Effect of flunarizine on electroencephalogram recovery and brain temperature in gerbils after brain ischemia.

BACKGROUND AND PURPOSE: This study was designed to determine whether flunarizine enhances the rate of brain recovery as measured by electroencephalography after cerebral ischemia and whether these effects are attributable to changes in brain temperature. METHODS: Male gerbils (n = 81) were treated with either 10 mg/kg flunarizine or its vehicle, beta-cyclodextrin, intraperitoneally, 60 minutes before bilateral carotid occlusion of either 4 or 6 minutes' duration. The electroencephalogram was continuously recorded in the preischemic, ischemic, and postischemic stages of the experiment and rated for the time necessary for the return of 4-6, 7-10, and 11-15 Hz activity. In a second set of experiments, intracerebral temperature was monitored for 60 minutes before ischemia, during 10 minutes of carotid occlusion, and for 60 minutes after ischemia. RESULTS: Flunarizine pretreatment resulted in significantly more rapid return of electroencephalographic activity in each of the three frequency categories monitored when compared with those animals pretreated with vehicle alone (p less than 0.001). Flunarizine had no effect on brain temperature before, during, or up to 60 minutes after termination of ischemia. CONCLUSIONS: Flunarizine, which has been of efficacy in reducing neuronal death, mortality, and functional impairment when administered after ischemic insults, may have prophylactic value in accelerating brain recovery from ischemia, but does not have this effect as a result of altered brain temperature.     

Brain metabolic and ionic responses to global brain ischemia in the newborn dog in vivo: 1. Methodological aspects

Abstract

A variety of methods has been used in order to obtain a state of acute cerebral ischemia. Most of these methods suffered from drawbacks such as irreversible ischemia, difficult to obtain total ischemia and heart injury. The aim of this study was to develop a new method for induction of global or partial cerebral ischemia in the newborn dog at various post-natal ages. A multi-parameter monitoring system (MPA) measures the metabolic (mitochondria NADH oxidation/reduction state), hemodynamic (reflectance), ionic (extracellular potassium and calcium) and electrical changes (ECoG) continuously and simultaneously In the puppy’s brain in vivo. A hole was made in the chest cavity, the two large arteries supplying blood to the brain, the brachiocephalic and the subclavian arteries (B + S) were isolated and occluded during the monitoring. In most of the animals, occlusion of these two arteries alone resulted in partial ischemia. For obtaining 1 00% ischemia, we occluded both the B + S arteries as well as the aortic arch. Immediately at the onset of ischemia, an increase (reduction) of NADH begins. During complete ischemia the average time until maximal increase was 4 min, compared to ischemia of up to 50% of the maximal reduction of the NADH where the average time was 1 min. After reperfusion of the brain, mitochondria recovery was very rapid and the average time until return of this parameter to its pre-ischemic level was 1.4±0.2 min. The ionic changes which occurred immediately upon the onset of ischemia were the accumulation of extracellular potassium ions was recorded. The rate of potassium ion accumulation was dependent on the severity of the ischemia (range 0.19±0.08-2.2±0.4 mM min^-1). The increase in the extracellular potassium ion concentration occurs in two stages, an initial slow stage and a second rapid stage (13.0±1.8 mM). The results presented in this paper suggest and prove the usefulness of a new approach for global and partial ischemia in the newborn dogs. In addition, our results assess the brain metabolic, ionic, hemodynamic and electrical responses to brain ischemia in the puppies. [Neurol Res 2000; 22: 505-511]     

Brain metabolic and ionic responses to global brain ischemia in the newborn dog in vivo: 1. Methodological aspects

