Distribution of inducible nitric oxide synthase and cell proliferation in rat brain after transient middle cerebral artery occlusion
Distribution of inducible nitric oxide synthase and cell proliferation in rat brain after transient middle cerebral artery occlusion
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DOI：
10.1016/j.brainres.2006.03.092
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发表时间：
2006-06
期刊：
影响因子：
2.9
通讯作者：
Y. Sehara;Takeshi Hayashi;K. Deguchi;S. Nagotani;Hanzhe Zhang;M. Shoji;K. Abe
中科院分区：
文献类型：
--
作者：
Y. Sehara;Takeshi Hayashi;K. Deguchi;S. Nagotani;Hanzhe Zhang;M. Shoji;K. Abe
一氧化氮（NO）在脑缺血期间可以是神经保护性的或神经毒性的，这取决于所涉及的NO合酶（NOS）亚型。诱导型一氧化氮合酶（inducible NOS，iNOS）除了对缺血性脑损伤具有神经毒性作用外，还通过阻断神经发生而对缺血性脑损伤的预后产生不良影响。因此，本实验研究了短暂性局灶性脑缺血后室管膜下区（SVZ）iNOS分布和细胞增殖的时空变化。短暂性大脑中动脉闭塞（tMCAO）90 min后，缺血中心区iNOS阳性细胞在1 ~ 21 d减少，而同侧缺血周围区iNOS阳性细胞在1 d和3 d增加。5-溴脱氧尿苷（BrdU）阳性细胞在3 ~ 21天出现在缺血核心区，3和7天出现在缺血周围区，7天在同侧SVZ增加。艾德-1阳性细胞出现于缺血3 ~ 21 d，部分细胞与BrdU或iNOS呈双阳性，但多数细胞BrdU阴性。本研究提示，星形胶质细胞在tMCAO后早期在缺血周围区生成，晚期从SVZ迁移到缺血周围区，iNOS表达的时间依赖性和空间变化可能参与了局灶性脑缺血后成体神经发生的增殖和分化。
Nitric oxide (NO) can be neuroprotective or neurotoxic during cerebral ischemia, depending on the NO synthase (NOS) isoform involved. In addition to neurotoxic effect in ischemic brain, inducible NOS (iNOS) also adversely affect ischemic outcome by blocking neurogenesis. In the present study, therefore, we studied the chronological and spatial change of the distribution of iNOS and cell proliferation in subventricular zone (SVZ) after transient focal cerebral ischemia. After 90 min of transient middle cerebral artery occlusion (tMCAO), iNOS-positive cells decreased in the ischemic core at 1 to 21 days, and increased in the ipsilateral periischemic area at 1 and 3 days. 5-Bromodeoxyuridine (BrdU)-positive cells appeared in the ischemic core at 3 to 21 days, appeared in the periischemic area at 3 and 7 days, and increased in the ipsilateral SVZ at 7 days. ED-1-positive cells appeared in the ischemic core at 3 to 21 days, and some of them were double positive with BrdU or iNOS, but the majority were BrdU-negative. The present study suggests that astrocytes are born within the periischemic area at early stage after tMCAO and migrate from SVZ into periischemic area at later stage, and that time-dependent and spatial changes of iNOS expression may be involved in the proliferation and differentiation of adult neurogenesis after focal cerebral ischemia.