The majority of the brain's vasculature is composed of intricate capillary networks lined by capillary pericytes. However, it remains unclear whether capillary pericytes influence blood flow. Using two-photon microscopy to observe and manipulate brain capillary pericytes in vivo, we find that their optogenetic stimulation decreases lumen diameter and blood flow, but with slower kinetics than similar stimulation of mural cells on upstream pial and precapillary arterioles. This slow vasoconstriction was inhibited by the clinically used vasodilator fasudil, a Rho-kinase inhibitor that blocks contractile machinery. Capillary pericytes were also slower to constrict back to baseline following hypercapnia-induced dilation, and slower to dilate towards baseline following optogenetically induced vasoconstriction. Optical ablation of single capillary pericytes led to sustained local dilation and a doubling of blood cell flux selectively in capillaries lacking pericyte contact. These data indicate that capillary pericytes contribute to basal blood flow resistance and slow modulation of blood flow throughout the brain.
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http://dx.doi.org/10.1038/s41593-020-00793-2 | DOI Listing |
Neuroscience
December 2024
Departamento de Neurobiología y Neuropatología, IIBCE, MEC, Montevideo, Uruguay. Electronic address:
Iron is one of the crucial elements for CNS development and function and its deficiency (ID) is the most common worldwide nutrient deficit in the world. Iron deficiency anemia (IDA) in pregnant women and infants is a worldwide health problem due to its high prevalence and its irreversible long-lasting effects on brain development. Even with iron supplementation, IDA during pregnancy and/or breastfeeding can result in irreversible cognitive, motor, and behavioral impairments.
View Article and Find Full Text PDFJ Biosci Bioeng
December 2024
Institute of Frontier Science and Technology, Okayama University of Science, Okayama 700-0005, Japan. Electronic address:
Vascular-like tissues composed of cells maintaining their shape and structure at any position in a culture dish without the use of gels or other artificial materials are ideal vascular models to test the effects of candidate drugs on cells without adsorption by artificial materials and analysis of structural changes over time. In this study, we aimed to prepare fiber-shaped cell aggregates composed of human umbilical vein endothelial and mesenchymal stem cells as vascular pericytes anchored to the bottom of culture dishes at a defined location using our developed cell self-aggregation technique and dumbbell-shaped culture groove. The fiber-shaped cell aggregates maintained their shape for at least two weeks without rupture, and histological analysis revealed that they formed a unique tissue structure with a gapless endothelial layer on the outer surface and capillary-like structures oriented in the same direction as the long axis of the fiber in the medial side.
View Article and Find Full Text PDFBiophys J
December 2024
Department of Pharmacology, Larner College of Medicine, Vermont Center for Cardiovascular and Brain Health, University of Vermont, Burlington, VT, 05405, USA. Electronic address:
Amyloid-beta (Aβ) peptide accumulation on blood vessels in the brain is a hallmark of neurodegeneration. While Aβ peptides constrict cerebral arteries and arterioles, their impact on capillaries is less understood. Aβ was recently shown to constrict brain capillaries through pericyte contraction, but whether-and if so how-Aβ affects endothelial cells (ECs) remains unknown.
View Article and Find Full Text PDFDiabetes
December 2024
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Miami Miller School of Medicine.
The COVID-19 pandemic has profoundly affected human health, yet the mechanisms underlying its impact on metabolic and vascular systems remain incompletely understood. Clinical evidence suggests that SARS-CoV-2 directly disrupts vascular homeostasis, with perfusion abnormalities observed in various tissues. The pancreatic islet, a key endocrine mini-organ reliant on its microvasculature for optimal function, may be particularly vulnerable.
View Article and Find Full Text PDFZhonghua Wei Zhong Bing Ji Jiu Yi Xue
November 2024
Department of Pediatric Critical Care Medicine, Affiliated People's Hospital of Guizhou Medical University, Guiyang 550000, Guizhou, China. Corresponding author: Huang Dong, Email:
Acute lung injury (ALI) is a common respiratory disease in clinical practice, which can progress to acute respiratory distress syndrome and endanger the patient's life. Pericytes are a class of cells that directly contact the microvascular basement membrane in the microvascular bed and communicate with endothelial cells, and their distribution and interaction with endothelial cells help to define and maintain local microvascular characteristics. In recent years, pericytes have became one of the most important indicators of ALI.
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