Florey Neuroscience Institute

Parkville, Australia

Florey Neuroscience Institute

Parkville, Australia
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Berg A.T.,Northern Illinois University | Berg A.T.,Childrens Memorial Hospital | Pardoe H.R.,Florey Neuroscience Institute | Pardoe H.R.,Brain Research Institute | And 4 more authors.
Neurology | Year: 2011

OBJECTIVES:: Epidemiologic evidence suggests the natural history of refractory mesial temporal lobe epilepsy is complicated, yet little is known about the hippocampus from the nontertiary center perspective. Methods: In a community-based cohort, individuals with nonsyndromic focal epilepsy with onset <16 years and controls had research MRI scans. Hippocampal (HC) volumes were manually measured, corrected for total brain volume, and converted to Z scores (ZHC) based on the controls'values. Volumes in cases and controls were compared. Results: Average volumes were not significantly different in cases with unknown cause (n = 117) relative to controls (n = 63). The group with structural and other conditions (n = 23) had significantly smaller volumes. Asymmetry (larger/smaller HC) did not vary among the 3 groups. Hippocampal variances were significantly larger in each epilepsy group relative to controls. In the unknown cause group, 25 (21%) had extreme values: 15 (13%) with ZHC >1.96; 10 (9%) with ZHC <-1.96. By contrast, 2/63 (3%) controls had extreme values (p = 0.001). Within the unknown cause group, temporal lobe epilepsy (TLE) cases were more likely to have extreme hippocampal volumes than non-TLE (31% vs 15%, p = 0.03). Extreme volumes were generally interpreted as normal visually. These anomalies were not associated with seizure remission or pharmacoresistance. Conclusions: Classic mesial TLE with hippocampal sclerosis is an uncommon finding in the general population. Volume anomalies, both large and small, are often bilateral. The significance of these findings is unclear; however, speculations regarding preexisting hippocampal pathology (e.g., dysplasia) as a factor in TLE and other neocortical epilepsies have been made by others. © 2011 by AAN Enterprises, Inc. ALL rights reserved.


Dibbens L.M.,University of South Australia | De Vries B.,Leiden University | Donatello S.,Free University of Colombia | Heron S.E.,University of South Australia | And 34 more authors.
Nature Genetics | Year: 2013

The majority of epilepsies are focal in origin, with seizures emanating from one brain region. Although focal epilepsies often arise from structural brain lesions, many affected individuals have normal brain imaging. The etiology is unknown in the majority of individuals, although genetic factors are increasingly recognized. Autosomal dominant familial focal epilepsy with variable foci (FFEVF) is notable because family members have seizures originating from different cortical regions. Using exome sequencing, we detected DEPDC5 mutations in two affected families. We subsequently identified mutations in five of six additional published large families with FFEVF. Study of families with focal epilepsy that were too small for conventional clinical diagnosis with FFEVF identified DEPDC5 mutations in approximately 12% of families (10/82). This high frequency establishes DEPDC5 mutations as a common cause of familial focal epilepsies. Shared homology with G protein signaling molecules and localization in human neurons suggest a role of DEPDC5 in neuronal signal transduction. © 2013 Nature America, Inc. All rights reserved.


PubMed | Florey Neuroscience Institute, Austin Health and New York University
Type: Journal Article | Journal: Magma (New York, N.Y.) | Year: 2016

To investigate the precision and accuracy of a new semi-automated method for kidney segmentation from single-breath-hold non-contrast MRI.The user draws approximate kidney contours on every tenth slice, focusing on separating adjacent organs from the kidney. The program then performs a sequence of fully automatic steps: contour filling, interpolation, non-uniformity correction, sampling of representative parenchyma signal, and 3D binary morphology. Three independent observers applied the method to images of 40 kidneys ranging in volume from 94.6 to 254.5 cm(3). Manually constructed reference masks were used to assess accuracy.The volume errors for the three readers were: 4.4% 3.0%, 2.9% 2.3%, and 3.1% 2.7%. The relative discrepancy across readers was 2.5% 2.1%. The interactive processing time on average was 1.5 min per kidney.Pending further validation, the semi-automated method could be applied for monitoring of renal status using non-contrast MRI.


