Statin inhibits kainic acid-induced seizure and associated inflammation and hippocampal cell death

• DOI: 10.1016/j.neulet.2008.05.112
• Publication Date: 2008-06-07T05:01:46Z
• Authors: Jin-Koo Lee; Je-Seong Won; Avtar K. Singh; Inderjit Singh
• Keywords: Inflammation; Male; 0301 basic medicine; Kainic Acid; Cell Death; Dose-Response Relationship, Drug; Tumor Necrosis Factor-alpha; Interleukin-1beta; Nitric Oxide Synthase Type II; Ectodysplasins; Hippocampus; Rats; 3. Good health; Rats, Sprague-Dawley; Disease Models, Animal; 03 medical and health sciences; Heptanoic Acids; Seizures; Atorvastatin; In Situ Nick-End Labeling; Animals; Pyrroles; Hydroxymethylglutaryl-CoA Reductase Inhibitors

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.