My laboratory employs a systems neuroscience approach to addressing pathophysiological changes in autonomic nervous system (e.g., gastrointestinal) functions following spinal cord injury (SCI). My ongoing, studies of post-SCI gastrointestinal dysfunction are revealing that substantial pathophysiological remodeling of the neural reflex circuits occurs following injury. Specifically, in neurally-intact organisms, vagal afferents increase firing rate in response to local gastrointestinal stimuli that result from the presence of food in the digestive system. This sensory information is relayed to the brainstem where appropriate reflex responses are integrated. Furthermore, the gastric neurocircuitry located within the medulla is also responsive to the same gastrointestinal peptides that have entered the circulation. At each of these points, sensitivity to an array of peptides (e.g., cholecystokinin, ghrelin) is significantly attenuated following SCI and provokes GI dysmotility. This suggests that the intrinsic circuitry of the GI tract is compromised after SCI even though it remains anatomically intact.
Project 1 addresses the changes in the voltage-gated channels necessary for propagating a nerve impulse following SCI. Using selective neurophysiological, immunocytochemical and molecular techniques to define the mechanisms resulting in the loss of vagal sensory signaling post-SCI.
Project 2 addresses a vastly understudied co-morbidity following SCI. Neurogenic bowel is a slow transit abnormality that is the most frequent gastrointestinal complaint of individuals with SCI. The GI tract is unique in that it has its own extensive intrinsic nervous system, the enteric nervous system (ENS), and has the ability to function quasi-autonomously. Normal colonic transit requires maintenance of the ENS and a syncytium of cells regulating contraction of the smooth muscle to modulate intrinsic reflexes and coordinate gut activity. While the function of the ENS is presumed to be preserved following SCI, the disruption of reflex colonic transit suggests otherwise. The current project studies the influence of oxidative stress on enteric nervous system-mediated colonic motility following a spinal cord injury (SCI). Learning how post-SCI reactive oxygen species (ROS) in the colon trigger the loss of the enteric neuromuscular junction that regulates colonic smooth muscle contraction.