Activation of cerebral peroxisome proliferator-activated receptors gamma exerts neuroprotection by inhibiting oxidative stress following pilocarpine-induced status epilepticus

• Published in: Brain research Vol. 1200; pp. 146 - 158
• Main Authors: Yu, Xin, Shao, Xiao-Guang, Sun, Hong, Li, Yong-Nan, Yang, Jun, Deng, Yan-Chun, Huang, Yuan-Gui
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 20.03.2008; Amsterdam Elsevier; New York, NY
• Subjects: Animals; Benzamides - pharmacology; Biological and medical sciences; Cell Death - drug effects; Cell Death - physiology; Convulsants; Disease Models, Animal; Glutathione - metabolism; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Heme Oxygenase (Decyclizing) - metabolism; Heme oxygenase-1; Hippocampus - drug effects; Hippocampus - metabolism; Hippocampus - physiopathology; Lipid Peroxidation - drug effects; Lipid Peroxidation - physiology; Lithium; Male; Medical sciences; Muscarinic Agonists; Nerve Degeneration - drug therapy; Nerve Degeneration - etiology; Nerve Degeneration - physiopathology; Nervous system (semeiology, syndromes); Neurology; Neuroprotection; Neuroprotective Agents - pharmacology; Oxidative stress; Oxidative Stress - drug effects; Oxidative Stress - physiology; Pilocarpine; PPAR gamma - agonists; PPAR gamma - antagonists & inhibitors; PPAR gamma - metabolism; PPARγ; Pyridines - pharmacology; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species - metabolism; Rosiglitazone; Status epilepticus; Status Epilepticus - chemically induced; Status Epilepticus - drug therapy; Status Epilepticus - physiopathology; Superoxide Dismutase - drug effects; Superoxide Dismutase - metabolism; Superoxide Dismutase-1; Thiazolidinediones - pharmacology; thiazolidinediones; 15d-PGJ 2; Oxidative stress; Neuroprotection; nuclear factor κB; CNS; HO-1; MDA; antioxidant response elements; NF-E2 related factor 2; NF-κB; SE; TZDs; Nrf2; reactive oxygen species; malondialdehyde; SnPP; GSH; diaminobenzidine; tin protoporphyrin; DAB; glutathione hormone; PPAR responsive elements; SOD; GP; heme oxygenase-1; PPREs; PPARγ; 15-deoxy-Δ12,14-prostaglandin J 2; central nervous system; status epilepticus; ARE; superoxide dismutase; ROS; Rosiglitazone; peroxisome proliferator-activated receptor gamma; glutathione peroxidase; Heme oxygenase-1; Status epilepticus; Nervous system diseases; Rat; Enzyme; Epilepsy; Rodentia; Central nervous system; PPARγ,Rosiglitazone,Oxidative stress,Neuroprotection,Heme oxygenase-1,Status epilepticus; Activation; Pilocarpine; Cerebral disorder; Encephalon; Oxygenase; Vertebrata; Mammalia; Animal; Central nervous system disease; Heme; Oxidoreductases; Peroxisome proliferator activated receptor
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2008.01.047

Abstract Status epilepticus (SE) can cause severe neuronal loss and oxidative damage. As peroxisome proliferator-activated receptor gamma (PPARγ) agonists possess antioxidative activity, we hypothesize that rosiglitazone, a PPARγ 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 PPARγ 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 PPARγ agonist might be a potential neuroprotective agent for epilepsy.