Exogenous CGRP Regulates Apoptosis and Autophagy to Alleviate Traumatic Brain Injury Through Akt/mTOR Signalling Pathway
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ORIGINAL PAPER
Exogenous CGRP Regulates Apoptosis and Autophagy to Alleviate Traumatic Brain Injury Through Akt/mTOR Signalling Pathway Jun Tian1,3 · Lei Yang4 · Pengfei Wang5 · Lijun Yang1,2 · Zhenzeng Fan1,2 Received: 25 May 2020 / Revised: 11 September 2020 / Accepted: 1 October 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract 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. Keywords TBI · CGRP · Signal transduction · Neurons · Cognition
Introduction
Jun Tian and Lei Yang contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11064-020-03141-9) contains supplementary material, which is available to authorized users.
Traumatic brain injury (TBI) is mainly caused by external mechanical forces, such as head bump, blow, or penetration [1]. As millions of patients still suffer from TBI every year, TBI has been one of the leading causes of death and disability worldwide [1–3]. In general, TBI comprises primary and secondary injuries based on various processes and stages after trauma [1]. The pathogenesis of TBI is complicated, which
* Lijun Yang [email protected]
3
Department of Neurosurgery, Shijiazhuang First Hospital, Shijiazhuang, Hebei Province, China
* Zhenzeng Fan [email protected]
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