Trauma-induced reactive gliosis is reduced after treatment with octanol and carbenoxolone
Trauma-induced reactive gliosis is reduced after treatment with octanol and carbenoxolone
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DOI：
10.1179/1743132810y.0000000020
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发表时间：
2011-07-01
影响因子：
1.9
通讯作者：
Nilsson, Michael
中科院分区：
文献类型：
--
作者：
Andersson, Helene C.;Anderson, Michelle F.;Nilsson, Michael
背景：脑损伤后反应性神经胶质瘤和瘢痕形成可抑制恢复过程。由于许多胶质细胞利用间隙连接进行细胞间信号传递，本研究调查了两种常用的间隙连接阻滞剂辛醇和卡贝诺洛酮是否可以减轻轻微创伤性脑损伤后的反应性胶质细胞增生。方法：成年雄性sd大鼠针径损伤前后30分钟分别给予辛醇（710 mg/kg）或卡贝诺龙（90 mg/kg）。为了标记细胞分裂，每天2次腹腔注射溴脱氧尿嘧啶（BrdU, 150 mg/kg），间隔8小时，2天后处死。使用免疫组织化学和western blot技术研究BrdU和反应性胶质细胞标记物[胶质纤维酸性蛋白（GFAP）、ED1和NG2]的免疫组织化学。结果：损伤后2 d，损伤部位周围细胞增殖增加，星形胶质细胞和小胶质细胞活化，NG2表达上调。损伤前给药辛醇和卡贝诺龙分别显著降低了60%和70%的细胞增殖。在损伤前后分别给予辛醇，GFAP免疫反应星形胶质细胞离伤口边缘的距离分别减少32%和18%。用辛醇治疗也使反应性小胶质细胞的数量减少了55%，并且在损伤前给药时，辛醇使NG2的表达距离减少了48%。结论：本研究表明，辛醇和卡贝诺酮可以减弱反应性胶质瘤的两个重要组成部分——细胞活化和增殖。
Background: Reactive gliosis and scar formation after brain injury can inhibit the recovery process. As many glial cells utilize gap junctions for intercellular signaling, this study investigated whether two commonly used gap junction blockers, octanol and carbenoxolone, could attenuate reactive gliosis following a minor traumatic brain injury.Methods: Octanol (710 mg/kg) or carbenoxolone (90 mg/kg) was administered 30 minutes before or after a needle track injury in adult male Sprague-Dawley rats. To mark dividing cells, animals were injected with bromodeoxyuridine (BrdU; 150 mg/kg) intraperitoneally two times per day, 8 hours apart and killed 2 days later. Immunohistochemistry for BrdU and markers for reactive glial cells [glial fibrillary acidic protein (GFAP), ED1, and NG2] were investigated using immunohistochemistry and western blot techniques.Results: Two days after injury, increased cellular proliferation, activated astrocytes and microglia, and upregulation of NG2 expression were observed surrounding the injury site. Octanol and carbenoxolone administrated prior to injury significantly decreased cell proliferation by 60 and 70% respectively. The distance of GFAP immunoreactive astrocytes from the wound margin was decreased by 32 and 18% when octanol was administrated prior to or post injury respectively. Treatment with octanol also decreased the number of reactive microglia by 55% and, when administrated prior to injury, octanol reduced the distance of NG2 expression from the wound by 48%.Conclusion: The present study demonstrates that two important components of reactive gliosis, cellular activation and proliferation, can be attenuated by octanol and carbenoxolone.