Neurosciences Unit

Perth, Australia

Neurosciences Unit

Perth, Australia
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Lee J.-M.,University of New South Wales | Tan V.,Macquarie University | Lovejoy D.,Macquarie University | Braidy N.,University of New South Wales | And 4 more authors.
Neuropharmacology | Year: 2017

Amyotrophic lateral sclerosis (ALS) is the most common adult-onset motor neuron disease characterized by a progressive degeneration of central and peripheral motor neurons, leading to the atrophy of voluntary muscles. It has been previously demonstrated that the kynurenine pathway (KP), the major biochemical pathway for tryptophan metabolism, is dysregulated in ALS. In particular, the neuroactive intermediate, quinolinic acid (QUIN) has been shown to accumulate with a concomitant decrease in other neuroprotective and immunomodulatory KP metabolites. Furthermore, multiple biochemical phenomena associated with QUIN cytotoxicity are present in ALS, suggesting that QUIN may play a substantial role in the pathogenesis of ALS. This review highlights the potential roles of QUIN in ALS, and explores KP modulation as a therapeutic candidate in ALS. This article is part of the Special Issue entitled ‘The Kynurenine Pathway in Health and Disease’. © 2016 Elsevier Ltd


Smith M.A.,Northumbria University | Smith M.A.,University of Western Australia | Riby L.M.,Northumbria University | Eekelen J.A.M.V.,University of Western Australia | And 3 more authors.
Neuroscience and Biobehavioral Reviews | Year: 2011

The brain relies upon glucose as its primary fuel. In recent years, a rich literature has developed from both human and animal studies indicating that increases in circulating blood glucose can facilitate cognitive functioning. This phenomenon has been termed the 'glucose memory facilitation effect'. The purpose of this review is to discuss a number of salient studies which have investigated the influence of glucose ingestion on neurocognitive performance in individuals with (a) compromised neurocognitive capacity, as well as (b) normally functioning individuals (with a focus on research conducted with human participants). The proposed neurocognitive mechanisms purported to underlie the modulatory effect of glucose on neurocognitive performance will also be considered. Many theories have focussed upon the hippocampus, given that this brain region is heavily implicated in learning and memory. Further, it will be suggested that glucose is a possible mechanism underlying the phenomenon that enhanced memory performance is typically observed for emotionally laden stimuli. © 2010 Elsevier Ltd.


Ganesan V.,Neurosciences Unit | Klein N.J.,Institute of Child Health and Great Ormond St Hospital for Children
Neurology | Year: 2012

Objective: Circulating endothelial cells (CECs) and microparticles (MPs) have been reported to reflect endothelial injury, cellular activation, and MP-mediated thrombin generation. We tested the hypothesis that these indices differ between children with cerebral arteriopathy and arterial ischemic stroke (AIS) recurrence, and those with a single event. Methods: This was a single-center cross-sectional study of 46 children with AIS and cerebral arteriopathy matched with pediatric controls. AIS recurrence was defined as new acute neurologic deficit with radiologic evidence of further cerebral infarction. CECs and MPs were identified with immunomagnetic bead extraction and flow cytometry, respectively.MP function as assessed by thrombin generation was determined using a fluorogenic assay. Results: Ten children had AIS recurrence while 36 had a single AIS event. CECs were raised in children with recurrent AIS, compared to those with no recurrence (p = 0.0001), and in controls (p = 0.0001). Total circulating annexin V1 MPs were significantly greater in children with recurrence than in those with no recurrence (p = 0.0020). These MPs were of endothelial or platelet origin, and a subpopulation expressed tissue factor. Finally, MP-mediated thrombin generation was enhanced in children with recurrent AIS compared to those with no recurrence (p = 0.0001), providing a link between inflammation, endothelial injury, and increased thrombotic tendency. Conclusion: Despite the wide spectrum of clinical and radiologic presentation of childhood AIS, indices of endothelial injury and cellular activation are different in patients with single and recurrent events. This novel approach has potential for furthering understanding of AIS pathophysiology and prognosis. © 2012 American Academy of Neurology.


