SPARC modulates the spinal cord neuroimmune response in experimental autoimmune encephalomyelitis

SPARC (Secreted Protein Acidic and Rich in Cysteine), a secreted glycoprotein, regulates proliferation, migration and differentiation. SPARC is highly expressed in glia and blood vessels during CNS development. SPARC expression is maintained in tissues undergoing rapid turnover and its expression is highly upregulated during injury or disease. SPARC’s modulatory activity in glia and endothelia during injury lead us to investigate the role of SPARC in an animal model of CNS inflammation and demyelination with known BBB dysfunction: Experimental Autoimmune Encephalomyelitis (EAE). We discovered that, in the spinal cord, SPARC is expressed and localized to developing endothelia and radial glia but is down-regulated and retained in specific subpopulations of glia in the adult spinal cord. During the repair response of EAE, CNS glia and endothelia recapitulate their developmental SPARC expression. Furthermore, in the absence of SPARC, EAE onset is delayed even though there is increased blood-brain barrier (BBB) permeability. We provide evidence that SPARC may play a role in neuro-immune and endothelial cross-talk during the repair response following EAE.Medicine, Faculty ofMedicine, Department ofExperimental Medicine, Division ofGraduat