Mural Cells in the Brain Capillaries: Pericytes

2021 ◽  
Author(s):  
Ruihua Sun ◽  
Wei Li ◽  
Chenhao Gao ◽  
Jiewen Zhang ◽  
Junkui Shang
Keyword(s):  
Brain Capillaries ◽  
Mural Cells ◽  
The Brain

scholarly journals Endothelial cell-specific reduction of heparan sulfate suppresses glioma growth in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Takamasa Kinoshita ◽  
Hiroyuki Tomita ◽  
Hideshi Okada ◽  
Ayumi Niwa ◽  
Fuminori Hyodo ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Heparan Sulfate ◽  
Vascular Endothelium ◽  
Wild Type ◽  
Brain Capillaries ◽  
Gene Encoding ◽  
Glioma Growth ◽  
Underlying Mechanisms ◽  
The Brain

Abstract Purpose Heparan sulfate (HS) is one of the factors that has been suggested to be associated with angiogenesis and invasion of glioblastoma (GBM), an aggressive and fast-growing brain tumor. However, it remains unclear how HS of endothelial cells is involved in angiogenesis in glioblastoma and its prognosis. Thus, we investigated the effect of endothelial cell HS on GBM development. Methods We generated endothelial cell-specific knockout of Ext1, a gene encoding a glycosyltransferase and essential for HS synthesis, and murine GL261 glioblastoma cells were orthotopically transplanted. Two weeks after transplantation, we examined the tumor progression and underlying mechanisms. Results The endothelial cell-specific Ext1 knockout (Ext1CKO) mice exhibited reduced HS expression specifically in the vascular endothelium of the brain capillaries compared with the control wild-type (WT) mice. GBM growth was significantly suppressed in Ext1CKO mice compared with that in WT mice. After GBM transplantation, the survival rate was significantly higher in Ext1CKO mice than in WT mice. We investigated how the effect of fibroblast growth factor 2 (FGF2), which is known as an angiogenesis-promoting factor, differs between Ext1CKO and WT mice by using an in vivo Matrigel assay and demonstrated that endothelial cell-specific HS reduction attenuated the effect of FGF2 on angiogenesis. Conclusions HS reduction in the vascular endothelium of the brain suppressed GBM growth and neovascularization in mice.

scholarly journals Mural Cell-Specific Deletion of Cerebral Cavernous Malformation 3 in the Brain Induces Cerebral Cavernous Malformations

2020 ◽  
Vol 40 (9) ◽  
pp. 2171-2186
Author(s):  
Kang Wang ◽  
Haifeng Zhang ◽  
Yun He ◽  
Quan Jiang ◽  
Yoshiaki Tanaka ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Adhesion Formation ◽  
Single Layer ◽  
Cerebral Cavernous Malformations ◽  
Mural Cell ◽  
Cavernous Malformations ◽  
Mural Cells ◽  
Brain Pericytes ◽  
The Brain ◽  
Specific Deletion

Objective: Cerebral cavernous malformations (CCM), consisting of dilated capillary channels formed by a single layer of endothelial cells lacking surrounding mural cells. It is unclear why CCM lesions are primarily confined to brain vasculature, although the 3 CCM-associated genes ( CCM1 , CCM2 , and CCM3 ) are ubiquitously expressed in all tissues. We aimed to determine the role of CCM gene in brain mural cell in CCM pathogenesis. Approach and Results: SM22α -Cre was used to drive a specific deletion of Ccm3 in mural cells, including pericytes and smooth muscle cells (Ccm3smKO). Ccm3smKO mice developed CCM lesions in the brain with onset at neonatal stages. One-third of Ccm3smKO mice survived upto 6 weeks of age, exhibiting seizures, and severe brain hemorrhage. The early CCM lesions in Ccm3smKO neonates were loosely wrapped by mural cells, and adult Ccm3smKO mice had clustered and enlarged capillary channels (caverns) formed by a single layer of endothelium lacking mural cell coverage. Importantly, CCM lesions throughout the entire brain in Ccm3smKO mice, which more accurately mimicked human disease than the current endothelial cell-specific CCM3 deletion models. Mechanistically, CCM3 loss in brain pericytes dramatically increased paxillin stability and focal adhesion formation, enhancing ITG-β1 (integrin β1) activity and extracellular matrix adhesion but reducing cell migration and endothelial cell-pericyte associations. Moreover, CCM3-wild type, but not a paxillin-binding defective mutant, rescued the phenotypes in CCM3-deficient pericytes. Conclusions: Our data demonstrate for the first time that deletion of a CCM gene in the brain mural cell induces CCM pathogenesis.

