| To investigate the function of neuronal Hif-1alpha in hypoxic-ischemic (HI) brain injury and the ability of hypoxic preconditioning (HP) to reduced HI brain injury, mice lacking neuronal Hif-1alpha (KO) were generated using Cre/loxP technology. Nissl, Fluoro-Jade, microtubule-associated protein 2 (MAP2) and glial fibrillary acidic protein (GFAP) staining indicated that neuron-specific deletion of Hif-1alpha increased susceptibility to brain injury in the hippocampus and striatum following both 30 and 50 min of HI. In comparison to control mice, expression of X-linked inhibitor of apoptosis (XIAP) protein was reduced in the hippocampi of KO mice suggesting that decreased levels of pro-survival proteins may contribute to the increased susceptibility of these animals to HI brain injury. The neuroprotective effects of HP were not abolished by deletion of Hif-1alpha in neurons. By contrast, 90 min of HP protected KO, but not control, mice from HI brain injury suggestive of compensatory changes in KO mice that enhanced the effects of HP. |
