Grants and Contracts Details
Most spinal cord injuries (SCI) occur near the neck. The cervical level of the spinal cord is located near this area. At this level are the connections to the cells which instruct the diaphragm, the major muscle used for breathing, to contract. Therefore, damage at the cervical level can lead to a paralyzed diaphragm and an inability to breathe and inspire air. Patients who survive this type of injury often need the use of a mechanical ventilator in order to survive. Use of the ventilator severely limits the quality of life of those injured and dramatically increases the demand for health care. However, despite these drastic interventions, the cervical injured patient is still susceptible to death due to respiratory complications. This application proposes to help improve survival, decrease early dependence on mechanical ventilation, and restore breathing after cervical spinal cord injury, as well as develop prognostic indicators for injury progression and recovery. Through these studies we endeavor to add to the standard of care for cervical SCI patients so as to lead to an improved quality of life, better-quality health care management, and improved functional outcomes. To accomplish these goals, we will address the question of whether cervical spinal cord pathways that have been damaged by injury can be made more efficacious to activate the diaphragm and support breathing. This important question has not been answered before and represents a significant gap in knowledge. One possible treatment to repair these connections and restore breathing is administration of the drug compound bisperoxovanadium (bpV for short). bpV can promote cell repair and protection, as well as significantly strengthen communication between cells. In our injury model, which leaves connections damaged, weakened, and needing help to activate the diaphragm, these drug properties can be useful and beneficial. Indeed our preliminary results show that bpV can promote the effectiveness of injured pathways and rescue breathing. This return of breathing function is robustly increased when combined with rehabilitation. We will also determine if we can relieve early dependence on mechanical ventilation with administration of theophylline, an already approved for human use drug which can increase the drive to breathe and which we have shown to have a direct effect on damaged respiratory motor pathways. To answer these questions, we will measure various respiratory motor outcomes, including diaphragm muscle activity recordings, as well as recording breathing patterns before and after injury and treatment. By recording breathing patterns we also aim to develop a way to non-invasively track a return of breathing activity from paralysis. The ultimate goal of our research is to make available to active duty military personnel and Veterans new medical treatments to restore breathing after SCI. We have identified that injured spinal pathways can be directly made more efficacious so as to restore breathing after SCI. We want to realize the potential of this medication (bpV) to promote the recovery of humans who receive a spinal cord injury at the cervical level and have compromised breathing. Thus, we are conducting the necessary pre-clinical trials in animals to optimize this treatment so that it can next be tested for efficacy in humans during early hospital management to promote functional outcomes. We are also studying a separate treatment (theophylline) that can be used to rescue breathing and promote survival in the seconds and minutes after a cervical spinal cord injury. This is a critical time for these patients, prior to their transport to a hospital setting. If determined to be effective, this treatment can be used in battlefield casualties and Veteran patients while en route to the hospital. Both of these approaches will be of immediate translational value, as administration of these pharmacological interventions is through simple injections and do not require invasive surgeries making utilization practical. Finally, we are developing and optimizing measurements of breathing pattern variability as a non-invasive marker of injury severity and prognosis. We envision these as an advanced vital sign with the potential to provide more personalized healthcare to SCI patients. This approach has clinical implication both on the battlefield immediately after injury, and during the long-term, hospital-based course of recovery and rehabilitation.
|Effective start/end date||8/15/16 → 8/14/21|
- Army Medical Research and Materiel Command: $852,402.00
Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.