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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Neural cell adhesion molecule (N-CAM) inhibits astrocyte proliferation after injury to different regions of the adult rat brain.
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Neural cell adhesion molecule (N-CAM) inhibits astrocyte proliferation after injury to different regions of the adult rat brain.

机译:神经细胞粘附分子(N-CAM)抑制成年大鼠大脑不同区域受伤后星形胶质细胞的增殖。

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摘要

After a penetrating lesion in the central nervous system, astrocytes enlarge, divide, and participate in creating an environment that adversely affects neuronal regeneration. We have recently shown that the neural cell adhesion molecule (N-CAM) partially inhibits the division of early postnatal rat astrocytes in vitro. In the present study, we demonstrate that addition of N-CAM, the third immunoglobulin-like domain of N-CAM, or a synthetic decapeptide corresponding to a putative homophilic binding site in N-CAM partially inhibits astrocyte proliferation after a stab lesion in the adult rat brain. Animals were lesioned in the cerebral cortex, hippocampus, or striatum with a Hamilton syringe and needle at defined stereotaxic positions. On one side, the lesions were concomitantly infused with N-CAM or with one of the N-CAM-related molecules. As a control, a peptide of the same composition as the N-CAM decapeptide but of random sequence was infused on the contralateral side of the brain. We consistently found that the population of dividing astrocytes was significantly smaller on the side in which N-CAM or one of the N-CAM-related molecules was infused than on the opposite side. The inhibition was greatest in the cortical lesion sites (approximately 50%) and was less pronounced in the hippocampus (approximately 25%) and striatum (approximately 20%). Two weeks after the lesion, the cerebral cortical sites infused with N-CAM continued to exhibit a significantly smaller population of dividing astrocytes than the sites on the opposite side. When N-CAM and basic fibroblast growth factor, which is known to stimulate astrocyte division in vitro, were coinfused into cortical lesion sites, astrocyte proliferation was still inhibited. These results suggest the hypothesis that, by reducing glial proliferation, N-CAM or its peptides may help create an environment that is more suitable for neuronal regeneration.
机译:在中枢神经系统中出现穿透性病变后,星形胶质细胞会扩大,分裂并参与创造不利影响神经元再生的环境。我们最近显示神经细胞粘附分子(N-CAM)部分抑制体外早期产后大鼠星形胶质细胞的分裂。在本研究中,我们证明添加N-CAM,N-CAM的第三个免疫球蛋白样结构域或对应于N-CAM中推定的同型结合位点的合成十肽能部分抑制星形胶质细胞在刺伤后的增殖。成年大鼠的大脑。用汉密尔顿注射器和针头在确定的立体定位位置将动物皮损于大脑皮层,海马或纹状体。一方面,将病变同时注入N-CAM或N-CAM相关分子之一。作为对照,将与N-CAM十肽相同组成但随机序列的肽注入脑的对侧。我们一致地发现,在输注N-CAM或与N-CAM相关的分子之一的一侧,星形胶质细胞的数量明显少于另一侧。抑制作用在皮质病变部位最大(约50%),在海马(约25%)和纹状体(约20%)中不明显。病变后两周,注入N-CAM的大脑皮层部位比对侧部位继续表现出明显较小的分裂星形胶质细胞。当将已知在体外刺激星形胶质细胞分裂的N-CAM和碱性成纤维细胞生长因子共同融合到皮层病变部位时,星形胶质细胞的增殖仍然受到抑制。这些结果表明,通过减少神经胶质细胞增殖,N-CAM或其肽可以帮助创造一个更适合神经元再生的环境的假设。

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