Apoptosis after traumatic brain injury has been shown to be a major factor influencing prognosis and outcome.Endoplasmic reticulum stress may be involved in mitochondrial mediated neuronal apoptosis.Therefore,endoplasmic reticulum stress has become an important mechanism of secondary injury after traumatic brain injury.In this study,a rat model of traumatic brain injury was established by lateral fluid percussion injury.Fluorescence assays were used to measure reactive oxygen species content in the cerebral cortex.West blot assays were used to determine expression of endoplasmic reticulum stress-related proteins.Hematoxylin-eosin staining was used to detect pathological changes in the cerebral cortex.Transmission electron microscopy was used to measure ultrastructural changes in the endoplasmic reticulum and mitochondria.Our results showed activation of the endoplasmic reticulum stress-related unfolded protein response.Meanwhile,both the endoplasmic reticulum stress response and mitochondrial apoptotic pathway were activated at different stages post-traumatic brain injury.Furthermore,pretreatment with the endoplasmic reticulum stress inhibitor,salubrinal (1 mg/kg),by intraperitoneal injection 30 minutes before injury significantly inhibited the endoplasmic reticulum stress response and reduced apoptosis.Moreover,salubrinal promoted recovery of mitochondrial function and inhibited activation of the mitochondrial apoptotic pathway post-traumatic brain injury.These results suggest that endoplasmic reticulum stress might be a key factor for secondary brain injury post-traumatic brain injury.