title: Peroxisome proliferator-activated receptor gamma agonist, rosiglitazone, suppresses CD40 expression and attenuates inflammatory responses after lithium pilocarpine-induced status epilepticus in rats.
abstract: Inflammatory responses in the brain are involved in the etiopathogenesis and sequelae of seizures. Ligation of microglial CD40 plays a role in the development of inflammatory responses in the central nervous system (CNS). Our study showed that there was an increased CD40 expression on activated microglia in the brain injury after lithium pilocarpine-induced status epilepticus (SE) in rats. Since peroxisome proliferator-activated receptor gamma (PPARgamma) acts as a regulator of CNS inflammation and a powerful pharmacological target for counteracting CNS diseases, we investigated the role of the PPARgamma agonist, rosiglitazone, in the modulation of CD40 expression and in the pathological processes of inflammation after SE. We found that rosiglitazone inhibited the expression of CD40, tumor necrosis factor (TNF-alpha), and microglial activation in different regions of hippocampus. The results were indicated by immunohistochemistry, Western blot, and ELISA, respectively. Rosiglitazone also prevented neuronal loss in the CA1 area after SE observed by Nissl-staining. These protective effects were significantly reversed by the co-treatment with T0070907, a selective antagonist of the PPARgamma, which clearly demonstrated a PPARgamma-dependent mechanism. Our data provide evidence that rosiglitazone considerably attenuates inflammatory responses after SE by suppressing CD40 expression and microglial activation. Our data also support the idea that rosiglitazone might be a potential neuroprotective agent in epilepsy.
authors.affiliation: Research Center of Epilepsy, Department of Neurology, Xijing Hospital, the Fourth Military Medicine University of Chinese PLA, Xi'an, Shaanxi Province, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
authors.forename: Yuangui
authors.initials: Y
authors.lastname: Huang
authors.forename: Xin
authors.initials: X
authors.lastname: Yu
authors.forename: Yongnan
authors.initials: Y
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Deng
authors.forename: Gang
authors.initials: G
authors.lastname: Zhao
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology / Q000627:therapeutic use; D015153:Blotting, Western; D001930:Brain Injuries / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D019013:CD40 Antigens / Q000378:metabolism*; D002493:Central Nervous System Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D004827:Epilepsy / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D018020:Lithium Compounds / Q000633:toxicity; D008297:Male; D047495:PPAR gamma / Q000819:agonists* / Q000037:antagonists & inhibitors; D010862:Pilocarpine / Q000633:toxicity; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D013226:Status Epilepticus / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D001549:Benzamides; D019013:CD40 Antigens; D018020:Lithium Compounds; D047495:PPAR gamma; D011725:Pyridines; C458508:T 0070907; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; D010862:Pilocarpine; D000077154:Rosiglitazone