Axonal injury from oxygen-glucose deprivation (OGD) is potentiated through excitotoxic mechanisms mediated by oligodendrocytes in cultures and brain slices (Baltan Tekkok et al, 2001; Underhill et al., SFN 2002). In the presence of primary oligodendrocytes, cultured axons become vulnerable to transient OGD or direct application of kainate. We examined the impact of microglia on cortical axons isolated in a modified Campenot chamber. 100 µM kainate application for two hours had no effect on cortical axons or on axons in co-culture with microglia, as assessed 24 hours later by length of SMI31 immunoreactive axons. Kainate also had no effect on the number of microglia as assessed by lectin immunochemistry. In contrast, brief OGD (10 min) substantially injured axons in co-culture with microglia, but had no effect on microglia or on axons in culture alone. OGD-induced axon injury was not blocked the non-NMDA receptor antagonist, CNQX (30 µM). Inhibition of nitric oxide synthase (NOS) activity with N-Nitro-L-arg...