Within the brain, traumatic brain injury (TBI) alters synaptic plasticity and increases neuroinflammation and neuronal death. Yet, there lacks effective TBI treatments providing pleiotropic beneficial effects on these diverse cellular processes necessary for functional recovery. Here, we show the diabetes drug, metformin, significantly improves cognitive functions after controlled cortical impact (CCI) injury in mice, showing improved spatial learning and nest building. Furthermore, injured animals treated with metformin exhibit increased ramification of microglia processes, indicating reduced neuroinflammation. Finally, metformin treatment in vitro increased neuronal activation of partitioning defective 1 (Par1), a family of Ser/Thr kinases playing a key role in synaptic plasticity and neuroinflammation. These results suggest metformin is a promising therapeutic agent for targeting multiple cellular processes necessary for functional TBI recovery.

在大脑内，创伤性脑损伤 (TBI) 会改变突触可塑性并增加神经炎症和神经元死亡。然而，缺乏对功能恢复所必需的这些不同的细胞过程提供多效性有益作用的有效 TBI 治疗。在这里，我们展示了糖尿病药物二甲双胍在小鼠受控皮质冲击 (CCI) 损伤后显着改善了认知功能，显示出改善的空间学习和筑巢能力。此外，用二甲双胍治疗的受伤动物表现出增加的小胶质细胞过程的分支，表明神经炎症减少。最后，体外二甲双胍治疗增加了分区缺陷 1 (Par1) 的神经元激活，这是一个在突触可塑性和神经炎症中起关键作用的 Ser/Thr 激酶家族。这些结果表明二甲双胍是一种很有前途的治疗剂，可靶向功能性 TBI 恢复所必需的多个细胞过程。