Cell Specific IL-1R1 in Focal and Diffuse TBI Models
NINDS - National Institute of Neurological Disorders and Stroke
About This Grant
Traumatic brain injury (TBI) is a strong environmental risk factor for dementia. The heterogeneity of TBI phenotypes (e.g., focal contusion vs. diffuse injury) is thought to contribute to the failure of clinical trials. Though pathoanatomically distinct, controlled cortical impact (CCI) and diffuse closed head injury (CHI) models each activate interleukin-1b, but cognitive outcome in IL-1 receptor 1 knockout (IL-1R1 KO) mice is improved after CHI but worse after CCI1, suggesting that targeting IL-1b may be harmful in some TBI patients. While provocative, these studies are inconclusive because of the potential for off target and developmental effects in constitutive IL1R1 KO mice. Alternatively, the divergent effects of IL-1R1 KO in the two models could depend on differences in cell-specific IL-1R1 signaling, or the timing of IL-1R1 signaling (e.g., beneficial early but detrimental later after injury). Preliminary data show improved cognitive outcome after repetitive CHI in constitutive neuronal IL-1R1 KO, and after CCI in endothelial IL-1R1 KO mice. However, whether IL-1R1 signaling is important initially, or whether persistent IL-1R1 activation in the chronic period of CHI or CCI maintains functional deficits and induces neurodegeneration remains unknown. This proposal leverages mice engineered for precise cellular and temporal control of brain IL-1R1 expression that will allow for rigorous determination of where (what cell type) and when targeting IL-1R1 can be beneficial in CHI vs. CCI. Our central hypothesis is that persistent neuronal IL-1R1 signaling drives cognitive deficits, synaptic dysfunction, and impaired neuronal proteostasis after CHI whereas endothelial IL-1R1 drives these neuronal processes after CCI. To test this hypothesis, we propose two Specific Aims: (1) Define brain cell type(s) that mediate post-injury motor and cognitive deficits via IL-1R1 in the chronic period of CCI and CHI, and (2) Test the contributions of endothelial and neuronal IL-1R1 to synaptic dysregulation and neurodegeneration in the chronic period of CCI and CHI.
Grant Summary
Cell Specific IL-1R1 in Focal and Diffuse TBI Models is a NINDS - National Institute of Neurological Disorders and Stroke grant providing up to $322K for university, nonprofit, healthcare org. Applications are due 2031-03-31 (open). Check eligibility and apply with FindGrants.
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How to Apply
Up to $322K
2031-03-31
- 1Confirm your organization is eligible for Cell Specific IL-1R1 in Focal and Diffuse TBI Models from NINDS - National Institute of Neurological Disorders and Stroke, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NINDS - National Institute of Neurological Disorders and Stroke before the deadline.
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Cell Specific IL-1R1 in Focal and Diffuse TBI Models: Frequently Asked Questions
Who is eligible for the Cell Specific IL-1R1 in Focal and Diffuse TBI Models?
Cell Specific IL-1R1 in Focal and Diffuse TBI Models is offered by NINDS - National Institute of Neurological Disorders and Stroke and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Cell Specific IL-1R1 in Focal and Diffuse TBI Models provide?
Cell Specific IL-1R1 in Focal and Diffuse TBI Models provides up to $322K per award from NINDS - National Institute of Neurological Disorders and Stroke. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Cell Specific IL-1R1 in Focal and Diffuse TBI Models deadline?
Applications for Cell Specific IL-1R1 in Focal and Diffuse TBI Models are due 2031-03-31 (open). Because deadlines can change, verify the date with the funder, NINDS - National Institute of Neurological Disorders and Stroke, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Cell Specific IL-1R1 in Focal and Diffuse TBI Models?
To apply for Cell Specific IL-1R1 in Focal and Diffuse TBI Models, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NINDS - National Institute of Neurological Disorders and Stroke.