[Corticoids protect oligodentrocyte precursor cells against cytokine-induced damage]

In preterm fetuses an ascending intrauterine inflammation before or during birth can be associated with periventricular leukomalacia (PVL). PVL is characterised by a disrupted. myelination [corrected] due to a loss of oligodendrocyte progenitors. Inflammatory cytokines not only induce apoptotic cell death but in addition prevent the differentiation of the immature A2B5 oligodendrocytc progenitors into the myelinating phenotype. The aim of the present study was to clarify whether corticosteroids can protect oligodendrocyte progenitors from such injury. Cultures [corrected] of more than 90 % A2B5 positive progenitors were prepared from neonatal sprague dawley rats. After 1 day in proliferation medium, cells were treated with interferon-gamma [corrected] (IFN-gamma; 10 U/ml) and tumour necrosis factor-alpha [corrected] (TNF-alpha; 10 ng/ml) for 48 h. In addition, corticosterone (C), deoxycorticosterone (DC), or dexamethasone (DEX) (1 micro M) were applied to the incubation medium of the study groups. After treatment cultures were transferred to media containing factors to promote differentiation of progenitors into thc myelinating phenotype. At culture day 9 total cell [corrected] number was determined. In addition, cells were analysed by immunocytochemistry for A2B5 as well. as by RT-PCR [corrected] and western-blot-analysis of the [corrected] myelin-specific proteins [corrected] MBP, MAG and CNP. Application of INF-gamma and TNF-alpha caused a dramatic decrease in cell number culture day 9 [corrected] More than 30 % of the surviving cells were A2B5-positive compared to 1 % in control dishes. Protein expression of MBP, MAG and CNP as well as mRNA expression, of MAG and MBP were considerably reduced after administration of INF- and TNF-. Co-treatment with, corticosteroids significantly increased total cell count, dexamethasone showing the strongest protective effect.Moreover, corticosteroids alleviated the cytokine induced inhibition in protein- and mRNA-expression [corrected] of MBP, MAG and CNP. Corticosteroids therefore protect oligodendrocyte progenitors from cytokine-induced cell damage.