title: Curcumin protects pre-oligodendrocytes from activated microglia in vitro and in vivo.
abstract: Infection and inflammation leading to injury or death of pre-oligodendrocytes (preOLs) is one of the principal initiating mechanisms in the pathogenesis of preterm periventricular leukomalacia (PVL). The present study explores the possible protective effect of curcumin against the toxicity of lipopolysaccharide (LPS)-activated microglia on preOLs in vitro and in vivo. In vitro, preOLs in coculture with microglia exhibited increased apoptosis after exposure to LPS. LPS also induced significantly increased expression of inducible nitric oxide synthase (iNOS) and NADPH oxidase (NOX) subunits, p67-phox and gp91-phox in microglia. Our results suggest that iNOS and NOX contribute to the apoptosis of preOLs by activated microglia. The potential anti-inflammatory effects of curcumin were tested to determine if they could help to minimize microglia-mediated damage. Curcumin (10 microg/ml) was found to significantly inhibit the apoptosis of preOL and expression of either iNOS or NOX in the LPS-activated microglia. In vivo, curcumin was administered (50 mg/kg/day, i.p.) to two-day-old neonatal Sprague-Dawley rats subjected to intracerebral injection of LPS. Treatment with curcumin either 1h before or immediately after LPS injection significantly ameliorated white matter injury and loss of preOLs, decreased activated microglia, and inhibited microglial expression of iNOS and translocation of p67phox and gp91phox to the microglial cell membranes in neonatal rat brains following LPS injection. These results suggest that curcumin has a protective effect on infection-driven white matter injury, which is associated with suppression of iNOS and NOX activation. Consequently, curcumin may have potential as a protective agent against immature white matter injury.
authors.affiliation: Shanghai Institute for Pediatric Research, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, PR China. waxflying@yahoo.com.cn
authors.forename: Liu-fang
authors.initials: LF
authors.lastname: He
authors.forename: Hui-Jin
authors.initials: HJ
authors.lastname: Chen
authors.forename: Long-hua
authors.initials: LH
authors.lastname: Qian
authors.forename: Guan-yi
authors.initials: GY
authors.lastname: Chen
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Buzby
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000254:growth & development; D002450:Cell Communication / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D003474:Curcumin / Q000494:pharmacology*; D004336:Drug Antagonism; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007969:Leukomalacia, Periventricular / Q000473:pathology / Q000517:prevention & control; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D017628:Microglia / Q000166:cytology / Q000187:drug effects*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects*; D010750:Phosphoproteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D018696:Neuroprotective Agents; D010750:Phosphoproteins; C079789:neutrophil cytosol factor 67K; D052247:Nitric Oxide Synthase Type II; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D003474:Curcumin