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。     

大脑中动脉瘤的显微外科治疗

报告34例大脑中动脉瘤显微外科手术的经验,其中1例有2个动脉瘤,共计35个动脉瘤.本组中大型和巨型动脉瘤14个(40%).除2个大脑中动脉主干梭形动脉瘤行动脉瘤包囊,2个巨型动脉瘤行M_1阻断伴颅内外动脉吻合外,其余(88%)均做动脉瘤颈夹闭或动脉瘤切除.无手术死亡,2例术后发生神经功能缺失.平均随访6年,优良率达93.8%.对手术入路、手术方法加以讨论.     

大脑中动脉瘤的显微手术治疗

目的探讨大脑中动脉瘤的显微手术治疗。方法回顾分析13例大脑动脉瘤的临床表现,影像学特点,手术治疗方法及随访结果。结果动脉瘤颈夹闭10例,夹闭＋包裹2例,瘤体切除1例。其中恢复正常或轻残10例,生活不能自理3例。结论大脑中动脉瘤往往以出血为首发症状,一旦确诊,尽早手术。术中注意防止动脉瘤破裂出血及脑血管痉挛。     

The transient intraluminal filament middle cerebral artery occlusion model as a model of endovascular thrombectomy in stroke

The clinical relevance of the transient intraluminal filament model of middle cerebral artery occlusion (tMCAO) has been questioned due to distinct cerebral blood flow profiles upon reperfusion between tMCAO (abrupt reperfusion) and alteplase treatment (gradual reperfusion), resulting in differing pathophysiologies. Positive results from recent endovascular thrombectomy trials, where the occluding clot is mechanically removed, could revolutionize stroke treatment. The rapid cerebral blood flow restoration in both tMCAO and endovascular thrombectomy provides clinical relevance for this pre-clinical model. Any future clinical trials of neuroprotective agents as adjuncts to endovascular thrombectomy should consider tMCAO as the model of choice to determine pre-clinical efficacy.     

Reduction of ischemic brain injury by anti-P-selectin monoclonal antibody after permanent middle cerebral artery occlusion in rat

Abstract

The selectin family of adhesion molecules is involved in adhesion of leukocyte to microcirculatory system and the transmigration into brain parenchyma. Although the role of P-selectin may be important in the pathogenesis of brain ischemia, a possible protective effect on ischemic brain injury by blocking P-selectin has not been reported. We have examined the effects of a novel anti-P-selectin antibody on ischemic brain injury after 24 h of permanent middle cerebral artery occlusion (MCAO) in rat. Male Wistar rats were subjected to MCAO by an insertion of a silicone rubber cylinder for 24 h. Anti-rat P-selectin monoclonal antibody, ARP 2-4 was injected intravenously at a dose of 1 mg kg^–1 at 5 min before the induction of MCAO. Control animals received the same volume of vehicle solution. Regional cerebral blood flow (rCBF) was measured immediately after and at 8 h of MCAO. At decapitation of rats at 24 h of permanent MCAO, infarct size was compared between the antibody and vehicle treated group. In addition, immunohisto- chemistry for leukocyte infiltration and HSP72, and histochemistry for TUNEL were also compared. Pretreatment with ARP 2-4 improved rCBF at 8 h of MCAO (55.4% ± 11.7% of control, n = 5) as compared to vehicle group (24.2% ± 77.8%, n = 5, p < 0.02). Although leukocyte infiltration was not normally detected by monoclonal antibodies for CD11a and CD18, it became remarkably evident at 7 day of MCAO. Although HSP72 and TUNEL were not also detected in sham control brains, they were induced in neurons of the MCA area at 7 day of MCAO. Treatment with ARP 2-4 significantly reduced the numbers of leukocyte and neurons with positive HSP72 and TUNEL stainings. These results demonstrated that an administration of a monoclonal antibody against P-selectin improved rCBF, and attenuated infarct size that was associated with reduction of leukocyte infiltration. Furthermore, treatment with the antibody reduced both HSP72 and TUNEL stainings. These data suggest an important role of P-selectin in ischemic brain damage, and a future therapeutic potential to human stroke patients. [Neurol Res 1999; 21: 269-276]     

