Vass K, Tomida S, Hossmann K A, Nowak T S, Klatzo I
Laboratory of Neuropathology and Neuroanatomical Sciences, National Institute of Neurological and Communicative Disorders and Stroke, Bethesda, MD 20892.
Acta Neuropathol. 1988;75(3):288-94. doi: 10.1007/BF00690537.
Three transient episodes of 5 min ischemia spaced at 1-h intervals were produced in Mongolian gerbils by bilateral carotid artery occlusion with an implanted vascular occlusion device. The interval of 1 h was chosen to allow for the development of post-ischemic hypoperfusion between the ischemic episodes. Three minutes and 1 h after each ischemic episode, and 6 and 24 h after the third occlusion, Evan's blue (EB) was injected intravenously to trace circulating blood, and the number of perfused capillaries was determined in various brain regions by fluorescence microscopy. Brain edema was evaluated by measuring specific gravity in tissue samples taken from adjacent areas. Repetitive ischemia caused progressively increasing brain edema and a progressive reduction of the number of perfused capillaries. Immediately after each ischemic episode, transient recruitment of capillaries occurred, thus excluding no-reflow as a main pathogenetic factor of microcirculatory disturbances. The pattern of microcirculation 6 and 24 h after the last occlusion revealed a redistribution of circulating blood, characterized by a reduction in the number of EB-filled capillaries associated with a noticeable dilatation of the larger vascular channels. Our studies suggest a close interrelationship between post-ischemic microcirculatory hypoperfusion and the development of brain edema, the degree and extent of which progresses with the repetition of ischemic episodes when they are carried out during the periods of hypoperfusion.
通过植入式血管闭塞装置双侧颈总动脉闭塞，在蒙古沙鼠中产生三次持续5分钟的短暂缺血发作，间隔1小时。选择1小时的间隔是为了使缺血发作之间出现缺血后低灌注。在每次缺血发作后3分钟和1小时，以及第三次闭塞后6小时和24小时，静脉注射伊文思蓝（EB）以追踪循环血液，并通过荧光显微镜在不同脑区确定灌注毛细血管的数量。通过测量从相邻区域采集的组织样本的比重来评估脑水肿。重复性缺血导致脑水肿逐渐加重，灌注毛细血管数量逐渐减少。每次缺血发作后立即出现毛细血管的短暂募集，因此排除了无复流作为微循环障碍的主要发病因素。最后一次闭塞后6小时和24小时的微循环模式显示循环血液重新分布，其特征是EB填充的毛细血管数量减少，同时较大血管通道明显扩张。我们的研究表明，缺血后微循环低灌注与脑水肿的发展之间存在密切的相互关系，当在低灌注期进行缺血发作时，脑水肿的程度和范围会随着缺血发作的重复而进展。
