 6 ones, 6-hour reperfusion with 20 ones, 12-hour reperfusion with 6 ones and 18-hour reperfusion with 6 rats. Main instruments were detailed as follows: magnetic head of rotating magnetic device was 6 cm in diameter; magnetic induction intensity at the surface of magnetic head was 0.25 T in silence; the maximal magnetic induction intensity was 0.09 T at the phase of rotation; the average rotating speed was 2500 r per minute.METHODS: The experiment was carried out in the China Medical University in March 2003. Focal cerebral ischemic animal models were established with modified Longa's method. Operation was the same in the sham operation, but the thread was inserted as 10 mm. Neurologic impairment was assessed with 5-rating method to screen out cases. Those survivals with grade 1 and grade 2 after ischemia for 2

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

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2010-01-01

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

  3. Effects of citicoline used alone and in combination with mild hypothermia on apoptosis induced by focal cerebral ischemia in rats.

    Science.gov (United States)

    Sahin, S; Alkan, T; Temel, S G; Tureyen, K; Tolunay, S; Korfali, E

    2010-02-01

    The effects of citicoline used either alone or in combination with hypothermia on the suppression of apoptotic processes after transient focal cerebral ischemia were investigated. Middle cerebral artery occlusion (MCAo) was performed for 2 hours on Sprague-Dawley (SD) rats using intraluminal thread insertion. The treatment groups were as follows: Group 1, sham-operated; Group 2, saline; Group 3, citicoline (400mg/kg intraperitoneal.); Group 4, hypothermia (34+/-1 degrees C); Group 5, citicoline+hypothermia. All rats were reperfused for 24 hours, and after sacrifice and transcardiac perfusion, immunohistochemical studies were performed for markers of apoptosis. In Group 2, the Bcl-2 immunostaining score (mean+/-standard deviation, 0.71+/-0.75) was lower compared to Groups 3, 4 and 5 (2.33+/-0.81; 3.00+/-0.00; 2.20+/-0.83; pciticoline with hypothermia is more effective than either used alone in ameliorating cerebral damage after transient focal ischemia.

  4. Neuroprotective Effects of Bone Marrow Mesenchymal Stem Cells on Bilateral Common Carotid Arteries Occlusion Model of Cerebral Ischemia in Rat

    Directory of Open Access Journals (Sweden)

    Bagher Pourheydar

    2016-01-01

    Full Text Available Cell therapy is the most advanced treatment of the cerebral ischemia, nowadays. Herein, we discuss the neuroprotective effects of bone marrow mesenchymal stem cells (BMSCs on rat hippocampal cells following intravenous injection of these cells in an ischemia-reperfusion model. Adult male Wistar rats were divided into 5 groups: control, sham (surgery without blockage of common carotid arteries, ischemia (common carotid arteries were blocked for 30 min prior to reperfusion, vehicle (7 days after ischemia PBS was injected via the tail vein, and treatment (injections of BMSC into the tail veins 7 days after ischemia. We performed neuromuscular and vestibulomotor function tests to assess behavioral function and, finally, brains were subjected to hematoxylin and eosin (H&E, anti-Brdu immunohistochemistry, and TUNEL staining. The ischemia group had severe apoptosis. The group treated with BMSCs had a lower mortality rate and also had significant improvement in functional recovery (P<0.001. Ischemia-reperfusion for 30 min causes damage and extensive neuronal death in the hippocampus, especially in CA1 and CA3 regions, leading to several functional and neurological deficits. In conclusion, intravenous injection of BMSCs can significantly decrease the number of apoptotic neurons and significantly improve functional recovery, which may be a beneficial treatment method for ischemic injuries.

  5. Anesthesia-Induced Hypothermia Attenuates Early-Phase Blood-Brain Barrier Disruption but Not Infarct Volume following Cerebral Ischemia.

    Science.gov (United States)

    Liu, Yu-Cheng; Lee, Yu-Da; Wang, Hwai-Lee; Liao, Kate Hsiurong; Chen, Kuen-Bao; Poon, Kin-Shing; Pan, Yu-Ling; Lai, Ted Weita

    2017-01-01

    Blood-brain barrier (BBB) disruption is thought to facilitate the development of cerebral infarction after a stroke. In a typical stroke model (such as the one used in this study), the early phase of BBB disruption reaches a peak 6 h post-ischemia and largely recovers after 8-24 h, whereas the late phase of BBB disruption begins 48-58 h post-ischemia. Because cerebral infarct develops within 24 h after the onset of ischemia, and several therapeutic agents have been shown to reduce the infarct volume when administered at 6 h post-ischemia, we hypothesized that attenuating BBB disruption at its peak (6 h post-ischemia) can also decrease the infarct volume measured at 24 h. We used a mouse stroke model obtained by combining 120 min of distal middle cerebral arterial occlusion (dMCAo) with ipsilateral common carotid arterial occlusion (CCAo). This model produced the most reliable BBB disruption and cerebral infarction compared to other models characterized by a shorter duration of ischemia or obtained with dMCAO or CCAo alone. The BBB permeability was measured by quantifying Evans blue dye (EBD) extravasation, as this tracer has been shown to be more sensitive for the detection of early-phase BBB disruption compared to other intravascular tracers that are more appropriate for detecting late-phase BBB disruption. We showed that a 1 h-long treatment with isoflurane-anesthesia induced marked hypothermia and attenuated the peak of BBB disruption when administered 6 h after the onset of dMCAo/CCAo-induced ischemia. We also demonstrated that the inhibitory effect of isoflurane was hypothermia-dependent because the same treatment had no effect on ischemic BBB disruption when the mouse body temperature was maintained at 37°C. Importantly, inhibiting the peak of BBB disruption by hypothermia had no effect on the volume of brain infarct 24 h post-ischemia. In conclusion, inhibiting the peak of BBB disruption is not an effective neuroprotective strategy, especially in comparison

  6. Neuroprotective efficacy and therapeutic time window of peroxynitrite decomposition catalysts in focal cerebral ischemia in rats#

    Science.gov (United States)

    Thiyagarajan, Meenakshisundaram; Kaul, Chaman Lal; Sharma, Shyam Sundar

    2004-01-01

    Free radicals have been implicated in cerebral ischemia reperfusion (IR) injury. Massive production of nitric oxide and superoxide results in continuous formation of peroxynitrite even several hours after IR insult. This can produce DNA strand nicks, hydroxylation and/or nitration of cytosolic components of neuron, leading to neuronal death. Peroxynitrite decomposition catalysts 5,10,15,20-tetrakis(N-methyl-4′-pyridyl)porphyrinato iron (III) (FeTMPyP) and 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrinato iron (III) (FeTPPS) have been demonstrated to protect neurons in in vitro cultures; however, their neuroprotective efficacy in cerebral IR injury has not been explored. In the present study, we investigated the efficacy and the therapeutic time window of FeTMPyP and FeTPPS in focal cerebral ischemia (FCI). FCI was induced according to the middle cerebral artery occlusion (MCAO) method. After 2 h of MCAO and 70 h of reperfusion, the extent of neurological deficits, infarct and edema volume were measured in Sprague–Dawley rats. FeTMPyP and FeTPPS were administered at different time points 2, 6, 9 and 12 h post MCAO. FeTMPyP and FeTPPS (3 mg kg−1, i.v.) treatment at 2 and 6 h post MCAO produced significant reduction in infarct volume, edema volume and neurological deficits. However, treatment at latter time points did not produce significant neuroprotection. Significant reduction of peroxynitrite in blood and nitrotyrosine in brain sections was observed on FeTMPyP and FeTPPS treatment. As delayed treatment of FeTMPyP and FeTPPS produced neuroprotection, we tested whether treatment had any influence over the apoptotic neuronal death. DNA fragmentation and in situ nick end-labeling assays showed that FeTMPyP and FeTPPS treatment reduced IR injury-induced DNA fragmentation. In conclusion, peroxynitrite decomposition catalysts (FeTMPyP and FeTPPS) produced prominent neuroprotection even if administered 6 h post MCAO and the neuroprotective effect is at least in

  7. Peroxisome proliferator-activated receptor-γ agonist 15d-prostaglandin J2 mediates neuronal autophagy after cerebral ischemia-reperfusion injury.

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    Feng Xu

    Full Text Available Peroxisome proliferator-activated receptor-γ (PPAR-γ has recently emerged as potential therapeutic agents for cerebral ischemia-reperfusion (I/R injury because of anti-neuronal apoptotic actions. However, whether PPAR-γ activation mediates neuronal autophagy in such conditions remains unclear. Therefore, in this study, we investigated the role of PPAR-γ agonist 15-PGJ(2 on neuronal autophagy induced by I/R. The expression of autophagic-related protein in ischemic cortex such as LC3-II, Beclin 1, cathepsin-B and LAMP1 increased significantly after cerebral I/R injury. Furthermore, increased punctate LC3 labeling and cathepsin-B staining occurred in neurons. Treatment with PPAR-γ agonist 15d-PGJ(2 decreased not only autophagic-related protein expression in ischemic cortex, but also immunoreactivity of LC3 and cathepsin-B in neurons. Autophagic inhibitor 3-methyladenine (3-MA decreased LC3-II levels, reduced the infarct volume, and mimicked some protective effect of 15d-PGJ(2 against cerebral I/R injury. These results indicate that PPAR-γ agonist 15d-PGJ(2 exerts neuroprotection by inhibiting neuronal autophagy after cerebral I/R injury. Although the molecular mechanisms underlying PPAR-γ agonist in mediating neuronal autophagy remain to be determined, neuronal autophagy may be a new target for PPAR-γ agonist treatment in cerebral I/R injury.

  8. Cerebral Ischemia Reperfusion Exacerbates and Pueraria Flavonoids Attenuate Depressive Responses to Stress in Mice

    Institute of Scientific and Technical Information of China (English)

    LAN Jiaqi; YAN Bin; ZHAO Yu'nan; WANG Daoyi; HU Jun; XING Dongming; DU Lijun

    2008-01-01

    Previous studies have shown that mice experiencing cerebral ischemia reperfusion (CIR) and stress can serve as a model of post stroke depression (PSD).The present study verified the acute antide-pressant effects of radix puerariae extract (PE) on PSD mice through behavior and gene expression ex-periments.CIR was found to reduce the sucrose consumption and tyrosine hydroxylase (TH) gene expres-sion.PE administration after CIR surgery was observed to significantly enhance the mRNA expression of TH in the hippocampus compared with the PSD group on Day 0 and Day 3 postsurgery.These findings in-dicate that PE contributes to the amelioration of behavior response in PSD mice,which is closely related with the protective effects of catecholamine synthesize against CIR brain damage.

  9. Neuroprotective effect of tyrosol on transient focal cerebral ischemia in rats.

    Science.gov (United States)

    Bu, Youngmin; Rho, Seongjoo; Kim, Jinmo; Kim, Mi Yeon; Lee, Dae Hee; Kim, Sun Yeou; Choi, Hoyoung; Kim, Hocheol

    2007-03-13

    Tyrosol (2-(4-hydroxyphenyl)ethanol) is a well-known phenolic compound with antioxidant properties that is present in wine, olive oil, and other plant-derived products. The purpose of this study was to determine the neuroprotective effect of tyrosol in a stroke animal model. By using the transient middle cerebral artery occlusion rat model (2 h of occlusion, 22 h of reperfusion), we investigated the effects of tyrosol on infarct volume and sensory motor function deficit by performing 2,3,5-triphenyltetrazolium chloride staining and behavior tests after ischemia. Tyrosol showed a dose-dependent neuroprotective effect that peaked at 64.9% in rats treated with 30 mg/kg of tyrosol. In rotarod, beam balance, and foot fault tests, tyrosol exhibited protective effects against the sensory motor dysfunction. In conclusion, our results suggest that tyrosol is an appropriate candidate to be used in stroke therapy.

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

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    Ming-Shu Xu

    2013-01-01

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

  11. Excessive supraventricular ectopic activity is indicative of paroxysmal atrial fibrillation in patients with cerebral ischemia.

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    Mark Weber-Krüger

    Full Text Available BACKGROUND: Detecting paroxysmal atrial fibrillation (PAF in patients with cerebral ischemia is challenging. Frequent premature atrial complexes (PAC/h and the longest supraventricular run on 24-h-Holter (SV-run(24 h, summarised as excessive supraventricular ectopic activity (ESVEA, may help selecting patients for extended ECG-monitoring, especially in combination with echocardiographic marker LAVI/a' (left atrial volume index/late diastolic tissue Doppler velocity. METHODS: Retrospective analysis from the prospective monocentric observational trial Find-AF (ISRCTN-46104198. Patients with acute stroke or TIA were enrolled at the University Hospital Göttingen, Germany. Those with sinus rhythm at presentation received 7-day Holter-monitoring. ESVEA was quantified in one 24-hour interval free from PAF. Echocardiographic parameters were assessed prospectively. RESULTS: PAF was detected in 23/208 patients (11.1%. The median was 4 [IQR 1; 22] for PAC/h and 5 [IQR 0; 9] for SV-run(24 h. PAF was more prevalent in patients with ESVEA: 19.6% vs. 2.8% for PAC/h >4 vs. ≤ 4 (p5 vs. ≤ 5 beats (p = 0.003. Patients with PAF showed more supraventricular ectopic activity: 29 PAC/h [IQR 9; 143] vs. 4 PAC/h [1]; [14] and longest SV-run(24 h = 10 [5]; [21] vs. 0 [0; 8] beats (both p4 and abnormal LAVI/a' showed high PAF-rates. CONCLUSIONS: ESVEA discriminated PAF from non-PAF beyond clinical factors including LAVI/a' in patients with cerebral ischemia. Normal LAVI/a'+PAC/h ≤ 4 ruled out PAF, while prevalence was high in those with abnormal LAVI/a'+PAC/h >4.

  12. Influence of pigment epithelium-derived factor on outcome after striatal cerebral ischemia in the mouse.

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    Marietta Zille

    Full Text Available We here suggest that pigment epithelium-derived factor (PEDF does not have an effect on lesion size, behavioral outcome, cell proliferation, or cell death after striatal ischemia in the mouse. PEDF is a neurotrophic factor with neuroprotective, antiangiogenic, and antipermeability effects. It influences self-renewal of neural stem cells and proliferation of microglia. We investigated whether intraventricular infusion of PEDF reduces infarct size and cell death, ameliorates behavioral outcome, and influences cell proliferation in the one-hour middle cerebral artery occlusion (MCAO mouse model of focal cerebral ischemia. C57Bl6/N mice were implanted with PEDF or artificial cerebrospinal fluid (control osmotic pumps and subjected to 60-minute MCAO 48 hours after pump implantation. They received daily BrdU injections for 7 days after MCAO in order to investigate cell proliferation. Infarct volumes were determined 24 hours after reperfusion using magnetic resonance imaging. We removed the pumps on day 5 and performed behavioral testing between day 7 and 21. Immunohistochemical staining was performed to determine the effect of PEDF on cell proliferation and cell death. Our model produced an ischemic injury confined solely to striatal damage. We detected no reduction in infarct sizes and cell death in PEDF- vs. CSF-infused MCAO mice. Behavioral outcome and cell proliferation did not differ between the groups. However, we cannot exclude that PEDF might work under different conditions in stroke. Further studies will elucidate the effect of PEDF treatment on cell proliferation and behavioral outcome in moderate to severe ischemic injury in the brain.

