Editorial: Small and mighty: Brain capillaries in health and disease

Bracko, Oliver; Harraz, Osama F.

doi:10.3389/fnmol.2022.1108978

Cited by 1 publication

(1 citation statement)

References 16 publications

(18 reference statements)

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“…Functional hyperemia is mediated by an ensemble of neurovascular coupling mechanisms that translate enhancements in neuronal activity to increases in local blood flow through the integrated activity of multiple cell types of the neurovascular unit, comprising (in addition to neurons) astrocytes, vascular endothelial cells (ECs), vascular smooth muscle cells (SMCs), and pericytes [2,[5][6][7][8]. Accumulating evidence has indicated that, among these cell types, brain capillary ECs, which are the building blocks of the vast, anastomosing network of capillaries-the smallest and most abundant vessels in the brain parenchyma-play a key role in linking neuronal activity to upstream arteriolar dilation [8][9][10]. Importantly, our recent study demonstrated that capillary EC inward-rectifier Kir2.1 channel is a critical player in the initiation of this inter-cellular communication [8].…”

Section: Introductionmentioning

confidence: 99%

Epidermal Growth Factor Receptors in Vascular Endothelial Cells Contribute to Functional Hyperemia in the Brain

Ferris,

Stine,

Hill-Eubanks

et al. 2023

IJMS

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Functional hyperemia—activity-dependent increases in local blood perfusion—underlies the on-demand delivery of blood to regions of enhanced neuronal activity, a process that is crucial for brain health. Importantly, functional hyperemia deficits have been linked to multiple dementia risk factors, including aging, chronic hypertension, and cerebral small vessel disease (cSVD). We previously reported crippled functional hyperemia in a mouse model of genetic cSVD that was likely caused by depletion of phosphatidylinositol 4,5-bisphosphate (PIP2) in capillary endothelial cells (EC) downstream of impaired epidermal growth factor receptor (EGFR) signaling. Here, using EC-specific EGFR-knockout (KO) mice, we directly examined the role of endothelial EGFR signaling in functional hyperemia, assessed by measuring increases in cerebral blood flow in response to contralateral whisker stimulation using laser Doppler flowmetry. Molecular characterizations showed that EGFR expression was dramatically decreased in freshly isolated capillaries from EC-EGFR-KO mice, as expected. Notably, whisker stimulation-induced functional hyperemia was significantly impaired in these mice, an effect that was rescued by administration of PIP2, but not by the EGFR ligand, HB-EGF. These data suggest that the deletion of the EGFR specifically in ECs attenuates functional hyperemia, likely via depleting PIP2 and subsequently incapacitating Kir2.1 channel functionality in capillary ECs. Thus, our study underscores the role of endothelial EGFR signaling in functional hyperemia of the brain.

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