Krupinski J, Kaluza J, Kumar P, Kumar S, Wang J M
Department of Neuropathology, Jagiellonian University, Kraków, Poland.
Stroke. 1994 Sep;25(9):1794-8. doi: 10.1161/01.str.25.9.1794.
Stroke is one of the most common causes of mortality and morbidity in the Western world. It results from the occlusion of a cerebral artery followed by severe disturbances in blood supply through microvessels to brain tissue. Despite an extensive literature its pathophysiology is poorly understood, and this has severely impeded the logical development of therapy.
Brains were obtained from 10 patients aged 46 to 85 years with survival times of 5 to 92 days after their stroke. Infarcted areas and representative control tissues from the contralateral uninvolved brain hemisphere were collected. Microvessel density was measured microscopically. A total of 6520 microvessels were scored in 10,801 areas. The level of activation of the endothelial cells was studied by immunohistochemistry using three monoclonal antibodies, viz, E-9, raised against activated endothelial cells; IG11, recognizing vascular cell adhesion molecule-1; and anti-proliferating cell nuclear antigen. Angiogenic activity in tissue extracts was examined using an in vivo chicken chorioallantoic membrane assay.
There was a statistically significant increase in the number of microvessels (Wilcoxon log-rank test; P < or = .01) in 9 of 10 infarcted brain tissues when compared with their contralateral normal hemisphere. In these patients the higher blood vessel counts correlated with longer survival, as ascertained by Spearman's p analysis (P < .02). The number of microvessels filled with blood cells was significantly lower in the infarcted hemispheres (P < .01). In contrast, statistically significant increased numbers of empty microvessels occurred in infarcted tissues compared with the contralateral hemisphere. Monoclonal antibody E-9 reacted weakly with normal-brain vascular endothelial cells; anti-proliferating cell nuclear antigen and IG11 were virtually negative. All three antibodies strongly stained the blood vessels of stroke tissues. The stroke tissues contained angiogenic activity, as shown by the induction of new blood vessels in a chorioallantoic membrane assay.
We have shown that stroke causes active angiogenesis that is more developed in the penumbra. Further experiments are needed to determine if this angiogenesis has beneficial effect.
中风是西方世界最常见的致死和致残原因之一。它是由脑动脉闭塞，随后通过微血管向脑组织的血液供应严重紊乱所致。尽管有大量文献报道，但其病理生理学仍知之甚少，这严重阻碍了治疗方法的合理发展。
从10例年龄在46至85岁之间的患者脑中获取样本，这些患者在中风后存活时间为5至92天。收集梗死区域以及对侧未受累脑半球的代表性对照组织。通过显微镜测量微血管密度。在10801个区域共对6520个微血管进行了评分。使用三种单克隆抗体通过免疫组织化学研究内皮细胞的活化水平，这三种抗体分别是：针对活化内皮细胞产生的E-9；识别血管细胞粘附分子-1的IG11；以及抗增殖细胞核抗原。使用体内鸡胚绒毛尿囊膜试验检测组织提取物中的血管生成活性。
与对侧正常半球相比，10个梗死脑组织中有9个的微血管数量有统计学意义的增加（Wilcoxon对数秩检验；P≤0.01）。通过Spearman秩分析确定，在这些患者中，较高的血管计数与更长的生存期相关（P<0.02）。梗死半球中充满血细胞的微血管数量明显更低（P<0.01）。相比之下，与对侧半球相比，梗死组织中无血细胞的微血管数量有统计学意义的增加。单克隆抗体E-9与正常脑血管内皮细胞反应较弱；抗增殖细胞核抗原和IG11几乎呈阴性。所有三种抗体均强烈染色中风组织的血管。如绒毛尿囊膜试验中新生血管的诱导所示，中风组织具有血管生成活性。
我们已经表明，中风会导致活跃的血管生成，这种血管生成在半暗带更为明显。需要进一步的实验来确定这种血管生成是否具有有益作用。