  13. Verapamil augments the neuroprotectant action of berberine in rat model of transient global cerebral ischemia.

    Science.gov (United States)

    Singh, Dhirendra Pratap; Chopra, Kanwaljit

    2013-11-15

    Various potential molecules with putative positive role in stroke pathology have failed to confer neuro-protection in animal models due to their insufficient bioavailability in brain. Efflux of these molecules by P-glycoprotein (P-gp), on blood brain barrier (BBB) is one of the reasons of their poor bioavailability. Berberine, have anti-inflammatory, antioxidant, anti-apoptotic properties, but also having low oral bioavailabilty. Verapamil, which increased the central nervous system uptake of few drugs, when concomitantly administered with berberine was evaluated in this animal model. Wistar rats were subjected to bilateral common carotid artery occlusion to induce acute cerebral ischemia for 15 min followed by reperfusion resulting in transient global cerebral ischemia. For 19 days berberine (5, 10, 20mg/kg, p.o.) alone and in similar doses concomitantly with verapamil (2mg/kg, p.o.) was evaluated employing various neuro-behavioral test, biochemical parameters and molecular estimations. The adjunction of berberine with verapamil improved the neurological outcome in a battery of behavioral paradigms, improved spatial memory in Morris water maze task, ameliorated the oxidative-nitrosative stress, increased acetylcholinesterase (AChE) activity, as well as improved mitochondrial complex (I, II, and IV) activity, reducing tumor necrosis factor-alpha, interleukin-1 beta and caspase-3 levels in brain tissues as compared to berberine alone group in ischemic rats. There is a strong possibility of improved brain bioavailabity of berberine when combined with verapamil. The findings suggested that the combination of berberine with verapamil, which could enhance its brain uptake, will surely provide a greater impact in neroprotection drug discovery for search of such combination.

  14. Different CT perfusion algorithms in the detection of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage

    Energy Technology Data Exchange (ETDEWEB)

    Cremers, Charlotte H.P. [University Medical Center Utrecht, Department of Neurology and Neurosurgery, Room G03.232, Brain Center Rudolf Magnus Department of Neurology and Neurosurgery, PO Box 85500, Utrecht (Netherlands); University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Dankbaar, Jan Willem; Bennink, Edwin; Velthuis, Birgitta K.; Schaaf, Irene C. van der [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Vergouwen, Mervyn D.I.; Rinkel, Gabriel J.E. [University Medical Center Utrecht, Department of Neurology and Neurosurgery, Room G03.232, Brain Center Rudolf Magnus Department of Neurology and Neurosurgery, PO Box 85500, Utrecht (Netherlands); Vos, Pieter C. [University Medical Center Utrecht, Image Sciences Institute, Utrecht (Netherlands)

    2015-05-01

    Tracer delay-sensitive perfusion algorithms in CT perfusion (CTP) result in an overestimation of the extent of ischemia in thromboembolic stroke. In diagnosing delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH), delayed arrival of contrast due to vasospasm may also overestimate the extent of ischemia. We investigated the diagnostic accuracy of tracer delay-sensitive and tracer delay-insensitive algorithms for detecting DCI. From a prospectively collected series of aSAH patients admitted between 2007-2011, we included patients with any clinical deterioration other than rebleeding within 21 days after SAH who underwent NCCT/CTP/CTA imaging. Causes of clinical deterioration were categorized into DCI and no DCI. CTP maps were calculated with tracer delay-sensitive and tracer delay-insensitive algorithms and were visually assessed for the presence of perfusion deficits by two independent observers with different levels of experience. The diagnostic value of both algorithms was calculated for both observers. Seventy-one patients were included. For the experienced observer, the positive predictive values (PPVs) were 0.67 for the delay-sensitive and 0.66 for the delay-insensitive algorithm, and the negative predictive values (NPVs) were 0.73 and 0.74. For the less experienced observer, PPVs were 0.60 for both algorithms, and NPVs were 0.66 for the delay-sensitive and 0.63 for the delay-insensitive algorithm. Test characteristics are comparable for tracer delay-sensitive and tracer delay-insensitive algorithms for the visual assessment of CTP in diagnosing DCI. This indicates that both algorithms can be used for this purpose. (orig.)

  15. Collateral blood flow in different cerebrovascular hierarchy provides endogenous protection in cerebral ischemia.

    Science.gov (United States)

    Luo, Chuanming; Liang, Fengyin; Ren, Huixia; Yao, Xiaoli; Liu, Qiang; Li, Mingyue; Qin, Dajiang; Yuan, Ti-Fei; Pei, Zhong; Su, Huanxing

    2016-11-15

    Collateral blood flow as vascular adaptions to focal cerebral ischemia is well recognized. However, few studies directly investigate the dynamics of collateral vessel recruitment in vivo and little is known about the effect of collateral blood flow in different cerebrovascular hierarchy on the neuropathology after focal ischemic stroke. Here, we report that collateral blood flow is critically involved in blood vessel compensations following regional ischemia. We occluded a pial arteriole using femtosecond laser ablating under the intact thinned skull and documented the changes of collateral flow around the surface communication network and between the surface communication network and subsurface microcirculation network using in vivo two photon microscopy imaging. Occlusion of the pial arteriole apparently increased the diameter and collateral blood flow of its leptomeningeal anastomoses, which significantly reduced the cortical infarction size. This result suggests that the collateral flow via surface communicating network connected with leptomeningeal anastomoses could greatly impact on the extent of infarction. We then further occluded the target pial arteriole and all of its leptomeningeal anastomoses. Notably, this type of occlusion led to reversals of blood flow in the penetrating arterioles mainly proximal to the occluded pial arteriole in a direction from the subsurface microcirculation network to surface arterioles. Interesting, the cell death in the area of ischemic penumbra was accelerated when we performed occlusion to cease the reversed blood flow in those penetrating arterioles, suggesting that the collateral blood flow from subsurface microcirculation network exerts protective roles in delaying cell death in the ischemic penumbra. In conclusion, we provide the first experimental evidence that collateral blood vessels at different cerebrovascular hierarchy are endogenously compensatory mechanisms in brain ischemia. This article is protected by

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

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    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.

  17. The effect of hypothermia on the expression of neurotrophin mRNA in the hippocampus following transient cerebral ischemia in the rat.

    Science.gov (United States)

    Boris-Möller, F; Kamme, F; Wieloch, T

    1998-12-10

    The expression of the mRNAs of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3) and the neurotrophin receptor, TrkB, was studied in the rat hippocampus by in situ hybridization following normothermic (37 degreesC) and protective hypothermic (33 degreesC) transient cerebral ischemia of 15 min duration. In the resistant dentate gyrus, normothermic ischemia transiently induced NGF mRNA at around 8 h of recovery, while the NT3 mRNA levels were depressed over at least a 24-h recovery period. The levels of BDNF and TrkB were transiently and markedly elevated with a maximal expression at 24 h of recovery. Intraischemic hypothermia reduced the induction of NGF mRNA, while the increase of BDNF mRNA expression occurred earlier during recovery, and the post-ischemic NT3 mRNA depression was not affected. Also, the expression of TrkB mRNA was enhanced, and occurred concomitantly with the elevation of BDNF mRNA. In contrast, there were no changes in neurotrophin and TrkB mRNA in the CA3 and CA1 regions. The expression of BDNF mRNA at 24 h after normothermic ischemia, was attenuated by intraischemic hypothermia. We conclude that, the expressions of NGF, BDNF, NT3 or TrkB mRNA in ischemia-sensitive hippocampal subregions are not increased by protective hypothermia. In contrast, hypothermia induces neurotrophin mRNA alterations in the ischemia-resistant dentate gyrus that may convey protection to sensitive regions.

  18. 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

  19. 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.

  20. Effect of Electroacupuncture on Expression of p53 Protein in Cerebral Cortex of Rats with Global Cerebral Ischemia/Reperfusion Injury

    Institute of Scientific and Technical Information of China (English)

    卜渊; 耿德勤; 葛巍; 徐兴顺; 曾因明

    2004-01-01

    Objective: To observe the effect of electroacupuncture (EA) on expression of p53 protein in cerebral cortex of senile rats with global cerebral ischemia/reperfusion (IR) injury and to explore its mechanism. Methods: The cerebral IR injury rat model was established referring to Pulsinelli 4-vessel occlusion method. Thirty-six SD rats were randomly and evenly divided into the control group, the IR group and the IR plus EA (IR-EA) group. The animals in the control group were subjected to electrocauterization of vertebral arteries in bilateral flank orifice alone with the general carotid arteries unoccluded.To rats in the IR-EA group, immediately and 24h, 48h, 72h after cerebral IR, EA treatment on bilateral acupoint "Zusanli"(ST36) was applied once a day, lasting for 60 minutes. After the final treatment, all the rats were sacrificed and their brains were taken to examine p53 protein expression by the immunohistochemical method. Results: Cells with positive p53 immunoreactivity in the cerebral cortex of rats in the IR group was significantly higher than that in the control group ( P<0.05), while that in the IR-EA group was significantly lower than that in the IR group (P<0.05). Conclusion: EA could remarkably reduce expression of p53 protein in the cerebral cortex of senile rats with global cerebral IR injury, which might be one of the means for EA to inhibit neuronal apoptosis after cerebral IR injury.

  1. 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

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

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    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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  4. Detection of cerebral ischemia using the power spectrum of the pulse wave measured by near-infrared spectroscopy.

    Science.gov (United States)

    Ebihara, Akira; Tanaka, Yuichi; Konno, Takehiko; Kawasaki, Shingo; Fujiwara, Michiyuki; Watanabe, Eiju

    2013-10-01

    The diagnosis and medical treatment of cerebral ischemia are becoming more important due to the increase in the prevalence of cerebrovascular disease. However, conventional methods of evaluating cerebral perfusion have several drawbacks: they are invasive, require physical restraint, and the equipment is not portable, which makes repeated measurements at the bedside difficult. An alternative method is developed using near-infrared spectroscopy (NIRS). NIRS signals are measured at 44 positions (22 on each side) on the fronto-temporal areas in 20 patients with cerebral ischemia. In order to extract the pulse-wave component, the raw total hemoglobin data recorded from each position are band-pass filtered (0.8 to 2.0 Hz) and subjected to a fast Fourier transform to obtain the power spectrum of the pulse wave. The ischemic region is determined by single-photon emission computed tomography. The pulse-wave power in the ischemic region is compared with that in the symmetrical region on the contralateral side. In 17 cases (85%), the pulse-wave power on the ischemic side is significantly lower than that on the contralateral side, which indicates that the transmission of the pulse wave is attenuated in the region with reduced blood flow. Pulse-wave power might be useful as a noninvasive marker of cerebral ischemia.

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

    Science.gov (United States)

    Guo, Zongjun; Wang, Lumin

    2012-07-25

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

  7. Cholinergic receptor blockade by scopolamine and mecamylamine exacerbates global cerebral ischemia induced memory dysfunction in C57BL/6J mice.

    Science.gov (United States)

    Ray, R S; Rai, S; Katyal, A

    2014-12-01

    Global cerebral ischemia/reperfusion (GCI/R) injury encompasses complex pathophysiological sequalae, inducing loss of hippocampal neurons and behavioural deficits. Progressive neuronal death and memory dysfunctions culminate from several different mechanisms like oxidative stress, excitotoxicity, neuroinflammation and cholinergic hypofunction. Experimental evidences point to the beneficial effects of cholinomimetic agents such as rivastigmine and galantamine in improving memory outcomes following GCI/R injury. However, the direct implications of muscarinic and nicotinic receptor blockade during global cerebral ischemia/reperfusion injury have not been investigated. Therefore, we evaluated the relative involvement of muscarinic and nicotinic receptors in spatial/associative memory functions and neuronal damage during global cerebral ischemia reperfusion injury. The outcomes of present study support the idea that preservation of both muscarinic and nicotinic receptor functions is essential to alleviate hippocampal neuronal death in CA1 region following global cerebral ischemia/reperfusion injury.

  8. 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.

  9. Acetylcholine- and sodium hydrosulfide-induced endothelium-dependent relaxation and hyperpolarization in cerebral vessels of global cerebral ischemia-reperfusion rat.

    Science.gov (United States)

    Han, Jun; Chen, Zhi-Wu; He, Guo-Wei

    2013-01-01

    We investigated the effects of endothelium-derived hyperpolarizing factor (EDHF) and the role of hydrogen sulphide (H2S) in the cerebral vasorelaxation induced by acetylcholine (ACh) in global cerebral ischemia-reperfusion (CIR) rats. CIR was induced by occlusion of bilateral carotid and vertebral arteries. Isolated arterial segments from the cerebral basilar (CBA) and middle artery (MCA) of CIR rats were studied in a pressurized chamber. Transmembrane potential was recorded using glass microelectrodes to evaluate hyperpolarization. In the CIR CBAs and MCAs preconstricted by 30 mM KCl, ACh induced concentration-dependent vasorelaxation and hyperpolarization that were partially attenuated by NG-nitro-l-arginine methyl ester (l-NAME, 30 μM) and l-NAME plus indomethacin (10 μM). The residual responses were abolished by the H2S inhibitor dl-propargylglycine (PPG, 100 μM). The H2S donor NaHS and l-Cys, the substrate of endogenous H2S synthase, elicited similar responses to ACh and was inhibited by tetraethylamonine (1 mM) or PPG. ACh induces EDHF-mediated vasorelaxation and hyperpolarization in rat cerebral arteries. These responses are up-regulated by ischemia-reperfusion while NO-mediated responses are down-regulated. Further, the ACh-induced, EDHF-mediated relaxation, and hyperpolarization and the inhibition of these responses are similar to the H2S-induced responses, suggesting that H2S is a possible candidate for EDHF in rat cerebral vessels.

  10. Cerebral Post-Transplant Lymphoproliferative Disorder Occurring after Renal Transplantation: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Suh, Jang Ho; Byun, Woo Mok; Kim, Hong Chul; Hwang, Min Su [Dept. of Radiology, Yeungnam University College of Medicine, Daegu (Korea, Republic of)

    2012-04-15

    Post-transplant lymphoproliferative disorder (PTLD) is a complication of organ transplantation and immunosuppression. A 36-year-old woman with a history of renal transplantation visited the hospital complaining of headache and on pathology was diagnosed with cerebral PTLD manifesting as multiple rim enhanced masses in both hemispheres. We report here a case of post-transplant lymphoproliferative disorder involving the cerebrum occurring after renal transplantation, and describe the MRI findings for this patient

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

    Directory of Open Access Journals (Sweden)

    Heurteaux Catherine

    2007-05-01

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

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

    Institute of Scientific and Technical Information of China (English)

    马瑞玲; 袁青

    2003-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Hyun Ah eKim

    2014-11-01

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

  14. 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.

