The Glymphatic System: A Beginner’s Guide

Aalling, Nadia; Munk, Anne Sofie Finmann; Lundgaard, Iben

doi:10.1007/s11064-015-1581-6

Cited by 1,491 publications

(1,447 citation statements)

References 134 publications

(188 reference statements)

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“…The recently discovered glymphatic brain clearance system uses physiological pulsations to clear the brain tissue by convecting water through the brain tissue via aquaporin AQP4 water channels especially during sleep (Iliff & Nedergaard, 2013; Jessen, Munk, Lundgaard, & Nedergaard, 2015; Nedergaard, 2013). In human brain, glymphatic system may be driven partially by respiratory and vasomotor control waves in addition to cardiac pulses (Kiviniemi et al., 2016).…”

Section: Discussionmentioning

confidence: 99%

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Altered physiological brain variation in drug‐resistant epilepsy

et al. 2018

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IntroductionFunctional magnetic resonance imaging (fMRI) combined with simultaneous electroencephalography (EEG‐fMRI) has become a major tool in mapping epilepsy sources. In the absence of detectable epileptiform activity, the resting state fMRI may still detect changes in the blood oxygen level‐dependent signal, suggesting intrinsic alterations in the underlying brain physiology.MethodsIn this study, we used coefficient of variation (CV) of critically sampled 10 Hz ultra‐fast fMRI (magnetoencephalography, MREG) signal to compare physiological variance between healthy controls (n = 10) and patients (n = 10) with drug‐resistant epilepsy (DRE).ResultsWe showed highly significant voxel‐level (p < 0.01, TFCE‐corrected) increase in the physiological variance in DRE patients. At individual level, the elevations range over three standard deviations (σ) above the control mean (μ) CVMREG values solely in DRE patients, enabling patient‐specific mapping of elevated physiological variance. The most apparent differences in group‐level analysis are found on white matter, brainstem, and cerebellum. Respiratory (0.12–0.4 Hz) and very‐low‐frequency (VLF = 0.009–0.1 Hz) signal variances were most affected.ConclusionsThe CVMREG increase was not explained by head motion or physiological cardiorespiratory activity, that is, it seems to be linked to intrinsic physiological pulsations. We suggest that intrinsic brain pulsations play a role in DRE and that critically sampled fMRI may provide a powerful tool for their identification.

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Section: Discussionmentioning

confidence: 99%

“…Prolonged vasodilatations may minimize glymphatic pulsation of the perivascular CSF reservoir and lead to altered tissue homeostasis and further to epileptic activity (Jessen et al., 2015). …”

Section: Discussionmentioning

confidence: 99%

Altered physiological brain variation in drug‐resistant epilepsy

et al. 2018

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“…Aβ deposition in the preclinical stage of AD appears to be associated with worse sleep quality (Ju et al, 2013; Spira and Gottesman, 2017) and was also associated with worse cognitive and memory performance (Molano et al, 2017). An alternative mechanism linking sleep and Aβ has been recently suggested (Mendelsohn and Larrick, 2013), whereby sleep can facilitate the removal of toxic proteins and other molecules from the brain through regulation of the ‘glymphatic’ system (Jessen et al, 2015). Extracellular Aβ is vacated by this mechanism twice as fast as during NREM SWS than during awake periods (Xie et al, 2013).…”

Section: Melatonin In the Treatment Of Circadian Rhythm And Sleep Dismentioning

confidence: 99%

New perspectives on the role of melatonin in human sleep, circadian rhythms and their regulation

Zisapel

2018

British J Pharmacology

565

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In mammals, a central circadian clock, located in the suprachiasmatic nuclei (SCN) of the hypothalamus, tunes the innate circadian physiological rhythms to the ambient 24 h light–dark cycle to invigorate and optimize the internal temporal order. The SCN‐activated, light‐inhibited production of melatonin conveys the message of darkness to the clock and induces night‐state physiological functions, for example, sleep/wake blood pressure and metabolism. Clinically meaningful effects of melatonin treatment have been demonstrated in placebo‐controlled trials in humans, particularly in disorders associated with diminished or misaligned melatonin rhythms, for example, circadian rhythm‐related sleep disorders, jet lag and shift work, insomnia in children with neurodevelopmental disorders, poor (non‐restorative) sleep quality, non‐dipping nocturnal blood pressure (nocturnal hypertension) and Alzheimer's disease (AD). The diminished production of melatonin at the very early stages of AD, the role of melatonin in the restorative value of sleep (perceived sleep quality) and its sleep‐anticipating effects resulting in attenuated activation of certain brain networks are gaining a new perspective as the role of poor sleep quality in the build‐up of β amyloid, particularly in the precuneus, is unravelled. As a result of the recently discovered relationship between circadian clock, sleep and neurodegeneration, new prospects of using melatonin for early intervention, to promote healthy physical and mental ageing, are of prime interest in view of the emerging link to the aetiology of Alzheimer's disease.Linked ArticlesThis article is part of a themed section on Recent Developments in Research of Melatonin and its Potential Therapeutic Applications. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.16/issuetoc

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“…The recent recognition of the intracerebral paravascular (glymphatic) circulation (Iliff & Nedergaard, 2013; Jessen, Munk, Lundgaard, & Nedergaard, 2015) links the cardiovascular disease and the vascular risk factors even closer to conditions presenting with disturbed CSF circulation. It is therefore of crucial importance to improve our understanding of the relation between these conditions and the cardiovascular comorbidity.…”

Section: Introductionmentioning

confidence: 99%

Cardiovascular risk factors in Chiari malformation and idiopathic intracranial hypertension

2017

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ObjectivesBoth Chiari malformation type 1 (CMI, i.e., the idiopathic caudal ectopy of cerebellar tonsils into foramen magnum) and idiopathic intracranial hypertension (IIH) are characterized by reduced intracranial compliance (ICC) due to disturbed circulation of cerebrospinal fluid (CSF). An increasing body of evidence links cardiovascular disease to CSF circulation disturbances. The aim of this study was to explore whether the prevalence of cardiovascular risk factors in patients with CMI or IIH is higher than in the general population.Materials and MethodsAmong the patients with CMI or IIH treated at our department during the period 2003–2014, we identified those with history of arterial hypertension (AH), myocardial infarction (MI), angina pectoris (AP), or diabetes mellitus (DM). For comparison with a control population, we retrieved information about the prevalence of AH, MI, AP, and DM among participants of the North‐Trøndelag Health Study 3 (HUNT3).ResultsData from 48 CMI and 52 IIH cases were available. Compared to data from the 42,461 individuals participating in the HUNT3, we found increased prevalence of DM in male CMI as well as female IIH cases, and of AH in female IIH cases. Body mass index (BMI) was significantly increased in both female and male IIH cases. Prevalence of MI and AP in the CMI and IIH cohorts was extremely low and therefore not further studied.ConclusionsThis study provided evidence of an increased prevalence of DM in male CMI as well as female IIH cases and of AH in female IIH cases. Although requiring further exploration, these findings point to AH and DM as potential risk factors in the pathophysiology of CMI and IIH.

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The Glymphatic System: A Beginner’s Guide

Cited by 1,491 publications

References 134 publications

Altered physiological brain variation in drug‐resistant epilepsy

Altered physiological brain variation in drug‐resistant epilepsy

New perspectives on the role of melatonin in human sleep, circadian rhythms and their regulation

Cardiovascular risk factors in Chiari malformation and idiopathic intracranial hypertension

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