The Role of HIF-Prolyl Hydroxylase in Maintaining the Morphological Integrity of the Cerebral Cortex During In Vivo Modeling of Acute Hypobaric Hypoxia

Hypoxia is a common pathological condition that contributes to the development of various neurological disorders. Hypoxia-inducible factor (HIF) represents a promising therapeutic target for enhancing resistance to hypoxia and correcting neuronal dysfunction in the post-hypoxic period. In this study, the effects of two classes of HIF-prolyl hydroxylase (HIF-PHD) inhibitors on the resistance of C57BL/6 mice to hypoxic injury were investigated. The findings demonstrated that the HIF-PHD inhibitors Roxadustat and Adaptaquin exert a neuroprotective effect in hypoxic conditions by increasing the animals' resistance to acute hypobaric hypoxia. Among the tested compounds, Adaptaquin at a dose of 10 mg/kg exhibited the highest efficacy, reducing neuronal damage and edema in the prefrontal cortex during the post-hypoxic period and promoting the recovery of cognitive and motor functions. These results suggest the potential of HIF-PHD inhibitors for the treatment of hypoxic brain injury and neurodegenerative diseases.