Postischemic spontaneous hyperthermia and its effects in middle cerebral artery occlusion in the rat

This study examined the time course and effects of postischemic spontaneous hyperthermia after transient and permanent focal ischemia. Rats underwent a 90-min, 120-min, or permanent middle cerebral artery occlusion (MCAO). Body temperatures started rising 15-20 min after MCAO and reached 39-40.5 degrees C during the first hour. Sustained hyperthermia was observed during the rest of the first 24 h. In another experiment, rats were subjected to the same interventions, but a normothermic body temperature was maintained. Spontaneous hyperthermia significantly increased the infarct volumes measured 48 h after MCAO in all groups. Reperfusion 2 h after the onset of ischemia was not beneficial in the hyperthermic animals in contrast to the normothermic group. We also examined the effect of spontaneous hyperthermia on the temporal progression of infarcted and penumbral areas 4, 12, or 48 h after MCAO. During spontaneous hyperthermia, penumbral areas became infarcted areas more rapidly, which was most expressed at 4 h. These findings demonstrate that severe spontaneous hyperthermia can occur in rats after MCAO and that it not only increases the infarct volumes in both transient and permanent ischemia, but also accelerates the incorporation of penumbral areas into necrotic areas, which significantly decreases the window of opportunity for therapeutic interventions.     

显微手术治疗大脑中动脉分叉部动脉瘤

目的 探讨大脑中动脉(MCA)分叉部动脉瘤的解剖特点、临床特征、影像学表现、显微手术技巧及临床疗效.方法 回顾分析41 例MCA 分叉部动脉瘤显微外科治疗患者的临床资料,39 例有动脉瘤破裂出血的临床表现,按Hunt-Hess 分级:0～Ⅰ级5 例,Ⅱ级15 例,Ⅲ级11 例,Ⅳ级9 例,Ⅴ级1 例.64 排螺旋CT 血管造影(CTA)确诊.41 例均行显微手术治疗,手术入路为翼点入路或扩大翼点入路.对多发动脉瘤采取早期与择期、一期与分期相结合的方法处理动脉瘤,原则是先处理破裂动脉瘤,再处理未破裂动脉瘤.结果 动脉瘤夹闭38 例,动脉瘤夹闭+包裹2 例,夹闭一侧动脉瘤,另一侧动脉瘤未处理1 例.依据GOS 判断:优良31 例,轻残6 例,重残2 例,死亡2 例.结论 显微外科手术治疗MCA 分叉部动脉瘤效果显著.熟悉MCA 分叉部动脉瘤的解剖特征有助于减少术中血管损伤和术后神经功能障碍;对合并脑内血肿的MCA 分叉部动脉瘤,应急诊手术清除血肿并夹闭动脉瘤.     

Brain edema after middle cerebral artery occlusion

The right middle cerebral artery (MCA) was occluded either during 30 min or permanently, in normotensive Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. The rats were killed 2, 6 or 24 h later. Brain specific gravity, an indicator of brain edema, was determined on samples from the prefrontal, frontal, parietal and occipital cortex and the caudate nucleus. In SHR the brain specific gravity was significantly reduced in the right hemisphere at 2, but not at 6 or 24 h after a temporary occlusion. After permanent ligation, the specific gravity markedly decreased with time in the right hemisphere in SHR with significant difference from WKY, as well as from the left hemisphere, at all intervals. Our data support the concept that chronic hypertension aggravates ischemic brain edema after an arterial ligation.     

