| First Author | Newell EA | Year | 2018 |
| Journal | eNeuro | Volume | 5 |
| Issue | 2 | PubMed ID | 29662944 |
| Mgi Jnum | J:262798 | Mgi Id | MGI:6161998 |
| Doi | 10.1523/ENEURO.0385-17.2018 | Citation | Newell EA, et al. (2018) Combined Blockade of Interleukin-1alpha and -1beta Signaling Protects Mice from Cognitive Dysfunction after Traumatic Brain Injury. eNeuro 5(2):ENEURO.0385-17.2018 |
| abstractText | 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)-1alpha and IL-1beta 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-1alpha and IL-1beta 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-1alpha, IL-beta, 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-1alpha or IL-1beta 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-1alpha or IL-1beta signaling. |
