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A control mechanism for intra-mural peri-arterial drainage via astrocytes: How neuronal activity could improve waste clearance from the brain

A control mechanism for intra-mural peri-arterial drainage via astrocytes: How neuronal activity could improve waste clearance from the brain
A control mechanism for intra-mural peri-arterial drainage via astrocytes: How neuronal activity could improve waste clearance from the brain
The mechanisms behind the clearance of soluble waste from deep within the parenchyma of the brain remain unclear. Experimental evidence reveals that one pathway for clearance of waste, termed intra-mural peri-arterial drainage (IPAD), is the rapid drainage of interstitial fluid along basement membranes (BM) of the smooth muscle cells of cerebral arteries; failure of IPAD is closely associated with the pathology of Alzheimer’s disease (AD), but its driving mechanism remains unclear. We have previously shown that arterial pulsations generated by the heart beat are not strong enough to drive IPAD. Here we present computational evidence for a mechanism for clearance of waste from the brain that is driven by functional hyperaemia, that is, the dilatation of cerebral arterioles as a consequence of increased nutrient demand from neurons. This mechanism is based on our model for the flow of fluid through the vascular BM. It accounts for clearance rates observed in mouse experiments, and aligns with pathological observations and recommendations to lower the individual risk of AD, such as mental and physical activity. Thus, our neurovascular hypothesis should act as the new working hypothesis for the driving force behind IPAD.
1932-6203
Diem, Alexandra K.
05354aac-509f-47df-a7fb-e157c6a34c72
Carare, Roxana O.
0478c197-b0c1-4206-acae-54e88c8f21fa
Weller, Roy O.
4a501831-e38a-4d39-a125-d7141d6c667b
Bressloff, Neil W.
4f531e64-dbb3-41e3-a5d3-e6a5a7a77c92
Diem, Alexandra K.
05354aac-509f-47df-a7fb-e157c6a34c72
Carare, Roxana O.
0478c197-b0c1-4206-acae-54e88c8f21fa
Weller, Roy O.
4a501831-e38a-4d39-a125-d7141d6c667b
Bressloff, Neil W.
4f531e64-dbb3-41e3-a5d3-e6a5a7a77c92

Diem, Alexandra K., Carare, Roxana O., Weller, Roy O. and Bressloff, Neil W. (2018) A control mechanism for intra-mural peri-arterial drainage via astrocytes: How neuronal activity could improve waste clearance from the brain. PLoS ONE, 13 (10), [e0205276]. (doi:10.1371/journal.pone.0205276).

Record type: Article

Abstract

The mechanisms behind the clearance of soluble waste from deep within the parenchyma of the brain remain unclear. Experimental evidence reveals that one pathway for clearance of waste, termed intra-mural peri-arterial drainage (IPAD), is the rapid drainage of interstitial fluid along basement membranes (BM) of the smooth muscle cells of cerebral arteries; failure of IPAD is closely associated with the pathology of Alzheimer’s disease (AD), but its driving mechanism remains unclear. We have previously shown that arterial pulsations generated by the heart beat are not strong enough to drive IPAD. Here we present computational evidence for a mechanism for clearance of waste from the brain that is driven by functional hyperaemia, that is, the dilatation of cerebral arterioles as a consequence of increased nutrient demand from neurons. This mechanism is based on our model for the flow of fluid through the vascular BM. It accounts for clearance rates observed in mouse experiments, and aligns with pathological observations and recommendations to lower the individual risk of AD, such as mental and physical activity. Thus, our neurovascular hypothesis should act as the new working hypothesis for the driving force behind IPAD.

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Accepted/In Press date: 22 September 2018
e-pub ahead of print date: 4 October 2018
Published date: 2018

Identifiers

Local EPrints ID: 424154
URI: http://eprints.soton.ac.uk/id/eprint/424154
ISSN: 1932-6203
PURE UUID: d2c77f9c-b1f0-4f1f-a426-2b581bcca1c6
ORCID for Alexandra K. Diem: ORCID iD orcid.org/0000-0003-1719-1942
ORCID for Roxana O. Carare: ORCID iD orcid.org/0000-0001-6458-3776

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Date deposited: 05 Oct 2018 11:30
Last modified: 26 Nov 2021 02:42

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Contributors

Author: Alexandra K. Diem ORCID iD
Author: Roy O. Weller

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