Dexmedetomidine attenuates endoplasmic reticulum stress-induced apoptosis and improves neuronal function after traumatic brain injury in mice.

Traumatic brain injury (TBI) is one of the leading causes of mortality and disability worldwide. Emerging studies have shown that endoplasmic reticulum (ER) stress plays an important role in the pathophysiology of TBI. Dexmedetomidine (Dex), a highly selective α2-adrenoreceptor agonist, has been shown to attenuate ER stress. However, there is no relevant research in the field of TBI. To study the effects of dexmedetomidine on TBI, we subjected mice to TBI with a controlled cortical impact (CCI) device. The expression levels of ER stress marker proteins and apoptosis-related proteins were evaluated by western blotting and immunofluorescence. Neuronal cell death was assessed by a terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labelling (TUNEL) assay. Neurological and motor deficits were assessed by modified neurological severity scores (mNSSs) and beam balance and beam walking tests. Brain water content and EB leakage were also assessed. Our group found that ER stress was significantly activated 72 h after TBI. Dexmedetomidine significantly reduced ER stress and ER stress-related neuronal apoptosis induced by experimental TBI. In addition, dexmedetomidine significantly improved neurological function and alleviated brain oedema. These findings indicate that dexmedetomidine alleviates severe, post-traumatic ER stress and attenuates secondary brain damage.