Astrocytic activation and delayed infarct expansion after permanent focal ischemia in rats.: Part I:: Enhanced astrocytic synthesis of S-100β in the periinfarct area precedes delayed infarct expansion
Astrocytic activation and delayed infarct expansion after permanent focal ischemia in rats.: Part I:: Enhanced astrocytic synthesis of S-100β in the periinfarct area precedes delayed infarct expansion
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DOI：
10.1097/00004647-200206000-00010
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发表时间：
2002-06-01
影响因子：
6.3
通讯作者：
Asano, T
中科院分区：
文献类型：
--
作者：
Matsui, T;Mori, T;Asano, T
星形细胞蛋白S-100β在微摩尔浓度下增强培养的星形胶质细胞诱导型一氧化氮合酶的表达，导致一氧化氮介导的共培养神经元死亡。本研究探讨了在大鼠大脑中动脉永久性闭塞后，梗死区内聚集的反应性星形胶质细胞产生的S-100β是否与梗死灶的延迟扩大有关。该模型脑梗塞体积在最初24小时迅速增加后减慢，至168小时仍保持增加趋势，与24小时比较有显著差异。在延迟扩大梗死灶体积前，梗死区同时表达S-100和胶质纤维酸性蛋白的反应性星形胶质细胞数、抗S-100β单抗夹心酶联免疫吸附测定法测定的组织S-100β水平、末端脱氧核苷酸转移酶介导的2‘-脱氧尿苷5’-三磷酸生物素缺口末端标记阳性细胞数均显著增加。脑脊液中S-100β的浓度呈双相升高，可能反映了脑缺血核心区星形胶质细胞的即刻释放，以及随后脑梗塞周围区反应性星形胶质细胞的产生。这些结果首次表明，反应性星形胶质细胞促进S-100β的合成参与了梗死灶周围区的炎症反应，这可能与作为细胞因子网络主要组成部分的迟发性梗死灶扩张有关。
An astrocytic protein S-100beta enhances the expression of inducible nitric oxide synthase in cultured astrocytes at micromolar concentrations, leading to nitric oxide-mediated death of cocultured neurons. The present study examined whether S-100beta production by reactive astrocytes accumulating within the periinfarct area was related to delayed expansion of infarct volume after permanent middle cerebral artery occlusion in the rat. After rapid increases during the initial 24 hours, the increase of infarct volume then decelerated while maintaining the increasing tendency until 168 hours in this model, attaining a significant difference compared with that at 24 hours. In the periinfarct area, the number of reactive astrocytes expressing both S-100 and glial fibrillary acidic protein, the tissue level of S-100beta as measured by the sandwich enzyme-linked immunosolvent assay method using anti-S-100beta monoclonal antibody, and the number of terminal deoxynucleotidyl transferase-mediated 2'-deox uridine 5'-triphosphatebiotin nick end labeling-positive cells were significantly increased preceding the delayed expansion of infarct volume. The CSF concentration of S-100beta showed a biphasic increase, presumably reflecting the immediate release from astrocytes within the ischemic core and the subsequent production in reactive e astrocytes within the periinfaret area. These results show for the first time that the enhanced synthesis of S-100beta by reactive astrocytes participates in the inflammatory responses within the periinfarct area, which may be related to the occurrence of delayed infarct expansion as a major component of the cytokine network.