This project aims to discover the nervous pathways and mechanisms in the brain that control body temperature. We hope to identify the nerve cells in the brain that detect increases in the core temperature of the body and determine the nervous pathways that project from them to increase blood flow to the skin when we become hot. This research may lead to a better understanding of heat exhaustion which is especially dangerous to the elderly.
Investigations Of Neural Pathways For Heat Loss And Heat Gain In Thermoregulation And Fever
Funder
National Health and Medical Research Council
Funding Amount
$349,486.00
Summary
This project aims to map the nerve pathways in the brain that participate in the regulation of body temperature in the laboratory rat. The area of the brain that will be studied is the hypothalamic region. We will determine how this region influences the constriction of blood vessels in the skin to reduce heat loss when an animal is exposed to a cool environment, or when it exhibits a fever in response to a bacterial infection. As well, we will compare the nervous pathway that controls the gener ....This project aims to map the nerve pathways in the brain that participate in the regulation of body temperature in the laboratory rat. The area of the brain that will be studied is the hypothalamic region. We will determine how this region influences the constriction of blood vessels in the skin to reduce heat loss when an animal is exposed to a cool environment, or when it exhibits a fever in response to a bacterial infection. As well, we will compare the nervous pathway that controls the generation of heat from fat tissue in response to cold or fever with those controlling blood flow to the skin. These nervous pathways may be critical for maintaining correct body temperature during general anaesthesia, infections or in the aged subjected to temperature extremes. Thus, they are of importance in the health and well-being of much of the population.Read moreRead less
Brain Control Of The Thermoregulatory Cutaneous Circulation: A Window To The Mind, And To The Neurobiology Of Clozapine
Funder
National Health and Medical Research Council
Funding Amount
$561,396.00
Summary
Patients suffering from schizophrenia benefit from medication. Discovering the brain mechanisms whereby the medications work is most important. Action of many important drugs have been established in experimental animals. This is a difficult task for anti-schizophrenia drugs because it is difficult to establish what animals are thinking or feeling, and it is doubtful whether animals ever suffer from schizophrenia. Thus it would be very advantageous to discover a physiological response, measurabl ....Patients suffering from schizophrenia benefit from medication. Discovering the brain mechanisms whereby the medications work is most important. Action of many important drugs have been established in experimental animals. This is a difficult task for anti-schizophrenia drugs because it is difficult to establish what animals are thinking or feeling, and it is doubtful whether animals ever suffer from schizophrenia. Thus it would be very advantageous to discover a physiological response, measurable in, for example, rats, that can serve as a marker of the animal s emotional responses to situations that would normally prove anxiety-provoking. The present grant is based on the discovery, in my laboratory, that stressful stimuli cause sudden falls in blood flow to the tail in rats. My laboratory is the first in the world to measure pulsatile blood flow to the tail in conscious rats, and this is why we made our discovery. My laboratory also discovered that clozapine, a drug of major theoretical and practical importance for the treatment of schizophrenia inhibits fright-induced constriction of the tail artery. Clozapine interacts with many potential neurotransmitters in the brain. Some very complex combinations of these interactions are presumably responsible for the drug s unique psychotherapeutic action in schizophrenia. Our discovery that clozapine inhibits fright-induced constriction of the tail artery means that we will be able to investigate clozapine s mechanisms of action. Results of our findings are genuinely likely to increase our understanding of how clozapine works in schizophrenia. This information should also provide clues as to the nature of the presently mysterious brain malfunctions that result in schizophrenia.Read moreRead less
Our lives depend upon maintaining the correct body temperature. Failure to regulate it properly may be lethal. This is particularly true in the elderly, who are more susceptible on the one hand to heat stroke and on the other to hypothermia. Many die each year from both these causes. Body temperature is regulated by the brain, yet our understanding of how and where in the brain this happens is poor. This proposal aims to work out the 'wiring diagram' of brain temperature control pathways in rats ....Our lives depend upon maintaining the correct body temperature. Failure to regulate it properly may be lethal. This is particularly true in the elderly, who are more susceptible on the one hand to heat stroke and on the other to hypothermia. Many die each year from both these causes. Body temperature is regulated by the brain, yet our understanding of how and where in the brain this happens is poor. This proposal aims to work out the 'wiring diagram' of brain temperature control pathways in rats and to begin to extend this knowledge to humans. This work will generate new knowledge about a vital function. The insights obtained will inform and guide future strategies in aged care, intensive care and perioperative care.Read moreRead less
Brain Pathways For Neurally-mediated Fever: From Vagal Afferent To Sympathetic Output To Brown Adipose Tissue Via Brain
Funder
