Enhanced brain angiogenesis in chronic cerebral hypoperfusion after administration of plasmid human vascular endothelial growth factor in combination with indirect vasoreconstructive surgery.
OBJECTIVE
Vascular endothelial growth factor (VEGF) is a secreted mitogen associated with angiogenesis. The conceptual basis for therapeutic angiogenesis after plasmid human VEGF gene (phVEGF) transfer has been established in patients presenting with limb ischemia and myocardial infarction. The authors hypothesized that overexpression of VEGF using a gene transfer method combined with indirect vasoreconstruction might induce effective brain angiogenesis in chronic cerebral hypoperfusion, leading to prevention of ischemic attacks.


METHODS
A chronic cerebral hypoperfusion model induced by permanent ligation of both common carotid arteries in rats was used in this investigation. Seven days after induction of cerebral hypoperfusion, encephalomyosynangiosis (EMS) and phVEGF administration in the temporal muscle were performed. Fourteen days after treatment, the VEGF gene therapy group displayed numbers and areas of capillary vessels in temporal muscles that were 2.2 and 2.5 times greater, respectively, in comparison with the control group. In the brain, the number and area of capillary vessels in the group treated with the VEGF gene were 1.5 and 1.8 times greater, respectively, relative to the control group.


CONCLUSIONS
In rat models of chronic cerebral hypoperfusion, administration of phVEGF combined with indirect vasoreconstructive surgery significantly increased capillary density in the brain. The authors' results indicate that administration of phVEGF may be an effective therapy in patients with chronic cerebral hypoperfusion, such as those with moyamoya disease.
Kusaka
Noboru
N
Department of Neurological Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
Sugiu
Kenji
K
Tokunaga
Koji
K
Katsumata
Atsushi
A
Nishida
Ayumi
A
Namba
Katsunari
K
Hamada
Hirofumi
H
Nakashima
Hiroyuki
H
Date
Isao
I
D000818:Animals; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000473:pathology / Q000601:surgery* / Q000628:therapy*; D002196:Capillaries; D002548:Cerebral Revascularization; D002908:Chronic Disease; D003131:Combined Modality Therapy; D015316:Genetic Therapy / Q000379:methods*; D008297:Male; D009072:Moyamoya Disease / Q000473:pathology / Q000601:surgery / Q000628:therapy; D018919:Neovascularization, Physiologic; D010957:Plasmids; D051381:Rats; D017208:Rats, Wistar; D013703:Temporal Muscle / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A