Neural progenitor cells regulate capillary blood flow in the postnatal subventricular zone
Benjamin Lacar1, Peter Herman, Jean-Claude Platel
1Department of Neurosurgery and Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06520-8082, USA.
Summary
Neural progenitor cells (NPCs) in the brain
Area of Science:
- Neuroscience
- Developmental Biology
- Vascular Biology
Background:
- Neural progenitor cell (NPC) proliferation in the postnatal subventricular zone (SVZ) is linked to increased blood flow.
- The cellular mechanisms governing this hemodynamic response in the SVZ are not well understood.
Purpose of the Study:
- To investigate the cellular and molecular mechanisms by which neural progenitor cells influence blood flow in the postnatal SVZ.
- To determine the role of B-cells and pericytes in regulating SVZ capillary hemodynamics.
Main Methods:
- Acute brain slice electrophysiology and calcium imaging.
- Pharmacological manipulation using P2Y(2/4) receptor agonists and blockers.
- Genetically engineered mouse models (transgenic and electroporation).
- In vivo blood flow monitoring using laser Doppler flowmetry.
Main Results:
- Calcium increases in pericytes and B-cells induced capillary constrictions via purinergic signaling.
- B-cells, upon calcium increase, release ATP activating pericyte P2Y(2/4) receptors, leading to vasoconstriction.
- Inhibition of P2Y(2/4) receptors resulted in vasodilation.
- Stimulating B-cells/NPCs in vivo increased SVZ blood flow.
Conclusions:
- Postnatal SVZ neural progenitor cells (B-cells) act as transducers of neurometabolic coupling.
- B-cells release ATP and vasodilating factors that modulate pericyte activity and regulate SVZ blood flow.
- These findings reveal a novel mechanism linking neural activity and vascular dynamics in brain development.
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