흥분성 신경전달물질의 Cortical Spreading Depression 유발에 대한 실험적 연구 : 대뇌피질 국소 도포를 위한 새 실험 모형 new topical application model = Initiation of cortical spreading depression by excitatory amino acids in rats

다국어 초록 (Multilingual Abstract)

The purpose of this study was to devise a new model for topical application of chemical substances to rat cerebral cortex that successfully and repeatedly initiated the CSD in conjunction with responses from various excitatory amino acids(EAAs). Various EAA agents, including glutamate itself, that act on single or multiple subtypes of EAA receptor were examined; kainate, aspartate, N-methyl-D-aspartate (NMDA), quisqualate, and alpha-amino-3 -hydroxy- 5-methyl-4-isoxazole-propriate (AMPA). Through the model with a specially designed well buried in 1.5 mm depth of the cerebral cortex, these chemical agents were topically applied to the cortical gray matter. Dose of EAA between 10^(-7) and 10^(-4) M concentration were escalated for triggering the CSD and its rate of consistency in triggering was also evaluated. Total of 50 Sprague-Dawley rats were used and divided into seven groups including the sham group.
The results are as follows:
1. CSDs were repeatedly initiated in all experimental groups with relatively consistent rates. Duration of CSDs were 1 - 4 minutes(mean 2.2±1.4) and amplitudes were 20 - 40 mV.
2. Effective dose_(50)(ED_(50)), that trigger over 50% of CSD, was 10^(-5) M(n=8) for glutamate, 10^(??) M(n=8) for aspartate, 10^(-5) M(n=7) for quisqualate, and 10^(??) M(n=7) for NMDA and kainate group.
3. Among those acting on the single receptor. AMPA was shown to be the most effective in triggering CSD, and NMDA, and kainate were in descending orders. Aspartate, that was known to act on multiple EAA receptors, showed highest rate of triggering CSD among all groups, but glutamate, known to act on all receptors of its subtypes, showed most consistent rate of triggering CSD at dose escalation study.
Some of possible factors that might be involved in these results would be the difference in number of receptors presented in various regions of cerebral cortex, receptor-specificity of various EAAs, and the mode of triggering of CSD, etc.. Results from present study showed that it was possible, by using newly devised in vivo rat model for topical application of chemical agents to the cerebral cortex, not only to initiate but also repeatedly produce CSDs without additional injuries to the cortex.