- Neuroscience of respiration and sleep
- Neuroendocrine regulation and behavior
- Heart Rate Variability and Autonomic Control
- Stress Responses and Cortisol
- Vagus Nerve Stimulation Research
- Circadian rhythm and melatonin
- Sleep and Wakefulness Research
- Blood Pressure and Hypertension Studies
- Adenosine and Purinergic Signaling
- Receptor Mechanisms and Signaling
- Nicotinic Acetylcholine Receptors Study
- Regulation of Appetite and Obesity
- Anesthesia and Neurotoxicity Research
- Nitric Oxide and Endothelin Effects
- Neuropeptides and Animal Physiology
- Sodium Intake and Health
- Birth, Development, and Health
- Dietary Effects on Health
- Neuroinflammation and Neurodegeneration Mechanisms
- Electrolyte and hormonal disorders
- Neuroscience and Neural Engineering
- Renin-Angiotensin System Studies
- Conducting polymers and applications
- Chemokine receptors and signaling
- Eicosanoids and Hypertension Pharmacology
The University of Melbourne
2014-2024
University of Bristol
2007-2021
Florey Institute of Neuroscience and Mental Health
2011-2021
Monash University
1999-2014
Universidade de São Paulo
2014
Baker Heart and Diabetes Institute
2014
NIHR Bristol Cardiovascular Biomedical Research Unit
2009-2013
University College London
2010
Bury College
2010
Wolfson Foundation
2010
Recently, the G protein-coupled receptor GPR30 has been identified as a novel oestrogen (ER). The distribution of thus far mapped only in rat central nervous system. This study was undertaken to map mouse brain and rodent peripheral tissues. Immunohistochemistry using an antibody against revealed high levels immunoreactivity (ir) forebrain (e.g. cortex, hypothalamus hippocampus), specific nuclei midbrain pontine locus coeruleus) trigeminal cerebellum Purkinje layer hindbrain adult brain. In...
We investigated a neural reflex that controls the strength of inflammatory responses to immune challenge - reflex. In anaesthetized rats challenged with intravenous lipopolysaccharide (LPS, 60 μg kg(-1)), we found strong increases in plasma levels key mediator tumour necrosis factor α (TNFα) 90 min later. Those were unaffected by previous bilateral cervical vagotomy, but enhanced approximately 5-fold if greater splanchnic sympathetic nerves had been cut. Sham surgery no effect, and...
Previous studies indicate that catheter-based renal denervation reduces blood pressure and norepinephrine spillover in human resistant hypertension. The effects of this procedure on afferent sensory efferent sympathetic nerves, the subsequent degree reinnervation, have not been investigated. We therefore examined level functional anatomic reinnervation at 5.5 11 months after using Symplicity Flex catheter. In normotensive anesthetized sheep (n=6), electric stimulation intact nerves increased...
Objective: To explore the hypothesis that beta-1 adrenoreceptor blockade may be protective through attenuation of sympathetic hyperactivity and catecholaminergic inflammatory effects on cardiac hepatic function. Design: Prospective, randomized, controlled study. Setting: Animal laboratory in a university medical center. Subjects: Male adult Wistar rats. Interventions: Peripheral β1-adrenoceptor daily intraperitoneal injection (metoprolol, 100 mg·kg−1; atenolol, 6 mg·kg−1) or central nervous...
Human gene-2 relaxin (H2 relaxin) is a pleiotropic hormone with powerful vasodilatory and anti-fibrotic properties which has led to its clinical evaluation provisional FDA approval as treatment for acute heart failure. The diverse effects of H2 are mediated via cognate G protein coupled-receptor (GPCR), Relaxin Family Peptide Receptor (RXFP1), leading stimulation combination cell signalling pathways that includes cyclic adenosine monophosphate (cAMP) extracellular-signal-regulated kinases...
Abstract Monitoring of bioelectric signals in peripheral sympathetic nerves small animal models is crucial to gain understanding how the autonomic nervous system controls specific body functions related disease states. Advances minimally-invasive electrodes for such recordings chronic conditions rely on electrode materials that show low-impedance ionic/electronic interfaces and elastic mechanical properties compliant with soft fragile nerve strands. Here we report a highly stretchable...
The present study investigated the topographical distribution of P2X(1)-P2X(6) receptor subtypes in rat and common marmoset hindbrain by immunohistochemistry. In addition, double-labeling immunofluorescence was used to determine extent colocalization between catecholamine cell groups various P2X receptors. data demonstrate a widespread pattern for all six receptors throughout both hindbrain, although distinctions species, brain nuclei, exist. rat, dense staining found nucleus solitary tract...
