| Title: |
Selective deletion of interleukin-1 alpha in microglia does not modify acute outcome but may regulate neurorepair processes after experimental ischemic stroke |
| Authors: |
Lemarchand, Eloïse; Grayston, Alba; Wong, Raymond; Rogers, Miyako; Ouvrier, Blake; Llewellyn, Benjamin; Webb, Freddie; Lénárt, Nikolett; Dénes, Ádám; Brough, David; Allan, Stuart M; Bix, Gregory J; Pinteaux, Emmanuel |
| Source: |
Lemarchand, E, Grayston, A, Wong, R, Rogers, M, Ouvrier, B, Llewellyn, B, Webb, F, Lénárt, N, Dénes, Á, Brough, D, Allan, S M, Bix, G J & Pinteaux, E 2025, 'Selective deletion of interleukin-1 alpha in microglia does not modify acute outcome but may regulate neurorepair processes after experimental ischemic stroke', Journal of Cerebral Blood Flow & Metabolism. https://doi.org/10.1177/0271678X251323371 |
| Publication Year: |
2025 |
| Collection: |
The University of Manchester: Research Explorer - Publications |
| Subject Terms: |
conditional gene knockout; interleukin-1 alpha; microglia; neurorepair; stroke |
| Description: |
Inflammation is a key contributor to stroke pathogenesis and exacerbates brain damage leading to poor outcome. Interleukin-1 (IL-1) is an important regulator of post-stroke inflammation, and blocking its actions is beneficial in pre-clinical stroke models and safe in the clinical setting. However, the distinct roles of the two major IL-1 receptor type 1 agonists, IL-1α and IL-1β, and the specific role of IL-1α in ischemic stroke remain largely unknown. Here we show that IL-1α and IL-1β have different spatio-temporal expression profiles in the brain after experimental stroke, with early microglial IL-1α expression (4 h) and delayed IL-1β expression in infiltrated neutrophils and a small microglial subset (24-72 h). We examined for the first time the specific role of microglial-derived IL-1α in experimental permanent and transient ischemic stroke through microglial-specific tamoxifen-inducible Cre-loxP-mediated recombination. Microglial IL-1α deletion did not influence acute outcome after ischemic stroke. However, microglial IL-1α knock out (KO) mice showed reduced peri-infarct vessel density and reactive astrogliosis at 14 days post-stroke, alongside long-term impaired functional recovery. Our study identifies for the first time a critical role for microglial IL-1α on post-stroke neurorepair and recovery, highlighting the importance of targeting specific IL-1 mechanisms in brain injury to develop effective therapies. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/vnd.openxmlformats-officedocument.wordprocessingml.document |
| Language: |
English |
| ISSN: |
0271-678X; 1559-7016 |
| Relation: |
info:eu-repo/semantics/altIdentifier/pissn/0271-678X; info:eu-repo/semantics/altIdentifier/eissn/1559-7016 |
| DOI: |
10.1177/0271678X251323371 |
| Availability: |
https://research.manchester.ac.uk/en/publications/e3dda82b-ab8f-43f3-9082-7824540c0967; https://doi.org/10.1177/0271678X251323371; https://pure.manchester.ac.uk/ws/files/362050840/JCBFM_Lemarchand_2025_Accepted_manuscript.docx; https://journals.sagepub.com/doi/10.1177/0271678X251323371 |
| Rights: |
info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.54F0DEF4 |
| Database: |
BASE |