大鼠大脑中动脉闭塞后丘脑calcineurin变化的研究

目的：揭示大脑中动脉闭塞后丘脑Calcineurin(CaN)的时空变化规律，探讨CaN的作用机制。方法：制备大鼠大脑中动脉永久性闭塞模型，分别测定缺血后不同时间点病灶侧丘脑CaN的活性和含量。结果：缺血后24h始丘脑CaN的含量下降且不恢复；CaN的活性与含量分离。结论：MCAO后丘脑CaN活性独特的时间变化规律显示其参与介导继发性丘脑损伤，可能具有毒性作用。     

大脑中动脉高密度征与磁敏感血栓征对大脑中动脉闭塞比较研究

目的比较研究大脑中动脉高密度征(HMCAS)和磁敏感血栓征(SVS)显示大脑中动脉(MCA)闭塞血栓的差异。方法回顾性分析41例临床及影像证实MCA近段闭塞急性脑梗死患者CT及MRI(包含SWI及MRA序列)影像资料。分析HMCAS、SVS显示责任血管血栓灵敏度、特异性、阳性预测值、阴性预测值及其相关性。结果 41例MCA区域急性脑梗死患者中,MRA显示27例同侧MCA近段闭塞,SWI显示21例SVS,CT显示22例HMCAS。HMCAS、SVS显示责任血管血栓灵敏度(78%,78%)、特异性(93%,100%)、阳性预测值(95%,100%)、阴性预测值(68%,70%)。在所有患者中,HMCAS与SVS对预测MCA近段是否闭塞具有高度的一致性(κ值分=0.853);在MRA证实MCA近段闭塞患者中,HMCAS与SVS有无对预测MCA近段是否闭塞具有良好的一致性(κ值分=0.786)。结论 HMCAS、SVS在显示MCA近段血栓具有较好的灵敏度及高度的特异性,并且两者之间具有良好的一致性。     

大脑中动脉主干闭塞的临床研究

目的研究大脑中动脉主干闭塞(MCAO)不同结局的临床表现和意义,以期探索缺血性脑血管病防治新思路。方法收集邢台市第九医院2016.12-2019.12连续行MRI和MRA检查且临床资料完整的12388例患者。从影像学上除外Willi’s环和其以前的颈内动脉闭塞及烟雾病。根据临床及影像学表现分为:MCAO伴恶性脑梗死组;MCAO伴普通脑梗死组;MCAO无症状三组。结果在12388例中有62例MCAO,占检查者的0.5%。62例MCAO伴恶性脑梗死者3例,占5.0%;脑梗死33例,占53.0%;无症状闭塞者26例,占42.0%。结论 MCAO即可有表现为严重的恶性脑梗死,或一般的脑梗死,无临床症状闭塞也不少见。     

大脑中动脉闭塞后calcineurin变化的研究

Calcineurin(CaN)为蛋白磷酸酶2B家族成员,是目前唯一已知的细胞内Ca~(2+)/钙调素依赖性蛋白磷酸酶。近来发现,CaN在细胞内钙超载引发的一系列病理反应中有关键性作用,永久性大脑中动脉闭塞后脑内不同区域CaN活性和量的变化尚无报道,本文旨在揭示其变化规律,探讨CaN在缺血性神经元损伤中的作用机制。     

选择性动脉溶栓治疗急性大脑中动脉闭塞的体会

目的探讨选择性动脉溶栓治疗急性大脑中动脉闭塞的效果。方法对临床初诊急性大脑中动脉闭塞的患者,经全脑血管造影证实大脑中动脉闭塞并系责任血管后,取尿激酶50万IU稀释在50 ml生理盐水中,先在1 min内推注10万IU,再按1万IU/min泵入,每10 min造影一次。50 min泵完尿激酶,对再通者,停止溶栓;不全开通者再追加20万IU尿激酶;若血管还未开通或开通不理想,改用微导丝对血栓或栓子进行机械碎栓。结果采用选择性动脉溶栓与机械碎栓相结合的治疗方法,12例完全再通,8例部分再通,1例溶栓后再闭塞。2例血管完全开通后合并出血。16例患者临床症状得到改善,2例出现新的脑梗死灶。结论对于基层医院,采取选择性动脉溶栓和机械碎栓结合的方法救治急性大脑中动脉闭塞,疗效满意。     

