Microglial cells in the healthy adult CNS possess a characteristic ramified morphology and show little or no expression of major histocompatibility complex (MHC) or adhesion molecules. In contrast, microglial cells isolated from newborn rat brains inevitably show a nonramified amoeboid morphology and express immunoeffector molecules, such as MHC class I and II, and various adhesion molecules thought to be markers of microglial activation. Furthermore, they produce large amounts of oxygen radicals. Treatment of cultured microglial cells with the antioxidants vitamin E (α‐tocopherol) and vitamin C (ascorbic acid) induced a ramified microglial morphology after 48 h in vitro, otherwise only seen in healthy adult CNS tissue or in co‐culture with astrocytes. Morphological transformation of microglial cells was quantified by morphometric analysis and was found to be statistically significant. Ramification of microglia induced by vitamin E was accompanied by downregulated expression of adhesion molecules leukocyte function antigen‐1, very late antigen‐4, and intercellular adhesion molecule‐1, as assessed by FACS analysis and immunocytochemistry. Moreover, cell numbers of microglia treated with vitamin E remained stable within 7 days in vitro, whereas untreated controls showed a cell loss of 81.5%. These data show that vitamin E acts as a protective compound in dissociated microglial cell cultures. In conclusion, our results suggest that vitamin E and vitamin C shift microglial morphology toward ramification and induce an immunological deactivation. These changes seem to be mediated by oxidative mechanisms. GLIA 22:180–188, 1998. © 1998 Wiley‐Liss, Inc.

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During brain development, the majority of neurons undergo programmed cell death. It is now clear that caspases are involved in this process of selective induction of neuronal apoptosis, yet the signals for this caspase activation remain undefined. As an upstream activator of these enzymes, the death receptor CD95 (Fas, APO1) was recently shown on neurons in the cornu ammonis (CA)2 and CA3 hippocampal subfields of early postnatal mice and rats. In vitro, cortical neuroblast cells are susceptible to CD95 ligand (CD95L, FasL, APO-1 L)-induced apoptosis. It was therefore suggested that the CD95/CD95L system is involved in neuronal apoptosis during hippocampal development. We therefore performed a blinded study comparing field size and neuronal density in the hippocampi of p20 CD95-deficient (lpr), CD95L-deficient (gld) and C57 mice. Whereas field sizes did not differ significantly between these strains, paired Mann-Whitney analyses revealed an increased number of neurons in the CA2 regions of CD95-deficient mice (P = 0.008), and minor, yet at 1% nonsignificant, differences between gld, lpr and C57 strains in the CA1 and CA3 regions. However, joint comparison of the three strains using the Kruskal-Wallis test rendered all differences insignificant. We conclude that the CD95/CD95L system is either not involved, or can be replaced by alternate mechanisms in the control of neuronal populations during hippocampal development.

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