Treatment of Lithium-Pilocarpine Induced Status Epilepticus Rat Models According to EEG Stage

J Korean Neurol Assoc > Volume 26(3); 2008 > Article

Journal of the Korean Neurological Association 2008;26(3): 200-208.

리튬-필로카르핀 유발 경련지속증 흰쥐 모델에서뇌파 단계에 따른 치료

전미영, 신원철b 김영인c 김재문d 서대원a,e

삼성생명과학연구소a, 경희대학교 의과대학 동서신의학병원 신경과b, 가톨릭의과대학 신경과학교실c,충남대학교 의과대학 신경과학교실d, 성균관의과대학 삼성서울병원 신경과e

Treatment of Lithium-Pilocarpine Induced Status Epilepticus Rat Models According to EEG Stage

Mi-Young Jeon

Samsung Biomedical Research Institutea, Seoul, Korea; Kyung Hee Neo Medical Center, Kyung Hee University College of Medicineb, Seoul, Korea; Catholic University College of Medicinec, Seoul, Korea; Chungnam National University College of Medicined, Daejeon, Korea; Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicinee, Seoul, Korea

Abstract

Background: EEG shows a sequence of progressive changes in status epilepticus (SE). Timely antiepileptic drug treatment is an important factor for the prognosis of SE. Here we investigated the effect of treatment according to EEG staging in a lithium-pilocarpine SE rat model.
Methods: By analyzing the on-going EEG of SE, we injected propofol (PF) or propofol and valproate (PF+VA) on each defined EEG stage [early period, merging stage; middle period, continuous stage; late period, early periodic epileptiform discharges stage (ePED)]. We measured the duration of each stage after the treatment and the number of principal cells at three hippocampal areas (CA1, CA3, dentate gyrus] after SE.
Results: Both PF- and PF+VA-treated groups showed lower mortality rate in the merging stage-treated subgroup than in ePED-treated subgroup. Seizure duration was significantly shortened in the merging stage of both PF- (p<0.005) and PF+VA-treated groups than in untreated group (p<0.002). The durations of the continuous stage and ePED were shortened in the merging stage-treated subgroup, but ePED duration did not decrease in ePED-treated subgroup. The shortening of the continuous stage and ePED was more prominent in the PF+VA-treated group than in PF-treated group. Neuronal loss in both PF- and PF+VA-treated groups was so severe that CA1 and CA3 neuronal loss was decreased more markedly in the ePED-treated group than in the merging stage-treated group (p<0.01).
Conclusions: Early therapy based on the defined EEG staging might be an effective option for shortening duration of SE and decreasing neuronal damage at the hippocampus. Early combination therapy adopting PF+VA requires further investigation for new treatment option.KeyWords:Pilocarpine, Status epilepticus, EEG, Propofol, Valproate