康复训练对大脑中动脉闭塞大鼠脑梗死灶周围GFAP表达的影响

目的　为研究康复训练对大鼠脑梗死灶周围胶质纤维酸性蛋白 (GFAP)表达的影响。方法　 4 0只Wistar大鼠采用 L onga颈外动脉线栓法制备大鼠大脑中动脉闭塞模型 ,随机分为康复组、造模对照组 ,康复组每天进行 1h滚筒、平衡木、转棒及网屏训练 ;造模对照组置于普通笼中饲养 ,不予以康复训练。每组随机分为 3d、7d、14 d、2 1d 4个时间点 ,每个时间点各 5只大鼠 ,分别于相应天数取脑 ,采用免疫组织化学方法观察每个时间点脑梗死灶周围 GFAP的表达。结果　康复组神经功能评分较造模对照组为好 (P<0 .0 5 ) ;GFAP阳性细胞于脑缺血 3d后即已出现 ,7d、14 d、2 1d大量表达 ,14 d为高峰 ,且康复组较造模对照组明显增多 (P<0 .0 5 )。随时间延长免疫组化染色变深。结论　康复训练能促进中枢神经系统表达较高水平的 GFAP。     

改良线栓法建立大鼠大脑中动脉闭塞模型及缺血区 HSP70 表达分析

目的建立大鼠大脑中动脉闭塞（MCAO）模型,分析缺血区脑组织内热休克蛋白HSP70的表达变化。方法将60只Wistar大鼠随机分为MCA0组及假手术组。采用改良栓线法建立MCAO模型．假手术组仅结扎右侧颈内动脉。苏木精-伊红染色观察两组脑组织镜下形态变化,免疫组织化学方法检测两组HSP70蛋白的表达,并进行统计学分析。结果MCAO组成功建模23例．建模成功率76．7％。苏木精-伊红染色显示：MCAO组标本存在典型缺血性损伤改变。MCAO组HSP70蛋白在6、12、24h的表达分别为7．32±0．894、12．61±0．937、14．83±1．395。假手术组为2．12±0．751、1．93±1．237、2．17±0．352;两组各时间点HSP70蛋白的表达差异均有统计学意义（P〈0．01）。结论采用改良线栓法建立的大鼠MCAO模型简便易行、成功率高。HSP70可能有增加神经元对缺血、缺氧的耐受性,抵抗进一步致死损伤的作用。     

双侧大脑中动脉狭窄/闭塞性病变的临床特征

目的探讨双侧大脑中动脉闭塞性病变的临床特征及可能的发病因素。方法回顾12例脑血管造影证实的双侧大脑中动脉闭塞性病变病例的临床、影像学及脑血流评价资料。对比分析临床、影像学及脑血流资料间相互关系及可能的病因探讨。结果右侧肢体偏瘫8例,左侧肢体偏瘫4例;MR检出病灶左侧大脑半球6个,右侧半球3个;DSA检出右侧大脑中动脉闭塞5支,中重度狭窄6支,轻度狭窄1支。左侧大脑中动脉闭塞3支,中重度狭窄6支,轻度狭窄3支;脑血流评价:12例患者TTP检查均见基底节区血流达峰时间延迟,其中9例右侧比左侧更明显;12例患者脑局部血流检查均见基底节区血流量降低:6例右侧比左侧更明显;99Tm 代谢12例中11例双侧均增高:7例左侧比右侧明显,4例右侧比左侧更明显;18F代谢12例中8例增高:6例左侧比右侧明显,2例右侧比左侧更明显;4例双侧均降低。结论双侧闭塞性病变大脑中动脉血管数无差异,血管闭塞性病变程度右侧重于左侧,而临床症状、体征、MR以左侧半球明显;推测双侧大脑中动脉病变是一慢性进展过程;动脉粥样硬化可能是其病因之一;免疫因素也可能参与发病过程。     

无症状大脑中动脉闭塞的临床研究

目的 探讨无症状大脑中动脉闭塞患者的临床和影像学特点.方法 回顾性分析2016年1月-2019年1月连续住院并行头颅MRA检查患者的临床及影像学资料,选择无症状性大脑中动脉主干闭塞患者作为研究对象,分析其临床和影像学特点.结果 研究共筛查3967例行头颅MRA检查的患者,其中无症状大脑中动脉闭塞者23例(0.58％),...     

