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2015 CPSR Trainee Award Winners DR. GINETTE HUPE (Supervisor: Dr. Paul Albert), Ottawa Hospital Research Institute and University of Ottawa Project Title: In vivo optogenetics to examine the role of serotonin modulation in the mediation of recovery from post-stroke depression Project Description: Patients recovering from stroke often experience a prolonged period of post-stroke depression (PSD) which is associated with poorer recovery and an increased risk of second stroke, suicide and death. Depression is associated with dysfunction in the serotonin system and is commonly treated with antidepressant medications (e.g., SSRIs) but many stroke patients with PSD do not show a significant improvement following antidepressant treatment. A better understanding of the underlying mechanisms of the serotonin system is needed to better develop more precise targeted therapies. Our research involves using optogenetics (which uses light to regulate brain activity) on post-stroke mice to examine how serotonin affects behavioural and cognitive symptoms, what brain areas are involved and could be therapeutic targets, and whether directly stimulating serotonin neurons will mediate a rapid improvement in anxiety or depression. DR. TIMAL KANNANGARA (Supervisors: Drs. Diane Lagace & Jean-Claude Béïque), University of Ottawa Project Title: Does altering intrinsic excitability modulate precursor-cells (PCs) during stroke recovery Project Description: After a stroke, there is an increase in the number of new cells that form in the brain and these cells often try to migrate to the brain area injured by the stroke; however, the majority of migrating cells do not survive. The goal of my project is to assess whether changing new cell activity is a viable therapeutic strategy to enhance stroke recovery. Using well-established mouse models for stroke and a variety of different methods to visualize and measure their function during recovery, I will increase the electrical activity of the new cells in the adult brain and assess if this increases the survival of the new cells and alters their ability to participate during recovery. I will also decrease the activity of the new cells, which researchers believe will decrease the survival of new cells during stroke recovery. Thus overall this project will identify how altering the activity level of the new cells changes their ability to survive and function during stroke recovery. LIAM KELLY (Supervisor: Dr. Michelle Ploughman), Memorial University of Newfoundland Project Title: The effects of aerobic exercise training compared to functional exercise training on cardiorespiratory fitness and resting substrate metabolism in chronic stroke Project Description: Low levels of cardiorespiratory fitness are characteristic of individuals who have a stroke. At Memorial University, Dr. Ploughman is examining the effects of aerobic exercise training (AET) or functional exercise training (FET) combined with cognitive training to enhance cognitive performance. The purpose of my project is to compare the effects of AET and FET on measurements of energy metabolism and cardiovascular function among chronic stroke patients and to describe the metabolic demands of FET. The hypothesis is that FET will lead to greater improvements in resting energy metabolism (i.e., increased resting metabolic rate and improved lipid metabolism) and functional recovery. By adding measurements of energy metabolism and cardiovascular function both at rest and during exercise, researchers can obtain valuable information that can be used to develop more efficient and feasible exercise interventions to promote functional recovery and decrease metabolic risk SÉBASTIEN MAILLÉ (Supervisor: Jean-Claude Béïque), University of Ottawa Project Title: Functional dissection of circuits involved in post-stroke depression Project Description: Post-stroke depression (PSD) impacts numerous facets of stroke recovery. Although antidepressant therapy provides some benefit, its efficacy is far from optimal. This is partly due to limited understanding of the etiology underlying PSD, as well as a limited therapeutic armamentarium to effectively treat it. For example, it is currently unknown how a cortical stroke alters information flow through distant moodrelated circuits and how that may be intimately involved in the genesis of PSD. Our multidisciplinary team will employ a vast repertoire of tools and techniques (e.g., wholecell electrophysiology, two-photon imaging and optogenetics) in a rat stroke model that will allow us to fully characterize the changes occurring in these affective networks following a stroke, both at the cellular and network levels. The goal is to functionally and mechanistically characterize the changes to affective networks induced by cortical strokes with the hope that it will open up new avenues for rational therapeutic strategies. MARIE-FRANCE PARÉ (Supervisor: Dr. Bernard Jasmin), University of Ottawa Project Title: Impact of "Exercise Mimetics" that Modulate Skeletal Muscle Phenotype on Brain Repair and Recovery Following Focal Ischemic Stroke Project Description: Exercise is known to decrease the likelihood of stroke, reduce the disability caused by stroke, and improve stroke recovery. Many people with stroke display significant reductions in mobility, which may prevent them from participating in exercise programs. Therefore, an attractive alternative to exercise for persons recovering from a stroke consists in the administration of drugs/small