スナネズミ海馬スライスにおけるin vitro虚血誘発性細胞内Ca`2+´濃度上昇に対するイブジラストの効果 マイクロフルオロメトリーによる検討

書誌事項

タイトル別名
  • Effect of ibudilast on in vitro ischemia-induced calcium mobilization in gerbil hippocampal slices. Evaluation using microfluorometry.
  • Evaluation using microfluorometry
  • マイクロフルオロメトリーによる検討

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抄録

We examined, by microfluorometry, whether or not 3-isobutyryl-2-isopropylpyrazolo [1, 5-a] pyridine (ibudilast) has any effect on in vitro ischemia-induced rises of intracellular Ca2+ concentration ([Ca2+] i) in the CA1 field of gerbil hippocampal slices. Transverse hippocampal slices (300 μm-thick) were loaded with rhod-2, a calcium ion-sensitive dye, and then transferred to a flow-through chamber mounted on an inverted fluorescence microscope. The changes in [Ca2+] i were measured using an intracellular calcium ion imaging system. When the slices were exposed to a glucose-free physiological medium equilibrated with a 95% N2/5% CO2 gas mixture (standard in vitro ischemic conditions), a large [Ca2+] i elevation was detected about 5 min after the beginning of the standard in vitro ischemic conditions. Howerver, the extent of in vitro ischemia-induced [Ca2+] i increase in the presence of 43 μM ibudilast was significantly depressed in all subregions of the hippocampal slices as compared with that under standard in vitro ischemic conditions. Similar [Ca22+] i increases in the CA1 field were induced by Ca2+-free in vitro ischemic conditions, a high concentration of KCl or each specific agonist for the glutamate receptor subtypes, N-methyl-D-aspartate, (s) -alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate and kainate; and these increases were also depressed in the presence of 43 μM ibudilast in the perfusion medium. The above findings indicate that ibudilast exerts an inhibitory effect on the in vitro ischemia-induced [Ca2+] i elevation and that this inhibitory effect is caused by decreases in Ca2+ influx through the agonist-gated Ca2+ channels and also the voltage-gated Ca2+ channels as well as in Ca2+ release from the intracellular Ca2+ stores. The present inhibitory effect of ibudilast on Ca2+ accumulation may be involved in the mechanisms whereby ibudilast can diminish ischemic injury in hippocampal CA1 neurons.

収録刊行物

  • 脳卒中

    脳卒中 17 (2), 137-144, 1995

    一般社団法人 日本脳卒中学会

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