Subventricular zone cytogenesis provides trophic support for neural repair in a mouse model of stroke

Author:

Williamson Michael R.ORCID,Le Stephanie P.,Franzen Ronald L.ORCID,Donlan Nicole A.,Rosow Jill L.,Nicot-Cartsonis Mathilda S.,Cervantes Alexis,Deneen BenjaminORCID,Dunn Andrew K.,Jones Theresa A.ORCID,Drew Michael R.ORCID

Abstract

AbstractStroke enhances proliferation of neural precursor cells within the subventricular zone (SVZ) and induces ectopic migration of newborn cells towards the site of injury. Here, we characterize the identity of cells arising from the SVZ after stroke and uncover a mechanism through which they facilitate neural repair and functional recovery. With genetic lineage tracing, we show that SVZ-derived cells that migrate towards cortical photothrombotic stroke in mice are predominantly undifferentiated precursors. We find that ablation of neural precursor cells or conditional knockout of VEGF impairs neuronal and vascular reparative responses and worsens recovery. Replacement of VEGF is sufficient to induce neural repair and recovery. We also provide evidence that CXCL12 from peri-infarct vasculature signals to CXCR4-expressing cells arising from the SVZ to direct their ectopic migration. These results support a model in which vasculature surrounding the site of injury attracts cells from the SVZ, and these cells subsequently provide trophic support that drives neural repair and recovery.

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary

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