National Health and Medical Research Council
Funding Amount
$405,223.00
Summary
Fever is one of the immune defence reactions to the invasion of microorganisms such as bacteria and viruses. Fever reflects increased heat production and decreased heat loss. Systems regulating heat production and heat loss are under brain control. To trigger fever, the immune system must alert the brain to the presence of infection. The general view of how the alerting system triggers fever is that it develops in sequential steps. Macrophages ingest microorganisms, and then regulatory proteins ....Fever is one of the immune defence reactions to the invasion of microorganisms such as bacteria and viruses. Fever reflects increased heat production and decreased heat loss. Systems regulating heat production and heat loss are under brain control. To trigger fever, the immune system must alert the brain to the presence of infection. The general view of how the alerting system triggers fever is that it develops in sequential steps. Macrophages ingest microorganisms, and then regulatory proteins (cytokines) are released. The cytokines enter the blood stream and are transported to the brain. Recently, the existence of another signalling pathway has been demonstrated. The pathway is via a special peripheral sensory nerve, the abdominal vagal sensory nerve. However, special neural pathways in the brain have not yet been clarified, even though several neural relay stations have been proposed. To elucidate neural pathways transmitting information of infection to the brain, both input and output of the pathway need to be specified. Specific outputs other than body temperature have not been determined, so far. I have recently developed a new reflex model, in which I focus on sympathetic nerves supplying the specialised fat tissue as an output as well as the vagus sensory nerve as an input. The fat tissue, brown adipose tissue (BAT), generates heat. When the vagus sensory nerve is stimulated electrically, BAT sympathetic nerve is activated. We were very exited when we discovered the potency of the combination in our rat model. We are now ready to elucidate brain pathways for neurally-mediated fever, using our new reflex model. Signalling to the brain via the nervous system is faster than via the blood stream, and thus must be very important for the earliest phase of fever. Understanding the neural pathways by which the brain perceives peripheral infection and triggers fever may promote beneficial aspects of the acute-phase immune reaction.Read moreRead less
Infrared Thermal Imaging: An Innovative Technique To Assess Peripheral Body Temperature.
Funder
National Health and Medical Research Council
Funding Amount
$192,710.00
Summary
Insomnia is a significant health issue, with 10-12% of the general population reporting sleeping difficulties requiring treatment. Pharmacological treatment with hypnotics-sedatives remain the main treatment strategy for most insomnias, despite the adverse side-effects. A better understanding of the physiological triggers for sleep will make it possible to develop more specific treatments for insomnia. Sleep onset is reported to be associated with changes in body temperature. Broadly speaking, s ....Insomnia is a significant health issue, with 10-12% of the general population reporting sleeping difficulties requiring treatment. Pharmacological treatment with hypnotics-sedatives remain the main treatment strategy for most insomnias, despite the adverse side-effects. A better understanding of the physiological triggers for sleep will make it possible to develop more specific treatments for insomnia. Sleep onset is reported to be associated with changes in body temperature. Broadly speaking, sleep onset has been linked with a rapid reduction in core temperature through increased peripheral heat loss. It has been suggested from this that sleep onset insomnia may result from the failure to efficiently lose heat at the periphery and thus, reduce core temperature. To date, the analysis of peripheral temperature physiology has been limited to single temperature thermistors attached to discrete body areas. This technique typically provides very limited information about the dynamic temperature changes. Recently, low cost, high resolution thermal imaging systems have become available, enabling the measurement of real-time changes in peripheral temperature across the whole body simultaneously. This development will help to significantly improve our understanding of the physiological mechanisms involved in both sleep onset and insomnia. The aim of this project then, is to determine whether an impaired capacity to lose heat at the periphery contributes to sleep onset insomnia in both young and older adults. The results of this project will provide insight into whether a reduced capacity to dissipate heat results in an extended sleep onset latency, greatly enhancing our knowledge of the physiology of sleep onset and sleep onset insomnia. In turn, treatments may be developed that directly manipulate the physiological triggers for sleep, minimising the dependence on sedative-hypnotics and the associated adverse effects of these agents.Read moreRead less
Functional Mapping Of Autonomic Control Circuits In The Human Brain
Funder
National Health and Medical Research Council
Funding Amount
$291,451.00
Summary
Nerves called sympathetic nerves stimulate the heart and raise blood pressure. The brain drives them when we are excited or frightened. It also over-drives them in cardiovascular diseases, and this makes matters worse. This project will use MRI brain scanning to investigate, for the first time, how the cerebral cortex and brain stem act together to control sympathetic nerves. Understanding how this system works normally will help tell us how it may malfunction, and what we can do to correct it.