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01-12-2020 | Stroke | Rapid Communications

CD137 Ligand-CD137 Interaction is Required For Inflammasome-Associated Brain Injury Following Ischemic Stroke

Authors: David Y. Fann, Emily Pauline Nickles, Luting Poh, Vismitha Rajeev, Sharmelee Selvaraji, Herbert Schwarz, Thiruma V. Arumugam

Published in: NeuroMolecular Medicine | Issue 4/2020

Abstract

The CD137L-CD137 axis is a potent co-stimulatory immune checkpoint regulator that forms a bidirectional signaling pathway between the CD137 ligand (CD137L) and CD137 receptor to regulate immunological activities. This study investigated the potential involvement of the CD137L-CD137 axis on inflammasome-associated brain injury and neurological deficits in a mouse model of focal ischemic stroke. Cerebral ischemia was induced in male C57BL/6J wild-type (WT), CD137L-deficient (CD137L KO) and CD137-deficient (CD137 KO) mice by middle cerebral artery occlusion (MCAO; 60 min), followed by reperfusion (6 h and 24 h). Brain infarct volume and neurological deficit scores were significantly lower in both CD137L KO and CD137 KO mice compared to WT controls. Moreover, CD137L-deficient brains had significantly lower levels of the pyroptotic protein, NT-Gasdermin D, while CD137-deficient brains had significantly lower levels of the pro-apoptotic proteins, cleaved caspase-3, pyroptotic protein, NT-Gasdermin D, and of the secondary pyroptotic protein NT-Gasdermin E, following ischemic stroke. This protection by CD137L and CD137 deletion was associated with a significant decrease in inflammasome signaling. In conclusion, our data provide evidence for the first time that the CD137L-CD137 axis contributes to brain injury and neurological deficits by activating the inflammasome signaling pathway following ischemic stroke.

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Title: CD137 Ligand-CD137 Interaction is Required For Inflammasome-Associated Brain Injury Following Ischemic Stroke
Authors: David Y. Fann
Emily Pauline Nickles
Luting Poh
Vismitha Rajeev
Sharmelee Selvaraji
Herbert Schwarz
Thiruma V. Arumugam
Publication date: 01-12-2020
Publisher: Springer US
Keyword: Stroke
Published in: NeuroMolecular Medicine / Issue 4/2020
Print ISSN: 1535-1084
Electronic ISSN: 1559-1174
DOI: https://doi.org/10.1007/s12017-020-08623-1

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CD137 Ligand-CD137 Interaction is Required For Inflammasome-Associated Brain Injury Following Ischemic Stroke

Abstract

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Abstract

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