title: Ischemia/Reperfusion-induced neovascularization in the cerebral cortex of the ovine fetus.
abstract: Information on the effects of injury on neovascularization in the immature brain is limited. We investigated the effects of ischemia on cerebral cortex neovascularization after the exposure of fetuses to 30 minutes of cerebral ischemia followed by 48 hours of reperfusion (I/R-48), 30 minutes of cerebral ischemia followed by 72 hours of reperfusion (I/R-72), or sham control treatment (Non-I/R). Immunohistochemical and morphometric analyses of cerebral cortex sections included immunostaining for glial fibrillary acidic protein and collagen type IV (a molecular component of the vascular basal lamina) to determine the glial vascular network in fetal brains and Ki67 as a proliferation marker. Cerebral cortices from I/R-48 and I/R-72 fetuses exhibited general responses to ischemia, including reactive astrocyte morphology, which was not observed in Non-I/R fetuses. Cell bodies of reactive proliferating astrocytes, along with large end-feet, surrounded the walls of cerebral cortex microvessels in addition to the thick collagen type IV-enriched basal lamina. Morphometric analysis of the Non-I/R group with the I/R-48 and I/R-72 groups revealed increased collagen type IV density in I/R-72 cerebral cortex microvessels (p < 0.01), which also frequently displayed a sprouting appearance characterized by growing tip cells and activated pericytes. Increases in cerebral cortex basic fibroblast growth factor were associated with neovascularization. We conclude that increased neovascularization in fetal cerebral cortices occurs within 72 hours of ischemia.
authors.affiliation: From the Human Anatomy and Histology Unit, Department of Basic Medical Sciences, Neurosciences, and Sensory Organs, Medical School of Bari University, Bari, Italy (DV, FG, MR); and Department of Pediatrics, The Alpert Medical School of Brown University, Women & Infants Hospital of Rhode Island (NA, GBS, JZ, BSS); and Department of Pathology and Neurosurgery, Rhode Island Hospital (EGS), Providence, Rhode Island.
authors.forename: Daniela
authors.initials: D
authors.lastname: Virgintino
authors.forename: Francesco
authors.initials: F
authors.lastname: Girolamo
authors.forename: Marco
authors.initials: M
authors.lastname: Rizzi
authors.forename: Nigar
authors.initials: N
authors.lastname: Ahmedli
authors.forename: Grazyna B
authors.initials: GB
authors.lastname: Sadowska
authors.forename: Edward G
authors.initials: EG
authors.lastname: Stopa
authors.forename: Jiyong
authors.initials: J
authors.lastname: Zhang
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Stonestreet
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000150:complications*; D002540:Cerebral Cortex / Q000196:embryology / Q000378:metabolism / Q000473:pathology*; D024141:Collagen Type IV / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000378:metabolism / Q000473:pathology; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D018613:Microscopy, Confocal; D009389:Neovascularization, Pathologic / Q000209:etiology* / Q000473:pathology*; D011247:Pregnancy; D015427:Reperfusion Injury / Q000150:complications*; D012756:Sheep; D013997:Time Factors
chemical_list: D024141:Collagen Type IV; D005904:Glial Fibrillary Acidic Protein; D019394:Ki-67 Antigen; D016222:Fibroblast Growth Factor 2