title: Increased expression of vascular endothelial growth factor attenuates contusion necrosis without influencing contusion edema after traumatic brain injury in rats.
abstract: To clarify the role of vascular endothelial growth factor (VEGF) in the formation of contusion edema and necrosis after traumatic brain injury, we examined the time course of changes in the VEGF expression (enzyme-linked immunosorbent assay), cerebrovascular permeability (extravasation of Evans blue), and water content (dry-wet weight method) of the contused brain tissue in a cortical impact injury model using rats. In addition, we tested the effects of administration of bevacizumab (VEGF monoclonal antibody) on changes in the cerebrovascular permeability and water content of the contused brain tissue, as well as the neurological deficits (rota rod test) and volume of contusion necrosis. Increased VEGF expression was maximal at 72 h after injury (p<0.003). Increases in cerebrovascular permeability and water content, however, became maximal within 24 h (p<0.001) after injury (p<0.01), respectively. Administration of bevacizumab did not influence these changes in cerebrovascular permeability and water content, but led to a significant rise in the neurological deficits at 72 h-14 days (p<0.05 or 0.01) and the volume of contusion necrosis at 21 days (p<0.001) after injury. These findings suggest that increased expression of VEGF after injury does not contribute to the formation of contusion edema, but attenuates the formation of contusion necrosis. This is probably because of an increased angiogenesis and improved microcirculation in the areas surrounding the core of contusion.
authors.affiliation: 1 Division of Neurosurgery, Department of Neurological Surgery, Nihon University School of Medicine , Tokyo, Japan .
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tado
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Mori
authors.forename: Masamichi
authors.initials: M
authors.lastname: Fukushima
authors.forename: Hideki
authors.initials: H
authors.lastname: Oshima
authors.forename: Takeshi
authors.initials: T
authors.lastname: Maeda
authors.forename: Atsuo
authors.initials: A
authors.lastname: Yoshino
authors.forename: Shin
authors.initials: S
authors.lastname: Aizawa
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Katayama
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000473:pathology; D001929:Brain Edema / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology*; D002199:Capillary Permeability; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D008297:Male; D009336:Necrosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
chemical_list: D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat