Recent advances in understanding brain capillary function

Goldstein, Gary W.; Betz, A. Lorris

doi:10.1002/ana.410140402

Cited by 102 publications

(31 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…1, inset). Goldstein and Betz (1983)]. The ac tive extrusion of K + from the brain to the blood and the corresponding entry of Na + from blood to brain are thought to be regulated , at least in part , by the membrane-bound enzyme Na + , K + -ATPase.…”

Section: Resultsmentioning

confidence: 99%

Specific Ouabain Binding to Brain Microvessels and Choroid Plexus

Harik

Doull

Dick

1985

J Cereb Blood Flow Metab

100

View full text Add to dashboard Cite

Summary:The energy-dependent transport of ions across the blood-brain barrier and the blood-cerebro spinal fluid barrier by N a + ,K + -ATPase is credited with an important role in brain homeostasis. In this study, we have assessed the relative enrichment of Na+ ,K+ ATPase in regional brain capillary preparations and in the choroid plexus by the quantitative determination of the cardiac glycoside binding sites in these preparations using [3H]ouabain as a ligand. We find that ouabain binds spe cifically to brain microvessels of the rat and the pig and to the choroid plexus of the pig in a saturable manner. The maximum density of ouabain binding sites in brain microvessels of both species is about one-fourth that of Abbreviation used: QNB, quinuclidinyl benzylate. 156the crude membranes of the cerebrum and cerebellum. The density of ouabain binding sites in the pig choroid plexus is intermediate between that of the brain and brain microvessels. We do not find regional differences in oua bain binding to membrane fractions of the cerebrum and cerebellum, nor any significant differences in ouabain binding to cerebral and cerebellar microvessels. These findings provide quantitative estimates of Na + ,K + ATPase in brain capillaries and choroid plexus.

show abstract

Section: Resultsmentioning

confidence: 99%

Specific Ouabain Binding to Brain Microvessels and Choroid Plexus

Harik

Doull

Dick

1985

J Cereb Blood Flow Metab

100

View full text Add to dashboard Cite

show abstract

“…This is unlikely because there seem to be no functional or morphological differences between capillaries in different cortical layers, 54 - 55 and studies assessing capillary plugging histologically (see above) found no preferential distribution regarding the cortical layers.…”

Section: Does Leukocyte Flogging Cause Postischemic Cortical Hypoperfmentioning

confidence: 96%

Cortical hypoperfusion after global forebrain ischemia in rats is not caused by microvascular leukocyte plugging.

Dirnagl

Niwa

Sixt

et al. 1994

Stroke

View full text Add to dashboard Cite

• Background and Purpose We tested the hypothesis that cerebral hypoperfusion after experimental global cerebral ischemia is caused by plugging of the microcirculation with activated leukocytes using in vivo microscopic observation of the behavior of leukocytes in the cortical microcirculation during the transition from postischemic hyperperfusion to hypoperfusion.Methods Anesthetized and ventilated rats (n=24) were equipped with a closed cranial window. Physiological variables and cortical regional cerebral blood flow (laser-Doppler flowmetry) were measured continuously. Leukocytes were labeled intravitally with rhodamine 6G and visualized in the microcirculation of the brain surface and outer layers of the cortex with confocal laser scanning microscopy from preischemia to 4 hours after reperfusion that followed 10 minutes of global cerebral ischemia (rCBF<10% of control).Results In controls (n=8), there were no signs of leukocyte activation over the 4-hour observation period. In ischemic rats (n=16), during the transition from hyperperfusion to hypoper-S evere transient global forebrain ischemia leads to a characteristic pattern of cerebral blood flow (CBF) changes in several species: After recirculation a short period of hyperperfusion develops, followed by prolonged hypoperfusion. -2 The factors causing this blood flow pattern and its consequences for ischemic damage are not fully understood.Generally, hyperperfusion is attributed to maximal vasodilation caused by the accumulation of vasodilator metabolic products, such as H + ,K + , nitric oxide, adenosine, etc, 2 -4 although neurogenic mechanisms may be involved as well.5 It is less clear what causes hypoperfusion. The concept of a mechanical obstruction of the postischemic microcirculation with subsequent hypoperfusion 6 or "no-reflow" 7 by leukocytes ("leukocyte plugging" 8 ) has received much attention. 910 Leukocytes may be activated during ischemia, and activated leukocytes interact with the vascular endothelium, possibly resulting in microvascular obstruction. 10 In skeletal muscle, Harris and Skalak" demonstrated that even a few activated leukocytes may have a profound impact on the resistance of microvascular networks and therefore blood flow.Received April 5, 1993; final revision received October 28, 1993; accepted January 5, 1994.From the Department of Neurology, Humboldt University, Berlin, Germany.Correspondence to Dr Ulrich Dirnagl, Department of Neurology, Humboldt University, Schumannstr 20/21, 10098 Berlin, Germany.fusion there was no change in the behavior of leukocytes. Most notably, no capillary pluggers were seen. In the postischemic period only a slight increase of the number of leukocytes rolling along or sticking to the venular endothelium was seen, and very few capillaries were plugged by leukocytes. Extravasation of leukocytes into the brain tissue was observed in 8 rats beginning 2 hours after ischemia with a variable degree between animals.Conclusions Because there was only mild activation of leukocyte-endothelium interaction w...

