The novel role of perivascular fibroblasts in secondary injury after cervical SCI
NINDS - National Institute of Neurological Disorders and Stroke
About This Grant
Spinal cord injury (SCI) is a devastating condition that causes profound physical and emotional suffering, yet effective treatments remain unavailable. Developing new therapies to mitigate SCI outcomes represents a critical unmet clinical need. Disruption of the blood-spinal cord barrier (BSCB) leads to peripheral immune cell infiltration, exacerbates neuroinflammation, and worsens secondary injury, ultimately causing tissue damage and functional deficits. Protecting the damaged BSCB offers a promising strategy to limit secondary injury and improve outcomes. However, no therapies targeting BSCB dysfunction are currently available. The overall goal of this application is to investigate the previously unexplored role of perivascular fibroblasts in BSCB dysfunction and secondary injury, focusing on identifying perivascular fibroblast-derived peptidase inhibitor 16 (PI16) as a novel therapeutic target for neuroprotection after SCI. Our preliminary studies suggest that activation of the IFNγ pathway plays a key role in activating perivascular fibroblasts and promoting fibrotic scar formation. These activated fibroblasts significantly upregulate PI16 expression, which is closely associated with BSCB dysfunction and exacerbated neuroinflammation. Notably, BSCB disruption, injury size, and functional deficits were significantly reduced in PI16 knockout mice following SCI. Furthermore, a PI16-neutralizing antibody demonstrated robust neuroprotective effects when injected into the injured spinal cord. Based on these strong preliminary data, we hypothesize that upregulation of PI16 in perivascular fibroblasts via IFNγ signaling increases BSCB leakage and immune cell infiltration, exacerbating neuroinflammation and secondary injury, ultimately leading to progressive tissue damage and functional loss following SCI. Therefore, blocking PI16 activity with a neutralizing antibody could protect against tissue loss and promote functional recovery. We will test this hypothesis through three specific aims. Aim 1 will investigate the mechanisms regulating the activation of perivascular fibroblasts and PI16 upregulation after SCI. Aim 2 will validate the key role of PI16 in BSCB permeability, tissue damage, and functional deficits following SCI. Aim 3 will assess the therapeutic potential of PI16-neutralizing antibody treatment after SCI. These studies will provide valuable insights into the new role of perivascular fibroblasts in secondary injury and identify fibroblast-derived PI16 as a novel therapeutic target for SCI. Importantly, we will evaluate the therapeutic potential of a clinically translatable PI16-neutralizing antibody. These studies could pave the way for developing new treatments to improve outcomes for patients with SCI.
Grant Summary
The novel role of perivascular fibroblasts in secondary injury after cervical SCI is a NINDS - National Institute of Neurological Disorders and Stroke grant providing up to $472K for university, nonprofit, healthcare org. Applications are due 2031-03-31 (open). Check eligibility and apply with FindGrants.
Focus Areas
Eligibility
How to Apply
Up to $472K
2031-03-31
- 1Confirm your organization is eligible for The novel role of perivascular fibroblasts in secondary injury after cervical SCI 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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The novel role of perivascular fibroblasts in secondary injury after cervical SCI: Frequently Asked Questions
Who is eligible for the The novel role of perivascular fibroblasts in secondary injury after cervical SCI?
The novel role of perivascular fibroblasts in secondary injury after cervical SCI 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 The novel role of perivascular fibroblasts in secondary injury after cervical SCI provide?
The novel role of perivascular fibroblasts in secondary injury after cervical SCI provides up to $472K 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 The novel role of perivascular fibroblasts in secondary injury after cervical SCI deadline?
Applications for The novel role of perivascular fibroblasts in secondary injury after cervical SCI 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 The novel role of perivascular fibroblasts in secondary injury after cervical SCI?
To apply for The novel role of perivascular fibroblasts in secondary injury after cervical SCI, 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.