
Melinda FitzgeraldCurtin University · Curtin Health Innovation Research Institute (CHIRI)
Melinda Fitzgerald
BSc (Hons), PhD
John Curtin Distinguished Professor
Deputy Vice-Chancellor, Research
Curtin University
About
159
Publications
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Introduction
Melinda Fitzgerald leads a team of 12 researchers and post-graduate students in research focused around understanding and preventing the loss of function that occurs following neurotrauma. Her team uses a range of innovative approaches to understand what happens in the brain following injury . She is leading the AUS-mTBI national consortia aiming to design and deliver the informatics approaches for predicting outcome following mild TBI.
Additional affiliations
February 2006 - July 2016
Education
January 1990 - February 1993
Publications
Publications (159)
This study evaluated the performance outcomes of headers during the FIFA Women's World Cup France 2019™. Video analysis was used to code performance outcomes of headers (uncontested and contested) and their descriptors (e.g., playing position, match situation, field location, and the distance the ball travelled). Descriptive statistics, and odds ra...
Background
The aim of this study was to develop a consensus-based set of indicators of high-quality acute moderate to severe traumatic brain injury (msTBI) clinical management that can be used to measure structure, process, and outcome factors that are likely to influence patient outcomes. This is the first stage of the PRECISION-TBI program, which...
Mild traumatic brain injury (mTBI) is the most common form of traumatic brain injury. Post-concussive symptoms typically resolve after a few weeks although up to 20% of people experience these symptoms for >3 months, termed persistent post-concussive symptoms (PPCS). Subtle white matter (WM) microstructural damage is thought to underlie neurologica...
Citation: Alanazi, N.; Fitzgerald, M.; Hume, P.; Hellewell, S.; Horncastle, A.; Anyaegbu, C.; Papini, M.G.; Hargreaves, N.; Halicki, M.; Entwistle, I.; et al. Concussion-Related Biomarker Variations in Retired Rugby Players and Implications for Neurodegenerative Disease Risk: The UK Rugby Health Study. Int. J. Mol. Sci. 2024, 25, 7811. https:// Abs...
The aim of the Australian Traumatic Brain Injury Initiative (AUS-TBI) is to design a data dictionary to inform data collection and facilitate prediction of outcomes for moderate-severe traumatic brain injury (TBI) across Australia. The process has engaged diverse stakeholders across six areas: social, health, clinical, biological, acute interventio...
The Australian Traumatic Brain Injury Initiative (AUS-TBI) aims to select a set of measures to comprehensively predict and assess outcomes following moderate-to-severe traumatic brain injury (TBI) across Australia. The aim of this article was to report on the implementation and findings of an evidence-based consensus approach to develop AUS-TBI rec...
The Australian Traumatic Brain Injury Initiative (AUS-TBI) aims to develop a health informatics approach to collect data predictive of outcomes for persons with moderate-severe TBI across Australia. Central to this approach is a data dictionary; however, no systematic reviews of methods to define and develop data dictionaries exist to-date. This ra...
The first aim of the Australian Traumatic Brain Injury Initiative (AUS-TBI) encompasses development of a set of measures that comprehensively predict outcomes for people with moderate-severe TBI across Australia. This process engaged diverse stakeholders and information sources across six areas: social, health, and clinical factors, biological mark...
Objectives:
People may experience a myriad of symptoms after mild traumatic brain injury (mTBI), but the relationship between symptoms and objective assessments is poorly characterized. This study sought to investigate the association between symptoms, resting heart rate (HR), and exercise tolerance in individuals following mTBI, with a secondary...
Introduction
Traumatic brain injury (TBI) is a heterogeneous condition in terms of pathophysiology and clinical course. Outcomes from moderate to severe TBI (msTBI) remain poor despite concerted research efforts. The heterogeneity of clinical management represents a barrier to progress in this area. PRECISION-TBI is a prospective, observational, co...
Introduction:
To quantify the incidence and characteristics of purposeful heading and other head impacts in professional women's football at the 2019 FIFA Women's World Cup™.
