Flow of cerebrospinal fluid is driven by arterial pulsations and is reduced in hypertension

Nature Communications, Journal Year: 2018, Volume and Issue: 9(1)

Published: Nov. 13, 2018

Flow of cerebrospinal fluid (CSF) through perivascular spaces (PVSs) in the brain is important for clearance metabolic waste. Arterial pulsations are thought to drive flow, but this has never been quantitatively shown. We used particle tracking quantify CSF flow velocities PVSs live mice. pulsatile and driven primarily by cardiac cycle. The speed arterial wall matches that CSF, suggesting motion principal driving mechanism, via a process known as pumping. Increasing blood pressure leaves artery diameter unchanged changes wall, increasing backflow thereby reducing net PVS. Perfusion-fixation alters normal direction causes 10-fold reduction PVS size. conclude velocimetry enables study unprecedented detail studying vivo avoids fixation artifacts.

Language: Английский

---

CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature

Nature Neuroscience, Journal Year: 2018, Volume and Issue: 21(10), P. 1380 - 1391

Published: Sept. 17, 2018

Language: Английский

---

Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms

Frontiers in Microbiology, Journal Year: 2021, Volume and Issue: 12

Published: June 23, 2021

The novel virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic of disease 2019 (COVID-19). Across the globe, subset patients who sustain an SARS-CoV-2 infection are developing wide range persistent symptoms that do not resolve over course many months. These being given diagnosis Long COVID or Post-acute sequelae COVID-19 (PASC). It is likely individual with PASC have different underlying biological factors driving their symptoms, none which mutually exclusive. This paper details mechanisms by RNA viruses beyond just be connected to long-term health consequences. also reviews literature on and other virus-initiated chronic syndromes such as post-Ebola myalgic encephalomyelitis/chronic fatigue (ME/CFS) discuss scenarios for symptom development. Potential contributors include consequences from injury one multiple organs, reservoirs in certain tissues, re-activation neurotrophic pathogens herpesviruses under conditions immune dysregulation, interactions host microbiome/virome communities, clotting/coagulation issues, dysfunctional brainstem/vagus nerve signaling, ongoing activity primed cells, autoimmunity due molecular mimicry between pathogen proteins. individualized nature suggests therapeutic approaches may required best manage care specific diagnosis.

Language: Английский

---

Intranasal Oxytocin: Myths and Delusions

Biological Psychiatry, Journal Year: 2015, Volume and Issue: 79(3), P. 243 - 250

Published: May 11, 2015

Language: Английский

---

Mechanisms of fluid movement into, through and out of the brain: evaluation of the evidence

Fluids and Barriers of the CNS, Journal Year: 2014, Volume and Issue: 11(1), P. 26 - 26

Published: Jan. 1, 2014

Interstitial fluid (ISF) surrounds the parenchymal cells of brain and spinal cord while cerebrospinal (CSF) fills larger spaces within around CNS. Regulation composition volume these fluids is important for effective functioning achieved by barriers that prevent free exchange between CNS blood mechanisms secrete controlled into distribute reabsorb it. Structures associated with this regular turnover include choroid plexuses, capillaries comprising blood-brain barrier, arachnoid villi perineural penetrating cribriform plate. ISF flow, estimated from rates removal markers brain, has been thought to reflect secretion across although questioned because measurements were made under barbiturate anaesthesia possibly affecting flow CSF influx parenchyma via perivascular routes may deliver independently barrier secretion. Fluid at provided specific transporters generate solute fluxes so creating osmotic gradients force water follow. Any due hydrostatic pressures driving soon ceases unless accompanied transport movements modify concentrations. be derived primarily plexuses. Flow measured using phase contrast magnetic resonance imaging reveal more rapid variable than previously supposed, even implying some circumstances net through cerebral aqueduct reversed third lateral ventricles. Such requires there alternative sites both generation CSF. Fluorescent tracer analysis shown can occur along periarterial spaces. Whether represents whether subsequent interstitium out cortex perivenous routes, described as glymphatic circulation, remains established. Modern techniques have revealed complex brain. This review provides a critical evaluation data.

