Characterization of the astrocytic response following experimental traumatic brain injury

The present work employs the lateral fluid percussion brain injury model to examine the temporal and regional response of astrocytes to brain injury. In chapter 2 we examine the expression of three proteins that are widely used to label astrocytes, glial fibrillary acidic protein, vimentin and S100, in various brain regions differing with regard to their pattern of neuronal cell loss. Our data indicate that although astrogliosis mirrors the spatial pattern of neuronal cell loss, the expression of vimentin and the cellular morphology of the astrocytes differ in regions where the blood brain barrier has been compromised.^ In chapter 3 we evaluate the number of astrocytes in the ipsilateral hippocampus and characterize the regional and temporal proliferation of astrocytes. Our study reveals a significant astrocyte cell loss in the ipsilateral hippocampus 1 week following lateral fluid percussion brain injury. We identify a small degree of astrocyte proliferation primarily in the injured cortex and hippocampus where the blood brain barrier is compromised. Astrocyte proliferation reached a maximum around 3 days, thereafter the majority of cells proliferating were microglia and inflammatory cells.^ One of the mechanisms proposed for the failure of neurons to regenerate after brain injury, is inhibition of neurite outgrowth by sulphated proteoglycans on the surface of reactive astrocytes. Chapter 4 therefore examines the expression of chondroitin sulphate proteoglycan and the syndecan core proteins that contain sulphated proteoglycan chains by reactive astrocytes. Since fibroblast growth factor 2 (FGF2) has been shown to be activated by a sulphated proteoglycan we have also investigated its expression in association with syndecan core protein expression. Syndecan 1 and 2 are shown to increase on the surface of all reactive astrocytes at the same time FGF-2 increases in the nucleus of reactive astrocytes. Chondroitin sulphate proteoglycan, on the other hand, is only expressed on astrocytes in regions where there is extensive neuronal cell loss and a compromised blood brain barrier, suggesting it may participate in forming an inhibitory scar to reseal the brain after injury.