DoH WA Sponsored Grants 2016-2017

Benefits of exercise on age-related changes in old spinal cords: implications for therapies to maintain and repair spinal cord function in elderly humans

Year: 2017

Spinal cord injury causes catastrophic loss of sensory and motor function. While factors controlling the repair of spinal cords after trauma have been widely studied in young adults, little is known about the situation in older spinal cords. With the rapidly ageing human population there is an urgency to understand age-related changes in the spinal cord that are likely contribute to loss of muscle function, frailty and increasing incidence of damaging falls. Importantly, such changes in older spinal cords almost certainly impair recovery from neurotrauma. Finally, we investigate the benefits of exercise on these changes in ageing spinal cords.

Interaction of brain state with low intensity repetitive transcranial magnetic stimulation to promote repair

Year: 2017

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 neuroplasticity to accelerate repair and improve function of abnormal circuits. We will combine electromagnetic brain stimulation with visual and motor behavioural tasks in mice to increase plasticity and promote brain repair. Our goal is to validate a therapeutic approach to decrease financial, social and emotional costs associated with neurological impairment.

Strengthening functional connectivity in the motor system to reduce falls following stroke

Year: 2017

Stroke is associated with increased falls and fall-related injury. Functional connectivity between cortical motor areas is critical for the execution of appropriate motor responses, like walking and balance tasks, which ultimately enable successful interaction with the environment. We will use novel non-invasive brain stimulation to characterise and strengthen functionally relevant connections between brain areas important for movement control in chronic stroke patients, and test whether strengthening these cortical connections improves balance and gait. Identifying the mechanisms of movement deficits leading to falls in stroke patients will allow the development of targeted, evidence-based interventions to improve movement recovery in this population.

CODE SPINE – Enabling the ‘ICED” (immediate cooling and emergency decompression) clinical trial for acute spinal cord injury in WA

Year: 2017

Traumatic SCI in WA has recently doubled to around 80 pa and is twice the national average. Although early decompression is increasingly recognized as beneficial, it is difficult to achieve, but recent data suggest that hypothermia can “buy time”. Recent feasibility studies conducted by us prior to ‘ICED’ (a randomised controlled trial [RCT] of ‘Immediate Cooling & Early Decompression’) have revealed that ethical and governance processes are highly complex and time-consuming yet must be finalized prior to the trial itself. Here, we investigate barriers and facilitators to implementing ICED in WA so as to ensure successful progress to the full trial.

Assessing rTMS for repair after spinal cord injury

Year: 2016

Repetitive transcranial magnetic stimulation (rTMS) is a method of electromagnetic brain stimulation that modulates cortical neuronal activity. It is emerging as a promising non-invasive tool for the treatment of spasticity, neuropathic pain, and somatomotor deficit after spinal cord injury (SCI). However, different protocols and methods of stimulation, as well as alternate cortical sites of stimulation, have not resulted in a unified methodology, or consistent therapeutic outcomes. Using a specific range of intensities and frequencies over time, we will determine the optimal rTMS protocol that improves functional (locomotor) outcomes after SCI in a defined animal model of cervical SCI.

Switching on regeneration: using microRNAs to promote CNS repair

Year: 2016

The mammalian central nervous system (CNS) cannot effectively regenerate, with dire consequence for those exposed to neurotrauma or spinal cord injury. In contrast, fish exhibit spontaneous regeneration of their CNS. We previously identified a genetic factor (miRNA-223) that is differentially expressed in zebrafish (upregulated) and rat (downregulated) during CNS regeneration. We also showed that decreasing miR-223 in zebrafish after a CNS injury inhibits regeneration. Here we test the ability of miR-223 to enhance axon regeneration in the rat CNS. Our research will identify the potential of miRNA-223 as a novel therapy for Neurotrauma or spinal cord injury in mammals including humans.

