Chronic cerebral hypoperfusion and reperfusion injury of restoration of normal perfusion pressure contributes to the neuropathological changes in rat brain

Restoration of normal perfusion pressure after resection of cerebral arteriovenous malformations (AVMs) is sometimes complicated by unexplained postoperative brain swelling and/or intracranial hemorrhage, which has been termed normal perfusion pressure breakthrough (NPPB). The precise mechanism of NPPB is still unclear. In this study, we investigated the time courses of blood-brain barrier (BBB) disruption, water content, neuronal apoptosis, myeloperoxidase (MPO) activity and superoxide dismutase (SOD) activity in the brain during restoration of normal perfusion pressure in a new rat model of chronic cerebral hypoperfusion associated with AVMs. Male Sprague-Dawley rats were randomly divided into either a sham-operated group, a control group, or a model group with reperfusion assessed at 1, 12, 24 and 72 h after restoration of normal perfusion pressure. BBB disruption was judged by extravasation of Evans blue (EB) dye. We observed that EB and water content in rat brains of the model group with reperfusion were significantly increased compared with the other groups. The most predominant increase occurred at 1 h after reperfusion, and the next at 24 h after reperfusion, representing biphasic changes which are similar to the pathological processes of acute cerebral ischemia/reperfusion injury. There was no difference of the percentage of apoptotic cells in rat brains between the sham-operated group and the control group using flow cytometry. No prominent apoptotic cells were found in the model group with reperfusion at 1 h. However, the percentage of apoptotic cells increased significantly in rat brains of the model group with reperfusion at 12 h, peaked at 24 h, and decreased at 72 h after reperfusion. Apoptotic cells were confirmed with electron microscopy and terminal deoxynuleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL). A significant enhancement of MPO activity in combination with reduction of SOD activity was seen at 12, 24 and 72 h in rat brains of the model group with reperfusion. Our data indicates that reperfusion after restoration of normal perfusion pressure with chronic cerebral hypoperfusion lead to secondary neuronal damage which may associate with cerebral ischemia/reperfusion injury.     

慢性脑低灌注动物模型再探讨

目的 建立一种新的慢性脑低灌注动脉模型，研究动脉和静脉循环对脑灌注压（CPP）的影响及正常灌注压恢复时脑组织病理变化。方法 24只SD大鼠随机分为模型组、动静脉瘘（AVF）组和假手术组。模型组动物行右侧颈外静脉－颈总动脉端侧吻合，同时结扎左侧横窦引流静脉及双侧颈外动脉。分别于术前、术后即刻和术后3个月检测各组动物平均动脉压（MAP）、颅内引流静脉压（DVP）和CPP。3个月后阻断AVF，定量检测血脑屏障（BBB）破坏程度和脑水含量。透射电镜观察脑组织超微结构。结果 动静脉分流术后MAP明显下降，DVP明显升高，CPP明显降低。术后3个月，模型组动物DVP仍明显升高，CPP明显降低，与其他两组动物相比差别有显著性。AVF阻断后模型组动物BBB明显破坏，脑水含量明显增加。电镜证实脑组织中有不同程度的血管源性脑水肿和（或）出血，并与脑部分毛细血管周围星形胶质细胞足突消失有关。结论 颈动静脉端侧吻合可导致CPP降低，静脉引流障碍进一步加重脑低灌注状态，并与灌注压突破密切相关。该动物模型符合人脑动静脉畸形的基本血流动力学特征。     

慢性脑低灌注诱导神经细胞凋亡的实验研究

亡的时程变化。方法30只SD大鼠随机分为对照组(n=5)、模型不灌注组(n=5)、模型再灌注组动物按正常灌注压恢复后不同时间点分组(0h,n=5;12h,n=5;24h,n=5;72h,n=5)。模型组动物行右侧颈外静脉-颈总动脉端侧吻合,同时结扎左侧横窦引流静脉和双侧颈外动脉。术后3个月,阻断颈部动静脉分流造成模型组动物脑组织再灌注。流式细胞仪定量检测并比较各组动物右侧大脑中动脉区脑组织中神经细胞凋亡率,透射电镜观察神经元的超微结构。结果术后3个月,对照组和模型不灌注组动物脑组织中神经细胞凋亡率无明显差别。模型组动物再灌注即刻(0h)未见明显的神经细胞凋亡,再灌注12h神经细胞凋亡率开始明显增加,24h达高峰,72h降低。电镜证实神经细胞凋亡的存在。结论在慢性脑低灌注状态下,恢复正常灌注压可导致继发性神经细胞损害,可能与脑动静脉畸形切除术后迟发性神经功能障碍有关。     

