Wilson C L, Maidment N T, Shomer M H, Behnke E J, Ackerson L, Fried I, Engel J
Department of Neurology, UCLA School of Medicine 90024, USA.
Epilepsy Res. 1996 Dec;26(1):245-54. doi: 10.1016/s0920-1211(96)00057-5.
Recent microdialysis studies of excitatory and inhibitory amino acid release associated with paroxysmal hippocampal activity have found significant increases in the hippocampus of epileptic patients, but minimal or variable increases in animal models. One possible reason for the difference is that the animal models employed in these studies have not adequately reflected the pathophysiology of human epilepsy. The present study sought to verify the amino acid release reported in human epileptic hippocampus and then employs animal studies using a chronic rat model of epilepsy, in which rats exhibit spontaneous seizure activity 3 to 4 months after injection of kainic acid into the hippocampus. In agreement with earlier reports, we found increases in glutamate, aspartate and GABA during seizures in human hippocampus. In addition we found increases in taurine which have not previously been reported. The chronic rat model shows increases in the same amino acids as in the human epileptic hippocampus, both during spontaneous seizures and stimulation evoked after-discharges (ADs). In contrast, minimal increases are elicited by hippocampal stimulation in control (non-kainate injected) animals. These results correlate with the degree of mossy fiber reorganization found in the dentate gyrus of kainate rats or epileptic humans.
近期关于与阵发性海马活动相关的兴奋性和抑制性氨基酸释放的微透析研究发现,癫痫患者海马中的这些氨基酸有显著增加,但在动物模型中增加极少或变化不定。造成这种差异的一个可能原因是,这些研究中使用的动物模型没有充分反映人类癫痫的病理生理学。本研究旨在验证人类癫痫海马中所报道的氨基酸释放情况,然后利用慢性大鼠癫痫模型进行动物研究,在该模型中,大鼠在向海马注射海藻酸3至4个月后会出现自发性癫痫活动。与早期报告一致,我们发现人类海马在癫痫发作期间谷氨酸、天冬氨酸和GABA增加。此外,我们还发现了此前未报道过的牛磺酸增加。慢性大鼠模型显示,在自发性癫痫发作和刺激诱发的后放电(ADs)期间,与人类癫痫海马中相同的氨基酸会增加。相比之下,对照(未注射海藻酸)动物的海马刺激引起的增加极少。这些结果与在海藻酸大鼠或癫痫患者齿状回中发现的苔藓纤维重组程度相关。