PDGFR-beta signaling mediates endogenous neurogenesis after postischemic neural stem/progenitor cell transplantation in mice

ABSTRACT

Objective

Although platelet-derived growth factor receptor (PDGFR)-β mediates the self-renewal and multipotency of neural stem/progenitor cells (NSPCs) in vitro and in vivo, its mechanisms of activating endogenous NSPCs following ischemic stroke still remain unproven.

Methods

The exogenous NSPCs were transplanted into the ischemic striatum of PDGFR-β conditionally neuroepithelial knockout (KO) mice at 24 h after transient middle cerebral artery occlusion (tMCAO). 5-Bromo-2’-deoxyuridine (BrdU) was intraperitoneally injected to label the newly formed endogenous NSPCs. Infarction volume was measured, and behavioral tests were performed. In the subventricular zone (SVZ), proliferation of endogenous NSPCs was tested, and synapse formation and expression of nutritional factors were measured.

Results

Compared with control mice, KO mice showed larger infarction volume, delayed neurological recovery, reduced numbers of BrdU positive cells, decreased expression of neurogenic factors (including neurofilament, synaptophysin, and brain-derived neurotrophic factor), and decreased synaptic regeneration in SVZ after tMCAO. Moreover, exogenous NSPC transplantation significantly alleviated neurologic dysfunction, promoted neurogenesis, increased expression of neurologic factors, and diminished synaptic deformation in SVZ of FL mice after tMCAO but had no beneficial effect in KO mice.

Conclusion

PDGFR-β signaling may promote activation of endogenous NSPCs after postischemic NSPC transplantation, and thus represents a novel potential regeneration-based therapeutic target.

KEYWORDS:

• Cerebral ischemia
• neural stem/progenitor cells
• platelet-derived growth factor receptor-beta
• transplantation
• brain-derived neurotrophic factor

Acknowledgments

We thank Julia Bates, PhD (Oxford Science Manuscripts) for her assistance in the preparation of this manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (Grant numbers: 81860228, 81460190 and 81360186). It was also supported by Dongguan Science and Technology of Social Development Program (Grant numbers: 20211800904462), the Natural Science Foundation of Inner Mongolia (Grant numbers: 2018MS03004), the Prior Science and Technology Activities Project of the Returned Overseas Chinese Scholars in the Inner Mongolia Autonomous Region, as well as the Medical and Health Planning Project of the Inner Mongolia Autonomous Region Health Planning Commission (Grant numbers: 201703009).