With millions of traumatic brain injury (TBI) patients every year, TBI is regarded as one of the leading causes of human death and disability. Calcitonin gene-related peptide (CGRP) has been domenstrated to be a potential therapeutic target for TBI. However, the detailed effect and underlying mechanism of CGRP on the injured brain after TBI has hardly been investigated. In this work, we established TBI models of mice and injected CGRP before and after modelling to study its effects on the brain lesion, neurological functions and behaviours, neuron apoptosis and autophagy after TBI. Impacts of introduced CGRP on the activation of Akt/mTOR signalling in the cortical tissues surrounding injured areas after TBI were also evaluated. It was found that CGRP was reduced after TBI, and gradually restored over time. CGRP administration significantly restored the brain lesion induced by TBI. The permeability of blood–brain barrier and brain edema was increased dramatically after TBI, which was ameliorated by exogenous CGRP. Moreover, several neurological behaviour tests were performed, showing that CGRP introduction also relieved the cognitive abilities of mice which were impaired after TBI. Enhancing apoptosis and autophagy of neurons in the cortical tissues of injury sites following TBI were also alleviated by CGRP administration. Besides, CGRP-treated brain cortical tissues showed increased activation of Akt/mTOR signalling after TBI. Therefore, the results suggest that exogenous CGRP plays a neuroprotective role in the injuryed brain after TBI, to relieve cell apoptosis and autophagy, at least partially through Akt/mTOR signalling pathway. This finding also provides more evidence for the treatment of TBI through introducing exogenous CGRP or its related drugs.

每年有数以百万计的创伤性脑损伤（TBI）患者，TBI被认为是人类死亡和残疾的主要原因之一。降钙素基因相关肽（CGRP）已被证明是TBI的潜在治疗靶标。然而，关于TBI后CGRP对脑损伤的详细作用及其潜在机制尚不清楚。在这项工作中，我们建立了小鼠的TBI模型，并在建模前后分别注射了CGRP，以研究其对TBI后脑损伤，神经功能和行为，神经元凋亡和自噬的影响。还评估了导入的CGRP对TBI后受损区域周围皮质组织中Akt / mTOR信号激活的影响。发现TBI后CGRP降低，并随时间逐渐恢复。CGRP管理可显着恢复TBI诱发的脑损伤。TBI后血脑屏障和脑水肿的通透性显着增加，外源性CGRP改善了通透性。此外，进行了几次神经行为学测试，表明CGRP的引入也减轻了TBI后受损的小鼠的认知能力。CGRP给药也减轻了TBI后损伤部位皮质组织中神经元的凋亡和自噬。此外，CGRP治疗的大脑皮质组织在TBI后显示出增强的Akt / mTOR信号激活。因此，结果表明，外源性CGRP至少在一定程度上通过Akt / mTOR信号通路在TBI后的受损脑中发挥神经保护作用，以减轻细胞凋亡和自噬。