NEOCORTICAL NEURAL SPROUTING, SYNAPTOGENESIS, AND BEHAVIORAL RECOVERY AFTER NEOCORTICAL INFARCTION IN RATS

NEOCORTICAL NEURAL SPROUTING, SYNAPTOGENESIS, AND BEHAVIORAL RECOVERY AFTER NEOCORTICAL INFARCTION IN RATS
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DOI:
10.1161/01.str.26.11.2135
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发表时间:
1995-11-01
期刊:
影响因子:
8.3
通讯作者:
HULSEBOSCH, CE
HULSEBOSCH, CE
中科院分区:
医学1区
文献类型:
--
作者:
STROEMER, RP;KENT, TA;HULSEBOSCH, CE

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背景和目的海马损伤的神经解剖学可塑性已得到很好的描述,但在新皮层中仍存在一些争议。本研究的目的是测量已知参与神经突生长或突触发生的蛋白质的新皮质分布和表达密度,并将新皮质表达与局灶性新皮质梗死后的行为恢复相关联。局灶性新皮层梗死创建一个限定的病变,在新皮层,提供了一个去神经刺激神经突起的生长和synaptogenes.Methods单侧新皮层缺血诱导的雄性自发性高血压Wistar大鼠(n = 4每个时间点)永久闭塞的远端大脑中动脉和同侧颈总动脉。为了确定轴突生长和/或突触发生的空间和时间分布,GAP-43,轴突生长锥上表达的生长相关蛋白,和突触囊泡上发现的钙结合蛋白突触素,通过免疫组织化学技术进行了检查。测量反应产物,并记录分布。由于所导致的梗死包括前肢新皮层的一部分,因此在用于免疫组织化学研究的相同大鼠上进行了使用埃尔南德斯和Sjuert的足错测试的前肢功能的行为评估。恢复时间分别为3,7,14,30,和60天后surgical.Results GAP-43和突触素蛋白表现出统计学显着增加的免疫反应产物的密度,由光密度测量在梗死大鼠的新皮层相比,假对照组。差距-43仅在第3、7和14天在梗塞的内侧和外侧的前肢、后肢和顶叶新皮层区域升高至统计学显著水平。与此相反,突触体蛋白的表达在3或7天没有统计学显著性变化,但在14,30和60天的前肢,后肢,顶叶新皮层区域内侧和外侧的梗死以及对侧顶叶新皮层表现出统计学显著性增加。前肢功能的行为评估表明,对侧的前肢放置在14天趋向于控制值的梗死,并没有显着差异,从控制30 day.Conclusions这些数据支持神经突起生长的发生,然后在新皮层,同侧和对侧的新皮层缺血突触发生,在空间和时间上都与行为恢复相对应的模式。因此,新皮层中的神经解剖学重塑提供了功能恢复的机制。
Background and Purpose Neuroanatomical plasticity is well described in lesions of the hippocampus but remains a subject of some controversy in the neocortex. The purpose of the present study was to measure the neocortical distribution and density of expression of proteins known to be involved in neurite growth or synaptogenesis and to correlate the neocortical expression with behavioral recovery after a focal neocortical infarction. Focal neocortical infarction creates a circumscribed lesion in the neocortex that provides a denervation stimulus for neurite growth and synaptogenesis.Methods Unilateral neocortical ischemia was induced in male spontaneously hypertensive Wistar rats (n = 4 per time point) by permanent occlusion of the distal middle cerebral artery and ipsilateral common carotid artery. To determine the spatial and temporal distribution of neurite growth and/or synaptogenesis, GAP-43, a growth-associated protein ex pressed on axonal growth cones, and synaptophysin, a calcium-binding protein found on synaptic vesicles, were examined by immunohistochemical techniques. The reaction product was measured, and the distribution was recorded. Since the resulting infarction included a portion of the forelimb neocortex, behavioral assessments of forelimb function that used the foot-fault test of Hernandez and Schallert were performed on the same rats used for immunohistochemical studies. Recovery times were 3, 7, 14, 30, and 60 days after surgery.Results Both GAP-43 and synaptophysin proteins demonstrated statistically significant increases in the density of immunoreaction product as determined by optical density measurements in the neocortex of infarcted rats compared with sham controls. The GAP-43 was elevated to statistically significant levels in forelimb, hindlimb, and parietal neocortical regions medial and lateral to the infarction only at days 3, 7, and 14. In contrast, synaptophysin demonstrated no statistically significant changes in expression at 3 or 7 days but demonstrated statistically significant increases at 14, 30; and 60 days in the forelimb, hindlimb, and parietal neocortical regions medial and lateral to the infarction as well as in the contralateral parietal neocortex. Behavioral assessment of forelimb function indicated impairment of forelimb placement on the side contralateral to the infarction that trended toward control values at 14 days and was not significantly different from controls by 30 days.Conclusions These data support the occurrence of neurite growth followed by synaptogenesis in the neocortex, ipsilateral and contralateral to neocortical ischemia, in a pattern that corresponds both spatially and temporally with behavioral recovery. Thus, neuroanatomical remodeling in the neocortex provides a mechanism for recovery of function.