ラットにおけるカイニン酸けいれん発作重積後のMRI所見と病理所見の関係

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  • An experimental study on the relation of T2-signal high intensity in MRI to histopathological changes in the kainic acid model of temporal lobe epilepsy in rats.

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側頭葉てんかんでは,てんかん焦点に一致してMRI T2高信号領域が見られ,FLAIR法でこれがより明瞭になるが,このMRI所見と病理組織学的変化との関係は必ずしもはっきりしていない。そこで,Sprague-Dawleyラットにカイニン酸(KA)でけいれん発作重積状態を起こし,経時的にMRIを記録するとともに,ニッスル染色,GFAP免疫染色での病理組織学的変化を調べて両者の関係について検討した。KA群では,MRIで1~8週間後のいずれにおいてもpiriform cortexからentorhinal cortexにかけて不整形のT2高信号領域がみられたが,stage3のけいれん発作しか出現しなかったラットではstage4,5が出現したラットに比べて程度が弱かった。組織学的には,CA1,subiculum,piriform cortex,entorhinal cortexで神経細胞の消失,濃染細胞の増加と萎縮,GFAP免疫反応の増強が見られたが,piriform cortex,entorhinal cortexでの神経細胞消失の程度はT2信 号の程度と相関せず,GFAP免疫反応が増強した領域に一致して高信号がみられた。しかし,海馬のGFAP免疫反応増強はMRI所見に反映されず,これはMRIの解像度の限界にもよると考えられた。

The relation of T2-signal high intensity areas observed in temporal lobe epilepsy to histopathological changes in limbic structures was examined in the rat kainic acid (KA) model of epilepsy. Male 8-week-old Sprague-Dawley rats were injected with 10mg/kg(i.p.) of KA or saline (control). Repetitive generalized convulsions (stage 3, or stage 4,5 seizures of amygdala kindled seizures) lasted for 3 to 4 hrs. were induced by KA injection in all rats. MRI was recorded on the day before the KA injection and 1, 2, 4, 8 weeks after the injection by fluid-attenuated inversion recovery method under deep pentobarbital anesthesia. Following the last MRI recording, rats were perfused with 4% paraformaldehyde (PFA) from left cardiac ventricle, post-fixed overnight in 4% PFA and brains were embedded in parafin. Coronal brain sections (6μm) were stained with cresyl violet, or mouse anti-GFAP antibody followed by biotinylated goat anti-mouse IgG and avidin-biotin-peroxidase (vectastain ABC kit). Irregularshaped moderate to severe high T2-signal areas were observed in bilateral piriform and entorhinal cortex in MRI. These high T2-signal areas were ovserved from 1 week after the KA injection to 8 weeks after the injection, and were more prominent in rats elicited stage 4 or 5 seizures than in rats elicited stage 3 seizures. Loss of pyramidal neurons and increased GFAP immunoreactivity were observed in piriform cortex, entorhinal cortex, CA1, subiculum, and hilus of dentate gyrus. The increase of GFAP immunoreactivity, but not the intensity of neuronal loss, in piriform and entorhinal cortex was almost correponded to the size and intensity of T2-signal. However, the increase of GFAP immunoreactivity in hippocampus was not detected as the increase of T2-signal in MRI. These findings indicate that astroglial reactions in piriform and entorhinal cortex are more sensitive to T2-weighted MRI than those in hippocampus.

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