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Epilepsy, Headache, Vertigo

開催日 2014/9/11
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

The prophylactic effect of early treatment with furosemide on autosomal dominant nocturnal frontal lobe epilepsy

  • P1-357
  • 山田 順子 / Junko Yamada:1,2 Zhu Gang / Gang Zhu:3 岡田 元宏 / Motohiro Okada:4 廣瀬 伸一 / Shinichi Hirose:5 柴 祐子 / Yuko Shiba:2 右田 啓介 / Keisuke Migita:2 上野 伸哉 / Shinya Ueno:2 兼子 直 / Sunao Kaneko:6 
  • 1:弘前大学 / Department of Biomedical Sciences Division of Medical Life Sciences Hirosaki University Graduate School of Health Sciences, Aomori, Japan 2:弘前大学大学院医学研究科脳神経生理学  / Department of Neurophysiology, Hirosaki University Graduate School of Medicine, Aomori Japan 3:Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, China / Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, China 4:三重大学大学院医学系研究科神経感覚医学 / Division of Neuroscience, Graduate School of Medicine, Mie University, Tsu, Japan  5:福岡大学医学部小児科 / Department of Pediatrics and Research Institute for the Molecular Pathomechanisms of Epilepsy, Fukuoka Uni 6:北東北てんかんセンター / North Tohoku Epilepsy Center, Minato Hospital, Hachinohe, Japan 

The transgenic rat strain S284L-TG harbors the S284L mutant of the neuronal nicotinic acetylcholine receptor alpha4 subunit gene (CHRNA4), which is responsible for human autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). S284L-TG rats have epileptic seizure phenotypes during slow-wave sleep, similar to those in NFLE. We previously demonstrated that GABAergic action of these rats was suppressed before the onset of ADNFLE seizures, and that glutamate release in the epileptic focus lesion was increased at the onset of epilepsy. Here, mRNA analysis revealed that Cl--accumulating Na-K-2Cl cotransporter 1 (NKCC1) levels were increased and Cl--extruding K-Cl cotransporter 1 and 2 (KCC1, KCC2) levels were decreased at the onset of ADNFLE seizures in S284L-TG rat frontal cortexes, which perturbed the GABAergic inhibitory system. The reversal potentials (EGABA) of GABAA receptor-mediated currents in cortical layer V pyramidal neurons of S284L-TG rats also changed their polarity from hyperpolarization to depolarization, and S284L-TG mEPSCs, but not mIPSCs, significantly increased in both amplitude and frequency. Administration of 25 mg/kg/day furosemide before, but not after, the onset of interictal discharges prevented idiopathic epileptic activity, reversed the depolarizing shift of EGABA and increased mEPSC amplitude to normal levels. These data indicate that early treatment with an agent that normalizes pathogenesis has a prophylactic effect on epilepsy. The present study suggests a novel antiepileptic therapeutic strategy for the prevention of ADNFLE.

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