Oxidative stress mediates hippocampal neuron death in rats after lithium-pilocarpine-induced status epilepticus.
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.
Department of Neurology, Qianfoshan Hospital, Medical School of Shandong University, No. 66, Jingshi Road, Jinan, Shandong 250014, PR China.
Jinzhi
J
Liu
Aihua
A
Wang
Lili
L
Li
Yanfei
Y
Huang
Ping
P
Xue
Aijun
A
Hao
D000818:Animals; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008094:Lithium / Q000633:toxicity; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010862:Pilocarpine / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D016559:Tacrolimus / Q000494:pharmacology
D007166:Immunosuppressive Agents; D010862:Pilocarpine; D009569:Nitric Oxide; D008315:Malondialdehyde; D008094:Lithium; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D053148:Caspase 3; D016559:Tacrolimus