延迟亚低温对自发性高血压大鼠永久性大脑中动脉闭塞作用的研究

目的建立自发性高血压大鼠(SHR)永久性大脑中动脉闭塞模型(pMCAO),观察亚低温对神经损伤的保护作用。方法将33只SHR随机分为①延迟2 h亚低温组[n=8,术后2 h给予(33±0.5)℃的全身亚低温];②延迟6 h亚低温组[n=9,术后6 h给予(33±0.5)℃的全身亚低温];③常温组(n=8,术后置于室温25℃);④假手术组(n=8,术中不插入线栓,术后置于室温25℃)。采用线栓法制作pMCAO模型。术后5 h,24 h,36 h对SHR进行神经行为学评分;并于术后36 h处死大鼠,制作脑冠状切片,尼氏染色后计算脑梗死体积、水肿程度;NeuN染色比较大鼠脑梗死周边和梗死核心区神经元的脱失。结果各组大鼠脑梗死后神经行为学评分差异无统计学意义。延迟2 h、6 h亚低温组的梗死体积分别较常温组减小23.75%(P<0.01)、18.72%(P<0.05);水肿程度减轻25.32%、21.52%(P<0.05)。神经元脱失情况:皮质梗死周边,延迟2 h、6 h亚低温组较常温组分别减少21.67%(P<0.01)、15.67%(P<0.05);而皮质梗死核心各手术组之间无明显差别。两亚低温组之间梗死体积、水肿程度及梗死周边神经元的脱失均无显著差异。结论亚低温治疗可以显著减小脑梗死体积和水肿程度。延迟6 h和延迟2 h亚低温治疗的效果无明显差异。     

大鼠大脑中动脉阻断可逆性局灶脑缺血模型的研究

采用普通外科手术，以一顶端贫成光滑圆球的4—0单丝尼龙线，可逆性阻断大鼠一侧大脑中动脉（MCA）的血流，制备局灶性脑缺血及再灌注模型。通过观察动物的神经行为学、脑电生理学及病理形态学变化情况，对该模型的可靠性进行客观评价。结果表明这种改良栓线法制备的模型操作简单，与临床缺血性脑卒中的发病情况相近似，适用于局灶性脑缺血及再灌注损伤机制的研究以及治疗手段的评价。     

两种局灶性脑缺血再灌注模型的比较

目的比较两种大鼠大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)局灶性脑缺血再灌注模型,寻找一种更加理想、稳定和可靠的模型。方法将22只SD大鼠随机分为颈外动脉插线组和颈总动脉插线组,采用线栓法建立大鼠脑缺血再灌注模型,MCAO2h再灌注24h,采用TTC染色和NF-κB免疫组化染色,并分别测定脑梗死体积和NF-κB表达量。结果两种插线方法都能造成大鼠局灶性脑梗死,颈外动脉插线组再灌注状态优于颈总动脉插线组,且脑梗死体积和NF-κB表达量均高于颈总动脉插线组。结论颈外动脉插线闭塞大脑中动脉是一种较为理想和可靠的大鼠MCAO局灶性脑缺血再灌注模型制作方法。     

经颈总动脉和经颈外动脉制作大鼠MCAO模型的比较

大鼠大脑中动脉闭塞模型（MCAO）是局灶性脑缺血再灌注的标准动物模型,该模型为研究人类局灶性脑缺血的疾病特点、发病机制及防治策略提供了可靠平台。本文综述了MCAO模型成功的评价标准,并从动物、线栓、原理、制备方法及改进等方面比较了经颈总动脉进线法和经颈外动脉进线法分别制备大鼠MCAO模型的特点,并对影响大鼠MCAO模型制备成功率的主要因素进行了综述和优化配置。     

Rat middle cerebral artery occlusion by an intraluminal thread compromises collateral blood flow

We compared in Wistar rats collateral blood flow through leptomeningeal anastomoses after middle cerebral artery occlusion using craniotomy (‘extravasal occlusion'), which results in a small volume of cerebral infarction, and after intraluminal thread occlusion (‘intravasal occlusion'), which produces a large volume of cerebral infarction. Simultaneous laser–Doppler flowmetry with two probes placed on the cerebral cortex was used to measure and compare collateral blood flow. Extravasal occlusion caused a cortical blood flow reduction along a gradient in lateral direction, whereas blood flow reduction after intravasal occlusion was more uniformly distributed. It is concluded that permanent intravasal occlusion compromises collateral blood flow and therefore may not be a suitable model for measuring the ability of pharmacotherapeutic agents, if any, to improve collateral blood flow acutely after middle cerebral artery occlusion. The two models can be useful for testing drugs on parenchymal neuroprotective properties. Thereby, the intraluminal technique is preferred because of the possibility to study reperfusion damage when transient occlusion is applied.     

