Induction of collateral circulation by hypoxia-inducible factor 1alpha decreased cerebral infarction in the rat.

BACKGROUND

We recently reported that hypoxia-inducible factor 1alpha (HIF-1alpha), HIF-2alpha and cyclooxygenase 2 naked DNA induced angiogenesis in a rat indirect bypass model. In this work, we investigated whether the collateral circulation induced by HIF-1alpha DNA affected the cerebral infarction.

METHODS

We utilized a rat encephalomyosynangiosis (EMS) model and inoculated HIF-1alpha DNA onto the brain surface. These treatments were performed before the cerebral infarction occurred. We thereafter performed middle cerebral artery occlusion on the fifth or tenth day after EMS.

RESULTS

A histological section treated with HIF-1alpha DNA for 10 days showed a well-developed collateral circulation (p<0.05) and a reduction in the infarction volume in comparison to the control DNA (p<0.01).

CONCLUSIONS

These results suggest the feasibility of a novel approach for the treatment of cerebral ischemia via the development of therapeutic collateral circulation, in which neovascularization may be indirectly achieved using a transcriptional regulatory strategy.