Thompson J.A.,Edith Cowan University | Cruickshank T.M.,Edith Cowan University | Penailillo L.E.,Edith Cowan University | Lee J.W.,Neurosciences Unit | And 5 more authors.
European Journal of Neurology | Year: 2013

Background and purpose: Despite advances in the understanding of Huntington's disease (HD), treatment remains symptomatic. Multidisciplinary rehabilitation, however, appears to impact disease progression. Here we show the feasibility, safety and efficacy of a 9-month multidisciplinary rehabilitation programme in a small cohort of patients with early-to-middle-stage HD. Methods: Twenty patients with HD were assigned to two groups, equally matched for cognitive and motor scores. One group received the intervention, whilst the other served as control. The Unified-Huntington's-Disease-Rating-Scale-Total-Motor-Score was the primary outcome measure. Neurocognitive/psychological tests, body composition, postural stability, strength and quality of life assessments were secondary outcome measures. Results: The intervention reduced motor and postural stability deterioration, with minor improvements in depression, cognition and quality of life. Significant gains were observed for fat-free mass and strength. Conclusion: This pilot study suggests that a prolonged multidisciplinary rehabilitation programme in early-to-middle-stage HD is feasible, well-tolerated and associated with therapeutic benefit. Further explorative, larger studies are warranted. © 2012 EFNS.


Squires N.,Speech Kingdom | Wills A.,Neurosciences Unit | Rowson J.,Queens Medical Center
Current Opinion in Otolaryngology and Head and Neck Surgery | Year: 2012

Purpose of review: Drooling is a distressing symptom for adults with neurological conditions and can be challenging for health professionals. This review will consider the physical and psychosocial impact of drooling and will discuss the current management options including behavioural, pharmacological and surgical approaches. Recent findings: A number of studies describe the use of botulinum toxin injections and irradiation of the salivary glands but no conclusive guidelines exist to recommend the most efficient dose or technique. The majority of saliva management studies focus on children with physical and/or cognitive disabilities and this evidence cannot be generalized to adults. There are relatively few studies that focus on saliva management in the adult neurological population. Summary: Drooling is distressing for patients and their families. Ideally an individual would have easy access to the most efficient treatment with the fewest side effects. More evidence is now available but a lack of consensus on management approach, treatment dose and administration technique still exists. The symptom of drooling is best managed by a multidisciplinary team, starting with a conservative approach and then leading to more invasive procedures as appropriate. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Nyaradi A.,University of Western Australia | Li J.,University of Western Australia | Li J.,Curtin University Australia | Li J.,Center for Social Science Research | And 5 more authors.
Frontiers in Human Neuroscience | Year: 2013

This review examines the current evidence for a possible connection between nutritional intake (including micronutrients and whole diet) and neurocognitive development in childhood. Earlier studies which have investigated the association between nutrition and cognitive development have focused on individual micronutrients, including omega-3 fatty acids, vitamin B12, folic acid, choline, iron, iodine and zinc, and single aspects of diet. The research evidence from observational studies suggests that micronutrients may play an important role in the cognitive development of children. However, the results of intervention trials utilising single micronutrients are inconclusive. More generally, there is evidence that malnutrition can impair cognitive development, whilst breastfeeding appears to be beneficial for cognition. Eating breakfast is also beneficial for cognition. In contrast, there is currently inconclusive evidence regarding the association between obesity and cognition. Since individuals consume combinations of foods, more recently researchers have become interested in the cognitive impact of diet as a composite measure. Only a few studies to date have investigated the associations between dietary patterns and cognitive development. In future research, more well designed intervention trials are needed, with special consideration given to the interactive effects of nutrients. © 2013 Nyaradi, Li, Hickling, Foster and Oddy.


Neirinckx V.,Neurosciences Unit | Cantinieaux D.,Neurosciences Unit | Coste C.,Neurosciences Unit | Rogister B.,Neurosciences Unit | And 3 more authors.
Stem Cells | Year: 2014

Since several years, adult/perinatal mesenchymal and neural crest stem cells have been widely used to help experimental animal to recover from spinal cord injury. More interestingly, recent clinical trials confirmed the beneficial effect of those stem cells, which improve functional score of patients suffering from such lesions. However, a complete understanding of the mechanisms of stem cell-induced recovery is seriously lacking. Indeed, spinal cord injuries gathered a wide range of biochemical and physiopathological events (such as inflammation, oxidative stress, axonal damage, demyelination, etc.) and the genuine healing process after cell transplantation is not sufficiently defined. This review aims to sum up recent data about cell therapy in spinal cord lesions using mesenchymal or recently identified neural crest stem cells, by describing precisely which physiopathological parameter is affected and the exact processes underlying the observed changes. Overall, although significant advances are acknowledged, it seems that further deep mechanistic investigation is needed for the development of optimized and efficient cell-based therapy protocols. © AlphaMed Press 2013.


