SNAP25 ameliorates cognitive impairment after subarachnoid hemorrhage in rats

Cognitive impairment can be a long-term complication after subarachnoid hemorrhage (SAH). The synaptosomal-associated protein of 25 kDa gene (SNAP25) is essential for the triggering of vesicular fusion and neurotransmitter release. The study aims to evaluate the effects and the possible mechanism of SNAP25 on cognitive impairment after SAH. Rats (N=60) were randomly assigned into five groups: Normal, Sham, SAH, SAH+NS, and SAH+SNAP25 group. SAH was induced by endovascular perforation. Neurological deficits, SAH severity, brain water content (BWC) and blood-brain barrier (BBB) permeability was determined. Spatial learning and memory abilities were tested by Morris water maze test. SNAP25 expression and the apoptosis of brain neurons were evaluated by immunohistochemical staining. The cytokines (IL-1 beta, IL-6, TNF-alpha) in brain tissues were detected by ELISA. The protein levels of apoptosis-related proteins (cleaved caspase-3, Bax) and synaptic plasticity-associated proteins (SYN, Arc and MAP-2) were analyzed by Western blot. This study demonstrated that intraperitoneal injection of SNAP25 accelerated the recovery of neurological dysfunction, effectively relieved subarachnoid hemorrhage, brain edema, and BBB disruption, and improved learning deficits as well as attenuated neuronal apoptosis in SAH rats. In addition, SNAP25 blocked the upregulation of pro-inflammatory factors and apoptosis-related genes, and promoted the expression of synaptic plasticity-associated proteins in rats after SAH. These results indicate that SNAP25 ameliorates cognitive impairment in rats after SAH, suggesting that SNAP25 may represent a novel effective target for the therapy for SAH.