Principles and Practices of Unbiased Stereology: An Introduction for Bioscientists (Johns Hopkins Univ. Retinal capillary perfusion: spatial and temporal heterogeneity. Dynamic endothelial cell rearrangements drive developmental vessel regression. How calcium signals in myocytes and pericytes are integrated across in situ microvascular networks and control microvascular tone. Photothrombotic induction of capillary ischemia in the mouse cortex during in vivo two-photon imaging. Retinal ischemia induces α-SMA-mediated capillary pericyte contraction coincident with perivascular glycogen depletion. Capillary K +-sensing initiates retrograde hyperpolarization to increase local cerebral blood flow. Animal cells connected by nanotubes can be electrically coupled through interposed gap-junction channels.
Brain tumour cells interconnect to a functional and resistant network. Mouse lines with photo-activatable mitochondria to study mitochondrial dynamics. Nanotubular highways for intercellular organelle transport. Rustom, A., Saffrich, R., Markovic, I., Walther, P. Morphological study of a connexin 43-GFP reporter mouse highlights glial heterogeneity, amacrine cells, and olfactory ensheathing cells. Theofilas, P., Steinhäuser, C., Theis, M. Correlative cryo-electron microscopy reveals the structure of TNTs in neuronal cells. Connexin channel permeability to cytoplasmic molecules. Fine intercellular connections in development: TNTs, cytonemes, or intercellular bridges? Cell Stress 4, 30–43 (2020). Intercapillary bridging cells: immunocytochemical characteristics of cells that connect blood vessels in the retina. A blood capillaries-bridging cell type in adult mammalian brains. Immunofluorescent imaging of capillaries and pericytes in human skeletal muscle and retina. Intervascular strands in the central nervous system. A comparative study of intervascular connective tissue strands in the central nervous system. Die gefassvermehrung in zentralnervensystem. Ueber die Ausbreitung des Epithelium im menschlichen Körper. NG2 cells generate both oligodendrocytes and gray matter astrocytes. Pericyte-mediated regulation of capillary diameter: a component of neurovascular coupling in health and disease. Capillary pericytes regulate cerebral blood flow in health and disease. Capillary pericytes express α-smooth muscle actin, which requires prevention of filamentous-actin depolymerization for detection. Cerebral microvascular pericytes and neurogliovascular signaling in health and disease. Our study thus defines IP-TNTs and characterizes their critical role in regulating neurovascular coupling in the living retina under both physiological and pathological conditions.Īttwell, D., Mishra, A., Hall, C. Notably, pharmacological blockade of Ca 2+ influx preserves IP-TNTs, rescues light-evoked capillary responses and restores blood flow after reperfusion. IP-TNT damage following ablation or ischaemia disrupts intercellular Ca 2+ waves, impairing blood flow regulation and neurovascular coupling. Using two-photon microscope live imaging, we demonstrate that retinal pericytes rely on IP-TNTs to control local neurovascular coupling and coordinate light-evoked responses between adjacent capillaries. We provide evidence that these (i) have an open-ended proximal side and a closed-ended terminal (end-foot) that connects with distal pericyte processes via gap junctions, (ii) carry organelles including mitochondria, which can travel along these processes, and (iii) serve as a conduit for intercellular Ca 2+ waves, thus mediating communication between pericytes. Here we identify nanotube-like processes that connect two bona fide pericytes on separate capillary systems, forming a functional network in the mouse retina, which we named interpericyte tunnelling nanotubes (IP-TNTs).
Pericytes are candidates to regulate microcirculatory blood flow because they are strategically positioned along capillaries, contain contractile proteins and respond rapidly to neuronal stimulation 3, 4, but whether they synchronize microvascular dynamics and neurovascular coupling within a capillary network was unknown.
Pericytes interact with endothelial cells and extend processes that wrap capillaries, covering up to 90% of their surface area 1, 2. Signalling between cells of the neurovascular unit, or neurovascular coupling, is essential to match local blood flow with neuronal activity.