Vascular endothelial growth factor A induces proliferation of adult neural progenitor cells in non-neurogenic periventricular regions of the adult mouse hindbrain.

BACKGROUND

In addition to the well-established neurogenic niche of the ventricular-subventricular zone (V-SVZ) of the lateral ventricles, neural stem/progenitor cells (NPCs) have been identified in the periventricular regions (PVRs) throughout the adult mouse ventricular system. The potential role of these NPCs in neuroplasticity or neurorestoration, however, remains largely unexplored.

OBJECTIVE

Given that vascular endothelial growth factor A (VEGF-A) has been shown to promote stem cell proliferation in the V-SVZ, this study aimed to investigate VEGF-A effects on NPC proliferation in mid- and hindbrain PVRs.

METHODS

Healthy adult male C57BL/6 mice received continuous intracerebroventricular infusions of VEGF-A or artificial cerebrospinal fluid for 7 days. To label proliferating cells, daily injections of thymidine analogues were administered. Proliferation was assessed in the PVRs of the medial wall of the lateral ventricles, the third ventricle, and the aqueduct/fourth ventricle (hindbrain).

RESULTS

Continuous VEGF-A infusion significantly increased overall cell proliferation in the third ventricle and hindbrain PVRs compared with controls, but not in the medial wall of the lateral ventricles. In hindbrain PVRs, the increase in proliferation was restricted to GFAP+Sox2+ NPCs. In contrast, in the wall of the third ventricle, VEGF-A infusion led to a significant reduction in ependymocyte proliferation, with no specific increase observed in other cell types.

CONCLUSION

While continuous intracerebroventricular VEGF-A infusion enhances NPC proliferation in mid- and hindbrain PVRs, total counts of proliferating cells remain low, and significant lineage progression is not observed. These findings challenge the proposed neurorestorative role of resident NPCs in these brain regions, particularly in the context of neurodegenerative disorders such as Parkinson's disease.