Stroke Research Group

Stroke Research Group

The objective of WANRI’s Stroke Research Group led by Adjunct Associate Professor Bruno Meloni and Clinical Professor Neville Knuckey is to develop treatments to minimise brain damage after stroke and cerebral ischaemia.

Stroke is Australia’s second biggest killer after coronary heart disease and a leading cause of disability. One in six people will suffer from a stroke during their lifetime with over 400,000 Australians currently living with the debilitating aftereffects of the disorder. By 2032, it is estimated that over 700,000 Australian will be living with the effects of stroke.

At present, available treatments are not satisfactory.  To this end, the Stroke Research Group have been:

i) identifying and characterising potential neuroprotective proteins

ii) assessing the potential of the sodium calcium exchanger (NCX) membrane ion transporter to protect neurons from ischaemia;

iii) assessing the efficacy of mild hypothermia when used with magnesium and other putative neuroprotective agents/treatments; and

iv) assessing the potential of arginine-rich peptides as neuroprotective agents.

 

Translational studies

In 2014, as a result of our research looking at the neuroprotective effects of combined mild hypothermia and magnesium therapy in stroke models, a clinical pilot study in a select group of stroke patients, will be performed at Sir Charles Gairdner Hospital (SCGH). The pilot study, will use mild hypothermia and magnesium therapy in stroke patients during and after mechanical thrombectomy (clot removal) to restore blood flow in a blocked cerebral artery. It is anticipated that this new therapy will be safe and improve patient outcomes based on comparison with historical controls.

Staff

Adjunct Associate Professor Bruno Meloni

Adjunct Associate Professor Meloni, head of laboratory research, obtained his BAppSci at Curtin University and completed both his Honours and PhD degrees at Murdoch University. In 1993, Bruno was awarded a Commonwealth AIDS Research Council Grant (CARG) Postdoctoral Fellowship to continue research at Murdoch University.

Full Biography

Clinical Professor Neville Knuckey

Clinical Professor Neville Knuckey, head of the Stroke Research Group, completed a degree in medicine at the University of Western Australia before undertaking training in Neurosurgery in Western Australia. He completed Neurosurgical Fellowships at The Johns Hopkins and Brown University in the USA. From 1986-1995 he was an Associate Professor in Neurosurgery at Brown University where his principle clinical interest was neurovascular surgery and where his laboratory research focused on mechanisms of neuroprotection.

Full Biography

Dr Jane Cross - Research Officer

Vince Clark - Research Officer

Students

Dr Diego Milani, MD - PhD Student
Adam Edwards - PhD Student
Li Shan Chiu- PhD Student
Gabriella MacDougall - Honours Student

Grants

Neurotrauma Research Program 2014

Awarded to characterise neuroprotective peptides.

Neuroprotective efficacy of poly-arginine peptides in cerebral ischaemia models and mechanism of action.

Meloni/Knuckey/Fitzgerald ($97,125)

Notre Dame University
Research Incentive Scheme Grant

To support arginine poly-peptide neuroprotection research.

Anderton/Meloni ($5,000)

UWA Pathfinder Grant

“A Pre-clinical assessment of poly-arginine peptides in stroke”.

Meloni (Stage 1: $11,000. Stage 2: $11,000)

Publications

Meloni, B.P. & Knuckey, N.W. (2015) Magnesium may provide further benefit to hypothermia following perinatal asphyxia encephalopathy, Journal of Perinatal Medicine, 43 (1), pp. 125-126.

Meloni, B.P., Brookes, L.M., Clark, V.W., Cross, J.L., Edwards, A.B., Anderton, R.S., Hopkins, R.M., Hoffmann, K. & Knuckey, N.W. (2015) Poly-arginine and arginine-rich peptides are neuroprotective in stroke models, Journal of Cerebral Blood Flow and Metabolism, 35 (6) pp. 993-1004.

Meloni, B.P., Milani D., Adam B. Edwards A.B., Anderton, R.S., O’Hare Doig, R.L., Fitzgerald M., Palmer T.N., Knuckey, N.W. (2015). Neuroprotective peptides fused to arginine-rich cell penetrating peptides: Neuroprotective mechanism likely mediated by peptide endocytic properties. Pharmacology and Therapeutics. In press.

Meloni BP, Craig AJ, Milech N, Hopkins RM, Watt PM, Knuckey NW. (2014). The Neuroprotective Efficacy of Cell-Penetrating Peptides TAT, Penetratin, Arg-9, and Pep-1 in Glutamic Acid, Kainic Acid, and In Vitro Ischemia Injury Models Using Primary Cortical Neuronal Cultures. Cell Mol Neurobiol 2014;34:173-181

Teoh J, Boulos S, Chieng J,  W. Knuckey NW, Meloni BP. (2014). Erythropoietin increases neuronal NDPKA expression, and NDPKA up-regulation as well as exogenous application protects cortical neurons from in vitro ischemia-related insults. Cellular and Molecular Neurobiology.  DOI 10.1007/s10571-013-0023-8.

Teoh J, Boulos S, Chieng J, Knuckey NW, Meloni BP. (2014). Over-expressing prohibitin (PHB) in neuronal cultures exacerbates cell death following hydrogen peroxide and l-glutamic acid induced injury.  Neuroscience and Medicine 5: 149-160.

Anderton RS, Meloni BP, Mastaglia FL, Boulos S. (2014). Investigation of a recombinant SMN protein delivery system to treat spinal muscular atrophy. Translational Neuroscience. 2014; 5(1):8-16.

Greene ID, Mastaglia F, Meloni BP, West KA, Chieng J, Mitchell CJ, Gai WP, Boulos S.  (2014).Evidence that the LRRK2 ROC domain Parkinson’s disease-associated mutants A1442P and R1441C exhibit increased intracellular degradation.  J Neuroscience Research 2014; 92(4):506-516.

Kanyenda LJ, Verdile G, Martins RN, Meloni BP, Chieng, J, Mastaglia FL, Laws SM, Anderton RS, Boulos, S. (2014). Is cholesterol and Aβ stress induced CD147 expression a protective response?: evidence that extracellular cyclophilin A mediated neuroprotection is reliant on CD147. Journal of Alzheimer’s Disease 39, 545–556.

Meloni BP and Knuckey NW (2014). Magnesium may provide further benefit to hypothermia following perinatal asphyxia encephalopathy. Journal of Perinatal Medicine, 43, 125-126. Letter to the Editor.

Meloni, B.P., Cross J.L., Brookes, L.M., Clark V.W., Campbell, K., Knuckey, N.W. (2013). Using FAST-Mag Protocol With Or Without Mild Hypothermia (35°C) Does Not Improve Outcome After Permanent MCAO In Rats. Magnesium Research, 26 (2): 67-73.

Cross, J.L., Boulos, B., Shepherd, K.L., Craig, A.J., Lee, S., Bakker, A.J., Knuckey, N.W, Meloni, B.P. (2012). High level over-expression of different NCX isoforms in HEK293 cells and primary neuronal cultures is protective following oxygen glucose deprivation, Neuroscience Research 73(3): 191-198.

Meloni, B.P., Meade, A.J., Kitikomolsuk, D., Knuckey, N.W. (2011). Characterisation of neuronal cell death in acute and delayed in vitro ischaemia (oxygen/glucose deprivation) models. Journal of Neuroscience Methods. 195: 67-74.

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