Hypoxic preconditioning protection is eliminated in HIF-1? knockout mice subjected to neonatal hypoxia-ischemia.

ABSTRACT: Hypoxic preconditioning (HPc) protects the neonatal brain in the setting of hypoxia-ischemia (HI). The mechanisms of protection may depend on activation of hypoxia-inducible factor (HIF-1?). This study sought to clarify the role of HIF-1? after HPc and HI.To induce HPc, HIF-1? knockout and wild-type (WT) mice were exposed to hypoxia at postnatal day 6. At day 7, the mice underwent HI. Brain injury was determined by histology. HIF-1?, downstream targets, and markers of cell death were measured by western blot.HPc protected the WT brain compared with WT without HPc, but did not protect the HIF-1? knockout brain. In WT, HIF-1? increased after hypoxia and after HI, but not with HPc. The HIF-1? knockout showed no change in HIF-1? after hypoxia, HI, or HPc/HI. After HI, spectrin 145/150 was higher in HIF-1? knockout, but after HPc/HI, it was higher in WT. Lysosome-associated membrane protein was higher in WT early after HI, but not later. After HPc/HI, lysosome-associated membrane protein was higher in HIF-1? knockout.These results indicate that HIF-1? is necessary for HPc protection in the neonatal brain and may affect cell death after HI. Different death and repair mechanisms depend on the timing of HPc.

SUBMITTER: Sheldon RA 

PROVIDER: S-EPMC4167022 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature