title: Vascular insufficiency, not inflammation, contributes to chronic gliosis in a rat CNS transplantation model.
abstract: OBJECTIVE
  There is considerable variability in the extent and nature of the glial response to injury and neurodegeneration. Transplantation of fetal cortical tissue onto the brain of neonatal host rats or mice results in region-specific changes dependent on where the fetal tissue is placed. These changes include chronic astrocytic and microglial gliosis, oxidative stress, and altered metabolism of a number of proteins associated with the pathogenesis of Alzheimer's disease. Such changes are only observed in heterotopic (cortex-to-midbrain) grafts and are not observed in homotopic cortex-to-cortex grafts. We investigated two possible triggers for the region-specific gliosis observed in our transplant model hypothesizing that either i) poor vascularization and lack of blood brain barrier integrity or ii) an inflammatory response initiated by the transplantation process, contributed to establishing chronic pathological changes.
  
  
  METHODS
  We analyzed the time course of neovascularization, blood brain barrier permeability and inflammation using a combination of immunohistochemistry, enzyme-linked immunosorbant assay and Evan's blue dye extravasation techniques.
  
  
  RESULTS
  Blood brain barrier permeability and altered neovascularization occurred prior to the onset of gliosis in heterotopic grafts.
  
  
  CONCLUSIONS
  These data suggest that ischemic conditions and blood brain barrier damage can be a primary mechanism that initiates chronic gliosis and associated inflammatory changes in central nervous system tissue.
authors.affiliation: School of Anatomy, Physiology and Human Biology, The University of Western Australia, WA, Australia.|School of Psychiatry and Clinical Neuroscience, The University of Western Australia, WA, Australia.|Experimental and Regenerative Neuroscience, School of Animal Biology, The University of Western Australia, WA, Australia.
authors.forename: Kristyn A
authors.initials: KA
authors.lastname: Bates
authors.affiliation: School of Anatomy, Physiology and Human Biology, The University of Western Australia, WA, Australia.|Department of Neurology, New York University Langone Medical Centre, NY, USA.
authors.forename: Eleanor S
authors.initials: ES
authors.lastname: Drummond
authors.affiliation: School of Anatomy, Physiology and Human Biology, The University of Western Australia, WA, Australia.
authors.forename: Greg S
authors.initials: GS
authors.lastname: Cozens
authors.affiliation: School of Anatomy, Physiology and Human Biology, The University of Western Australia, WA, Australia.|Western Australian Neuroscience Research Institute, Perth, Australia.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Harvey
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001812:Blood-Brain Barrier / Q000473:pathology*; D020214:Cerebrovascular Trauma / Q000209:etiology*; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D016332:Fetal Tissue Transplantation / Q000379:methods*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000150:complications* / Q000601:surgery*; D009389:Neovascularization, Pathologic / Q000209:etiology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
chemical_list: D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D019408:Platelet Endothelial Cell Adhesion Molecule-1
keywords: Astrocytes; blood brain barrier; gliosis; inflammation; neovascularization; transplantation