Sphingosine-1-phosphate signalling in aneurysmal subarachnoid haemorrhage: basic science to clinical translation
Sphingosine-1-phosphate signalling in aneurysmal subarachnoid haemorrhage: basic science to clinical translation
Sphingosine-1-phosphate (S1P) is generated intracellularly and, when transported to the extracellular compartment, predominantly signals through S1P receptors. The S1P signalling pathway has been implicated in the pathophysiology of neurological injury following aneurysmal subarachnoid haemorrhage (aSAH). In this review, we bring together all the available data regarding the role of S1P in neurological injury following aSAH. There is agreement in the literature that S1P increases in the cerebrospinal fluid following aSAH and leads to cerebral artery vasospasm. On the other hand, the role of S1P in the parenchyma is less clear cut, with different studies arguing for beneficial and deleterious effects. A parsimonious interpretation of this apparently conflicting data is presented. We discuss the potential of S1P receptor modulators, in clinical use for multiple sclerosis, to be repurposed for aSAH. Finally, we highlight the gaps in our knowledge of S1P signalling in humans, the clinical challenges of targeting the S1P pathway after aSAH and other research priorities.
Outcome, Sphingosine-1-phosphate, Sphingosine-1-phosphate receptor modulators, Subarachnoid haemorrhage
Gaastra, Ben
c7b7f371-706b-4d59-9150-94e8f254e205
Zhang, John
dd0aee1e-3c1f-4cf6-a7de-5c1b7d06b9c6
Tapper, Will
9d5ddc92-a8dd-4c78-ac67-c5867b62724c
Bulters, Diederik
d6f9644a-a32f-45d8-b5ed-be54486ec21d
Galea, Ian
66209a2f-f7e6-4d63-afe4-e9299f156f0b
7 February 2023
Gaastra, Ben
c7b7f371-706b-4d59-9150-94e8f254e205
Zhang, John
dd0aee1e-3c1f-4cf6-a7de-5c1b7d06b9c6
Tapper, Will
9d5ddc92-a8dd-4c78-ac67-c5867b62724c
Bulters, Diederik
d6f9644a-a32f-45d8-b5ed-be54486ec21d
Galea, Ian
66209a2f-f7e6-4d63-afe4-e9299f156f0b
Gaastra, Ben, Zhang, John, Tapper, Will, Bulters, Diederik and Galea, Ian
(2023)
Sphingosine-1-phosphate signalling in aneurysmal subarachnoid haemorrhage: basic science to clinical translation.
Translational Stroke Research.
(doi:10.1007/s12975-023-01133-9).
Abstract
Sphingosine-1-phosphate (S1P) is generated intracellularly and, when transported to the extracellular compartment, predominantly signals through S1P receptors. The S1P signalling pathway has been implicated in the pathophysiology of neurological injury following aneurysmal subarachnoid haemorrhage (aSAH). In this review, we bring together all the available data regarding the role of S1P in neurological injury following aSAH. There is agreement in the literature that S1P increases in the cerebrospinal fluid following aSAH and leads to cerebral artery vasospasm. On the other hand, the role of S1P in the parenchyma is less clear cut, with different studies arguing for beneficial and deleterious effects. A parsimonious interpretation of this apparently conflicting data is presented. We discuss the potential of S1P receptor modulators, in clinical use for multiple sclerosis, to be repurposed for aSAH. Finally, we highlight the gaps in our knowledge of S1P signalling in humans, the clinical challenges of targeting the S1P pathway after aSAH and other research priorities.
Text
s12975-023-01133-9
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More information
Accepted/In Press date: 25 January 2023
e-pub ahead of print date: 7 February 2023
Published date: 7 February 2023
Additional Information:
Funding Information:
BG is funded by the Royal College of Surgeons of England, Society of British Neurological Surgeons, Barrow Foundation, Guarantors of Brain and the Institute for Life Sciences at the University of Southampton. For the purpose of open access, the authors have applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.
Publisher Copyright:
© 2023, The Author(s).
Keywords:
Outcome, Sphingosine-1-phosphate, Sphingosine-1-phosphate receptor modulators, Subarachnoid haemorrhage
Identifiers
Local EPrints ID: 475102
URI: http://eprints.soton.ac.uk/id/eprint/475102
ISSN: 1868-601X
PURE UUID: 5d48a2ec-657d-4968-b376-15c1cc3f488d
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Date deposited: 10 Mar 2023 17:30
Last modified: 17 Mar 2024 04:07
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Author:
John Zhang
Author:
Diederik Bulters
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