Progesterone and vitamin D: Improvement after traumatic brain injury in middle-aged rats.
Progesterone and vitamin D: Improvement after traumatic brain injury in middle-aged rats.
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DOI：
10.1016/j.yhbeh.2013.06.009
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发表时间：
2013-08
影响因子：
3.5
通讯作者：
Stein, Donald G.
中科院分区：
文献类型：
--
作者：
Tang, Huiling;Hua, Fang;Wang, Jun;Sayeed, Iqbal;Wang, Xiaojing;Chen, Zhengjia;Yousuf, Seema;Atif, Fahim;Stein, Donald G.
关键词：
黄体酮（PROG）和维生素D激素（VDH）在治疗创伤性脑损伤（TBI）方面都显示出前景。两者都调节细胞凋亡、炎症、氧化应激和兴奋性毒性。我们研究了21天的VDH缺乏是否会改变TBI后的认知行为，以及在双侧内侧额叶皮质挫伤的VDH缺乏的中年大鼠中，PROG和VDH联合使用是否比单独使用任何一种激素更能改善行为和形态学结果。伤后1小时腹腔注射PROG （16 mg/kg）和VDH（5µg/kg）。损伤后7天皮下注射8个额外剂量的PROG。VDH缺乏本身并没有显著降低基线行为功能或加重受损的认知结果。联合治疗在保留空间记忆和参考记忆方面有中度改善，但不明显优于PROG单药治疗。然而，联合治疗可显著减少神经元丢失和反应性星形胶质细胞的增殖，并且在阻止MAP-2降解方面比单独使用VDH或PROG表现出更好的效果。VDH+PROG联合治疗可以减轻老年受试者脑损伤的一些潜在的长期、微妙的病理生理后果。
Progesterone (PROG) and vitamin D hormone (VDH) have both shown promise in treating traumatic brain injury (TBI). Both modulate apoptosis, inflammation, oxidative stress, and excitotoxicity. We investigated whether 21 days of VDH deficiency would alter cognitive behavior after TBI and whether combined PROG and VDH would improve behavioral and morphological outcomes more than either hormone alone in VDH-deficient middle-aged rats given bilateral contusions of the medial frontal cortex. PROG (16 mg/kg) and VDH (5 µg/kg) were injected intraperitoneally 1 hour post-injury. Eight additional doses of PROG were injected subcutaneously over 7 days post-injury. VDH deficiency itself did not significantly reduce baseline behavioral functions or aggravate impaired cognitive outcomes. Combination therapy showed moderate improvement in preserving spatial and reference memory but was not significantly better than PROG monotherapy. However, combination therapy significantly reduced neuronal loss and the proliferation of reactive astrocytes, and showed better efficacy compared to VDH or PROG alone in preventing MAP-2 degradation. VDH+PROG combination therapy may attenuate some of the potential long-term, subtle, pathophysiological consequences of brain injury in older subjects.
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