Nyaradi A.,University of Western Australia | Foster J.K.,University of Western Australia | Foster J.K.,Curtin University Australia | Foster J.K.,Neurosciences Unit | And 7 more authors.
Journal of Child Psychology and Psychiatry and Allied Disciplines | Year: 2014

Background The aim of the study was to investigate prospective associations between dietary patterns and cognitive performance during adolescence. Methods Participants were sourced from the Western Australian Pregnancy Cohort (Raine) Study that includes 2868 children born between 1989 and 1992 in Perth, Western Australia. When the children were 17 years old (2006-2009), cognitive performance was assessed using a computerized cognitive battery of tests (CogState) that included six tasks. Using a food frequency questionnaire administered when the children were 14 years old (2003-2006), 'Healthy' and 'Western' dietary patterns were identified by factor analysis. Associations between dietary patterns at 14 years of age and cognitive performance at 17 years of age were assessed prospectively using multivariate regression models. Results Dietary and cognitive performance data were available for 602 participants. Following adjustment for the 'Healthy' dietary pattern, total energy intake, maternal education, family income, father's presence in the family, family functioning and gender, we found that a longer reaction time in the detection task (β =.016; 95% CI: 0.004; 0.028; p =.009) and a higher number of total errors in the Groton Maze Learning Test - delayed recall task (β =.060; 95% CI: 0.006; 0.114; p =.029) were significantly associated with higher scores on the 'Western' dietary pattern. The 'Western' dietary pattern was characterized by high intakes of take-away food, red and processed meat, soft drink, fried and refined food. We also found that within the dietary patterns, high intake of fried potato, crisps and red meat had negative associations, while increased fruit and leafy green vegetable intake had positive associations with some aspects of cognitive performance. Conclusion Higher dietary intake of the 'Western' dietary pattern at age 14 is associated with diminished cognitive performance 3 years later, at 17 years. © 2014 The Authors. Journal of Child Psychology and Psychiatry. © 2014 Association for Child and Adolescent Mental Health.


Jadhav T.,Great Ormond Street Hospital for Children NHS Trust | Cross J.H.,Great Ormond Street Hospital for Children NHS Trust | Cross J.H.,University College London | Cross J.H.,Neurosciences Unit
Current Treatment Options in Neurology | Year: 2012

Surgery for refractory epilepsy in appropriately selected children is effective. The key factors influencing a good outcome are careful selection of candidates, early referral to pediatric epilepsy surgical unit, underlying neuropathology and the completeness of surgical resection of the seizure focus. Although the primary aim of a surgery is seizure freedom, benefits are also seen in cognitive development. Early prompt referral is therefore desired to optimise outcome. Focal resections involving the temporal and frontal lobes are the common resective procedures in children, with cortical malformations the most common underlying pathology. Hemispherectomy or multilobar procedures are more commonly performed in children younger than four years. Seizure free rates reach 60-80 %. The availability of newer techniques for presurgical evaluation, along with invasive intracranial electroencephalographic (EEG) recording, has facilitated surgical consideration. Resective surgery may also be beneficial for children who may appear to have bilateral or generalised clinical or EEG features associated with focal lesions on MRI. Vagal Nerve Stimulation (VNS) and corpus callosotomy are employed for selected candidates not suitable for resective surgery with good results. © Springer Science+Business Media, LLC 2012.


Merema M.R.,Edith Cowan University | Speelman C.P.,Edith Cowan University | Foster J.K.,Curtin University Australia | Foster J.K.,Neurosciences Unit | Kaczmarek E.A.,Edith Cowan University
American Journal of Geriatric Psychiatry | Year: 2013

Objectives: To examine whether depressive symptoms are useful predictors of subjective memory complaints in community-dwelling older adults, beyond the predictive utility already provided by memory performance and characteristics of personality. Design: Using hierarchical regression, we examined the relationship between depressive symptoms and subjective memory complaints, controlling for age, gender, education, memory performance, conscientiousness, and neuroticism. Participants: Community-dwelling older adults aged 66 to 90 years (N = 177) who responded to a newspaper advertisement for a memory study in Perth, Western Australia. Measurements: The General Frequency of Forgetting scale (for memory complaints), Depression Anxiety Stress Scales (for depressive symptoms), NEO-Five Factor Inventory (for conscientiousness and neuroticism), and the Visual Reproduction and Logical Memory subtests from the Wechsler Memory Scale'4th Edition (for visual and verbal memory). Results: The hierarchical regression analysis indicated that while depressive symptoms significantly predicted memory complaints after variance associated with age, gender, education, memory performance, and conscientiousness was partialled out, they accounted for almost none of the variance in complaints when neuroticism was partialled out. Conclusions: The well-established relationship between depression and memory complaints may exist in some community-dwelling older adult populations only on account of the manner in which both are associated with neuroticism. © 2013 American Association for Geriatric Psychiatry.

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