The following projects were funded in the Fall 2014 Seed Grant competition:
Development of measurement tools to study hybrid exercise as a novel rehabilitation tool to improve cardiovascular and locomotor outcomes after SCI
Researcher: Dr. Jaimie Borisoff
Proposal: We propose to develop a set of tools for measuring the power output of different cardiovascular exercise machines commonly used by people with spinal cord injury (SCI). These tools are needed in order to effectively study the outcomes of different types of exercise after SCI. Specifically, we will instrument four “hybrid” machines that incorporate arm-driven exercise combined with passive leg movements, each of which provide a different position (seated, semi-recumbent, and standing) and style of exercise (cycling or lever-driven). One of the machines is a new design under development at BCIT that aims to provide arm-driven stepping-like leg movements while standing, thus providing cardiovascular exercise, weight bearing, and the potential for improved walking function. Hybrid exercise has the potential to improve cardiovascular outcomes over and above that possible with arm exercise alone, and at the same time offer the potential for functional neurological improvements through the stepping-like motions performed by users. Furthermore, the ability to exercise while standing offers potential benefits to bone density in the legs – a common problem for people with chronic SCI. The ability to accurately measure power output (which is not available to the degree necessary in commercially available machines) will let us compare a host of physiological outcomes, both while acutely using the machines (e.g. VO2max), as well as in intervention studies that aim to follow people over several weeks in prescribed exercise programs (e.g. long-term heart health). We eventually hope to be able to make recommendations about which types of hybrid exercise are most effective for people with SCI, as well as using these tools to study a new design under development that aims to greatly extend the benefits afforded by hybrid exercise. Hybrid exercise offers the potential for both quality of life improvements (e.g. heart health), as well as functional walking improvements following SCI.
Quantitative MRI in assessing white matter damage following SCI
Researcher: Dr. Piotr Kozlowski
Proposal: Spinal cord injury (SCI) is a devastating event that affects mostly young, healthy individuals and results in lifelong disability. Despite extensive research efforts significant neurological disability remains an ongoing challenge for many SCI patients. Significant interest has been directed towards cell therapies potentially capable of restoring at least some nerve connections, which would lead to functional recovery. There is a number of ongoing or recently completed clinical trials of cell therapies for SCI. The success of these therapies is critically dependent on the ability to accurately assess the damage prior to initiating the therapy and the effectiveness of the treatment throughout it. For that a noninvasive imaging technique capable of assessing the damage in spinal cord is needed. Recently we have developed a novel imaging technique that showed potential for assessing spinal cord damage non-invasively. We propose to further validate this technique in a special pre-clinical model of injury that mimics damage and spontaneous regeneration of the spinal cord. If successful, our novel techniques will facilitate more effective assessment of the efficacy of a cell therapy in pre-clinical models. This will provide a powerful tool for evaluating novel therapeutic strategies in SCI. Eventually, the technique developed and validated throughout this research may be transferred to clinical environment. If successful, our pre-clinical study will lay the groundwork for these future clinical applications.
Pain in the neck: Relationship between cervical spinal cord microstructure, metabolite concentrations, and neuropathic pain after SCI
Researcher: Dr. John Kramer
Proposal: Chronic pain represents a major problem for people living with spinal cord injury. One form of particularly debilitating chronic pain is related directly to damage in the spinal cord, so-called “neuropathic pain”. Neuropathic pain affects up to 50% of people with spinal cord injury and includes “burning/cold” or “tingling” sensations in areas of skin that are otherwise sensationless. There is no cure for neuropathic pain, and current treatment options are limited mainly to managing pain symptoms, which only works for some people. The cause of neuropathic pain is not well understood, which makes coming up with effective treatments, and ultimately a cure, very difficult.
Recent advances using magnetic resonance imaging (MRI) now allow us to study damage in spinal cords of people living with a spinal cord injury. The goal of our research is to use advanced MRI techniques to answer why some individuals develop neuropathic pain after spinal cord injury but others do not. We hink that the location and type of damage in the spinal cord, as well as changes in how cells in the nervous system function, will be important to address this question. People with and without neuropathic pain will undergo MRI scans of their spinal cord and brain and will be asked to fill out a questionnaire that measures how bad their pain is on average. We will then examine our findings from the MRI to see if neuropathic pain is linked to specific types of spinal cord tissue damage. Our long-term goal is to understand the cause of neuropathic pain so that drugs can be developed to more effectively manage symptoms and hopefully repair damage permanently.
PhD proteins as novel targets for SCI neuroprotection and repair
Researcher: Dr. Matt Ramer
Proposal: Astrocytes are cells of the brain and spinal cord that serve many functions including: establishing the barrier between blood and the brain, conveying nutrients and waste between nerve cells and the circulation, and modulating how neurons communicate with each other. Astrocytes also respond to changing oxygen levels in the brain and spinal cord, and can increase the production of red blood cells when oxygen levels drop. In spinal cord injury, astrocytes form some of the most challenging barriers to recovery: they become “reactive”, forming an impenetrable scar at the injury site which does not allow regeneration of injured nerve fibres. Away from the scar, reactive astrocytes participate in the development of neuropathic pain, a major impediment to rehabilitation. We hypothesize that the ability of astrocytes to sense oxygen levels plays a part in these consequences of spinal cord injury. Oxygen sensing within astrocytes is carried out by a group of molecules called the prolyl hydroxylase domain proteins (PHDs). In preliminary studies (in Belgium), I found that mice lacking one of the three variants (PHD1) have remarkable quiescent astrocytes in the spinal cord – they do not react to injury, and mice lacking PHD1 do not develop neuropathic pain. What is more is that white blood cells known as macrophages invade the central nervous system after injury to a greater extent in mice lacking PHD1 than in wild-type mice, and they gain access by using astrocytes as bridges. While these macrophages have typically been thought of as destructive, we have found that they are more reparative than usual in the absence of PHD1. We will generate mice lacking PHD1, then use mice to ask whether nerve fibre growth, glial scar formation and macrophage invasion are modified in such a way as to promote functional recovery (improved movement and decreased pain) following spinal cord injury, or following disconnections of spinal nerves from the cord. These studies will, for the first time, investigate the role of oxygen sensing proteins as a therapeutic target for spinal cord injury.
Don’t sugar coat it: Cardiac consequences of developing type 2 diabetes after SCI
Researcher: Dr. Chris West
Proposal: People with spinal cord injury (SCI) are at an increased risk of developing Type 2 diabetes which likely contributes to the high incidence of cardiovascular disease in this population. Currently, no studies have investigated the development of Type 2 diabetes in people with SCI and in particular studied the effect that developing Type 2 diabetes has on the heart of people with SCI. The aim of the present study is to develop an animal model of SCI combined with Type 2 diabetes. We will then use this model to see whether Type 2 diabetes progresses quicker after SCI, whether the presence of Type 2 diabetes after SCI impairs function of the heart, and what mechanisms might be responsible for the negative impact of diabetes on heart function. It is expected that the results from this study will reveal substantial new insight into the cardiovascular effects of developing Type 2 diabetes after SCI. Should we find that Type 2 diabetes impairs heart function then this will lead to further studies aimed at treating/preventing the development of Type 2 diabetes in people with SCI. By identifying the consequences of Type 2 diabetes and by developing ways to treat/prevent Type 2 diabetes it is expected that this research will aid in the clinical management and treatment of individuals with SCI and significantly improve quality of life for these individuals.