NRP/Department of Health WA Sponsored Grants
The Department of Health partners with Neurotrauma Research Program (NRP) aiming at reducing impact of brain trauma and spinal cord injuries.
The Department of Health partners with Neurotrauma Research Program (NRP) aiming at reducing impact of brain trauma and spinal cord injuries.
This project will establish and evaluate the first regional and metropolitan support groups specifically for Aboriginal brain injury survivors and their families to encourage social and emotional wellbeing, and ultimately improve health outcomes for this under-served population. The groups will employ Aboriginal facilitators to offer ongoing, culturally secure psychosocial support, education, practical problem-solving, yarning and socialization to help avoid social isolation for Aboriginal brain injury survivors and their families. The study will use participatory action research methodology to ensure the groups meet participants’/community needs and monitor the development and outcomes of the groups over a six month period.
Spinal cord injury (SCI) increases all-cause mortality, resulting partly from a loss of muscle mass (the origin of important anti-inflammatory signaling molecules) and physical inactivity. We recently showed that isometric “strength training” performed by electrically stimulating the thigh muscles of people with SCI increased muscle mass, reduced spasticity, and improved blood biomarkers of health (cholesterol profile, systemic inflammation). We will now test the effects of electrically-stimulated eccentric strength training, where the muscle lengthens during activation. This type of training has been shown to promote greater muscle mass and health gains in non-clinical subjects but has not been tested after SCI.
Myelin is an insulating substance in the brain that allows nerve cells to function normally. Loss of insulating myelin is a feature of damaged nerve tissue after neurotrauma. However it is not yet known what drives myelin loss. We will test the hypothesis that the cells that mature to make myelin are damaged by free radicals, leading to disruption of blood vessels in the brain and reduced ability to make myelin. We will use an inhibitor of the damage to test whether we can preserve myelin in its normal compact structure.
Increases life expectancy has resulted unprecedented numbers of older drivers on the road, which has contributed to a greater number of road accidents involving older adults. Notably, many of the accidents are explained, in part, by the compromised executive decision-making process with advance age. Here, we propose a novel approach to improve executive decision-making process using transcranial alternating current stimulation (tACS) which is capable of increasing or decreasing the oscillatory rhythms in the brain networks in a frequency-dependent manner. The project will test this novel solution aimed at improving driving skills in older adults, which would reduce road accidents.
We will use AAV vectors to induce expression of collapsin response mediator protein 2 (CRMP-2) in corticospinal (CSN) and neighbouring cortical neurons, to determine if transduction of CSN enhances behavioural recovery after spinal cord injury (SCI). To preserve injured spinal tissue and enhance plasticity and regrowth of corticospinal axons we will also graft rat mesenchymal precursor cells at the injury site. Following on from our successful thoracic injury studies in rat, here we will use a cervical SCI model. In rodents the corticospinal projection is critically important in controlling forelimb function, and in humans is essential for fine manipulatory control.
Despite increasing evidence for neuroplasticity in the adult brain, it is not yet possible to fully reverse injury to the highly ordered neural circuits that underpin complex behaviour. The aim of this application is to understand how we can reliably induce neuro plasticity to accelerate repair and improve function of abnormal circuits. We will combine electromagnetic brain stimulation with visual and motor interventions in mice to increase plasticity and promote brain repair. Our goals is to validate a therapeutic approach to decrease financial, social and emotional costs associated with neurological impairment.
Repetitive transcranial magnetic stimulation is a technique that induces plasticity in the brain and holds great promise for promoting repair after neurotrauma. However, therapeutic outcomes tend to be variable across individuals: it is likely that rTMS is poorly applied because the mechanisms are poorly understood. Research has largely been carried out in humans, making it impossible to identify the cells that are stimulated by rTMS. Here we propose experiments in transgenic mice that will identify the cells and circuits activated by different frequencies of rTMS. Our results will inform the development of rTMS protocols that deliver targeted therapeutic outcomes.
