Neuromodulation Promotes Tissue Regeneration Over Fibrosis
Abstract
Background: Combat extremity injuries are typified by severe trauma to multiple musculoskeletal tissues. These injuries are known force-subtractors and source of long-term disability. This project directly addresses the FY20PRORP ARA Focus Area of Retention Strategies by testing how neuromodulation can improve healing outcomes for multi-tissue extremity injuries, ultimately restoring tissue function and affecting return to duty. The outcomes of this research will evaluate clinically available therapeutics as potential modulators of nerve-mediated tissue regeneration and attempt to identify novel neuromodulation therapeutic targets. Objective and Hypothesis: The unifying objective of the study is to regulate nerve signaling peptides that influence the tissue healing response, ultimately to discern how neuromodulation can facilitate tissue regeneration over fibrosis. We hypothesize that specific neuropeptides released from injured neurons may be regulated to (i)promote tissue growth, (ii) block cellular senescence and (iii) reduce collagen production following complex tissue injury. Specific Aims: To test our hypothesis, an established animal model of tissue regeneration will be compared to typical fibrotic healing through three aims: Aim 1: Functionally test how afferent nerve-produced Calcitonin Gene Related Protein (CGRP) regulates tissue fibrosis. The working hypothesis is that upregulation of CGRP in injured Mus tissue promotes excessive scar tissue. Aim 2: Functionally test how afferent nerve-produced tachykinins (TK) regulate tissue regeneration. The working hypothesis is that high production of TK peptides in injured Acomys tissue promotes tissue regeneration. Aim 3: Identify other neuropeptides that regulate cytoprotective activity during tissue regeneration which may yield additional therapeutic targets.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2023
- Accession Number
- AD1219290
Entities
People
- Jennifer Simkin
Organizations
- LSU Health Sciences Center New Orleans