Experimental rat model of chronic cerebral hypoperfusion–reperfusion mimicking normal perfusion pressure breakthrough phenomenon

BackgroundNormal perfusion pressure breakthrough (NPPB) phenomenon is a major life-threatening complication that restricts the treatment of complex intracranial arteriovenous malformations. The aim of the study it to develop a rat model mimicking NPPB phenomenon that enables the evaluation of any therapy to prevent such complication.MethodsTwenty Wistar male rats were randomly assigned to either a study or a control group. Study animals underwent an end-to-side left external jugular vein-common carotid artery anastomosis and ligation of bilateral external carotid arteries. Control animals only underwent ligation of bilateral external carotid arteries. All animals were sacrificed sixty days after the procedure. Hemodynamic parameters [mean arterial pressure (MAP), intracranial pressure (ICP) and cerebral perfusion pressure (CPP)], blood–brain barrier (BBB) permeability (measured by fluorescein staining) and histological features were then compared between both groups.ResultsA significant decrease in MAP and CPP was confirmed in the study group. An increase in ICP was also observed. A significant decrease in MAP and CPP was also present in the study group when comparing preoperative values with those recorded on days 0 (postoperative), 7 and 60. Fluorescein staining findings were consistent with signs of BBB disruption in study animals. Histological analysis demonstrated an increased number of pyknotic neurons in the ipsilateral hemisphere of rat brains included in the study group.ConclusionThese results confirm that this model mimics a vascular steal state with chronic cerebral hypoperfusion comparable to patients with AVMs behavior and disruption of the BBB after fistula closure comparable to NPPB phenomenon disorders.     

ET_A受体mRNA在慢性低灌注状态脑组织中的表达

目的 :研究低灌注状态脑组织内皮素受体 (ETAR)的 m RNA表达。方法 :建立左侧颈外静脉与颈总动脉行端侧吻合的 SD大鼠模型 ,测定吻合形成后脑血液动力学及软脑膜与脑表面组织内皮素 (ET- 1)改变 ,应用逆转录 - PCR(RT- PCR)方法检测该组织 ETARm RNA表达。结果 :大鼠静动脉的端侧吻合形成动静脉分流 ,左侧局部脑血流量显著降低 ,形成脑低灌注状态 ,低灌注侧脑组织中 ET- 1增加 ,ETARm RNA表达显著下降。吻合口阻断后 ,左侧大脑血流量显著增加 ,ET- 1进一步增加 ,ETARm RNA表达改变不明显。结论 :长期的低灌注脑缺血后 ETARm RNA的表达下降 ,使得脑血管自动调节功能下降可导致“正常灌注压突破”。     

Phosphodiesterase III inhibition promotes differentiation and survival of oligodendrocyte progenitors and enhances regeneration of ischemic white matter lesions in the adult mammalian brain

Vascular dementia is caused by blockage of blood supply to the brain, which causes ischemia and subsequent lesions primarily in the white matter, a key characteristic of the disease. In this study, we used a chronic cerebral hypoperfusion rat model to show that the regeneration of white matter damaged by hypoperfusion is enhanced by inhibiting phosphodiesterase III. A rat model of chronic cerebral hypoperfusion was prepared by bilateral common carotid artery ligation. Performance at the Morris water-maze task, immunohistochemistry for bromodeoxyuridine, as well as serial neuronal and glial markers were analyzed until 28 days after hypoperfusion. There was a significant increase in the number of oligodendrocyte progenitor cells in the brains of patients with vascular dementia as well as in rats with cerebral hypoperfusion. The oligodendrocyte progenitor cells subsequently underwent cell death and the number of oligodendrocytes decreased. In the rat model, treatment with a phosphodiesterase III inhibitor prevented cell death, markedly increased the mature oligodendrocytes, and promoted restoration of white matter and recovery of cognitive decline. These effects were cancelled by using protein kinase A/C inhibitor in the phosphodiesterase III inhibitor group. The results of our study indicate that the mammalian brain white matter tissue has the capacity to regenerate after ischemic injury.     

