The neurosteroids progesterone and allopregnanolone reduce cell death, gliosis, and functional deficits after traumatic brain injury in rats
The neurosteroids progesterone and allopregnanolone reduce cell death, gliosis, and functional deficits after traumatic brain injury in rats
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DOI：
10.1089/neu.2005.22.106
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发表时间：
2005-01-01
影响因子：
4.2
通讯作者：
Stein, DG
中科院分区：
文献类型：
--
作者：
Djebaili, M;Guo, QM;Stein, DG
本报告比较了黄体酮及其代谢物异孕酮对脑外伤后早期损伤级联（细胞凋亡）和长期功能缺陷的影响。在双侧额叶皮质挫伤后1 h、6 h，连续5天注射孕酮（16 mg/kg）或异孕酮（4、8、16 mg/kg）。在损伤后1天内，孕酮和异孕酮均可降低促凋亡蛋白caspase-3和Bax的表达以及细胞凋亡DNA的断裂。孕酮和异孕酮还能在损伤后24小时降低病变部位胶质原纤维酸蛋白（GFAP）阳性星形胶质细胞的大小。与假手术对照组相比，受伤后19天，给予孕酮或三种剂量的异孕酮中的任何一种的受伤大鼠在大细胞基底核中有相同数量的chat阳性细胞。在损伤后19天，给予孕酮或异孕酮（8 mg/kg）的大鼠在空间学习任务中的表现比只给药的大鼠有所改善。这些结果为黄体酮和异孕酮的抗凋亡和抗星形胶质细胞作用提供了证据，并有助于解释为什么在损伤后给予神经类固醇的动物有更好的认知表现。
This report compares the effects of progesterone and its metabolite, allopregnanolone, on the early injury cascade (apoptosis) and long-term functional deficits after TBI. Progesterone (16 mg/kg) or allopregnanolone (4, 8, or 16 mg/kg) were injected at 1 h, 6 h, and then for 5 consecutive days after bilateral contusions of the frontal cortex in adult male rats. Within one day after injury, progesterone and allopregnanolone reduced both the expression of pro-apoptotic proteins caspase-3 and Bax, and apoptotic DNA fragmentation. Progesterone and allopregnanolone also reduced the size of glial fibrillary acid protein (GFAP)-positive astrocytes at the lesion site 24 h after injury. Compared to sham-operated controls at 19 days after injury, injured rats given either progesterone or any of three doses of allopregnanolone had equivalent numbers of ChAT-positive cells in the nucleus basalis magnocellularis. At 19 days post-injury, rats given progesterone or allopregnanolone (8 mg/kg) showed improved performance in a spatial learning task compared to injured rats given only the vehicle. These results provide evidence of the anti-apoptotic and anti-astrogliotic effects of progesterone and allopregnanolone and help to explain why better cognitive performance is observed after injury when animals are given either neurosteroid.