Department of Pharmacology and University of Toronto Epilepsy Research Program, University of Toronto, Toronto, Ontario, Canada.
Epilepsia. 2010 Sep;51(9):1729-35. doi: 10.1111/j.1528-1167.2010.02524.x.
Racine's classic study suggested that after discharge thresholds were reduced in the primary stimulation site (amygdala) of kindled rats, but that that they were not reduced in secondary (nonstimulated) sites. However, recent reports of neurochemical changes related to excitation and inhibition in nonstimulated sites in kindled brains would be expected to cause reductions in afterdischarge thresholds in these sites. More recently Sanei et al. have reported a significant threshold reduction in the piriform cortex of amygdala- and hippocampus-kindled cats, but not in the entorhinal cortex. The present study was designed to determine whether the results of Sanei et al. in cats could be replicated in rats kindled in the amygdala-a model commonly used in studies of seizure mechanisms and anticonvulsant drug development.
Adult, male Long-Evans rats were kindled in the amygdala or given matched handling. Beginning 48 h following the last stimulation, afterdischarge thresholds were determined in the ipsilateral piriform and entorhinal cortices. Amygdala thresholds were determined 24 h later.
Afterdischarge thresholds were significantly reduced in both the amygdala and the ipsilateral entorhinal cortex of amygdala-kindled rats. Afterdischarge thresholds in the piriform cortex did not differ significantly between kindled and control subjects.
These data suggest that threshold reduction occurs outside the primary kindling site in rats as well as in cats. Extrafocal changes in afterdischarge threshold may be functionally important, and might possibly relate to extrafocal neurochemical changes and progressive generalization of seizure discharge from discrete focal sites.
拉辛的经典研究表明,在点燃大鼠初级刺激部位(杏仁核)的放电阈值降低后,而在次级(未刺激)部位则没有降低。然而,最近有报道称,与点燃大脑中未刺激部位的兴奋和抑制有关的神经化学变化,预计会导致这些部位的后放电阈值降低。最近,Sanei 等人报告称,在杏仁核和海马点燃的猫的梨状皮层中,后放电阈值显著降低,但在内嗅皮层中没有降低。本研究旨在确定 Sanei 等人在杏仁核点燃的猫中得到的结果是否可以在杏仁核点燃的大鼠中复制,这是一种常用于研究癫痫机制和抗惊厥药物开发的模型。
成年雄性 Long-Evans 大鼠在杏仁核中被点燃或给予匹配的处理。在最后一次刺激后 48 小时,测定同侧梨状和内嗅皮层的后放电阈值。24 小时后测定杏仁核阈值。
杏仁核点燃大鼠的杏仁核和同侧内嗅皮层的后放电阈值均显著降低。梨状皮层的后放电阈值在点燃组和对照组之间无显著差异。
这些数据表明,在大鼠中,除了初级点燃部位外,放电阈值也会在其他部位降低。后放电阈值的额外变化可能具有功能重要性,并且可能与额外的神经化学变化和从离散的焦点部位逐渐泛化的癫痫放电有关。