An experimental study on the mechanism underlying the onset of temporal lobe epilepsy.

• Project/Area Number: 12670940
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Okayama University
• Principal Investigator: YAMADA Norihito Dept of Neuropsychiatry, Medical School, Lecturer, 医学部附属病院, 講師 (10240029)
• Co-Investigator(Kenkyū-buntansha): 佐藤 俊樹 岡山大学, 医学部・附属病院, 助手 (30304348) ; 児玉 昌純 岡山大学, 医学部・附属病院, 助手 (00325101)
• Project Period (FY): 2000 – 2002
• Project Status: Completed (Fiscal Year 2002)
• Budget Amount: ¥1,800,000 (Direct Cost: ¥1,800,000); Fiscal Year 2002: ¥500,000 (Direct Cost: ¥500,000); Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000); Fiscal Year 2000: ¥600,000 (Direct Cost: ¥600,000)
• Keywords: temporal lobe epilepsy / animal model / status epilepticus / hippocampus / deep prepiriform cortex / adenosine receptors / けいれん重積 / 間欠的電気刺激 / 深部梨状葉皮質 / ラット

Research Abstract

We investigated whether the electrical massed stimulation with aminophylline, which is an denosine antagonist caused the self-sustained status epilepticus and delayed kindling effect in the rat brain. The main aim in this study is to elicit status epilepticus effectively avoid neuronal damage by stimulation itself making duration and intensity of the stimulation as small as possible. First, we stimulated into the ventral hippocampus (vHIPP) to demonstrate seizure susceptibility electrophysiologicaly using retest stimulation protocol. Furthermore, the necessity of aminophylline for induction of status epilepticus was investigated. The rats were stimulated (20 Hz, 20 s, ADT+25 μA, every 1 minute) into the vHIPP with aminophylline or saline pretreatment. Stimulation was continued until the animals reached to self-sustained status epilepticus, and the stimulation number was limited to 100. Self-sustained staus epilepticus was observed 57% in stimulated rats. Two and 8 weeks after the masse d stimulation, the retest stimulations consisting of 10 stimulation epochs were applied to the vHIPP, using the same conditions as those for the massed stimulation. Eight weeks after massed stimulation, the seizure severity and the maximum continuous afterdischarge (AD) duration was increased (P<0.05). There were no significant differences between the animals with and without aminophylline. Second, the rats were stimulated into the DPC using the same conditions as for the first experiment. Self-sustained status epilepticus was observed 93% in stimulated rats. Retest stimulations into the vHIPP, the total AD duration was significantly longer and mean seizure severity was increased 2 and 8 weeks after massed stimulation (P<0.05, respectively). Third, a long-term followup study revealed that interictal discharges originated from the vHIPP were observed 10-16 weeks after massed stimulation, and massive neuronal damages were observed in the area CA1, CA3 and dentate hilus 16 weeks after induction of status epilepticus. Massed stimulations of an extrahippocampal limbic structure (the DPC) which is distant from the hippocampus can produce long term seizure susceptibility in the vHIPP with aminophylline pretreatment. This model will be useful for studying the epileptogenic mechanisms underlying the origin of TLE.

Research Products

• [Publications] Wake, Y. et al.: "Experimental model of status epilepticus induced by intermittent electrical stimulations of the deep prepiriform cortex cause seizure susceptibility in the hippocampus"Epilepia. (印刷中). (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Wake, Y. et al.: "Experimental model of status epilepticus induced by intermittent electrical stimulations of the deep prepiriform cortex cause seizure susceptibility in the hippocampus"Epilepsia. in press. (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Wake, Y., Yamada, N.et al.: "Experimental Model of Status Epileptics by Intermittent Electrical Stimulations of the Deep Prepiriforn Cortex Cause Seizure Susceptibility at Hippocampus"Epilepsia. (In press). (2003)
• [Publications] Wake, Y.: "Experimental model of status epilepticus induced by intermittent electrical stimulations of the deep prepiriform cortex cause seizme susceptibil at hippocan"Epilepsia(Suprl). (発表予定).