NRP's Research Focus
The following is a list of the projects our researchers are currently working on:
Basic Science Projects, 2011-2012
Assist. Prof J Rodger, Dr R Sherrard, Prof S Dunlop
Optimising pulsed magnetic fields to promote repair and recovery from neurotrauma
Pulsed magnetic fields provide significant therapeutic benefits in a variety of neurological conditions, but little is known about the underlying mechanisms. This project will systematically quantify, for the first time, how magnetic fields of different frequencies and intensities affect the structure and function of single neurons using in vitro models. Optimal parameters will then be applied to an in vivo model of neurotrauma. The study will advance our understanding of how pulsed magnetic fields repair brain connectivity and restore behaviour and stands to directly and significantly improve current clinical practice.
Assist. Prof M Fitzgerald, Prof S Dunlop, Prof A Harvey
Optimising treatment of secondary degeneration with 670nm red light
Following injury to the central nervous system, the outcome often worsens due to secondary degeneration; control of this process is crucial for maintaining function. We have demonstrated that treating secondary degeneration with 670nm red light using an LED array improved functional outcomes, but the length of treatment required for long term benefit is unknown. This project seeks to define the optimal time of treatment with the red light and determine the long term effects. Optimising treatment of secondary degeneration using 670nm light could provide a safe, easy, readily available and non- invasive early intervention for reducing the impact of neurotrauma.
Assist. Prof J Rodger, Adj A/Prof B Meloni, Dr J Bourne
Testing novel transcranial magnetic stimulation protocols to improve neuro-protection and functional recovery after stroke
Pulsed magnetic fields provide significant therapeutic benefits following stroke in humans. However, because of the scarcity of animal studies, little is known about how repetitive transcranial magnetic stimulation (rTMS) works and how it could be optimised. This project will focus on an animal model of ischaemic stroke and assess tissue loss, regenerative sprouting and behavioural recovery following combinatorial rTMS treatments. The study will determine an ideal rTMS treatment protocol that will optimally repair brain connectivity and improve behaviour following stroke and other kinds of (traumatic) brain injury.
Prof S Dunlop, Assist. Prof M Fitzgerald, Assist. Prof J Rodger, Prof T Salt
Loss of function in spared neural circuits during secondary degeneration and potential rescue with infrared light
Following neurotrauma, spared tissue is vulnerable to secondary degeneration and its rescue is an important therapeutic goal. Dunlop and Fitzgerald have recently established a partial optic nerve cut model in rat and have shown that near infrared light appears to limit early secondary damage and, crucially, preserves vision. However, the investigators do not know why spared axon terminals lose their function without treatment nor how infrared light rescues function. Electrophysiological recording and anatomical tracing will be used to examine spared axons terminals and determine how near infrared light helps them to work normally, thereby preserving vision.
Prof A Harvey, Assist. Prof J Rodger
Anatomical and behavioural analysis of axonal regeneration & target reinnervation after gene- and pharmaco-therapy
Over the past several years, Harvey and his group have developed and optimized a clinically relevant protocol for the treatment of neurotrauma, involving the combined use of AAV gene therapy, pharmacotherapy and tissue transplantation. Using an adult animal visual system as an experimental model these investigators will now use this optimized protocol to maximize the survival and regeneration of injured retinal ganglion cells and determine: (i) the extent to which regenerate axons can reinnervate visual centres in the brain in an orderly fashion and (ii) if the reinnervation is associated with recovery of visual function.
Assist. Prof J Rodger, Dr K Carter
The role of gene regulation by micro-RNA sequences during central nerve regeneration
MicroRNAs (miRNAs) are strands of genetic material that regulate messenger RNA expression in cells, often associated with gene silencing. miRNAs are differentially expressed in patients with neurodegenerative disorders, suggesting that they might have key regulatory roles in neurodegeneration. Rodger and Carter will perform a 'cross-species comparative bioinformatic analysis' to identify miRNAs that could potentially influence neuronal survival and regeneration. They will then use molecules that alter miRNA expression to explore the therapeutic potential of miRNAs in the injured brain.
