Gotts Jeffrey E, Chesselet Marie-Françoise
Department of Neurology, Geffen School of Medicine at UCLA, 710 Westwood Plaza, RNRC B114, Los Angeles, CA 90095, USA.
Exp Neurol. 2005 Jul;194(1):139-50. doi: 10.1016/j.expneurol.2005.02.001.
One of the effects of cortical lesions is to produce cell proliferation in the subventricular zone (SVZ), a neurogenic zone of the adult brain distal from the lesion. The mechanisms of these effects are unknown. Recent evidence points to a relationship between the vasculature and neurogenesis both in vitro and in vivo. In the present study, we asked whether cortical lesions induced vascular modifications in the distal SVZ in vivo. Lesions of the frontoparietal cortex were produced by thermocoagulation of pial blood vessels, a method that leads to highly reproducible loss of all cortical layers, sparing the corpus callosum and underlying striatum. These lesions induced increased immunoreactivity for vascular endothelial growth factor (VEGF) around the walls of SVZ vessels, at a considerable distance from the lesion. Vascular permeability was markedly increased in both the SVZ and RMS by 3 days after the injury. A dramatic increase in endothelial proliferation was followed by expansion of the local SVZ vascular tree 7 days after the injury. This time course corresponded to the proliferative changes in the SVZ, and a tight correlation was observed between the number of blood vessels and the increase in SVZ cell number. The data demonstrate that thermocoagulatory cortical lesions induce distal vascular changes that could play a role in lesion-induced SVZ expansion.
皮质损伤的影响之一是在脑室下区(SVZ)产生细胞增殖,SVZ是成人大脑远离损伤部位的一个神经发生区。这些影响的机制尚不清楚。最近的证据表明,在体外和体内,脉管系统与神经发生之间存在关联。在本研究中,我们探讨了皮质损伤在体内是否会诱导远端SVZ的血管改变。通过热凝软脑膜血管造成额顶叶皮质损伤,该方法可导致所有皮质层高度可重复的损伤,而胼胝体和深层纹状体不受影响。这些损伤在距离损伤部位相当远的SVZ血管壁周围诱导血管内皮生长因子(VEGF)免疫反应性增加。损伤后3天,SVZ和RMS的血管通透性均显著增加。损伤后7天,内皮细胞增殖急剧增加,随后局部SVZ血管树扩张。这个时间进程与SVZ的增殖变化相对应,并且观察到血管数量与SVZ细胞数量的增加之间存在紧密的相关性。数据表明,热凝性皮质损伤诱导远端血管改变,这可能在损伤诱导的SVZ扩张中起作用。