Activation of cerebral peroxisome proliferator-activated receptors gamma exerts neuroprotection by inhibiting oxidative stress following pilocarpine-induced status epilepticus.
Status epilepticus (SE) can cause severe neuronal loss and oxidative damage. As peroxisome proliferator-activated receptor gamma (PPARgamma) agonists possess antioxidative activity, we hypothesize that rosiglitazone, a PPARgamma agonist, might protect the central nervous system (CNS) from oxidative damage in epileptic rats. Using a lithium-pilocarpine-induced SE model, we found that rosiglitazone significantly reduced hippocampal neuronal loss 1 week after SE, potently suppressed the production of reactive oxygen species (ROS) and lipid peroxidation. We also found that treatment with rosiglitazone enhanced antioxidative activity of superoxide dismutase (SOD) and glutathione hormone (GSH), together with decreased expression of heme oxygenase-1 (HO-1) in the hippocampus. The above effects of rosiglitazone can be blocked by co-treatment with PPARgamma antagonist T0070907. The current data suggest that rosiglitazone exerts a neuroprotective effect on oxidative stress-mediated neuronal damage followed by SE. Our data also support the idea that PPARgamma agonist might be a potential neuroprotective agent for epilepsy.
Yu
Xin
X
Research Center of Epilepsy, Department of Neurology, Xijing Hospital Fourth Military Medical University, 17 Changle West Road, Xi'an, Shaanxi 710032, China.
Shao
Xiao-Guang
XG
Sun
Hong
H
Li
Yong-Nan
YN
Yang
Jun
J
Deng
Yan-Chun
YC
Huang
Yuan-Gui
YG
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D003292:Convulsants; D004195:Disease Models, Animal; D005978:Glutathione / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008094:Lithium; D008297:Male; D018721:Muscarinic Agonists; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D047495:PPAR gamma / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D010862:Pilocarpine; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077154:Rosiglitazone; D013226:Status Epilepticus / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D045162:Thiazolidinediones / Q000494:pharmacology*
D001549:Benzamides; D003292:Convulsants; D018721:Muscarinic Agonists; D018696:Neuroprotective Agents; D047495:PPAR gamma; D011725:Pyridines; D017382:Reactive Oxygen Species; C458508:T 0070907; D045162:Thiazolidinediones; D010862:Pilocarpine; D000077154:Rosiglitazone; D008094:Lithium; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D005978:Glutathione