title: Optimal dose of plasmid vascular endothelial growth factor for enhancement of angiogenesis in the rat brain ischemia model.
abstract: Vascular endothelial growth factor (VEGF) administration has recently been assessed as a therapeutic strategy for ischemic diseases including brain ischemia because of its angiogenic effect. However, VEGF also causes detrimental adverse effects by increasing vascular permeability. This study examined whether plasmid human VEGF (phVEGF) administration induced angiogenic effects in the rat brain ischemia model caused by permanent ligation of both common carotid arteries, and investigated the occurrence of adverse effects. Administration of various doses (0-200 microg) of phVEGF in the temporal muscle was followed by encephalo-myo-synangiosis. Thirty days after treatment, the numbers and areas of capillaries per field in the extracted brains were analyzed with the National Institutes of Health Image software program. The maximal angiogenic effect occurred with a 100 microg dose of phVEGF in the numbers and areas of capillaries in the VEGF-treated brains. Histological examination showed no apparent adverse effects in the brain parenchyma even at the highest administration dose (200 microg) of phVEGF. The maximal angiogenic effect at the optimal dose of phVEGF can be considered under the threshold to cause serious adverse effects in the rat brain.
authors.affiliation: Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. katsu55@jasmine.ocn.ne.jp
authors.forename: Atsushi
authors.initials: A
authors.lastname: Katsumata
authors.forename: Kenji
authors.initials: K
authors.lastname: Sugiu
authors.forename: Koji
authors.initials: K
authors.lastname: Tokunaga
authors.forename: Noboru
authors.initials: N
authors.lastname: Kusaka
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Watanabe
authors.forename: Ayumi
authors.initials: A
authors.lastname: Nishida
authors.forename: Katsunari
authors.initials: K
authors.lastname: Namba
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hamada
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakashima
authors.forename: Isao
authors.initials: I
authors.lastname: Date
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000627:therapeutic use*; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002196:Capillaries / Q000254:growth & development / Q000294:innervation / Q000473:pathology; D002548:Cerebral Revascularization / Q000379:methods*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000473:pathology; D006801:Humans; D008297:Male; D018919:Neovascularization, Physiologic / Q000235:genetics* / Q000502:physiology; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000502:physiology / Q000627:therapeutic use*
chemical_list: D043925:Angiogenesis Inducing Agents; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A