Pentoxifylline does not reduce cerebral ischemic edema in hypertensive rats

Continuous infusion of pentoxifylline 0.30 mg per kg per min starting 30 min after occlusion of the middle cerebral artery did not reduce the development of cerebral edema, as measured by specific gravity 6 h after occlusion in spontaneously hypertensive rats. On the contrary, in the parietal region the specific gravity was significantly lower in treated rats, indicating an increased water content. Thus, this study failed to show any beneficial effect of pentoxifylline in brain edema during early permanent ischemia.     

大脑中动脉供血区大面积脑梗死患者出现致死性脑水肿的早期预测因素

目的 分析大脑中动脉供血区大面积脑梗死患者出现致死性脑水肿的早期预测因素.方法 回顾性研究大脑中动脉供血区大面积脑梗死患者发病24 h内的临床、实验室、影像学因素 病例组为死于致死性脑水肿的患者,对照组为其余存活者.结果 共有72例患者入院,病例组26例,对照组46例 多变量logistic回归分析显示,2组的发病24 h内NIHSS评分（P=0.017）和脑梗死类型（P=0.001）2个因素有显著差异.结论 发病24 h内NIHSS评分≥24、脑梗死范围＞大脑中动脉供血区可能是大脑中动脉供血区大面积脑梗死患者出现致死性脑水肿的早期独立预测因素.     

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)     

生物波调控因子对实验性脑梗死大鼠脑组织NF-κB表达的影响

目的:探讨生物波调控因子(BRF)对实验性脑梗死大鼠脑组织NF-κB表达的影响。方法:成年健康雄性SD大鼠90只随机假手术组、生理盐水组、BRF治疗组。制备大脑中动脉梗死(MCAO)模型,术后1h以1ml/100g的剂量分别腹腔注射1.25%BRF溶液和生理盐水,此后1次/d。进行行为学评分、干湿重法测定脑组织含水量、HE染色观察组织病理学改变、免疫组织化学方法测定脑组织NF-κB的表达。结果:(1)MCAO模型大鼠术后各时间点BRF治疗组的行为学评分较生理盐水组降低。(2)与假手术组比较,BRF治疗组和生理盐水组缺血脑组织含水量于24h开始明显升高,48h达高峰,持续至72h,7d明显下降。除6h外在各时间点均有显著性差异。BRF治疗组脑组织水肿程度减轻,48h脑含水量明显低于生理盐水组。(3)缺血区炎细胞浸润和NF-κB阳性细胞表达于梗死后6h开始增多,48h达高峰,持续至7d。假手术组未见明显炎细胞浸润,可见少量散在的NF-κB阳性细胞。BRF治疗组病理损伤减轻,术后48h、72h脑组织NF-κB阳性细胞表达明显低于生理盐水组。结论:生物波调控因子可以减轻梗死后脑水肿,降低脑组织NF-κB的表达,对大鼠脑组织的缺血损伤产生保护作用。     

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]     

BRF对局灶性脑梗死大鼠脑组织IGF-1表达的影响

目的:探讨生物波调控因子BRF(Bio-wave regulationfactor)对实验性脑梗死大鼠脑组织中IGF-1表达水平的影响。方法:健康雄性SD大鼠90只,制成大脑中动脉梗死(MCAO)模型,随机分为3组,即BRF组、生理盐水和假手术组,各组又分为6,24,48,72h,7d5个亚组。BRF组为腹腔注射给药,生理盐水组给同体积的生理盐水,于相应时间点进行行为学评分、脑含水量及脑组织中IGF-1的表达。结果:①组织含水量:与假手术组相比,其他各组在各时间段均增加。其中术后48hBRF组低于同期的生理盐水组,P<0.05。②IGF-1阳性细胞表达:与假手术组相比,其他各组在各时间段均增加,梗死后6h开始增多,72h达高峰。术后72hBRF组高于同期的生理盐水组,P<0.05。结论:BRF可促进IGF-1表达,升高脑组织IGF-1含量,减轻局灶性脑梗死引起的缺血性损伤。     

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.     

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.     

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。     

Infarcts in the middle cerebral artery territory

Correlates of the size of infarcts, the time from stroke to death, and the mechanisms of death were studied in 77 consecutive patients who died from infarction in the middle cerebral artery territory. The area of infarcts was assessed by planimetry on schemas of representative brain levels and the results were expressed as a ratio of infarcted area on the whole MCA territory. No clear relationship was found between the size of infarcts in the MCA territory, and any of the characteristics of the patients, but extensive infarcts were more frequent when the internal carotid artery was occluded. No evidence was found of an adverse effect of age, diabetes or initial hyperglycemia on the size of infarcts. The mechanisms of death were not linked to sex, age, high blood pressure, diabetes, blood glucose level at admission, presence and location of an arterial occlusion, or etiology of the infarct. On the contrary, they varied as a function of interval from stroke to death. Transtentorial herniation, the main cerebral cause of death, occured mainly in the first week and was related to the large size of infarcts. Rare recurrences of stroke and frequent extracerebral mechanisms of death (mainly pneumonia, pulmonary embolism and cardiopathy) occurred later on.     

