IL-1R1 signaling in TBI: assessing chronic impacts and neuroinflammatory dynamics in a mouse model of mild closed-head injury
Year: 2023
Type: article
Abstract: Neuroinflammation contributes to secondary injury cascades following traumatic brain injury (TBI), with alternating waves of inflammation and resolution. Interleukin-1 (IL-1), a critical neuroinflammatory mediator originating from brain endothelial cells, microglia, astrocytes, and peripheral immune cells, is acutely overexpressed after TBI, propagating secondary injury and tissue damage. IL-1 affects blood-brain barrier permeability, immune cell activation, and neural plasticity. Despite the complexity of cytokine signaling post-TBI, we hypothesize that IL-1 signaling specifically regulates neuroinflammatory response components. Using a closed-head injury (CHI) TBI model, we investigated IL-1's role in the neuroinflammatory cascade with a new global knock-out (gKO) mouse model of the IL-1 receptor (IL-1R1), which efficiently eliminates all IL-1 signaling. We found that IL-1R1 gKO attenuated behavioral impairments 14 weeks post-injury and reduced reactive microglia and astrocyte staining in the neocortex, corpus callosum, and hippocampus. We then examined whether IL-1R1 loss altered acute neuroinflammatory dynamics, measuring gene expression changes in the neocortex at 3, 9, 24, and 72 h post-CHI using the NanoString Neuroinflammatory panel. Of 757 analyzed genes, IL-1R1 signaling showed temporal specificity in neuroinflammatory gene regulation, with major effects at 9 h post-CHI. IL-1R1 signaling specifically affected astrocyte-related genes, selectively upregulating chemokines like Ccl2, Ccl3, and Ccl4, while having limited impact on cytokine regulation, such as Tnfα. This study provides further insight into IL-1R1 function in amplifying the neuroinflammatory cascade following CHI in mice and demonstrates that suppression of IL-1R1 signaling offers long-term protective effects on brain health.
Source: Journal of Neuroinflammation
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,490
Awards: Cell-Specific Actions of IL-1 / IL-1R1 Signaling Following Traumatic Brain Injury, Neuroinflammation, Neuronal IL-1R1, and Behavior, Understanding the immune response after mild TBI: Do endothelial cells play a major role?, Training in Translational Research in Alzheimer's and Related Dementias (TRIAD), Neuronal IL-1R1 Signaling in Mild Closed Head Injury, Neurobiology of CNS Injury and Repair
OpenAlex ID: W4387965940