  15. Neuroprotective Effect of Sodium Butyrate against Cerebral Ischemia/Reperfusion Injury in Mice

    Directory of Open Access Journals (Sweden)

    Jing Sun

    2015-01-01

    Full Text Available Sodium butyrate (NaB is a dietary microbial fermentation product of fiber and serves as an important neuromodulator in the central nervous system. In this study, we further investigated that NaB attenuated cerebral ischemia/reperfusion (I/R injury in vivo and its possible mechanisms. NaB (5, 10 mg/kg was administered intragastrically 3 h after the onset of reperfusion in bilateral common carotid artery occlusion (BCCAO mice. After 24 h of reperfusion, neurological deficits scores were estimated. Morphological examination was performed by electron microscopy and hematoxylin-eosin (H&E staining. The levels of oxidative stress and inflammatory cytokines were assessed. Apoptotic neurons were measured by TUNEL; apoptosis-related protein caspase-3, Bcl-2, Bax, the phosphorylation Akt (p-Akt, and BDNF were assayed by western blot and immunohistochemistry. The results showed that 10 mg/kg NaB treatment significantly ameliorated neurological deficit and histopathology changes in cerebral I/R injury. Moreover, 10 mg/kg NaB treatment markedly restored the levels of MDA, SOD, IL-1β, TNF-α, and IL-8. 10 mg/kg NaB treatment also remarkably inhibited the apoptosis, decreasing the levels of caspase-3 and Bax and increasing the levels of Bcl-2, p-Akt, and BDNF. This study suggested that NaB exerts neuroprotective effects on cerebral I/R injury by antioxidant, anti-inflammatory, and antiapoptotic properties and BDNF-PI3K/Akt pathway is involved in antiapoptotic effect.

  16. Identification and Functional Analysis of MicroRNAs in Mice following Focal Cerebral Ischemia Injury

    Directory of Open Access Journals (Sweden)

    Cuiying Liu

    2015-10-01

    Full Text Available Numerous studies have demonstrated that genes, RNAs, and proteins are involved in the occurrence and development of stroke. In addition, previous studies concluded that microRNAs (miRNAs or miRs are closely related to the pathological process of ischemic and hypoxic disease. Therefore, the aims of this study were to quantify the altered expression levels of miRNAs in the infarct region 6 h after middle cerebral artery occlusion (MCAO-induced focal cerebral ischemia in mice using a large-scale miRNAs microarray. Firstly, MCAO-induced cerebral ischemic injuries were investigated by observing the changes of neurological deficits, infarct volume and edema ratio. One hundred and eighteen differentially expressed miRNAs were identified in the infarct region of mice following the MCAOs compared with sham group (p < 0.05 was considered as significant. Among these 118 significantly expressed microRNAs, we found that 12 miRNAs were up-regulated with fold changes lager than two, and 18 miRNAs were down-regulated with fold changes less than 0.5 in the infarct region of mice following the 6 h MCAOs, compared with the sham group. Then, these 30 miRNAs with expression in fold change larger than two or less than 0.5 was predicted, and the functions of the target genes of 30 miRNAs were analyzed using a bioinformatics method. Finally, the miRNA-gene network was established and the functional miRNA-mRNA pairs were identified, which provided insight into the roles of the specific miRNAs that regulated specified genes in the ischemic injuries. The miRNAs identified in this study may represent effective therapeutic targets for stroke, and further study of the role of these targets may increase our understanding of the mechanisms underlying ischemic injuries.

  17. 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.

  18. Effect of Xingnaojing Injection (醒脑静注射液) on Hippocampal N-methyl-D-aspartic Acid Receptors of Focal Cerebral Ischemia in Rats

    Institute of Scientific and Technical Information of China (English)

    沈思钰; 蔡定芳; 陈伟华; 刘静; 陈虎; 应健

    2003-01-01

    Objective: To observe and elucidate the neuroprotective effect of Xingnaojing (XNJ) injection on hippocampal N-methyl-D-aspartic acid (NMDA) receptors of focal cerebral ischemia in rats. Methods: Cerebral ischemia was established by occluding the middle cerebral artery with an intraluminal suture technique in rats. Neurological deficit score, infarct volume and quantity of NMDA receptors were estimated in all groups and compared. Results: After being treated with XNJ, the score decreased in the initial 6 hours and infarct volume decreased in 24 hours. And within 24 hours,the quantity of NMDA receptors obviously decreased compared with the model group(P<0.01). It indicated that XNJ could ameliorate neurological behavior of middle cerebral artery occlusion rats and down-regulate the expression of hippocampal NMDA receptors. Conclusion: The neuroprotective effect of XNJ on focal cerebral ischemia is possibly related to down-regulating the expression of NMDA receptors in rats.

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

    Science.gov (United States)

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

    2017-04-01

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

  20. YiQiFuMai Powder Injection Ameliorates Cerebral Ischemia by Inhibiting Endoplasmic Reticulum Stress-Mediated Neuronal Apoptosis

    Directory of Open Access Journals (Sweden)

    Guosheng Cao

    2016-01-01

    Full Text Available YiQiFuMai (YQFM powder injection as a modern preparation derived from Sheng Mai San, a traditional Chinese medicine, has been widely used in the treatment of cardiovascular and cerebrovascular diseases. However, its neuroprotective effect and underlying mechanism in cerebral ischemia remain to be explored. The present study was designed to investigate the neuroprotective effect of YQFM on endoplasmic reticulum (ER stress-mediated neuronal apoptosis in the permanent middle cerebral artery occlusion- (MCAO- injured mice and the oxygen-glucose deprivation- (OGD- induced pheochromocytoma (PC12 cells. The results showed that single administration of YQFM (1.342 g/kg, i.p. could reduce the brain infarction and improve the neurological deficits and the cerebral blood flow (CBF after MCAO for 24 h in mice. Moreover, incubation with YQFM (100, 200, and 400 μg/mL could increase the cell viability, decrease the caspase-3 activity, and inhibit the cell apoptosis in OGD-induced PC12 cells for 12 h. In addition, YQFM treatment could significantly modulate cleaved caspase-3 and Bcl-2 expressions and inhibit the expressions of ER stress-related marker proteins and signaling pathways in vivo and in vitro. In conclusion, our findings provide the first evidence that YQFM ameliorates cerebral ischemic injury linked with modulating ER stress-related signaling pathways, which provided some new insights for its prevention and treatment of cerebral ischemia diseases.

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

    Science.gov (United States)

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

    2013-07-12

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

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

    Science.gov (United States)

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

    2015-09-01

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

  3. Neuroprotective effect of pretreatment with ganoderma lucidum in cerebral ischemia/reperfusion injur y in rat hippocampus

    Institute of Scientific and Technical Information of China (English)

    Wangxin Zhang; Qiuling Zhang; Wen Deng; Yalu Li; Guoqing Xing; Xianjun Shi; Yifeng Du

    2014-01-01

    Ganoderma lucidum is a traditional Chinese medicine, which has been shown to have both an-ti-oxidative and anti-inlfammatory effects, and noticeably decreases both the infarct area and neuronal apoptosis of the ischemic cortex. This study aimed to investigate the protective effects and mechanisms of pretreatment with ganoderma lucidum (by intragastric administration) in cerebral ischemia/reperfusion injury in rats. Our results showed that pretreatment with ganoder-ma lucidum for 3 and 7 days reduced neuronal loss in the hippocampus, diminished the content of malondialdehyde in the hippocampus and serum, decreased the levels of tumor necrosis fac-tor-αand interleukin-8 in the hippocampus, and increased the activity of superoxide dismutase in the hippocampus and serum. hTese results suggest that pretreatment with ganoderma lucidum was protective against cerebral ischemia/reperfusion injury through its anti-oxidative and an-ti-inlfammatory actions.

  4. Feasibility of establishing cerebral ischemia models by using aerocyst-blocking bilateral ascending pharyngeal artery of piglets Imaging assessment

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: The cerebral ischemia and ischemia/reperfusion animal models are used to simulate the human cerebrovascular diseases is one of the popular topics of neurological science recently. To study the pathophysiology, pathogenesis, prophylaxis and treatment of ischemic cerebrovascular diseases and to establish the ideal animal model that is the most similar to the human cerebral ischemia, are the topics that the people generally cared about.OBJECTIVE: To evaluate the effects of aerocyst-blocking bilateral ascending pharyngeal artery on the establishment of cerebral ischemia models by using digital subtraction angiography (DSA), magnetic resonance diffusion-weighted imaging (DWI) and magnetic resonance perfusion-weighted imaging (PWI). DESIGN: Repetitive measure animal experiment.SETTING: Zhongshan Hospital Affiliated to Dalian University.MATERIALS: The experiment was carried out in the Animal Laboratory (Provincial Laboratory),Zhongshan Hospital of Dalian Univeristy from January to May 2006. A total of 14 domestic piglets, of 6 months old, weighing 12 - 15 kg, of either gender, were selected from Animal Experimental Center, Dalian University. Multistar T.O.P digital subtraction angiography machine was provided by Siemens Company,German.METHODS: Aerocyst-blocking bilateral ascending pharyngeal artery was used to establish cerebral ischemia models. And then, Multistar T.O.P. DSA was used for imaging of cerebral vessels before blocking, during blocking and at 0.5 and 2 hours after ischemia perfusion. GE Signa 1.5 T supraconduction magnetic resonance imaging was used for DWI examination; in addition, PWI was used based on focal sites and areas.Otherwise, magnetic resonance imaging (MRI) was used to detect signal changes of T1WI and T2WI in ischemic areas.MAIN OUTCOME MEASURES: Analytic results of DSA, DWI, PWI and MRI.RESULTS: All 14 experimental piglets were involved in the final analysis. ① DSA: The blood flow of bilateral ascending pharyngeal arteries and its

  5. 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

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    Chun-juan Jiang

    2016-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-09-01

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

  10. Delayed cerebral ischemia associated with reversible cerebral vasoconstriction in a patient with Moyamoya disease with intraventricular hemorrhage: Case report.

    Science.gov (United States)

    Matsuoka, Go; Kubota, Yuichi; Okada, Yoshikazu

    2015-06-01

    We describe a case of cerebral infarctions caused by transient vasoconstrictions in the posterior circulation 2 weeks after intraventricular hemorrhage without subarachnoid hemorrhage in a 35-year-old patient with Moyamoya disease. To our knowledge, this is the first case report where diffuse segmental vasoconstrictions of the basilar and posterior cerebral arteries were recognized after intraventricular hemorrhage in Moyamoya disease. The patient complained of severe and acute-onset headache 14 days after the intraventricular hemorrhage, which had a different character and severity from the one she complained of at the onset of intraventricular hemorrhage. Finally, headache disappeared within 1 month and vasoconstriction resolved in 2 months. Reversible cerebral vasoconstriction syndrome was under consideration for the etiology of her condition because of the "thunderclap" characteristics of the headache and the delayed timing of occurrence of the vasoconstriction. This case report informs and alerts neurologists, neurosurgeons and neuroradiologists who observe and treat patients with Moyamoya disease that vasoconstriction in the posterior circulation may occur after intraventricular hemorrhage in these patients.

  11. Bone marrow stromal cells can promote the neurogenesis in subventricular zone in the rat with focal cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Pushuai Wen

    2010-01-01

    Full Text Available   Abstract Introdution: Stroke is one of the most common diseases caused by occlusion or rupture of blood vessels in brain. It brings heavily loads for families and societies. Although some new strategies including treatment of tissue plasminogen activator have been applied in the clinic, these methods do not have perfect effect. Accordingly, more effective therapeutic strategies need to be developed. This study was conducted to investigate the action of bone marrow stromal cells (BMSC on the neural stem cells in the subventricular zone of the rat after focal cerebral ischemia. Methods: The rats were induced to permanent focal cerebral ischemia models with middle cerebral artery occlusion (MCA0. Test groups consisted of three groups: MCAO alone, intravenous infusion of 1 ml PBS at 24 hours after MCAO, and intravenous infusion of 2×106 BMSCs 24 hours after MCAO. Then, the groups were divided to investigate at 7 and 14 days after MACO. Neurological functions were detected to use Zausinger evaluation; meanwhile, 5-bromodeoxyuridine was injected to label the proliferating cells in the subventricular zone, and double-immunofluoroscent technologies were used to identify the cell type.  Results: Neurological functional scores of BMSCs-treated group were higher than other two groups (p<0.05 at 7 and 14 days after MACO. BrdU-positive cells in SVZ of ipsilateral ischemia of BMSCs-treated group were more than two controls (p<0.05 at 14 days after MCAO; double-immunofluorescence label demonstrated that BrdU-positive cells co-located with markers of neuron and astrocyte.   Discussion: BMSCs can promote the neurological function of the rats with permanent focal cerebral ischemia, which may associate with the neurogenesis in the subventricular zone.

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

    Directory of Open Access Journals (Sweden)

    Sakiko Suzuki

    2011-01-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

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

    OpenAIRE

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

    2011-01-01

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

  15. Tin chloride enhances parvalbumin-positive interneuron survival by modulating heme metabolism in a model of cerebral ischemia.

    Science.gov (United States)

    Li Volti, Giovanni; Zappalà, Agata; Leggio, Gian Marco; Mazzola, Carmen; Drago, Filippo; La Delia, Francesco; Serapide, Maria Francesca; Pellitteri, Rosalia; Giannone, Ignazio; Spatuzza, Michela; Cicirata, Valentina; Cicirata, Federico

    2011-03-29

    SnCl(2) has been reported to increase the expression of heme-oxygenase 1 (HO-1), a major antioxidant enzyme, and to decrease ischemic injury, in non-nervous tissues. This study examined the neuroprotective effect of SnCl(2) in the hippocampus of rats submitted to cerebral ischemia. SnCl(2) was administered 18 h before bilateral carotids obstruction. Changes in HO-1 expression and activity, heme content, inducible nitric oxide synthase (iNOS) expression and parvalbumin positive interneuron survival were studied. Thereafter both behavior and memory recovery were tested. The administration of SnCl(2) increased the expression of HO-1 protein and HO activity in the hippocampus and concomitantly decreased heme content at both mitochondrial and nuclear level. Furthermore, ischemized animals showed a strong increase in iNOS expression in the hippocampus, where a loss of parvalbumin positive interneurons also occurred. Pre-treatment with SnCl(2), decreased both iNOS expression in ischemized rats and increased cell survival. The beneficial effects of SnCl(2) were prevented by concomitant treatment with SnMP, a strong inhibitor of HO activity. SnCl(2) also caused an improvement in short term memory recovery. Our results showed that following SnCl(2) administration, HO-1 is strongly induced in the hippocampus and modulate iNOS expression, resulting in a strong neuroprotective effect.

  16. Expression of nerve growth factor precursor, mature nerve growth factor and their receptors during cerebral ischemia-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Guoqian He; Jian Guo; Jiachuan Duan; Wenming Xu; Ning Chen; Hongxia Li; Li He

    2011-01-01

    We investigated nerve growth factor precursor (proNGF) and mature NGF expression in ischemic and non-ischemic cortices after cerebral ischemia-reperfusion injury.In both ischemic and non-ischemic cortices, proNGF was found to be present in the extracellular space and cytoplasm.In addition, mature NGF was expressed in extracellular space, but with a very low signal.In ischemic cortex only, proNGF was significantly decreased, reaching a minimal level at 1 day.Mature NGF was increased at 4 hours, then reached a minimal level at 3 days.The p75 neurotrophin receptor (p75NTR) was significantly decreased after ischemia, and increased at 3 days after ischemia.These results confirmed that proNGF was the predominant form of NGF during the pathological process of cerebral ischemia-reperfusion injury.In addition, our findings suggest that ischemic injury may influence the conversion of proNGF to mature NGF, and that proNGF/p75NTR may be involved in reperfusion injury.

  17. Comparison of antioxidant activity of hydroethanolic fresh and aged garlic extracts and their effects on cerebral ischemia.

