{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:18:11Z","timestamp":1791317891109,"version":"4.3.1"},"reference-count":32,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2007,6,18]],"date-time":"2007-06-18T00:00:00Z","timestamp":1182124800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Glia"],"published-print":{"date-parts":[[2007,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Proinflammatory cytokine\u2010mediated injury to oligodendrocyte progenitor cells (OPCs) has been proposed as a cause of periventricular leukomalacia (PVL), the most common brain injury found in preterm infants. Preventing death of OPCs is a potential strategy to prevent or treat PVL. In the current study, we utilized an <jats:italic>in vitro<\/jats:italic> cell culture system to investigate the effect of insulin\u2010like growth factor\u20101 (IGF\u20101) on tumor necrosis factor\u2010\u03b1 (TNF\u03b1)\u2010induced OPC injury and the possible mechanisms involved. OPCs were isolated from neonatal rat optic nerves and cultured in chemically defined medium (CDM) supplemented with platelet\u2010derived growth factor and basic fibroblast growth factor. Exposure to TNF\u03b1 resulted in death of OPCs. IGF\u20101 protected OPCs from TNF\u03b1 cytotoxicity in a dose\u2010dependent manner as measured by the XTT and TUNEL assays. IGF\u20101 activates both the PI3K\/Akt and the extracellular signal\u2010regulated kinase (ERK) pathway. However, IGF\u20101\u2010enhanced cell survival signals were mediated by the PI3K\/Akt, but not by the ERK pathway, as evidenced by the observation that IGF\u20101\u2010enhanced cell survival was partially abrogated by Akti, the Akt inhibitor, or wortmannin, the PI3K inhibitor, but not by PD98059, the MAPK kinase\/ERK kinase inhibitor. The downstream events of IGF\u20101\u2010triggered survival signals included phosphorylation of BAD, blockade of TNF\u03b1\u2010induced translocation of Bax from the cytosol to the mitochondrial membrane, and suppression of caspase\u20109 and caspase\u20103 activation. These observations indicate that the protection of OPCs by IGF\u20101 is mediated, at least partially, by interruption of the mitochondrial apoptotic pathway via activation of PI3K\/Akt. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/glia.20530","type":"journal-article","created":{"date-parts":[[2007,6,18]],"date-time":"2007-06-18T17:50:13Z","timestamp":1182189013000},"page":"1099-1107","source":"Crossref","is-referenced-by-count":107,"title":["IGF\u20101 protects oligodendrocyte progenitors against TNF\u03b1\u2010induced damage by activation of PI3K\/Akt and interruption of the mitochondrial apoptotic 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