show abstract

“…The brain endothelium is a dynamic interface that functions as a potentially immunoreactive surface for the modulation of immune and inflammatory responses (27,28). Endothelial cells form an integral part of the blood-brain barrier (BBB), a selectively permeable transport barrier for substance exchange across capillary walls (29,30). Infection of human brain capillary endothelial (HBCE) cells may alter the immunoreactivity of the endothelium or compromise the integrity of the BBB.…”

Section: For a Review) Human Immunodeficiency Virus (Hiv) Hasmentioning

confidence: 99%

Human immunodeficiency virus infection of human brain capillary endothelial cells occurs via a CD4/galactosylceramide-independent mechanism.

Moses

Bloom

Pauza

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

208

121

View full text Add to dashboard Cite

Neuropathologic studies of AIDS patients have shown that brain capillary endothelial cells are a cellular target for human immunodeficiency virus (HIV) in vivo. We have established in vitro cultures of primary human brain capillary endothelial (HBCE) cells. Using this model system, we have shown a signifcant HIV infection of HBCE cells that is productive yet noncytopathic. The infection is mediated by a cellular interaction with gpl20 that does not involve CD4 or galactosylceramide. HIV infection of HBCE cells may contribute to AIDS-associated neuropathology by disturbing the physiology of the endothelium and directly or indirectiy facilitating dissemination of virus to the central nervous system. AIDS patients develop a characteristic neuropathology accompanied by motor, sensory, and cognitive disorders (see ref. 1 for a review). Human immunodeficiency virus (HIV) has been cultured from the brain, spinal cord, and cerebrospinal fluid ofAIDS patients (2-4). Examination ofpostmortem brain sections by immunocytochemistry, in situ hybridization, and electron microscopy has identified cells of the macrophage lineage as the principal cellular target for HIV (5-12). Viral proteins and nucleic acids are also localized in brain capillary endothelial cells of AIDS patients (7,9,13,14) and simian immunodeficiency virus-infected rhesus macaques (15). HIV is detected at lower frequency in astrocytes (9,10,13,16).While HIV infection is clearly associated with pathological changes and neurological impairment, the relationship between tissue infection and disease manifestation remains unclear. Central nervous system (CNS) pathology could arise from direct infection of brain tissue by HIV or from the indirect effects of systemic or local viral infection such as the production of neurotoxic viral (17-21) or virally induced cellular proteins (22,23) and cytokines (24,25). The brain endothelium is a dynamic interface that functions as a potentially immunoreactive surface for the modulation of immune and inflammatory responses (27,28). Endothelial cells form an integral part of the blood-brain barrier (BBB), a selectively permeable transport barrier for substance exchange across capillary walls (29, 30). Infection of human brain capillary endothelial (HBCE) cells may alter the immunoreactivity of the endothelium or compromise the integrity of the BBB. These perturbations could contribute to immunopathological processes and allow neurotoxic substances access to the brain. In addition, HIV infected endothelium may constitute an entry portal for HIV into the CNS.We report here on the development of an in vitro system to examine the interaction of HIV with HBCE cells. We have developed and characterized pure cultures of primary HBCE cells and have established that they can be productivelyThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.infected by HIV in vitro. The natur...

show abstract

Recent advances in understanding brain capillary function

Cited by 102 publications

References 69 publications

Specific Ouabain Binding to Brain Microvessels and Choroid Plexus

Specific Ouabain Binding to Brain Microvessels and Choroid Plexus

Cortical hypoperfusion after global forebrain ischemia in rats is not caused by microvascular leukocyte plugging.

Human immunodeficiency virus infection of human brain capillary endothelial cells occurs via a CD4/galactosylceramide-independent mechanism.

Contact Info

Product

Resources

About