A variety of methods has been used in order to obtain a state of acute cerebral ischemia. Most of these methods suffered from drawbacks such as irreversible ischemia, difficult to obtain total ischemia and heart injury. The aim of this study was to develop a new method for induction of global or partial cerebral ischemia in the newborn dog at various post-natal ages. A multi-parameter monitoring system (MPA) measures the metabolic (mitochondria NADH oxidation/reduction state), hemodynamic (reflectance), ionic (extracellular potassium and calcium) and electrical changes (ECoG) continuously and simultaneously in the puppy's brain in vivo. A hole was made in the chest cavity, the two large arteries supplying blood to the brain, the brachiocephalic and the subclavian arteries (B + S) were isolated and occluded during the monitoring. In most of the animals, occlusion of these two arteries alone resulted in partial ischemia. For obtaining 100% ischemia, we occluded both the B + S arteries as well as the aortic arch. Immediately at the onset of ischemia, an increase (reduction) of NADH begins. During complete ischemia the average time until maximal increase was 4 min, compared to ischemia of up to 50% of the maximal reduction of the NADH where the average time was 1 min. After reperfusion of the brain, mitochondria recovery was very rapid and the average time until return of this parameter to its pre-ischemic level was 1.4 +/- 0.2 min. The ionic changes which occurred immediately upon the onset of ischemia were the accumulation of extracellular potassium ions was recorded. The rate of potassium ion accumulation was dependent on the severity of the ischemia (range 0.19 +/- 0.08-2.2 +/- 0.4 mM min-1). The increase in the extracellular potassium ion concentration occurs in two stages, an initial slow stage and a second rapid stage (13.0 +/- 1.8 mM). The results presented in this paper suggest and prove the usefulness of a new approach for global and partial ischemia in the newborn dogs. In addition, our results assess the brain metabolic, ionic, hemodynamic and electrical responses to brain ischemia in the puppies.     

A quantitative morphological assessment of the effect of lidoflazine and deferoxamine therapy on global brain ischaemia

The effect of the combination of two drugs, i.e. lidoflazine (a calcium antagonist), and deferoxamine (an iron chelator) was evaluated following 15 min global brain ischaemia (GBI) and reperfusion in dogs in a randomized blind study. GBI was produced by complete cardiac arrest of 15 min duration. Histopathological analysis performed on in situ fixed brains 40 h post-resuscitation revealed diffuse microhaemorrhages in the control group. These were noted rarely in the treatment group, the mean value of foci of microhaemorrhages/20 low power fields (LPF) being 5.2 in the treatment group versus 28 in the control group (p > 0.001). Diffuse coagulative necrosis of neurons (ischaemic cell change) in the cerebral cortex, especially lamina 3, hippocampus, striatum, brain stem and cerebellum was present in all cases. Quantitation of the degree of cellular damage obtained by counting the number of anoxic neurons (in consistent regions of the brain) with the use of an image analysis system, revealed no significant difference between the 2 groups. The mean percentages of the ischaemic neurons in the control group in the various areas studied were: parietal cortex, 22.25; hippocampus, 50.37 and cerebellum (Purkinje cells), 66.75; and in the treatment group 25.3, 55.04 and 70.6 respectively. Thus, the lidoflazine-deferoxamine regimen significantly reduced the incidence of microhaemorrhages in the brain, but it did not have any protective effect against anoxic neuronal injury 40 h post-ischaemia in this experimental model of GBI of 15 min duration.     

A quantitative morphological assessment of the effect of lidoflazine and deferoxamine therapy on global brain ischaemia

The effect of the combination of two drugs, i.e. lidoflazine (a calcium antagonist), and deferoxamine (an iron chelator) was evaluated following 15 min global brain ischaemia (GBI) and reperfusion in dogs in a randomized blind study. GBI was produced by complete cardiac arrest of 15 min duration. Histopathological analysis performed on in situ fixed brains 40 h post-resuscitation revealed diffuse microhaemorrhages in the control group. These were noted rarely in the treatment group, the mean value of foci of microhaemorrhages/20 low power fields (LPF) being 5.2 in the treatment group versus 28 in the control group (p less than 0.001). Diffuse coagulative necrosis of neurons (ischaemic cell change) in the cerebral cortex, especially lamina 3, hippocampus, striatum, brain stem and cerebellum was present in all cases. Quantitation of the degree of cellular damage obtained by counting the number of anoxic neurons (in consistent regions of the brain) with the use of an image analysis system, revealed no significant difference between the 2 groups. The mean percentages of the ischaemic neurons in the control group in the various areas studied were: parietal cortex, 22.25; hippocampus, 50.37 and cerebellum (Purkinje cells), 66.75; and in the treatment group 25.3, 55.04 and 70.6 respectively. Thus, the lidoflazine-deferoxamine regimen significantly reduced the incidence of microhaemorrhages in the brain, but it did not have any protective effect against anoxic neuronal injury 40 h post-ischaemia in this experimental model of GBI of 15 min duration.     

