UCLA

Stroke is a leading cause of adult disability without treatment for long-term recovery. Stroke itself induces a wide-range of repair mechanisms, including the proliferation and long-distance migration of immature neurons (neuroblasts) from the subventricular zone (SVZ) to peri-infarct tissue. These neuroblasts localize to angiogenic blood vessels, forming a neurovascular niche in the peri-infarct zone. The reciprocal signaling between neuroblasts and endothelial cells has not been clearly characterized. A genome-wide expression profiling of stroke-induced neuroblasts and angiogenic vessels in the neurovascular niche led to the discovery of three differentially-regulated ligands derived from neuroblasts. These ligands are Wingless 7a (Wnt7a), pleiotrophin (PTN), and chemokine (C-C motif) ligand 9 (CCL9). Mechanistic gain- and loss-of function studies show Wnt7a, PTN, and CCL9 mediate neural and vascular repair in the subacute and chronic periods after an ischemic cortical stroke.