Neuroinflammation is an important mediator of secondary injury pathogenesis that exerts dual beneficial and detrimental effects on pathophysiology of the central nervous system (CNS) after traumatic brain injury (TBI). Fluvoxamine is a serotonin selective reuptake inhibitor (SSRI) and has been reported to have the anti-inflammatory properties. However, the mechanisms and therapeutic effects of fluvoxamine in neuroinflammation after TBI have not be defined. In this study, we showed that fluvoxamine inhibited peripheral immune cell infiltration and glia activation at 3 days in mice subjected to TBI. Fluvoxamine treatment promoted microglial/macrophage phenotypic transformation from pro-inflammatory M1-phenotype to anti-inflammatory M2-phenotype in in vivo and in vitro experiments. In addition, fluvoxamine treatment attenuated neuronal apoptosis, blood–brain barrier (BBB) disruption, cerebrovascular damage, and post-traumatic edema formation, thereby improving neurological function of mice subjected to TBI. These findings support the clinical evaluation of fluvoxamine as a neuroprotective therapy for TBI.

中文翻译：

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在创伤性脑损伤小鼠模型中，氟伏沙明通过抑制外周白细胞浸润和小胶质细胞/巨噬细胞的 M1 极化来提供神经保护

神经炎症是继发性损伤发病机制的重要介质，对创伤性脑损伤 (TBI) 后的中枢神经系统 (CNS) 的病理生理学产生有益和有害的双重影响。Fluvoxamine 是一种血清素选择性再摄取抑制剂 (SSRI)，据报道具有抗炎特性。然而，氟伏沙明在 TBI 后神经炎症中的作用机制和治疗效果尚未明确。在这项研究中，我们发现氟伏沙明在接受 TBI 的小鼠中在 3 天时抑制外周免疫细胞浸润和神经胶质细胞活化。氟伏沙明治疗在体内和体外促进小胶质细胞/巨噬细胞表型从促炎 M1 表型向抗炎 M2 表型转变实验。此外，氟伏沙明治疗可减轻神经元凋亡、血脑屏障 (BBB) 破坏、脑血管损伤和创伤后水肿形成，从而改善 TBI 小鼠的神经功能。这些发现支持氟伏沙明作为 TBI 的神经保护疗法的临床评估。