慢性低灌注脑组织中NPY1受体mRNA的表达

目的:研究低灌注状态脑组织神经肽Y1受体的mRNA表达。方法:建立左侧颈外静脉与颈总动脉端侧吻合的大鼠模型,测定吻合形成后脑血流动力学及脑组织神经肽Y(NPY)改变,检测该组织NPY1R mRNA表达。结果:大鼠静脉动脉端侧吻合形成动静脉分流,左侧局部脑血流量显著降低,脑组织中NPY增加,NPY1R mRNA表达下降。吻合口阻断后,左侧大脑血流量显著增加,NPY1R mRNA表达进一步减低。结论:长期低灌注脑缺血后NPY1R减少,使脑血管自动调节功能下降导致“正常灌注压突破”。     

脑动静脉畸形实验模型及其血流动力学研究

目的　建立脑动静脉畸形 (AVM)模型 ,检测其血流动力学改变。方法　将大鼠左侧颈外静脉与颈总动脉行端侧吻合 ,测定吻合前后及模型动物饲养 16周后的血流动力学改变。结果　大鼠静脉动脉的端侧吻合形成动静脉分流 ,左侧局部脑血流量显著降低、右侧颈外静脉压增加、颈总动脉压降低 ,血流速度增快。16周后左侧局部脑血流量较动静脉吻合形成即刻升高、右侧颈外静脉压和颈总动脉血流速度进一步增加 ,右侧颈总动脉压无明显改变。结论　大鼠颈部动静脉分流形成低灌注压、高血流量、静脉高压的模型 ,符合 AVM的血流动力学特征。长期的脑低灌注压使脑血管反应改变 ,脑血流量有所增加     

甲烯土霉素在脑缺血动物实验中的治疗作用

目的探讨实验性脑缺血嗜中性粒细胞（ＮＣ）的浸润规律及甲烯土霉素（ＭＣ）对其影响。方法采用线栓法制成大脑中动脉脑缺血模型，测定脑组织中髓过氧化物酶（ＭＰＯ）活性，并观察神经病学评分及脑组织病理学改变。结果脑缺血及再灌组局灶性缺血脑组织有ＭＰＯ活性、ＮＣ浸润。ＭＣ能有效地降低局灶性缺血脑组织ＭＰＯ活性，减少ＮＣ浸润数量，减轻脑组织缺血坏死程度，改善缺血后神经功能损害。结论局灶性缺血脑组织中有ＮＣ浸润，后者参与脑缺血损伤的病理生理过程，ＭＣ可通过减轻ＮＣ介导的脑损伤而发挥重要的脑保护作用。     

慢性全脑低灌注大鼠血脑屏障的改变及MMP-9表达的实验研究

目的观察慢性全脑低灌注大鼠模型血脑屏障的改变及MMP-9的表达并探讨其意义。方法雄性SD大鼠，随机分成7组，模型组鼠行双侧颈总动脉分期永久结扎制备慢性全脑低灌注大鼠模型，正常对照组分离出颈总动脉后不予结扎即缝合皮肤。采用HE染色法、辣根过氧化物酶（HRP）染色法及免疫组织化学染色法观察正常对照组及模型组各个时间点（3、24、48h、3d、1和2周）海马区锥体细胞的变化、血脑屏障的变化及脑组织MMP-9的表达。结果通过光学显微镜观察，发现HRP的反应产物和MMP-9的表达主要出现于模型组海马区血管周围，模型制备3h后即开始出现，随着全脑低灌注时间的延长，其表达量逐渐增加，至第3d时表达最明显，1周时开始下降，2周时降至最低，而在正常对照组鼠的脑中未发现HRP的反应产物和MMP-9的表达。同时还发现，海马区锥体细胞从3h起即开始变性、固缩、坏死，随着全脑低灌注时间的延长，海马区完整的细胞逐渐减少。结论慢性全脑低灌注大鼠模型制作的早期，MMP-9的表达增加，通过破坏血脑屏障，促进海马区锥体细胞的损害。     