A change of P-selectin immunoreactivity in rat brain after transient and permanent middle cerebral artery occlusion

Abstract

Although the role of an adhesion molecule such as P-selectin may be important in the pathogenesis of stroke, temporal, spacial, and cellular profiles of the expression ofsuch a protein has not been fully studied in the case ofthe middle cerebral artery (MCA) occlusion and reperfusion in rat brain. Change in expression of immunoreactive P-selectin was examined in rat brain after transient MCA occlusion (MCAO) in comparison to that of permanent occlusion with an anti-P-selectin monoclonal antibody. Western blot analyses were performed to ensure the selective detection of immunoreactive P-selectin protein with the monoclonal antibody using brain homogenates before and after MCAO. Temporal, spacial, and cellular changes of P-selectin expressions were evaluated with rat brain sections at 2, 8 h, 1 and 3 days of permanent MCAO, and at 2, 8 h, 1, 3 and 7 days of reperfusion after 1 h of transient MCAO. Western blot showed a single band with a molecular weight of 140 kOa for both cases with permanent occlusion and reperfusion. P-selectin immunoreactivity was not normally present in rat brain sections. However, it was expressed mainly in the post-capillary venules of the cerebral cortex and caudate in the MCA territory with a peak at 2-8 h after permanent occlusion and at 8 h to 1 day after the reperfusion. The expression was diminished by 1 day ofpermanent occlusion and 3 days of reperfusion. The maximum staining in the case of permanent MCAO was stronger than the case with reperfusion. However, spacial distribution of the staining was similar in the cerebral cortex and caudate between the cases with permanent or transient MCAO. These results suggest a different temporal but similar spacial and cellular expression of P-selectin immunoreactivity between permanent occlusion and reperfusion of MCA in rat brain. [Neural Res 1998; 20: 463–469]     

Peripheral and central administration of neuropeptide Y in a rat middle cerebral artery occlusion stroke model reduces cerebral blood flow and increases infarct volume

Recent studies have shown increased immunoreactivity for neuropeptide Y (NPY) within the perilesional cortex following experimental middle cerebral artery occlusion (MCAO) or focal excitotoxic damage. Downregulation of the NPY Y1 receptor gene using an antisense oligodeoxynucleotide produced a doubling of the infarct volume, implying that NPY may mediate neuroprotection against focal ischemia. The effects of treatment with NPY on infarct volume and hemodynamic parameters were investigated in the present study. Adult male Sprague-Dawley rats were anesthetized with sodium pentobarbital to undergo right-sided endovascular MCAO for 2 h. A single dose of NPY was given via intracarotid injection (10 microg/kg) at the beginning of reperfusion, intracisternal injection (10 or 30 microg/kg) at 30 min of ischemia, or intracerebroventricular (i.c.v.) injection (10 or 70 microg/kg) at 30 min of ischemia. Control groups received the vehicle only via the same route. Body temperature was maintained constant, and hemodynamic parameters were monitored during anesthesia. Laser Doppler flowmetry was used to monitor the regional cerebral blood flow (rCBF) during ischemia and reperfusion in some rats. The rats were decapitated on day 3, and their brains were cut into 2-mm thick coronal slices before reaction with a 2% solution of 2,3,5-triphenyltetrazolium chloride to reveal the infarct. Compared to the respective control groups, NPY treatment via any method of administration increased the relative infarct volume. Suppression of rCBF was observed during reperfusion. These results indicate that peripheral or central administration of NPY impairs reperfusion following experimental MCAO and worsens the outcome of focal cerebral ischemia.     

Histopathological effects of delayed reperfusion after middle cerebral artery occlusion in the anesthetized baboon

In patients with middle cerebral artery (MCA) territory stroke, attempts to recanalize the brain are currently being extended beyond the classic 3-h time window. Mechanical thrombectomy is particularly attractive as it may carry lesser risks of severe hemorrhagic transformation than thrombolysis. However, whether late reperfusion per se promotes hemorrhagic transformation and increases infarct volume as compared to permanent occlusion is unclear. There is no study of the histopathologic sequelae of late reperfusion following MCA occlusion (MCAo) in the non-human primate. Five young adult baboons completed a specially designed protocol of 20-h MCAo (under etomidate anaesthesia), followed by 4-week survival and finally perfusion-fixation. Infarct volume was measured histologically using validated stereological methods. The results were compared to our previously published series of 6 h and permanent MCAo performed with identical experimental and post mortem procedures. An infarct was present in each baboon, consistently involving the caudate head, internal capsule and putamen; the adjacent inferior frontal cortex was involved in one subject. Infarct volume was significantly larger than with 6 h MCAo, as expected, but did not differ from permanent MCAo. There was no evidence of hemorrhage around the infarcted area in any animal. We found that following a 20 h ischemic episode, the infarct volume was similar to that found with permanent occlusion, with no evidence of hemorrhagic transformation. Cautiously extrapolating to the human situation, our findings suggest that even late mechanical recanalization may not promote brain damage and could be considered in selected cases.     

