With one-million dollars in funding from the National Institutes of Health, Harry Goshgarian, PhD, professor of anatomy, is trying to understand the mechanisms that unmask the latent motor pathways which restore function to muscles paralyzed by spinal cord injuries. His research project entitled "Drug-Induced Motor Recovery After Spinal Cord Injury" proposes pharmacological manipulations of the respiratory system to enhance the body’s respiratory centers and restore function to respiratory muscles.
Dr. Goshgarian’s research focus is two-fold. First, he will determine the specific pharmacological mechanisms of methylxanthines on latent motor pathway activation. Secondly, he will determine if methylxanthines can be used to achieve long-term functional restitution of the diaphragm after cervical spinal cord injury.
Dr. Goshgarian will test the following hypotheses:
-that activation of the latent crossed phrenic pathway by methylxanthines is mediated by central neuronal adenosine receptor antagonism;
-that of the four cloned adenosine receptor subtypes, antagonism of the A1 receptor primarily mediates hemidiaphragmatic functional recovery in rats subjected to a C2 spinal cord hemisection;
-and that oral administration of theophylline in C2 spinal hemisected rats will not only induce, but also chronically maintain function in the previously paralyzed ipsilateral hemidiaphragm.
Although theophylline is already used clinically in cases of respiratory dysfunction such as asthma, the drug has never been used to activate latent respiratory pathways and to improve respiratory muscle function following spinal cord injury in humans. Dr. Goshgarian and his colleagues have recently initiated clinical studies to test the possibility that theophylline may have therapeutic effects in spinal cord injured patients.
"We are very excited about the potential impact of these studies," said Dr. Goshgarian. "If theophylline works in humans with spinal cord injuries as we have seen it work in laboratory animals, then we may be able to wean ventilator-dependent patients off of mechanical ventilator support much sooner after their injury than has presently been possible."