Righting Reflex Predicts Long-Term Histological and Behavioral Outcomes in a Closed Head Model of Traumatic Brain Injury

Blunt impact produces a heterogeneous brain injury in people and in animal models of traumatic brain injury. We report that a single closed head impact to adult C57/BL6 mice produced two injury syndromes (CHI-1 and CHI-2). CHI-1 mice spontaneously reinitiated breathing after injury while CHI-2 mice had prolonged apnea and regained breathing only after cardiopulmonary resuscitation and supplementation of 100% O2. The CHI-1 group significantly regained righting reflex more rapidly than the CHI-2 group. At 7 days post-injury, CHI-1, but not CHI-2 mice, acquired but had no long-term retention of an active place avoidance task. The behavioral deficits of CHI-1 and CHI-2 mice were retained one-month after the injury. CHI-1 mice had loss of hippocampal neurons and localized white matter injury at one month after injury. CHI-2 had a larger loss of hippocampal neurons and more widespread loss of myelin and axons. High-speed videos made during the injury were followed by assessment of breathing and righting reflex. These videos show that CHI-2 mice experienced a larger vertical g-force than CHI-1 mice. Time to regain righting reflex in CHI-2 mice significantly correlated with vertical g-force. Thus, physiological responses occurring immediately after injury can be valuable surrogate markers of subsequent behavioral and histological deficits.钝性冲击可在人类与创伤性脑损伤（traumatic brain injury, TBI）动物模型中诱发异质性脑损伤。本研究发现，对成年C57/BL6小鼠施加单次闭合性头部冲击，可诱导两种损伤综合征（CHI-1与CHI-2）：CHI-1组小鼠在损伤后可自主恢复呼吸，且恢复翻正反射（righting reflex）的速度显著快于CHI-2组；而CHI-2组小鼠则出现长时间呼吸暂停，仅经心肺复苏与100%氧气补给后方可恢复自主呼吸。损伤后第7天，CHI-1组小鼠能够习得主动位置回避任务，但无法长期保留该行为能力，CHI-2组小鼠则未习得该任务。两组小鼠的行为缺陷在损伤后1个月仍持续存在。损伤后1个月时，CHI-1组小鼠出现海马神经元丢失与局灶性白质损伤；CHI-2组小鼠的海马神经元丢失程度更为严重，且髓鞘与轴突的丢失范围更广泛。研究人员在冲击过程中录制高速视频，并于后续对小鼠的呼吸与翻正反射进行评估，结果显示CHI-2组小鼠承受的垂直方向g力（g-force）显著高于CHI-1组，且CHI-2组小鼠恢复翻正反射所需的时间与垂直g力呈显著相关。综上，损伤后即刻出现的生理反应可作为后续行为与组织学缺陷的有效替代标志物。