Studies on the white matter damage after ischemia of perforating brain artery.

迄今为止，尚无与人类腔隙性脑梗死相关的腔隙性脑梗死动物模型。在本研究中，我们的目的是建立一个新的模型，腔隙性脑卒中的结果，在原位小穿通动脉闭塞颈内动脉，脉络膜前动脉（AchA）闭塞。使用改良的永久MCA闭塞方法，对重19-42 kg的墨西哥无毛小型猪进行AchA闭塞，使动物恢复24小时、2天、1周、4周和其他天数。本方案提供了91.4%的成功生产内囊的比率。对于MMEP结果，在AchA闭塞的前6 - 15分钟之间暴露于缺血的内囊组织被认为是半暗带。腔隙性脑梗死动物组在卒中发作后通常表现出神经功能缺损的体征。虽然一定程度的运动功能障碍仍未恢复，但在缺血后12天，神经功能障碍自发恢复到与对照组动物几乎相同。组织病理学观察显示内囊病变呈时间依赖性逐渐扩大，尤其是缺血后1周内病变明显扩大（P<0.05）。超微结构分析揭示了白色物质缺血扩张机制的特点。在梗死周围区，轴突最初肿胀并伴有水肿形成。最后轴突受到可逆性损伤，推测是由于轴突内Ca ~（2+）超载所致。这种连锁反应可能会进一步增加暴露轴突的脆弱性，从而诱导缺血性损伤的扩大。内囊小血管数量在缺血前后保持不变，即使在慢性期也是如此。这可能归因于细胞易感性的差异。

There has been no previous animal model of lacunar infarction relevant to the lacunar infarction of human so far. In this study, we aimed to develop a new model of lacunar stroke in gyrencephalic brain as a result of in situ small perforating arterial occlusion of internal carotid artery, anterior choroidal artery (AchA) occlusion. Mexican hairless miniature pigs, weighing 19-42 kg, were undergone to AchA occlusion, using a modification of the permanent MCA occlusion method Animals were allowed to recover for 24 hours, 2 days, 1 week, 4 weeks and other days. The present protocol provided a 91.4% rate in successful production of the internal capsule. For MMEP results, internal capsule tissues that were exposed to ischemia between the first 6 - 15 minutes of AchA occlusion were considered penumbra zone. Lacunar infarction animal group usually displayed signs of neurological deficit after stroke onset. Although some degree of motor deficit remains to be unrecovered, the neurological deficit spontaneously recovered to became nearly same as to the control animals at 12 day after ischemia. On the other hand, histopathological study revealed that the lesion of internal capsule expands gradually as time dependent manner which is particularly attributed to significant expansion of the ischemic lesion during the first week after ischemia (P<0.05). Ultrastructural analysis unveiled the characteristics in terms of the mechanism of expansion in white matter ischemia. At peri-infarct zone the axon was initially swollen accompanied with the edema formation. Finally the axon was ireversiblly damaged presumably due to the Ca2+ overload in axons. This chain reaction might further increase the vulnarability of the exposed axon to induce the expansion of the ishemic lesion. The small vessels amount at internal capsule remains constant before and after ischemia, even in the chronic phase. This is probably attributed to the difference in cellular susceptibility.