Mechanisms to explain the reverse perivascular transport of solutes out of the brain

Schley, David; Carare-Nnadi, R.; Please, Colin P.; Perry, V. Hugh; Weller, Roy O.

doi:10.1016/j.jtbi.2005.07.005

Cited by 265 publications

(262 citation statements)

References 32 publications

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“…VRS, also called perivascular spaces, surround the walls of arteries, arterioles, veins, and venules stretching from the subarachnoid space into the brain parenchyma (Virchow 1851;Robin 1859;Zhang et al 1990;Kwee and Kwee 2007;He et al 2012). VRS are the main pathways for the elimination of interstitial fluid and solutes such as amyloid-beta (Abeta) from the grey matter of the brain (Schley et al 2006;Weller et al 2009). Blood in hematomas may leak out via VRS (He et al 2012), thus forming the perivascular extension of hematomas.…”

Section: Discussionmentioning

confidence: 99%

Intracerebral Hematoma Extends via Perivascular Spaces and Perineurium

Yin

Lü

Qiu

et al. 2013

Tohoku J. Exp. Med.

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Intracerebral hemorrhage (ICH) is a devastating disorder associated with high morbidity and mortality. ICH results in the formation of hematoma that affects not only the primary site of injury but also the remote regions. In fact, hematoma can extend via perivascular spaces (also called Virchow-Robin spaces, VRS) and perineurium in an animal model of ICH. In the present study, we used magnetic resonance imaging (MRI) with susceptibility-weighted imaging (SWI) to investigate the characteristics of the perivascular and perineural extensions of hematomas in patients with ICH. A total of 20 ICH patients without secondary subarachnoid and secondary intraventricular hemorrhages were recruited. Brain MRI scans, including SWI, T1, and T2-weighted images, were performed between 17 h to 7 days after the onset of ICH. MRI with SWI revealed that paramagnetic substances spread along the VRS or the perineurium. Such distribution could cause the formation of cerebral microbleeds (CMBs). However, the distribution of remote hemorrhagic lesions varied, depending on the size and location of the original hematoma. The unenhanced CT scans of the 20 patients did not show any hyperdensity around the blood vessels and nerve tracts outside the hematoma. These results indicate the perivascular and perineural extensions of hematomas in patients with ICH, which is formed by the leakage of the original hematoma via the VRS or perineurium. We also provide a new explanation for the series of pathological processes involved in ICH, including the remote effects of hematoma and the formation of CMBs in patients with ICH.

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Section: Discussionmentioning

confidence: 99%

Intracerebral Hematoma Extends via Perivascular Spaces and Perineurium

Yin

Lü

Qiu

et al. 2013

Tohoku J. Exp. Med.

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“…Lymphatic drainage driven by filtration pressure, contraction of adjacent muscles and pulsations of neighbouring arteries (Schley et al 2006;Gupta et al 2009) predicts the subarachnoid space to be compliant, but with minimal deformation throughout the cardiac cycle, which would translate to a lymphatic component that is less than that previously predicted using animals (Boulton et al 1998b).…”

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confidence: 95%

Cerebrospinal fluid dynamics in the human cranial subarachnoid space: an overlooked mediator of cerebral disease. II. In vitro arachnoid outflow model

Holman

Kurtcuoglu

Grzybowski

2010

J. R. Soc. Interface.

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The arachnoid membrane (AM) and granulations (AGs) are important in cerebrospinal fluid (CSF) homeostasis, regulating intracranial pressure in health and disease. We offer a functional perspective of the human AM's transport mechanism to clarify the role of AM in the movement of CSF and metabolites. Using cultures of human AG cells and a specialized perfusion system, we have shown that this in vitro model mimics the in vivo characteristics of unidirectional fluid transport and we present the first report of serum-free permeability values (92.5 ml min 21 mm Hg 21 cm 22 ), which in turn are in agreement with the CSF outflow rates derived from a dynamic, in vivo magnetic resonance imaging-based computational model of the subarachnoid cranial space (130.9 ml min 21 mm Hg 21 cm 22). Lucifer yellow permeability experiments have verified the maintenance of tight junctions by the arachnoidal cells with a peak occurring around 21 days post-seeding, which is when all perfusion experiments were conducted. Addition of ruthenium red to the perfusate, and subsequent analysis of its distribution post-perfusion, has verified the passage of perfusate via both paracellular and transcellular mechanisms with intracellular vacuoles of approximately 1 mm in diameter being the predominant transport mechanism. The comparison of the computational and in vitro models is the first report to measure human CSF dynamics functionally and structurally, enabling the development of innovative approaches to modify CSF outflow and will change concepts and management of neurodegenerative diseases resulting from CSF stagnation.

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“…Theoretical modeling suggests that perivascular drainage may be driven by the contrary wave that follows arterial pulsations (Schley et al, 2006). Age-related arteriosclerosis and the resulting reduction in pulse amplitude appear to reduce the force and efficiency of drainage, leading to accumulation of Ab in the basement membranes as CAA.…”

Section: Introductionmentioning

confidence: 99%

Regional differences in the morphological and functional effects of aging on cerebral basement membranes and perivascular drainage of amyloid‐β from the mouse brain

et al. 2013

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SummaryDevelopment of cerebral amyloid angiopathy (CAA) and Alzheimer's disease (AD) is associated with failure of elimination of amyloid-b (Ab) from the brain along perivascular basement membranes that form the pathways for drainage of interstitial fluid and solutes from the brain. In transgenic APP mouse models of AD, the severity of cerebral amyloid angiopathy is greater in the cerebral cortex and hippocampus, intermediate in the thalamus, and least in the striatum. In this study we test the hypothesis that age-related regional variation in (1) vascular basement membranes and (2) perivascular drainage of Ab contribute to the different regional patterns of CAA in the mouse brain. Quantitative electron microscopy of the brains of 2-, 7-, and 23-month-old mice revealed significant age-related thickening of capillary basement membranes in cerebral cortex, hippocampus, and thalamus, but not in the striatum. Results from Western blotting and immunocytochemistry experiments showed a significant reduction in collagen IV in the cortex and hippocampus with age and a reduction in laminin and nidogen 2 in the cortex and striatum. Injection of soluble Ab into the hippocampus or thalamus showed an agerelated reduction in perivascular drainage from the hippocampus but not from the thalamus. The results of the study suggest that changes in vascular basement membranes and perivascular drainage with age differ between brain regions, in the mouse, in a manner that may help to explain the differential deposition of Ab in the brain in AD and may facilitate development of improved therapeutic strategies to remove Ab from the brain in AD.

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Mechanisms to explain the reverse perivascular transport of solutes out of the brain

Cited by 265 publications

References 32 publications

Intracerebral Hematoma Extends via Perivascular Spaces and Perineurium

Intracerebral Hematoma Extends via Perivascular Spaces and Perineurium

Cerebrospinal fluid dynamics in the human cranial subarachnoid space: an overlooked mediator of cerebral disease. II. In vitro arachnoid outflow model

Regional differences in the morphological and functional effects of aging on cerebral basement membranes and perivascular drainage of amyloid‐β from the mouse brain

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