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

目前还没有与人类腔隙性脑梗死相关的腔隙性脑梗死动物模型。在这项研究中，我们的目的是建立一种由颈内动脉原位小穿孔动脉闭塞、脉络膜前动脉（AchA）闭塞导致的脑回头脑腔隙性卒中的新模型。采用改良的MCA永久闭塞法，对体重19-42 kg的墨西哥无毛小型猪进行AchA闭塞，动物恢复24小时、2天、1周、4周及其他天数。目前的方案提供了91.4%的成功率生产内胶囊。对于MMEP结果，在AchA闭塞的前6 - 15分钟内暴露于缺血的内囊组织被认为是半暗带。腔隙性梗死动物组在脑卒中后常表现为神经功能缺损。虽然部分运动缺陷仍未恢复，但在缺血后12天，神经功能缺陷自然恢复，与对照组基本相同。另一方面，组织病理学研究显示，内囊病变呈时间依赖性逐渐扩大，特别是缺血病变在缺血后1周内明显扩大（P<0.05）。超微结构分析揭示了脑白质缺血扩张的特点和机制。在梗死周围区，轴突最初肿胀并伴有水肿形成。最后，轴突被不可逆地破坏，可能是由于轴突Ca2+超载。这种连锁反应可能进一步增加暴露轴突的易损性，从而诱导缺血损伤的扩大。缺血前后，甚至在慢性期，内囊小血管数量保持不变。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.