Regional cerebral blood flow after occlusion of the middle cerebral artery

Occlusions of the middle cerebral artery (MCA) are mostly of embolic origin (appr. 80%) and give rise to about one third of all ischemic strokes, most of these being major strokes. MCA occlusions lasting for less than 1/2 h are tolerated without occurrence of permanent tissue damage. Occlusions lasting between 1/2 h to 4-8 h lead to permanent tissue damage and neurological deficits that are proportional to the duration of occlusion. Maximal tissue damage is obtained after 4-8 h occlusion. A cerebral blood flow of 8-23 ml/100 gr/min is sufficient for cellular viability but insufficient for normal tissue function ("ischemic penumbra"). Cellular function is completely abolished in the interval 8-16 ml/100 gr/min and flow at that level is tolerated only for 1-3 h before neuronal death ensues. In the interval 18-23 ml/100 gr/min there is some functional activity although it is reduced. Experimental and clinical evidence suggests that flow in this interval may be tolerated for several days, months or even longer ("chronic ischemic penumbra"). After MCA occlusion the blood flow falls below 8 ml/100 gr/min in most cases and permanent MCA occlusion always leads to relatively large areas of frank infarction. The ischemic infarcts may be surrounded by collaterally perfused areas where the blood flow is pressure-dependent (impaired autoregulation) and quite commonly insufficient for normal neuronal function (below 23 ml/100 gr/min). Such collaterally perfused areas may include a "chronic ischemic penumbra". Emboli causing MCA occlusions commonly disintegrate and/or migrate more peripherally within the first few weeks post stroke. This leads to reperfusion and changes of ischemic infarcts into hyperemic infarcts where flow is severely increased. The vascular reactivity is completely abolished in hyperemic infarcts and the hyperemic state lasts for about two weeks. Probably, anemic infarcts are equivalent to ischemic infarcts while the hemorrhagic variety is equivalent to hyperemic infarcts. The "partial infarct" with selective neuronal necrosis occurs in experimental animals after MCA occlusions of less than four h but not after permanent MCA occlusion. The significance of partial infarction in human stroke is not clarified. The extent of irreversible tissue damage can be reduced only if therapy sets in within 4-8 h after the occlusion. If a "chronic penumbra" exists the extension of reversible tissue damage can be reduced if therapy aimed at increasing the blood flow in the penumbra sets in within weeks or even months after the stroke.(ABSTRACT TRUNCATED AT 400 WORDS)     

Outcome following occlusion of the middle cerebral artery

Outcome was studied prospectively in 28 consecutive patients with occlusion of the middle cerebral artery (MCA). They comprise a subgroup of 101 consecutive patients with TIA or stroke less than or equal to 75 years of age, admitted within 72 h after the stroke. Cerebral angiography and CT-scan were performed within 1-2 days of admission. CT-scan was repeated 6 months later. Functional status on admission, 3 and 6 months after the stroke was evaluated using the Rankin disability scale (score 1-2: independent of others care, score 3-5: dependent on others care). The degree of hemiparesis was measured using the Medical Research Council's score. Thirteen had infarcts with a diameter less than or equal to 3 cm (mean 2.5 +/- 0.9 cm); 15 had infarcts greater than 3 cm (mean 6.3 +/- 1.4 cm); 10 had trunk occlusions; 18 had branch occlusions. MCA occlusions with large infarcts and severe hemiparesis on admission carried a poor outcome. Eleven (85%) of 13 patients with the case in only 1 (7%) of the 15 with infarcts greater than 3 cm, the remaining 14 (93%) had either died (40%) or were dependent (53%) (p less than 0.00005). Eleven (85%) of 13 patients with mild hemiparesis on admission were independent, while 13 (87%) of 15 with moderate or severe hemiparesis on admission had either died (40%) or were dependent on others' care (47%) 6 months after the stroke (p less than 0.0004). Type of occlusion (branch trunk) was a poor predictor of outcome.     

