Glibenclamide reduces secondary brain injury in a SAH rat model by reducing brain swelling and modulating inflammatory response

BACKGROUND: Early brain injury (EBI) after subarachnoid hemorrhage (SAH) is a new therapeutic target. Sulfonylurea receptor 1 (SUR1) is expressed in nerve cells, glial cells, and vascular endothelial cells in EBI. SUR1 promotes intracellular inflow of Na and Ca ions, resulting in cell swelling and depolarization, and finally cell death. Glibenclamide reduced cerebral edema and mortality in a basic study of cerebral ischemia. However, the effects of glibenclamide on EBI have not been fully elucidated. This study examined the inhibitory effect of glibenclamide on EBI. METHODS: Rats were divided into the sham group, SAH-control group, and SAH-glibenclamide group. The water content of the brain was measured using the dry-wet method. In addition, the brain was divided into the cortex, putamen, and hippocampus, and expression of inflammatory cytokines was evaluated by the polymerase chain reaction method. In addition, microglia in the brain were evaluated immunohistologically. RESULTS: Water content of the brain was significantly decreased in the SAH-glibenclamide group compared to the SAH-control group. Interleukin-1beta (IL-1p), tumor necrosis factor alpha (TNFa), and nuclear factor-kappa B significantly increased in the cerebral cortex after SAH. IL-1p and TNFa in the cortex were significantly decreased in the SAH-glibenclamide group compared to the SAH-control group. Immunohistochemical staining confirmed that SAH causes extensive microglial activation in the brain, which was suppressed by glibenclamide. CONCLUSIONS: The present study showed that glibenclamide suppressed cerebral edema and activation of microglia and hypersecretion of inflammatory cytokines. Glibenclamide is a potential therapeutic method which may significantly improve the functional prognosis. (Cite this article as: Kajimoto R, Igarashi T, Moro N, Oshima H, Suma T, Otani N, et al. Glibenclamide reduces secondary brain injury in a SAH rat model by reducing brain swelling and modulating inflammatory response. J Neurosurg Sci 2023;67:431-8. DOI: 10.23736/S0390-5616.22.05271-7)