Soluble Nogo66
receptor-Fc protein (
sNgR-Fc) enhances axonal regeneration following central nervous system injury. However, the underlying mechanisms remain unclear. In this study, we investigated the effects of
sNgR-Fc on the proliferation and differentiation of neural progenitor cells. The photothrombotic cortical injury model of
ischemic stroke was produced in the parietal cortex of Sprague-Dawley rats. The rats with photothrombotic cortical injury were randomized to receive infusion of 400 μg/kg
sNgR-Fc (
sNgR-Fc group) or an equal volume of
phosphate-buffered saline (photothrombotic cortical injury group) into the lateral ventricle for 3 days. The effects of
sNgR-Fc on the proliferation and differentiation of endogenous neural progenitor cells were examined using
BrdU staining. Neurological function was evaluated with the Morris water maze test. To further examine the effects of
sNgR-Fc treatment on neural progenitor cells, photothrombotic cortical injury was produced in another group of rats that received
transplantation of neural progenitor cells from the hippocampus of embryonic Sprague-Dawley rats. The animals were then given an infusion of
phosphate-buffered saline (neural progenitor cells group) or
sNgR-Fc (
sNgR-Fc + neural progenitor cells group) into the lateral ventricle for 3 days.
sNgR-Fc enhanced the proliferation of cultured neural progenitor cells in vitro as well as that of endogenous neural progenitor cells in vivo, compared with
phosphate-buffered saline, and it also induced the differentiation of neural progenitor cells into neurons. Compared with the photothrombotic cortical injury group, escape latency in the Morris water maze and neurological severity score were greatly reduced, and distance traveled in the target quadrant was considerably increased in the
sNgR-Fc group, indicating a substantial improvement in neurological function. Furthermore, compared with
phosphate-buffered saline infusion,
sNgR-Fc infusion strikingly improved the survival and differentiation of grafted neural progenitor cells. Our findings show that
sNgR-Fc regulates neural progenitor cell proliferation, migration and differentiation. Therefore,
sNgR-Fc is a potential novel
therapy for
stroke and
neurodegenerative diseases, The protocols were approved by the Committee on the Use of Live Animals in Teaching and Research of the University of Hong Kong (approval No. 4560-17) in November, 2015.