Effects of low molecular weight heparin-superoxide dismutase conjugate on serum levels of nitric oxide, glutathione peroxidase, and myeloperoxidase in a gerbil model of cerebral ischemia/reperfusion injury

BACKGROUND： Several studies have demonstrated that low molecular weight heparin-superoxide dismutase （LMWH-SOD） conjugate may exhibit good neuroprotective effects on cerebral ischemia/reperfusion injury though anticoagulation, decreasing blood viscosity, having anti-inflammatory activity, and scavenging oxygen free radicals. OBJECTIVE： To investigate the intervention effects of LMWH-SOD conjugate on serum levels of nitric oxide （NO）, glutathione peroxidase （GSH-Px）, and myeloperoxidase （MPO） following cerebral ischemia/reperfusion injury. DESIGN, TIME AND SETTING： A randomized, controlled, and neurobiochemical experiment was performed at the Institute of Biochemical Pharmacy, School of Pharmaceutical Sciences, Shandong University between April and July 2004. MATERIALS： A total of 60 Mongolian gerbils of either gender were included in this study. Total cerebral ischemia/reperfusion injury was induced in 50 gerbils by occluding bilateral common carotid arteries. The remaining 10 gerbils received a sham-operation （sham-operated group）. Kits of SOD, NO, and MPO were sourced from Nanjing Jiancheng Bioengineering Institute, China. LMWH, SOD, and LMWH-SOD conjugates were provided by Institute of Biochemistry and Biotechnique, Shandong University, China. METHODS： Fifty successful gerbil models of total cerebral ischemia/reperfusion injury were evenly randomized to five groups： physiological saline, LMWH-SOD, SOD, LMWH ＋ SOD, and LMWH. At 2 minutes prior to ischemia, 0.5 mL/65 g physiological saline, 20 000 U/kg LMWH-SOD conjugate, 20 000 U/kg SOD, a mixture of SOD （20 000 U/kg） and LMWH （LMWH dose calculated according to weight ratio, LMWH： SOD = 23.6：51）, and LMWH （dose as in the LMWH ＋ SOD group） were administered through the femoral artery in each above-mentioned group, respectively. MAIN OUTCOME MEASURES： Serum levels of NO, MPO, and GSH-Px. RESULTS： Compared with 10 sham-operated gerbils, the cerebral ischemia/reperfusion injury gerbils exhibited decreased s     

A model of the pathophysiology of cerebral arteriovenous malformations by a carotid-jugular fistula in the rat

A model of a carotid-jugular fistula in the rat was created such that the arterial feeding vessel is derived from the intracranial arterial circulation and the venous drainage communicates with a major intracranial venous drainage system. This fistula was created in 28 rats on the right side with an additional 11 rats designed as controls with a right carotid ligation and 6 rats without previous surgery. After 12 weeks convalescence, 6 rats with a carotid-jugular fistula and 6 rats without previous surgery underwent cerebral angiography. All fistulae were patent and the model was verified. All of the 33 remaining rats underwent regional cerebral blood flow (rCBF) determination by [14C]iodoantipyrine autoradiography under barbiturate anesthesia. Of the rats with the fistula, 11 had this fistula obliterated 5 min prior to rCBF determination ('closed' group) while 11 had rCBFs determined with the fistula ('open' group). The rCBF was measured from each hemisphere from 7 anatomical regions. The rCBF in the control animals ranged from a median of 82 to 112 ml/100 g/min, in the 'open fistula' group 46 to 68 ml/100 g/min, and in the 'closed' group 118 to 187 ml/100 g/min. This experimental model stimulates the pathophysiologic perturbations in the parenchyma induced by cerebral arteriovenous malformations. It supports the findings that non-infarctional hypoperfusion can result from arteriovenous malformations and that following extirpation of arteriovenous malformations hyperemia may ensue.     