Screen-imaging guidance using a modified portable video macroscope for middle cerebral artery occlusion

The use of operating microscopes is limited by the focal length.Surgeons using these instruments cannot simultaneously view and access the surgical field and must choose one or the other.The longer focal length (more than 1 000 mm) of an operating telescope permits a position away from the operating field,above the surgeon and out of the field of view.This gives the telescope an advantage over an operating microscope.We developed a telescopic system using screen-imaging guidance and a modified portable video macroscope constructed from a Computar MLH-10 × macro lens,a DFK-21AU04 USB CCD Camera and a Dell laptop computer as monitor screen.This system was used to establish a middle cerebral artery occlusion model in rats.Results showed that magnification of the modified portable video macroscope was appropriate (5-20 ×) even though the Computar MLH-10 × macro lens was placed 800 mm away from the operating field rather than at the specified working distance of 152.4 mm with a zoom of 1-40 ×.The screen-imaging telescopic technique was clear,life-like,stereoscopic and matched the actual operation.Screen-imaging guidance led to an accurate,smooth,minimally invasive and comparatively easy surgical procedure.Success rate of the model establishment evaluated by neurological function using the modified neurological score system was 74.07%.There was no significant difference in model establishment time,sensorimotor deficit and infarct volume percentage.Our findings indicate that the telescopic lens is effective in the screen surgical operation mode referred to as long distance observation and short distance operation and that screen-imaging guidance using an modified portable video macroscope can be utilized for the establishment of a middle cerebral artery occlusion model and micro-neurosurgery.     

Apparent diffusion coefficient evaluation for secondary changes in the cerebellum of rats after middle cerebral artery occlusion

Supratentorial cerebral infarction can cause functional inhibition of remote regions such as the cerebellum, which may be relevant to diaschisis. This phenomenon is often analyzed using positron emission tomography and single photon emission CT. However, these methods are expensive and radioactive. Thus, the present study quantified the changes of infarction core and remote regions after unilateral middle cerebral artery occlusion using apparent diffusion coefficient values. Diffu- sion-weighted imaging showed that the area of infarction core gradually increased to involve the cerebral cortex with increasing infarction time. Diffusion weighted imaging signals were initially in- creased and then stabilized by 24 hours. With increasing infarction time, the apparent diffusion co- efficient value in the infarction core and remote bilateral cerebellum both gradually decreased, and then slightly increased 3-24 hours after infarction. Apparent diffusion coefficient values at remote regions （cerebellum） varied along with the change of supratentorial infarction core, suggesting that the phenomenon of diaschisis existed at the remote regions. Thus, apparent diffusion coefficient values and diffusion weighted imaging can be used to detect early diaschisis.     

Health status and life satisfaction after decompressive craniectomy for malignant middle cerebral artery infarction

Objectives –  To study the long-term outcome in patients with malignant middle cerebral artery (MCA) infarction treated with decompressive craniectomy. The outcome is described in terms of survival, impairment, disabilities and life satisfaction.
Materials and methods –  Patients were examined at a minimum of 1 year (mean 2.9, range 1–6) after the surgery and classified according to the Glasgow Outcome Scale (GOS), the National Institutes of Health Stroke scale (NIHSS), the Barthel Index (BI), the short-form health survey (SF-36) and the life satisfaction checklist (LiSat-11).
Results –  Eighteen patients were included. The long-term survival was 78%. The mean NIHSS score was 13.8 (range 6–20). No patient was left in a vegetative state. The mean BI was 63.9 (5-100). The SF-36 scores showed that the patients' view of their health was significantly lower in most items compared with that of a reference group. According to the LiSat checklist, 83% found their life satisfying/rather satisfying and 17% found their life rather dissatisfying/dissatisfying.
Conclusion –  We conclude that the patients remained in an impaired neurological condition, but had fairly good insight into their limitations. Although their life satisfaction was lower compared with that of the controls, the majority felt that life in general could still be satisfying.     

恶性大脑中动脉综合征43例临床分析

目的探讨大脑中动脉主干梗死的病因、临床表现及疗效。方法对43例恶性大脑中动脉综合征临床表现、头颅CT、MRI、MRA、TCD、空腹血糖、血脂等危险因素进行分析。结果大脑中动脉主干梗死以栓塞多见，早期栓塞面积越大、血糖水平越高，预后越差。结论发现缺血性脑血管的危险因素，有利于预防恶性大脑中动脉综合征发生。     

恶性大脑中动脉综合征43例临床分析

目的探讨大脑中动脉主干梗死的病因、临床表现及疗效。方法对43例恶性大脑中动脉综合征临床表现、头颅CT、MRI、MRA、TCD、空腹血糖、血脂等危险因素进行分析。结果大脑中动脉主干梗死以栓塞多见,早期栓塞面积越大、血糖水平越高,预后越差。结论发现缺血性脑血管的危险因素,有利于预防恶性大脑中动脉综合征发生。     

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。