- Neuroscience and Neuropharmacology Research
- Ion channel regulation and function
- Epilepsy research and treatment
- Cardiac electrophysiology and arrhythmias
- Receptor Mechanisms and Signaling
- Genetics and Neurodevelopmental Disorders
- Mast cells and histamine
- Pharmacological Effects and Toxicity Studies
- Neuropeptides and Animal Physiology
- Adenosine and Purinergic Signaling
- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience and Neural Engineering
- Olfactory and Sensory Function Studies
- CRISPR and Genetic Engineering
- Lipid Membrane Structure and Behavior
- Polyamine Metabolism and Applications
- Pancreatic function and diabetes
- Animal Genetics and Reproduction
- Neural dynamics and brain function
- Asthma and respiratory diseases
- Autophagy in Disease and Therapy
- Extracellular vesicles in disease
- Tryptophan and brain disorders
- Neurological Complications and Syndromes
- Brain Metastases and Treatment
Royal Children's Hospital
2025
Murdoch Children's Research Institute
2025
The University of Melbourne
2014-2024
Monash University
1972-2024
Rutgers New Jersey Medical School
2023
Rutgers, The State University of New Jersey
2023
The Royal Melbourne Hospital
2013-2022
Alfred Health
2019-2022
The Alfred Hospital
2020
Australian National University
2002-2004
Microglial activation is an integral part of neuroinflammation associated with many neurodegenerative conditions. Interestingly, a number conditions exhibit enhanced P2X 7 receptor (P2X R) expression in the neuroinflammatory foci where activated microglia are coexisting feature. Whether R overexpression driving microglial or, conversely, consequence not known. We report that alone purinergic R, absence pathological insults, sufficient to drive and proliferation rat primary hippocampal...
Absence seizures are a common seizure type in children with genetic generalized epilepsy and characterized by temporary loss of awareness, arrest physical activity, accompanying spike-and-wave discharges on an electroencephalogram. They arise from abnormal, hypersynchronous neuronal firing brain thalamocortical circuits. Currently available therapeutic agents only partially effective act multiple molecular targets, including γ-aminobutyric acid (GABA) transaminase, sodium channels, calcium...
Low-voltage-activated, or T-type, calcium (Ca 2+ ) channels are believed to play an essential role in the generation of absence seizures idiopathic generalized epilepsies (IGEs). We describe a homozygous, missense, single nucleotide (G C) mutation Ca v 3.2 T-type channel gene ( Cacna1h genetic epilepsy rats from Strasbourg (GAERS) model IGE. The GAERS gcm produces arginine proline (R1584P) substitution exon 24 , encoding portion III–IV linker region 3.2. segregates codominantly with number...
To investigate the relationship of glutamate and transporter expression in human gliomas surrounding peritumoral brain to presence tumor-associated seizures (TAS).We studied a retrospective (group 1: 190 patients) then prospective 2: 98 cohort patients who underwent craniotomy for supratentorial glioma. Tumor peritumor tissue specimens were assayed concentration glial transporters. Differences between seizure (TAS) seizure-free (non-TAS) groups compared.A total 42% had TAS, with 95% first...
Summary Purpose Ethosuximide ( ESX ) is a drug of choice for the symptomatic treatment absence seizures. Chronic with has been reported to have disease‐modifying antiepileptogenic activity in WAG /Rij rat model genetic generalized epilepsy GGE Here we examined whether chronic (1) possesses effects rats from Strasbourg GAERS , (2) associated mitigation behavioral comorbidities, and (3) influences gene expression somatosensory cortex region where seizures are thought originate. Methods...
Enhanced expression of the purinergic P2X7 receptor (P2X7R) occurs in several neuroinflammatory conditions where increased microglial activation is a co-existing feature. receptors can function either as cation channel or, upon continued stimulation, large pore. P2X7R-over-expression alone sufficient to drive and proliferation process that P2X7R pore dependent, although biological signaling pathway through which this remains unclear. Once activated, microglia are known release number...
Diabetic heart disease morbidity and mortality is escalating. No specific therapeutics exist mechanistic understanding of diabetic cardiomyopathy etiology lacking. While lipid accumulation a recognized cardiomyocyte phenotype diabetes, less known about glycolytic fuel handling storage. Based on in vitro studies, we postulated the operation an autophagy pathway myocardium for glycogen homeostasis - glycophagy. Here visualize occurrence cardiac glycophagy show that characterized by marked...
Studies in animal models and patients have implicated changes hyperpolarization-activated cyclic nucleotide-gated cation channel (HCN) expression the pathogenesis of temporal lobe epilepsy (TLE). However, nature HCN during epileptogenic process their commonality across different TLE is unknown. Here HCN1 HCN2 mRNA was quantitatively measured at time points epileptogenesis two distinct TLE; kainic acid (KA)-induced status epilepticus (SE) amygdala kindling models.Hippocampal subregions (CA1,...
Originally derived from a Wistar rat strain, proportion of which displayed spontaneous absence-type seizures, Genetic Absence Epilepsy Rats Strasbourg (GAERS) represent the most widely utilized animal model genetic generalized epilepsy. Here we compare seizure, behavioral, and brain morphometric characteristics four main GAERS colonies that are being actively studied internationally: two Melbourne (MELB STRAS-MELB), one Grenoble (GREN), Istanbul (ISTAN).Electroencephalography (EEG)...
Genetic alterations have been identified in the CACNA1H gene, encoding Ca
Temporal lobe epilepsy (TLE) is the most common form of drug resistant epilepsy. Current treatment symptomatic, suppressing seizures, but has no disease modifying effect on epileptogenesis. We examined effects Z944, a potent T-type calcium channel antagonist, as an anti-seizure agent and against progression kindling in amygdala model TLE. The efficacy Z944 (5mg/kg, 10mg/kg, 30mg/kg 100mg/kg) was assessed fully kindled rats (5 class V seizures) compared to vehicle, ethosuximide (ETX,...
Summary Objective Evidence from animal and human studies indicates that epilepsy can affect cardiac function, although the molecular basis of this remains poorly understood. Hyperpolarization‐activated cyclic nucleotide‐gated ( HCN ) channels generate pacemaker activity modulate cellular excitability in brain heart, with altered expression function associated cardiomyopathies. Whether is heart association has not been investigated previously. We studied electrophysiologic properties channel...
Low-voltage-activated or T-type Ca2+ channels play a key role in the generation of seizures absence epilepsy. We have described homozygous, gain function substitution mutation (R1584P) CaV3.2 channel gene (Cacna1h) Genetic Absence Epilepsy Rats from Strasbourg (GAERS). The non-epileptic control (NEC) rats, derived same original Wistar strains as GAERS but selectively in-breed not to express seizures, are null for R1584P mutation. To study effects this rats who otherwise NEC genetic...
Objective The Genetic Absence Epilepsy Rats from Strasbourg (GAERS) are an inbreed Wistar rat strain widely used as a model of genetic generalised epilepsy with absence seizures. As in humans, the architecture that results generalized GAERS is poorly understood. Here we present strain-specific variants found among epileptic and their related Non-Epileptic Control (NEC) strain. NEC represent powerful opportunity to identify neurobiological factors associated phenotype. Methods We performed...