Reinnervation of Paralyzed Limb Muscle by Nerve-Muscle-Endplate Grafting Technique
Abstract
The proposed research project addresses the Topic Area of Tissue Regeneration. Specifically, it is relevant to two Areas of Encouragement: development of novel therapies to repair neurosensory damage, maintain the distal end organ interface, or regenerate the neuromuscular junction for reinnervation of end organs during peripheral nerve regeneration; and development of novel therapies for regeneration of functional skeletal muscle, particularly treatments for volumetric muscle loss. Activity of skeletal muscles in the body is controlled by the nervous system through peripheral nerves. If a nerve is damaged, the muscle it innervates becomes paralyzed. Peripheral nerve injuries (PNIs) to the extremity are common in both military and civilian circumstances. Military limb trauma and PNIs are caused by combat wounds (blast injuries and gunshot) and non-combat injuries (falls, stress fractures, military training or managing equipment). In the civilian population, extremity injuries and PNIs are mainly caused by vehicle accidents, penetrating trauma, and surgical intervention. PNI is a major source of chronic disabilities, which limit the opportunities to work and diminish the quality of life. A damaged nerve needs to be repaired to restore its function. A great need exists to find novel ways to treat PNIs, as current methods do not work in all patients, with only about 50% of patients regaining useful function. These poor results are largely due to the fact that fewer nerve fibers can pass through the site of repair to reinnervate specialized structures on the muscle fibers called motor endplates (MEPs), which are extremely important for muscles to contract properly. Recognizing the need for a better treatment approach, we developed a novel surgical technique called “nerve-muscle-endplate grafting in the native motor zone (NMEG-NMZ).” NMEG-NMZ has unique advantages over current surgical approaches that we have shown in previous experiments in rats. When we denervated the sternomastoid muscle in the neck and then reinnervated it using our NMEG-NMZ approach, we observed 82% of functional recovery, which was further improved to 90% by adding methods that stimulate nerve growth (i.e., application of certain protein factors or brief electrical stimulation). The proposed research will measure how well NMEG-NMZ can reinnervate denervated limb muscles in rats, both immediately following injury and after a 3-month delay. This is important, because military injuries of this type cannot always be immediately treated, and with other surgical methods, delay worsens the chance of successful recovery. We will also determine the beneficial effects of incorporating various methods that stimulate nerve growth into the process. If successful, this project will make important scientific advances in the field of neuroregeneration and reinnervation. Near term, it will propel further research to identify ideal conditions by which NMEG-NMZ results in optimal recovery. Long term, the ultimate goal of this research is to introduce the NMEG-NMZ technique into clinical practice to treat military Service members, Veterans, and civilians who need muscle reinnervation following PNIs. The potential benefit of application of NMEG-NMZ to treat PNI-induced human paralyzed limbs would be substantial.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010195
Entities
People
- Liancai Mu
Organizations
- Hackensack University Medical Center
- United States Army