Metabolic and ionic responses to global brain ischemia in the newborn dog in vivo: II. Post-natal age aspects

The main difference between newborn and adult brains is expressed in the relative resistance of the newborn brain to oxygen deprivation. The aim of the present study was to examine the effect of global ischemia in canine puppies of three different ages on the metabolic, ionic and electrical activity of the brain and to study the basic mechanisms underlying the relative resistance of the newborn brain in ischemic episode. The puppies were divided into three age groups. The young group included 0-6-day-old puppies (n = 16), the intermediate group included 7-19-day-old puppies (n = 21), and the 'adult' group included puppies aged 20 days or more (n = 17). Statistical analysis of the results led to the following conclusions: The younger the puppy, the longer is the time until the occurrence of the secondary reflectance increase SRI (13.0 +/- 1.9 min vs. 5.3 +/- 0.5 min). The younger the puppy, the longer the time until onset of potassium leakage from the cells (0.9 +/- 0.1 min vs. 0.35 +/- 0.05 min) and the lower the amount of potassium leakage (9.6 +/- 2.8 mM vs. 21.7 +/- 4.8 mM). The rate of pumping of the potassium ions into the cells during the recovery stage was higher in the oldest group (1.2 +/- 0.2 mM min-1 vs. 0.38 +/- 0.1 mM min-1). It was possible to speculate that in the young puppies there is uncoupling of the oxidative phosphorylation from respiration and as a result, there is a lower, if any, rate of ATP synthesis. It seems that the newborn brain is able to cope with a decrease in available energy for a longer period of time. This is apparently due to differences in membrane characteristics and an improved ability to retain ionic equilibrium across both sides of the membrane.     

沙土鼠脑缺血再灌注诱导线粒体通透性转换和氟桂嗪的影响

目的　进一步探讨盐酸氟桂嗪对缺血再灌注后神经细胞保护作用的机制。方法　制作沙土鼠全脑缺血 /再灌注模型 ,随机分为脑缺血组、氟桂嗪预处理组和对照组 ,分别于术后 1h、6h、1d分离前脑线粒体 ,用分光光度法检测线粒体通透性转换以及线粒体游离Ca2 + 的含量。结果　 (1)前脑线粒体游离Ca2 +浓度在缺血再灌注后 1h、6h、1d均高于氟桂嗪预处理和对照组 (P <0 .0 1或P <0 .0 5 ) ,以缺血再灌注后 6h最明显 (P <0 .0 1) ;(2 )缺血再灌注后 1h、6h、1d前脑线粒体通透性转换开放程度较对照组和氟桂嗪预处理组均高 (P <0 .0 5 ) ;(3)氟桂嗪预处理组以缺血再灌注后 6h前脑线粒体通透性转换开放程度降低最为显著(P <0 .0 1)。结论　氟桂嗪抑制急性脑缺血再灌注诱导的线粒体通透性转换     

Effect of brain microdialysis on aminergic transmitter levels in repeated cerebral global transient ischemia in rat

The effect of repeated transient global ischemia and microdialysis on changes in aminergic neurotransmitter release was investigated using the rat four-vessel occlusion model of global ischemia. To examine the possible transient or permanent changes in neurotransmitter release, ischemia was induced at varying time points in 5 groups of rats. The first ischemia occurred either 24 h (groups I, II, IV, V) or 96 h (group III) following vertebral artery electro-coagulation and guide probe implantation(s), and the second ischemia was induced either 48 h (groups I, IV, V) or 72 h (group II) following the first ischemia. To assess the consequence of repeated microdialysis on the results, one group of rats (group IV) was not dialysed during the first ischemia and another group (group V) was bilaterally dialysed during the second ischemia. Finally, amphetamine-induced neurotransmitter release was also studied in rats submitted to ischemia and compared with that in normal rats. In each case, dopamine, serotonin and their main metabolites were measured by HPLC with electrochemical detection. Monoamine release was inhibited during the second episode of transient ischemia; this non-release was linked to the repeated microdialysis and not to the repeated ischemia. Although the results of chronic studies using brain microdialysis have been widely recognized as valid, the findings presented here indicate that combined with ischemia, probe reinsertion modifies the level of neurotransmitter release.     

