Convection of Cerebral Interstitial Fluid and Its Role in Brain Volume Regulation

Cserr, Helen F.; DePasquale, Michael; Patlak, Clifford S.; Pullen, R. G. L.

doi:10.1111/j.1749-6632.1986.tb27144.x

Cited by 71 publications

(40 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Even then, it was thought that ISF secreted at the BBB may drain along perivascular spaces out of the brain and into the CSF to clear the brain of waste [38,186], a concept revisited 60 years later by Helen Cserr to explain how the brain, lacking the classical lymphatics of the periphery, might accomplish efficient waste removal [32,36,37]. Importantly, Cserr and colleagues [32][33][34][35][36] revived an earlier idea that a convective or bulk flow of ISF occurred along specialized pathways in the brain to communicate with and drain to the CSF. The key experiments involved the injection of small volumes (< 1 µl) of 2000 kDa blue dextran [36] or 40 kDa horseradish peroxidase [33] into the caudate nucleus.…”

Section: Blood Vessels and The Perivascular Spacementioning

confidence: 99%

The role of brain barriers in fluid movement in the CNS: is there a ‘glymphatic’ system?

et al. 2018

View full text Add to dashboard Cite

Brain fluids are rigidly regulated to provide stable environments for neuronal function, e.g., low K + , Ca 2+ , and protein to optimise signalling and minimise neurotoxicity. At the same time, neuronal and astroglial waste must be promptly removed. The interstitial fluid (ISF) of the brain tissue and the cerebrospinal fluid (CSF) bathing the CNS are integral to this homeostasis and the idea of a glia-lymph or 'glymphatic' system for waste clearance from brain has developed over the last 5 years. This links bulk (convective) flow of CSF into brain along the outside of penetrating arteries, glia-mediated convective transport of fluid and solutes through the brain extracellular space (ECS) involving the aquaporin-4 (AQP4) water channel, and finally delivery of fluid to venules for clearance along peri-venous spaces. However, recent evidence favours important amendments to the 'glymphatic' hypothesis, particularly concerning the role of glia and transfer of solutes within the ECS. This review discusses studies which question the role of AQP4 in ISF flow and the lack of evidence for its ability to transport solutes; summarizes attributes of brain ECS that strongly favour the diffusion of small and large molecules without ISF flow; discusses work on hydraulic conductivity and the nature of the extracellular matrix which may impede fluid movement; and reconsiders the roles of the perivascular space (PVS) in CSF-ISF exchange and drainage. We also consider the extent to which CSF-ISF exchange is possible and desirable, the impact of neuropathology on fluid drainage, and why using CSF as a proxy measure of brain components or drug delivery is problematic. We propose that new work and key historical studies both support the concept of a perivascular fluid system, whereby CSF enters the brain via PVS convective flow or dispersion along larger caliber arteries/arterioles, diffusion predominantly regulates CSF/ISF exchange at the level of the neurovascular unit associated with CNS microvessels, and, finally, a mixture of CSF/ISF/waste products is normally cleared along the PVS of venules/veins as well as other pathways; such a system may or may not constitute a true 'circulation', but, at the least, suggests a comprehensive re-evaluation of the previously proposed 'glymphatic' concepts in favour of a new system better taking into account basic cerebrovascular physiology and fluid transport considerations.

show abstract

Section: Blood Vessels and The Perivascular Spacementioning

confidence: 99%

The role of brain barriers in fluid movement in the CNS: is there a ‘glymphatic’ system?

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Previous studies have also indicated that a luminally located BBB Na + transport pathway plays a major role in this phenomenon, although the transporter(s) involved have not been identified (Betz, 1996;Ennis et al, 1996;Schielke et al, 1991). Under healthy, normoxic conditions, the BBB endothelium normally generates up to 30% of the volume of brain interstitial fluid by mechanisms that involve luminal Na + and Cl − transporters (Cserr et al, 1989;Keep, 1993), which very likely work in conjunction with abluminal Na/K ATPase and Cl − efflux pathways. This BBB secretion of Na + , Cl − , and water into the brain appears to be greatly increased by conditions present during cerebral ischemia.…”

mentioning

confidence: 99%

Bumetanide Inhibition of the Blood-Brain Barrier Na-K-Cl Cotransporter Reduces Edema Formation in the Rat Middle Cerebral Artery Occlusion Model of Stroke

O’Donnell

Tran

Lam

et al. 2004

J Cereb Blood Flow Metab

222

258

View full text Add to dashboard Cite

Summary:Increased transport of Na + across an intact bloodbrain barrier (BBB) participates in edema formation during the early hours of cerebral ischemia. In previous studies, the authors showed that the BBB Na-K-Cl cotransporter is stimulated by factors present during ischemia, suggesting that the cotransporter may contribute to the increased brain Na + uptake in edema. The present study was conducted to determine (1) whether the Na-K-Cl cotransporter is located in the luminal membrane of the BBB, and (2) whether inhibition of the BBB cotransporter reduces brain edema formation. Perfusion-fixed rat brains were examined for cotransporter distribution by immunoelectron microscopy. Cerebral edema was evaluated in rats subjected to permanent middle cerebral artery occlusion (MCAO) by magnetic resonance diffusion-weighted imaging and calculation of apparent diffusion coefficients (ADC). The immunoelectron microscopy studies revealed a predominant (80%) luminal membrane distribution of the cotransporter. Magnetic resonance imaging studies showed ADC ratios (ipsilateral MCAO/contralateral control) ranging from 0.577 to 0.637 in cortex and striatum, indicating substantial edema formation. Intravenous bumetanide (7.6-30.4 mg/kg) given immediately before occlusion attenuated the decrease in ADC ratios for both cortex and striatum (by 40-67%), indicating reduced edema formation. Bumetanide also reduced infarct size, determined by TTC staining. These findings suggest that a luminal BBB Na-K-Cl cotransporter contributes to edema formation during cerebral ischemia. Key Words: Cotransport-Blood-brain barrier-Stroke, Cerebral ischemiaCerebral edema-Bumetanide.Brain edema that forms during the early hours of ischemic stroke involves a net uptake of Na + and water from blood into brain across an intact blood-brain barrier

show abstract

“…The central nervous system (CNS) is composed of a tightly interwoven network of neuronal and glial elements (e.g., Cserr and Bundgaard, 1986). There is increasing evidence that glial cells are capable of extensive intercellular communication including glialglial and bidirectional glial-neuronal signaling (Barres, 1991;Finkbeiner, 1993).…”

Section: Discussionmentioning

confidence: 99%

Excitotoxic damage of retinal glial cells depends upon normal neuron-glial interactions

Heidinger

Dreyfus

Sahel

et al. 1998

Glia

View full text Add to dashboard Cite

Convection of Cerebral Interstitial Fluid and Its Role in Brain Volume Regulation

Cited by 71 publications

References 14 publications

The role of brain barriers in fluid movement in the CNS: is there a ‘glymphatic’ system?

The role of brain barriers in fluid movement in the CNS: is there a ‘glymphatic’ system?

Bumetanide Inhibition of the Blood-Brain Barrier Na-K-Cl Cotransporter Reduces Edema Formation in the Rat Middle Cerebral Artery Occlusion Model of Stroke

Excitotoxic damage of retinal glial cells depends upon normal neuron-glial interactions

Contact Info

Product

Resources

About