Prof D Robertson, A/Prof W Mulders, Assist. Prof J Rodger
Molecular changes in the central nervous system associated with inner ear trauma
Inner ear trauma causes changes in nerve cell electrical firing in the brain. Such alterations are likely to underlie sensory disturbances such as tinnitus (noises or ringing in the ears), commonly associated with inner ear damage. This group will study the associated molecular changes that also occur in the brain, gaining a deeper understanding of the fundamental mechanisms of the brain's response to sensory trauma. A drug treatment to reverse both electrical and molecular changes will be tested. These findings may translate to other troublesome sensory disturbances such as neuropathic pain and phantom limb sensations that result from injury to peripheral sensory nerves.
Assist. Prof S Hodgetts
Immunomodulation to enhance improved functional recovery after spinal cord injury using transplanted human bone marrow stromal cells in combinatorial therapies
In previous NRP-funded studies, Hodgetts demonstrated that mesenchymal progenitor cells isolated from the bone marrow of human patients with spinal cord injury (SCI) markedly improve tissue sparing and functional (locomotory) recovery when transplanted in animal models of SCI. He now aims to enhance the effects of hBMSC therapy by modifying the host immune response in order to (i) reduce secondary inflammatory damage and (ii) increase the survival of donor hBMSCs following transplantation. For example, antibodies that block the deleterious effects of specific inflammatory factors and deplete 'Natural Killer' immune cells that target and attack donor hBMSCs will be used to further enhance neuro-regeneration and improve the recovery of locomotor function. If successful, this research will help pave the way for human clinical trials of combinatorial therapies to enhance recovery following SCI.
Assist. Prof M Fitzgerald
Combinatorial treatments for secondary degeneration using ion channel inhibitors
Following injury to the central nervous system, the outcome often worsens due to secondary degeneration involving uncontrolled calcium flux. Control of this process is crucial for maintaining function. Clinical trials using single ion channel antagonists have been disappointing and combinatorial strategies are widely acknowledged as necessary. However, long term outcomes of treatment of secondary degeneration with multiple ion channel inhibitors are unknown. This project aims to define the optimal combination of ion channel inhibitors and determine the long term effects. Optimising treatment of secondary degeneration with combinations of ion channel inhibitors could provide an effective intervention for treatment of neurotrauma.
Prof N Knuckey, Adj A/Prof B Meloni, Dr S. Boulos, Dr K. Campbell
Enhancing neuro-protective efficacy of mild hypothermia / magnesium therapy following cerebral ischaemia/stroke
Cerebral ischaemia, or oxygen starvation in the brain, occurs when there is a reduced blood supply following stroke, traumatic brain injury (TBI) or cardiac arrest. This group, comprised of clinical and basic researchers, has previously shown that combined magnesium therapy and hypothermia (cooling of the body) is neuro-protective following cerebral ischaemia. More recently, the investigators demonstrated that two specific proteins have neuro-protective properties in vitro. This project will assess, in an animal model, whether these proteins can increase the therapeutic window and the neuro-protective effect of magnesium/hypothermia therapy following cerebral ischaemia/stroke. Success may well pave the way to translation to human clinical studies.
Clinical Research Projects, 2011-2012
Prof M Stacey, A/Prof J Swaine, Senior Research Fellow Delia Hendrie
A randomised controlled trial of an individualised self-management program to prevent pressure ulcers following spinal cord injury
Pressure ulcers are a serious and common complication following spinal cord injury (SCI), often requiring long periods of bed rest, hospitalisation and associated physical deconditioning. This study will design a new evidence-based Individualised Pressure Ulcer Prevention Self-management Program for individuals with SCI, by integrating biofeedback from ultrasound, interface pressure mapping and transcutaneous oxygen monitoring into a standard program. The aim is to increase self-efficacy, pressure ulcer knowledge, satisfaction and participation. Seventy-two individuals with spinal cord injuries will be recruited and randomized into this new and innovative program or the standard (existing) pressure ulcer prevention program. In addition to clinical outcomes, resource utilization and cost effectiveness of the new program will be determined.
A/Prof Garry Allison, Prof S Dunlop, A/Prof John Buchanan
Central modulation of lower limb tone following acquired brain injury: role of sub-maximal loading on neurological outputs & function
Controlling leg movement is fundamental to many key functional activities and tasks, such as transferring from chair to bed, or from a sitting position to standing, and of course walking. Individuals who cannot do these tasks have severely compromised independence and require substantial assistance and healthcare resources. Individuals with acquired brain injuries have an altered ability to control the neural circuits supplying the leg muscles. To date, no assessment techniques are sensitive enough to measure the extent of neural control. This clinical and experimental study examines 1) leg control during a functional task and 2) how specific neurological rehabilitation exercises may improve leg control and thereby improve function.
