Genetic drivers of cerebral blood flow dysfunction in TBI: a speculative synthesis

Frederick A. Zeiler , Eric P. Thelin , Joseph Donnelly , Andrew R. Stevens , Peter Smielewski , Marek Czosnyka , P. J Hutchinson , D.K. Menon

Abstract

Cerebral autoregulatory dysfunction after traumatic brain injury (TBI) is strongly linked to poor global outcome in patients at 6 months after injury. However, our understanding of the drivers of this dysfunction is limited. Genetic variation among individuals within a population gives rise to single-nucleotide polymorphisms (SNPs) that have the potential to influence a given patient’s cerebrovascular response to an injury. Associations have been reported between a variety of genetic polymorphisms and global outcome in patients with TBI, but few studies have explored the association between genetic variants and cerebrovascular function after injury. In this Review, we explore polymorphisms that might play an important part in cerebral autoregulatory capacity after TBI. We outline a variety of SNPs, their biological substrates and their potential role in mediating cerebrovascular reactivity. A number of candidate polymorphisms exist in genes that are involved in myogenic, endothelial, metabolic and neurogenic vascular responses to injury. Furthermore, polymorphisms in genes involved in inflammation, the central autonomic response and cortical spreading depression might drive cerebrovascular reactivity. Identification of candidate genes involved in cerebral autoregulation after TBI provides a platform and rationale for further prospective investigation of the link between genetic polymorphisms and autoregulatory function.
Author Frederick A. Zeiler - [University of Cambridge]
Frederick A. Zeiler,,
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, Eric P. Thelin - [University of Cambridge]
Eric P. Thelin,,
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, Joseph Donnelly - [University of Cambridge]
Joseph Donnelly,,
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, Andrew R. Stevens - [University of Cambridge]
Andrew R. Stevens,,
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, Peter Smielewski - [University of Cambridge]
Peter Smielewski,,
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, Marek Czosnyka (FEIT / PE)
Marek Czosnyka,,
- The Institute of Electronic Systems
, P. J Hutchinson - [University of Cambridge]
P. J Hutchinson,,
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, D.K. Menon - [University of Cambridge]
D.K. Menon,,
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Journal seriesNature Reviews Neurology, ISSN 1759-4758, (A 50 pkt)
Issue year2019
Vol15
No1
Pages25-39
Publication size in sheets0.7
ASJC Classification2804 Cellular and Molecular Neuroscience; 2728 Clinical Neurology
DOIDOI:10.1038/s41582-018-0105-9
URL https://www.nature.com/articles/s41582-018-0105-9
Languageen angielski
Score (nominal)50
ScoreMinisterial score = 50.0, 11-07-2019, ArticleFromJournal
Publication indicators Scopus Citations = 1; WoS Citations = 0; Scopus SNIP (Source Normalised Impact per Paper): 2017 = 4.434; WoS Impact Factor: 2017 = 19.819 (2) - 2017=20.888 (5)
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