Department of Emergency Medicine, Emory University, Atlanta, GA 30322, USA.
Horm Behav. 2013 Aug;64(3):527-38. doi: 10.1016/j.yhbeh.2013.06.009. Epub 2013 Jul 27.
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 h 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.
孕激素（PROG）和维生素 D 激素（VDH）在治疗创伤性脑损伤（TBI）方面均显示出良好的效果。两者均可调节细胞凋亡、炎症、氧化应激和兴奋毒性。我们研究了 VDH 缺乏症是否会改变 TBI 后的认知行为，以及在双侧额皮质挫伤的中年 VDH 缺乏大鼠中，与单独使用 PROG 或 VDH 相比，联合使用 PROG 和 VDH 是否能改善行为和形态学结局。PROG（16mg/kg）和 VDH（5μg/kg）在损伤后 1 小时经腹腔注射。损伤后 7 天内，另外 8 次皮下注射 PROG。VDH 缺乏本身并未显著降低基线行为功能或加重认知障碍的结果。联合治疗显示在保存空间和参考记忆方面有适度的改善，但与 PROG 单药治疗相比并无显著优势。然而，与 VDH 或 PROG 单独治疗相比，联合治疗在预防 MAP-2 降解方面可显著减少神经元丢失和反应性星形胶质细胞的增殖，显示出更好的疗效。VDH+PROG 联合治疗可能会减轻老年患者脑损伤的一些潜在的长期、微妙的病理生理后果。