Language: Английский

---

Molecular pathophysiology of cerebral edema

Journal of Cerebral Blood Flow & Metabolism, Journal Year: 2015, Volume and Issue: 36(3), P. 513 - 538

Published: Nov. 16, 2015

Advancements in molecular biology have led to a greater understanding of the individual proteins responsible for generating cerebral edema. In large part, study edema is maladaptive ion transport. Following acute CNS injury, cells neurovascular unit, particularly brain endothelial and astrocytes, undergo program pre- post-transcriptional changes activity channels transporters. These can result transport generation abnormal osmotic forces that, ultimately, manifest as This review discusses past models current knowledge regarding cellular pathophysiology

Language: Английский

---

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

Acta Neuropathologica, Journal Year: 2018, Volume and Issue: 135(3), P. 387 - 407

Published: Feb. 10, 2018

Brain fluids are rigidly regulated to provide stable environments for neuronal function, e.g., low K+, Ca2+, and protein optimise signalling minimise neurotoxicity. At the same time, astroglial waste must be promptly removed. The interstitial fluid (ISF) of brain tissue cerebrospinal (CSF) bathing CNS integral this homeostasis idea a glia-lymph or 'glymphatic' system clearance from has developed over last 5 years. This links bulk (convective) flow CSF into along outside penetrating arteries, glia-mediated convective transport solutes through extracellular space (ECS) involving aquaporin-4 (AQP4) water channel, finally delivery venules peri-venous spaces. However, recent evidence favours important amendments hypothesis, particularly concerning role glia transfer within ECS. review discusses studies which question AQP4 in ISF lack its ability solutes; summarizes attributes ECS that strongly favour diffusion small large molecules without flow; work on hydraulic conductivity nature matrix may impede movement; reconsiders roles perivascular (PVS) CSF-ISF exchange drainage. We also consider extent is possible desirable, impact neuropathology drainage, why using as proxy measure components drug problematic. propose new key historical both support concept system, whereby enters via PVS dispersion larger caliber arteries/arterioles, predominantly regulates CSF/ISF at level neurovascular unit associated with microvessels, and, finally, mixture CSF/ISF/waste products normally cleared venules/veins well other pathways; such not constitute true 'circulation', but, least, suggests comprehensive re-evaluation previously proposed concepts better taking account basic cerebrovascular physiology considerations.

Language: Английский

---

Blood GFAP as an emerging biomarker in brain and spinal cord disorders

Nature Reviews Neurology, Journal Year: 2022, Volume and Issue: 18(3), P. 158 - 172

Published: Feb. 3, 2022

Language: Английский

---

The Glymphatic System and Waste Clearance with Brain Aging: A Review

Gerontology, Journal Year: 2018, Volume and Issue: 65(2), P. 106 - 119

Published: July 11, 2018

The glymphatic system is a glial-dependent waste clearance pathway in the brain, place of lymphatic vessels, dedicated to drain away soluble proteins and metabolic products. Specifically, network serves as “front end” for clearance, connected downstream an authentic network, associated with dura covering brain well cranial nerves large vessels at skull exits. anatomical functional interconnections between these two networks are not completely understood. Several key physiological processes have been identified that control transport function from brain. In this review, we aim provide overview discussion concept behind system, current evidence, controversies, while specifically focusing on consequences aging evidence its existence human Discovering novel strategies optimizing maintaining efficient across lifespan may future prove be important preventing cognitive decline sustaining healthy aging.

Language: Английский

---

Brain-wide glymphatic enhancement and clearance in humans assessed with MRI

JCI Insight, Journal Year: 2018, Volume and Issue: 3(13)

Published: July 11, 2018

To what extent does the subarachnoid cerebrospinal fluid (CSF) compartment communicate directly with extravascular of human brain tissue? Interconnection between CSF and perivascular spaces is reported in some animal studies, but controversy, vivo tracer studies humans are lacking. In present work, we examined distribution a by MRI over prolonged time span. For this, included reference cohort, representing close to healthy individuals, cohort patients dementia anticipated compromise circulation (idiopathic normal pressure hydrocephalus). The contrast agent gadobutrol, which confined intact blood-brain barrier, was used as tracer. Standardized T1-weighted scans were performed before after intrathecal gadobutrol at defined points, including 24 hours, 48 4 weeks. All aligned regions segmented using FreeSurfer, changes normalized T1 signals quantified percentage change from baseline. study provides evidence access all subregions substance administered intrathecally. Clearance delayed cohort. These observations translate previous findings into open new prospects concerning treatment regimens, contrast-enhanced MRI, assessment clearance function.

Language: Английский

---