Multifaceted therapy after global brain ischemia in monkeys

The pathophysiology of postischemic encephalopathy is complex, and includes tissue acidosis, edema, hypoperfusion, membrane dysfunction, impaired energy production, and possibly hypermetabolism. We tested the hypothesis that this multifactorial clinical problem must be approached with multifaceted therapy, with specific treatment aimed at each of the above postischemic changes. Eighteen minutes of complete global brain ischemia was produced with a higher pressure neck cuff in pigtailed monkeys. Control treatment postischemia (n = 9): 1) Normotension (MAP greater than or equal to 80 mmHg) restored within 2 min postischemia, 2) controlled ventilation for 24 hours with PaCO2 = 25 mmHg, 3) normothermia, and 4) phenytoin seizure prophylaxis from 20 hours postischemia. Experimental treatment (n = 10): Control treatment plus the following modifications: 1) Hemodilution to hematocrit 25% at 1-4 min postischemia, 2) brief hypertension (MAP 130 mmHg for 5 min) after accomplished hemodilution, 3) hypothermia for 6 hours, 4) pentobarbital 30 mg/kg i.v., 5) dexamethasone 4 mg/kg i.v. Outcome was evaluated at 96 hours postischemia by overall performance categories (OPC) (OPC I = normal, OPC V = brain death), neurologic deficit (ND) scores (100% ND = brain death, 0% ND = normal), and histologic damage scores of the brains. Results: Brain death developed in 1/9 control and 0/10 treated animals. The number of awake monkeys (OPC I and II) at 96 hours postischemia was significantly higher in the treated group (7/10) than in the control group (2/9) (p = 0.05). The median ND scores for the two groups were 16 and 35% respectively (p greater than 0.05). The results strongly suggest that postischemic treatment may be beneficial and that a multifaceted therapeutic approach is worth pursuing.     

Ultrastructural and ionic studies in global ischemic dog brain

Summary A time course of tissue ionic changes, and their relation to ultrastructural findings during reperfusion following a 15-min global ischemic brain insult was studied in a dog model. Parietal cortex was analyzed for Ca, Na, K, Mg and Fe in controls and after 10 min, 2, 4, and 8 h of reperfusion. After 8 h of reperfusion, the mean values (mol/g tissue wet wt.) for Ca (control=1.43, 8 h=2.76) and Na (control 60.4, 8 h=107.4) doubled and K (control=90.4, 8 h=48.5) decreased to half that of the control. Ultrastructural studies and subcellular localization of calcium in parietal cortex of in situ-fixed brains after 8 h showed cortical neurons with clumping of nuclear chromatin, dilatation of endoplasmic reticulum and disruption of plasma membranes. Large amounts of electron-dense precipitates of calcium were present within dilated astrocytic processes, synaptic vesicles, cytoplasm of edematous dendrites and mitochondria. Cortical neurons from postischemic dogs without reperfusion showed only slight chromatin clumping and edema of astrocytic processes, but no calcium accumulation. The large ionic shifts noted between 4 and 8 h of reperfusion, indicate a progressive inability of the cells to maintain normal transmembrane gradients of these ions and may reflect a membrane destructive process, as demonstrated ultrastructurally at 8 h. Enhanced calcium entry into the neuron during reperfusion appears to be a part of the cytotoxic mechanism leading to neuronal necrosis.Supported by Contract No DAMD 85-17-4200 from the United States Army Medical Research and Development Command and a grant from the College of Human Medicine, Michigan State University. This work was presented at the 70th Annual Meeting of the American Association of Pathology, St. Louis, MO, April 16, 1986     

Effects of pentobarbital on brain lipid metabolism during global ischemia

It is known that pentobarbital, which has been used for severe brain infarct or head injury as a brain protective drug, inhibits the increase of free fatty acids (FFAs) liberated from membrane phospholipids during ischemia. However, the mechanisms of FFA liberation from phospholipids and the mode of action of pentobarbital are still unclear. Therefore we have investigated the effects of induction of global ischemia and pentobarbital pretreatment upon lipid metabolism in rat brain. Brain ischemia was evoked by rat decapitation and pentobarbital (60 mg/kg) was administered i.p. for 15 min prior to decapitation. Removed brains were incubated for 1, 5, 15 or 30 min at 37 degrees C and then quickly frozen in liquid nitrogen. After extraction of lipids from the brains, neutral lipid and phospholipid compositions were analyzed by thin-layer and gas-liquid chromatography. The results demonstrated that FFAs, either unsaturated or saturated, were rapidly accumulated in the brain during early period of ischemia, but attenuated significantly by pentobarbital pretreatment. Pentobarbital attenuated the accumulations of stearic and arachidonic acids, with little effect on palmitic and oleic acids. Diacylglycerol (DG), which is considered to be as a plausible candidate for the source of FFA, was also produced in the ischemic brain, and its acyl chain composition was similar to that of liberated FFAs. Furthermore, the increase of DG was inhibited significantly by pentobarbital anesthesia. In particular, pentobarbital attenuated the accumulation of DG enriched in arachidonic and stearic acids. This fatty acyl composition resembled the principal composition of phosphatidylinositol (PI) in rat brain.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mechanisms of brain injury after global cerebral ischemia

