Loss of Regulator of G-Protein Signaling 5 Leads to Neurovascular Protection in Stroke

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Özen, IlknurLund University,Lunds universitet,Translationell Neurologi,Forskargrupper vid Lunds universitet,Translational Neurology (TNY),Lund University Research Groups (author)

Loss of Regulator of G-Protein Signaling 5 Leads to Neurovascular Protection in Stroke

Article/chapterEnglish2018

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2018
9 s.

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LIBRIS-ID:oai:lup.lub.lu.se:23c4edf1-3e0d-42c0-92d6-8ae1812f5a73
https://lup.lub.lu.se/record/23c4edf1-3e0d-42c0-92d6-8ae1812f5a73URI
https://doi.org/10.1161/STROKEAHA.118.020124DOI
http://kipublications.ki.se/Default.aspx?queryparsed=id:139137337URI

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Language:English
Summary in:English

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Subject category:art swepub-publicationtype
Subject category:ref swepub-contenttype

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Background and Purpose- In ischemic stroke, breakdown of the blood-brain barrier (BBB) aggravates brain damage. Pericyte detachment contributes to BBB disruption and neurovascular dysfunction, but little is known about its regulation in stroke. Here, we investigated how loss of RGS5 (regulator of G protein signaling 5) in pericytes affects BBB breakdown in stroke and its consequences. Method- We used RGS5 knockout and control mice and applied a permanent middle cerebral occlusion model. We analyzed pericyte numbers, phenotype, and vessel morphology using immunohistochemistry and confocal microscopy. We investigated BBB breakdown by measuring endothelial coverage, tight junctions, and AQP4 (aquaporin 4) in addition to BBB permeability (fluorescent-conjugated dextran extravasation). Tissue hypoxia was assessed with pimonidazole hydrochloride and neuronal death quantified with the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Results- We demonstrate that loss of RGS5 increases pericyte numbers and their endothelial coverage, which is associated with higher capillary density and length, and significantly less BBB damage after stroke. Loss of RGS5 in pericytes results in reduced vascular leakage and preserved tight junctions and AQP4, decreased cerebral hypoxia, and partial neuronal protection in the infarct area. Conclusions- Our findings show that loss of RGS5 affects pericyte-related BBB preservation in stroke and identifies RGS5 as an important target for neurovascular protection.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Neurologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Neurology hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Kardiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Cardiac and Cardiovascular Systems hsv//eng
aquaporin 4
blood-brain barrier
ischemia
neuroprotection
pericytes

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Roth, MichaelaLund University,Lunds universitet,Translationell Neurologi,Forskargrupper vid Lunds universitet,Translational Neurology (TNY),Lund University Research Groups(Swepub:lu)med-mr8 (author)
Barbariga, MarcoLund University,Lunds universitet,Translationell Neurologi,Forskargrupper vid Lunds universitet,Translational Neurology (TNY),Lund University Research Groups(Swepub:lu)med-mb11 (author)
Gaceb, AbderahimLund University,Lunds universitet,Translationell Neurologi,Forskargrupper vid Lunds universitet,Translational Neurology (TNY),Lund University Research Groups(Swepub:lu)med-agc (author)
Deierborg, TomasLund University,Lunds universitet,Neuroinflammation,Forskargrupper vid Lunds universitet,Lund University Research Groups(Swepub:lu)expb-tol (author)
Genové, GuillemKarolinska Institutet,Karolinska Institute (author)
Paul, GesineLund University,Lunds universitet,Translationell Neurologi,Forskargrupper vid Lunds universitet,Translational Neurology (TNY),Lund University Research Groups,Skåne University Hospital(Swepub:lu)mphy-pge (author)
Translationell NeurologiForskargrupper vid Lunds universitet (creator_code:org_t)

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In:Stroke49:9, s. 2182-21901524-4628

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By the author/editor: Özen, Ilknur; Roth, Michaela; Barbariga, Marco; Gaceb, Abderahim; Deierborg, Tomas; Genové, Guillem; show more...; Paul, Gesine; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Neurology

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