Sex-Dependent Pathology in the HPA Axis at a Sub-acute Period After Experimental Traumatic Brain Injury.
Sex-Dependent Pathology in the HPA Axis at a Sub-acute Period After Experimental Traumatic Brain Injury.
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DOI：
10.3389/fneur.2020.00946
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发表时间：
2020
影响因子：
3.4
通讯作者：
Thomas TC
中科院分区：
文献类型：
--
作者：
Bromberg CE;Condon AM;Ridgway SW;Krishna G;Garcia-Filion PC;Adelson PD;Rowe RK;Thomas TC
美国每年报告的创伤性脑损伤（TBI）超过280万例，其中75%以上为轻度TBI，弥漫性轴索损伤（DAI）为主要病理。TBI引发应激反应，刺激下丘脑-垂体-肾上腺（HPA）轴同时与DAI负责反馈调节的大脑区域。虽然男性和女性的情感症状发生率都很高，但女性的表现更为普遍和严重。很少有研究纵向评估了轻度TBI后迟发性情感症状的病因，甚至更少的研究将女性纳入实验设计。在本研究中采用的实验性TBI模型中，在雄性大鼠中，在损伤后2个月时已经报道了慢性HPA失调的证据，在损伤后7天（DPI）在脑的其他区域中具有峰值神经病理学。我们预测导致雄性和雌性大鼠HPA轴失调的机制在7 DPI（亚急性时间点）最为明显。年轻成年年龄匹配的雄性和自然循环的雌性Sprague道利大鼠进行中线液压冲击损伤（mFPI）或假手术。评价下丘脑和海马中促肾上腺皮质激素释放激素、神经胶质增生和糖皮质激素受体（GR）水平，沿着基线血浆促肾上腺皮质激素（ACTH）和肾上腺重量。下丘脑室旁核中的小胶质细胞反应表明，与性别匹配的假手术相比，雄性动物有轻度神经炎症，但雌性动物没有。在海马齿状回的小胶质细胞激活的证据是强大的，在两种性别相比，未受伤的假，有证据表明性别和损伤之间的显着相互作用的小胶质细胞计数。GFAP强度和星形胶质细胞数量随着损伤而增加，指示星形胶质细胞增多。GR蛋白水平升高30%，在海马的女性相比，性别匹配的假。这些数据表明迟发性HPA轴失调之前的DAI后亚急性病理生理学的性别差异。进一步了解导致DAI后迟发性HPA轴失调的病因，可以确定稳定反馈，减轻症状，提高康复和整体恢复的疗效的目标。
Over 2.8 million traumatic brain injuries (TBIs) are reported in the United States annually, of which, over 75% are mild TBIs with diffuse axonal injury (DAI) as the primary pathology. TBI instigates a stress response that stimulates the hypothalamic-pituitary-adrenal (HPA) axis concurrently with DAI in brain regions responsible for feedback regulation. While the incidence of affective symptoms is high in both men and women, presentation is more prevalent and severe in women. Few studies have longitudinally evaluated the etiology underlying late-onset affective symptoms after mild TBI and even fewer have included females in the experimental design. In the experimental TBI model employed in this study, evidence of chronic HPA dysregulation has been reported at 2 months post-injury in male rats, with peak neuropathology in other regions of the brain at 7 days post-injury (DPI). We predicted that mechanisms leading to dysregulation of the HPA axis in male and female rats would be most evident at 7 DPI, the sub-acute time point. Young adult age-matched male and naturally cycling female Sprague Dawley rats were subjected to midline fluid percussion injury (mFPI) or sham surgery. Corticotropin releasing hormone, gliosis, and glucocorticoid receptor (GR) levels were evaluated in the hypothalamus and hippocampus, along with baseline plasma adrenocorticotropic hormone (ACTH) and adrenal gland weights. Microglial response in the paraventricular nucleus of the hypothalamus indicated mild neuroinflammation in males compared to sex-matched shams, but not females. Evidence of microglia activation in the dentate gyrus of the hippocampus was robust in both sexes compared with uninjured shams and there was evidence of a significant interaction between sex and injury regarding microglial cell count. GFAP intensity and astrocyte numbers increased as a function of injury, indicative of astrocytosis. GR protein levels were elevated 30% in the hippocampus of females in comparison to sex-matched shams. These data indicate sex-differences in sub-acute pathophysiology following DAI that precede late-onset HPA axis dysregulation. Further understanding of the etiology leading up to late-onset HPA axis dysregulation following DAI could identify targets to stabilize feedback, attenuate symptoms, and improve efficacy of rehabilitation and overall recovery.
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影响因子：
5.3
作者：
Cope, Elise C.;LaMarca, Elizabeth A.;Gould, Elizabeth
通讯作者：
Gould, Elizabeth
影响因子：
4.2
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影响因子：
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作者：
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8.2
作者：
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Kline AE