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Peer-reviewedCC BY-NC-ND 4.0Neuroreport

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

  • Mareike Fauser1
  • Roy Bockholt2,3
  • Silke Keiner4
  • Grit Weselek1
  • Andreas Hermann5,6,7
  • Christoph Redecker8
  • Alexander Storch1,5,7
8 affiliations
  1. 1Department of Neurology, University Medical Center Rostock, Rostock
  2. 2Departments of Neurology
  3. 3Psychotherapy and Psychosomatic Medicine, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden
  4. 4Department of Neurology, Jena University Hospital, Jena
  5. 5German Centre for Neurodegenerative Diseases (DZNE) Rostock/Greifswald
  6. 6Translational Neurodegeneration Section ‘Albrecht Kossel’, Department of Neurology
  7. 7Center for Transdisciplinary Neurosciences Rostock (CTNR), Rostock University Medical Center, Rostock
  8. 8Department of Neurology and Neurogeriatrics, Medical School OWL, Klinikum Lippe, Bielefeld University, Lemgo, Germany
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Abstract

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.

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Cite

BibTeXRIS
BibTeX
@article{fauser2026vascular,
  title = {{Vascular endothelial growth factor A induces proliferation of adult neural progenitor cells in non-neurogenic periventricular regions of the adult mouse hindbrain}},
  author = {Mareike Fauser and Roy Bockholt and Silke Keiner and Grit Weselek and Andreas Hermann and Christoph Redecker and Alexander Storch},
  journal = {Neuroreport},
  year = {2026},
  month = oct,
  doi = {10.1097/wnr.0000000000002312},
  url = {https://doi.org/10.1097/wnr.0000000000002312},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Vascular endothelial growth factor A induces proliferation of adult neural progenitor cells in non-neurogenic periventricular regions of the adult mouse hindbrain
AU  - Mareike Fauser
AU  - Roy Bockholt
AU  - Silke Keiner
AU  - Grit Weselek
AU  - Andreas Hermann
AU  - Christoph Redecker
AU  - Alexander Storch
PY  - 2026
DA  - 2026/10/28
JO  - Neuroreport
DO  - 10.1097/wnr.0000000000002312
UR  - https://doi.org/10.1097/wnr.0000000000002312
AB  - 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.
SN  - 0959-4965
SN  - 1473-558X
ER  -