The hypothalamoneurohypophyseal system (HNS) consists of the large peptidergic magnocellular neurons supraoptic hypo thalamic nucleus (SON) and paraventricular hypothalamic (PVN), axons which course through internal zone median eminence terminate at blood capillaries posterior lobe pituitary gland. HNS is a specialized brain neurosecretory apparatus responsible for production antidiuretic peptide hormone vasopressin (VP). VP maintains water balance by promoting conservation level kidney....
The splanchnic anti-inflammatory pathway has been proposed as the efferent arm of inflammatory reflex. Although much evidence points to spleen principal target organ where sympathetic nerves inhibit immune function, a systematic study locate organ(s) not yet made. In anesthetized rats made endotoxemic with lipopolysaccharide (LPS, 60 µg/kg iv), plasma levels tumor necrosis factor-α (TNF-α) were measured in animals cut (SplancX) or sham-cut (Sham) nerves. We confirm here that disengagement...
We have employed microarray technology using Affymetrix 230 2.0 genome chips to initially catalog the transcriptome of subfornical organ (SFO) under control conditions and also evaluate changes (common differential) in gene expression induced by challenges fluid food deprivation. identified a total 17,293 genes tagged as present one our three experimental conditions, transcripts, which were then used basis for further filtering statistical analysis. In total, 46 was changed SFO following...
NO is implicated as a major modulator of central nervous circuits regulating cardiovascular activity. Based on previous data, we hypothesized that overactivity endothelial synthase (eNOS) within the nucleus tractus solitarii (NTS) could contribute to hypertension in spontaneously hypertensive rat (SHR). Using real-time PCR, found endogenous eNOS mRNA was greater NTS mature, but not juvenile prehypertensive SHRs compared with aged-matched Wistar Kyoto (WKY) rats. To test functional...
Following an immune challenge, there is two-way communication between the nervous and systems. It proposed that a neural reflex--the inflammatory reflex--regulates plasma levels of key proinflammatory cytokine TNF-α, its efferent pathway in splanchnic sympathetic nerves. The evidence for this reflex based on experiments anesthetized animals, but anesthesia itself suppresses inflammation, confounding interpretation. Here, we show previous section nerves strongly enhances TNF-α conscious rats...
Maternal social stress during late pregnancy programs hypothalamo-pituitary-adrenal (HPA) axis hyper-responsiveness to stressors, such that adult prenatally stressed (PNS) offspring display exaggerated HPA responses a physical stressor (systemic interleukin-1β; IL-1β) in adulthood, compared with controls. IL-1β acts via noradrenergic relay from the nucleus tractus solitarii (NTS) corticotropin releasing hormone neurons paraventricular (PVN). Neurosteroids can reduce responses, so...
The Na-K-2Cl cotransporter 2 (NKCC2) was thought to be kidney specific. Here we show expression in the brain hypothalamo-neurohypophyseal system (HNS), wherein upregulation follows osmotic stress. HNS controls stability through synthesis and release of neuropeptide hormone, arginine vasopressin (AVP). AVP travels bloodstream kidney, where it promotes water conservation. Knockdown NKCC2 elicited profound effects on fluid balance following ingestion a high-salt solution—rats produced...
Neuroinflammation is a common feature in renovascular, obesity-related, and angiotensin II mediated hypertension. There evidence that increased release of the pro-inflammatory cytokine tumour necrosis factor-α (TNF-α) contributes to development hypertension, but underlying neural mechanisms are unclear. Here, we investigated whether TNF-α stimulates neurons area postrema (AP), circumventricular organ, elicit sympathetic excitation, increases blood pressure (BP).In rats with renovascular AP...
Electrical stimulation applied to individual organs, peripheral nerves, or specific brain regions has been used treat a range of medical conditions. In cardiovascular disease, autonomic dysfunction contributes the disease progression and electrical vagus nerve pursued as treatment for purpose restoring balance. However, this approach lacks selectivity in activating function- organ-specific vagal fibers and, despite promising results many preclinical studies, so far failed translate into...
Objective: For several chronic inflammatory disease states, therapy is enhanced by improving the pharmacokinetic properties of anti-inflammatory drugs through conjugation with polyethylene glycol. We hypothesized that part beneficial action PEGylated may be derived from glycol (PEG) itself. Design: Randomized, double-blinded, controlled ex vivo and in laboratory studies. Setting: University research laboratories. Subjects: Human neutrophils mononuclear cells, macrophage cell line, adult rats...