Cerebral ischemia results in a rapid depletion of energy stores that triggers a complex cascade of cellular events such as cellular depolarization and Ca2+ influx, resulting in excitotoxic cell death. The critical determinant of severity of brain injury is the duration and severity of the ischemic insult and early restoration of CBF. Induced therapeutic hypothermia following CA is the only strategy that has demonstrated improvement in outcomes in prospective, randomized clinical trials. Although pharmacologic neuro-protection has been disappointing thus far in a variety of experimental animal models, further research efforts are directed at using some agents that demonstrate marginal or moderate efficacy in combination with hypothermia. Although the signal transduction pathways and intracellular molecular events during cerebral ischemia and reperfusion are complex, potential therapeutic neuroprotective strategies hold promise for the future.     

Partial or global rat brain ischemia: The SCOT model

A model for inducing partial (PBI) or global brain ischemia (GBI) in awake or anesthetized rats was obtained by ligating one subclavian and both carotid arteries (for PBI) or both subclavian-carotid arteries (for GBI). Rats were intubated and ventilated mechanically then subjected to a midline ventral incision from larynx to xiphoid process. The thorax was entered to expose the aortic arch and either one or both subclavians were ligated to eliminate each vertebral artery supply to brain. After chest closure the common carotid arteries were exposed and immediately ligated or else catheter snares were installed to induce ischemia at a later date. PBI was induced in 3 groups of rats for 7, 30 and 60 days while GBI was given for 5, 10, 30 and 75 minutes in 4 other groups. EEG became flat within 15 seconds after GBI and cortical cerebral blood flow (CBF) was reduced to "zero." EEG was unaffected after PBI but cortical CBF was reduced from a mean 118 ml/100 g tissue/min to 77 ml after 7 days. Morphological damage of CA1 hippocampal neurons after GBI or PBI was found reproducible and time dependent on ischemic duration. Acute cell damage rose from 5-95% in CA1 as GBI duration increased from 5-75 minutes. Similarly, chronic cell damage of CA1 increased as ischemic duration continued from 7-60 days in rats subjected to PBI. The advantages of the present model provide the option of inducing partial or global brain ischemia and of introducing postischemic reperfusion in awake or anesthetized preparations without the use of drugs, blood pressure manipulation or direct contact with brain tissue.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of S-adenosyl-L-methionine on rat brain oxidative stress damage in a combined model of permanent focal ischemia and global ischemia-reperfusion

We analyzed the effects of S-adenosyl-L-methionine (SAM) on tissue oxidative status in a combined model of permanent focal ischemia and global reperfusion in the rat brain. The production of thiobarbituric acid reactive substances (TBARS) was measured under basal conditions and after induction with ferrous salt as an indicator of brain lipid peroxidation. Total, oxidized and reduced glutathione were measured as indicators of the antioxidant defense capacity of brain tissue. Mitochondrial reduction of tetraphenyl tetrazolium (TPT) was quantified morphometrically. Results obtained in vitro showed that incubation with SAM reduced lipid peroxidation, with a maximum inhibition of 65.12+/-5.99% after incubation with 1 mmol/l; glutathione production was not significantly modified. In the brain ischemia-reperfusion model, TBARS production increased and glutathione content decreased, and mitochondrial reduction of TPT decreased significantly after ischemia-reperfusion in areas dependent on carotid circulation. The administration of 50 mg/kg SAM per day for 3 days led to the inhibition of brain lipid peroxidation and increased total glutathione production. These changes were accompanied by an increase in mitochondrial capacity to reduce TPT. We conclude that SAM reduces oxidative damage in the rat brain in an experimental model of ischemia-reperfusion.     

GABA受体在脑缺血中的作用

GABA是哺乳类动物中枢神经系统中的一种抑制性氨基酸递质，通过其三种受体发挥生理作用。随着对脑缺血损伤机制的研究，科学工作者发现，GABA的三种受体在脑缺血损伤与修复中发挥了重要的作用。本文对GABA受体与脑缺血的关系做一综述。     

