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Carcinoembryonic antigen-related cell adhesion molecule 1 inhibits MMP-9-mediated blood-brain-barrier breakdown in a mouse model for ischemic stroke

Standard

Carcinoembryonic antigen-related cell adhesion molecule 1 inhibits MMP-9-mediated blood-brain-barrier breakdown in a mouse model for ischemic stroke. / Ludewig, Peter; Sedlacik, Jan; Gelderblom, Mathias; Bernreuther, Christian; Korkusuz, Yücel; Wagener, Christoph; Gerloff, Christian; Fiehler, Jens; Magnus, Tim; Horst, Andrea Kristina.

in: CIRC RES, Jahrgang 113, Nr. 8, 27.09.2013, S. 1013-22.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Ludewig, P, Sedlacik, J, Gelderblom, M, Bernreuther, C, Korkusuz, Y, Wagener, C, Gerloff, C, Fiehler, J, Magnus, T & Horst, AK 2013, 'Carcinoembryonic antigen-related cell adhesion molecule 1 inhibits MMP-9-mediated blood-brain-barrier breakdown in a mouse model for ischemic stroke', CIRC RES, Jg. 113, Nr. 8, S. 1013-22. https://doi.org/10.1161/CIRCRESAHA.113.301207

APA

Ludewig, P., Sedlacik, J., Gelderblom, M., Bernreuther, C., Korkusuz, Y., Wagener, C., Gerloff, C., Fiehler, J., Magnus, T., & Horst, A. K. (2013). Carcinoembryonic antigen-related cell adhesion molecule 1 inhibits MMP-9-mediated blood-brain-barrier breakdown in a mouse model for ischemic stroke. CIRC RES, 113(8), 1013-22. https://doi.org/10.1161/CIRCRESAHA.113.301207

Vancouver

Ludewig P, Sedlacik J, Gelderblom M, Bernreuther C, Korkusuz Y, Wagener C et al. Carcinoembryonic antigen-related cell adhesion molecule 1 inhibits MMP-9-mediated blood-brain-barrier breakdown in a mouse model for ischemic stroke. CIRC RES. 2013 Sep 27;113(8):1013-22. https://doi.org/10.1161/CIRCRESAHA.113.301207

Bibtex

@article{03c8a99f73704376a1299782289ca133,
title = "Carcinoembryonic antigen-related cell adhesion molecule 1 inhibits MMP-9-mediated blood-brain-barrier breakdown in a mouse model for ischemic stroke",
abstract = "RATIONALE: Blood-brain-barrier (BBB) breakdown and cerebral edema result from postischemic inflammation and contribute to mortality and morbidity after ischemic stroke. A functional role for the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) in the regulation of reperfusion injury has not yet been demonstrated.OBJECTIVE: We sought to identify and characterize the relevance of CEACAM1-expressing inflammatory cells in BBB breakdown and outcome after ischemic stroke in Ceacam1(-/-) and wild-type mice.METHODS AND RESULTS: Focal ischemia was induced by temporary occlusion of the middle cerebral artery with a microfilament. Using MRI and Evans blue permeability assays, we observed increased stroke volumes, BBB breakdown and edema formation, reduction of cerebral perfusion, and brain atrophy in Ceacam1(-/-) mice. This translated into poor performance in neurological scoring and high poststroke-associated mortality. Elevated neutrophil influx, hyperproduction, and release of neutrophil-related matrix metalloproteinase-9 in Ceacam1(-/-) mice were confirmed by immune fluorescence, flow cytometry, zymography, and stimulation of neutrophils. Importantly, neutralization of matrix metalloproteinase-9 activity in Ceacam1(-/-) mice was sufficient to alleviate stroke sizes and improve survival to the level of CEACAM1-competent animals. Immune histochemistry of murine and human poststroke autoptic brains congruently identified abundance of CEACAM1(+)matrix metalloproteinase-9(+) neutrophils in the ischemic hemispheres.CONCLUSIONS: CEACAM1 controls matrix metalloproteinase-9 secretion by neutrophils in postischemic inflammation at the BBB after stroke. We propose CEACAM1 as an important inhibitory regulator of neutrophil-mediated tissue damage and BBB breakdown in focal cerebral ischemia.",
author = "Peter Ludewig and Jan Sedlacik and Mathias Gelderblom and Christian Bernreuther and Y{\"u}cel Korkusuz and Christoph Wagener and Christian Gerloff and Jens Fiehler and Tim Magnus and Horst, {Andrea Kristina}",
year = "2013",
month = sep,
day = "27",
doi = "10.1161/CIRCRESAHA.113.301207",
language = "English",
volume = "113",
pages = "1013--22",
journal = "CIRC RES",
issn = "0009-7330",
publisher = "Lippincott Williams and Wilkins",
number = "8",

