The Ageing Brain: Investigating the Role of Age in Changes to the Human Cerebral Microvasculature With an in silico Model

Graff, Barnaby J, Payne, Stephen J and El-Bouri, Wahbi K ORCID: 0000-0002-2732-5927 (2021) The Ageing Brain: Investigating the Role of Age in Changes to the Human Cerebral Microvasculature With an in silico Model. Frontiers in Aging Neuroscience, 13. 632521-.

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Official URL: http://dx.doi.org/10.3389/fnagi.2021.632521

Abstract

<jats:p>Ageing causes extensive structural changes to the human cerebral microvasculature, which have a significant effect on capillary bed perfusion and oxygen transport. Current models of brain capillary networks in the literature focus on healthy adult brains and do not capture the effects of ageing, which is critical when studying neurodegenerative diseases. This study builds upon a statistically accurate model of the human cerebral microvasculature based on <jats:italic>ex-vivo</jats:italic> morphological data. This model is adapted for “healthy” ageing using <jats:italic>in-vivo</jats:italic> measurements from mice at three distinct age groups—young, middle-aged, and old. From this new model, blood and molecular exchange parameters are calculated such as permeability and surface-area-to-volume ratio, and compared across the three age groups. The ability to alter the model vessel-by-vessel is used to create a continuous gradient of ageing. It was found that surface-area-to-volume ratio reduced in old age by 6% and permeability by 24% from middle-age to old age, and variability within the networks also increased with age. The ageing gradient indicated a threshold in the ageing process around 75 years old, after which small changes have an amplified effect on blood flow properties. This gradient enables comparison of studies measuring cerebral properties at discrete points in time. The response of middle aged and old aged capillary beds to micro-emboli showed a lower robustness of the old age capillary bed to vessel occlusion. As the brain ages, there is thus increased vulnerability of the microvasculature—with a “tipping point” beyond which further remodeling of the microvasculature has exaggerated effects on the brain. When developing <jats:italic>in-silico</jats:italic> models of the brain, age is a very important consideration to accurately assess risk factors for cognitive decline and isolate early biomarkers of microvascular health.</jats:p>

Item Type:	Article
Uncontrolled Keywords:	capillaries, cerebral blood flow, healthy ageing, micro-emboli, neurodegenaration
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User:	Symplectic Admin
Date Deposited:	24 Aug 2021 07:48
Last Modified:	18 Jan 2023 21:32
DOI:	10.3389/fnagi.2021.632521
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3134483