Methods:
This cross-sectional cohort study analysed purposeful headers (uncontested and contested) and their characteristics (e.g. playing position, match situation, field...
Background:
The Australian Traumatic Brain Injury Initiative (AUS-TBI) is developing a data resource to enable improved outcome prediction for people with moderate-severe TBI (msTBI) across Australia. Fundamental to this resource is the collaboratively designed data dictionary. This systematic review and consultation aimed to identify acute interv...
In this series of 8 papers, the AUS-TBI consortium describes the Australian approach used to select the common data elements collected acutely, that have been shown to predict longer term outcome following moderate-severe TBI across the lifespan. This paper presents the unified single data dictionary, together with additional measures chosen to fac...
Background:
The objective of the Australian Traumatic Brain Injury (AUS-TBI) Initiative is to develop a data dictionary to inform data collection and facilitate prediction of outcomes of people who experience moderate-severe TBI in Australia. The aim of this systematic review was to summarise the evidence of the association between demographic, in...
The Australian Traumatic Brain Injury Initiative (AUS-TBI) aims to co-design a data resource to predict outcomes for people with moderate-severe traumatic brain injury (TBI) across Australia. Fundamental to this resource is the data dictionary, which is an ontology of data items. Here, we report the systematic review and consensus process for inclu...
Severe traumatic brain injury (TBI) is a major cause of morbidity and mortality globally. The Brain Trauma Foundation guidelines advocate for the maintenance of a cerebral perfusion pressure (CPP) between 60 and 70 mmHg following severe TBI. However, such a uniform goal does not account for changes in cerebral autoregulation (CA). CA refers to the...
Understanding the chemical events following trauma to the central nervous system could assist in identifying causative mechanisms and potential interventions to protect neural tissue. Here, we apply a partial optic nerve transection model of injury in rats and use synchrotron X-ray fluorescence microscopy (XFM) to perform elemental mapping of metal...
Mild traumatic brain injury (mTBI) accounts for 80–90% of all TBI. Post-mTBI symptoms are measured using the Post-Concussion Symptom Scale (PCSS); however, symptom heterogeneity limits specificity. Better understanding of the neuropathophysiology underlying post-concussion symptoms could enhance diagnostic accuracy. We explored the association betw...
Background:
Cardiovascular changes, such as altered heart rate and blood pressure, have been identified in some individuals following mild traumatic brain injury (mTBI) and may be related to disturbances of the autonomic nervous system and cerebral blood flow.
Methods:
We conducted a scoping review according to PRISMA-ScR guidelines across six d...
Traumatic brain injury is common, and often results in debilitating consequences. Even mild traumatic brain injury leaves approximately 20% of patients with symptoms that persist for months. Despite great clinical need there are currently no approved pharmaceutical interventions that improve outcomes after traumatic brain injury. Increased understa...
Background
An estimated 99 in 100,000 people experience a traumatic brain injury (TBI), with 85% being mild (mTBI) in nature. The Post-Concussion Symptom Scale (PCSS), is a reliable and valid measure of post-mTBI symptoms; however, diagnostic specificity is challenging due to high symptom rates in the general population. Understanding the neurobiol...
Optic nerve injury causes secondary degeneration, a sequela that spreads damage from the primary injury to adjacent tissue, through mechanisms such as oxidative stress, apoptosis, and blood-brain barrier (BBB) dysfunction. Oligodendrocyte precursor cells (OPCs), a key component of the BBB and oligodendrogenesis, are vulnerable to oxidative deoxyrib...
Adolescence is a critical period of postnatal development characterized by social, emotional, and cognitive changes. These changes are increasingly understood to depend on white matter development. White matter is highly vulnerable to the effects of injury, including secondary degeneration in regions adjacent to the primary injury site which alters...
Traumatic intracranial hypertension (tIH) is a common and potentially lethal complication of moderate to severe traumatic brain injury (m-sTBI). It often develops with little warning and is managed reactively with the tiered application of intracranial pressure (ICP)-lowering interventions administered in response to an ICP rising above a set thres...
