Department of Neurology, Chi Mei Medical Center, Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan.
Prog Neuropsychopharmacol Biol Psychiatry. 2013 Aug 1;45:207-14. doi: 10.1016/j.pnpbp.2013.05.016. Epub 2013 Jun 11.
Excessive release of glutamate is believed to be a major component of cell damage following excitotoxicity associated with epilepsy. Bupropion, an atypical antidepressant, has been shown to inhibit glutamate release from rat cerebrocortical nerve terminals. The present study was undertaken to investigate whether bupropion has anti-seizure and anti-excitotoxic effects by using a kainic acid (KA) rat seizure model, an animal model for temporal lobe epilepsy and excitotoxic neurodegeneration. Our results show that bupropion (10 or 50mg/kg), administrated intraperitoneally to the rats 30 min before the KA (15 mg/kg) intraperitoneal injection, increased the seizure latency and decreased the seizure score. Bupropion pretreatment attenuated KA-induced neuronal cell death and microglia activation in the CA3 region of the hippocampus. Furthermore, KA-induced c-Fos expression and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation in the hippocampus were also reduced by bupropion pretreatment. These results suggest that bupropion has therapeutic potential in the treatment of seizure and other neurological diseases associated with excitotoxicity.
谷氨酸的过度释放被认为是与癫痫相关的兴奋毒性后细胞损伤的主要组成部分。安非他酮，一种非典型的抗抑郁药，已被证明能抑制大鼠脑皮质神经末梢谷氨酸的释放。本研究旨在通过使用海人酸（KA）大鼠癫痫模型（颞叶癫痫和兴奋性神经退行性变的动物模型）来研究安非他酮是否具有抗癫痫和抗兴奋毒性作用。我们的结果表明，安非他酮（10 或 50mg/kg），在腹腔注射 KA（15mg/kg）前 30 分钟腹腔注射，可延长癫痫发作潜伏期，降低癫痫发作评分。安非他酮预处理可减轻 KA 诱导的海马 CA3 区神经元细胞死亡和小胶质细胞激活。此外，KA 诱导的 c-Fos 表达和细胞外信号调节激酶 1/2（ERK1/2）磷酸化也被安非他酮预处理所减少。这些结果表明，安非他酮在治疗癫痫和其他与兴奋毒性相关的神经疾病方面具有治疗潜力。
