Endoplasmic reticulum stress-induced apoptosis in the penumbra aggravates secondary damage in rats with traumatic brain injury

Neuronal apoptosis is mediated by intrinsic and extrinsic signaling pathways such as the membrane-mediated,mitochondrial,and endoplasmic reticulum stress pathways.Few studies have examined the endoplasmic reticulum-mediated apoptosis pathway in the penumbra after traumatic brain injury,and it remains unclear whether endoplasmic reticulum stress can activate the caspase-12-dependent apoptotic pathway in the traumatic penumbra.Here,we established rat models of fluid percussion-induced traumatic brain injury and found that protein expression of caspase-12,caspase-3 and the endoplasmic reticulum stress marker 78 k Da glucose-regulated protein increased in the traumatic penumbra 6 hours after injury and peaked at 24 hours.Furthermore,numbers of terminal deoxynucleotidyl transferase-mediated d UTP nick end labeling-positive cells in the traumatic penumbra also reached peak levels 24 hours after injury.These findings suggest that caspase-12-mediated endoplasmic reticulum-related apoptosis is activated in the traumatic penumbra,and may play an important role in the pathophysiology of secondary brain injury.