Normobaric oxygen therapy inhibits HIF-1α and VEGF expression in perihematoma and reduces neurological function defects

It is unknown whether normobaric oxygen (NBO) therapy exerts neuroprotective effects against human intracerebral hemorrhage (ICH). In this study, the potential of NBO therapy for salvaging brain damage following ICH was investigated in a rodent model with oxygen delivered at different concentrations. A total of 164 male Sprague-Dawley rats were induced with ICH using a collagenase injection and divided randomly into one ICH control group (no treatment, n=86) and three NBO treatment groups (35, 50, or 90% oxygen, n=26/group). Twenty-six rats were used as sham controls. The Neurological Severity Score (NSS) was evaluated. Contents of brain water, hypoxia-inducible factor 1α (HIF-1α), and vascular endothelial growth factor (VEGF) were measured in the perihematoma. A cellular apoptosis assay was performed. Compared with the sham control group, the ICH control group had higher NSS following ICH, which peaked at 24 h and began to decrease after 72 h. ICH rats also showed higher contents of brain water, HIF-1α, and VEGF (peaked at 72 h) in the ipsilateral perihematoma tissue than in the contralateral brain tissue. Compared with the ICH control group, all NBO groups showed improved NSSs, decreased contents of brain water, HIF-1α and VEGF, and fewer apoptotic cells in the perihematoma at 72 h after ICH, but statistical significance of these changes was achieved only with oxygen delivered at 90% (P<0.05, two-way analysis of variance). These results suggest that NBO therapy with oxygen delivered at 90% conferred best neuroprotection to ICH rats, potentially through amelioration of brain edema by suppressing HIF-1α and VEGF expression in the perihematoma.