Hypoxia and hypoxia-inducible factor modulated gene expression in brain: involvement in neuroprotection and cell death

Hypoxia, due to impaired cerebral blood flow, has hazardous effects on brai n structure and function. Therefore, mechanisms should exist to meet the ne eds for hypoxic adaptation via regulation of gene expression. Signaling bet ween the O-2 sensor and the regulator(s) of transcription is only partially characterized and requires regulatory transcription factors. Among these r egulatory proteins, hypoxia-inducible factor-1 (HIF-1) appears to have a ke y role. HIF-1 modulates gene activity in response to low O-2 tensions in th e developing and in the adult brain. Moderate hypoxia may elicit autoprotec tive mechanisms or hypoxia-induced regulators can contribute to mechanisms leading to cell death. Moreover, reactivation of embryonic gene expression may occur after injury-induced hypoxia. Thus, analyses of embryonic and pat hogenic models should help to understand how hypoxia-mediated proliferative /cell death processes are involved in brain development and in the pathogen esis of acute or chronic neurodegenerative brain diseases.