title: Endothelinergic signaling during recovery of brain cortical lesions.
abstract: OBJECTIVE
  Recovery of brain lesions has been associated with increased activation and migration of endogenous neural stem cells, glia, and endothelium. To understand the role of endothelinergic signaling in these phenomena we studied devascularizing lesions of mouse brain cortex. Our specific aims were to: (i) describe the endothelinergic cell phenotypes appearing within the lesions; and (ii) evaluate the effect of endothelinergic blockade on the injured cortex.
  
  
  METHODS
  C57BL/6 mice were anesthetized and submitted to devascularization lesions of the right M1 cortical area. A group of mice was daily treated with tezosentan, a dual endothelinergic receptor blocker. Mice were euthanatized 5 days after surgery and the injured area was studied with immunohistochemistry for endothelin, endothelin receptor B, glial fibrillary acidic protein, prominin-1, nestin, and phospho-histone H3.
  
  
  RESULTS
  The injured cortex exhibited a large increase of multipolar endothelin(+), endothelin receptor B(+), glial fibrillary acidic protein(+), prominin-1(+), and nestin(+) cells. These markers appeared in different combinations. Tezosentan treatment reduced the perilesional expression of glial fibrillary acidic protein and decreased the number of proliferating cell nuclei displaying phospho-histone H3.
  
  
  CONCLUSIONS
  Our observations suggest that endothelinergic cells surrounding the lesion belong to a mixed population including reactive glia and neural progenitor cells. Findings in tezosentan-treated mice probably reflect a decrease of reactive gliosis with a still unknown effect on neural progenitor cells.
authors.affiliation: Facultad de Ciencias Biomédicas, Universidad Austral, Pilar B1629AHJ, Argentina.
authors.forename: Mauricio M
authors.initials: MM
authors.lastname: Castañeda
authors.forename: Marisa A
authors.initials: MA
authors.lastname: Cubilla
authors.forename: Tomás
authors.initials: T
authors.lastname: Bachor
authors.forename: Angela M
authors.initials: AM
authors.lastname: Suburo
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D044022:Receptor, Endothelin A / Q000502:physiology; D044023:Receptor, Endothelin B / Q000502:physiology; D020127:Recovery of Function / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology / Q000502:physiology
chemical_list: D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B