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。     

猫大脑中动脉闭塞后缺血脑组织早期葡萄糖代谢的研究

目的 通过正电子发射体层摄影术（PET）检查,了解猫大脑中动脉闭塞（MCAO）后缺血区脑组织葡萄糖代谢的变化。方法 经眶电凝猫左侧MCA,制成永久性局灶性脑缺血模型,在电凝MCA前15min,静脉注射18氟化脱氧葡萄糖（fluorine-18-fluorodeoxyglucise,^18FDG),MCAO后15min,1h,3h及6h分别行^18FDG-PET数据采集,并与对照组及对侧相应区域比较,以了解MCAO早期缺血脑组织葡萄糖代谢的变化;同时行神经功能评分及病理学检查,以证实梗死范围,结果 脑缺血后,左侧MCA皮层分布区的葡萄糖代谢明显增高,且随着时间的延长该代谢增高区逐渐集中;病理检查证实,该代谢增高区与缺血区相一致,其最后的浓聚区即为坏死中心区。结论 脑缺血后,脑组织缺血区早期出现葡萄糖代谢增高现象,与以往报道的脑缺血PET的实验结果相反。     

低剖面可视化腔内支撑装置血管内治疗症状性大脑中动脉狭窄

目的 探讨应用低剖面可视化腔内支撑装置（LVIS）治疗症状性大脑中动脉狭窄的安全性和有效性。方法 分析2018年6月—2021年6月广东省中山市人民医院脑血管介入科应用LVIS治疗有完整随访资料的症状性大脑中动脉狭窄患者23例。记录手术成功率、并发症发生情况及支架内再狭窄情况,平均随访6~32个月。结果 23例患者均成功释放支架,术后1例出现远隔部位再灌注出血,经积极保守治疗后好转。1例出现支架内血栓,经抽吸血栓后稍好转。1例仍有短暂性脑缺血发作,造影复查发现支架内再狭窄,通过球囊扩张血管成形,效果良好。术前和术后的狭窄率及NIHSS评分比较,差异有统计学意义（P<0.05）。结论 应用LVIS治疗症状性大脑中动脉狭窄可行、有效。 [国际神经病学神经外科学杂志, 2023, 50(2): 44-48]     

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。     

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.     

大脑中动脉狭窄或闭塞显微手术治疗单中心经验并文献复习

目的 探讨颞浅动脉-大脑中动脉(STA-MCA)搭桥术治疗成人大脑中动脉狭窄或闭塞的疗效.方法 回顾性分析31例行STA-MCA搭桥术治疗的大脑中动脉狭窄或闭塞患者的临床资料,术前均行全脑血管造影(DSA)评价颈外动脉-颞浅动脉、颈内动脉、大脑中动脉的狭窄程度,CT灌注成像(CTP)评估脑血流灌注情况.手术采用经额颞入...     

Alteplase treatment does not increase brain injury after mechanical middle cerebral artery occlusion in the rat

Recanalization of an occluded vessel with recombinant tissue plasminogen activator is an effective strategy for treating acute ischemic stroke. Recombinant tissue plasminogen activator is administered as alteplase, a formulation containing many excipients including L-arginine, the substrate for nitric oxide production. Most studies fail to compare the effects of alteplase on brain injury to its L-arginine carrier solution. This study aimed to verify the previously reported detrimental effects of alteplase after cerebral ischemia and delineate the contribution of L-arginine. Male Wistar rats, subjected to 90 minutes of intraluminal middle cerebral artery occlusion (MCAO), were administered alteplase, the carrier solution or saline upon reperfusion. Neither alteplase nor the carrier affected cerebral blood flow (CBF) restoration throughout the first 60 minutes of reperfusion. Alteplase treatment was associated with increased mortality after MCAO. Twenty-four hours after MCAO, neurologic function and infarct volume did not differ between rats treated with alteplase, the carrier solution, or saline. Irrespective of treatment group, infarct volume was correlated with CBF during reperfusion, neuroscore, and peri-infarct depolarizations. These results suggest that alteplase treatment, independent of thrombolysis, does not cause increased ischemic injury compared with its appropriate carrier solution, supporting the continued use of alteplase in eligible ischemic stroke patients.     