    Science.gov (United States)

    Cervantes, Maria Isabel; de Oca Balderas, Pavel Montes; de Jesús Gutiérrez-Baños, José; Orozco-Ibarra, Marisol; Fernández-Rojas, Berenice; Medina-Campos, Omar Noel; Espinoza-Rojo, Mónica; Ruiz-Tachiquín, Martha; Ortiz-Plata, Alma; Salazar, Ma Isabel; Rubio-Osornio, Moisés; Castañeda-Saucedo, Eduardo; Pedraza-Chaverri, José; Calzada, Fernando; Aguilera, Penélope

    2013-09-01

    Antioxidant properties and protective effect of aged garlic extract (AGE) and of 20% hydroethanolic fresh extracts from garlic clove (GCE) and skin (GSE) on cerebral ischemia were evaluated by administering extracts at the beginning of reperfusion in a rat model of stroke. All three extracts scavenged superoxide anion, peroxynitrite anion, and peroxyl radicals, but with different efficiencies; furthermore, GCE and GSE scavenged hydroxyl radicals and GSE scavenged singlet oxygen. These extracts significantly prevented reduction of neuronal nuclear antigen in the infarcted area, although no improvement in neurological function was observed. Importantly, GCE and GSE contained S-allylcystein, a compound associated with AGE's neuroprotective effect against damage induced by cerebral ischemia. Extracts decreased mRNA expression of NR1- and NR2B-NMDA-receptor subunits and prevented ischemia-induced reduction in mitochondrial potential and in ATP synthesis. These results indicate that antioxidants present in garlic extracts may regulate ROS concentrations during ischemia, favour pro-survival pathways, and attenuate mitochondrial dysfunction.

  18. Angiopoietin-1 mRNA expression in estradiol-treated ovariectomized rats with focal cerebral ischemia after reperfusion

    Institute of Scientific and Technical Information of China (English)

    Ling Tang; Jun Zuo; Yonghong Wang; Yuanda Zhou; Haixia He

    2008-01-01

    BACKGROUND: Epidemiologic studies have indicated that the incidence of stroke in premenopausal females is lower than in males at the same age, but it significantly rises in postmenopausal females. Estrogen is used clinically to alleviate injury caused by cerebral ischemia. It has been hypothesized that the neuroprotective role of estrogen relates to angiopoietin (Angpt), which plays an important role in vascularization, vascular remodeling and maturation.OBJECTIVE: To observe and validate the effect of estradiol on angiopoietin-1 (Angpt1) mRNA expression in ovariectomized rats with focal cerebral ischemia alter reperfusion, so as to explore the molecular mechanisms of estradiol-mediated protection from cerebral ischemic damage.DESIGN, TIME AND SETTING: Randomized, controlled, molecular biology, prospective animal study. The experiment was performed at the Central Laboratory of Chongqing Medical University from September to December 2005.MATERIALS: Fifty healthy female wild type (WT) rats aged 6 months and fifty female rats aged 6 months with knockout of the estrogen-alpha receptor gene (ERKO).METHODS: WT rats and ERKO rats were divided into estradiol and control groups (n = 25), and injected intramuscularly with estradiol benzoate (100 μg/kg per day) or corn oil (1 mL/kg per day) for 7 days, 30 days after bilateral ovariectomy. Rat models of cerebral ischemia/reperfusion were established with the middle cerebral artery occlusion method. After 30 minutes of middle cerebral artery occlusion, rats from the estradiol and control groups were injected intramuscularly with estradiol benzoate or corn oil at the above dose.MAIN OUTCOME MEASURES: We used radio-immunity analysis and laser-Doppler flowmetry to measure plasma estradiol levels and changes in cerebral blood flow. We used immunohistochemical staining of CD34 epitopes to measure changes in the capillary density in brain following cerebral ischemia/reperfusion, and quantitative RT-PCR analysis to assess m

  19. Targeting Glial Mitochondrial Function for Protection from Cerebral Ischemia: Relevance, Mechanisms, and the Role of MicroRNAs

    Directory of Open Access Journals (Sweden)

    Le Li

    2016-01-01

    Full Text Available Astrocytes and microglia play crucial roles in the response to cerebral ischemia and are effective targets for stroke therapy in animal models. MicroRNAs (miRs are important posttranscriptional regulators of gene expression that function by inhibiting the translation of select target genes. In astrocytes, miR expression patterns regulate mitochondrial function in response to oxidative stress via targeting of Bcl2 and heat shock protein 70 family members. Mitochondria play an active role in microglial activation, and miRs regulate the microglial neuroinflammatory response. As endogenous miR expression patterns can be altered with exogenous mimics and inhibitors, miR-targeted therapies represent a viable intervention to optimize glial mitochondrial function and improve clinical outcome following cerebral ischemia. In the present article, we review the role that astrocytes and microglia play in neuronal function and fate following ischemic stress, discuss the relevance of mitochondria in the glial response to injury, and present current evidence implicating miRs as critical regulators in the glial mitochondrial response to cerebral ischemia.

  20. 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.

  1. 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.

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

    Science.gov (United States)

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

    2016-06-15

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

  3. Uric Acid Is Protective After Cerebral Ischemia/Reperfusion in Hyperglycemic Mice.

    Science.gov (United States)

    Justicia, Carles; Salas-Perdomo, Angélica; Pérez-de-Puig, Isabel; Deddens, Lisette H; van Tilborg, Geralda A F; Castellví, Clara; Dijkhuizen, Rick M; Chamorro, Ángel; Planas, Anna M

    2016-12-15

    Hyperglycemia at stroke onset is associated with poor long-term clinical outcome in numerous studies. Hyperglycemia induces intracellular acidosis, lipid peroxidation, and peroxynitrite production resulting in the generation of oxidative and nitrosative stress in the ischemic tissue. Here, we studied the effects of acute hyperglycemia on in vivo intercellular adhesion molecule-1 (ICAM-1) expression, neutrophil recruitment, and brain damage after ischemia/reperfusion in mice and tested whether the natural antioxidant uric acid was protective. Hyperglycemia was induced by i.p. administration of dextrose 45 min before transient occlusion of the middle cerebral artery. Magnetic resonance imaging (MRI) was performed at 24 h to measure lesion volume. A group of normoglycemic and hyperglycemic mice received an i.v. injection of micron-sized particles of iron oxide (MPIOs), conjugated with either anti-ICAM-1 antibody or control IgG, followed by T2*w MRI. Neutrophil infiltration was studied by immunofluorescence and flow cytometry. A group of hyperglycemic mice received an i.v. infusion of uric acid (16 mg/kg) or the vehicle starting after 45 min of reperfusion. ICAM-1-targeted MPIOs induced significantly larger MRI contrast-enhancing effects in the ischemic brain of hyperglycemic mice, which also showed more infiltrating neutrophils and larger lesions than normoglycemic mice. Uric acid reduced infarct volume in hyperglycemic mice but it did not prevent vascular ICAM-1 upregulation and did not significantly reduce the number of neutrophils in the ischemic brain tissue. In conclusion, hyperglycemia enhances stroke-induced vascular ICAM-1 and neutrophil infiltration and exacerbates the brain lesion. Uric acid reduces the lesion size after ischemia/reperfusion in hyperglycemic mice.

  4. Effects of ligustrazine on somatosensory evoked potential in normal rabbits and rabbits with cerebral ischemia-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Deshan Liu; Shuli Wang; Yuanyuan Hao

    2006-01-01

    BACKGROUND: Somatosensory evoked potential (SEP) has become a method with higher sensitivity and specificity than electroencephalogram in detecting the brain function and the region, range and degree of ischemia. However, the effects of ligustrazine on SEP is still not clear.OBJECTIVE: To study the protective effects of ligustrazini injection on cerebral ischemia-reperfusion injury.DESIGN: Auto-control study, random grouping.SETTING: Qilu Hospital of Shandong University.MATERIALS: The experiment was completed in the Cerebral Functional Room of Qilu Hospital Affiliated to Shandong University from March 2002 to June 2004. A totally of 24 healthy Harbin rabbits were randomly divided into blank control group (n=8), model control group (n=8) and ligustrazine treatment group (n=8).Hydrochloric ligustrazine injection, 40 mg/2 mL each ampoule, was provided by the Third Pharmaceutical Factory of Beijing (certification: 93035236273). The main component was hydrochloric ligustrazine and the chemical name was 2, 3, 5, 6-tetramethyl pyrazine hydrochloride.METHODS: ① Modeling method: The bilateral common carotid artery ligation was adopted to make the model. ② Index of cerebral functional lesion evaluated with SEP during ischemia-reperfusion: DISA 2000C neuromyoeletrometer provided by Dantec Electronics Ltd, Denmark was used to detect SEP. ③ Interventional process: Blank control group: The latencies and amplitudes of SEP were measured before injection with 1.5 mg/kg ligustrazine and at the points of 15 minutes, 20 minutes, 30 minutes, 60 minutes, 90 minutes and 120 minutes after injection. Ligustrazine treatment group: Rabbits were injected with 1.5 mg/kg ligustrazine, and those of model control group were injected the same volume of saline. Thirty minutes later, the bilateral common carotid artery of the rabbits all had been ligated for 30 minutes, and then reperfused for 120 minutes. The latencies and amplitudes of SEP were measured before injection, before ligation, at

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  6. Amelioration of cerebral ischemia-reperfusion injury based on liposomal drug delivery system with asialo-erythropoietin.

    Science.gov (United States)

    Ishii, Takayuki; Asai, Tomohiro; Oyama, Dai; Fukuta, Tatsuya; Yasuda, Nodoka; Shimizu, Kosuke; Minamino, Tetsuo; Oku, Naoto

    2012-05-30

    Cerebral ischemia-reperfusion (I/R) injury induces secondary cerebral damage. As drugs for treating this type of injury have shown poor efficacy and adverse side effects in clinical trials, a novel therapeutic strategy has been long awaited. In this study, we focused on the disruption of the blood-brain barrier after stroke, and applied a liposomal drug delivery system (DDS) designed to enhance the pharmacological effect of the neuroprotectant and to avoid side effects. PEGylated liposomes were injected at varying time after the start of reperfusion in transient middle cerebral artery occlusion (t-MCAO) model rats. The results showed PEGylated liposomes accumulated in the ischemic hemisphere at an early stage after reperfusion and were retained in the lesion for at least 24h after injection. We also investigated the effectiveness of asialo-erythropoietin (AEPO)-modified PEGylated liposomes (AEPO-liposomes) in treating the cerebral I/R injury. AEPO-liposome treatment significantly reduced TTC-defined cerebral legion following cerebral I/R injury, and ameliorated motor function compared with vehicle and AEPO treatment. In conclusion, these results indicate that AEPO-liposomes are a promising liposomal formulation for protecting the brain from I/R injury, and that this liposomal DDS has potential as a novel strategy for the treatment of cerebral I/R injury.

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

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

    Science.gov (United States)

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

    2011-03-04

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

  10. Na(+)/Ca(2+) exchanger 2 is neuroprotective by exporting Ca(2+) during a transient focal cerebral ischemia in the mouse.

    Science.gov (United States)

    Jeon, Daejong; Chu, Kon; Jung, Keun-Hwa; Kim, Manho; Yoon, Byung-Woo; Lee, C Justin; Oh, Uhtaek; Shin, Hee-Sup

    2008-05-01

    Na(+)/Ca(2+) exchanger (NCX), by mediating Na(+) and Ca(2+) fluxes bi-directionally, assumes a role in controlling the Ca(2+) homeostasis in the ischemic brain. It has been suggested that the three isoforms of NCX (NCX1, 2 and 3) may be differentially involved in permanent cerebral ischemia. However, the role of NCX2 has not been defined in ischemic reperfusion injury after a transient focal cerebral ischemia. Furthermore, it is not known whether NCX2 imports or exports intracellular Ca(2+) ([Ca(2+)](i)) following ischemia and reperfusion. To define the role of NCX2 in ischemia and reperfusion, we examined mice lacking NCX2, in vivo and in vitro. After an in vitro ischemia, a significantly slower recovery in population spike amplitudes, a sustained elevation of [Ca(2+)](i) and an increased membrane depolarization were developed in the NCX2-deficient hippocampus. Moreover, a transient focal cerebral ischemia in vivo produced a larger infarction and more cell death in the NCX2-deficient mouse brain. In particular, in the wild type brain, NCX2-expressing neurons were largely spared from cell death after ischemia. Our results suggest that NCX2 exports Ca(2+) in ischemia and thus protects neuronal cells from death by reducing [Ca(2+)](i) in the adult mouse brain.

  11. EFFECT OF ELECTROACUPUNCTURE ON SYNAPTIC PLASTICITY OF HPPOCAMPAL NEURONS IN CEREBRAL ISCHEMIA RATS

    Institute of Scientific and Technical Information of China (English)

    杨卓欣; 于海波; 王玲; 张家维

    2004-01-01

    Objective:To observe the effect of electroacupuncture (EA) on synaptic structure of hippocampal nerve felts and synaptophysin(SYN)expression in rats with cerebral ischemic injury. Methods: Sixty Wistar rats were randomized into sham-operation group, cerebral ischemia (CI) group and EA group, each of which was further divided into 1week (W) and 5W subgroups. CI injury model was established by occlusion of the bilateral common carotid arteries. "Baihui"(百会 GV 20), "Dazhui" (大椎 GV 14), "Renzhong"(人中 GV 26) and "Guanyuan"(关元 CV 4) were punctured and stimulated electrically. The brain tissue sections containing hippocampus region were stained with immunohistochemical technique and observed under light microscope and transmission electronic microscope. Results: After CI, the ischemic injury as degeneration of the presynapse compositions, decrease of the synaptic numeral density, and low expression of SYN were observed in hippocampal CA1 area. By the 5th week after CI, the neonatal synapses of CI and EA groups appeared, and SYN expression was upregulated. In EA group, the recovery of the numeral density of synapses was especially noticeable, being 93.8% of that of sham-operation group and significantly higher than that in CI group (P<0.01). Compared with sham-operation group, the calibrated optical density (COD) values of SYN increased to 70% in CI group, and 93.3% in EA group, and COD value in EA group was significantly higher than that in CI group (P<0.01). Conclusion: EA can function in promoting synaptic regeneration and enhancing and perfecting the actions of the reconstructed synapses in hippocampal CA1 area in CI rats.

  12. 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.

  13. Bone Morphogenetic Protein-7 Ameliorates Cerebral Ischemia and Reperfusion Injury via Inhibiting Oxidative Stress and Neuronal Apoptosis

    Directory of Open Access Journals (Sweden)

    Haitao Pei

    2013-11-01

    Full Text Available Previous studies have indicated that bone morphogenetic protein-7 (BMP-7 is neuroprotective against cerebral ischemia/reperfusion (IR injury. The present study was undertaken to determine the molecular mechanisms involved in this effect. Adult male Wistar rats were subjected to 2 h of transient middle cerebral artery occlusion (MCAO, followed by 24 h of reperfusion. BMP-7 (10−4 g/kg or vehicle was infused into rats at the onset of reperfusion via the tail vein. Neurological deficits, infarct volume, histopathological changes, oxidative stress-related biochemical parameters, neuronal apoptosis, and apoptosis-related proteins were assessed. BMP-7 significantly improved neurological and histological deficits, reduced the infarct volume, and decreased apoptotic cells after cerebral ischemia. BMP-7 also markedly enhanced the activities of antioxidant enzymes superoxide dismutase (SOD and glutathione peroxidase (GSH-PX, and reduced the level of malondialdehyde (MDA in IR rats. In addition, Western blot analysis indicated that BMP-7 prevented cytochrome c release, inhibited activation of caspase-3, caspase-9 and caspase-8. Our data suggested that BMP-7 has protective effects against cerebral IR injury in rats, and the neuroprotective effects may be attributed to attenuating oxidative stress and inhibiting neuronal apoptosis.

