VEGF protein associates to neurons in remote regions following cortical infarct
VEGF protein associates to neurons in remote regions following cortical infarct
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DOI：
10.1038/sj.jcbfm.9600320
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发表时间：
2007-01-01
影响因子：
6.3
通讯作者：
Nudo, Randolph J.
中科院分区：
文献类型：
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作者：
Stowe, Ann M.;Plautz, Erik J.;Nudo, Randolph J.
血管内皮生长因子(VEGF)被认为有助于中风后的神经保护和血管生成。虽然在动物模型中已经证实了实验性缺血后血管内皮生长因子的表达增加，但这些研究几乎只集中在梗死区和梗死区周围。本研究调查了在初级运动皮质(M1)梗死后三天，血管内皮生长因子与偏远皮质区神经元的关系。虽然这些偏远地区不在缺血性损伤的直接影响范围内，但远端可塑性与功能恢复有关。在这项研究中，皮质内微刺激技术确定了非人类灵长类动物的初级和运动前皮质区域。用免疫组织化学方法检测神经元和血管内皮生长因子蛋白的表达。体视学技术定量评估了梗死区和梗死区周围、M1后肢、M1口腔面部和腹侧运动前手部表现以及非运动控制区中神经元-血管内皮生长因子的相关性。结果表明，血管内皮生长因子蛋白显著增加了梗死区和梗死区周围特定偏远皮质区神经元的联系。血管内皮生长因子与神经元的相关性增加仅限于在功能和/或行为上与梗死区相关的皮质区域。口面部M1区和非运动控制区无明显增加。我们推测，在这些与功能相关的远程皮质区域，神经元血管内皮生长因子的增强可能通过神经保护或诱导远程血管生成参与卒中后功能的恢复。
Vascular endothelial growth factor ( VEGF) is thought to contribute to both neuroprotection and angiogenesis after stroke. While increased expression of VEGF has been demonstrated in animal models after experimental ischemia, these studies have focused almost exclusively on the infarct and peri-infarct regions. The present study investigated the association of VEGF to neurons in remote cortical areas at three days after an infarct in primary motor cortex (M1). Although these remote areas are outside of the direct influence of the ischemic injury, remote plasticity has been implicated in recovery of function. For this study, intracortical microstimulation techniques identified primary and premotor cortical areas in a non-human primate. A focal ischemic infarct was induced in the M1 hand representation, and neurons and VEGF protein were identified using immunohistochemical procedures. Stereological techniques quantitatively assessed neuronal-VEGF association in the infarct and peri-infarct regions, M1 hindlimb, M1 orofacial, and ventral premotor hand representations, as well as non-motor control regions. The results indicate that VEGF protein significantly increased association to neurons in specific remote cortical areas outside of the infarct and peri-infarct regions. The increased association of VEGF to neurons was restricted to cortical areas that are functionally and/or behaviorally related to the area of infarct. There was no significant increase in M1 orofacial region or in non-motor control regions. We hypothesize that enhancement of neuronal VEGF in these functionally related remote cortical areas may be involved in recovery of function after stroke, through either neuroprotection or the induction of remote angiogenesis.