慢性静脉压增高状态下脑微循环的动态研究

目的 研究慢性静脉压增高状态下脑微循环的动态变化。方法 选择Wistar雄性大鼠16只(对照组A n=6;实验组B n=10),全身麻醉下行右侧颈总动脉与右侧颈外静脉端端吻合。利用激光多普勒扫描技术测定吻合前-后以及2周后吻合部结扎前-后脑表25处局部脑血流(ICBF)和局部脑血流量(ICBV)的变化,区域脑血流(rCBF)和区域脑血流量(rCBV)分别用各自的25个数据的中位数表示。A组:单纯右颈总动脉结扎;B组:右颈总动脉与右颈外静脉端端吻合。结果 A组的两侧大脑半球以及B组的左侧大脑半球吻合前后rCBF、rCBV的变化无统计学意义,B组的右侧大脑半球吻合前后rCBF rCBV也无统计学意义,但2周后rCBF显著降低(p<0.05),rCBV显著增高(P<0.05),吻合部结扎后rCBF即刻增高(P<0.05),rCBV即刻降低(P<0.05):结论 一侧颈总动脉-颈外静脉吻合模型对研究慢性静脉压增高状态下脑缺血的研究具有实用价值;在慢性静脉压增高状态下结扎动静脉短路后,脑灌注压迅速上升,CBF得到改善。     

依达拉奉对慢性脑低灌注大鼠脑自由基代谢及海马CA1区HIF-1α表达的影响

目的:观察依达拉奉对慢性脑低灌注大鼠前脑组织SOD、MDA代谢变化及海马CA1区HIF-1α表达的影响,并探讨其意义。方法:实验分假手术组,模型组及依达拉奉组,后两组采用永久性大鼠双侧劲总动脉结扎术(2-vesselocclusion,2VO)制备慢性脑低灌注模型,各组在术后八周后行水迷宫试验后断头,取前脑组织制备成10%脑组织匀浆检测其SOD活性及MDA含量,并采用免疫组化技术观察海马CA1区HIF-1α表达变化。结果:模型组与假手术组相比水迷宫完成时间显著延长(P<0.05),前脑组织SOD活性降低,MDA含量增加(P<0.01),海马CA1区可见HIF-1α少量表达。依达拉奉组较模型组水迷宫结果显著改善(P<0.01),前脑组织SOD活性增加,MDA含量减少(P<0.01),且海马CA1区可见HIF-1α大量表达。结论:慢性脑低灌注可显著损害大鼠空间学习记忆能力,依达拉奉可能通过抑制黄嘌呤氧化酶和次黄嘌呤氧化酶活性,降低羟自由基的浓度,促进HIF-1α表达等多种途径改善血管性认知障。     

褪黑素对大鼠脑缺血时白细胞浸润和 ICAM-1表达的影响

目的研究褪黑素(melatonin,MT)对大鼠脑缺血损伤缺血区髓过氧化物酶(myeloperoxidase,MPO)的活性及细胞间黏附分子-1(intercellular adhesion molecule-1,ICAM-1)表达的影响。方法线栓法造成大鼠大脑中动脉栓塞制成脑缺血模型,手术分为正常对照组、缺血组、MT治疗组,MT治疗组缺血前30min给予MT (20mg/kg)腹腔注射。术后在相应时间点取缺血侧脑组织,用分光光度计检测MPO的活性,用免疫组化检测I- CAM-1蛋白的表达。结果与正常对照组比较,缺血组各时间点MPO的活性及ICAM-1蛋白的表达均升高,而与缺血组比较MT治疗组各时间点MPO的活性及ICAM-1蛋白的表达均降低。结论MT可能能通过降低MPO的活性即抑制白细胞的浸润和降低ICAM-1蛋白的表达,对缺血的脑组织产生保护作用。     

