Anticonvulsant effect of dexmedetomidine in a rat model of self-sustaining status epilepticus with prolonged amygdala stimulation

Neurosci Lett. 2013 May 24:543:17-21. doi: 10.1016/j.neulet.2013.03.036. Epub 2013 Apr 8.

Abstract

Status epilepticus (SE), leading to 27 percent mortality in adult patients, becomes refractory to firstline intravenous diazepam, with prolonged seizure duration. The mechanism could be attributed to the declined inhibitory action of GABA; therefore, alternative medications acting on other targets are necessary. The aim of the present study was to examine whether DEX, a highly specific central α2-adrenoreceptor agonist, could show the anticonvulsant effect on self-sustaining SE (SSSE), and to explore the involved mechanisms. Five minutes after SSSE, which was induced in adult Wistar rats by constant amygdala stimulation for 25 min, DEX was injected intraperitoneally at two dosages (50/100 μg/kg). The number and cumulative time of repeated seizures were recorded; the levels of Glu/GABA and glutathione/malondialdehyde (GSH/MDA) in hippocampus tissue were detected. The results showed that DEX effectively decreased the number and cumulative time of repeated seizures, alleviated the levels of Glu and GSH/MDA in hippocampus tissue, but no effect was detected on the level of GABA, suggesting that DEX could be a potential agent for the treatment of SSSE, the possible mechanisms were antioxidation and inhibition of the Glu release.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-2 Receptor Agonists / pharmacology*
  • Adrenergic alpha-2 Receptor Agonists / therapeutic use
  • Amygdala / physiopathology*
  • Animals
  • Anticonvulsants / pharmacology*
  • Anticonvulsants / therapeutic use
  • Dexmedetomidine / pharmacology*
  • Dexmedetomidine / therapeutic use
  • Electric Stimulation
  • Glutamic Acid / metabolism
  • Glutathione / metabolism
  • Hippocampus / metabolism
  • Male
  • Malondialdehyde / metabolism
  • Rats
  • Rats, Wistar
  • Status Epilepticus / drug therapy
  • Status Epilepticus / physiopathology*
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Adrenergic alpha-2 Receptor Agonists
  • Anticonvulsants
  • Glutamic Acid
  • Malondialdehyde
  • gamma-Aminobutyric Acid
  • Dexmedetomidine
  • Glutathione