Vascular instability and neurological morbidity in sickle cell disease: An integrative framework
Vascular instability and neurological morbidity in sickle cell disease: An integrative framework
It is well-established that patients with sickle cell disease (SCD) are at substantial risk of neurological complications, including overt and silent stroke, microstructural injury, and cognitive difficulties. Yet the underlying mechanisms remain poorly understood, partly because findings have largely been considered in isolation. Here, we review mechanistic pathways for which there is accumulating evidence and propose an integrative systems-biology framework for understanding neurological risk. Drawing upon work from other vascular beds in SCD, as well as the wider stroke literature, we propose that macro-circulatory hyper-perfusion, regions of relative micro-circulatory hypo-perfusion, and an exhaustion of cerebral reserve mechanisms, together lead to a state of cerebral vascular instability. We suggest that in this state, tissue oxygen supply is fragile and easily perturbed by changes in clinical condition, with the potential for stroke and/or microstructural injury if metabolic demand exceeds tissue oxygenation. This framework brings together recent developments in the field, highlights outstanding questions, and offers a first step toward a linking pathophysiological explanation of neurological risk that may help inform future screening and treatment strategies.
Stotesbury, Hanne
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Kawadler, Jamie M.
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Hales, Patrick W.
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Saunders, Dawn E.
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Clark, Christopher A.
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Kirkham, Fenella J.
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13 August 2019
Stotesbury, Hanne
18b70efc-1896-481c-8d26-ecf0b8b45d0a
Kawadler, Jamie M.
7d035760-69ea-4b6c-8a7a-771b73453db8
Hales, Patrick W.
4f79496e-1c36-4bba-bb4d-d46974307f4f
Saunders, Dawn E.
9d877417-e3ee-493d-9477-a66b47c3455d
Clark, Christopher A.
b7466af5-d869-466d-8733-6a450950ae3c
Kirkham, Fenella J.
1dfbc0d5-aebe-4439-9fb2-dac6503bcd58
Stotesbury, Hanne, Kawadler, Jamie M., Hales, Patrick W., Saunders, Dawn E., Clark, Christopher A. and Kirkham, Fenella J.
(2019)
Vascular instability and neurological morbidity in sickle cell disease: An integrative framework.
Frontiers in Neurology, 10, [871].
(doi:10.3389/fneur.2019.00871).
Abstract
It is well-established that patients with sickle cell disease (SCD) are at substantial risk of neurological complications, including overt and silent stroke, microstructural injury, and cognitive difficulties. Yet the underlying mechanisms remain poorly understood, partly because findings have largely been considered in isolation. Here, we review mechanistic pathways for which there is accumulating evidence and propose an integrative systems-biology framework for understanding neurological risk. Drawing upon work from other vascular beds in SCD, as well as the wider stroke literature, we propose that macro-circulatory hyper-perfusion, regions of relative micro-circulatory hypo-perfusion, and an exhaustion of cerebral reserve mechanisms, together lead to a state of cerebral vascular instability. We suggest that in this state, tissue oxygen supply is fragile and easily perturbed by changes in clinical condition, with the potential for stroke and/or microstructural injury if metabolic demand exceeds tissue oxygenation. This framework brings together recent developments in the field, highlights outstanding questions, and offers a first step toward a linking pathophysiological explanation of neurological risk that may help inform future screening and treatment strategies.
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fneur-10-00871
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Accepted/In Press date: 26 July 2019
Published date: 13 August 2019
Identifiers
Local EPrints ID: 434062
URI: http://eprints.soton.ac.uk/id/eprint/434062
ISSN: 1664-2295
PURE UUID: 161a1f8f-0129-4ecb-b203-6e0cfa31ef8b
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Date deposited: 11 Sep 2019 16:30
Last modified: 17 Mar 2024 02:53
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Author:
Hanne Stotesbury
Author:
Jamie M. Kawadler
Author:
Patrick W. Hales
Author:
Dawn E. Saunders
Author:
Christopher A. Clark
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