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A High Output Method to Isolate Cerebral Pericytes from Mouse
Published on: January 14, 2020
Mild pericyte deficiency is associated with aberrant brain microvascular flow in aged PDGFRβ+/- mice
Ashley N Watson1, Andree-Anne Berthiaume1,2, Anna V Faino3
1Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.
Abstract:
The receptor tyrosine kinase PDGFRβ is essential for pericyte migration to the endothelium. In mice lacking one allele of PDGFRβ (PDGFRβ+/-), previous reports have described an age-dependent loss of pericytes in the brain, leading to cerebrovascular dysfunction and subsequent neurodegeneration reminiscent of that seen in Alzheimer's disease and vascular dementia. We examined 12-20-month-old PDGFRβ+/- mice to better understand how pericyte loss affects brain microvascular structure and perfusion in vivo. We observed a mild reduction of cortical pericyte number in PDGFRβ+/- mice (27% fewer cell bodies) compared to controls, but no decrease in pericyte coverage of the endothelium. This mild degree of pericyte loss caused no discernable change in cortical microvascular density, length, basal diameter or reactivity to hypercapnia. Yet, it was associated with an increase in basal blood cell velocity, primarily in pre-capillary arterioles. Taken together, our results suggest that mild pericyte loss can lead to aberrant cerebral blood flow despite a lack of apparent effect on microvascular structure and reactivity.
Insights
Mild pericyte loss in PDGFRβ+/- mice alters cerebral blood flow velocity. Despite no structural changes in brain microvasculature, this pericyte reduction impacts blood flow dynamics.
Area of Science:
- Neuroscience
- Vascular Biology
- Cell Biology
Background:
- Platelet-derived growth factor receptor beta (PDGFRβ) is crucial for pericyte function.
- Pericyte loss in the brain is linked to neurodegenerative diseases like Alzheimer's.
- PDGFRβ+/- mice exhibit age-dependent pericyte reduction.
Purpose of the Study:
- To investigate the in vivo effects of mild pericyte loss on brain microvascular structure and perfusion.
- To analyze the impact of reduced PDGFRβ signaling on cerebral hemodynamics.
Main Methods:
- Utilized 12-20-month-old PDGFRβ+/- mice and control littermates.
- Assessed cortical pericyte number and coverage using microscopy.
- Measured microvascular density, diameter, and reactivity to hypercapnia.
- Quantified basal blood cell velocity in cerebral microvasculature.
Main Results:
- A 27% reduction in cortical pericyte cell bodies was observed in PDGFRβ+/- mice.
- No significant decrease in pericyte coverage of the endothelium was found.
- Microvascular density, length, diameter, and hypercapnic reactivity remained unchanged.
- An increase in basal blood cell velocity was noted in pre-capillary arterioles.
Conclusions:
- Mild pericyte loss, even without affecting microvascular structure, can disrupt cerebral blood flow.
- Aberrant cerebral blood flow dynamics may occur in conditions with subtle pericyte deficits.
- Findings suggest a dissociation between microvascular structure and perfusion regulation.