Traumatic brain injury (TBI) continues to substantially impact the lives of millions of people around the world annually. Community-based prevention and support of TBI are particularly challenging and underresearched aspects of TBI management. Ongoing cognitive, emotional, and other effects of TBI are not immediately obvious in community settings s...
While it is well-established that bone responds dynamically to mechanical loading, the effects of mild traumatic brain injury (mTBI) on cranial bone composition are unclear. We hypothesized that repeated mTBI (rmTBI) would change the microstructure of cranial bones, without gross skull fractures. To address this, young adult female Piebald Viral Gl...
Introduction:
Evidence suggests that maintaining a higher level of cardiorespiratory fitness (CRF) later in life can offer some protection against brain volume loss as we age. By contrast, mild traumatic brain injury (mTBI) could accelerate age-related cortical atrophy. The current study sought to examine whether variations in the CRF level modifi...
Background
Accurate data on the types of healthcare people seek in the early stages following mild traumatic brain injury (mTBI) in Australia is lacking. We sought to investigate the types of healthcare people seek following mTBI, including seeking no care at all; ascertain the demographic, pre- and peri-injury factors, and symptom characteristics...
Predicting and optimizing outcomes after traumatic brain injury (TBI) remains a major challenge because of the breadth of injury characteristics and complexity of brain responses. AUS-TBI is a new Australian Government–funded initiative that aims to improve personalized care and treatment for children and adults who have sustained a TBI. The AUS-TB...
Mild traumatic brain injury (mTBI) causes structural, cellular and biochemical alterations which are difficult to detect in the brain and may persist chronically following single or repeated injury. Lipids are abundant in the brain and readily cross the blood-brain barrier, suggesting that lipidomic analysis of blood samples may provide valuable in...
Background: With the adoption of multimodal neuromonitoring techniques, a large amount of high resolution neurophysiological data is generated during the treatment of patients with moderate to severe traumatic brain injury (m-sTBI) that is available for further analysis. The Monitoring with Advanced Sensors, Transmission and E-Resuscitation in Trau...
While it is well-established that bone responds dynamically to mechanical loading, the effects of mild traumatic brain injury (mTBI) on cranial bone composition are unclear. We hypothesized that repeated mTBI (rmTBI) would change the microstructure of cranial bones, without gross skull fractures. To address this, young adult female Piebald Viral Gl...
Background
Traumatic brain injury (TBI) has been recognised as an important global health priority. Mild traumatic brain injury (mTBI), also known as concussion, accounts for up to 90% of all TBI diagnoses. Accumulating evidence also suggests that mTBI may be a risk factor for later‐life cognitive decline and neurodegeneration, including Alzheimer’...
Cuprizone is a copper-chelating agent that induces pathology similar to that within some multiple sclerosis (MS) lesions. The reliability and reproducibility of cuprizone for inducing demyelinating disease pathology depends on the animals ingesting consistent doses of cuprizone. Cuprizone-containing pelleted feed is a convenient way of delivering c...
Traumatic brain injury (TBI) is a common but heterogeneous injury underpinned by numerous complex and interrelated pathophysiological mechanisms. An essential trace element, iron is abundant within the brain and involved in many fundamental neurobiological processes, including oxygen transportation, oxidative phosphorylation, myelin production and...
Introduction
Mild traumatic brain injury (mTBI) is a complex injury with heterogeneous physical, cognitive, emotional and functional outcomes. Many who sustain mTBI recover within 2 weeks of injury; however, approximately 10%–20% of individuals experience mTBI symptoms beyond this ‘typical’ recovery timeframe, known as persistent post-concussion sy...
Background
Cellular responses at the sub-acute phase of mild traumatic brain injury (mTBI), and their contribution to ongoing damage, are unclear, complex and require simultaneous assessment of multiple cells to elucidate.
