Abstract
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.
MeSH terms
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Animals
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Benzamides / pharmacology
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Cell Death / drug effects
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Cell Death / physiology
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Convulsants
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Disease Models, Animal
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Glutathione / metabolism
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Heme Oxygenase (Decyclizing) / metabolism
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Hippocampus / drug effects*
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Hippocampus / metabolism
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Hippocampus / physiopathology
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Lipid Peroxidation / drug effects
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Lipid Peroxidation / physiology
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Lithium
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Male
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Muscarinic Agonists
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Nerve Degeneration / drug therapy*
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Nerve Degeneration / etiology
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Nerve Degeneration / physiopathology
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Neuroprotective Agents / pharmacology
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Oxidative Stress / drug effects*
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Oxidative Stress / physiology
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PPAR gamma / agonists*
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PPAR gamma / antagonists & inhibitors
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PPAR gamma / metabolism
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Pilocarpine
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Pyridines / pharmacology
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Rats
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Rats, Sprague-Dawley
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Reactive Oxygen Species / metabolism
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Rosiglitazone
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Status Epilepticus / chemically induced
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Status Epilepticus / drug therapy*
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Status Epilepticus / physiopathology
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Superoxide Dismutase / drug effects
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Superoxide Dismutase / metabolism
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Superoxide Dismutase-1
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Thiazolidinediones / pharmacology*
Substances
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Benzamides
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Convulsants
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Muscarinic Agonists
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Neuroprotective Agents
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PPAR gamma
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Pyridines
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Reactive Oxygen Species
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T 0070907
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Thiazolidinediones
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Pilocarpine
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Rosiglitazone
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Lithium
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Heme Oxygenase (Decyclizing)
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Hmox1 protein, rat
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Sod1 protein, rat
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Superoxide Dismutase
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Superoxide Dismutase-1
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Glutathione