Wagner Amy K, Willard Lauren A, Kline Anthony E, Wenger Michael K, Bolinger Bryan D, Ren Dianxu, Zafonte Ross D, Dixon C Edward
Department of Physical Medicine and Rehabilitation, University of Pittsburgh, 3471 Fifth Avenue, Suite 201 Pittsburgh, PA 15213, USA.
Brain Res. 2004 Feb 13;998(1):113-21. doi: 10.1016/j.brainres.2003.11.027.
Female sex hormones are acutely neuroprotective in experimental models of traumatic brain injury (TBI). Because hormonal profiles are known to vary with estrous cycle stage, the purpose of this study was to evaluate how pre-injury estrous stage affects motor and cognitive performance after experimental TBI. We also sought to compare post-injury behavioral performance in males vs. females. Under anesthesia, male (n=18) and female (n=35) Sprague-Dawley rats underwent either controlled cortical impact (CCI) injury (2.7 mm; 4 m/s) or sham operations. Females were grouped according to estrous stage (proestrous or non-proestrous) at the time of surgery. Motor function was assessed pre-injury and for the first 5 days after surgery using beam balance and walking tasks. Spatial memory was assessed beginning 14 days post-injury utilizing the Morris water maze (MWM) task. No significant differences were found on any task between injured females regardless of estrous cycle stage. Females performed significantly better than males on both motor tasks, but gender did not influence MWM performance. Mixed effects multivariate analysis corroborated these results by showing that pre-injury serum hormone levels had little affect on behavioral performance. The results suggest that the presence of endogenous circulating hormones, rather than hormonal status at time of injury, may confer early neuroprotection in females after TBI. The impact of early neuroprotection on later behavioral outcome and the anatomic structural specificity of hormonal neuroprotection require further study.
在创伤性脑损伤（TBI）实验模型中，女性性激素具有急性神经保护作用。由于已知激素水平会随发情周期阶段而变化，本研究的目的是评估伤前发情阶段如何影响实验性TBI后的运动和认知表现。我们还试图比较雄性和雌性大鼠伤后的行为表现。在麻醉状态下，18只雄性和35只雌性Sprague-Dawley大鼠接受了控制性皮质撞击（CCI）损伤（2.7毫米；4米/秒）或假手术。雌性大鼠在手术时根据发情阶段（动情前期或非动情前期）分组。在伤前以及术后的前5天，使用平衡木和行走任务评估运动功能。在伤后14天开始，利用莫里斯水迷宫（MWM）任务评估空间记忆。无论发情周期阶段如何，受伤雌性大鼠在任何任务上均未发现显著差异。在两项运动任务中，雌性大鼠的表现均明显优于雄性大鼠，但性别并未影响MWM任务的表现。混合效应多变量分析证实了这些结果，表明伤前血清激素水平对行为表现影响不大。结果表明，内源性循环激素的存在而非受伤时的激素状态，可能在TBI后为雌性大鼠提供早期神经保护。早期神经保护对后期行为结果的影响以及激素神经保护的解剖结构特异性需要进一步研究。
