Discovery

Sponsor:

Duration: 2010 to 2013

Abstract:

Spinal cord injury (SCI) reduces life span. People with SCI develop heart disease at a younger age and a higher frequency than other people. We do not know why this occurs. Cardiovascular disease in people with SCI may not related be to usual risk factors, such as unhealthy diet or lack of exercise. In most people, the body makes automatic adjustments to keep blood pressure within a normal range. Many people with spinal cord injuries (SCIs) do not have normal control over their blood pressure : it varies over a wide range. People with SCI experience large drops in blood pressure in response to sitting upright. This condition is called “orthostatic hypotension” or OH. People with SCI also experience dangerous elevations in blood pressure. This condition is called “autonomic dysreflexia” or AD. The events that cause AD can be very mild, such as a full bladder or bowel, or even a tight belt or shoelace. Both OH and AD reduce quality of life for people with SCI. For example, OH causes fatigue and interferes with rehabilitation. If left untreated, AD can result in stroke and even
death. Over the long term, we do not know how these dramatic blood pressure changes affect the cardiovascular system in people with SCI.

This project will determine whether the violent swings in blood pressure experienced bypeople with SCI cause damage to the blood vessels. The structure and function of the blood
vessels is important for normal control of blood pressure. If daily swings in blood pressure damage blood vessels, this will increase the risk of heart disease and stroke in people with SCI. We will also examine whether exercise can prevent damage to blood vessels that occur after SCI.

Sponsor:

Duration: 2010 to 2015

Abstract:

The proposed infrastructure will help to build a multi-disciplinary Autonomic Research Laboratory that will focus on investigating mechanisms of abnormal cardiovascular control that result from spinal cord injury (SCI). Developing novel therapeutic approaches to eliminating autonomic dysfunction and ultimately decreasing cardiovascular-related death and disease among individuals with paralysis will be the major focus of the proposed infrastructure. The infrastructure will be situated within the newly-opened Blusson Spinal Cord Centre (BSSC): home to the International Collaboration on Repair Discoveries (ICORD).

Sponsor:

Duration: 2011 to 2013

Abstract:

Spinal cord injury (SCI) results in structural and functional alterations of pelvic organs. For high SCI, stimulation of pelvic organs often results in autonomic dysreflexia (AD), involving potentially life-threatening spikes in blood pressure. It has been proposed that plasticity within the damaged cord uderlies AD, but little work has been done on possible peripheral mechanisms. This is surprising given that peripheral tissues govern the growth and phenotype of neurons which innervate them. We have found that SCI elicits aberrant growth of sympathetic axons into sensory ganglia, which we hypothesize to be dependent on nerve growth factor (NGF), massively upregulated in the bladder following SCI. We will also investigate reciprocal plasticity: NGF-sensitive sensory axon sprouting in pelvic sympathetic ganglia, and examine the relationship between sprouting, pelvic organ cross-sensitization and AD. Finally, we will test an NGF antagonist’s ability to block or reverse aberrant plasticity, and the functional consequences thereof.

Sponsor: College of Pharmacy

Duration: 2011 to 2013

Abstract:

Damage to the spinal cord disrupts autonomic pathways and consequently perturbs cardiovascular homeostasis. Cardiovascular complications in the early stages of high SCI can be life-threatening, and include bradyarrhythmias, cardiac arrest, and hypotension. While many of these conditions improve in the weeks following SCI, cardiovascular control does not usually return to normal. Cervical and high-thoracic SCI can alter cardiovascular responses to exercise, impair circadian oscillations in blood pressure, and produce autonomic dysreflexia (AD), a condition characterized by episodes of extreme hypertension.

Findings in both animal models and individuals with SCI provide some insight into injury-induced changes that might contribute to disordered cardiovascular control. However, we are far from a complete understanding of mechanisms that underlie the increased risks of cardiovascular disease associated with chronic SCI.  In order to improve quality of life and increase longevity for those with SCI, research that investigates various mechanisms underlying mechanisms of this devastating injury is imperative.

We now know that SCI triggers plasticity in multiple divisions of the central nervous system (CNS) that are critical to cardiovascular control.  However, the majority of studies were focused only on evaluation of the spinal cord neurons involved in cardiovascular control following SCI. This important body of knowledge represents only a fraction of the processes governing cardiovascular function: considerably less is known about SCI-induced changes in the brainstem cardiovascular neurons.

Understanding SCI-induced changes in the brains stem neurons, and how such changes progress over time following injury, is a critical first step toward developing and testing therapeutic interventions in order to reestablish brainstem and spinal cord connections and to improve the cardiovascular outcome of SCI.