Our group focuses on the mechanisms that enable the body to deliver oxygen to the right places at the right time,
What impact will this research have?
Our work is not just focused on molecular studies, we also study changes in activation states in histology, we aim to understand changes in regulatory states in vivo, and we also study changes in normal people undertaking mild stress, such as eating or even pregnancy, or much deeper stress such as patients unwell with cardiovascular disease.
Current projects and goals
Role of PACAP in the regulation of arterial blood pressure
PACAP is a polypeptide that is present throughout the brain and plays an important role in controlling sympathetic nerve activity and BP. We have discovered that it is present in neurons in the brainstem spinal cord, sympathetic nerves and adrenal medulla that are critical in the regulation of arterial blood pressure. Two disease states that we have a major interest in investigating, in which PACAP plays an important role are epilepsy and sleep apnoea. Studies that are currently underway include molecular studies, histological studies, physiological and pharmacological studies.
Role of microglia and inflammation in the regulation of arterial blood pressure
Traditionally, microglia – the macrophages of the brainstem – are not considered to play a soothing role in the regulation of neuronal function. Recently, we discovered that during epilepsy, microglia interact with sympathetic neurons in order to manage their level of excitation. We consider this to be an extremely important mechanistic finding and there is a great deal more to be investigated. Opportunities exist to study this question using functional neuroanatomy with novel monoclonal antibodies that we have invented and with regulatory, physiological and pharmacological methods.
Role of the brainstem in metabolic syndrome
In addition to its well-known function in monitoring oxygen and acidity in blood, the brain also monitors temperature, glucose levels, lipids and electrolytes. The ability of the brain to achieve these latter functions occurs because of its exposure in the hypothalamus to circulating concentrations of angiotensin II and insulin. Specific receptors within the hypothalamus respond to these concentrations of peptide and cause changes in the activity of cardiovascular neurons in the brainstem leading to changes in efferent sympathetic activity to different populations of neurons. Our understanding of these changes, and the way that these changes are regulated, is at its earliest stage. Certainly, it seems likely that errors in function in relation to brain monitoring of insulin could easily lead to a metabolic syndrome with weight gain, hypertension, dyslipidaemia and diabetes. It is our intention, to develop a number of projects related to the questions raised above that would be suitable for long or short term study. For example, in the past, we have studied the effects of intermittent hypoxia as a way of investigating experimental sleep apnoea. In this project, we propose intermittent hyperglycaemia and intermittent hyperlipidaemia as a method of simulating the metabolic syndrome. In order to assess the involvement of neurons in the brain that are considered to play an important role in the metabolic syndrome, we would increase or decrease the activity of the arcuate nucleus or the orexin neurons.
We would also examine known models of diabetes or obesity or hypertension and repeat the studies in these in order to see if there are any interaction effects within the brainstem or hypothalamus. Animal models to be used would include the spontaneously hypertensive rat, the obese rats, and diabetic rats.
Opportunities are also available for students with a background in biomedical engineering to undertake studies that involve sampling of data from people or patients. Studies in the past have included changing position from lying to standing and feeding in males and females, patients with glaucoma, and women that were normal and that were normal but pregnant. The advantage that we have in our studies is that we possess a device that can measure continuous arterial blood pressure noninvasively from the finger, so that we can then derive an approximate value of sympathetic nerve activity from the systolic BP waveform. This value and the many other values that can be derived allow the student to obtain a considerable amount of data from even a small number of cases.