Department of Neurology, Qianfoshan Hospital, Medical School of Shandong University, No. 66, Jingshi Road, Jinan, Shandong 250014, PR China.
Seizure. 2010 Apr;19(3):165-72. doi: 10.1016/j.seizure.2010.01.010. Epub 2010 Feb 10.
Oxidative stress, which is defined as the over-production of free radicals, can dramatically alter neuronal function and has been linked to status epilepticus (SE). The pathological process and underlying mechanisms involved in the oxidative stress during SE are still not fully clear. In the current study, SE was induced in rats by lithium-pilocarpine administration. Our data show that hippocampal neuron death occurs at 6h and is sustained for 7 days after SE. The production of nitric oxide (NO) started to increase at 30 min and was evident at 6h and 7 days after SE, which coincided with increased expression of neuronal nitric oxide synthase (nNOS), inducible nitric oxide synthase (iNOS) and malondialdehyde (MDA) after SE, whereas, activated caspase-3 prominently appeared at 7 days after SE. Further, FK506, an immunosuppressant, partially rescued the neuron death and attenuated the expression of NO, nNOS, iNOS, MDA and activated caspase-3. Taken together, our study indicates that oxidative stress mediated hippocampal neuron death occurs prior to caspase-3 activation and that FK506 plays an important role in protecting hippocampal neurons during status epilepticus.
氧化应激是指自由基的过度产生，它可以显著改变神经元的功能，并与癫痫持续状态（SE）有关。SE 期间氧化应激的病理过程和潜在机制尚不完全清楚。在本研究中，通过锂-匹罗卡品给药诱导大鼠 SE。我们的数据表明，海马神经元死亡发生在 SE 后 6 小时，并持续 7 天。一氧化氮（NO）的产生在 30 分钟开始增加，并在 SE 后 6 小时和 7 天明显增加，这与 SE 后神经元型一氧化氮合酶（nNOS）、诱导型一氧化氮合酶（iNOS）和丙二醛（MDA）的表达增加一致，而激活的 caspase-3 在 SE 后 7 天明显出现。此外，免疫抑制剂 FK506 部分挽救了神经元死亡，并减弱了 NO、nNOS、iNOS、MDA 和激活的 caspase-3 的表达。综上所述，我们的研究表明，氧化应激介导的海马神经元死亡发生在 caspase-3 激活之前，FK506 在 SE 期间保护海马神经元中发挥重要作用。
