title: Roles of endothelial cell migration and apoptosis in vascular remodeling during development of the central nervous system.
abstract: OBJECTIVE
  To examine the roles of apoptosis, macrophages, and endothelial cell migration in vascular remodeling during development of the central nervous system.
  
  
  METHODS
  The terminal deoxynucleotide transferase-mediated dUTP nick end labeling (TUNEL) technique was combined with Griffonia simplicifolia isolectin B4 histochemistry to detect apoptotic endothelial cells in retinal whole-mount preparations derived from rats at various stages of postnatal development as well as from rat pups exposed to hyperoxia. Macrophages were detected by immunohistochemistry with the monoclonal antibody ED1, and proliferating endothelial cells were identified by incorporation of bromodeoxyuridine.
  
  
  RESULTS
  Only small numbers of TUNEL-positive endothelial cells were detected during normal development of the retinal vasculature, with the apoptotic cell density in the inner plexus peaking during the first postnatal week and decreasing markedly during the second week, at a time when vessel retraction was widespread. Neither apoptotic endothelial cells nor macrophages were apparent at sites of initiation of vessel retraction. TUNEL-positive endothelial cells were observed in vessels destined to remain. Hyperoxia induced excessive vessel withdrawal, resulting in the generation of isolated vascular segments containing apoptotic endothelial cells. A topographical analysis showed low numbers of proliferating endothelial cells at sites of angiogenesis whereas vascular proliferation was increased in the adjacent inner plexus.
  
  
  CONCLUSIONS
  Endothelial cell apoptosis and macrophages do not initiate vessel retraction, but rather contribute to the removal of redundant cells throughout the vasculature. We suggest that vessel retraction is mediated by endothelial cell migration and that endothelial cells derived from retracting vascular segments are redeployed in the formation of new vessels. Only when retraction results in compromised circulation and redeployment is not possible, does endothelial cell apoptosis occur.
authors.affiliation: Department of Anatomy and Histology, Institute for Biomedical Research, University of Sydney, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Hughes
authors.forename: T
authors.initials: T
authors.lastname: Chang-Ling
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D017209:Apoptosis; D001973:Bromodeoxyuridine; D002465:Cell Movement; D002490:Central Nervous System / Q000098:blood supply* / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D002560:Cerebrovascular Circulation; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006651:Histocytochemistry; D018496:Hyperoxia / Q000378:metabolism / Q000503:physiopathology; D020287:In Situ Nick-End Labeling; D037102:Lectins / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008833:Microcirculation; D018919:Neovascularization, Physiologic; D037121:Plant Lectins; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000166:cytology / Q000254:growth & development; D009418:S100 Proteins / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D005904:Glial Fibrillary Acidic Protein; C045475:Griffonia simplicifolia lectins; D037102:Lectins; D037121:Plant Lectins; D009418:S100 Proteins; C110294:S100A1 protein; D001973:Bromodeoxyuridine