285815 20260402150209.0 10.1172/JCI199818 doi pmid:41734021 pmid pmc:PMC13038205 pmc 0021-9738 ISSN 1558-8238 ISSN DZNE-2026-00351 English 610 Li, Tao 0 Inflammasome adaptor ASC promotes sustained neuroinflammation and mild cognitive impairment in a closed-head injury model. Ann Arbor, Mich. 2026 ASCJ article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1775134735_15916 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote Mild traumatic brain injury (mTBI) from a closed-head injury (CHI) can lead to prevalent neuropsychiatric disorders, including mood disorders and an increased risk for neurodegenerative diseases and dementia. Inflammasomes are molecular complexes crucial for neuroinflammation and secondary damage after trauma, however their role in mild CHI (mCHI) is poorly understood. In this study, we investigate the cellular expression of inflammasome-related genes and their functional significance in CHI models. Single-cell RNA-seq analysis of cortical tissue after trauma revealed selective expression of Asc (also known as Pycard), which encodes the inflammasome adaptor apoptosis-associated Speck-like protein containing a caspase recruitment domain (ASC), predominantly in microglial clusters. Sustained upregulation of inflammasome-related proteins, microglia activation, and astrocyte reactivity persisted up to 21 days in a model for mTBI, with significant reduction of this pattern in Asc-/- mice. Importantly, mild cognitive impairment induced after mCHI was largely abrogated in Asc-/- mice. These findings suggest that ASC, as the primary inflammasome adaptor, plays a critical role in sustaining neuroinflammation and contributes to cognitive deficits after mCHI. This study provides insights into the molecular neuroinflammatory mechanisms underlying CHI, potentially informing future therapeutic strategies. 352 - Disease Mechanisms (POF4-352) G:(DE-HGF)POF4-352 POF4-352 POF IV 0 Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de Dementia Other Inflammation Other Innate immunity Other Neuroscience Other Transcriptomics Other CARD Signaling Adaptor Proteins NLM Chemicals Inflammasomes NLM Chemicals Pycard protein, mouse NLM Chemicals Animals MeSH CARD Signaling Adaptor Proteins: genetics MeSH CARD Signaling Adaptor Proteins: metabolism MeSH Mice MeSH Cognitive Dysfunction: pathology MeSH Cognitive Dysfunction: metabolism MeSH Cognitive Dysfunction: genetics MeSH Cognitive Dysfunction: etiology MeSH Inflammasomes: genetics MeSH Inflammasomes: metabolism MeSH Disease Models, Animal MeSH Mice, Knockout MeSH Neuroinflammatory Diseases: pathology MeSH Neuroinflammatory Diseases: metabolism MeSH Neuroinflammatory Diseases: genetics MeSH Neuroinflammatory Diseases: etiology MeSH Male MeSH Brain Concussion: pathology MeSH Brain Concussion: genetics MeSH Brain Concussion: metabolism MeSH Microglia: pathology MeSH Microglia: metabolism MeSH Mice, Inbred C57BL MeSH Castro-Gomez, Mario Sergio P:(DE-2719)9002230 1 dzne Botella Lucena, Pablo 2 Vieira-Saecker, Ana P:(DE-2719)9000382 3 Schwartz, Stephanie P:(DE-2719)9000454 4 Ding, Yingying 5 Deng, Yushuang P:(DE-2719)9001013 6 dzne Gou, Maling 7 Stein, Valentin 8 Golenbock, Douglas T P:(DE-2719)9001335 9 Latz, Eicke P:(DE-2719)2000062 10 dzne Heneka, Michael T P:(DE-2719)2000008 11 10.1172/JCI199818 Vol. 136, no. 7, p. e199818 PERI:(DE-600)2018375-6 7 e199818 The journal of clinical investigation 136 2026 0021-9738 http://pub.dzne.de/record/285815/files/DZNE-2026-00351.pdf Restricted http://pub.dzne.de/record/285815/files/DZNE-2026-00351.pdf?subformat=pdfa pdfa Restricted External Institute I:(DE-HGF)0 Extern 1 P:(DE-2719)9002230 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 6 P:(DE-2719)9001013 External Institute I:(DE-HGF)0 Extern 10 P:(DE-2719)2000062 DE-HGF Gesundheit Neurodegenerative Diseases G:(DE-HGF)POF4-350 G:(DE-HGF)POF4-352 G:(DE-HGF)POF4 G:(DE-HGF)POF4-300 G:(DE-HGF)POF Disease Mechanisms 0 JCR StatID:(DE-HGF)0100 StatID J CLIN INVEST : 2022 2024-12-27 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2024-12-27 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2024-12-27 DBCoverage StatID:(DE-HGF)0501 StatID DOAJ Seal 2024-02-16T10:37:49Z DBCoverage StatID:(DE-HGF)0500 StatID DOAJ 2024-02-16T10:37:49Z Peer Review StatID:(DE-HGF)0030 StatID DOAJ : Peer review 2024-02-16T10:37:49Z Creative Commons Attribution CC BY (No Version) LIC:(DE-HGF)CCBYNV V:(DE-HGF) DOAJ 2024-02-16T10:37:49Z DBCoverage StatID:(DE-HGF)0600 StatID Ebsco Academic Search 2024-12-27 Peer Review StatID:(DE-HGF)0030 StatID ASC 2024-12-27 DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2024-12-27 DBCoverage StatID:(DE-HGF)1050 StatID BIOSIS Previews 2024-12-27 DBCoverage StatID:(DE-HGF)0160 StatID Essential Science Indicators 2024-12-27 DBCoverage StatID:(DE-HGF)1030 StatID Current Contents - Life Sciences 2024-12-27 DBCoverage StatID:(DE-HGF)1190 StatID Biological Abstracts 2024-12-27 WoS StatID:(DE-HGF)0113 StatID Science Citation Index Expanded 2024-12-27 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2024-12-27 IF >= 15 StatID:(DE-HGF)9915 StatID J CLIN INVEST : 2022 2024-12-27 Article Processing Charges StatID:(DE-HGF)0561 StatID 2024-12-27 Fees StatID:(DE-HGF)0700 StatID 2024-12-27 I:(DE-2719)1013005 AG Ehninger Translational Biogerontology 0 journal EDITORS VDBINPRINT I:(DE-2719)1013005 UNRESTRICTED