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Impairment of glymphatic pathway function promotes tau pathology after traumatic brain injury
- Source :
- The Journal of neuroscience : the official journal of the Society for Neuroscience. 34(49)
- Publication Year :
- 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.
- Subjects :
- Male
Pathology
medicine.medical_specialty
Traumatic brain injury
Tau protein
tau Proteins
Mice
Cerebrospinal fluid
medicine
Dementia
Animals
Cerebrospinal Fluid
Aquaporin 4
Mice, Knockout
biology
General Neuroscience
Neurodegeneration
Extracellular Fluid
Neurofibrillary Tangles
Articles
medicine.disease
Mice, Inbred C57BL
Brain Injuries
Nerve Degeneration
biology.protein
Glymphatic system
Tauopathy
Psychology
Neuroscience
Subjects
Details
- ISSN :
- 15292401
- Volume :
- 34
- Issue :
- 49
- Database :
- OpenAIRE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Accession number :
- edsair.doi.dedup.....90a232009e3dfbfb20b4c7257ffa4ff8