New method
An 11-colour flow cytometry method for analysing brain cells was evaluated in a weight-drop rat model of repeated m...
Repeated sub-concussive impact (e.g. soccer ball heading), a significantly lighter form of mild traumatic brain injury, is increasingly suggested to cumulatively alter brain structure and compromise neurobehavioural function in the long-term. However, the underlying mechanisms whereby repeated long-term sub-concussion induces cerebral structural an...
Background
General Practitioners (GPs) may be called upon to assess patients who have sustained a concussion despite limited information being available at this assessment. Information relating to how concussion is actually being assessed and managed in General Practice is scarce. This study aimed to identify characteristics of current Western Aust...
Mild traumatic brain injury (mTBI) accounts for a large majority of traumatic brain injuries sustained globally each year. Older adults, who are already susceptible to age-related declines to neurocognitive health, appear to be at an increased risk of both sustaining an mTBI and experiencing slower or impaired recovery. There is also growing eviden...
Repeated sub-concussive impact ( e.g. soccer ball heading), a significantly lighter form of mild traumatic brain injury, is increasingly suggested to cumulatively alter brain structure and compromise neurobehavioural function in the long-term. However, the underlying mechanisms whereby repeated long-term sub-concussion induces cerebral structural a...
Background: Mild traumatic brain injury (mTBI) results from an external force to the head or body causing neurophysiological changes within the brain. The number and severity of symptoms can vary, with some individuals experiencing rapid recovery, and others having persistent symptoms for months to years, impacting their quality of life. Current re...
There is limited data surrounding incidence and prevalence of concussion and the resulting post-concussion states. This creates difficulty when investigating ways to optimise patient management. It is proposed that a registry of patients presenting with symptoms and signs after a concussion, as part of a large scale TBI registry across Australia, w...
Reducing the extent of secondary degeneration following spinal cord injury (SCI) is necessary to preserve function, but treatment options have thus far been limited. A combination of the ion channel inhibitors Lomerizine (Lom), YM872 and oxATP, to inhibit voltage-gated Ca2+ channels, Ca2+ permeable AMPA receptors, and purinergic P2X7 receptors resp...
Whilst detrimental effects of repeated sub-concussive impacts on neurophysiological and behavioral function are increasingly reported, the underlying mechanisms are largely unknown. Here, we report that repeated sub-concussion with a light weight drop (25 g) in wild-type PVG rats for 2 weeks does not induce detectable neuromotor dysfunction assesse...
Traumatic brain injury (TBI) and spinal cord injury (SCI) present a significant contribution to the global disease burden. White matter tracts are susceptible to both the physical forces of trauma and cascades of pathological secondary degeneration. Oligodendrocytes, the myelinating cells of the CNS, and their precursors are particularly vulnerable...
Diffusible ions (Na⁺, K⁺, Mg²⁺, Ca²⁺, Cl–) are vital for healthy function of all cells, especially brain cells. Unfortunately, the diffusible nature of these ions renders them difficult to study with traditional microscopy in situ within ex vivo brain tissue sections. This mini-review examines the recent progress in the field, using direct elementa...
Transferrin (Tf)-functionalized p(HEMA-ran-GMA) nanoparticles were designed to incorporate and release a water-soluble combination of three ion channel antagonists, namely zonampanel monohydrate (YM872), oxidized adenosine triphosphate (oxATP) and lomerizine hydrochloride (LOM) identified as a promising therapy for secondary degeneration that follo...
Background:
Persisting post-concussion symptoms (PPCS) is a complex, multifaceted condition in which individuals continue to experience the symptoms of mild traumatic brain injury (mTBI; concussion) beyond the timeframe that it typically takes to recover. Currently, there is no way of knowing which individuals may develop this condition.
Method:...
This chapter will discuss the context within which traumatic brain injury (TBI) and in particular mild TBI is investigated principally in an emergency setting. It provides background in relation to health system burden and discusses the cognitive processes involved in the assessment and follow-up of patients with TBI. This then leads to a discussio...
