Umeano Odera, Wang Haichen, Dawson Hana, Lei Beilei, Umeano Afoma, Kernagis Dawn, James Michael L
Odera Umeano, School of Medicine, Duke University, Durham, NC 27710, United States.
World J Crit Care Med. 2017 May 4;6(2):107-115. doi: 10.5492/wjccm.v6.i2.107.
To address the hypothesis that young, gonad-intact female mice have improved long-term recovery associated with decreased neuroinflammation compared to male mice.
Eight to ten week-old male, female, and ovariectomized (OVX) mice underwent closed cranial impact. Gonad-intact female mice were injured only in estrus state. After injury, between group differences were assessed using complementary immunohistochemical staining for microglial cells at 1 h, mRNA polymerase chain reaction for inflammatory markers at 1 h after injury, Rotarod over days 1-7, and water maze on days 28-31 after injury.
Male mice had a greater area of injury ( = 0.0063), F4/80-positive cells ( = 0.032), and up regulation of inflammatory genes compared to female mice. Male and OVX mice had higher mortality after injury when compared to female mice ( = 0.043). No group differences were demonstrated in Rotarod latencies ( = 0.62). OVX mice demonstrated decreased water maze latencies compared to other groups ( = 0.049).
Differences in mortality, long-term neurological recovery, and markers of neuroinflammation exist between female and male mice after moderate traumatic brain injury (MTBI). Unexpectedly, OVX mice have decreased long term neurological function after MTBI when compared to gonad intact male and female mice. As such, it can be concluded that the presence of female gonadal hormones may influence behavioural outcomes after MTBI, though mechanisms involved are unclear.
探讨与雄性小鼠相比，性腺未受损的年轻雌性小鼠是否因神经炎症减轻而具有更好的长期恢复能力这一假设。
对8至10周龄的雄性、雌性及去卵巢（OVX）小鼠进行闭合性颅脑撞击。性腺未受损的雌性小鼠仅在发情期受伤。损伤后，通过在伤后1小时对小胶质细胞进行补充免疫组织化学染色、在伤后1小时对炎症标志物进行mRNA聚合酶链反应、在第1至7天进行转棒试验以及在伤后第28至31天进行水迷宫试验来评估组间差异。
与雌性小鼠相比，雄性小鼠的损伤面积更大（P = 0.0063）、F4/80阳性细胞更多（P = 0.032）且炎症基因上调。与雌性小鼠相比，雄性和OVX小鼠在损伤后的死亡率更高（P = 0.043）。转棒试验潜伏期无组间差异（P = 0.62）。与其他组相比，OVX小鼠的水迷宫潜伏期缩短（P = 0.049）。
中度创伤性脑损伤（MTBI）后，雌性和雄性小鼠在死亡率、长期神经恢复及神经炎症标志物方面存在差异。出乎意料的是，与性腺未受损的雄性和雌性小鼠相比，OVX小鼠在MTBI后的长期神经功能下降。因此，可以得出结论，雌性性腺激素的存在可能会影响MTBI后的行为结果，但其涉及的机制尚不清楚。