Targeting four-stranded DNA conformations to enable axonal regeneration following neurotrauma

Year: 2016

We will obtain the first genome-wide maps of the occurrence of G-quadruplex DNA (G4-DNA) in human astrocytes and identify genes that display alternations in G4-DNA formation during astrogliosis. Transcriptome and proteome profiling will enable us to determine how alternations in G4-DNA in gene promoters affect gene expression at both the RNA and protein levels. The genome-wide maps will enable us to identify target genes implicated in astrogliosis for precision-targeted genome engineering, where altering G4-DNA formation could result in down-regulation of many of the stress-induced genes in reactive astrocytes and hence promote a regenerative environment

Urinary tract management and infection control after Spinal Cord Injury (SCI)

Year: 2016

Secondary urinary tract infection (UTI) is common following SCI. Early, frequent UTIs are debilitating, often leading to chronic bladder and renal problems. Protocols for urinary tract management differ at Australian Spinal Units and the association between protocols and infection incidence is unknown. This knowledge translation project, part of a national initiative to optimise bladder health following SCI, involves three components: evidence review to determine best practice; an audit to determine current practices and urinary infection incidence in acute SCI in Western Australia; and an exploration of barriers and facilitators to improving practice. Findings will inform national guidelines for optimising post-SCI bladder management.

How long are you distracted?
An investigation of ongoing impairments arising from driving interruptions

Year: 2016

Becoming distracted while driving significantly increases the risk of serious accidents, injuries and fatalities. Recent evidence suggests this risk may be further compounded by the fact that distraction related interruptions can impact task performance even after the initial distraction has ended. To date, little research has examined the time-course of recovery from interruptions while driving. The current research will address this crucial gap by determining how long driver hazard perception is impaired after different types of interruption, and the effectiveness of driver training intervention designed to protect against the disruptiveness of interruptions.

A tailored music therapy and real-time biofeedback mobile phone app to promote motor rehabilitation following neurotrauma.

Year: 2016

The use of music therapy to improve recovery of movement following neurological injury is gaining momentum; however, progress in the field is limited by the separation of music and feedback about movement in relation to the music. We have developed a novel Mobile Software Application (app) — GotRhythm—that uses mobile phones and wireless wearable sensors to deliver music therapy to patients with real-time bio-feedback. Here, we test the effect of the GotRhythm app on motor performance and brain function in people with brain injuries from motor vehicle accidents. The GotRhythm app is simple, cheap, and self-administered, increasing motivation and compliance.

Characterising the role of the dynamic epigenome in Neurotrauma

Year: 2016

There is increasing evidence that brain stimulation or injury alters epigenetic modifications of the genome in neurons and glia. We will investigate whether repetitive transcranial magnetic stimulation (rTMS), a non-invasive brain stimulation method that improves brain connectivity and function following injury, can induce epigenome alterations that promote repair after injury. We will identify epigenomic and regulatory changes that occur during neurotrauma and rTMS-induced repair, in order to elucidate the cellular mechanisms of functional recovery from neurotrauma. Manipulation of epigenetic patterns non-invasively via rTMS during long-term rehabilitation may lead to improved return of function in recent and long-term neurotrauma patients.

Use of novel self assembling peptide hydrogels in spinal cord repair

Year: 2016

Contusion spinal cord injury (SCI) results in large cysts and glial scars which effectively “seal off” the injury, making nerve regrowth and/or regeneration almost impossible. To date, the use of scaffolds to facilitate regrowth across this hostile environment has been limited. Self-assembling peptide (SAP) hydrogels are novel bioactive scaffolds, providing superior structural support, low cytotoxicity and improved tissue repair in vivo in the brain. We will pioneer novel SAP scaffolds to facilitate axonal regrowth/regeneration after SCI alone and combined with our proven mesenchymal precursor cells (MPC) transplantation which consistently limits tissue loss, promotes morphological sparing and functional improvement following SCI.

Identification of biomarkers that correlate with clinical features and outcomes following concussion

Year: 2016

Following mild traumatic brain injury (mTBI)/ concussion, the symptoms of most patients resolve within a few days to weeks. However, a small but significant proportion develop debilitating post-concussion syndrome (PCS). Currently it is not possible to determine who will develop PCS. We will conduct specialized imaging, neuropsychological tests and assess blood biomarkers at the time of presentation to hospital and 28 days later. We aim to identify indicators to predict if mTBI will develop into PCS. In future, patients showing these indicators would then be identified as likely to benefit from follow-up care and could be targeted for therapeutic interventions.