molecules collectively referred to as “exercise mimetics” (EM, so-called because they induce adaptations in skeletal muscle that mimic those seen following endurance exercise). In my doctoral work, I am investigating the therapeutic potential of EMs in the recovery of cognitive and motor function following a stroke, examining in particular the role of the muscle secretome in this process. The hypothesis is that neurologically active molecules will be secreted by skeletal muscle following treatment with EMs, as they are in response to exercise, thereby offering important benefits effects to the brain during stroke recovery. DR. ALISON SCHINKEL-IVY (Supervisor: Dr. Avril Mansfield), Toronto Rehabilitation Institute – University Health Network Project Title: Changes in post-perturbation reactive balance control in individuals with stroke following a six-week perturbation-based training program Project Description: The risk of falling is very high post-stroke and falls and fear of falling are significant barriers to independent mobility, leading to functional decline and reduced quality of life. Falls occur due to a failure to recover from a loss of balance. No exercise intervention effectively prevents falls among individuals with stroke. However, pilot studies suggest that perturbation-based balance training (PBT) may improve the effectiveness of balance reactions post-stroke. Therefore, the aim of the current study is to quantify changes in features of reactive balance control that occur with a 6-week PBT program. As the PBT program consists primarily of standing perturbations, this trial will determine if the training translates to improved recovery from slips. The hypothesis is that the PBT group will demonstrate greater improvements in reactive balance control than a traditional balance training group. DR. LISA SHEEHY (Supervisors: Drs. Heidi Sveistrup, Hillel Finestone, and Martin Bilodeau), Bruyère Research Institute, University of Ottawa Project Title: To determine whether sitting exercises, administered via virtual reality training (VRT) as an adjunct stroke rehabilitation therapy, can improve sitting balance Project Description: Sitting balance is often affected by stroke, resulting in functional impairment (e.g. reaching) and reduced mobility (e.g. getting out of bed). Improvements in balance and motor function can be obtained by task-specific training but the patient must be motivated to perform a task or exercise repeatedly to obtain the most benefit. Virtual Reality Training (VRT) allows patients to do specific exercises while interacting with a video game interface. It is reported to be enjoyable and may encourage repetition of therapeutic exercises. The focus of this study is to determine whether sitting exercises, administered via VRT (using Jintronix system), as an adjunct stroke rehabilitation therapy, can improve sitting balance. Showing that the addition of VRT improves sitting ability and function more than standard inpatient rehabilitation will provide evidence to support its implementation in inpatient and subsequently outpatient rehabilitation programmes and potentially increase the quality of life of stroke survivors. TIJANA SIMIC (Supervisor: Dr. Elizabeth Rochon), Toronto Rehabilitation Institute – University Health Network Project Title: Aphasia therapy: Are executive control processes predictive of treatment gains and generalization? Project Description: Aphasia, the inability to produce or understand language, is a common consequence of stroke. A frustrating type of aphasia, anomia, involves difficulty naming people, places and actions. Executive control (EC) – loosely conceptualized as a supervisory system for higher-level cognitive functions – may be a critical factor. According to The Unity and Diversity Model, there are three distinct EC processes and one common unifying factor. This project will examine which EC processes influence treatment outcomes and generalization in post-stroke aphasia. Participants will undergo a sound-based anomia treatment that requires patients to name a picture stimulus and to study five phonological components associated with that stimulus (e.g., rhyme word, first and last sound, number of syllables). The hypothesis is that naming will improve after treatment and those with higher performance in the EC processes will show larger treatment effects. FARANAK VAHID-ANSARI (Supervisor: Dr. Paul Albert), Ottawa Hospital Research Institute and University of Ottawa Project Title: A new preclinical model of post-stroke depression using endothelin1-induced focal ischemia in the mouse mPFC Project Description: Post-stroke depression (PSD) is common following stroke and linked with poorer outcomes. Current treatments such as antidepressants (e.g., SSRIs) take weeks to work and are only 50% effective. There is very little preclinical work published on PSD relative to recovery of motor function, due in part to lack of a good, reliable preclinical PSD model. A better model would provide the opportunity to better understand underlying mechanisms of PSD and ways to treat it. Using a novel endothelin-1 mouse model of PSD developed in Dr. Albert’s lab, it was possible to assess the effects of two clinically-relevant interventions, exercise and/or antidepressant SSRIs. Initial experiments showed that chronic SSRI-use alone or in combination with exercise (running wheel) was greatest for reversing the anxiety symptoms common with PSD. Future experiments will test ways to amplify or augment this SSRI/exercise-induced behavioural recovery from PSD.