Sexual dimorphism in the inflammatory response to traumatic brain injury.
Sexual dimorphism in the inflammatory response to traumatic brain injury.
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作者：
Villapol S;Loane DJ;Burns MP
驻留小胶质细胞的激活以及外周巨噬细胞的浸润是对创伤性脑损伤（TBI）的关键神经炎症反应，与神经元死亡直接相关。此前曾报道过 TBI 反应中的性别差异，但尚不清楚 TBI 后神经炎症进展是否存在性别差异。我们将雄性和雌性小鼠暴露于中度至重度受控皮质冲击损伤中，并使用免疫荧光和原位杂交分析研究了 TBI 急性和慢性阶段的神经胶质细胞活化。我们发现，在受伤后 7 天以内，性反应完全不同。 TBI 引起雄性小鼠皮层小胶质细胞/巨噬细胞快速而显着的激活，具有显着的激活表型，产生促炎细胞因子（IL-1β 和 TNFα）和抗炎细胞因子（Arg1 和 TGFβ），具有单相、持续峰值 1 至 7 天。相比之下，TBI 导致女性小胶质细胞/巨噬细胞表型不太强，双相促炎反应峰值出现在 4 小时和 7 天，抗炎 mRNA 峰值出现延迟，出现在 30 天。我们进一步报告说，雌性小鼠在 TBI 后免受急性细胞损失，而雄性小鼠在 TBI 后 7 天表现出星形胶质细胞增多、神经元死亡和病变体积增加。总的来说，这些发现表明，在受伤后的急性和亚急性阶段，与雌性小鼠相比，TBI 会导致雄性小鼠出现更具侵袭性的神经炎症。了解性如何影响脑损伤后神经炎症的进程是开发个性化和有效的 TBI 治疗方法的重要一步。
The activation of resident microglial cells, alongside the infiltration of peripheral macrophages, are key neuroinflammatory responses to traumatic brain injury (TBI) that are directly associated with neuronal death. Sexual disparities in response to TBI have been previously reported, however it is unclear whether a sex difference exists in neuroinflammatory progression after TBI. We exposed male and female mice to moderate-to-severe controlled cortical impact injury and studied glial cell activation in the acute and chronic stages of TBI using immunofluorescence and in situ hybridization analysis. We found that the sex response was completely divergent up to 7 days post-injury. TBI caused a rapid and pronounced cortical microglia/macrophage activation in male mice with a prominent activated phenotype that produced both pro- (IL-1β and TNFα) and anti-inflammatory (Arg1 and TGFβ) cytokines with a single-phase, sustained peak from 1 to 7 days. In contrast, TBI caused a less robust microglia/macrophage phenotype in females with biphasic pro-inflammatory response peaks at 4 hours and 7 days, and a delayed anti-inflammatory mRNA peak at 30 days. We further report that female mice were protected against acute cell loss after TBI, with male mice demonstrating enhanced astrogliosis, neuronal death, and increased lesion volume through 7 days post-TBI. Collectively, these findings indicate that TBI leads to a more aggressive neuroinflammatory profile in male compared to female mice during the acute and sub-acute phases post-injury. Understanding how sex affects the course of neuroinflammation following brain injury is a vital step toward developing personalized and effective treatments for TBI.
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影响因子：
3.3
作者：
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