Neuroinflammation mediated by microglia and oxidative stress play pivotal roles in the development of chronic temporal lobe epilepsy (TLE). We postulated that kainic acid (KA)-Induced status epilepticus triggers microglia-dependent inflammation, leading to neuronal damage, a lowered seizure threshold, and the emergence of spontaneous recurrent seizures (SRS). Extensive evidence from our laboratory suggests that dextromethorphan (DM), even in ultra-low doses, has anti-inflammatory and neuroprotective effects in many animal models of neurodegenerative disease. Our results showed that administration of DM (10 ng/kg per day; subcutaneously via osmotic minipump for 4 weeks) significantly mitigated the residual effects of KA, including the frequency of SRS and seizure susceptibility. In addition, DM-treated rats showed improved cognitive function and reduced hippocampal neuronal loss. We found suppressed microglial activation-mediated neuroinflammation and decreased expression of hippocampal gp91^phox and p47^phox proteins in KA-induced chronic TLE rats. Notably, even after discontinuation of DM treatment, ultra-low doses of DM continued to confer long-term anti-seizure and neuroprotective effects, which were attributed to the inhibition of microglial NADPH oxidase 2 as revealed by mechanistic studies.

小胶质细胞和氧化应激介导的神经炎症在慢性颞叶癫痫（TLE）的发展中发挥着关键作用。我们假设红藻氨酸（KA）诱导的癫痫持续状态会触发小胶质细胞依赖性炎症，导致神经元损伤、癫痫阈值降低以及自发性复发性癫痫发作（SRS）的出现。我们实验室的大量证据表明，即使是超低剂量的右美沙芬 (DM)，在许多神经退行性疾病动物模型中也具有抗炎和神经保护作用。我们的结果表明，DM 给药（每天 10 ng/kg；通过微型渗透泵皮下注射 4 周）可显着减轻 KA 的残留影响，包括 SRS 频率和癫痫易感性。此外，接受 DM 治疗的大鼠表现出认知功能改善和海马神经元损失减少。我们发现KA 诱导的慢性 TLE 大鼠中小胶质细胞激活介导的神经炎症受到抑制，海马 gp91 ^phox和 p47 ^{phox蛋白表达减少。}值得注意的是，即使在停止 DM 治疗后，超低剂量的 DM 仍能继续产生长期的抗癫痫和神经保护作用，机制研究表明，这归因于对小胶质细胞 NADPH 氧化酶 2 的抑制。