PMID- 10065460 OWN - NLM STAT- MEDLINE DCOM- 19990421 LR - 20131121 IS - 0006-8969 (Print) IS - 0006-8969 (Linking) VI - 51 IP - 1 DP - 1999 Jan TI - [Ibudilast prevents oxygen-glucose deprivation-induced oligodendroglial injury]. PG - 49-54 AB - Previously we have demonstrated that ibudilast, which is used clinically for treating patients with asthma and cerebrovascular diseases, prevents excitotoxicity of oligodendroglial lineage mediated by Ca2+ influx via non-N-methyl-D-aspartate (NMDA) glutamate 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 12 h and subsequent reoxygenation for 2 h. Cell damage was evaluated by measuring activity of lactate dehydrogenase (LDH) released into the culture medium. OGD for 12 h 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 > or = 50 microM. 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 > or = 10 microM, at least 100 microM 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. FAU - Yoshioka, A AU - Yoshioka A AD - Department of Neurology, Kanazawa Medical University, Ishikawa, Japan. FAU - Yamaya, Y AU - Yamaya Y FAU - Hirose, G AU - Hirose G LA - jpn PT - English Abstract PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Japan TA - No To Shinkei JT - No to shinkei = Brain and nerve JID - 0413550 RN - 0 (Bronchodilator Agents) RN - 0 (Pyridines) RN - 0 (Vasodilator Agents) RN - DCR9Z582X0 (Epoprostenol) RN - E0399OZS9N (Cyclic AMP) RN - H2D2X058MU (Cyclic GMP) RN - IY9XDZ35W2 (Glucose) RN - M0TTH61XC5 (ibudilast) SB - IM MH - Animals MH - Bronchodilator Agents/*pharmacology MH - Cell Hypoxia/*drug effects MH - Cells, Cultured MH - Cyclic AMP/analysis MH - Cyclic GMP/analysis MH - Epoprostenol/pharmacology MH - Glucose/*metabolism MH - Oligodendroglia/*drug effects MH - Pyridines/pharmacology MH - Rats MH - Vasodilator Agents/*pharmacology EDAT- 1999/03/05 00:00 MHDA- 1999/03/05 00:01 CRDT- 1999/03/05 00:00 PHST- 1999/03/05 00:00 [pubmed] PHST- 1999/03/05 00:01 [medline] PHST- 1999/03/05 00:00 [entrez] PST - ppublish SO - No To Shinkei. 1999 Jan;51(1):49-54.