lunes, 22 de enero de 2018

El sistema glimfático / The glymphatic system

Enero 22, 2018. No. 2971

El sistema glimfático: una guía para principiantes.
El sistema glimfático es un sistema de eliminación de residuos macroscópico recientemente descubierto que utiliza un sistema único de túneles perivasculares, formado por células astrogliales, para promover la eliminación eficiente de proteínas solubles y metabolitos del sistema nervioso central. Además de la eliminación de desechos, el sistema glimfático también facilita la distribución de varios compuestos en el cerebro, incluyendo glucosa, lípidos, aminoácidos, factores de crecimiento y neuromoduladores. Curiosamente, el sistema glimfático funciona principalmente durante el sueño y se desconecta en gran medida durante la vigilia. La necesidad biológica de dormir en todas las especies puede por lo tanto reflejar que el cerebro debe entrar en un estado de actividad que permita la eliminación de productos de desecho potencialmente neurotóxicos, incluido el β-amiloide. Dado que el concepto del sistema glimfático es relativamente nuevo, revisaremos aquí sus elementos estructurales básicos, organización, regulación y funciones. También discutiremos los estudios recientes que indican que la función glimfatica se suprime en varias enfermedades y que la falla de la función glimfatica a su vez puede contribuir a la patología en trastornos neurodegenerativos, lesión cerebral traumática y apoplejía.
The Glymphatic System: A Beginner's Guide.
Neurochem Res. 2015 Dec;40(12):2583-99. doi: 10.1007/s11064-015-1581-6. Epub 2015 May 7.
The glymphatic system is a recently discovered macroscopic waste clearance system that utilizes a unique system of perivascular tunnels, formed by astroglial cells, to promote efficient elimination of soluble proteins and metabolites from the central nervous system. Besides waste elimination, the glymphatic system also facilitates  brain-wide distribution of several compounds, including glucose, lipids, amino acids, growth factors, and neuromodulators. Intriguingly, the glymphatic system function mainly during sleep and is largely disengaged during wakefulness. The biological need for sleep across all species may therefore reflect that the brain must enter a state of activity that enables elimination of potentially neurotoxic waste products, including β-amyloid. Since the concept of the glymphatic system is relatively new, we will here review its basic structural elements, organization, regulation, and functions. We will also discuss recent studies indicating that glymphatic function is suppressed in various diseases and that failure of glymphatic function in turn might contribute to pathology in neurodegenerative disorders, traumatic brain injury and stroke.
KEYWORDS: Aging; Astrocytes; Cerebrospinal fluid secretion; Neurodegenerative diseases; Perivascular spaces; Sleep; The glymphatic system; Traumatic brain injury; Virchow-Robin spaces
La anestesia general inhibe la actividad del sistema glimfático
General Anesthesia Inhibits the Activity of the "Glymphatic System".
Theranostics. 2018 Jan 1;8(3):710-722. doi: 10.7150/thno.19154. eCollection 2018.
INTRODUCTION: According to the "glymphatic system" hypothesis, brain waste clearance is mediated by a continuous replacement of the interstitial milieu by a bulk flow of cerebrospinal fluid (CSF). Previous reports suggested that this cerebral CSF circulation is only active during general anesthesia or sleep, an effect mediated by the dilatation of the extracellular space. Given the controversies regarding the plausibility of this phenomenon and the limitations of currently available methods to image the glymphatic system, we developed original whole-brain in vivo imaging methods to investigate the effects of general anesthesia on the brain CSF circulation. METHODS: We used magnetic resonance imaging (MRI) and near-infrared fluorescence imaging (NIRF) after injection of a paramagnetic contrast agent or a fluorescent dye in the cisterna magna, in order to investigate the impact of general anesthesia (isoflurane, ketamine or ketamine/xylazine) on the intracranial CSF circulation in mice. RESULTS:In vivo imaging allowed us to image CSF flow in awake and anesthetized mice and confirmed the existence of a brain-wide CSF circulation. Contrary to what was initially thought, we demonstrated that the parenchymal CSF circulation is mainly active during wakefulness and significantly impaired during general anesthesia. This effect was especially significant when high doses of anesthetic agent were used (3% isoflurane). These results were consistent across the different anesthesia regimens and imaging modalities. Moreover, we failed to detect a significant change in the brain extracellular water volume using diffusion weighted imaging in awake and anesthetized mice. CONCLUSION: The parenchymal diffusion of small molecular weight compounds from the CSF is active during wakefulness. General anesthesia has a negative impact on the intracranial CSF circulation, especially when using a high dose of anesthetic agent.
KEYWORDS: Alzheimer; anesthesia; choroid plexus.; glymphatic system; magnetic resonance imaging
La interferencia del sistema glimfático como mediador del trauma cerebral y la encefalopatía traumática crónica.
Glymphatic system disruption as a mediator of brain trauma and chronic traumatic encephalopathy.
Neurosci Biobehav Rev. 2018 Jan;84:316-324. doi: 10.1016/j.neubiorev.2017.08.016. Epub 2017 Aug 30.
Traumatic brain injury (TBI) is an increasingly important issue among veterans, athletes and the general public. Difficulties with sleep onset and maintenance are among the most commonly reported symptoms following injury, and sleep debt is associated with increased accumulation of beta amyloid (Aβ) and phosphorylated tau (p-tau) in the interstitial space. Recent research into the glymphatic system, a lymphatic-like metabolic clearance mechanism in the central nervous system (CNS) which relies on cerebrospinal fluid (CSF), interstitial fluid (ISF), and astrocytic processes, shows that clearance is potentiated during sleep. This system is damaged in the acute phase following mTBI, in part due to re-localization of aquaporin-4 channels away from astrocytic end feet, resulting in reduced potential for waste removal. Long-term consequences of chronic dysfunction within this system in the context of repetitive brain trauma and insomnia have not been established, but potentially provide one link in the explanatory chain connecting repetitive TBI with later neurodegeneration. Current research has shown p-tau deposition in perivascular spaces and along interstitial pathways in chronic traumatic encephalopathy (CTE), pathways related to glymphatic flow; these are the main channels by which metabolic waste is cleared. This review addresses possible links between mTBI-related damage to glymphatic functioning and physiological changes found in CTE, and proposes a model for the mediating role of sleep disruption in increasing the risk for developing CTE-related pathology and subsequent clinical symptoms following repetitive brain trauma.
KEYWORDS: Aquaporin 4; Chronic traumatic encephalopathy; Glymphatic system; Insomnia; Sleep; Traumatic brain injury
Safe Anaesthesia Worldwide
Delivering safe anaesthesia to the world's poorest people
World Congress on Regional Anesthesia & Pain Medicine
April 19-21, 2018, New York City, USA
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Anestesiología y Medicina del Dolor

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