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Spatiotemporal sphingosine-1-phosphate receptor 3 expression within the cerebral vasculature after ischemic stroke

Matuskova, Hana LU ; Porschen, Lisa T. LU ; Matthes, Frank LU ; Lindgren, Arne G. LU ; Petzold, Gabor C. and Meissner, Anja LU orcid (2024) In iScience 27(6).
Abstract

Sphingosine-1-phosphate receptors (S1PRs) are promising therapeutic targets in cardiovascular disease, including ischemic stroke. However, important spatiotemporal information for alterations of S1PR expression is lacking. Here, we investigated the role of S1PR3 in ischemic stroke in rodent models and patient samples. We show that S1PR3 is acutely upregulated in perilesional reactive astrocytes after stroke, and that stroke volume and behavioral deficits are improved in mice lacking S1PR3. Further, we find that administration of an S1PR3 antagonist at 4-h post-stroke, but not at later timepoints, improves stroke outcome. Lastly, we observed higher plasma S1PR3 concentrations in experimental stroke and in patients with ischemic stroke.... (More)

Sphingosine-1-phosphate receptors (S1PRs) are promising therapeutic targets in cardiovascular disease, including ischemic stroke. However, important spatiotemporal information for alterations of S1PR expression is lacking. Here, we investigated the role of S1PR3 in ischemic stroke in rodent models and patient samples. We show that S1PR3 is acutely upregulated in perilesional reactive astrocytes after stroke, and that stroke volume and behavioral deficits are improved in mice lacking S1PR3. Further, we find that administration of an S1PR3 antagonist at 4-h post-stroke, but not at later timepoints, improves stroke outcome. Lastly, we observed higher plasma S1PR3 concentrations in experimental stroke and in patients with ischemic stroke. Together, our results establish S1PR3 as a potential drug target and biomarker in ischemic stroke.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Biological sciences, Molecular neuroscience, Natural sciences, Neuroscience, Pathophysiology, Physiology
in
iScience
volume
27
issue
6
article number
110031
publisher
Elsevier
external identifiers
  • pmid:38868192
  • scopus:85194360267
ISSN
2589-0042
DOI
10.1016/j.isci.2024.110031
language
English
LU publication?
yes
id
6e077bbf-cb03-4cc3-b418-43a4ed959ca8
date added to LUP
2024-08-14 15:24:40
date last changed
2024-08-15 03:00:06
@article{6e077bbf-cb03-4cc3-b418-43a4ed959ca8,
  abstract     = {{<p>Sphingosine-1-phosphate receptors (S1PRs) are promising therapeutic targets in cardiovascular disease, including ischemic stroke. However, important spatiotemporal information for alterations of S1PR expression is lacking. Here, we investigated the role of S1PR3 in ischemic stroke in rodent models and patient samples. We show that S1PR3 is acutely upregulated in perilesional reactive astrocytes after stroke, and that stroke volume and behavioral deficits are improved in mice lacking S1PR3. Further, we find that administration of an S1PR3 antagonist at 4-h post-stroke, but not at later timepoints, improves stroke outcome. Lastly, we observed higher plasma S1PR3 concentrations in experimental stroke and in patients with ischemic stroke. Together, our results establish S1PR3 as a potential drug target and biomarker in ischemic stroke.</p>}},
  author       = {{Matuskova, Hana and Porschen, Lisa T. and Matthes, Frank and Lindgren, Arne G. and Petzold, Gabor C. and Meissner, Anja}},
  issn         = {{2589-0042}},
  keywords     = {{Biological sciences; Molecular neuroscience; Natural sciences; Neuroscience; Pathophysiology; Physiology}},
  language     = {{eng}},
  month        = {{06}},
  number       = {{6}},
  publisher    = {{Elsevier}},
  series       = {{iScience}},
  title        = {{Spatiotemporal sphingosine-1-phosphate receptor 3 expression within the cerebral vasculature after ischemic stroke}},
  url          = {{http://dx.doi.org/10.1016/j.isci.2024.110031}},
  doi          = {{10.1016/j.isci.2024.110031}},
  volume       = {{27}},
  year         = {{2024}},
}