Remyelination failure following white matter stroke: new targets for repair identified by oligodendrocyte progenitor cell transcriptome database.
White matter stroke is a common problem in the elderly population and makes up one third of all ischemic stroke cases. Stroke causes localized process of white matter cell death but also a subsequent regenerative response with the activation of oligodendrocyte progenitor cells (OPCs). This dissertation details the OPC regenerative response and their cellular fate in a mouse model of white matter stroke. The stroke environment supports successful OPC proliferation but lacks pro-myelinating factors that lead to OPC differentiation arrest. Novel transcriptome studies are conducted for genomic comparison of progenitors across two stroke time points in order to determine the molecular systems underlying OPC differentation arrest. The resulting transcriptome database contained several previously described inhibitory mechanisms in addition to novel targets, most important of which were Matrilin 2 and Inhibin A. In-vitro studies confirmed the contrasting effects of Matrilin 2 and Inhibin A on OPC differentiation and oligodendrocyte maturation that makes them promising therapeutic targets for white matter stroke recovery.