Administration of Simvastatin After Kainic Acid-Induced Status Epilepticus Restrains Chronic Temporal Lobe Epilepsy

PLoS One. 2011;6(9):e24966. doi: 10.1371/journal.pone.0024966. Epub 2011 Sep 19.

Abstract

In this study, we examined the effect of chronic administration of simvastatin immediately after status epilepticus (SE) on rat brain with temporal lobe epilepsy (TLE). First, we evaluated cytokines expression at 3 days post KA-lesion in hippocampus and found that simvastatin-treatment suppressed lesion-induced expression of interleukin (IL)-1β and tumor necrosis factor-α (TNF-α). Further, we quantified reactive astrocytosis using glial fibrillary acidic protein (GFAP) staining and neuron loss using Nissl staining in hippocampus at 4-6 months after KA-lesion. We found that simvastatin suppressed reactive astrocytosis demonstrated by a significant decrease in GFAP-positive cells, and attenuated loss of pyramidal neurons in CA3 and interneurons in dentate hilar (DH). We next assessed aberrant mossy fiber sprouting (MFS) that is known to contribute to recurrence of spontaneous seizure in epileptic brain. In contrast to the robust MFS observed in saline-treated animals, the extent of MFS was restrained by simvastatin in epileptic rats. Attenuated MFS was related to decreased neuronal loss in CA3 and DH, which is possibly a mechanism underlying decreased hippocampal susceptibility in animal treated with simvastatin. Electronic encephalography (EEG) was recorded during 4 to 6 months after KA-lesion. The frequency of abnormal spikes in rats with simvastatin-treatment decreased significantly compared to the saline group. In summary, simvastatin treatment suppressed cytokines expression and reactive astrocytosis and decreased the frequency of discharges of epileptic brain, which might be due to the inhibition of MFS in DH. Our study suggests that simvastatin administration might be a possible intervention and promising strategy for preventing SE exacerbating to chronic epilepsy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticholesteremic Agents / therapeutic use
  • Behavior, Animal / drug effects
  • Chronic Disease
  • Cytokines / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Epilepsy, Temporal Lobe / complications
  • Epilepsy, Temporal Lobe / physiopathology
  • Epilepsy, Temporal Lobe / prevention & control*
  • Excitatory Amino Acid Agonists / toxicity
  • Kainic Acid / toxicity*
  • Male
  • Mossy Fibers, Hippocampal / drug effects*
  • Mossy Fibers, Hippocampal / pathology
  • Neurons / drug effects*
  • Neurons / pathology
  • Rats
  • Rats, Wistar
  • Simvastatin / therapeutic use*
  • Status Epilepticus / chemically induced*
  • Status Epilepticus / pathology

Substances

  • Anticholesteremic Agents
  • Cytokines
  • Excitatory Amino Acid Agonists
  • Simvastatin
  • Kainic Acid