Endoplasmic reticulum stress mediates cortical neuron apoptosis after experimental subarachnoid hemorrhage in rats

Neuronal apoptosis plays an important pathological process in early brain injury (EBI) after subarachnoid hemorrhage (SAH). This pathological process leads to a poor neurological prognosis for patients. This study aimed to investigate whether endoplasmic reticulum (ER) stress mediates cortical neuron apoptosis in EBI after SAH.

Eighty-four male Sprague-Dawley rats were randomly assigned to different groups as follows: the control and the 3, 6, 12, 24, 48, and 72 h groups after SAH. The SAH model was established by injecting 0.3 mL of nonheparinized blood into the prechiasmatic cistern. Hematoxylin-eosin staining, Garcia scoring, Western blotting, transmission electron microscopy, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were performed.

SAH reduced the neurological scores and reached a trough at 24 h after the SAH. The GRP78 expression was significantly upregulated at 6 h after the SAH, peaked at 24 h after the SAH, and then decreased. By comparison, the CHOP, caspase-12, ASK1, and p-c-Jun N-terminal kinase expressions were significantly upregulated at 12 h after the SAH and peaked at 24 h after the SAH. The most serious swelling of the rough ER was observed at 24 h after the SAH and remained notably swollen at 72 h after the SAH. The number of TUNEL-positive cells substantially increased significantly at 12 h after the SAH, and the neuronal apoptosis decreased ratio after reaching a peak at 24 h after the SAH. The apoptosis ratio at 72 h after the SAH was still significantly different from the ratio in the control group.

Our study clearly demonstrated that ER stress mediates cortical neuron apoptosis after experimental subarachnoid hemorrhage in rats.