scholarly journals Influence of Traumatic Brain Injury on Extracellular Tau Elimination at the Blood-Brain Barrier

2021 ◽  
Author(s):  
Maxwell Eisenbaum ◽  
Andrew Pearson ◽  
Arissa Gratkowski ◽  
Benoit Mouzon ◽  
Michael Mullan ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Blood Brain Barrier ◽  
Head Trauma ◽  
Brain Barrier ◽  
Post Injury ◽  
Caveolin 1 ◽  
Mural Cells ◽  
The Brain ◽  
Angiopoietin 1

Abstract Repetitive head trauma has been associated with the accumulation of tau species in the brain. Our prior work showed brain vascular mural cells contribute to tau processing in the brain, and that these cells progressively degenerate following repetitive mild traumatic brain injury (r-mTBI). The current studies investigated the role of the cerebrovasculature in the elimination of extracellular tau from the brain, and the influence of r-mTBI on these processes. Following intracranial injection, the levels of exogenous tau residing in the brain were elevated in a mouse model of r-mTBI at 12 months post-injury compared to r-sham mice, indicating reduced tau elimination from the brain following head trauma. This may be the result of decreased caveolin-1 mediated tau efflux at the blood-brain barrier (BBB), as the caveolin inhibitor, methyl-β-cyclodextrin, significantly reduced tau uptake in isolated cerebrovessels and significantly decreased the basolateral-to-apical transit of tau across an in vitro model of the BBB. Moreover, we found that the upstream regulator of endothelial caveolin-1, Mfsd2a, was elevated in r-mTBI cerebrovessels compared to r-sham, which coincided with a decreased expression of cerebrovascular caveolin-1 at 6 months post-injury. Lastly, angiopoietin-1, a mural cell-derived protein governing endothelial Mfsd2a expression, was secreted to a greater extent from r-mTBI cerebrovessels compared to r-sham animals. Thus, in the chronic phase post-injury, release of angiopoietin-1 from degenerating mural cells downregulates caveolin-1 expression in brain endothelia, resulting in decreased tau elimination across the BBB, which may describe the accumulation of tau species in the brain following head trauma.

Iron uptake in relation to transferrin degradation in brain and other tissues of rats

1992 ◽  
Vol 263 (4) ◽  
pp. R924-R929 ◽  
Author(s):  
M. E. Strahan ◽  
A. Crowe ◽  
E. H. Morgan
Keyword(s):  
Iron Uptake ◽  
Brain Capillaries ◽  
Total Rate ◽  
The Brain ◽  
Rat Reticulocytes ◽  
Rate Of Accumulation

The possibility that iron uptake by the brain involves transcytosis of the iron-transferrin complex across the brain capillaries, followed by degradation of the transferrin (Tf) within the brain, was investigated using diferric 125I-[59Fe]Tf and [59Fe]Tf coupled to 125I-tyramine cellobiose (TC). The radiolabeled catabolic products of proteins labeled with 125I-TC remain in the cells where degradation occurs. The TCTf complex behaved normally with respect to its ability to donate iron to rat reticulocytes in vitro or to the brain, liver, kidneys, and femurs in vivo. In the brain there was little difference in the uptake of 125I derived from Tf and TCTf, and the amounts were equivalent to only a small fraction of the 59Fe uptake. Hence, the rate of Tf catabolism in the brain was insufficient to account for the rate of accumulation of iron from plasma Tf. It was concluded that Tf recycles to the plasma after delivering its iron to the brain. The uptake of 125I from TCTf by the liver and kidneys accounted for 40-50% of the total rate of Tf catabolism. This indicated that they were important but not the only sites of degradation of this protein.