Cerebral endothelial microvilli following global brain ischemia in dogs

Cerebral blood vessels (BVs) of dogs subjected to global brain ischemia by complete cardiac arrest of 15 min followed by 8 h of reperfusion, were studied in neocortex and hippocampus by means of transmission electron microscopy. Widespread endothelial microvilli were present in the postischemic animals. The number of endothelial microvilli in the postischemic animals (mean/BV in the neocortex = 3.26 and in the hippocampus = 2.54) was significantly larger than that in the non-ischemic controls (mean/BV in the neocortex = 1.39 and in the hippocampus = 0.84), P for both regions being less than 0.05. Arterioles, venules and capillaries, all were equally affected. Endothelial pinocytotic vesicles were also observed frequently in the postischemic dogs. Marked pericapillary swelling of astrocytic foot processes was present in the surrounding neuropil. It is concluded that the prominent cerebral endothelial microvilli recognized after 8 h of reperfusion following cardiac arrest in this experimental model of global brain ischemia, may play a significant role in the development of delayed postischemic hypoperfusion.     

脑温不同对大鼠缺血脑组织c-fos和bcl-2表达的影响

目的 :研究脑缺血后不同脑温对相关基因表达的影响 ,探讨亚低温脑保护作用的机制。方法 :Sprague -Dawley(SD)大鼠 ,随机分为常温 (37- 38℃ )脑缺血、亚低温 (31- 32℃ )脑缺血、高温 (41- 4 2℃ )脑缺血和假手术组 ,每组 12只动物。脑缺血动物模型采用改良的Pulsinelli四动脉阻断法。脑组织中Fos和bcl- 2蛋白的检测采用链菌素亲生物素 -过氧化酶连接法 (SP)免疫组织化学技术。结果 :常温脑缺血再灌注可诱导Fos蛋白的表达 ,亚低温可使Fos蛋白的表达提早而增多 ,高温却使脑缺血时Fos蛋白的表达减少。常温脑缺血再灌注可诱导大脑皮质bcl- 2蛋白表达 ;亚低温增加bcl- 2蛋白表达 ;高温减少bcl- 2蛋白表达。结论 :脑缺血后即时开始亚低温可增加Fos和bcl- 2蛋白的表达 ,是亚低温脑保护作用的机制 ;脑缺血后高温则加剧脑缺血损伤     

Cerebral protective effect of flunarizine in a canine model of cerebral ischemia

Recently there is the hypothesis proposing that ischemic brain damage is associated with intracellular accumulation of calcium (Ca++). Therefore a variety of experiments have been carried out to investigate whether a Ca++-entry blocker was able to protect against brain damage caused by ischemia. The purpose of the present experiment is to study the protective effects of a Ca++ antagonist, flunarizine, on cerebral ischemia. In this experiment fifteen dogs were subjected to ischemia, using the "canine model of the completely ischemic brain regulated with a perfusion method" in which the cerebral blood flow (CBF) can be fully regulated. Five animals served as untreated controls, ten received treatment with flunarizine (1 mg/kg in five dogs and 3 mg/kg in five dogs, respectively). This agent was administered intravenously 20 minutes prior to the production of ischemia, when cerebral blood flow was reduced to one-tenth its normal value while monitoring CBF by means of a laser-Doppler flow meter. After one hour CBF was restored and the recovery of electrical activity of the brain and the degree of brain swelling were observed for three hours. At the end of the experiments, the degree of extravasation of Evans blue in the excised brain was examined. With regard to the recovery of EEG, no recovery of EEG was seen subsequent to recirculation except one dog in the control group. Whereas in the groups treated with flunarizine, remarkable recovery of EEG was found following recirculation in a dose dependent fasion.(ABSTRACT TRUNCATED AT 250 WORDS)     

蛇床子素在缺血再灌注脑损伤模型中的脑保护作用

目的研究蛇床子素（osthole）在缺血再灌注脑损伤中的脑保护作用。方法实验用SD大鼠55只随机分为假手术组、模型组和三个不同剂量给药组（Ost）,其中模型组和给药组采用四血管阻塞法大鼠全脑缺血模型（4VO模型）。各给药组于缺血15min再灌注后1h给予5mg／kg、25mg／kg、125mg／kg蛇床子素腹腔注射治疗。各实验组动物在进行神经功能学评分后,分别用于分析海马CA1区细胞组织形态学变化和caspase3蛋白半定量分析,评价蛇床子素在缺血再灌注脑损伤后的脑保护作用。结果缺血15min再灌注后1h给药的各蛇床子素治疗组大鼠的行为学评分和组织形态学分析结果均明显优于模型组（P〈0．01）并在25mg／kg剂量时表现出最大保护效果,其caspase3表达水平显著降低。结论蛇床子素在脑缺血再灌注脑损伤后有一定的脑保护作用。