Impairment of paravascular clearance pathways in the aging brain
Benjamin T. Kress,Jeffrey J. Iliff,Jeffrey J. Iliff,Maosheng Xia,Maosheng Xia,Minghuan Wang,Helen S. Wei,Douglas M. Zeppenfeld,Lulu Xie,Hongyi Kang,Qiwu Xu,Jason Liew,Benjamin A. Plog,Fengfei Ding,Fengfei Ding,Rashid Deane +15 more
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TLDR
Evaluating the efficiency of CSF–ISF exchange and interstitial solute clearance is impaired in the aging brain found that bulk flow drainage via the glymphatic system is driven by cerebrovascular pulsation, and is dependent on astroglial water channels that line paravascular CSF pathways.Abstract:
Objective: In the brain, protein waste removal is partly performed by paravascular pathways that facilitate convective exchange of water and soluble contents between cerebrospinal fluid (CSF) and interstitial fluid (ISF). Several lines of evidence suggest that bulk flow drainage via the glymphatic system is driven by cerebrovascular pulsation, and is dependent on astroglial water channels that line paravascular CSF pathways. The objective of this study was to evaluate whether the efficiency of CSF–ISF exchange and interstitial solute clearance is impaired in the aging brain. Methods: CSF–ISF exchange was evaluated by in vivo and ex vivo fluorescence microscopy and interstitial solute clearance was evaluated by radiotracer clearance assays in young (2–3 months), middle-aged (10–12 months), and old (18–20 months) wild-type mice. The relationship between age-related changes in the expression of the astrocytic water channel aquaporin-4 (AQP4) and changes in glymphatic pathway function was evaluated by immunofluorescence. Results: Advancing age was associated with a dramatic decline in the efficiency of exchange between the subarachnoid CSF and the brain parenchyma. Relative to the young, clearance of intraparenchymally injected amyloid-b was impaired by 40% in the old mice. A 27% reduction in the vessel wall pulsatility of intracortical arterioles and widespread loss of perivascular AQP4 polarization along the penetrating arteries accompanied the decline in CSF–ISF exchange. Interpretation: We propose that impaired glymphatic clearance contributes to cognitive decline among the elderly and may represent a novel therapeutic target for the treatment of neurodegenerative diseases associated with accumulation of misfolded protein aggregates. ANN NEUROL 2014;76:845–861read more
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The Neurovascular Unit Coming of Age: A Journey through Neurovascular Coupling in Health and Disease
TL;DR: Evidence supports a conceptual shift in the mechanisms of neurovascular coupling, from a unidimensional process involving neuronal-astrocytic signaling to local blood vessels to a multidimensional one in which mediators released from multiple cells engage distinct signaling pathways and effector systems across the entire cerebrovascular network in a highly orchestrated manner.
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The Glymphatic System: A Beginner’s Guide
TL;DR: The glymphatic system is a recently discovered macroscopic waste clearance system that utilizes a unique system of perivascular tunnels, formed by astroglial cells, to promote efficient elimination of soluble proteins and metabolites from the central nervous system.
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Clearance systems in the brain—implications for Alzheimer disease
Jenna M. Tarasoff-Conway,Roxana O. Carare,Ricardo S. Osorio,Lidia Glodzik,Tracy Butler,Els Fieremans,Leon Axel,Henry Rusinek,Charles Nicholson,Berislav V. Zlokovic,Blas Frangione,Kaj Blennow,Joël Ménard,Henrik Zetterberg,Thomas Wisniewski,Mony J. de Leon +15 more
TL;DR: The clearance systems of the brain as they relate to proteins implicated in AD pathology are described, with the main focus on Aβ.
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Physiology of astroglia
TL;DR: Astrocytes are tightly integrated into neural networks and act within the context of neural tissue; astrocytes control homeostasis of the CNS at all levels of organization from molecular to the whole organ.
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The glymphatic pathway in neurological disorders
TL;DR: The observed reduction in CSF clearance was associated with increasing grey-matter concentrations of Aβ in the human brain, consistent with findings in mice showing that decreased glymphatic function leads to Aβ accumulation and the development of neurodegenerative diseases.
References
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