Impairment of Glymphatic Pathway Function Promotes Tau Pathology after Traumatic Brain Injury
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Open Access
- 3 December 2014
- journal article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 34 (49), 16180-16193
- https://doi.org/10.1523/jneurosci.3020-14.2014
Abstract
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.Keywords
This publication has 61 references indexed in Scilit:
- Cerebral Arterial Pulsation Drives Paravascular CSF–Interstitial Fluid Exchange in the Murine BrainJournal of Neuroscience, 2013
- ‘Hit & Run’ Model of Closed-Skull Traumatic Brain Injury (TBI) Reveals Complex Patterns of Post-Traumatic AQP4 DysregulationJournal of Cerebral Blood Flow & Metabolism, 2013
- Chronic Traumatic Encephalopathy in Blast-Exposed Military Veterans and a Blast Neurotrauma Mouse ModelScience Translational Medicine, 2012
- In VivoMicrodialysis Reveals Age-Dependent Decrease of Brain Interstitial Fluid Tau Levels in P301S Human Tau Transgenic MiceJournal of Neuroscience, 2011
- Pathogenic protein seeding in alzheimer disease and other neurodegenerative disordersAnnals of Neurology, 2011
- Effect of Decompressive Craniectomy on Aquaporin-4 Expression after Lateral Fluid Percussion Injury in RatsJournal of Neurotrauma, 2011
- SIMVASTATIN ATTENUATES MICROGLIAL CELLS AND ASTROCYTE ACTIVATION AND DECREASES INTERLEUKIN-1B LEVEL AFTER TRAUMATIC BRAIN INJURYNeurosurgery, 2009
- Neurovascular mechanisms of Alzheimer's neurodegenerationTrends in Neurosciences, 2005
- Aquaporin‐4 facilitates reabsorption of excess fluid in vasogenic brain edemaThe FASEB Journal, 2004
- Documented head injury in early adulthood and risk of Alzheimer’s disease and other dementiasNeurology, 2000