School of Medicine, Division of Neurosurgery, Department of Neurological Surgery, Nihon University, Tokyo, Japan.
School of Medicine, Division of Neurosurgery, Department of Neurological Surgery, Nihon University, Tokyo, Japan -
J Neurosurg Sci. 2023 Aug;67(4):431-438. doi: 10.23736/S0390-5616.22.05271-7. Epub 2022 Apr 5.
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.
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.
Water content of the brain was significantly decreased in the SAH-glibenclamide group compared to the SAH-control group. Interleukin-1beta (IL-1β), tumor necrosis factor alpha (TNFα), and nuclear factor-kappa B significantly increased in the cerebral cortex after SAH. IL-1β and TNFα 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.
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.
蛛网膜下腔出血（SAH）后早期脑损伤（EBI）是一个新的治疗靶点。磺酰脲受体 1（SUR1）在 EBI 中的神经细胞、神经胶质细胞和血管内皮细胞中表达。SUR1 促进细胞内 Na 和 Ca 离子内流，导致细胞肿胀和去极化，最终导致细胞死亡。格列本脲在脑缺血的基础研究中减少脑水肿和死亡率。然而，格列本脲对 EBI 的影响尚未完全阐明。本研究探讨了格列本脲对 EBI 的抑制作用。
将大鼠分为假手术组、SAH 对照组和 SAH-格列本脲组。采用干湿法测量脑含水量。此外，将脑分为皮质、纹状体和海马，并通过聚合酶链反应法评估炎症细胞因子的表达。此外，通过免疫组织化学评估脑内小胶质细胞。
与 SAH 对照组相比，SAH-格列本脲组脑含水量明显降低。SAH 后皮质中白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNFα）和核因子-κB 显著增加。与 SAH 对照组相比，SAH-格列本脲组皮质中的 IL-1β 和 TNFα 明显减少。免疫组织化学染色证实，SAH 导致脑内广泛的小胶质细胞激活，格列本脲抑制了这种激活。
本研究表明，格列本脲抑制脑水肿和小胶质细胞激活以及炎症细胞因子的过度分泌。格列本脲是一种潜在的治疗方法，可能显著改善功能预后。
