[1400W blocks death pathway of LPS-induced activated-microglia to preOLs].

Objective To explore the efficacy of inductible nitric oxide synthase(iNOS) inhibitor 1400W in vivo in blocking the death pathway of lipopolysaccharide(LPS)-induced activated-microglia to preoligodendrocytes(preOLs) in neonatal rats with infective-type periventricular leukomalacia(PVL) induced by LPS.Methods Two-day-old neonatal rats were randomly divided into: a sham-operated group,an untreated PVL group,and four 1400W-treated PVL groups that were subcutaneously administrated with 20 mg/kg of 1400W at 0 h,8 hrs,16 hrs,and 24 hrs after LPS induction,respectively.The brain specimens were obtained 5 days after LPS induction.The pathological assessment of cerebral white matter was performed under a light microscope.Concentrations of nitric oxide(NO) were measured by nitric acid-deoxidize colorimetry.Synthesis of iNOS was determined by Western blot analysis.Peroxynitrite(ONOO-) level and the amount of preOLs were determined by immunocytochemistry.Results The obvious injuries of periventricular white matter,massive loss of positive O4-labelled preOLs,and increased levels of NO,ONOO-and iNOS were observed in neonatal rats with PVL.Compared to the untreated PVL group,the use of 1400W at 0 h,8 hrs and 16 hrs after LPS induction significantly improved white matter injuries,reduced the levels of NO,ONOO-and iNOS,and increased the amount of O4-labelled preOLs.However,the use of 1400W at 24 hrs after LPS induction did not result in the improvements.Conclusions iNOS inhibitor 1400W can effectively block the toxicity of LPS-activated microglia to preOLs and protect cerebral white matter through inhibiting iNOS and reducing the production of NO and ONOO-.The use of 1400W within 16 hrs after LPS induction may provide cerebral protections in neonatal rats with PVL.