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

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

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

  15. 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

  16. Characteristics Analysis of Chinese Medicine Active Components Preventing and Treating Cerebral Ischemia%中药活性成分防治脑缺血特点分析

    Institute of Scientific and Technical Information of China (English)

    李瑞奇; 白明; 苗明三

    2013-01-01

    目的:探讨中药活性成分防治脑缺血的特点及机制.方法:归纳各类中药活性成分对脑缺血模型的作用及防治脑缺血的特点,总结各类中药活性成分防治脑缺血的共性机制.结果:防治脑缺血的中药多为活血化疼类、清热解毒类,各类中药活性成分防治脑缺血的机制有共通之处.结论:不同种类的中药活性成分防治脑缺血的机制对筛选特效药物具有重要意义.%Objective:To discuss the characteristics and mechanisms of Chinese medicine active components preventing and treating cerebral ischemia.Methods:Induced activities of Chinese medicine active components on cerebral ischemia model and characteristics of preventing cerebral ischemia,and summed up common mechanisms of Chinese medicine active components preventing and treating cerebral ischemia.Results:Much of the TCM which can prevent and treat cerebral ischemia are TCM of promoting blood circulation and removing blood stssis and TCM of clearing heat and detoxicating,and there are commonality for mechanisms among various types of Chinese medicine active components preventing and treating cerebral ischemia.Conclusion:Mechanisms of different types of Chinese medicine active components preventing and treating cerebral ischemia have important significance to screen specific drugs.

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

    Institute of Scientific and Technical Information of China (English)

    Feng Gao; Zhiqiang Yi; Guijun Lin

    2006-01-01

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

  18. Combined intra-arterial thrombolysis and neuprotectant agents reduce cerebral infarction in rabbits with experimental acute cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Pei Shi

    2006-01-01

    BACKGROUND:The intra-arterial thrombolytic therapy is one of main methods for more patients to obtain bene-fits.The percentage of arterial recanalization treated with intre-arterial therapy is higher than with intra-venous therapy.next,the dose of thrombolytic medicines is lower and the therapeutic time window may be possibly longer.Related researches are focus on intra-artedal thrombolysis combining with neuprotectant agents to treat acute ischemic stroke.The results show that combination of them can further prolong the therapeutic time window.improve the percentage of arterial recanalization and reduce cerebral infarction volume.OBJECTIVE:To observe the effect of single thmmbolitic therapy combined with neuroprotectant agents in the treatment of acute ischemic stroke.DESIGN:Randomized block design.SETTING:Xinhua Hospital of Xixiang City.Henan Province.MATERIALS:Thirty-six adult male white rabbits.weighing 1.5-2.0 kg.dean grade.were provided by Expedmental Animal Center of Xinxiang Medical College.All rabbits were randomly divided into three groups:intra-arterial thrombolysis control group.corenalin control group and combination group with 12 in each group.Urekinase was provided by Beijing Saisheng Pharmaceutical Co.,Ltd.(batch number:020923);corenalin by Sanjing Pharmaceutical Co.,Ltd.of Harbin Pharmacautical Group(batch number:021106):nimodipine by Shandong Xihua Pharmaceutical Co.,Ltd.(batch number:020611):contrast medium IOPAMlR0300 by Bracco s.P.a.Milano italian (batch number:0584);2,3,5-triphenyltetrazolium chloride(TTC)by Beijing Mashi Fine ChemicaL Product Co.,Ltd.(batch number:020926).METHODS: The experiment was camed out in the Department of Intervention. Second People's Hospital of Xinxiang from September 2002 to May 2003.①According to techniques of Benes et al and Zhu et al,animal models with acute ischemia were established.Two hours later.the therapy began.Intra-artedal thrombolysis control group:5 000 U/kg urokinase was dripped in Ieft common

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

    Institute of Scientific and Technical Information of China (English)

    Yun LIAO; Rui WANG; Xi-can TANG

    2004-01-01

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

  20. Transient cerebral ischemia in an elderly patient with patent foramen ovale and atrial septal aneurysm.

    Science.gov (United States)

    Merante, Alfonso; Gareri, Pietro; Castagna, Alberto; Marigliano, Norma Maria; Candigliota, Mafalda; Ferraro, Alessandro; Ruotolo, Giovanni

    2015-01-01

    Cerebrovascular disease is one of the most common causes of cerebrovascular morbidity and mortality in developed countries; up to 40% of acute ischemic strokes in young adults are cryptogenic in nature - that is, no cause is determined. However, in more than half of these patients, patent foramen ovale (PFO) is seen along with an increased incidence of atrial septal aneurysm (ASA). The following is a report of an interesting case: a 68-year-old man with ASA and transient cerebral ischemia. Transesophageal echocardiography (TEE) showed the presence of ASA; a test with microbubbles derived from a mixture of air and saline or colloids pointed out a shunt on the foramen ovale following Valsalva's maneuver. The patient underwent percutaneous transcatheter closure of the interatrial communication by an interventional cardiologist. TEE and transcranial Doppler or TEE with the microbubbles test are the recommended methods for detecting and quantifying intracardiac shunts, both at rest and following Valsalva's maneuver. In patients following the first event of transient ischemic attack, and without clinical and anatomical risk factors (such as the presence of ASA, PFO, and basal shunt), pharmacological treatment with antiplatelets or anticoagulants is closely recommended. On the contrary, in patients following the first event of transient ischemic attack, or a recurrent event during antiplatelet treatment, the percutaneous closure of PFO is recommended.

  1. Ultrasound-enhanced protective effect of tetramethylpyrazine against cerebral ischemia/reperfusion injury.

    Directory of Open Access Journals (Sweden)

    Chunbing Zhang

    Full Text Available In traditional Chinese medicine, Ligusticum wallichii (Chuan Xiong and its bioactive ingredient, tetramethylpyrazine (TMP, have been used to treat cardiovascular diseases and to relieve various neurological symptoms, such as those associated with ischemic injury. In the present study, we investigated whether ultrasound (US exposure could enhance the protective effect of TMP against cerebral ischemia/reperfusion (I/R injury. Glutamate-induced toxicity to pheochromocytoma (PC12 cells was used to model I/R injury. TMP was paired with US to examine whether this combination could alleviate glutamate-induced cytotoxicity. The administration of TMP effectively protected cells against glutamate-induced apoptosis, which could be further enhanced by US-mediated sonoporation. The anti-apoptotic effect of TMP was associated with the inhibition of oxidative stress and a change in the levels of apoptosis-related proteins, Bcl-2 and Bax. Furthermore, TMP reduced the expression of proinflammatory cytokines such as TNF-α and IL-8, which likely also contributes to its cytoprotective effects. Taken together, our findings suggest that ultrasound-enhanced TMP treatment might be a promising therapeutic strategy for ischemic stroke. Further study is required to optimize ultrasound treatment parameters.

  2. Serial MRI study of the enhanced therapeutic effects of liposome-encapsulated citicoline in cerebral ischemia.

    Science.gov (United States)

    Ramos-Cabrer, Pedro; Agulla, Jesús; Argibay, Bárbara; Pérez-Mato, María; Castillo, José

    2011-02-28

    Liposome encapsulation of active principles enhances their bioavailability to the brain. We investigated whether encapsulation of citicoline in liposomes increases its therapeutic effects in ischemia, performing a longitudinal MRI study of lesion volumes and edema in an animal model of stroke. Nineteen rats were submitted to permanent occlusion of the middle cerebral artery and treated with: (1) saline, (2) intraperitoneal citicoline (500mg/kg), (3) intravenous citicoline (48mg/kg), and (4) intravenous liposome-encapsulated citicoline (48mg/kg). Lesion volumes were measured by MRI at days 0, 1, 3 and 7 following surgery. Encapsulation in liposomes increased the therapeutic effects of citicoline, as reflected by a 32% reduction of the infarct sizes at day 7, in contrast with controls where infarct sizes at day 7 increased by 39%, respect to values at day 0. Intravenously injected citicoline reduced infarct sizes by 9% while intraperitoneal citicoline resulted in an increase of infarct sizes by 10%. A slight (not significant) reduction of edema formation was observed for animals treated with citicoline, in all of its delivery forms. Liposome-encapsulated citicoline causes a noticeable reduction in lesion volumes as compared to free citicoline (either i.p. or i.v.) at days 1, 3 and 7 following permanent stroke.

  3. Effect of Magnesium on Nitric Oxide Synthase of Neurons in Cortex during Early Period of Cerebral Ischemia

    Institute of Scientific and Technical Information of China (English)

    SUN Xiu; MEI Yuanwu; TONG E'tang

    2000-01-01

    To investigate the effect of magnesium on nitric oxide synthase (NOS) of neurons in cortex during early cerebral ischemic period, a rat model of middle cerebral artery occlusion (MCAO) was established. The results showed that the NOS activity of neurons in cortex was increased significantly at 15 min after MCAO, reached its peak at 30 min after MCAO and returned to normal levels at 60 min after MCAO. The NOS activity of neurons in the magnesium-treated group was decreased significantly as compared with that in the ischemic group at 15 min and 30min after MCAO respectively. The results suggested that magnesium could inhibit the elevated NOS activity of neurons in cortex induced by cerebral ischemia.

  4. Exploring the role of MKK7 in excitotoxicity and cerebral ischemia: a novel pharmacological strategy against brain injury

    Science.gov (United States)

    Vercelli, A; Biggi, S; Sclip, A; Repetto, I E; Cimini, S; Falleroni, F; Tomasi, S; Monti, R; Tonna, N; Morelli, F; Grande, V; Stravalaci, M; Biasini, E; Marin, O; Bianco, F; di Marino, D; Borsello, T

    2015-01-01

    Excitotoxicity following cerebral ischemia elicits a molecular cascade, which leads to neuronal death. c-Jun-N-terminal kinase (JNK) has a key role in excitotoxic cell death. We have previously shown that JNK inhibition by a specific cell-permeable peptide significantly reduces infarct size and neuronal death in an in vivo model of cerebral ischemia. However, systemic inhibition of JNK may have detrimental side effects, owing to blockade of its physiological function. Here we designed a new inhibitor peptide (growth arrest and DNA damage-inducible 45β (GADD45β-I)) targeting mitogen-activated protein kinase kinase 7 (MKK7), an upstream activator of JNK, which exclusively mediates JNK's pathological activation. GADD45β-I was engineered by optimizing the domain of the GADD45β, able to bind to MKK7, and by linking it to the TAT peptide sequence, to allow penetration of biological membranes. Our data clearly indicate that GADD45β-I significantly reduces neuronal death in excitotoxicity induced by either N-methyl-D-aspartate exposure or by oxygen–glucose deprivation in vitro. Moreover, GADD45β-I exerted neuroprotection in vivo in two models of ischemia, obtained by electrocoagulation and by thromboembolic occlusion of the middle cerebral artery (MCAo). Indeed, GADD45β-I reduced the infarct size when injected 30 min before the lesion in both models. The peptide was also effective when administrated 6 h after lesion, as demonstrated in the electrocoagulation model. The neuroprotective effect of GADD45β-I is long lasting; in fact, 1 week after MCAo the infarct volume was still reduced by 49%. Targeting MKK7 could represent a new therapeutic strategy for the treatment of ischemia and other pathologies involving MKK7/JNK activation. Moreover, this new inhibitor can be useful to further dissect the physiological and pathological role of the JNK pathway in the brain. PMID:26270349

  5. Rolipram improves cognition, reduces anxiety- and despair-like behaviors and impacts hippocampal neuroplasticity after transient global cerebral ischemia.

    Science.gov (United States)

    Soares, Lígia Mendes; De Vry, Jochen; Steinbusch, Harry W M; Milani, Humberto; Prickaerts, Jos; Weffort de Oliveira, Rúbia M

    2016-06-21

    Cognitive impairment, anxiety- and depressive-like symptoms are well recognized outcome of cerebral ischemia in clinical and preclinical settings. Rolipram, a phosphodiesterase-4 (PDE-4) inhibitor, improves cognition and produces anxiolytic- and antidepressant-like effects in rodents. Rolipram also exerts anti-inflammatory effects and enhances survival of newborn hippocampal neurons in mice subjected to transient global cerebral ischemia. Here, we evaluated the effects of chronic rolipram treatment in mice subjected to transient global brain ischemia. C56B6/7 mice were subjected to bilateral common carotid artery occlusion (BCCAO) and were then tested in a multi-tiered behavioral battery including the elevated zero maze (EZM), open field (OF), object location test (OLT), and forced swim test (FST). We also investigated the effects of rolipram on hippocampal neurodegeneration and the expression of the neuronal plasticity markers doublecortin (DCX) and microtubule-associated protein (MAP-2). Ischemic mice exhibited memory deficits OLT, higher levels of anxiety EZM and behavioral despair FST. BCCAO caused neuronal loss in the CA3 hippocampal subfield and basolateral amygdala (BLA). In the hippocampus of BCCAO mice, a disrupted neuronal plasticity was evidenced by decreased DCX expression. Chronic treatment with rolipram attenuated the behavioral effects of BCCAO. Rolipram also decreased neurodegeneration in the CA3 while it increased dendritic arborization of DCX-immunoreactive (DCX-IR) neurons and microtubule associate MAP-2 expression in the hippocampus of BCCAO mice. These data suggest that chronic inhibition of PDE-4 can be a useful therapeutic strategy to improve the emotional and cognitive outcomes of transient global cerebral ischemia.

  6. Anti-apoptotic effects of aspirin following cerebral ischemia-reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    Liying Qiu; Bin Du; Ying Li; Hongbin Fan; Zhiyong Yang

    2008-01-01

    BACKGROUND: The pharmacological effects of aspirin on apoptosis are complex. The underlying mechanisms have not been properly defined. OBJECTIVE: To observe the effect of different doses of aspirin on brain cell apoptosis following focal cerebral ischemia-reperfusion injury (CIRI) in rats. DESING, TIME AND SETTING: A randomized, controlled, animal experiment, performed at the School of Medicine and Pharmaceutics, Jiangnan University between June and October 2006. MATERIALS: Twenty-six male, adult, Sprague Dawley rats (grade II), weighing 240-290 g, were obtained from Shanghai Experimental Animal Center, Chinese Academy of Sciences. Aspirin was provided by Sigma (USA). METHODS: The rats were randomly divided into four groups: sham-operation (SO), CIRI+ vehicle, CIRI+ aspirin (6 mg/kg), and CIRI + aspirin (60 mg/kg). Rats in the lesion groups were intragastrically administrated saline, aspirin (6 mg/kg), or aspirin (60 mg/kg), respectively. MAIN OUTCOME MEASURES: The number of pyramidal neurons with normal appearance in the cerebral cortex at 2-4 mm from the midline; apoptotic cell death as measured by TUNEL; Bcl-2 and Bax protein localization was determined by immunohistochemistry; maiondiaidehyde (MDA) and super oxidation (SOD) content were determined by biochemistry method; adenosine triphosphate (ATP) content measured by capillary electrophoresis. RESULTS: Following CIRI, the following parameters were altered compared with sham-operated animals: the number of neurons with normal appearance was significantly reduced in the cerebral cortex; the number of apoptotic cells increased; Bax protein expression was enhanced; and the ratio between Bcl-2 and Bax decreased. In addition, MDA content increased significantly, whereas ATP content decreased (P < 0.01 ). Aspirin ameliorated the loss of healthy pyramidal neurons. Both 6 and 60 mg/kg aspirin increased the ratio between Bcl-2 and Bax, with no significant difference between the treatment groups. In addition, 60 mg

  7. 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.

