A bloody brake on myelin repair

Nave, Klaus‐Armin; Ehrenreich, Hannelore

doi:10.1038/d41586-017-08232-2

Cited by 6 publications

(6 citation statements)

References 12 publications

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“…We also demonstrated a novel function of myelin in regulating ISF drainage and substance transport in the brain ECS. Myelin is crucial for supporting axonal metabolism and speeding up electrical conduction along neural pathways [22-24]. In the present study, we observed that the traced ISF moved along the myelin fiber tracts from the deep nuclei to the superficial cortex; and in the opposite direction, the compact myelin fiber fascicles acted as a barrier impeding movement to adjacent ECS divisions.…”

Section: Discussionsupporting

confidence: 49%

The Drainage of Interstitial Fluid in the Deep Brain is Controlled by the Integrity of Myelination

Wang

Cui³

et al. 2019

Aging and disease

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In searching for the drainage route of the interstitial fluid (ISF) in the deep brain, we discovered a regionalized ISF drainage system as well as a new function of myelin in regulating the drainage. The traced ISF from the caudate nucleus drained to the ipsilateral cortex along myelin fiber tracts, while in the opposite direction, its movement to the adjacent thalamus was completely impeded by a barrier structure, which was identified as the converged, compact myelin fascicle. The regulating and the barrier effects of myelin were unchanged in AQP4-knockout rats but were impaired as the integrity of boundary structure of drainage system was destroyed in a demyelinated rat model. We thus proposed that the brain homeostasis was maintained within each ISF drainage division locally, rather than across the brain as a whole. A new brain division system and a new pathogenic mechanism of demyelination are therefore proposed.

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Section: Discussionsupporting

confidence: 49%

The Drainage of Interstitial Fluid in the Deep Brain is Controlled by the Integrity of Myelination

Wang

Cui³

et al. 2019

Aging and disease

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“…In a demyelinating injury model, therapeutic depletion of fibrinogen decreases BMP pathway activation, increases the number of mature oligodendrocytes within lesions and enhances remyelination 142 . Therefore, fibrinogen is a newly recognized blood-derived regulator of BMP receptor signalling and pro-inflammatory innate immune responses that changes the molecular composition of the stem cell niche after vascular disruption to direct stem cell fate and function 152,153 . Fibrinogen-induced signalling pathways may be important for neurological diseases in which remyelination fails, such as MS, neonatal brain injury and stroke, and in conditions with aberrant cell fate determination or disrupted repair, such as brain and spinal cord injury, cancer, cardiovascular disease and fibrosis.…”

Section: Regeneration and Repairmentioning

confidence: 99%

Fibrinogen in neurological diseases: mechanisms, imaging and therapeutics

2018

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The blood coagulation protein fibrinogen is deposited in the brain in a wide range of neurological diseases and traumatic injuries with blood-brain barrier (BBB) disruption. Recent research has uncovered pleiotropic roles for fibrinogen in the activation of CNS inflammation, induction of scar formation in the brain, promotion of cognitive decline and inhibition of repair. Such diverse roles are possible in part because of the unique structure of fibrinogen, which contains multiple binding sites for cellular receptors and proteins expressed in the nervous system. The cellular and molecular mechanisms underlying the actions of fibrinogen are beginning to be elucidated, providing insight into its involvement in neurological diseases, such as multiple sclerosis, Alzheimer disease and traumatic CNS injury. Selective drug targeting to suppress the damaging functions of fibrinogen in the nervous system without affecting its beneficial effects in haemostasis opens a new fibrinogen therapeutics pipeline for neurological disease.

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“…Myelin sheaths are well known to facilitate rapid action potential propagation along axons, through their lipid-rich, multilamellar composition ( Nave and Werner, 2014 ; Stadelmann et al, 2019 ), their physiology ( Suminaite et al, 2019 ), and their role in organising key ion channels along axonal subdomains, such as nodes of Ranvier ( Sherman and Brophy, 2005 ; Stassart et al, 2018 ). In addition, myelin sheaths are thought to represent a conduit for the metabolic support of axons by oligodendrocytes, which has also been proposed to regulate axonal function and integrity ( Nave, 2010 ; Nave and Ehrenreich, 2018 ) ( Figure 3 ). Furthermore, the fact that myelination can be modified by neuronal activity ( Figure 3 ), and that changes in myelination can affect conduction, has led to the hypothesis that activity regulated myelination may contribute to nervous system plasticity ( Fields, 2015 ; Chang et al, 2016 ; Almeida and Lyons, 2017 ; Monje, 2018 ; Suminaite et al, 2019 ).…”

Section: Glial Cells In the Zebrafish; Origins Differentiation And Functionmentioning

confidence: 99%

Insights Into Central Nervous System Glial Cell Formation and Function From Zebrafish

Neely

Lyons

2021

Front. Cell Dev. Biol.

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The term glia describes a heterogenous collection of distinct cell types that make up a large proportion of our nervous system. Although once considered the glue of the nervous system, the study of glial cells has evolved significantly in recent years, with a large body of literature now highlighting their complex and diverse roles in development and throughout life. This progress is due, in part, to advances in animal models in which the molecular and cellular mechanisms of glial cell development and function as well as neuron-glial cell interactions can be directly studied in vivo in real time, in intact neural circuits. In this review we highlight the instrumental role that zebrafish have played as a vertebrate model system for the study of glial cells, and discuss how the experimental advantages of the zebrafish lend themselves to investigate glial cell interactions and diversity. We focus in particular on recent studies that have provided insight into the formation and function of the major glial cell types in the central nervous system in zebrafish.

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A bloody brake on myelin repair

Cited by 6 publications

References 12 publications

The Drainage of Interstitial Fluid in the Deep Brain is Controlled by the Integrity of Myelination

The Drainage of Interstitial Fluid in the Deep Brain is Controlled by the Integrity of Myelination

Fibrinogen in neurological diseases: mechanisms, imaging and therapeutics

Insights Into Central Nervous System Glial Cell Formation and Function From Zebrafish

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