Bechdolf A.,University of Cologne | Bechdolf A.,University of Melbourne | Wood S.J.,University of Melbourne | Wood S.J.,University of Birmingham | And 13 more authors.
Psychiatry Research - Neuroimaging | Year: 2012

There are now numerous reports of neuroanatomical abnormalities in people with bipolar disorder. However, it remains unclear whether those abnormalities predate the onset of the illness. In this cross-sectional magnetic resonance imaging study, we assessed 11 young people clinically at ultra-high risk of development of psychosis (UHR), who all developed bipolar I or II disorder by follow-up (median time to onset 328. days - UHR-BP), 11 matched UHR participants, who had no psychiatric diagnosis after at least 12. months of follow-up (UHR-Well) and 11 matched healthy controls (HC). Our main outcome measures were amygdala, hippocampus, insula, lateral ventricular and whole brain volumes. Amygdala and insula volume reductions were more pronounced in the UHR-BP than in the UHR-Well and HC group. Lateral ventricle, whole-brain and hippocampal volumes did not differ between groups. If these findings are confirmed, they suggest that imaging investigations could help to distinguish people who will subsequently develop bipolar disorder from those who will not, at least in symptomatically enriched samples. © 2011 Elsevier Ireland Ltd.


A mechanism is provided for utilizing a nanodevice to distinguish molecules with different structure. The molecules translocate through or across a nanochannel filled with a electrolyte solution. An electrical signal through the nanochannel is measured for every translocation event. Inner surfaces of the nanochannel include a functional layer, which is a coating to functionalize the nanochannel, in which the functional layer is configured to interact with predetermined ones of the molecules during translocation events. It is determined that a combination of at least two different molecules is formed based on predetermined ones of the molecules interacting with the functional layer to change the electrical signal and/or change a translocation time for the translocation event.


Denham M.,University of Melbourne | Denham M.,Lund University | Thompson L.H.,Lund University | Thompson L.H.,Florey Neuroscience Institute | And 5 more authors.
Stem Cells | Year: 2010

Generation of mesencephalic dopamine (mesDA) neurons from human embryonic stem cells (hESCs) requires several stages of signaling from various extrinsic and intrinsic factors. To date, most methods incorporate exogenous treatment of Sonic hedgehog (SHH) to derive mesDA neurons. However, we and others have shown that this approach is inefficient for generating FOXA2+ cells, the precursors of mesDA neurons. As mesDA neurons are derived from the ventral floor plate (FP) regions of the embryonic neural tube, we sought to develop a system to derive FP cells from hESC. We show that forced expression of the transcription factor GLI1 in hESC at the earliest stage of neural induction, resulted in their commitment to FP lineage. The GLI1+ cells coexpressed FP markers, FOXA2 and Corin, and displayed exocrine SHH activity by ventrally patterning the surrounding neural progenitors. This system results in 63% FOXA2+ cells at the neural progenitor stage of hESC differentiation. The GLI1-transduced cells were also able to differentiate to neurons expressing tyrosine hydroxylase. This study demonstrates that GLI1 is a determinant of FP specification in hESC and describes a highly robust and efficient in vitro model system that mimics the ventral neural tube organizer. © AlphaMed Press.


Cheang M.Y.,Royal Melbourne Hospital | Manning N.,Royal Melbourne Hospital | Churilov L.,Florey Neuroscience Institute | Mitchell P.,Royal Melbourne Hospital | And 2 more authors.
Journal of Clinical Neuroscience | Year: 2014

Intravenous recombinant tissue plasminogen activator is associated with significant recanalisation failure in the setting of large artery occlusion. Endovascular treatment by stentriever achieves improved rates of recanalisation but its impact on clinical outcomes remains unclear. We hypothesise that successful recanalisation, unattentuated by age and stroke severity, is associated with improved clinical outcomes in patients treated with the Solitaire stentriever (ev3 Endovascular, Plymouth, MN, USA). We conducted a retrospective study of 60 consecutive acute ischaemic stroke patients treated with the Solitaire stentriever. The data included demographics, vascular risk factors, ictal onset time, National Institutes of Health Stroke Scale (NIHSS) score at presentation, angiographic findings, post-procedure imaging, and clinical follow-up. Recanalisation success was defined as a thrombolysis in cerebral infarction score (TICI) ≥ 2b. Good clinical outcome was defined as a modified Rankin Scale score (mRS) ≤ 2 at 3 months. Of the 60 patients, the mean age was 64.1 (standard deviation 13.4) years and 68.3% were men. Median NIHSS score at presentation was 18 (interquartile range 14-22). Successful recanalisation (TICI ≥ 2b) was achieved in 44 patients (73.3%). Of these 44 patients, 25 patients (56.8%) achieved mRS ≤ 2 at 3 months. Multiple logistic regression showed significant association between recanalisation success and improved clinical outcome (p = 0.019). Of all patients, four (6.7%) developed symptomatic intracranial haemorrhage. Overall mortality was 28.3%. In conclusion, the Solitaire stentriever was associated with improved recanalisation rates. We showed that successful recanalisation is associated with good clinical outcomes after adjustments for age, sex and stroke severity. © 2013 Elsevier Ltd. All rights reserved.


