Effect of deferoxamine-activated hypoxia inducible factor-1 on the brainstem following subarachnoid haemorrhage

Hypoxia inducible factor-1 (HIF-1) is a transcription factor that regulates the expression of various neuroprotective genes. The goal of this study was to clarify the relationship between HIF-1α expression and subarachnoid haemorrhage (SAH) and to determine the effects of the deferoxamine (DFO)-induced increase in HIF-1α protein levels on the brainstem and the basilar artery (BA) following experimental SAH. Rat single- (10min, 6 h, Day 1, Day 2) and double-haemorrhage (Day 7) models of SAH were used. The time course of HIF-1α protein levels of the brainstems and the diameter of the BA was assessed. After an induction of double-haemorrhage in rats, DFO was injected intraperitoneally and HIF-1α protein expression, activity in the brainstems, the diameter of the BA and the brainstem blood flow were assessed. The expression of HIF-1α protein was significantly greater at 10 min and 7 days after SAH. The increase of HIF-1α protein correlated with the degree of cerebral vasospasm. An injection of DFO resulted in significant increases in HIF-1α protein expression and activity in the brainstem of rats with SAH. These results indicate that DFO-induced increase in HIF-1α protein levels and activity exerts neuroprotective and antivasospastic effects. DFO may be a potential therapeutic tool for cerebral vasospasm after SAH.