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Impairment of glymphatic pathway function promotes tau pathology after traumatic brain injury

The Journal of neuroscience, 2014-12, Vol.34 (49), p.16180-16193 [Peer Reviewed Journal]

Copyright © 2014 the authors 0270-6474/14/3416180-14$15.00/0. ;Copyright © 2014 the authors 0270-6474/14/3416180-14$15.00/0 2014 ;ISSN: 0270-6474 ;EISSN: 1529-2401 ;DOI: 10.1523/jneurosci.3020-14.2014 ;PMID: 25471560

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Title:
Impairment of glymphatic pathway function promotes tau pathology after traumatic brain injury
Author: Iliff, Jeffrey J ; Chen, Michael J ; Plog, Benjamin A ; Zeppenfeld, Douglas M ; Soltero, Melissa ; Yang, Lijun ; Singh, Itender ; Deane, Rashid ; Nedergaard, Maiken
Subjects: Animals ; Aquaporin 4 - genetics ; Brain Injuries - complications ; Brain Injuries - genetics ; Brain Injuries - metabolism ; Brain Injuries - pathology ; Cerebrospinal Fluid - metabolism ; Extracellular Fluid - metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Nerve Degeneration - genetics ; Nerve Degeneration - metabolism ; Nerve Degeneration - pathology ; Neurofibrillary Tangles - genetics ; Neurofibrillary Tangles - metabolism ; Neurofibrillary Tangles - pathology ; tau Proteins - metabolism
Is Part Of: The Journal of neuroscience, 2014-12, Vol.34 (49), p.16180-16193
Description: Traumatic brain injury (TBI) is an established risk factor for the early development of dementia, including Alzheimer's disease, and the post-traumatic brain frequently exhibits neurofibrillary tangles comprised of aggregates of the protein tau. We have recently defined a brain-wide network of paravascular channels, termed the "glymphatic" pathway, along which CSF moves into and through the brain parenchyma, facilitating the clearance of interstitial solutes, including amyloid-β, from the brain. Here we demonstrate in mice that extracellular tau is cleared from the brain along these paravascular pathways. After TBI, glymphatic pathway function was reduced by ∼60%, with this impairment persisting for at least 1 month post injury. Genetic knock-out of the gene encoding the astroglial water channel aquaporin-4, which is importantly involved in paravascular interstitial solute clearance, exacerbated glymphatic pathway dysfunction after TBI and promoted the development of neurofibrillary pathology and neurodegeneration in the post-traumatic brain. These findings suggest that chronic impairment of glymphatic pathway function after TBI may be a key factor that renders the post-traumatic brain vulnerable to tau aggregation and the onset of neurodegeneration.
Publisher: United States: Society for Neuroscience
Language: English
Identifier: ISSN: 0270-6474
EISSN: 1529-2401
DOI: 10.1523/jneurosci.3020-14.2014
PMID: 25471560
Source: GFMER Free Medical Journals
MEDLINE
PubMed Central
Alma/SFX Local Collection

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Impairment of glymphatic pathway function promotes tau pathology after traumatic brain injury

Copyright © 2014 the authors 0270-6474/14/3416180-14$15.00/0. ;Copyright © 2014 the authors 0270-6474/14/3416180-14$15.00/0 2014 ;ISSN: 0270-6474 ;EISSN: 1529-2401 ;DOI: 10.1523/jneurosci.3020-14.2014 ;PMID: 25471560

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