Garcia J H, Liu K F, Yoshida Y, Lian J, Chen S, del Zoppo G J
Department of Pathology (Neuropathology), Henry Ford Hospital, Detroit, Michigan 48202-2689.
Am J Pathol. 1994 Jan;144(1):188-99.
The results of several experimental studies of focal ischemia and anecdotal observations suggest that leukocytes may contribute to the injury initiated by an arterial occlusion. The timing and the nature of leukocyte responses in evolving brain infarcts (either human or experimental) are incompletely characterized. This is a study of experimental brain lesions in 96 Wistar rats that underwent occlusion of a large intracranial artery for variable intervals ranging between 30 minutes and 7 days. The experimental model, based on the occlusion of a middle cerebral artery ostium via the insertion of a nylon monofilament through the external carotid artery, does not require opening the skull; therefore, the inflammatory response is not influenced by the effects of craniotomy and changes in intracranial pressure are only those induced by the ischemic lesion. All 96 animals having the same type of arterial occlusion developed an ischemic brain lesion (limited to the territory of the corresponding artery) that evolved into an area of extensive neuronal necrosis over a period of 6 to 12 hours followed by pan-necrosis (infarct) approximately 60 hours later. In this study, leukocytes (in particular polymorphonuclear cells) were detected in the microvessels (capillaries and venules) of the ischemic hemisphere as early as 30 minutes after the arterial occlusion. Numbers of intravascular neutrophils peaked at 12 hours, whereas intraparenchymal granulocytes were most numerous at 24 hours; a few granulocytes were visible in the brain infarct as late as day 7. Circulating monocytes were first detected within the capillaries/venules of the ischemic area after 4 to 6 hours. Platelet aggregates were more abundant in the arterial than the venous side of the circulation, and luminal obstruction of arteries by platelet aggregates became noticeable only 48 hours after the arterial occlusion. Fibrin thrombi were conspicuous for their absence. These observations provide the background for studies that will attempt to unravel the relationship between the biological responses of leukocytes and neuronal necrosis secondary to focal ischemia.
多项局灶性缺血实验研究结果及一些轶事性观察表明，白细胞可能在动脉闭塞引发的损伤中起作用。在逐渐发展的脑梗死（无论是人类还是实验性的）中，白细胞反应的时间和性质尚未完全明确。本研究对96只Wistar大鼠进行实验性脑损伤研究，这些大鼠的一条大颅内动脉被闭塞不同时间间隔，范围从30分钟到7天。该实验模型通过经颈外动脉插入尼龙单丝闭塞大脑中动脉开口，无需打开颅骨；因此，炎症反应不受开颅手术影响，颅内压变化仅由缺血性病变引起。所有96只接受相同类型动脉闭塞的动物均出现缺血性脑损伤（局限于相应动脉供血区域），在6至12小时内发展为广泛的神经元坏死区域，约60小时后出现全坏死（梗死）。在本研究中，早在动脉闭塞后30分钟就在缺血半球的微血管（毛细血管和小静脉）中检测到白细胞（特别是多形核细胞）。血管内中性粒细胞数量在12小时达到峰值，而实质内粒细胞在24小时最多；直到第7天在脑梗死中仍可见少数粒细胞。循环单核细胞在4至6小时后首次在缺血区域的毛细血管/小静脉内被检测到。血小板聚集体在循环的动脉侧比静脉侧更丰富，动脉内血小板聚集体造成的管腔阻塞直到动脉闭塞后48小时才变得明显。未发现明显的纤维蛋白血栓。这些观察结果为试图阐明白细胞生物学反应与局灶性缺血继发神经元坏死之间关系的研究提供了背景。
