Affiliations: [a] School of Anatomy, Physiology and Human Biology, The University of Western Australia, WA, Australia | [b] School of Psychiatry and Clinical Neuroscience, The University of Western Australia, WA, Australia | [c] Experimental and Regenerative Neuroscience, School of Animal Biology, The University of Western Australia, WA, Australia | [d] Department of Neurology, New York University Langone Medical Centre, NY, USA | [e] Western Australian Neuroscience Research Institute, Perth, Australia
Correspondence:
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Corresponding author: Kristyn A. Bates, Experimental and Regenerative Neuroscience, School of Animal Biology, M317, The University of Western Australia, 35 Stirling Highway Perth, WA 6009, Australia. Tel.: +61 08 6488 7515; Fax: +61 08 6488 7527; E-mail: [email protected].
Abstract: 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.
