Neuronal nitric oxide synthase expression is induced in neocortical astrocytes after spreading depression
Neuronal nitric oxide synthase expression is induced in neocortical astrocytes after spreading depression
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DOI：
10.1097/00004647-199801000-00008
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发表时间：
1998-01-01
影响因子：
6.3
通讯作者：
Kraig, RP
中科院分区：
文献类型：
--
作者：
Caggiano, AO;Kraig, RP
扩散性抑制（SD）可增加缺血性损伤的易感性或延迟保护。由于一氧化氮可调节缺血性损伤，我们研究了SD改变一氧化氮合酶（NOS）的表达是否可以解释SD对缺血的影响。此外，SD后表达NOS的细胞的身份是重要的，因为SD导致细胞内环境的异质性、细胞类型特异性变化，这可以控制NOS活性。免疫组织化学、计算机图像分析和Western blotting显示，SD后6 h和3d，体感皮质神经元型NOS（nNOS）阳性细胞数明显增多（P < 0.05和0.01），而诱导型NOS表达无明显变化。nNOS和胶质细胞酸性蛋白的双标记鉴定这些nNOS阳性细胞为星形胶质细胞。在SD期间，通过用硝普钠或N-A-硝基-L-精氨酸甲酯（LNAM）处理大鼠来检查NO产生的改变对诱导的nNOS表达的影响。nNOS表达增加被硝普钠和苯丙氨酸或苯丙氨酸单独抑制，但LNAM不能。由于SD在与缺血性超敏反应和缺血耐受相关的时间点增加星形胶质细胞nNOS表达，SD调节缺血性损伤的能力必须是复杂的，可能涉及NOS，但也涉及其他因素。
Spreading depression (SD) confers either increased susceptibility to ischemic injury or a delayed protection. Because nitric oxide modulates ischemic injury, we investigated if altered expression of nitric oxide synthase (NOS) by SD could account for the effect of SD on ischemia. Furthermore, the identity of cells expressing NOS after SD is important since SD results in heterogeneous, cell type-specific changes in intracellular environment, which can control NOS activity. Immunohistochemical, computer-based image analyses and Western blotting show that the number of neuronal NOS (nNOS)-positive cells in the somatosensory cortex was significantly increased at 6 hours and 3 days after SD (P < 0.05 and 0.01, respectively), whereas inducible NOS expression remained unchanged. Double-labeling of nNOS and glial fibrillary acidic protein identified these nNOS-positive cells as astrocytes. The effect of altered NO production on induced nNOS expression was examined by treating rats with sodium nitroprusside or N-A-nitro-L-arginine methyl ester (LNAM) during SD. Increased nNOS expression was prevented by sodium nitroprusside and phenylephrine or phenylephrine alone, but not LNAM. Because SD increased astrocytic nNOS expression at time points correlating with both ischemic hypersensitivity and ischemic tolerance, the ability of SD to modulate ischemic injury must be complex, perhaps involving NOS but other factors as well.