# Neuromuscular junction as a therapeutic target to improve post-traumatic outcomes

> **NIH NIH R01** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2022 · $376,075

## Abstract

Project Summary
Severe hemorrhage from extremity injuries is a significant cause of battlefield deaths and preventable trauma
fatalities in civilian medicine. Tourniquet use is the most effective means of arresting life-threatening limb
hemorrhage in the pre-hospital setting and creating bloodless surgical fields in orthopedic and vascular
surgeries; however, tourniquet-related ischemia and subsequent reperfusion (IR) can cause serious IR injuries.
These IR injuries have led to the limitations of tourniquet use. Exploring the mechanisms and finding effective
therapies can resolve the limitations of tourniquet use and improve outcomes and quality of life in post-
traumatic patients. The neuromuscular junction is structured to transmit electrical signals from motor nerve
terminals to nicotinic acetylcholine receptors (nAChRs) for affecting muscle function. Our pilot data
demonstrated that some nAChR clusters are fragmented in mice with 6 weeks of tourniquet-induced IR.
Therefore, in Aim 1, we will determine the relationship between the fragmentation of nAChR clusters and
muscle contractile dysfunction in long-term tourniquet-induced IR. Additionally, our preliminary studies have
targeted a specific signaling pathway that links fragmentation of nAChR clusters in the injured muscle, namely
the inflammatory cytokine-cyclin-dependent kinase 5 (Cdk5-catenin-rapsyn signaling pathway. In Aim 2, we will
test if the inflammatory cytokine-Cdk5-catenin-rapsyn signaling pathway mediates fragmentation of nAChR
clusters in long-term tourniquet-induced IR. In Aim 3, we will investigate the therapeutic effect of a novel anti-
inflammatory drug on long-term functional and structural recovery of the neuromuscular junction via inhibition
of pro-inflammatory cytokines in mouse models of tourniquet/IR injury. We will design in vitro and in vivo
studies to address our overarching hypothesis that anti-inflammation will promote repair of the neuromuscular
junction. Overall, proposed studies will unveil cellular and molecular mechanisms responsible for long-term
neuromuscular junction disorder in tourniquet-induced IR. These studies will provide further information that
the neuromuscular junction could be a potential therapeutic target in tourniquet/IR injuries, especially through
the application of a novel anti-inflammatory drug in this proposal. This approach has significant potential to
resolve the limitations of clinical tourniquet use, thereby improving outcomes and quality of life in post-
traumatic patients.

## Key facts

- **NIH application ID:** 10420384
- **Project number:** 1R01GM145736-01
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** Yu-Long Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $376,075
- **Award type:** 1
- **Project period:** 2022-07-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10420384

## Citation

> US National Institutes of Health, RePORTER application 10420384, Neuromuscular junction as a therapeutic target to improve post-traumatic outcomes (1R01GM145736-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10420384. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*