Spinal injury can damage the pathway that carries motor signals from the brain to spinal cord and this leads to muscle weakness. We propose that specific patterns of voluntary exercise of one muscle group can strengthen connections in the spinal cord to the motor nerve cells that carry signals to other non-exercised muscles, and so can improve voluntary strength of those muscles. The project will test this proposal in able bodied people and then in people with incomplete spinal cord injury. If the proposal is correct then these studies will be the first steps to a low-cost adjunct to rehabilitation.
Institutions
Recovery after incomplete spinal cord injury (I-SCI) can be potentiated by repetitive transcranial magnetic stimulation (rTMS)1,2 of the brain. Current rTMS protocols use high stimulation intensities, which can cause discomfort and pain, limit the application duration of rTMS and might cause unwanted stimulation of deeper brain areas 3. Preclinical work from our group has shown that low-intensity rTMS can induce plastic changes and affect behaviour 4–7. In the current proposal we will test the safety and feasibility of a stimulation protocol mimicking that used in our preclinical work, and measure outcomes using robotics and neurophysiology.
Institutions
Bladder dysfunction and urinary tract infections (UTIs) are common after SCI, causing significant morbidity. Self-management is complex, Our recent pilot study interviewing community-living individuals with SCI indicated, in the year post-hospital discharge, they frequently struggled to follow catheterisation and infection control advice due to lifestyle issues, a situation further complicated by inconsistent urological follow up. This study builds on our pilot data to better understand the lived experience of neurogenic bladder. We will investigate adherence to medically prescribed bladder management, perceived barriers to optimal self-care, symptomatic UTI incidence and urological review status which will inform of improvement of community outcomes.
Institutions
Loss of insulating myelin is a feature of damaged nerve tissue after neurotrauma. However it is not yet known what drives death of the cells that make myelin. We will test the hypothesis that the DNA of cells that make myelin is damaged by free radicals, leading to those cells abnormally dividing and therefore dying. We will use an inhibitor of cell division to test whether we can reverse the damage and preserve myelin in its normal compact structure.
Institutions
Mild traumatic brain injury, also referred to as concussion, accounts for 70-85% of traumatic brain injury in Australia and worldwide. 20% of people who suffer a mild traumatic brain injury go on to have long lasting symptoms including problems thinking, depression and headaches (called post-concussion syndrome). We currently cannot predict which patients will go on to have long term problems, so patients are not appropriately directed to treatment. In this Project we will validate a likely combination of psychological outcomes, blood biomarkers and advanced imaging as a way of predicting post-concussion syndrome following mild traumatic brain injury.
Institutions
Poly-arginine peptide are a novel class of neuroprotective agents with demonstrated benefits in experimental neurotrauma, however the mechanisms by which this occurs have not been fully investigated. Since mitochondria are cell structures critically involved in cell survival and energy production, and preliminary evidence shows poly-arginine peptides restores the latter after injury, this application will examine how these peptides influence neuronal mitochondrial function after a mechanically induced injury. We will determine if poly-arginine peptides mitigate cell death and whether this aligns with mitochondrial localisation, and further explore what mitochondrial structures are potentially affected by these peptides to exert beneficial effects.
Institutions
Brain stimulation offers enormous potential to repair the injured brain by inducing neuroplasticity. However, we still do not understand how brain stimulation works, which significantly blunts its efficacy and application. In this project I study how one form of brain stimulation, repetitive transcranial magnetic stimulation (rTMS) works in injured brains. I use fluorescent and fMRI imaging techniques in preclinical models to study the effects of rTMS on neuronal activity in injured brains. Our results will reveal how rTMS protocols can be used to drive plasticity and promote long lasting therapeutic changes in brain connectivity and behaviour.
Institutions
Self-renewal and multipotency are central features that make stem cells promising candidates for therapy following injury to the brain and spinal cord. However we are yet to fully understand what are the pivotal factors that determine if the stem cells differentiate into a neuron or a glial cell or become quiescent. We propose to unravel this particular phenomenon by integrating medical bionics technology with genomics and bioinformatics to develop the first comprehensive map for programming stem cell differentiation. The outcomes of this project will make a landmark contribution towards realising stem cell based therapy for Neurotrauma a reality.