Middle cerebral artery occlusion in the rat: consistent protocol for a model of stroke

Variability in the effects of the intraluminal suture method of middle cerebral artery occlusion (MCAO) in the rat has been a common and disadvantageous finding. Therefore, we systematically investigated the effects of suture type and rat strain on outcome. First, the clinical and neuropathological effects of permanent MCAO with either an uncoated or a silicone-coated nylon suture were studied over 7  days in Sprague–Dawley rats ( n =36 for each type of suture). Outcome was less severe with the uncoated compared with the silicone-coated suture (e.g. total cerebral infarct volume at 24  h before any fatalities was 119.9±79.8  mm³ , cf. 183.0±36.5 mm³ , n =12 for each, P <0.05; and overall mortality rate was 12.5% cf. 33%, respectively), but much more variable (coefficient of variation was 66.6% cf. 19.9%, respectively). Second, being more consistent in its effects, the silicone-coated suture was further studied in Wistar and Fischer-344 rats ( n =12 for each). Seventy-five per cent of the Wistar's died prematurely from gross hemispheric oedema. Motor deficit and extent of infarction in the Fischer-344 rats were both significantly greater compared with Sprague-Dawley rats (e.g. total cerebral infarct volume at 24  h in the former was 253.6±25.4  mm³ , n =11, P <0.05), and more consistent (coefficient of variation was only 10.0%). It was concluded that the silicone-coated suture and the Fischer-344 rats strain produced the most consistent results and their novel combination provides a reliable acute stroke model.     

应用CT密度差后处理技术早期诊断大脑中动脉供血区脑梗死

目的　研究应用CT密度差后处理技术早期诊断大脑中动脉 (MCA)梗死的可行性。方法　对临床考虑为MCA梗死 ,发病 1～ 3h患者行CT扫描 ,随机分为两组 ,用密度差后处理组 5 0例 ,不用密度差后处理组 5 0例 ,于发病 2 4h后进行CT跟踪观察。结果　应用密度差后处理组 ,梗死后 <6 0min、6 0～ 119min、12 0～ 180min确诊例数分别为 1例 (1/ 7)、2 9例 (2 9/ 32 ,90 .6 % )、11例 (11/11) ,而不用密度差后处理组只在发病 12 0～ 180min确诊 2例 (2 / 11)。结论　利用CT密度差后处理技术能对MCA梗死的患者作出早期诊断。     

Discrepancy between cell injury and benzodiazepine receptor binding after transient middle cerebral artery occlusion in rats

We investigated postischemic alterations in benzodiazepine receptor, D1 dopamine receptor, and muscarinic acetylcholine receptor binding after transient middle cerebral artery (MCA) occlusion in rats using [3H]-flumazenil, [3H]-SCH23390, and [3H]-N-methyl-4-piperidyl benzilate ([3H]-NMPB), respectively, as radioligand. These ligand bindings were determined at 3 and 24 h and at 3 and 7 days after ischemia/reperfusion of MCA by using autoradiographic methods. Ischemic cell injury was clearly detected from 3 h after ischemia/reperfusion and progressively increased from 3-24 h after ischemia/reperfusion of MCA. The area of cell injury reached maximum at 24 h after ischemia/reperfusion of MCA. [3H]-SCH23390 binding was reduced to 47% of the contralateral side at 3 days after ischemia/reperfusion of MCA. After 7 days, [3H]-SCH23390 binding was further reduced by 20% in the striatum. [3H]-NMPB binding was slightly decreased in both the striatum and cerebral cortex at 3 days after ischemia/reperfusion of MCA, and [3H]-NMPB binding in the striatum and cerebral cortex were reduced to 42 and 62% of the contralateral side at 7 days after ischemia/reperfusion of MCA. [3H]-NMPB was also decreased at 24 h. In contrast, [3H]-flumazenil binding was not decreased in the striatum and cerebral cortex within 7 days after ischemia/reperfusion of MCA. These results suggest that [3H]-SCH23390 and [3H]-NMPB binding do not correlate with cell injury by ischemia/reperfusion, although vulnerability to ischemia/reperfusion was observed with these receptors. In addition, central benzodiazepine receptor imaging might be essentially stable to neuronal cell injury induced by transient focal cerebral ischemia in rats, in contrast to the results of PET studies.