Loyola University Chicago, Department of Otolaryngology, Burn Shock Trauma Research Institute, Loyola University Chicago, 2160 South 1st Avenue, Maywood, IL 60153, the United States of America; Burn Shock Trauma Research Institute, Loyola University Chicago, 2160 South 1st Avenue, Maywood, IL 60153, the United States of America; Edward Hines Jr. VA Hospital Research Service, Hines, IL 60141, the United States of America.
Loyola University of Chicago, Biomedical Graduate School, 2160 South 1st Avenue, Maywood, IL 60153, the United States of America.
Behav Brain Res. 2022 Sep 5;433:113998. doi: 10.1016/j.bbr.2022.113998. Epub 2022 Jul 7.
Repetitive mild traumatic brain injury (rmTBI) results in a myriad of symptoms, including vestibular impairment. The mechanisms underlying vestibular dysfunction in rmTBI patients remain poorly understood. Concomitantly, acute hypogonadism occurs following TBI and can persist chronically in many patients. Using a repetitive mild closed-head animal model of TBI, the role of testosterone on vestibular function was tested. Male Long Evans Hooded rats were randomly divided into sham or rmTBI groups. Significant vestibular deficits were observed both acutely and chronically in the rmTBI groups. Systemic testosterone was administered after the development of chronic vestibular dysfunction. rmTBI animals given testosterone showed improved vestibular function that was sustained for 175 days post-rmTBI. Significant vestibular neuronal cell loss was, however, observed in the rmTBI animals compared to Sham animals at 175 days post-rmTBI and testosterone treatment significantly improved vestibular neuronal survival. Taken together, these data demonstrate a critical restorative role of testosterone in vestibular function following rmTBI. This study has important clinical implications because it identifies testosterone treatment as a viable therapeutic strategy for the long-term recovery of vestibular function following TBI.
重复性轻度创伤性脑损伤 (rmTBI) 可导致多种症状，包括前庭功能障碍。rmTBI 患者前庭功能障碍的机制仍不清楚。同时，TBI 后会发生急性性腺功能减退症，许多患者会持续存在慢性性腺功能减退症。本研究使用重复性轻度闭合性颅脑创伤动物模型，测试了睾酮对前庭功能的作用。雄性 Long Evans Hooded 大鼠随机分为假手术或 rmTBI 组。rmTBI 组在急性和慢性时均观察到明显的前庭功能障碍。在慢性前庭功能障碍发生后给予全身睾酮。rmTBI 动物给予睾酮后表现出改善的前庭功能，可持续至 rmTBI 后 175 天。然而，与假手术动物相比，rmTBI 动物在 rmTBI 后 175 天观察到明显的前庭神经元细胞丢失，睾酮治疗显著改善了前庭神经元的存活。总之，这些数据表明睾酮在 rmTBI 后前庭功能恢复中具有关键的修复作用。这项研究具有重要的临床意义，因为它确定了睾酮治疗是 TBI 后长期恢复前庭功能的可行治疗策略。
