Intraspinal transplantation of subventricular zone-derived neural progenitor cells improves phrenic motor output after high cervical spinal cord injury

Abstract Following spinal cord injury (SCI), intraspinal transplantation of neural progenitor cells (NPCs) harvested from the forebrain sub-ventricular zone (SVZ) can improve locomotor outcomes. Cervical SCI often results in respiratory-related impairments, and here we used an established model cervical SCI (C2 hemisection, C2Hx) to confirm the feasibility of mid-cervical transplantation of SVZ-derived NPCs and the hypothesis that that this procedure would improve spontaneous respiratory motor recovery. NPCs were isolated from the SVZ of enhanced green fluorescent protein (GFP) expressing neonatal rats, and then intraspinally delivered immediately caudal to an acute C2Hx lesion in adult non-GFP rats. Whole body plethysmography conducted at 4 and 8 wks post-transplant demonstrated increased inspiratory tidal volume in SVZ vs. sham transplants during hypoxic ( P  = 0.003) or hypercapnic respiratory challenge ( P  = 0.019). Phrenic nerve output was assessed at 8 wks post-transplant; burst amplitude recorded ipsilateral to C2Hx was greater in SVZ vs. sham rats across a wide range of conditions ( e.g. , quiet breathing through maximal chemoreceptor stimulation; P P