  8. Soluble epoxide hydrolase gene deletion improves blood flow and reduces infarct size after cerebral ischemia in reproductively senescent female mice

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    Kristen L Zuloaga

    2015-01-01

    Full Text Available Soluble epoxide hydrolase (sEH, a key enzyme in the metabolism of vasodilatory epoxyeicosatrienoic acids (EETs, is sexually dimorphic, suppressed by estrogen, and contributes to underlying sex differences in cerebral blood flow and injury after cerebral ischemia. We tested the hypothesis that sEH inhibition or gene deletion in reproductively senescent (RS female mice would increase cerebral perfusion and decrease infarct size following stroke. RS (15-18 month old and young (3-4 month old female sEH knockout (sEHKO mice and wild type (WT mice were subjected to 45 min middle cerebral artery occlusion (MCAO with laser Doppler perfusion monitoring. WT mice were treated with vehicle or a sEH inhibitor t-AUCB at the time of reperfusion and every 24hrs thereafter for 3 days. Differences in regional cerebral blood flow were measured in vivo using optical microangiography. Infarct size was measured 3 days after reperfusion. Infarct size and cerebral perfusion 24h after MCAO were not altered by age. Both sEH gene deletion and sEH inhibition increased cortical perfusion 24h after MCAO. Neither sEH gene deletion nor sEH inhibition reduced infarct size in young mice. However, sEH gene deletion, but not sEH inhibition of the hydrolase domain of the enzyme, decreased infarct size in RS mice. Results of these studies show that sEH gene deletion and sEH inhibition enhance cortical perfusion following MCAO and sEH gene deletion reduces damage after ischemia in RS female mice; however this neuroprotection in absent is young mice.

  9. Down-regulation of Bcl-2 in rat substantia nigra after focal cerebral ischemia.

    Science.gov (United States)

    Arango-Dávila, Cesar A; Cardona-Gomez, Gloria P; Gallego-Gomez, Juan C; Garcia-Segura, Luis M; Pimienta, Hernán J

    2004-06-28

    After occlusion of the middle cerebral artery in rats, a robust neuronal loss occurs in the ipsilateral substantia nigra reticulata. In this study we have assessed whether degeneration of the substantia nigra is accompanied by changes in the expression of the anti-apoptotic protein Bcl-2. Neuronal loss was assessed by neuronal nuclei (NeuN) immunoreactivity. A significant decrease of Bcl-2 expression was observed in the substantia nigra 12, 24 and 72 h after middle cerebral artery occlusion. These results suggest that the secondary neuronal loss in the substantia nigra could be related with the modification of proteins regulating programmed cell death. Exo-focal cell death may explain the appearance of neuropsychiatric symptoms that are not correlated with the primary site of lesion.

  10. Ginkgo biloba extract (EGb761) and FK506 preserve energy metabolites in the striatum during focal cerebral ischemia and reperfusion in gerbils monitored by microdialysis.

    Science.gov (United States)

    Lin, Jing-Ying; Cheng, Fu-Chou; Chung, Shu-Ying; Lin, Ming-Cheng

    2004-01-01

    Cell death after cerebral ischemia is mediated by the accumulation of excitatory amino acids, calcium influx into cells and the generation of free radicals. The aim of this study was to evaluate changes in energy-related metabolites in the striatum of gerbils subjected to focal cerebral ischemia after pretreatment with Ginkgo biloba extract (EGb761), a well-known antioxidant, and FK506, a calcium-dependent phosphatase calcineurin inhibitor. Ischemia was induced by occlusion of the right common carotid artery and the right middle cerebral artery for 60 min. A microdialysis probe was inserted into the right striatum to monitor extracellular glucose, lactate and pyruvate levels. This study showed decreases in glucose (10% of the baseline), pyruvate (20% of the baseline) and lactate (60% of the baseline), and a 5-fold increase in the lactate to pyruvate ratio during ischemia in the control group. Both EGb761 treatment and the combination (EGb761 and FK506) therapy significantly preserved glucose (50% of the baseline) and pyruvate (60% of the baseline) levels during ischemia. The marked increase in the lactate to pyruvate ratio was not observed in the combination group. These results suggest that preservation of cellular energy metabolism during cerebral ischemia and after restoration with reperfusion may contribute to the neuroprotective effects of EGb761 and FK506.

  11. Exendin-4, a glucagon-like peptide-1 receptor agonist, provides neuroprotection in mice transient focal cerebral ischemia.

    Science.gov (United States)

    Teramoto, Shinichiro; Miyamoto, Nobukazu; Yatomi, Kenji; Tanaka, Yasutaka; Oishi, Hidenori; Arai, Hajime; Hattori, Nobutaka; Urabe, Takao

    2011-08-01

    Glucagon-like peptide-1 (GLP-1) is an incretin hormone known to stimulate glucose-dependent insulin secretion. The GLP-1 receptor agonist, exendin-4, has similar properties to GLP-1 and is currently in clinical use for type 2 diabetes mellitus. As GLP-1 and exendin-4 confer cardioprotection after myocardial infarction, this study was designed to assess the neuroprotective effects of exendin-4 against cerebral ischemia-reperfusion injury. Mice received a transvenous injection of exendin-4, after a 60-minute focal cerebral ischemia. Exendin-4-treated vehicle and sham groups were evaluated for infarct volume, neurologic deficit score, various physiologic parameters, and immunohistochemical analyses at several time points after ischemia. Exendin-4 treatment significantly reduced infarct volume and improved functional deficit. It also significantly suppressed oxidative stress, inflammatory response, and cell death after reperfusion. Furthermore, intracellular cyclic AMP (cAMP) levels were slightly higher in the exendin-4 group than in the vehicle group. No serial changes were noted in insulin and glucose levels in both groups. This study suggested that exendin-4 provides neuroprotection against ischemic injury and that this action is probably mediated through increased intracellular cAMP levels. Exendin-4 is potentially useful in the treatment of acute ischemic stroke.

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

    Science.gov (United States)

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

    2015-09-10

    Accumulated evidence suggests that enhanced neurogenesis stimulated by ischemic injury contributes to stroke outcome. However, it is unclear whether hyperglycemia, which is frequently tested positive in patients with acute ischemic stroke, influences stroke-induced neurogenesis. The aim of the present study is to examine the effect of hyperglycemia on stroke-induced neurogenesis in a rat model of transient focal cerebral ischemia. For this purpose, adult male Sprague-Dawley rats (220-250 g) were subjected to 90 min of middle cerebral artery occlusion (MCAO). Glucose was administered during ischemia to produce target blood levels ranging from 4.83 ± 0.94 mM (normoglycemia) to 20.76 ± 1.56 mM. To label proliferating cells in ischemic ipsilateral subventricular zone (SVZ) of lateral ventricles, 5'-bromo-2'-deoxyuridine (BrdU) was injected 24h after MCAO. Brains were harvested 2h post-BrdU to evaluate the effects of hyperglycemia on infarct volume and SVZ cell proliferation. Rats that were severely hyperglycemic (19.26 ± 1.48 mM to 20.76 ± 1.56 mM) during ischemia had 24.26% increase in infarct volume (Phyperglycemia (9.43 ± 1.39-10.13 ± 1.24 mM). Our findings indicate that severe instead of mild hyperglycemia exacerbates ischemic injury and inhibits stroke-induced SVZ neurogenesis by a mechanism involving suppression of CREB and BDNF signaling.

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

    Directory of Open Access Journals (Sweden)

    Cristiane Iozzi Silva

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

  14. Absolute Cerebral Blood Flow Infarction Threshold for 3-Hour Ischemia Time Determined with CT Perfusion and 18F-FFMZ-PET Imaging in a Porcine Model of Cerebral Ischemia.

    Science.gov (United States)

    Wright, Eric A; d'Esterre, Christopher D; Morrison, Laura B; Cockburn, Neil; Kovacs, Michael; Lee, Ting-Yim

    2016-01-01

    CT Perfusion (CTP) derived cerebral blood flow (CBF) thresholds have been proposed as the optimal parameter for distinguishing the infarct core prior to reperfusion. Previous threshold-derivation studies have been limited by uncertainties introduced by infarct expansion between the acute phase of stroke and follow-up imaging, or DWI lesion reversibility. In this study a model is proposed for determining infarction CBF thresholds at 3hr ischemia time by comparing contemporaneously acquired CTP derived CBF maps to 18F-FFMZ-PET imaging, with the objective of deriving a CBF threshold for infarction after 3 hours of ischemia. Endothelin-1 (ET-1) was injected into the brain of Duroc-Cross pigs (n = 11) through a burr hole in the skull. CTP images were acquired 10 and 30 minutes post ET-1 injection and then every 30 minutes for 150 minutes. 370 MBq of 18F-FFMZ was injected ~120 minutes post ET-1 injection and PET images were acquired for 25 minutes starting ~155-180 minutes post ET-1 injection. CBF maps from each CTP acquisition were co-registered and converted into a median CBF map. The median CBF map was co-registered to blood volume maps for vessel exclusion, an average CT image for grey/white matter segmentation, and 18F-FFMZ-PET images for infarct delineation. Logistic regression and ROC analysis were performed on infarcted and non-infarcted pixel CBF values for each animal that developed infarct. Six of the eleven animals developed infarction. The mean CBF value corresponding to the optimal operating point of the ROC curves for the 6 animals was 12.6 ± 2.8 mL·min-1·100g-1 for infarction after 3 hours of ischemia. The porcine ET-1 model of cerebral ischemia is easier to implement then other large animal models of stroke, and performs similarly as long as CBF is monitored using CTP to prevent reperfusion.

  15. Absolute Cerebral Blood Flow Infarction Threshold for 3-Hour Ischemia Time Determined with CT Perfusion and 18F-FFMZ-PET Imaging in a Porcine Model of Cerebral Ischemia.

    Directory of Open Access Journals (Sweden)

    Eric A Wright

    Full Text Available CT Perfusion (CTP derived cerebral blood flow (CBF thresholds have been proposed as the optimal parameter for distinguishing the infarct core prior to reperfusion. Previous threshold-derivation studies have been limited by uncertainties introduced by infarct expansion between the acute phase of stroke and follow-up imaging, or DWI lesion reversibility. In this study a model is proposed for determining infarction CBF thresholds at 3hr ischemia time by comparing contemporaneously acquired CTP derived CBF maps to 18F-FFMZ-PET imaging, with the objective of deriving a CBF threshold for infarction after 3 hours of ischemia. Endothelin-1 (ET-1 was injected into the brain of Duroc-Cross pigs (n = 11 through a burr hole in the skull. CTP images were acquired 10 and 30 minutes post ET-1 injection and then every 30 minutes for 150 minutes. 370 MBq of 18F-FFMZ was injected ~120 minutes post ET-1 injection and PET images were acquired for 25 minutes starting ~155-180 minutes post ET-1 injection. CBF maps from each CTP acquisition were co-registered and converted into a median CBF map. The median CBF map was co-registered to blood volume maps for vessel exclusion, an average CT image for grey/white matter segmentation, and 18F-FFMZ-PET images for infarct delineation. Logistic regression and ROC analysis were performed on infarcted and non-infarcted pixel CBF values for each animal that developed infarct. Six of the eleven animals developed infarction. The mean CBF value corresponding to the optimal operating point of the ROC curves for the 6 animals was 12.6 ± 2.8 mL·min-1·100g-1 for infarction after 3 hours of ischemia. The porcine ET-1 model of cerebral ischemia is easier to implement then other large animal models of stroke, and performs similarly as long as CBF is monitored using CTP to prevent reperfusion.

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

    Directory of Open Access Journals (Sweden)

    Yu-Shuang Chai

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

  17. Doxycycline, a matrix metalloprotease inhibitor, reduces vascular remodeling and damage after cerebral ischemia in stroke-prone spontaneously hypertensive rats.

    Science.gov (United States)

    Pires, Paulo W; Rogers, Curt T; McClain, Jonathon L; Garver, Hannah S; Fink, Gregory D; Dorrance, Anne M

    2011-07-01

    Matrix metalloproteases (MMPs) are a family of zinc peptidases involved in extracellular matrix turnover. There is evidence that increased MMP activity is involved in remodeling of resistance vessels in chronic hypertension. Thus we hypothesized that inhibition of MMP activity with doxycycline (DOX) would attenuate vascular remodeling. Six-week-old male stroke-prone spontaneously hypertensive rats (SHRSP) were treated with DOX (50 mg·kg(-1)·day(-1) in the drinking water) for 6 wk. Untreated SHRSP were controls. Blood pressure was measured by telemetry during the last week. Middle cerebral artery (MCA) and mesenteric resistance artery (MRA) passive structures were assessed by pressure myography. MMP-2 expression in aortas was measured by Western blot. All results are means ± SE. DOX caused a small increase in mean arterial pressure (SHRSP, 154 ± 1; SHRSP + DOX, 159 ± 3 mmHg; P Damage after transient cerebral ischemia (transient MCA occlusion) was reduced in SHRSP + DOX (20.7 ± 4 vs. 45.5 ± 5% of hemisphere infarcted; P damage after cerebral ischemia.

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

    Institute of Scientific and Technical Information of China (English)

    陈玲; 骆明军; 明建扩; 陈邦国

    2003-01-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

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    Shuai Hou

    2016-05-01

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

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

    Science.gov (United States)

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

    2015-07-01

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

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

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    Tao-Jie Ren

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

  3. Methylophiopogonanone A Protects against Cerebral Ischemia/Reperfusion Injury and Attenuates Blood-Brain Barrier Disruption In Vitro.

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    Mingbao Lin

    Full Text Available Methylophiopogonanone A (MO-A, an active homoisoflavonoid of the Chinese herb Ophiopogon japonicus which has been shown to have protective effects on cerebral ischemia/reperfusion (I/R injury, has been demonstrated to have anti-inflammatory and anti-oxidative properties. However, little is known about its role in cerebral I/R injury. Therefore, in this study, by using a middle cerebral artery occlusion (MCAO and reperfusion rat model, the effect of MO-A on cerebral I/R injury was examined. The results showed that MO-A treatment reduced infarct volume and brain edema, improved neurological deficit scores, reversed animal body weight decreases, and increased animal survival time in the stroke groups. Western blotting showed that MO-A suppressed MMP-9, but restored the expression of claudin-3 and claudin-5. Furthermore, transmission electron microscopy were monitored to determine the blood-brain barrier (BBB alterations in vitro. The results showed that MO-A markedly attenuated BBB damage in vitro. Additionally, MO-A inhibited ROS production in ECs and MMP-9 release in differentiated THP-1 cells in vitro, and suppressed ICAM-1 and VCAM-1 expression in ECs and leukocyte/EC adhesion. In conclusion, our data indicate that MO-A has therapeutic potential against cerebral I/R injury through its ability to attenuate BBB disruption by regulating the expression of MMP-9 and tight junction proteins.