羧乙基锗倍半氧化物对大鼠脑缺血再灌注损伤的保护作用

采用结扎双侧颈总动脉后再通的方法复制大鼠脑缺血再灌注损伤模型，通过测定再灌注后大鼠海马组织中脂质过氧化产物丙二醛（ＭＤＡ），超氧化物歧化酶（ＳＯＤ）与谷胱甘肽过氧化物酶（ＧＳＨ—Ｐｘ）及ＡＴＰａｓｅ的活性，观察了有机锗─羧乙基锗倍半氧化物（ＣＧＳ）对大鼠脑缺血再灌注后大鼠海马组织中ＭＤＡ水平，明显保护ＳＯＤ、ＧＳＨ─Ｐｘ、Ｎａ＋Ｋ＋─ＡＴＰａｓｅ及Ｃａ２＋─ＡＴ─Ｐａｓｅ活性。表明ＣＧＳ对大鼠脑缺血再灌注损伤具有保护作用。     

Regional cerebral blood flow during hypoxia-ischemia in immature rats

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[14C]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 (intrinsic vulnerability) may influence the heterogeneous pattern of damage seen within individual structures.     

慢性低灌注状态对大鼠脑部能量代谢及学习记忆功能的影响

目的探讨慢性低灌注状态下脑部能量代谢改变对认知功能的影响和可能的影响机制.方法雄性SD大鼠60只,随机分为3组:缺血1月组25只,缺血3月组25只,对照组10只.缺血组大鼠行双侧颈总动脉结扎,在试验的不同阶段对各组大鼠行水迷宫试验和跳台试验,并按期取脑行ATP酶、乳酸脱氢酶(LDH)组织化学染色.结果各缺血组大鼠在行为学功能上较对照组有显著减退,缺血3月组更为明显.各缺血组大鼠海马CA1区ATP酶活性显著降低、乳酸脱氢酶活性升高.结论经双侧颈总动脉永久结扎后形成的脑部慢性低灌注状态并导致的神经元能量代谢水平降低和功能紊乱可能引起认知功能减退.     

慢性脑低灌注对血脑屏障的影响

目的 通过建立一种新的慢性脑低灌注动物模型，探讨慢性脑低灌注对血脑屏障的影响以及正常灌注压突破(NPPB)发生的组织学基础。方法 21只SD大鼠随机分组：假手术组、模型组动物按动静脉分流术后不同时间点(12h、24h、72h、1w、3w、3m)分组。采用免疫组化方法，研究慢性脑低灌注状态下VEGF蛋白表达的时程变化、血管生成和星形胶质细胞反应。结果 VEGF蛋白表达主要位于血管内皮细胞胞浆，在假手术组动物脑组织中呈低水平表达，模型组动物脑组织中VEGF蛋白表达于术后24h开始升高，1w达高峰，持续表达到术后3w，3m恢复到基础水平。模型组动物脑组织中微血管数量于术后1w开始明显增加，一直维持到术后3m，而星形胶质细胞未见明显的增生反应。结论 慢性脑低灌注可持续性诱导VEGF蛋白表达，并与血管生成有一定关系；血管生成与星形胶质细胞反应不协调影响了血脑屏障的结构完整性，可能是导致NPPB的一个重要因素。     

Effect of coenzyme Q10 (CoQ10) on superoxide dismutase activity in ET-1 and ET-3 experimental models of cerebral ischemia in the rat

The aim of the work was to evaluate the influence of CoQ10 on superoxide dismutase (SOD) activity levels in the rat model of cerebral ischemia induced by endothelins (ET-1 or ET-3). ETs (20 pmol) were injected into the right lateral cerebral ventricle and immediately CoQ10 was given intraperitoneally (10 mg/kg b.w.). In the brains of experimental animals subjected both to ET-1 and ET-2 administration there was observed a decrease of SOD activity in the brain stem, in the cerebrallum and in the cerebral cortex at all time intervals. ET-1, as compared to ET-3 evoked longer lasting disturbances in SOD activity. In the cerebellum and in the cerebral cortex positive effect of CoQ10 and recovery to the control values was noted after 4 hours in the group subjected to ET-3 injection and after 24 hours in the ET-1 treated animal. Investigated brain areas showed different sensitivity to ETs. Above data may indicate on beneficial effect CoQ10 in the cerebral ischemia via decrease of free radicals concentration.