The therapeutic hypothermia is an effective tool for TBI‐associated brain impairment, but its side effects limit in clinical routine use. Hypothermia up‐regulates RNA‐binding motif protein 3 (RBM3), which is verified to protect synaptic plasticity. Here, we found that cognitive and LTP deficits, loss of spines, AD‐like tau pathologies are displayed one month after TBI in mice. In contrast, the deficits of LTP and cognitive, loss of spines and tau abnormal phosphorylation at several sites are obviously reversed in TBI mice combined with hypothermia pre‐treatment (HT). But, the neuroprotective role of HT disappears in TBI mouse models under condition of blocking RBM3 expression with RBM3 shRNA. In other hand, overexpressing RBM3 by AAV‐RBM3 plasmid can mimic HT‐like neuroprotection against TBI‐induced chronic brain injuries, such as improving LTP and cognitive, loss of spines and tau hyperphosphorylation in TBI mouse models. Taken together, hypothermia pre‐treatment reverses TBI‐induced chronic AD‐like pathology and behaviour deficits in RBM3 expression dependent manner, RBM3 may be a potential target for neurodegeneration diseases including Alzheimer disease.

中文翻译：

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RBM3 的过表达减轻了小鼠 TBI 诱导的行为障碍和 AD 样 tau 蛋白病变。

低温治疗是治疗 TBI 相关脑损伤的有效工具，但其副作用限制了临床常规使用。低温会上调 RNA 结合基序蛋白 3 (RBM3)，经证实可保护突触可塑性。在这里，我们发现小鼠 TBI 后 1 个月表现出认知和 LTP 缺陷、棘丢失、AD 样 tau 蛋白病理。相比之下，在结合低温预处理（HT）的 TBI 小鼠中，LTP 和认知缺陷、棘突缺失和 tau 蛋白异常磷酸化在几个部位得到明显逆转。但是，在用 RBM3 shRNA 阻断 RBM3 表达的条件下，HT 的神经保护作用在 TBI 小鼠模型中消失。另一方面，通过 AAV-RBM3 质粒过表达 RBM3 可以模拟 HT 样神经保护作用，对抗 TBI 诱导的慢性脑损伤，例如在 TBI 小鼠模型中改善 LTP 和认知能力、棘丢失和 tau 过度磷酸化。总之，低温预处理以 RBM3 表达依赖性方式逆转 TBI 诱导的慢性 AD 样病理和行为缺陷，RBM3 可能是包括阿尔茨海默病在内的神经退行性疾病的潜在靶点。