Ms T Pereira, Ms J Holding, Ms J Brayshaw
What is the effect of cranioplasty on functional performance in an acquired brain injured population?
Patients with acquired brain injury (ABI) may undergo craniectomy or surgical removal of a bone flap to manage the dangerously high intracranial pressure that often occurs in the acute phase. Cranioplasty or replacement of the bone flap is performed at a later date. In 2008, thirty Western Australian patients received a cranioplasty. It has been noted that whilst awaiting cranioplasty, some patients may deteriorate in function and experience symptoms such as headache, vertigo, cognitive impairment and changes in mood. These symptoms have been observed to lessen after cranioplasty, with subsequent improvements in patients' cognitive performance and function. In this study, Occupational Therapists at Royal Perth Hospital will assess six ABI patients with a craniectomy, before and after cranioplasty is performed, to determine the nature of any significant functional changes that might occur following this procedure.
A/Prof G Thickbroom, Dr M Byrnes, Dr D Edwards
Cortical plasticity after spinal cord injury - measurement & modulation
Brain plasticity is known to contribute to recovery of function after stroke, but to date it is still unclear how the brain adapts to spinal cord injury (SCI). Building on Thickbroom's previous NRP-funded research, this project will explore and enhance activity dependent brain plasticity using magnetic brain stimulation. The aim is to promote functional recovery, on the basis that cortical plasticity contributes to recovery regardless of the level at which injury to the central nervous system occurs. The investigators will study the changes that occur in the motor area of the brain after SCI, and safe and non-invasive magnetic brain stimulation methods that Thickbroom has refined over the last few years will be used to enhance brain plasticity and thereby improve motor output and function. This study has important implications for clinical rehabilitation after SCI and brain injury.
Dr M Byrnes, Ms J Beilby, Mr M Hart, Prof S Schug
A randomised controlled trial in Acceptance and Commitment Therapy for neurotrauma patients experiencing chronic pain
Acceptance and Commitment Therapy (ACT) programs have recently proliferated in clinical and medical settings. These innovative programs have proven to be clinically effective in reducing co-morbid depression, anxiety, stress, and chronic pain in individuals suffering from chronic medical conditions. The aims of this research project are to:
- engage and treat patients with spinal cord injury and stroke who are experiencing chronic musculoskeletal and neuropathic pain using an ACT group program;
- evaluate the effectiveness of the ACT group program on aspects of pain severity, psychosocial functioning, quality of life and values-directed living during the chronic phases of the rehabilitation process; and
- identify psychosocial and behavioural predictors of the treatment response.
Prof S Brown, Assist. Prof S Stone, Prof S Webb, Dr N Henry, Prof S Rao, Prof D Fatovich, A/Prof D Arendts
Leukocyte cell signaling after traumatic brain injury: correlation with clinical outcomes
Brain injury is the main cause of death and permanent disability in trauma patients presenting to WA hospital emergency departments. Patient outcomes after traumatic brain injury (TBI) are generally poor. One factor that contributes to poor outcomes is the activation of the immune system which releases inflammatory proteins that contribute to ongoing neuro-inflammation. The aim of this study is to investigate changes in the activation of genes that regulate production of these inflammatory proteins during the hours and days following TBI and correlate these results with patient outcomes. This process will identify proteins that may provide future targets for treatments that will reduce the negative long term effects of brain injuries.
A/Prof D Blacker, Dr D Prentice, Dr T Alvaro
A pilot study of combined intravenous minocycline and tPA for ischaemic stroke; a strategy to reduce haemorrhagic transformation
Intravenous tissue plasmingen activator (tPA) is an approved therapy for ischaemic stroke - the kind caused by a blood clot, which prevents blood and oxygen reaching brain tissue. A worrisome side effect of tPA is haemorrhagic transformation, ie bleeding into the damaged brain tissue. This occurs in over 6% of stroke patients treated with tPA and is associated with a mortality rate of approximately 50%. Minocycline is an antibiotic with properties that may protect brain tissue in stroke. Early studies confirm its safety in stroke patients. In vivo experiments combining the two agents have shown reductions in haemorrhage. This team of Perth neurologists will study the therapies in combination in human patients, with the aim of reducing brain haemorrhages and thereby minimising subsequent functional deficits associated with ischaemic stroke.
