jueves, 26 de abril de 2018

Líquido cefalorraquídeo / Cerebrospinal fluid

Abril 25, 2018. No. 3062
Circulación del líquido cefalorraquídeo: ¿Qué sabemos y cómo lo sabemos?
Cerebrospinal fluid circulation: What do we know and how do we know it?
Khasawneh AH, Garling RJ, Harris CA.
Brain Circ 2018;4:14-8.
The central nervous system's (CNS) complicated design is a double-edged sword. On the one hand, the complexity is what gives rise to higher order thinking; but on the other hand, damage to the CNS evokes its unforgiving nature. The cerebrospinal fluid (CSF) circulation system is an intricate system embedded in and around the CNS that has been the topic of debate since it was first described in the 18thcentury. It is underscored by the choroid plexus's distinct vascular network which has conventionally been seen as the most prominent structure in CSF production through a variety of active transporters and channels. Despite the ubiquity of this circulation system in vertebrates, some aspects remain understudied. Recent advances in scientific methodology and experimentation have proven to be effective tools for elucidating the mechanisms of the CSF circulation system and the pathological conditions associated with its malfunction. In this review, we capitulate the classical understanding of CSF physiology as well as a new, emerging theory on CSF production.
Keywords: Absorption, circulation, CSF flow, production
Interacción entre la barrera hematoencefálica y el sistema glimfático en la eliminación de solutos.
Interaction between blood-brain barrier and glymphatic system in solute clearance.
Neurosci Biobehav Rev. 2018 Mar 30;90:26-33. doi: 10.1016/j.neubiorev.2018.03.028. [Epub ahead of print]
Neurovascular pathology concurs with protein accumulation, as the brain vasculature is important for waste clearance. Interstitial solutes, such as amyloid-β, were previously thought to be primarily cleared from the brain by blood-brain barrier transport. Recently, the glymphatic system was discovered, in which cerebrospinal fluid is exchanged with interstitial fluid, facilitated by the aquaporin-4 water channels on the astroglial endfeet. Glymphatic flow can clear solutes from the interstitial space. Blood-brain barrier transport and glymphatic clearance likely serve complementary roles with partially overlapping mechanisms providing a well-conditioned neuronal environment. Disruption of these mechanisms can lead to protein accumulation and may initiate neurodegenerative disorders, for instance amyloid-β accumulation and Alzheimer's disease. Although both mechanisms seem to have a similar purpose, their interaction has not been clearly discussed previously. This review focusses on this interaction in healthy and pathological conditions. Future health initiatives improving waste clearance might delay or even prevent onset of neurodegenerative disorders. Defining glymphatic flow kinetics using imaging may become an alternative way to identify those at risk of Alzheimer's disease.
KEYWORDS: Alzheimer's disease; Amyloid-β; BBB; Blood-brain barrier; Clearance; Glymphatic system; Imaging
El papel de las barreras cerebrales en el movimiento de fluidos en el SNC: ¿existe un sistema "glimfático"?
The role of brain barriers in fluid movement in the CNS: is there a 'glymphatic' system?
Abbott NJ1, Pizzo ME2,3, Preston JE4, Janigro D5,6, Thorne RG7,8,9,10,11,12.
Acta Neuropathol. 2018 Mar;135(3):387-407. doi: 10.1007/s00401-018-1812-4. Epub 2018 Feb 10.
Brain fluids are rigidly regulated to provide stable environments for neuronal function, e.g., low K+, Ca2+, 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.
KEYWORDS: Blood-brain barrier; Cerebrospinal fluid; Extracellular space; Glymphatic; Interstitial fluid; Perivascular space

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