}

RIS

TY - JOUR

T1 - Carcinoembryonic antigen-related cell adhesion molecule 1 inhibits MMP-9-mediated blood-brain-barrier breakdown in a mouse model for ischemic stroke

AU - Ludewig, Peter

AU - Sedlacik, Jan

AU - Gelderblom, Mathias

AU - Bernreuther, Christian

AU - Korkusuz, Yücel

AU - Wagener, Christoph

AU - Gerloff, Christian

AU - Fiehler, Jens

AU - Magnus, Tim

AU - Horst, Andrea Kristina

PY - 2013/9/27

Y1 - 2013/9/27

N2 - RATIONALE: Blood-brain-barrier (BBB) breakdown and cerebral edema result from postischemic inflammation and contribute to mortality and morbidity after ischemic stroke. A functional role for the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) in the regulation of reperfusion injury has not yet been demonstrated.OBJECTIVE: We sought to identify and characterize the relevance of CEACAM1-expressing inflammatory cells in BBB breakdown and outcome after ischemic stroke in Ceacam1(-/-) and wild-type mice.METHODS AND RESULTS: Focal ischemia was induced by temporary occlusion of the middle cerebral artery with a microfilament. Using MRI and Evans blue permeability assays, we observed increased stroke volumes, BBB breakdown and edema formation, reduction of cerebral perfusion, and brain atrophy in Ceacam1(-/-) mice. This translated into poor performance in neurological scoring and high poststroke-associated mortality. Elevated neutrophil influx, hyperproduction, and release of neutrophil-related matrix metalloproteinase-9 in Ceacam1(-/-) mice were confirmed by immune fluorescence, flow cytometry, zymography, and stimulation of neutrophils. Importantly, neutralization of matrix metalloproteinase-9 activity in Ceacam1(-/-) mice was sufficient to alleviate stroke sizes and improve survival to the level of CEACAM1-competent animals. Immune histochemistry of murine and human poststroke autoptic brains congruently identified abundance of CEACAM1(+)matrix metalloproteinase-9(+) neutrophils in the ischemic hemispheres.CONCLUSIONS: CEACAM1 controls matrix metalloproteinase-9 secretion by neutrophils in postischemic inflammation at the BBB after stroke. We propose CEACAM1 as an important inhibitory regulator of neutrophil-mediated tissue damage and BBB breakdown in focal cerebral ischemia.

AB - RATIONALE: Blood-brain-barrier (BBB) breakdown and cerebral edema result from postischemic inflammation and contribute to mortality and morbidity after ischemic stroke. A functional role for the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) in the regulation of reperfusion injury has not yet been demonstrated.OBJECTIVE: We sought to identify and characterize the relevance of CEACAM1-expressing inflammatory cells in BBB breakdown and outcome after ischemic stroke in Ceacam1(-/-) and wild-type mice.METHODS AND RESULTS: Focal ischemia was induced by temporary occlusion of the middle cerebral artery with a microfilament. Using MRI and Evans blue permeability assays, we observed increased stroke volumes, BBB breakdown and edema formation, reduction of cerebral perfusion, and brain atrophy in Ceacam1(-/-) mice. This translated into poor performance in neurological scoring and high poststroke-associated mortality. Elevated neutrophil influx, hyperproduction, and release of neutrophil-related matrix metalloproteinase-9 in Ceacam1(-/-) mice were confirmed by immune fluorescence, flow cytometry, zymography, and stimulation of neutrophils. Importantly, neutralization of matrix metalloproteinase-9 activity in Ceacam1(-/-) mice was sufficient to alleviate stroke sizes and improve survival to the level of CEACAM1-competent animals. Immune histochemistry of murine and human poststroke autoptic brains congruently identified abundance of CEACAM1(+)matrix metalloproteinase-9(+) neutrophils in the ischemic hemispheres.CONCLUSIONS: CEACAM1 controls matrix metalloproteinase-9 secretion by neutrophils in postischemic inflammation at the BBB after stroke. We propose CEACAM1 as an important inhibitory regulator of neutrophil-mediated tissue damage and BBB breakdown in focal cerebral ischemia.

U2 - 10.1161/CIRCRESAHA.113.301207

DO - 10.1161/CIRCRESAHA.113.301207

M3 - SCORING: Journal article

C2 - 23780386

VL - 113

SP - 1013

EP - 1022

JO - CIRC RES

JF - CIRC RES

SN - 0009-7330

IS - 8

ER -