Ferguson Lindsay, Giza Christopher C, Serpa Rebecka O, Greco Tiffany, Folkerts Michael, Prins Mayumi L
University of California Los Angeles, David Geffen School of Medicine, Department of Neurosurgery, Brain Injury Research Center, Los Angeles, CA, United States.
University of California Los Angeles, Steve Tisch BrainSPORT Program, Los Angeles, CA, United States.
Front Neurol. 2021 Jan 8;11:616661. doi: 10.3389/fneur.2020.616661. eCollection 2020.
Adolescents and young adults have the highest incidence of mild traumatic brain injury (mTBI); sport-related activities are a major contributor. Roughly a third of these patients diagnosed with mTBI are estimated to have received a subsequent repeat mTBI (rTBI). Previously, animal studies have only modeled mTBI in sedentary animals. This study utilizes physical activity as a dependent variable prior to rTBI in adolescent rats by allowing voluntary exercise in males, establishing the rat athlete (rathlete). Rats were given access to locked or functional running wheels for 10 d prior to sham or rTBI injury. Following rTBI, rathletes were allowed voluntary access to running wheels beginning on different days post-injury: no run (rTBI+no run), immediate run (rTBI+Immed), or 3 day delay (rTBI+3dd). Rats were tested for motor and cognitive-behavioral (anxiety, social, memory) and mechanosensory (allodynia) dysfunction using a novel rat standardized concussion assessment tool on post-injury days 1,3,5,7, and 10. Protein expression of brain derived neurotrophic factor (BDNF) and proliferator-activated gamma coactivator 1-alpha (PGC1α) was measured in the parietal cortex, hippocampus, and gastrocnemius muscle. Sedentary shams displayed lower anxiety-like behaviors compared to rathlete shams on all testing days. BDNF and PGC1α levels increased in the parietal cortex and hippocampus with voluntary exercise. In rTBI rathletes, the rTBI+Immed group showed impaired social behavior, memory impairment in novel object recognition, and increased immobility compared to rathlete shams. All rats showed greater neuropathic mechanosensory sensitivity than previously published uninjured adults, with rTBI+3dd showing greatest sensitivity. These results demonstrate that voluntary exercise changes baseline functioning of the brain, and that among rTBI rathletes, delayed return to activity improved cognitive recovery.
青少年和青年发生轻度创伤性脑损伤（mTBI）的几率最高；与运动相关的活动是主要原因。据估计，这些被诊断为mTBI的患者中约有三分之一随后又遭受了重复性轻度创伤性脑损伤（rTBI）。此前，动物研究仅在久坐不动的动物身上模拟mTBI。本研究将体力活动作为青春期大鼠rTBI之前的一个因变量，通过让雄性大鼠进行自愿运动，建立了大鼠运动员模型（rathlete）。在假手术或rTBI损伤前10天，让大鼠使用锁定或可正常使用的跑轮。rTBI后，rTBI大鼠在损伤后的不同日期开始可以自愿使用跑轮：不运动（rTBI + 不运动）、立即运动（rTBI + 立即运动）或延迟3天运动（rTBI + 3天延迟）。在损伤后的第1、3、5、7和10天，使用一种新型大鼠标准化脑震荡评估工具对大鼠的运动和认知行为（焦虑、社交、记忆）以及机械感觉（痛觉过敏）功能障碍进行测试。在顶叶皮质、海马体和腓肠肌中测量脑源性神经营养因子（BDNF）和增殖激活γ共激活因子1α（PGC1α）的蛋白表达。在所有测试日，久坐不动的假手术大鼠与大鼠运动员假手术大鼠相比，表现出较低的焦虑样行为。自愿运动使顶叶皮质和海马体中的BDNF和PGC1α水平升高。在rTBI大鼠中，与大鼠运动员假手术大鼠相比，rTBI + 立即运动组表现出社交行为受损、新物体识别记忆受损以及不动时间增加。所有大鼠都表现出比之前报道的未受伤成年大鼠更高的神经性机械感觉敏感性，rTBI + 3天延迟组表现出最高的敏感性。这些结果表明，自愿运动改变了大脑的基线功能，并且在rTBI大鼠中，延迟恢复活动可改善认知恢复。
