Abstract
Object. 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.
| Original language | English |
|---|---|
| Pages (from-to) | 882-890 |
| Number of pages | 9 |
| Journal | Journal of Neurosurgery |
| Volume | 103 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Nov 2005 |
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Keywords
- Angiogenesis
- Chronic cerebral hypoperfusion
- Indirect vasoreconstruction
- Moyamoya disease
- Rat
- Vascular endothelial growth factor
ASJC Scopus subject areas
- Clinical Neurology
- Neuroscience(all)
Cite this
Enhanced brain angiogenesis in chronic cerebral hypoperfusion after administration of plasmid human vascular endothelial growth factor in combination with indirect vasoreconstructive surgery. / Kusaka, Noboru; Sugiu, Kenji; Tokunaga, Koji; Katsumata, Atsushi; Nishida, Ayumi; Namba, Katsunari; Hamada, Hirofumi; Nakashima, Hiroyuki; Date, Isao.
In: Journal of Neurosurgery, Vol. 103, No. 5, 11.2005, p. 882-890.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Enhanced brain angiogenesis in chronic cerebral hypoperfusion after administration of plasmid human vascular endothelial growth factor in combination with indirect vasoreconstructive surgery
AU - Kusaka, Noboru
AU - Sugiu, Kenji
AU - Tokunaga, Koji
AU - Katsumata, Atsushi
AU - Nishida, Ayumi
AU - Namba, Katsunari
AU - Hamada, Hirofumi
AU - Nakashima, Hiroyuki
AU - Date, Isao
PY - 2005/11
Y1 - 2005/11
N2 - Object. 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.
AB - Object. 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.
KW - Angiogenesis
KW - Chronic cerebral hypoperfusion
KW - Indirect vasoreconstruction
KW - Moyamoya disease
KW - Rat
KW - Vascular endothelial growth factor
UR - http://www.scopus.com/inward/record.url?scp=32044451582&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=32044451582&partnerID=8YFLogxK
U2 - 10.3171/jns.2005.103.5.0882
DO - 10.3171/jns.2005.103.5.0882
M3 - Article
C2 - 16304993
AN - SCOPUS:32044451582
VL - 103
SP - 882
EP - 890
JO - Journal of Neurosurgery
JF - Journal of Neurosurgery
SN - 0022-3085
IS - 5
ER -