title: Stroke-evoked angiogenesis results in a transient population of microvessels.
abstract: The role of angiogenesis after stroke is unclear; if angiogenesis supports long-term recovery of blood flow, then microvessel hyperdensity consequent to angiogenesis should persist in infarcted cortex. Here, we assess the long-term stability of ischemia-induced microvessels after 2-h transient rat middle cerebral artery occlusion (tMCAo) followed by 30, 90, or 165 days of reperfusion. Stereological measures of microvessel density were taken adjacent to and within cortical cysts. Vascular permeability was documented by extravasation of immunoglobulin (IgG) and of fluorescein-dextran. After 30 days reperfusion, a significantly increased microvessel volume density (V(V)) was restricted to the inner margin of cystic infarcts as compared with the region external to the infarct or contralateral control cortex (F=42.675, P<0.001). The hyperdense ischemic vasculature was abnormally leaky to IgG and fluorescein-dextran. Between 30 and 90 days of reperfusion, this vessel hyperdensity regressed significantly and then regressed further but less drastically between 90 and 165 days. Phagocytic macrophages were restricted to the infarct and dynamic changes in their number correlated with microvessel regression. Additional ED-1 labeled inflammatory cells were widely distributed inside and external to the infarct, even after 165 days of reperfusion. These data show that ischemia evoked angiogenesis results, at least in part, in transient populations of leaky microvessels and phagocytic macrophages. This suggests that a major role of this angiogenesis is for the removal of necrotic brain tissue.
authors.affiliation: Department of Neurosciences, UCSD School of Medicine, Veterans Administration Medical Center, San Diego, California 92161, USA.
authors.forename: Sung Wook
authors.initials: SW
authors.lastname: Yu
authors.forename: Beth
authors.initials: B
authors.lastname: Friedman
authors.forename: Qun
authors.initials: Q
authors.lastname: Cheng
authors.forename: Patrick D
authors.initials: PD
authors.lastname: Lyden
mesh_terms: D000818:Animals; D002196:Capillaries / Q000473:pathology; D002452:Cell Count; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D007249:Inflammation / Q000473:pathology; D007958:Leukocyte Count; D008264:Macrophages / Q000473:pathology / Q000502:physiology; D008297:Male; D009336:Necrosis; D009389:Neovascularization, Pathologic / Q000473:pathology*; D009474:Neurons / Q000473:pathology; D010586:Phagocytes / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000473:pathology*