症状性大脑中动脉不同部位闭塞的临床和影像特征

目的 分析单侧大脑中动脉闭塞(MCAO)的脑梗死患者的临床和影像学特征,并探讨不同部位MCAO的脑梗死发病机制及出血转化的相关因素.方法 选取MCAO急性脑梗死患者159例,根据闭塞部位分为近端MCAO组和远端MCAO组,比较两组临床和影像学特征,采用多因素Logistics回归分析不同部位MCAO出血转化的独立危险因...     

Expressions of P-selectin- and HSP72-like immunoreactivities in rat brain after transient middle cerebral artery occlusion

The role of an adhesion molecule such as P-selectin may be important in the pathogenesis of stroke. However, temporal, spatial and cellular profiles of the expression of such a protein have not been fully studied. Change of immunoreactive P-selectin was examined in rat brain after transient middle cerebral artery (MCA) occlusion in comparison with that of 72 kDa heat shock protein (HSP72) which is a well known marker of cell injury. Western blot analyses were performed to ensure the selective detection of immunoreactive P-selectin and HSP72 proteins with each antibody using brain samples before and after ischemia. Temporal, spatial and cellular changes of immunohistochemical expressions of P-selectin and HSP72 were evaluated with rat brain sections at 2 and 8 h, and 1, 3 and 7 days of reperfusion after 1 h of MCA occlusion (MCAO). Hematoxylin-eosin (HE) staining was performed to evaluate brain cell damage at 3 and 7 days of reperfusion. Western blot showed a single band at molecular weights of 140 and 72 kDa for P-selectin and HSP72, respectively, only after ischemia. No significant band was observed without primary antibody. P-selectin-like immunoreactivity was not normally present in rat brain sections. However, it was expressed mainly in the post-capillary venules of the cerebral cortex and caudate in the MCA territory with a peak at 8 h to 1 day. The expression was diminished by 3 days of reperfusion. An immunoreactive HSP72 was scarcely present in the cerebral cortex and caudate of the sham control brain. However, the protein was induced in neurons of the MCA territory. The HSP72 induction was gradually intensified from 8 h with peaks at 1 day in the cortex and at 3 days in the caudate. The immunoreactivity decreased by 7 days. Histopathological study with HE staining showed no evident cell damage at 3 and 7 days of reperfusion. The present results indicate that temporal, spatial and cellular differences were present in the expressions of immunoreactive P-selectin and HSP72 proteins. P-selectin was expressed from an earlier stage of reperfusion in post-capillary venules, and the expression became maximum at the same time both in the cerebral cortex and caudate. In contrast, HSP72 induction began later in neurons and reached maximum at a different time between the cortex and caudate.     

Local hemodynamic changes during transient middle cerebral artery occlusion and recirculation in the rat: a [C]iodoantipyrine autoradiographic study

We evaluated acute alterations of local cerebral perfusion following 30 min of transient right proximal middle cerebral artery (MCA) clip-occlusion in the rat and following two intervals of postischemic reperfusion. Local cerebral blood flow (1CBF) was assessed by [¹⁴C]iodoantipyrine autoradiography. Brain temperature was controlled at 35.5–36.5°C throughout the experiment. We measured ICBF in four groups of rats: (a) sham-operated controls (n = 5), (b), following 30 min MCA occlusion (n = 5), (c) following 30 min of MCA occlusion with 15-min reperfusion (n = 6) and (d) following 30 min of MCA with 120-min reperfusion (n = 6). 1CBF was measured in seven regions of the ischemic and non-ischemic hemispheres. MCA occlusion induced an ipsilateral reduction of 1CBF, which was most severe in the parietal cortex (8.4 ± 4.0% of control, mean ± S.D.), and dorsolateral caudoputamen (20.0 ± 13.4% of control). 1CBF in the non-ischemic hemisphere and in ipsilateral regions lying outside the MCA territory also decreased significantly. 1CBF recovery was incomplete when assessed following only 15 min of reperfusion. Reperfusion of 120 min led to return of cortical CBF to control levels, but 1CBF in the caudoputamen remained depressed (50–55% of control values). Caudoputaminal CBF and cortical CBF values were highly correlated with one another under normal and ischemic conditions, but this correlation was disrupted following reperfusion. On the basis of these results, we speculate that, if a means were found to enhance the early recovery of 1CBF following transient ischemia, this might expand the therapeutic window of opportunity for the institution of other neuroprotective strategies.