Paravascular spaces: entry to or exit from the brain?

Abstract

New Findings What is the topic of this review? In this symposium report, we review the glymphatic clearance from the brain. What advances does it highlight? Evaluation of the evidence indicates that cerebrospinal fluid flows along paravascular spaces at the surface of the brain. However, bulk flow along penetrating arteries into the brain, followed by exit along veins, requires further confirmation. Clearance from the brain, based on mixing, might provide an alternative explanation for experimental findings. Abstract The interstitial fluid of the brain provides the environment for proper neuronal function. Maintenance of the volume and composition of interstitial fluid requires regulation of the influx and removal of water, ions, nutritive and waste products. The recently described glymphatic pathway might contribute to some of these functions. It is proposed that cerebrospinal fluid enters the brain via paravascular spaces along arteries, mixes with interstitial fluid, and leaves the brain via paravascular spaces along veins. In this symposium report, we review the glymphatic concept, its concerns, and alternative views on interstitial fluid–cerebrospinal fluid exchange.

Vascular microdomain signalling and possible novel treatments in cardiovascular diseases

“…This modulation significantly potentiates the magnitude of agonist‐induced changes in vascular tone. This is supported by experimental findings from mice bearing a mutation in the Na + ,K + ‐ATPase α2 isoform, which is known to be characteristic for familial hemiplegic migraine type 2 (Staehr et al, ). Accordingly, Staehr et al.…”

“…Cerebrovascular homeostasis was also addressed by discussion of the mechanisms involved in the regulation of interstitial fluid, i.e. cerebrospinal fluid exchange (Bakker, Naessens, & VanBavel, ). C. Garland discussed the role of ion channels in bidirectional interaction between vascular endothelial and smooth muscle cells, leading to generation of rhythmic arterial contraction, vasomotion and its significance for microvascular reactivity.…”

“…() proposed exclusive importance of this Src‐kinase‐dependent signal transduction for the cerebral circulation, where it, along with other targets, modulates the sensitivity of contractile machinery for intracellular Ca 2+ . This is mediated through phosphorylation of the regulatory myosin phosphatase targeting protein, which in turn affects cerebrovascular diameter (Staehr et al, ). This modulation significantly potentiates the magnitude of agonist‐induced changes in vascular tone.…”

“…Bakker et al. () discuss possible mechanisms behind the exchange of water and osmolytes between interstitial and cerebrospinal fluid. It is of obvious importance that the brain interstitial fluid volume and composition are regulated.…”

“…Although there is no doubt regarding the existence of these paravascular spaces, Bakker et al. () indicate important unresolved issues. Despite the fact that movement of cerebrospinal fluid along arteries at the brain surface is confirmed, an alternative explanation for tracer spreading along parenchymal arteries suggests the role of fluid mixture rather than bulk flow.…”