scholarly journals Amyloid β oligomers constrict human capillaries in Alzheimer’s disease via signaling to pericytes

Science ◽  
2019 ◽  
Vol 365 (6450) ◽  
pp. eaav9518 ◽  
Author(s):  
Ross Nortley ◽  
Nils Korte ◽  
Pablo Izquierdo ◽  
Chanawee Hirunpattarasilp ◽  
Anusha Mishra ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Reactive Oxygen Species ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Oxygen Species ◽  
Brain Capillaries ◽  
Disease Relevance ◽  
The Brain ◽  
Capillary Walls

Cerebral blood flow is reduced early in the onset of Alzheimer’s disease (AD). Because most of the vascular resistance within the brain is in capillaries, this could reflect dysfunction of contractile pericytes on capillary walls. We used live and rapidly fixed biopsied human tissue to establish disease relevance, and rodent experiments to define mechanism. We found that in humans with cognitive decline, amyloid β (Aβ) constricts brain capillaries at pericyte locations. This was caused by Aβ generating reactive oxygen species, which evoked the release of endothelin-1 (ET) that activated pericyte ETA receptors. Capillary, but not arteriole, constriction also occurred in vivo in a mouse model of AD. Thus, inhibiting the capillary constriction caused by Aβ could potentially reduce energy lack and neurodegeneration in AD.

Screen filtration pressure of homologous and heterologous blood and electroencephalogram

1964 ◽  
Vol 206 (4) ◽  
pp. 811-814 ◽  
Author(s):  
Hans Hirsch ◽  
Roy L. Swank ◽  
Marianne Breuer ◽  
Wolfgang Hissen
Keyword(s):  
Blood Flow ◽  
Electrical Activity ◽  
Blood Cells ◽  
Perfusion Pressure ◽  
Glass Wool ◽  
Brain Capillaries ◽  
Perfusion Rate ◽  
Brain Waves ◽  
Filtration Pressure ◽  
The Brain

The character and duration of electrical activity arising from a completely isolated cat's head was dependent upon the screen filtration pressure (SFP) of the heparinized oxygenated blood with which it was perfused. If the SFP was above normal the amplitude and frequency of the EEG first decreased, then the brain waves disappeared. The duration of time from the beginning of perfusion until these changes in the EEG occurred was inversely related to the SFP of the perfused blood. Also, the perfusion rate was inversely related to the SFP provided the perfusion pressure remained the same. It is believed that the increase in SFP and changes in EEG and blood flow were due to the presence in the blood of aggregates of blood cells (platelets and leucocytes) which obstructed the brain capillaries. It would appear that heterologous (dog) as well as homologous (cat) blood can be effectively used to perfuse the isolated cat's head provided the blood has a normal SFP. In practice, this was made possible by filtering the blood continuously through Pyrex glass wool.

cAMP-Mediated regulation of the permeability in the brain capillaries

1975 ◽  
Vol 31 (5) ◽  
pp. 582-584 ◽  
Author(s):  
F. Joó ◽  
Z. Rakonczay ◽  
M. Wollemann
Keyword(s):  
Brain Capillaries ◽  
The Brain

The Neurovascular Unit: Focus on the Regulation of Arterial Smooth Muscle Cells

2020 ◽  
Vol 16 (5) ◽  
pp. 502-515 ◽  
Author(s):  
Patrícia Quelhas ◽  
Graça Baltazar ◽  
Elisa Cairrao
Keyword(s):  
Blood Flow ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Blood Vessels ◽  
Neurovascular Unit ◽  
Muscle Cells ◽  
Cerebral Blood Vessels ◽  
Mural Cells ◽  
Brain Pericytes ◽  
The Brain

