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Updated: Jun 6, 2025
Assessment of Vascular Regeneration in the CNS Using the Mouse Retina
Published on: June 23, 2014
Downregulation of Notch Signaling-Stimulated Genes in Neurovascular Unit Alterations Induced by Chronic Cerebral
Dewen Ru1,2,3, Zengyu Zhang3,4, Meng Liu1
1Department of Neurosurgery, Jinshan Hospital, Fudan University, Shanghai, China.
Background:
Chronic cerebral hypoperfusion (CCH) is a key contributor to vascular cognitive impairment (VCI) and is typically associated with blood-brain barrier (BBB) damage. This study investigates the pathological mechanisms underlying CCH-induced neurovascular unit (NVU) alterations.
Methods:
A mouse model of CCH was established using the bilateral common carotid artery stenosis (BCAS) procedure. Decreased cerebral blood flow (CBF) and impaired BBB integrity were assessed. Brain microvessel (BMV)-specific transcriptome profiles were analyzed using RNA-seq, supplemented with published single-cell RNA-seq data.
Results:
RNA-seq revealed neuroinflammation-related gene activation and significant downregulation of Notch signaling pathway genes in BMVs post-BCAS. Upregulated differentially expressed genes (DEGs) were enriched in microglia/macrophages, while downregulated DEGs were prominent in endothelial cells and pericytes. Enhanced activation of vascular-associated microglia (VAM) was linked to neurovascular alterations.
Conclusion:
CCH induces significant NVU changes, marked by microglia-associated neuroinflammation and Notch signaling downregulation. These insights highlight potential therapeutic targets for treating neuroinflammatory and vascular-related neurodegenerative diseases.
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