Journal article
Combined Blockade of Interleukin-1α and -1β Signaling Protects Mice from Cognitive Dysfunction after Traumatic Brain Injury
eNeuro, Vol.5(2), p.ENEURO.0385-17.2018
03/01/2018
DOI: 10.1523/ENEURO.0385-17.2018
PMCID: PMC5898697
PMID: 29662944
Abstract
Diffuse activation of interleukin-1 inflammatory cytokine signaling after traumatic brain injury (TBI) elicits progressive neurodegeneration and neuropsychiatric dysfunction, and thus represents a potential opportunity for therapeutic intervention. Although interleukin (IL)-1α and IL-1β both activate the common type 1 IL-1 receptor (IL-1RI), they manifest distinct injury-specific roles in some models of neurodegeneration. Despite its potential relevance to treating patients with TBI, however, the individual contributions of IL-1α and IL-1β to TBI-pathology have not been previously investigated. To address this need, we applied genetic and pharmacologic approaches in mice to dissect the individual contributions of IL-1α, IL-β, and IL-1RI signaling to the pathophysiology of fluid percussion–mediated TBI, a model of mixed focal and diffuse TBI. IL-1RI ablation conferred a greater protective effect on brain cytokine expression and cognitive function after TBI than did individual IL-1α or IL-1β ablation. This protective effect was recapitulated by treatment with the drug anakinra, a recombinant naturally occurring IL-1RI antagonist. Our data thus suggest that broad targeting of IL-1RI signaling is more likely to reduce neuroinflammation and preserve cognitive function after TBI than are approaches that individually target IL-1α or IL-1β signaling.
Details
- Title: Subtitle
- Combined Blockade of Interleukin-1α and -1β Signaling Protects Mice from Cognitive Dysfunction after Traumatic Brain Injury
- Creators
- Elizabeth A Newell - Department of PediatricsBrittany P Todd - Department of PediatricsJolonda Mahoney - Department of PediatricsAndrew A Pieper - Department of PsychiatryPolly J Ferguson - Department of PediatricsAlexander G Bassuk - Department of Pediatrics
- Resource Type
- Journal article
- Publication Details
- eNeuro, Vol.5(2), p.ENEURO.0385-17.2018
- DOI
- 10.1523/ENEURO.0385-17.2018
- PMID
- 29662944
- PMCID
- PMC5898697
- NLM abbreviation
- eNeuro
- ISSN
- 2373-2822
- eISSN
- 2373-2822
- Publisher
- Society for Neuroscience
- Grant note
- Titan Neurology Research Fund Mary Alice Smith Fund for Neuropsychiatry Research K12 HD027748; R01NS098590; R01AR059703 / HHS | National Institutes of Health (NIH) Brockman Medical Research Foundation
- Alternative title
- Impact of IL-1RI Blockade on TBI
- Language
- English
- Date published
- 03/01/2018
- Academic Unit
- Neurology; Psychiatry; Critical Care; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Rheumatology, Allergy, and Immunology; Neurology (Pediatrics)
- Record Identifier
- 9984070520202771
Metrics
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