Goh C.,Royal Melbourne Hospital | Churilov L.,University of Melbourne | Churilov L.,Florey Neuroscience Institute | Mitchell P.,Royal Melbourne Hospital | And 2 more authors.
American Journal of Neuroradiology | Year: 2013

BACKGROUND AND PURPOSE: Antiplatelet therapy is associated with decreased ischemic events after neurointerventional procedures. Antiplatelet resistance negates the protective effects of antiplatelet medication, leading to a higher incidence of ischemic events. A possible link between antiplatelet hyper-response and increased hemorrhagic complications has been inadequately investigated. We aimed to examine the correlation between antiplatelet hyper-response and the risk of hemorrhagic complications. MATERIALS AND METHODS: Patients who were treated with antiplatelet medications and underwent neurointerventional procedures were prospectively recruited. We collected the following data: demographics, vascular risk factors, antiplatelet and anticoagulation treatment, antiplatelet responsiveness, coagulation profile, and hemorrhagic complications. P2Y12 receptor-mediated platelet inhibition was tested by using the VerifyNow assay device. The primary end points were postprocedural major and minor hemorrhagic complications. Receiver operator characteristic analysis was used to evaluate the percentage of platelet inhibition as a diagnostic tool for bleeding events. The association between hemorrhage and percentage of platelet inhibition was investigated by using logistic regression modeling. RESULTS: Forty-seven patients were enrolled. The mean age was 56 ± 12 years, and 28% were men. Ten patients (21.3%) developed hemorrhagic complications. Clopidogrel response was higher in patients with a major bleeding complication compared with those with minor or no bleeding (median, 94% versus 24% platelet inhibition; P = .0084). Of the 7 patients (14.9%) defined as hyper-responders with ≥72% platelet inhibition, 42.8% had a major bleeding complication. CONCLUSIONS: Hyper-response to clopidogrel is associated with increased risk of hemorrhagic complications. Larger studies are urgently needed to validate a clinically useful threshold to define clopidogrel hyper-response and to examine the clinical effects of antiplatelet dosage adjustment.


Thompson L.H.,Florey Neuroscience Institute | Parish C.L.,Florey Neuroscience Institute
Methods in Molecular Biology | Year: 2013

Cell therapy is a promising experimental treatment for Parkinson's disease (PD). It is based on the idea that new dopamine neurons transplanted directly into the forebrain of the patient can structurally and functionally compensate for those lost to the disease in order to restore motor function. While there is a highly active field of research focused on the development of stem cell-based procedures, fetal tissue remains the "gold standard" as a safe and reliable source of dopamine neuron progenitors capable of structural and functional integration with existing motor circuitry following transplantation. This chapter describes the basic procedures for preparation of dopamine progenitor rich cell suspensions of ventral mesencephalon as well as implantation into the unilateral 6-hydroxydopamine model of PD and assessment of functional impact according to drug-induced rotational behavior. The description assumes a basic knowledge of animal handling and stereotaxic surgical procedures in rodents. © Springer Science+Business Media New York 2013.


PubMed | Florey Neuroscience Institute
Type: | Journal: Methods in molecular biology (Clifton, N.J.) | Year: 2013

Cell therapy is a promising experimental treatment for Parkinsons disease (PD). It is based on the idea that new dopamine neurons transplanted directly into the forebrain of the patient can structurally and functionally compensate for those lost to the disease in order to restore motor function. While there is a highly active field of research focused on the development of stem cell-based procedures, fetal tissue remains the gold standard as a safe and reliable source of dopamine neuron progenitors capable of structural and functional integration with existing motor circuitry following transplantation. This chapter describes the basic procedures for preparation of dopamine progenitor rich cell suspensions of ventral mesencephalon as well as implantation into the unilateral 6-hydroxydopamine model of PD and assessment of functional impact according to drug-induced rotational behavior. The description assumes a basic knowledge of animal handling and stereotaxic surgical procedures in rodents.

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