Vascular insufficiency, not inflammation, contributes to chronic gliosis in a rat CNS transplantation model

Restor Neurol Neurosci. 2016;34(2):313-23. doi: 10.3233/RNN-150591.


Purpose: 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.

Conclusion: 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.

Keywords: Astrocytes; blood brain barrier; gliosis; inflammation; neovascularization; transplantation.

MeSH terms

  • Animals
  • Animals, Newborn
  • Blood-Brain Barrier / pathology*
  • Cerebrovascular Trauma / etiology*
  • Chronic Disease
  • Cytokines / metabolism
  • Disease Models, Animal
  • Embryo, Mammalian
  • Fetal Tissue Transplantation / methods*
  • Glial Fibrillary Acidic Protein / metabolism
  • Gliosis / complications*
  • Gliosis / surgery*
  • Neovascularization, Pathologic / etiology*
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Rats
  • Rats, Inbred F344
  • Time Factors


  • Cytokines
  • Glial Fibrillary Acidic Protein
  • Platelet Endothelial Cell Adhesion Molecule-1