Effects of deferoxamine-activated hypoxia-inducible factor-1 on the brainstem after subarachnoid hemorrhage in rats

Tomohito Hishikawa, Shigeki Ono, Tomoyuki Ogawa, Koji Tokunaga, Kenji Sugiu, Isao Date

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)

Abstract

OBJECTIVE: Hypoxia-inducible factor (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-1 expression and subarachnoid hemorrhage (SAH) and to characterize the effects of deferoxamine (DFO)-induced increases in HIF-1 protein levels on the brainstem and the basilar artery (BA) after experimental SAH. METHODS: Rat single- and double-hemorrhage models (injected on Days 0 and 2) of SAH were used. We assessed the time courses for HIF-1 protein levels in the brainstems and the BA diameters within 10 minutes and 6 hours on Days 1 and 2 in the single-SAH model, and also on Day 7 in the double-SAH model. After induction of double hemorrhage in rats, DFO was injected intraperitoneally. We then evaluated HIF-1 protein expression and brainstem activity, BA diameter, and brainstem blood flow. RESULTS: After the rats experienced SAH, HIF-1 protein expression was significantly greater at 10 minutes in the single-injection model and at 7 days in the double-injection model than at similar time points in the control group, and these increases correlated with degrees of cerebral vasospasm. DFO injection resulted in significant increases in HIF-1 protein expression and activity in the brainstems of rats with SAH, compared with the rats with SAH that were given placebos, and the rats without SAH in the double-hemorrhage model. Cerebral vasospasm and reduction of brainstem blood flow were significantly attenuated in the rats that were administered DFO. CONCLUSION: These results show that a DFO-induced increase in HIF-1 protein level and activity exerts significant attenuation of BA vasospasm and reduction of brainstem blood flow in the rat model of SAH. DFO may be a promising agent for treating clinical SAH.

Original languageEnglish
Pages (from-to)232-240
Number of pages9
JournalNeurosurgery
Volume62
Issue number1
DOIs
Publication statusPublished - Jan 2008

Keywords

  • Brainstem
  • Cerebral vasospasm
  • Deferoxamine
  • Hypoxia-inducible factor-1
  • Rats
  • Subarachnoid hemorrhage

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

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