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.
Anan
Mitsuhiro
M
Department of Neurosurgery, Oita University School of Medicine, Yufu, Oita, Japan.
Abe
Tatsuya
T
Shimotaka
Kazunori
K
Kamida
Tohru
T
Kubo
Takeshi
T
Fujiki
Minoru
M
Kobayashi
Hidenori
H
D000818:Animals; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D002536:Cerebral Arteries / Q000187:drug effects / Q000378:metabolism; D002544:Cerebral Infarction / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D003097:Collateral Circulation / Q000187:drug effects* / Q000235:genetics; D004247:DNA / Q000235:genetics / Q000494:pharmacology*; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D004247:DNA