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

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND: It is known that intravenous anesthetic etomidate fat emulsion has cerebral protection.Now many scholars focus on the research of its cerebral protection from molecular biology, but the mechanism of cerebral protection is still fully unclear.OBJECTIVE: To observe the influence of etomidate fat emulsion on the [Ca2+]i in hippocampal neurons during the transient cerebral ischemia injury in rats.DESIGN: Randomized controlled observation.SETTING: Weifang Medical College.MATERIALS: This study was carried out in the functional laboratory of Weifang Medical College between October 2005 and March 2006. Twenty-four male healthy Wistar rats, aged 3 to 4 months, were involved.Etomidate fat emulsion was provided by the limited company of En-hua Medical Bloc in Jiangsu Province (code of H20020511) and the other agents and materials were provided by Laboratory Center of Weifang Medical College.METHODS: The 24 Wistar rats were randomized into 3 groups: sham-operation group, model group and etomidate preconditioning group, with 8 rats in each. Rat models of transient cerebral ischemia injury were made by the ligation of bilateral carotid arteries combined with descending blood pressure in the latter two groups. Before ischemia (ligation of bilateral common carotid artery), rats in the etomidate preconditioning group were intraperitoneally injected with 12 mg/kg etomidate fat emulsion and then persistently intraperitoneally injected with etomidate fat emulsion at 1.0 mg/kg per minute. Rats in the model group were not administrated. Rats in the sham-operation group were only performed bilateral common carotid artery isolation. When rats were modeled, their brain tissues were quickly taken out and detected.MAIN OUTCOME MEASURES: Change of the fluorescence pixel value of the [Ca2+]i in each group by the laser scanning confocal microscope.RESULTS: Twenty-four rats were involved in the final analysis. Fluorescence pixel value in the sham-operation group was in the low level

  5. The role of tumor necrosis factor-α and TNF-α receptors in cerebral arteries following cerebral ischemia in rat

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    Chen Qing-Wen

    2011-08-01

    Full Text Available Abstract Background Tumour necrosis factor-α (TNF-α is a pleiotropic pro-inflammatory cytokine, which is rapidly upregulated in the brain after injury. TNF-α acts by binding to its receptors, TNF-R1 (p55 and TNF-R2 (p75, on the cell surface. The aim of this study was first to investigate if there is altered expression of TNF-α and TNF-α receptors in cerebral artery walls following global or focal ischemia, and after organ culture. Secondly, we asked if the expression was regulated via activation of the MEK-ERK1/2 pathway. Methods The hypothesis was tested in vivo after subarachnoid hemorrhage (SAH and middle cerebral artery occlusion (MCAO, and in vitro by organ culture of isolated cerebral arteries. The localization and amount of TNF-α, TNF-α receptor 1 and 2 proteins were analysed by immunohistochemistry and western blot after 24 and 48 h of organ culture and at 48 h following SAH or MCAO. In addition, cerebral arteries were incubated for 24 or 48 h in the absence or presence of a B-Raf inhibitor (SB386023-b, a MEK- inhibitor (U0126 or an NF-κB inhibitor (IMD-0354, and protein expression evaluated. Results Immunohistochemistry revealed enhanced expression of TNF-α, TNF-R1 and TNF-R2 in the walls of cerebral arteries at 48 h after MCAO and SAH compared with control. Co-localization studies showed that TNF-α, TNF-R1 and TNF-R2 were primarily localized to the cell membrane and the cytoplasm of the smooth muscle cells (SMC. There was, in addition, some expression of TNF-R2 in the endothelial cells. Immunohistochemistry and western blot analysis showed that these proteins were upregulated after 24 and 48 h in culture, and this upregulation reached an apparent maximum at 48 h of organ culture. Treatment with U0126 significantly reduced the enhanced SMC expression of TNF-α, TNF-R1 and TNF-R2 immunoreactivities after 24 and 48 h of organ culture. The Raf and NF-κB inhibitors significantly reduced organ culture induced TNF-α expression

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

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    Oumei Cheng

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

  7. Unsupervised nonlinear dimensionality reduction machine learning methods applied to multiparametric MRI in cerebral ischemia: preliminary results

    Science.gov (United States)

    Parekh, Vishwa S.; Jacobs, Jeremy R.; Jacobs, Michael A.

    2014-03-01

    The evaluation and treatment of acute cerebral ischemia requires a technique that can determine the total area of tissue at risk for infarction using diagnostic magnetic resonance imaging (MRI) sequences. Typical MRI data sets consist of T1- and T2-weighted imaging (T1WI, T2WI) along with advanced MRI parameters of diffusion-weighted imaging (DWI) and perfusion weighted imaging (PWI) methods. Each of these parameters has distinct radiological-pathological meaning. For example, DWI interrogates the movement of water in the tissue and PWI gives an estimate of the blood flow, both are critical measures during the evolution of stroke. In order to integrate these data and give an estimate of the tissue at risk or damaged; we have developed advanced machine learning methods based on unsupervised non-linear dimensionality reduction (NLDR) techniques. NLDR methods are a class of algorithms that uses mathematically defined manifolds for statistical sampling of multidimensional classes to generate a discrimination rule of guaranteed statistical accuracy and they can generate a two- or three-dimensional map, which represents the prominent structures of the data and provides an embedded image of meaningful low-dimensional structures hidden in their high-dimensional observations. In this manuscript, we develop NLDR methods on high dimensional MRI data sets of preclinical animals and clinical patients with stroke. On analyzing the performance of these methods, we observed that there was a high of similarity between multiparametric embedded images from NLDR methods and the ADC map and perfusion map. It was also observed that embedded scattergram of abnormal (infarcted or at risk) tissue can be visualized and provides a mechanism for automatic methods to delineate potential stroke volumes and early tissue at risk.

  8. Middle cerebral artery remodeling following transient brain ischemia is linked to early postischemic hyperemia: a target of uric acid treatment.

    Science.gov (United States)

    Onetti, Yara; Dantas, Ana P; Pérez, Belén; Cugota, Roger; Chamorro, Angel; Planas, Anna M; Vila, Elisabet; Jiménez-Altayó, Francesc

    2015-04-15

    Ischemia impairs blood supply to the brain, and reperfusion is important to restore cerebral blood flow (CBF) and rescue neurons from cell death. However, reperfusion can induce CBF values exceeding the basal values before ischemia. This hyperemic effect has been associated with a worse ischemic brain damage, albeit the mechanisms that contribute to infarct expansion are not clear. In this study, we investigated the influence of early postischemic hyperemia on brain damage and middle cerebral artery (MCA) properties and the effect of treatment with the endogenous antioxidant uric acid (UA). The MCA was occluded for 90 min followed by 24 h reperfusion in adult male Sprague-Dawley rats. Cortical CBF increases at reperfusion beyond 20% of basal values were taken as indicative of hyperemia. UA (16 mg/kg) or vehicle (Locke's buffer) was administered intravenously 135 min after MCA occlusion. Hyperemic compared with nonhyperemic rats showed MCA wall thickening (sham: 22.4 ± 0.8 μm; nonhyperemic: 23.1 ± 1.2 μm; hyperemic: 27.8 ± 0.9 at 60 mmHg; P < 0.001, hyperemic vs. sham) involving adventitial cell proliferation, increased oxidative stress, and interleukin-18, and more severe brain damage. Thus MCA remodeling after ischemia-reperfusion takes place under vascular oxidative and inflammatory stress conditions linked to hyperemia. UA administration attenuated MCA wall thickening, induced passive lumen expansion, and reduced brain damage in hyperemic rats, although it did not increase brain UA concentration. We conclude that hyperemia at reperfusion following brain ischemia induces vascular damage that can be attenuated by administration of the endogenous antioxidant UA.

  9. Changes in neuronal apoptosis and apoptosis modulatory factors in cerebral ischemia/reperfusion

    Institute of Scientific and Technical Information of China (English)

    Liying Qiu; Ying Li; Hongbin Fan; Bin Du; Zhiyong Yang; Jianqing Cheng

    2007-01-01

    BACKGROUND: The high concentration of glutamate release is the main cause for neuronal cell death. The relationship between glutamate level and apoptosis during ischemia/reperfusion injury is still unclear. OBJECTIVE: To observe the neuronal apoptosis at 24 and 72 hours following cerebral ischemia/reperfusion in rats, and analyze the possible influencing factors. DESIGN: A randomized controlled animal experiment. SETTING: School of Medicine, Southern Yangtze University.MATERIALS: Totally 30 male adult Sprague Dawley (SD) rats of clean grade, weighing 240 - 290 g, were obtained from Shanghai Experimental Animal Center, Chinese Academy of Sciences. The rats were randomly divided into sham-operated group (n=10) and model group (n=20). Each group was observed at 24 and 72 hours after ischemia/reperfusion, 5 rats at each time point in the sham-operated group, whereas 12 at 24 hours and 8 at 72 hours in the model group. Kits for determining apoptosis and Bcl-2 were bought from Wuhan Boster Biological Technology, Co., Ltd.; Kit for calcineurin from Nanjing Jiancheng Bioengineering Institute.METHODS: The experiment was carried out in the Functional Scientific Research Room of Southern Yangtze University from June to October in 2006.①Right middle cerebral artery was occluded by inserting a thread through internal carotid artery (ICA). The surgical process for the sham-operated rats was the same as that in the model group except a nylon suture inserted the ICA. According to Longa five-degree standard, the neurological deficit evaluation of rats was evaluated after surgery, and grades 1-3 were taken as successful model establishment. The blood was recirculated by withdrawing the nylon filament under anesthesia at 2 hours after ischemia in successful rat models.②After reperfusion, the brain tissue was quickly removed at 24 or 72 hours and the slices were obtained from optic chiasma to funnel manubrium. The changes of the number of apoptotic cells were observed using the

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

    Institute of Scientific and Technical Information of China (English)

    Eun Joo Bae; Seongkweon Hong; Dong Won Kim; Jun Hwi Cho; Yun Lyul Lee; Moo-Ho Won; Joon Ha Park; Bai Hui Chen; Bing Chun Yan; Bich Na Shin; Jeong Hwi Cho; In Hye Kim; Ji Hyeon Ahn; Jae Chul Lee; Hyun-Jin Tae

    2015-01-01

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

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

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    Eun Joo Bae

    2015-01-01

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

  12. Quantification of infarct size on focal cerebral ischemia model of rats using a simple and economical method.

    Science.gov (United States)

    Yang, Y; Shuaib, A; Li, Q

    1998-10-01

    Quantification of infarct size is a very useful index to assess models of focal cerebral ischemia and effects of new therapies. Currently-used image analysis systems to carry out this task usually involve dedicated and expensive equipment. We present a low-cost and simple method to perform the image acquisition and analysis. Twelve Wistar rats were subject to focal cerebral ischemia and scarified 24 h after the insult. 2,3,5-triphenyl tetrazolium chloride (TTC) stain was used as a conventional method to differentiate ischemic damage from healthy brain tissue. Digital images were captured from the stained coronal sections using a flatbed color scanner and analyzed with a commercial image processing software. To evaluate the accuracy and reproducibility of this method, the data obtained with the current procedure was correlated with those from a dedicated standard image analysis system and intra-observor correlation coefficient was estimated. Also the sensitivity of this method in quantification of infarct volume was tested in two different experimental settings. There was close correlation in the outcome of infarct size measurement between the current method and the standard system (r = 0.93, p < 0.001). A high agreement of measurement of the percentage of infarct volume between two different examiners with the same source of samples (r = 0.98, p < 0.001). We demonstrated that this method was sensitive in detection of difference of infarct sizes when placebo-treated animals (n = 6) were compared to the group treated with a neuroprotective agent (n = 6). Our data demonstrated that ischemic lesion of focal cerebral ischemia in rat can be accurately and reproducibly quantified using this method. The low-cost and simplicity of this method may facilitate the application in determination of ischemic damage.

  13. Natriuretic peptides for the detection of paroxysmal atrial fibrillation in patients with cerebral ischemia--the Find-AF study.

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    Rolf Wachter

    Full Text Available BACKGROUND AND PURPOSE: Diagnosis of paroxysmal atrial fibrillation (AF can be challenging, but it is highly relevant in patients presenting with sinus rhythm and acute cerebral ischemia. We aimed to evaluate prospectively whether natriuretic peptide levels and kinetics identify patients with paroxysmal AF. METHODS: Patients with acute cerebral ischemia were included into the prospective observational Find-AF study. N-terminal pro brain-type natriuretic peptide (NT-proBNP, brain-type natriuretic peptide (BNP and N-terminal pro atrial-type natriuretic peptide (NT-proANP plasma levels were measured on admission, after 6 and 24 hours. Patients free from AF at presentation received 7 day Holter monitoring. We prospectively hypothesized that patients presenting in sinus rhythm with NT-proBNP>median were more likely to have paroxysmal AF than patients with NT-proBNPmedian (239 pg/ml, 17.9% had paroxysmal AF in contrast to 7.4% with NT-proBNP<239 pg/ml (p = 0.025. The ratio of early (0 h to late (24 h plasma levels of NT-proBNP showed no difference between both groups. For the detection of paroxysmal atrial fibrillation, BNP, NT-proBNP and NT-proANP at admission had an area under the curve in ROC analysis of 0.747 (0.663-0.831, 0.638 (0.531-0.744 and 0.663 (0.566-0.761, respectively. In multivariate analysis, BNP was the only biomarker to be independently predictive for paroxysmal atrial fibrillation. CONCLUSIONS: BNP is independently predictive of paroxysmal AF detected by prolonged ECG monitoring in patients with cerebral ischemia and may be used to effectively select patients for prolonged Holter monitoring.

  14. Peripheral benzodiazepine receptors and cerebral ischemia%外周型苯二氮革受体与脑缺血

    Institute of Scientific and Technical Information of China (English)

    程超; 陈春富

    2009-01-01

    1he increased peripheral benzodiazepine receptors are more significant than normal ones after cerebral ischemia. Its main reactions are the multiple pathological changes,including microglial activation, participating in neuroinflammation response, and regulation of mitochondrial function. Using radionuclide-laheled specific ligands of the peripheral benzodiaz-epine receptor (such as PK11195) for in vivo imaging contribute to the location and quantitative detection for brain injury and the study of the pathophysiological changes after cerebral ischemi-a. In addition, this receptor is promising to become a new target of neuroprotective treatment.This article reviews the recent progress in research on peripheral benzodiazepine receptors and cerebral ischemia.%脑缺血后,外周型苯二氮革受体较正常时有明显增加,主要反应为小胶质细胞的活化、参与神经炎症反应以及线粒体功能调节等多途径病理学变化.应用放射性核素标记的特异性外周型苯二氮革受体配体(如PK11195)进行体内成像,有助于对脑损伤进行定位和定量检测以及研究脑缺血后病理生理学改变.另外,该受体还有望成为神经保护治疗的新靶点.文章就外周型苯二氮革受体与脑缺血的研究进展做一综述.

  15. Salvinorin A administration after global cerebral hypoxia/ischemia preserves cerebrovascular autoregulation via kappa opioid receptor in piglets.

