Department of Neurology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel; Department of Neurology, The Chaim Sheba Medical Center, Ramat Gan 5266202, Israel.
Department of Neurology, The Chaim Sheba Medical Center, Ramat Gan 5266202, Israel.
Mol Cell Neurosci. 2021 Mar;111:103586. doi: 10.1016/j.mcn.2020.103586. Epub 2021 Jan 4.
Mild traumatic brain injury (mTBI) is common and associated with cognitive impairment. Stress and mTBI are known to modulate the neural function. The present study aims at exploring the effect of prior stress exposure on cognitive function following mTBI.
Eight weeks old male ICR mice were subjected to either stress induced by forced swimming stress alone, stress followed by an immediate mTBI, or stress followed by 30 min break and then mTBI. We had two control groups: SHAM group - a control group which was not exposed to stress nor to mTBI and control mTBI group - a control group which was exposed only to TBI with no stress. Mice were weighed prior and at 12, 24 h and 1 week following interventions. Motor evaluation was conducted by rotarod. Behavioral changes were evaluated using open field, Y maze, elevated plus maze and staircase tests, at 12 h and 1 week following interventions. Brain levels of NMDAR subunits (R1, R2A, R2B), GABAR1, glucocorticoid and mineralocorticoid receptors (GR, MR) were evaluated using western blot.
Stress alone, mTBI alone, and stress followed by immediate mTBI resulted in a significant weight loss compared to control (p < 0.05). Stress 30 min prior to mTBI had a protective effect on weight (p = 0.14 compared to control). The stress and mTBI alone groups showed reduced time at the center of the open field arena 1 week after intervention (p < 0.05 for both). Time in the novel arm of the Y maze was significantly shorter in the mTBI and stress followed by delayed mTBI (p = 0.02). Immediate stress prior to mTBI had normalized times in the novel arm (p = 0.95 compared to control). Combination of stress and mTBI significantly modified NMDAR subunits levels (increased NMDAR1, p < 0.008, decreased NMDAR2A p = 0.02) as well as increased MR levels (p = 0.04).
Exposure to stress prior to mTBI may improve the cognitive consequences of mTBI. These data may point towards a novel, unexpected role of stress as a possible resilience mechanism in the setting of mTBI.
轻度创伤性脑损伤（mTBI）很常见，并且与认知障碍有关。压力和 mTBI 已知会调节神经功能。本研究旨在探讨先前的应激暴露对 mTBI 后认知功能的影响。
8 周龄雄性 ICR 小鼠分别接受强迫游泳应激单独、应激后立即 mTBI、应激后 30 分钟休息后再 mTBI。我们有两个对照组：SHAM 组 - 未暴露于应激或 mTBI 的对照组和仅接受 TBI 而无应激的对照 mTBI 组。小鼠在干预前和干预后 12、24 小时和 1 周时称重。通过转棒进行运动评估。在干预后 12 小时和 1 周时，使用开阔场、Y 迷宫、高架十字迷宫和楼梯测试评估行为变化。使用 Western blot 评估 NMDAR 亚基（R1、R2A、R2B）、GABAR1、糖皮质激素和盐皮质激素受体（GR、MR）的脑水平。
单独应激、单独 mTBI 以及应激后立即 mTBI 与对照组相比均导致显著的体重减轻（p < 0.05）。应激 30 分钟前 mTBI 对体重有保护作用（与对照组相比，p = 0.14）。单独应激和 mTBI 组在干预后 1 周时在开阔场中心的停留时间减少（两者均为 p < 0.05）。Y 迷宫新臂的时间明显短于 mTBI 和应激后延迟 mTBI（p = 0.02）。mTBI 前立即应激使新臂的时间正常化（与对照组相比，p = 0.95）。应激和 mTBI 的组合显著改变了 NMDAR 亚基水平（增加 NMDAR1，p < 0.008，减少 NMDAR2A，p = 0.02）以及增加 MR 水平（p = 0.04）。
mTBI 前暴露于应激可能会改善 mTBI 的认知后果。这些数据可能指向应激作为 mTBI 情况下可能的恢复机制的一种新的、意外作用。
