Status epilepticus (SE) is a life-threatening neurological disorder that causes neuronal death and glial activation. Studies have explained the clinical side effects and lack of effectiveness of neurological disorder treatments based on sex-related differences in brain structure and function. However, the sex-specific outcomes of seizure disorders and the underlying mechanisms remain unknown. We compared SE-induced behavioral and pathophysiological changes in male and female mice. The time taken to reach stage 6 seizure following pilocarpine injection was shorter in male mice than in female mice, and the prevalence of SE was higher in male mice than in female mice. Fluoro-Jade B staining revealed more extensive SE-induced hippocampal neuronal death in male mice than in female mice. Glial cells were more activated in male mice than in female mice. In contrast, astrocyte-derived γ-aminobutyric acid (GABA)-immunostaining was less expressed in male mice than in female mice. Moreover, the mRNA levels of inflammatory cytokines released from activated glial cells were higher in male mice than in female mice. Notably, the mRNA level of astrocytic γ-aminobutyric acid transporter (GAT-3) involved in extracellular GABA uptake was lower in female mice than in male mice, while the mRNA levels of glutamate/aspartate transporter (GLAST (EAAT1)) and glutamate transporter (GLT-1 (EAAT2)) involved in extracellular glutamate uptake were higher in female mice. Our findings suggest that male mice are more vulnerable to SE than female mice, resulting in more extensive neuronal cell death and glial activation in male mice, partly due to increased GAT-3 expression that subsequently leads to reduced glial fibrillary acidic protein (GFAP)-positive GABA content assessed with anti-GABA antibodies.

癫痫持续状态 (SE) 是一种危及生命的神经系统疾病，可导致神经元死亡和神经胶质激活。研究已经解释了基于大脑结构和功能的性别相关差异的神经系统疾病治疗的临床副作用和缺乏有效性。然而，癫痫症的性别特异性结果和潜在机制仍然未知。我们比较了雄性和雌性小鼠中 SE 诱导的行为和病理生理变化。注射毛果芸香碱后达到第 6 阶段癫痫发作所需的时间在雄性小鼠中比雌性小鼠短，并且雄性小鼠的 SE 患病率高于雌性小鼠。Fluoro-Jade B 染色显示雄性小鼠比雌性小鼠更广泛的 SE 诱导的海马神经元死亡。雄性小鼠的神经胶质细胞比雌性小鼠更活跃。相比之下，星形胶质细胞衍生的 γ-氨基丁酸 (GABA) 免疫染色在雄性小鼠中的表达低于雌性小鼠。此外，雄性小鼠的活化神经胶质细胞释放的炎性细胞因子的 mRNA 水平高于雌性小鼠。值得注意的是，雌性小鼠中参与细胞外 GABA 摄取的星形胶质细胞 γ-氨基丁酸转运蛋白 (GAT-3) 的 mRNA 水平低于雄性小鼠，而谷氨酸/天冬氨酸转运蛋白 (GLAST (EAAT1)) 和谷氨酸转运蛋白的 mRNA 水平(GLT-1 (EAAT2)) 参与细胞外谷氨酸摄取在雌性小鼠中更高。我们的研究结果表明，雄性小鼠比雌性小鼠更容易受到 SE，导致雄性小鼠更广泛的神经元细胞死亡和神经胶质激活，