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    Zhenhong Wang

    Full Text Available BACKGROUND: Cerebral hypoxia/ischemia (HI is not uncommon during the perinatal period. If occurring, it can result in severe neurologic disabilities that persist throughout life. Salvinorin A, a non-opioid Kappa opioid receptors (KOR selective agonist, has the potential to address this devastating situation. We have demonstrated that salvinorin A administration before HI, preserves pial artery autoregulative function through both the KOR and extracellular signal-regulated kinases (ERK pathways. In the present study, we tested the hypothesis that administration of salvinorin A after HI could preserve cerebral autoregulation via KOR and ERK pathway. METHODOLOGY/PRINCIPAL FINDINGS: The response of the pial artery to hypercapnia, hypotension and isoproterenol were monitored before and 1 hour after HI in piglets equipped with a cranial window. Four groups of drug administration were performed after HI. The control group had DMSO (1 µl/kg, i.v. administrated immediately after HI. Two salvinorin A treated groups had salvinorin A (10 µg/kg, i.v. administrated 0 and 30 min after HI, respectively. The 4(th group had salvinorin A and the KOR antagonist norbinaltorphimine (Nor-BIN, 1 µM topical co-administrated 0 min after HI (n = 5. The dilation responses of the pial artery to hypercapnia and hypotension were impaired after global HI and were preserved with salvinorin A administration immediately or 30 min after HI. The preservation of autoregulation was abolished when nor-BIN was administered. Levels of phosphor-ERK(pERK/ERK in the cerebrospinal fluid (CSF were measured before and 1 hour after HI. After HI, the pERK/ERK levels significantly increased in both DMSO control group and salvinorin A and nor-BIN co-administration group. The elevated levels of pERK/ERK were not observed with salvinorin A only groups. CONCLUSIONS: Salvinorin A administration 0 and 30 min after HI preserves autoregulation of pial artery to hypercapnia and hypotension via

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

    Institute of Scientific and Technical Information of China (English)

    Gang Chen; Qiang Fu; Jiangbei Cao; Weidong Mi

    2012-01-01

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

  17. Alleviation of glutamate mediated neuronal insult by piroxicam in rodent model of focal cerebral ischemia: a possible mechanism of GABA agonism.

    Science.gov (United States)

    Bhattacharya, Pallab; Pandey, Anand Kumar; Paul, Sudip; Patnaik, Ranjana

    2014-12-01

    Neurotransmitter imbalance is an inevitable outcome in cerebral ischemia that leads to neuronal death. In the present study, we evaluated the effects of piroxicam, a nonsteroidal anti-inflammatory drug (NSAID), on extracellular brain glutamate and γ-aminobutyric acid (GABA) release, survival time, and neuronal cell death. Transient focal cerebral ischemia in male Charles Foster rat led to neuronal infarction and compromised intrinsic antioxidant status. Thirty-minute preadministration of piroxicam (10 mg/kg b.w.) showed a significant (P piroxicam administration in stroke rat significantly reduced (P piroxicam attenuates extracellular glutamate release and also reduces neuronal cell death due to reduction in oxidative stress in cerebral ischemia. Our results also indicate a consequent increase of extracellular GABA in brain regions administered with piroxicam, which hints that piroxicam alleviates glutamate excitotoxicity possibly by GABA agonism.

  18. Radix Ilicis Pubescentis total flavonoids combined with mobilization of bone marrow stem cells to protect against cerebral ischemia/reperfusion injury

    OpenAIRE

    Ming-san Miao; Lin Guo; Rui-qi Li; Xiao Ma

    2016-01-01

    Previous studies have shown that Radix Ilicis Pubescentis total flavonoids have a neuroprotective effect, but it remains unclear whether Radix Ilicis Pubescentis total flavonoids have a synergistic effect with the recombinant human granulocyte colony stimulating factor-mobilized bone marrow stem cell transplantation on cerebral ischemia/reperfusion injury. Rat ischemia models were administered 0.3, 0.15 and 0.075 g/kg Radix Ilicis Pubescentis total flavonoids from 3 days before modeling to 2 ...

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

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

  20. Neuroprotective effect of an angiotensin receptor type 2 agonist following cerebral ischemia in vitro and in vivo

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    Lee Seyoung

    2012-08-01

    Full Text Available Abstract Background Intracerebral administration of the angiotensin II type 2 receptor (AT2R agonist, CGP42112, is neuroprotective in a rat model of ischemic stroke. To explore further its possible cellular target(s and therapeutic utility, we firstly examined whether CGP42112 may exert direct protective effects on primary neurons following glucose deprivation in vitro. Secondly, we tested whether CGP42112 is effective when administered systemically in a mouse model of cerebral ischemia. Methods Primary cortical neurons were cultured from E17 C57Bl6 mouse embryos for 9 d, exposed to glucose deprivation for 24 h alone or with drug treatments, and percent cell survival assessed using trypan blue exclusion. Ischemic stroke was induced in adult male C57Bl6 mice by middle cerebral artery occlusion for 30 min, followed by reperfusion for 23.5 h. Neurological assessment was performed and then mice were euthanized and infarct and edema volume were analysed. Results During glucose deprivation, CGP42112 (1x10-8 M and 1x10-7 M reduced cell death by ~30%, an effect that was prevented by the AT2R antagonist, PD123319 (1x10-6 M. Neuroprotection by CGP42112 was lost at a higher concentration (1x10-6 M but was unmasked by co-application with the AT1R antagonist, candesartan (1x10-7 M. By contrast, Compound 21 (1x10-8 M to 1x10-6 M, a second AT2R agonist, had no effect on neuronal survival. Mice treated with CGP42112 (1 mg/kg i.p. after cerebral ischemia had improved functional outcomes over vehicle-treated mice as well as reduced total and cortical infarct volumes. Conclusions These results indicate that CGP42112 can directly protect neurons from ischemia-like injury in vitro via activation of AT2Rs, an effect opposed by AT1R activation at high concentrations. Furthermore, systemic administration of CGP42112 can reduce functional deficits and infarct volume following cerebral ischemia in vivo.

  1. Proteasome alteration and delayed neuronal death in hippocampal CA1 and dentate gyrus regions following transient cerebral ischemia

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    Pengfei Ge; Tianfei Luo; Jizhou Zhang; Haifeng Wang; Wenchen Li; Yongxin Luan; Feng Ling; Yi'nan Luo

    2009-01-01

    BACKGROUND:Proteasome dysfunction has been reported to induce abnormal protein aggregation and cell death.OBJECTIVE:To investigate the effect of proteasome changes on delayed neuronal death in CA1 and dentate gyrus (DG) regions of the rat hippocampus following transient cerebral ischemia.DESIGN,TIME AND SETTING:A randomized,controlled animal experiment.The study was performed at the Department of Biochemistry and Molecular Biology,Norman Bethune Medical College of Jilin University,from September 2006 to May 2008.MATERIALS:Rabbit anti-19S S10B polyclonal antibody was purchased from Bioreagents,USA;propidium iodide and fluorescently-labeled goat anti-rabbit IgG were purchased from Jackson Immunoresearch,USA;hematoxylin and eosin staining solution was purchased from Sigma,USA;LSM 510 confocal microscope was purchased from Zeiss,Germany.METHODS:A total of 40 healthy Wistar rats,male,4 months old,were randomly divided into sham surgery group (n=8) and model group (n=32).Ischemic models were established in the model group by transient clamping of the bilateral carotid arteries and decreased blood pressure.After 20 minutes of global ischemia,the clamp was removed to allow blood flow for 30 minutes,4,24,and 72 hours,respectively,with 8 rats at each time point.The bilateral carotid arteries were not ligated in the sham surgery group.MAIN OUTCOME MEASURES:Neuronal death in the CA1 and DG regions was observed by hematoxylin-eosin staining.Proteasome expression in CA1 and DG region neurons was detected by immunohistochemistry.RESULTS:Hematoxylin-eosin staining showed neuronal death in the CA1 region alone at 72 hours of reperfusion following ischemia.In comparison to the sham surgery group,a significant decrease in proteasome expression was observed,by immunohistochemistry,in the CA1 and DG regions in the model group,following 30 minutes,4,24,and 72 hours of reperfusion (P<0.01).After 72 hours of reperfusion following ischemia,proteasome expression had almost completely

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

    Science.gov (United States)

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

    2012-02-01

    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 inflammatory responses, poly-IC elicits only modest systemic inflammation. Results show that poly-IC is a new powerful prophylactic treatment that offers promise as a clinical therapeutic strategy to minimize damage in patient populations at risk of ischemic injury.

  3. Transient focal cerebral ischemia/reperfusion induces early and chronic axonal changes in rats: its importance for the risk of Alzheimer's disease.

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    Qinan Zhang

    Full Text Available The dementia of Alzheimer's type and brain ischemia are known to increase at comparable rates with age. Recent advances suggest that cerebral ischemia may contribute to the pathogenesis of Alzheimer's disease (AD, however, the neuropathological relationship between these two disorders is largely unclear. It has been demonstrated that axonopathy, mainly manifesting as impairment of axonal transport and swelling of the axon and varicosity, is a prominent feature in AD and may play an important role in the neuropathological mechanisms in AD. In this study, we investigated the early and chronic changes of the axons of neurons in the different brain areas (cortex, hippocampus and striatum using in vivo tracing technique and grading analysis method in a rat model of transient focal cerebral ischemia/reperfusion (middle cerebral artery occlusion, MCAO. In addition, the relationship between the changes of axons and the expression of β-amyloid 42 (Aβ42 and hyperphosphorylated Tau, which have been considered as the key neuropathological processes of AD, was analyzed by combining tracing technique with immunohistochemistry or western blotting. Subsequently, we found that transient cerebral ischemia/reperfusion produced obvious swelling of the axons and varicosities, from 6 hours after transient cerebral ischemia/reperfusion even up to 4 weeks. We could not observe Aβ plaques or overexpression of Aβ42 in the ischemic brain areas, however, the site-specific hyperphosphorylated Tau could be detected in the ischemic cortex. These results suggest that transient cerebral ischemia/reperfusion induce early and chronic axonal changes, which may be an important mechanism affecting the clinical outcome and possibly contributing to the development of AD after stroke.

  4. 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.

  5. A type-II positive allosteric modulator of α7 nAChRs reduces brain injury and improves neurological function after focal cerebral ischemia in rats.

    Directory of Open Access Journals (Sweden)

    Fen Sun

    Full Text Available In the absence of clinically-efficacious therapies for ischemic stroke there is a critical need for development of new therapeutic concepts and approaches for prevention of brain injury secondary to cerebral ischemia. This study tests the hypothesis that administration of PNU-120596, a type-II positive allosteric modulator (PAM-II of α7 nicotinic acetylcholine receptors (nAChRs, as long as 6 hours after the onset of focal cerebral ischemia significantly reduces brain injury and neurological deficits in an animal model of ischemic stroke. Focal cerebral ischemia was induced by a transient (90 min middle cerebral artery occlusion (MCAO. Animals were then subdivided into two groups and injected intravenously (i.v. 6 hours post-MCAO with either 1 mg/kg PNU-120596 (treated group or vehicle only (untreated group. Measurements of cerebral infarct volumes and neurological behavioral tests were performed 24 hrs post-MCAO. PNU-120596 significantly reduced cerebral infarct volume and improved neurological function as evidenced by the results of Bederson, rolling cylinder and ladder rung walking tests. These results forecast a high therapeutic potential for PAMs-II as effective recruiters and activators of endogenous α7 nAChR-dependent cholinergic pathways to reduce brain injury and improve neurological function after cerebral ischemic stroke.

  6. Effects of strain, body mass, and thread tip preparation on the establishment of focal cerebral ischemia mouse models

    Institute of Scientific and Technical Information of China (English)

    Xuemei Chen; Yun Xu

    2008-01-01

    BACKGROUND: What are the successful factors of the establishment of the thread-blocking method for focal cerebral ischemia/reperfusion mouse models?OBJECTIVE: To study the effects of strain, body mass, and thread tip preparation for the establishment of focal cerebral ischemia mouse models by using middle cerebral artery occlusion (MCAO).DESIGN: Observational contrast animal study.SETTING: Gulou Hospital, Medical College of Nanjing University.MATERIALS: ① The following experiment was performed at the Animal Experimental Center, Gulou Hospital Affiliated to Medical College of Nanjing University from December 2006 to April 2007. Sixty male white Kunming mice, whose body masses were 18–22 g (n =40), 25–29 g (n =10) and 30–33 g (n =10), as well as 10 male C57BL/6J mice, whose body mass was 18–22 g, were provided by the Animal Experimental Center, Gulou Hospital Affiliated to Medical College of Nanjing University. All mice were 10–12 weeks old. The project received confirmed consent from the local ethics committee. ②Experimental materials: tripheryltetrazolium hydrochloride (TTC) and 0.1% poly-L-lysine were provided by Sigma Company, USA; citromint was provided by Shanghai Lingfeng Chemical Company Limited. METHODS: ① Strain comparison: Ten white Kunming mice (weighing 18–22 g) and ten C57BL/6J mice (weighing 18–22 g) were selected. ② Comparison of body mass: Thirty white Kunming mice, whose body masses were 18–22 g (n =10), 25–30 g (n =10), and 30–35 g (n =10), were divided into groups. ③ Comparison of thread tip preparation: White Kunming mice weighing 18–22 g were divided into a poly-L-lysine line group and general line group, with 10 mice in each group. Mice in these two groups, which were respectively treated with poly-L-lysine or nothing, underwent MCAO. ④ All experimental mice received MCAO. Three hours after ischemia, and 24 hours after reperfusion, neurological deficit scores were measured and a success rate of model

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  8. Oxidative damage following cerebral ischemia depends on reperfusion - a biochemical study in rat

    DEFF Research Database (Denmark)

    Nita, D A; Nita, V; Spulber, S;

    2002-01-01

    The extent of brain injury during reperfusion appears to depend on the experimental pattern of ischemia/reperfusion. The goals of this study were: first, to identify the rate of free radicals generation and the antioxidant activity during ischemia and reperfusion by means of biochemical measureme...

  9. Effect of olive oil on the cerebral reperfusion following ischemia injuries in rat

    Directory of Open Access Journals (Sweden)

    Javad Raouf Sarshoori

    2014-05-01

    Conclusion: The findings of the current study indicated that olive oil effectively reduced ischemia, helped to the reperfusion of injuries, and improved neurological outcome. Olive oil is also a potent neuroprotective factor that is able to prevent neurodegeneration of transient focal ischemia in the beginning of reperfusion at ischemic areas.

  10. Optimal compatible doses and effects of ephedrine and naloxone on neural plasticity in cerebral ischemia/reperfusion rats

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

    BACKGROUND: Ephedrine promotes neural plasticity in rats following cerebral iscbemia/reperfusion injury. Ephedrine has been combined with naloxone in some studies, and it has been confirmed that their combination has synergistic effects on increasing neural plasticity following cerebral ischemia/reperfusion injury.OBJECTIVE: To investigate the effects of ephedrine combined with various doses of naloxone on neural plasticity and to find an optimal dose of naloxone in rats after cerebral ischemia/reperfusion injury by analyzing growth associated protein-43 (GAP-43), synaptophysin and β -endorphin expression in the hippocampal CA3 area.DESIGN, TIME AND SETTING: This immunohistochemical, randomized, controlled, animal experiment was performed at the Chongqing Research Institute of Pediatrics, China from September 2007 to June 2008.MATERIALS: Ephedrine hydrochloride injection and naloxone hydrochloride injection were respectively purchased from Shandong Lvliang Pharmaceutical Factory, China and Sichuan Jingwei Pharmaceutical Co.,Ltd., China. A total of 192 healthy adult Sprague Dawley rats were used to establish models of left middle cerebral artery occlusion using the suture occlusion method.METHODS: At 2 hours following cerebral ischemia, the rats were intraperitoneally injected with 1.5 mg/kg/d ephedrine (ephedrine group), with 0.1, 0.2, or 0.3 mg/kg/d naloxone (low, moderate and high doses of naloxone groups), with 1.5 mg/kg/d ephedrine + 0. 1, 0.2, or 0.3 mg/kg/d naloxone (ephedrine + low,moderate and high doses of naloxone groups), and with 0.5 mL saline (model group), respectively.MAIN OUTCOME