Statin inhibits kainic acid-induced seizure and associated inflammation and hippocampal cell death.
Statins are inhibitors of HMG-CoA reductase that have been recently recognized as anti-inflammatory and neuroprotective drugs. Herein, we investigated anti-excitotoxic and anti-seizure effects of statins by using kainic acid (KA)-rat seizure model, an animal model for temporal lobe epilepsy and excitotoxic neurodegeneration. We observed that pre-treatment with Lipitor (atorvastatin) efficiently reduced KA-induced seizure activities, hippocampal neuron death, monocyte infiltration and proinflammatory gene expression. In addition, we also observed that lovastatin treatment attenuated KA- or glutamate-induced excitotoxicity of cultured hippocampal neurons. These observations suggest a potential for use of statin treatment in modulation of seizures and other neurological diseases associated with excitotoxicity.
Lee
Jin-Koo
JK
Department of Pediatrics, Medical University of South Carolina, Charleston, SC 29425, USA.
Won
Je-Seong
JS
Singh
Avtar K
AK
Singh
Inderjit
I
D000818:Animals; D000069059:Atorvastatin; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D053331:Ectodysplasins / Q000378:metabolism; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D020287:In Situ Nick-End Labeling / Q000379:methods; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D053583:Interleukin-1beta / Q000378:metabolism; D007608:Kainic Acid; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011758:Pyrroles / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D053331:Ectodysplasins; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D053583:Interleukin-1beta; D011758:Pyrroles; D014409:Tumor Necrosis Factor-alpha; D000069059:Atorvastatin; D052247:Nitric Oxide Synthase Type II; D007608:Kainic Acid