Cerebral ischemia induces angiogenesis within and around infarcted tissue. The protection of existing and growth of new blood vessels may contribute to a more favorable outcome. The present study assessed whether angiogenesis can be used as a marker for neurodegeneration/neuroprotection in a model of hypoxia'ischemia (HI). Increased CD31 immunoreactivity 7 days post-HI indicated increased angiogenesis compared to controls (P < 0.001). Treatment with the GABAA receptor modulator, clomethiazole (CMZ; 414 mg/kg/day), normalized the level of angiogenesis compared to HI + saline (P < 0.001). Conversely, the non-selective nitric oxide synthase (NOS) inhibitor, l-NAME (5 mg/kg/day), markedly decreased angiogenesis compared to controls (P < 0.001). Circulating plasma levels of IL-1', IL-1ÃŸ and GM-CSF were significantly elevated post-HI. CMZ treatment attenuated these increases while also stimulating IL-10 levels. l-NAME treatment did not alter IL-1' or IL-1ÃŸ levels, but decreased endogenous IL-10 levels and exacerbated the ischemic lesion (P < 0.001). CMZ treatment has been shown to increase NOS levels, while l-NAME halted the HI-induced increase in NOS activity (P < 0.001). We conclude that angiogenesis can be used as a marker of neurodegeneration/neuroprotection for cerebral HI and is correlated to NOS activity and circulating inflammatory mediators.