title: The PPARγ agonist rosiglitazone prevents cognitive impairment by inhibiting astrocyte activation and oxidative stress following pilocarpine-induced status epilepticus.
abstract: Epilepsy is commonly associated with cognitive impairment. Astrocyte activation and oxidative stress occur following seizures, and play a role in the pathological injury of epilepsy with cognitive impairment. The peroxisome proliferator-activated receptor gamma (PPARγ) has been shown to exhibit neuroprotective and antioxidative effects in CNS diseases. Thus, we hypothesized that rosiglitazone, a PPARγ agonist, would prevent cognitive impairment by inhibiting astrocyte activation and regulating glutathione (GSH) homeostasis after status epilepticus (SE). Using a lithium pilocarpine-induced SE model, we found that rosiglitazone significantly prevented cognitive impairment induced by SE, and potently inhibited astrocyte activation with maintenance of GSH homeostasis in the hippocampus after SE. These protective effects were significantly reversed by co-treatment with the PPARγ antagonist T0070907. These data suggest that rosiglitazone can improve cognitive impairment, and inhibit astrocyte activation and oxidative damage following SE. Rosiglitazone may be a promising agent for treatment of epilepsy involving SE-induced cognitive impairment.
authors.affiliation: Department of Neurology, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, NO.157 West 5 Road, Xi'an, 710004, Shaanxi Province, China. sunhongxjt@yahoo.cn
authors.forename: Sun
authors.initials: S
authors.lastname: Hong
authors.forename: Yu
authors.initials: Y
authors.lastname: Xin
authors.forename: Wu
authors.initials: W
authors.lastname: HaiQin
authors.forename: Zhang
authors.initials: Z
authors.lastname: GuiLian
authors.forename: Zhang
authors.initials: Z
authors.lastname: Ru
authors.forename: Zhan
authors.initials: Z
authors.lastname: ShuQin
authors.forename: Wang
authors.initials: W
authors.lastname: HuQing
authors.forename: Yao
authors.initials: Y
authors.lastname: Li
authors.forename: Du
authors.initials: D
authors.lastname: Yun
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001253:Astrocytes / Q000187:drug effects*; D001549:Benzamides / Q000008:administration & dosage; D002452:Cell Count; D003072:Cognition Disorders / Q000209:etiology* / Q000517:prevention & control*; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D018021:Lithium Chloride / Q000633:toxicity; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D047495:PPAR gamma / Q000819:agonists / Q000037:antagonists & inhibitors; D010862:Pilocarpine / Q000633:toxicity; D011725:Pyridines / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D013226:Status Epilepticus / Q000139:chemically induced / Q000150:complications / Q000473:pathology*; D013599:Systole; D045162:Thiazolidinediones / Q000627:therapeutic use*
chemical_list: D001549:Benzamides; D005904:Glial Fibrillary Acidic Protein; D047495:PPAR gamma; D011725:Pyridines; C458508:T 0070907; D045162:Thiazolidinediones; D010862:Pilocarpine; D000077154:Rosiglitazone; D018021:Lithium Chloride; D005978:Glutathione; D019803:Glutathione Disulfide