Wright David K, O'Brien Terence J, Shultz Sandy R, Mychasiuk Richelle
Anatomy and Neuroscience The University of Melbourne Parkville Victoria 3010 Australia.
The Florey Institute of Neuroscience and Mental Health Parkville Victoria 3052 Australia.
Ann Clin Transl Neurol. 2017 Jul 26;4(9):640-654. doi: 10.1002/acn3.441. eCollection 2017 Sep.
Whether sex differences contribute to the heterogeneity of mild traumatic brain injury (mTBI) and repeated mTBI (RmTBI) outcomes in adolescents is unknown. Therefore, this study examined changes in, and differences between, male and female rats following single mTBI and RmTBI.
Rats were given a single mTBI, RmTBI (i.e., 3), or sham injuries. Injuries were administered using a lateral impact model that mimics forces common in human mTBI. After the final injury, rats underwent extensive behavioral testing to examine cognition, motor function, and anxiety- and depressive-like behavior. Postmortem analyses investigated gene expression and structural changes in the brain.
Many of the outcomes exhibited a sex-dependent response to RmTBI. While all rats given RmTBI had deficits in balance, motor coordination, locomotion, and anxiety-like behavior, only male rats given RmTBI had short-term working memory deficits, whereas only females given RmTBI had increased depressive-like behavior. Volumetric and diffusion weighted MRI analyses found that while RmTBI-induced atrophy of the prefrontal cortex was greater in female rats, only the male rats exhibited worse white matter integrity in the corpus callosum following RmTBI. Sex-dependent changes in brain expression of mRNA for glial fibrillary acidic protein, myelin basic protein, and tau protein were also observed following injury.
These findings suggest that in adolescent mTBI, sex matters; and future studies incorporating both male and females are warranted to provide a greater understanding of injury prognosis and better inform clinical practice.
青少年轻度创伤性脑损伤（mTBI）和重复性轻度创伤性脑损伤（RmTBI）结果的性别差异是否导致其异质性尚不清楚。因此，本研究检测了雄性和雌性大鼠在单次mTBI和RmTBI后的变化及差异。
给大鼠施加单次mTBI、RmTBI（即3次）或假损伤。损伤采用侧方撞击模型，模拟人类mTBI常见的受力情况。最后一次损伤后，对大鼠进行广泛的行为测试，以检测认知、运动功能以及焦虑样和抑郁样行为。死后分析研究大脑中的基因表达和结构变化。
许多结果显示出对RmTBI的性别依赖性反应。虽然所有接受RmTBI的大鼠在平衡、运动协调、运动能力和焦虑样行为方面都有缺陷，但只有接受RmTBI的雄性大鼠有短期工作记忆缺陷，而只有接受RmTBI的雌性大鼠有抑郁样行为增加。容积和扩散加权MRI分析发现，虽然RmTBI诱导的雌性大鼠前额叶皮质萎缩更严重，但只有雄性大鼠在RmTBI后胼胝体的白质完整性更差。损伤后还观察到胶质纤维酸性蛋白、髓鞘碱性蛋白和tau蛋白的大脑mRNA表达存在性别依赖性变化。
这些发现表明，在青少年mTBI中，性别很重要；未来有必要纳入雄性和雌性的研究，以更好地理解损伤预后并为临床实践提供更充分的信息。