The neurovascular unit is a physiological unit present in the brain, which is constituted by elements of the nervous system (neurons and astrocytes) and the vascular system (endothelial and mural cells). This unit is responsible for the homeostasis and regulation of cerebral blood flow. There are two major types of mural cells in the brain, pericytes and smooth muscle cells. At the arterial level, smooth muscle cells are the main components that wrap around the outside of cerebral blood vessels and the major contributors to basal tone maintenance, blood pressure and blood flow distribution. They present several mechanisms by which they regulate both vasodilation and vasoconstriction of cerebral blood vessels and their regulation becomes even more important in situations of injury or pathology. In this review, we discuss the main regulatory mechanisms of brain smooth muscle cells and their contributions to the correct brain homeostasis.

Pathogenesis of Brain Edema and Hemorrhage: Role of the Brain Capillary

PEDIATRICS ◽  
1979 ◽  
Vol 64 (3) ◽  
pp. 357-360
Author(s):  
Gary W. Goldstein
Keyword(s):  
Endothelial Cells ◽  
Brain Edema ◽  
Tight Junctions ◽  
Interstitial Fluid ◽  
Water Soluble ◽  
Brain Capillaries ◽  
Reye's Syndrome ◽  
Anatomic Site ◽  
Brain Capillary ◽  
The Brain

It has recently been shown that the endothelial cells in brain capillaries are the anatomic site of the blood-brain barrier, and that these endothelial cells act to maintain a constant composition and volume of brain interstitial fluid.1-3 Defects in brain capillary function appear to play a role in the pathogenesis of brain edema and hemorrhage in a wide variety of diseases. Conditions as diverse as intraventricular hemorrhage of the premature, asphyxia neonatorum, lead poisoning, head injury, Reye's syndrome, osmolar coma, and the brain edema surrounding a tumor or abscess may all share the common feature of brain capillary failure. In this review, I will consider some recent advances in our understanding of the brain microvasculature that may explain their unusual susceptibility to injury. Brain capillaries have a number of important differences from capillaries in other organs. A schematic of a typical brain capillary is shown in the Figure. Unlike systemic capillaries, the endothelial cells in brain capillaries are joined together by tight junctions.3 These cellular junctions are present around the entire circumference of the capillary tube. The result is a continuous layer of endothelial cells that effectively separate the plasma from the interstitial fluid of the brain. The tight junctions are composed of a series of complex interdigitations that create a barrier so complete that water-soluble molecules and ions are unable to move into the brain between the endothelial cells. In other organs, the capillaries do not have tight junctions, and sugars, amino acids, ions, and drugs readily diffuse between endothelial cells into the interstitial fluid.

scholarly journals Diverse Functions of Pericytes in Cerebral Blood Flow Regulation and Ischemia

2015 ◽  
Vol 35 (6) ◽  
pp. 883-887 ◽  
Author(s):  
Francisco Fernandez-Klett ◽  
Josef Priller
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cerebral Ischemia ◽  
Brain Damage ◽  
Neuronal Activity ◽  
Flow Regulation ◽  
Functional Hyperemia ◽  
Mural Cells ◽  
Ischemic Tissue ◽  
The Brain

Pericytes are mural cells with contractile properties. Here, we provide evidence that microvascular pericytes modulate cerebral blood flow in response to neuronal activity (‘functional hyperemia’). Besides their role in neurovascular coupling, pericytes are responsive to brain damage. Cerebral ischemia is associated with constrictions and death of capillary pericytes, followed by fibrotic reorganization of the ischemic tissue. The data suggest that precapillary arterioles and capillaries are major sites of hemodynamic regulation in the brain.

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