Injury to the central nervous system is exacerbated by secondary degeneration. Previous research has shown that a combination of orally and locally administered ion channel inhibitors following partial optic nerve injury protects the myelin sheath and preserves function in the ventral optic nerve, vulnerable to secondary degeneration. However, loca...
Nanoparticle drug delivery applications have predominantly focused on the entrapment and delivery of hydrophobic molecules with poor water solubility. However, benefits can also be obtained from nanoparticle-based delivery of hydrophilic therapeutics. This study reports on the development of a p(HEMA-ran-GMA)-based nanoparticle synthesized via a sp...
Background
Multiple sclerosis (MS) has been shown to feature oxidative damage, which can be modelled using the cuprizone model of demyelinating disease. Oxidative damage can occur as a result of excessive influx of calcium ions (Ca2+) and oligodendroglia are particularly vulnerable. However, the effects of limiting excess Ca2+ influx on oxidative d...
The adsorption of serum proteins on the surface of nanoparticles (NPs) delivered into a biological environment has been known to alter NP surface properties and consequently their targeting efficiency. In this present article we use random copolymer (p(HEMA-ran-GMA)) - based NPs synthesized using 2-hydroxyethyl methacrylate (HEMA) and glycidyl meth...
Following mild traumatic brain injury (mTBI), further mild impacts can exacerbate negative outcomes. To compare chronic damage and deficits following increasing numbers of repeated mTBIs, a closed‐head weight‐drop model of repeated mTBI was used to deliver 1, 2 or 3 mTBIs to adult female rats at 24 h intervals. Outcomes were assessed at 3 months fo...
Following neurotrauma, secondary degeneration of neurons and glia adjacent to the injury leads to further functional loss. A combination of ion channel inhibitors (lomerizine + oxATP + YM872) has been shown to be effective at limiting structural and functional loss due to secondary degeneration. Here we assess efficacy of the combination where oxAT...
Injury to the central nervous system is characterized by damage that spreads from the initial point of impact into the surrounding adjacent tissue, in a phenomenon referred to as secondary degeneration. The optic nerve can be used to effectively model injury and secondary degeneration to white matter tracts. Partial transection of the dorsal aspect...
Gold nanorods are one of the most widely explored inorganic materials in nanomedicine for diagnostics, therapeutics and sensing¹. It has been shown that gold nanorods are not cytotoxic and localize within cytoplasmic vesicles following endocytosis, with no nuclear localization2,3, but other studies have reported alterations in gene expression profi...
In the paper “Oligodendroglia are particularly vulnerable to oxidative damage after neurotrauma in vivo,” we determined the extent of oxidative damage to specific cellular subpopulations and structures within regions vulnerable to secondary degeneration and assessed the effect this had on oligodendroglial function. Comparative assessment of oxidati...
Following mild traumatic brain injury (mTBI), the ionic homeostasis of the central nervous system (CNS) becomes imbalanced. Excess Ca2+ influx into cells triggers molecular cascades, which result in detrimental effects. The authors assessed the effects of a combination of ion channel inhibitors (ICI) following repeated mTBI (rmTBI). Adult female ra...
Background:
Following injury to the central nervous system, increased microglia, secretion of pro- and anti-inflammatory cytokines, and altered blood-brain barrier permeability, a hallmark of degeneration, are observed at and immediately adjacent to the injury site. However, few studies investigate how regions remote from the primary injury could...
Loss of function following injury to the CNS is worsened by secondary degeneration of neurons and glia surrounding the injury and is initiated by oxidative damage. However, it is not yet known which cellular populations and structures are most vulnerable to oxidative damage in vivo. Using Nanoscale secondary ion mass spectrometry (NanoSIMS), oxidat...
Following injury to the central nervous system, axons and myelin distinct from the initial injury site undergo changes associated with compromised function. Quantifying such changes is important to understanding the pathophysiology of neurotrauma; however, most studies to date used 2 dimensional (D) electron microscopy to analyse single sections, t...