Morphometric analysis of CNS microvascular endothelium

Coomber, Brenda L.; Stewart, Patricia A.

doi:10.1016/0026-2862(85)90042-1

Cited by 178 publications

(100 citation statements)

References 39 publications

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“…The literature reports little regional variation of the mean capillary diameter (Hunziker et aI., 1979;Pawlik et aI., 1981;Coomber and Stewart, 1985). Rosolowsky and Weiss (1986) found no significant changes of capillary diameter between regions of occluded (60 min) and nonoccluded myocardium of rabbits.…”

Section: Methodological Issuesmentioning

confidence: 99%

Reduction of Functional Capillary Density in Human Brain after Stroke

Gjedde

Kuwabara

Hakim

1990

J Cereb Blood Flow Metab

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Summary:The blood flow of brain tissue often returns to normal after an ischemic episode. As "luxury" rather than "reactive" reperfusion, this hyperemia is associated with low metabolism. It is not known to what extent the high blood flow accompanies a high, normal, or low den sity of capillaries. The resolution of this question may indicate whether the functional capillary density is vari able and, if so, whether it is coupled to blood flow or metabolism. To answer these questions, we defined func tional capillaries as capillaries that transport glucose. We then calculated the density of functional capillaries (D cap) and the mean time of transit of blood through the capil laries (tca p) from hemodynamic variables obtained in vivo by positron tomography of five patients afflicted by cere bral ischemic stroke. Each patient was studied twice, within 36 h of the insult and 1 week later. We identified nominally "ischemic" regions in the first study as cortical gray matter regions, contiguous with the ischemic focus,The density of capillaries varies between the re gions of the brain (Craigie, 1945). The variation ap pears to have a cytoarchitectural basis, suggesting that the total number of capillaries in any region is a reflection of the normal average energy require ment of that region. However, evidence from other organs in animal experiments suggests that not all capillaries in a brain region function equally well as

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Section: Methodological Issuesmentioning

confidence: 99%

Reduction of Functional Capillary Density in Human Brain after Stroke

Gjedde

Kuwabara

Hakim

1990

J Cereb Blood Flow Metab

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“…The diameter of large arteries and veins can be made up of dozens of ECs, whereas the smallest capillary is formed by a single EC folding onto itself to form the lumen of the vessel (Aird 2007a,b). These CNS microvascular ECs are extremely thin cells that are 39% less thick than muscle ECs, with a distance of less than a quarter of a micron separating the lumenal from the parenchymal surface (Coomber and Stewart 1985).…”

Section: Endothelial Cellsmentioning

confidence: 99%

“…CNS ECs are held together by tight junctions (TJs), which greatly limit the paracellular flux of solutes (Reese and Karnovsky 1967;Brightman and Reese 1969;Westergaard and Brightman 1973). CNS ECs undergo extremely low rates of transcytosis as compared with peripheral ECs, which greatly restricts the vesicle-mediated transcellular movement of solutes (Coomber and Stewart 1985). This tight paracellular and transcellular barrier creates a polarized cell with distinct lumenal and ablumenal membrane compartments such that movement between the blood and the brain can be tightly controlled through regulated cellular transport properties (Betz and Goldstein 1978;Betz et al 1980).…”

Section: Endothelial Cellsmentioning

confidence: 99%

The Blood–Brain Barrier

Daneman

Prat

2015

Cold Spring Harb Perspect Biol

2,456

1,829

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Blood vessels are critical to deliver oxygen and nutrients to all of the tissues and organs throughout the body. The blood vessels that vascularize the central nervous system (CNS) possess unique properties, termed the blood-brain barrier, which allow these vessels to tightly regulate the movement of ions, molecules, and cells between the blood and the brain. This precise control of CNS homeostasis allows for proper neuronal function and also protects the neural tissue from toxins and pathogens, and alterations of these barrier properties are an important component of pathology and progression of different neurological diseases. The physiological barrier is coordinated by a series of physical, transport, and metabolic properties possessed by the endothelial cells (ECs) that form the walls of the blood vessels, and these properties are regulated by interactions with different vascular, immune, and neural cells. Understanding how these different cell populations interact to regulate the barrier properties is essential for understanding how the brain functions during health and disease.

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“…where PS is the permeability-surface area product of the capillaries, 8 is the average thickness of the capillary wall (= 100 A) (Coomber and Stewart, 1985;Molnar et al, unpublished observations), D is the aqueous diffusion constant of albumin (6.4 cm2/s x 10-7; value corrected to 37°C) (Edsal, 1953;Putnam, 1965;Peters, 1970), a is the average radius of the albumin mole cule (3 nm),1 p is the radius of the pore, and N is the number of pores per unit mass of tissue. If K/D is ap proximately constant (i.e., varies by <30%) for different size molecules, then the "holes" or "pores" in the capil lary membrane must be large enough so that the steric hinderance factor is negligible for these molecules.…”

Section: (5)mentioning

confidence: 99%

Dexamethasone Effects on [¹²⁵I]Albumin Distribution in Experimental RG-2 Gliomas and Adjacent Brain

Nakagawa¹,

Groothuis

Owens³

et al. 1987

J Cereb Blood Flow Metab

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Summ ary: A total of 72 RG-2 transplanted gliomas were studied in 58 rats at three time points (1, 30, 240 min) after intravenous injection of [125Ilradioiodinated serum albumin ([125I]RISA). The animals were divided into two groups: a control group that received no treatment and a second group that was treated with five doses of 1.5 mg/kg of dexamethasone over 2.5 days. 687comparison of the tumor influx constants in control an imals and the aqueous diffusion constants of two different size molecules (RISA and amino isobutyric acid) suggests that the "pores" across RG-2 capillaries are large and may not restrict the free diffusion of RISA (estimated minimum pore diameter > 36 nm) and that the total pore area is -6.2 x 10-5 cm2 g-I in RG-2 tumor tissue. The second model, which allows for diffusion and solvent drag of RISA across tumor capillaries and through the tissue, was used to analyze the distribution profiles of RISA in peripheral tumor and adjacent brain. This anal ysis was consistent with a small bulk flow of plasma-de rived edema fluid (capillary filtration rate = 0.8 I·d g-I min -I) and a larger component of free diffusion of RISA ( K = 2 fLl g-I min-I) through pores in the tumor vessels of control animals. Dexamethasone treatment markedly reduced or eliminated the filtration of plasma-derived fluid across tumor capillaries and the movement of RISA through the extracellular space by solvent drag. These effects may be mediated by a reduction in the size of the extracellular space and/or a decrease in the pore size of tumor capillaries and could represent an important mech anism for corticosteroid control of tumor and peri tumoral brain edema.

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Morphometric analysis of CNS microvascular endothelium

Cited by 178 publications

References 39 publications

Reduction of Functional Capillary Density in Human Brain after Stroke

Reduction of Functional Capillary Density in Human Brain after Stroke

The Blood–Brain Barrier

Dexamethasone Effects on [¹²⁵I]Albumin Distribution in Experimental RG-2 Gliomas and Adjacent Brain

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Morphometric analysis of CNS microvascular endothelium

Cited by 178 publications

References 39 publications

Reduction of Functional Capillary Density in Human Brain after Stroke

Reduction of Functional Capillary Density in Human Brain after Stroke

The Blood–Brain Barrier

Dexamethasone Effects on [125I]Albumin Distribution in Experimental RG-2 Gliomas and Adjacent Brain

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Dexamethasone Effects on [¹²⁵I]Albumin Distribution in Experimental RG-2 Gliomas and Adjacent Brain