Ibudilast Prevents Oxygen-Glucose Deprivation-Induced Oligodendroglial Injury.
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Accession number;99A0252782
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| Title;Ibudilast Prevents Oxygen-Glucose Deprivation-Induced Oligodendroglial Injury. |
| Author;
YOSHIOKA AKIRA
(Kanazawa Med. Univ.)
YAMAYA YOKO
(Kanazawa Med. Univ.)
HIROSE GENJIRO
(Kanazawa Med. Univ.)
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Journal Title;Brain Nerve
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Journal Code:Z0685A
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ISSN:0006-8969
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VOL.51;NO.1;PAGE.49-54(1999)
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| Figure&Table&Reference;FIG.5, TBL.1, REF.27 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;Previously we have demonstrated that ibudilast, which is used clinically for treating patients with asthma and cerebrovascular diseases, prevents excitotoxicity of oligodeiidroglial lineage mediated by Ca2+ influx via non-N-methyl-D-aspartate(NMDA) glutaniate receptor(GluR) channels. We here present a finding that ibudilast prevents oxygen-glucose deprivation(OGD)-induced oligodendroglial injury. The oligodendrocyte-like cells(OLC), differentiated from the CG-4 cell line established from rat oligodendrocyte-type-2 astrocyte(O-2A) progenitor cells, were exposed to hypoxia in the absence of glucose for 12h and subsequent reoxygenation, for 2h. Cell damage was evaluated by measuring activity of lactate dehydrogenase(LDH) released into the culture medium. OGD for 12h induced 30 to 50% LDH release into the medium. OLC damage induced by deprivation of oxygen and glucose was prevented by ibudilast at concentrations of .GEQ.50.MU.M. The protection given by ibudilast against OGD-induced injury was enhanced by prostacyclin (PGI2). OGD-induced OLC injury was prevented by 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX), an inhibitor of non-NMDA GluR or deprivation of Ca2+ from culture medium. While ibudilast increased intracellular cAMP at concentrations of .GEQ.10.MU.M, at least 100.MU.M concentrations were needed to increase intracellular cGMP. Therefore, we concluded that ibudilast prevented OGD-induced oligodendroglial injury possibly by increasing intracellular cAMP which modulates Ca2+ influx via non-NMDA GluR channels. (author abst.) |
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