Changes In Pelvic Autonomic Neurons After Spinal Nerve Injury
Funder
National Health and Medical Research Council
Funding Amount
$176,734.00
Summary
This project is about the effects of spinal injury on autonomic neurons that control the bladder, lower bowel and reproductive organs. One of the consequences of some types of spinal injury is that there are no signals being sent from the spinal cord to the nerve cells outside the cord, and this leads to poor bladder control, impotence, etc. We are mimicking this problem experimentally by damaging the spinal nerves that carry these signals. We have found that after this type of damage the pelvic ....This project is about the effects of spinal injury on autonomic neurons that control the bladder, lower bowel and reproductive organs. One of the consequences of some types of spinal injury is that there are no signals being sent from the spinal cord to the nerve cells outside the cord, and this leads to poor bladder control, impotence, etc. We are mimicking this problem experimentally by damaging the spinal nerves that carry these signals. We have found that after this type of damage the pelvic autonomic neurons make many new connections between each other, and the types of new connections depend on which spinal nerves have been injured. This leads to the question: are these new connections good or bad? ie are they helpful in trying to get organ control back to normal or will they stop the correct connections from the spinal cord from being made in the future? This project addresses these questions by using sophisticated techniques for staining and visualising individual nerve fibres growing out from the spinal cord. We will track how well these fibres grow back and connect with the pelvic autonomic neurons. In particular, we will see whether they make correct connections, and if these connections are influenced by the new fibres that have grown between the autonomic neurons in the interim period. We will also do physiological tests to see if the new connections have the correct function. The ultimate aim of these studies is not only to understand more about regeneration, but to see what determines whether the correct connections have been made - and ideally, to give us insight into how we can make regeneration work more quickly and accurately. We believe that this work is an important adjunct to other studies on spinal injury, which mostly focuses on regaining voluntary motor control (e.g. walking); however loss of bladder, bowel and reproductive function is another important quality of life issue for spinal injury patients.Read moreRead less
Plasticity And Regeneration Of Bladder Motor Nerve Circuits After Injury
Funder
National Health and Medical Research Council
Funding Amount
$333,313.00
Summary
Our goal is to determine ways of improving the recovery of bladder-controlling nerves after they are injured, which has devastating effects on bladder function. This can happen because of lumbosacral spinal nerve damage or pelvic surgery. We also expect to establish broad principles that may be tested in other neurological conditions that affect bladder function, such as neurodegenerative disorders (e.g. diabetes) and spinal cord injury.
Modulation Of Autonomic Nerve Growth By Guidance Factors
Funder
National Health and Medical Research Council
Funding Amount
$393,277.00
Summary
Our goal is to understand how adult nerves are affected by injury so that we can devise therapies to make them regrow better. We will focus on nerves that control the urogenital organs because these are often injured during surgical procedures (e.g. prostatectomy, hysterectomy), with devastating effects on patients' quality of life. In this project we will investigate how naturally-occurring growth-inhibitory molecules affect nerve regrowth after injury in the pelvic nervous system.
Peripheral Mechanisms Involved In Autonomic Hyperreflexia
Funder
National Health and Medical Research Council
Funding Amount
$229,917.00
Summary
Bladder distension or minor unheeded injuries below the lesion in spinally injured people often lead to episodes of high blood pressure that may cause stroke or death. These events require emergency hospitalization and are expensive as well as dangerous. After spinal injury, the control of sympathetic nerves that supply arteries and regulate blood pressure is lost. However, the nerves below the injury remain in place and the spinal cord below the lesion contains connections that can activate the ....Bladder distension or minor unheeded injuries below the lesion in spinally injured people often lead to episodes of high blood pressure that may cause stroke or death. These events require emergency hospitalization and are expensive as well as dangerous. After spinal injury, the control of sympathetic nerves that supply arteries and regulate blood pressure is lost. However, the nerves below the injury remain in place and the spinal cord below the lesion contains connections that can activate them. Signals from the bladder or skin enter the remaining lower part of the spinal cord and activate the sympathetic supply generating a rise in blood pressure. This project will test the hypothesis that increased sensitivity of arteries to the chemicals released from the sympathetic nerves leads to excessive vessel constriction, contributing to the exaggerated increase in pressure. We will investigate arteries removed from rats with experimental spinal transection. We will test the contractions of the arteries (a) to sympathetic nerve stimulation and (b) to the chemicals noradrenaline, adenosine 5'-triphosphate (ATP) and neuropeptide Y that are normally released during nerve activity. We will determine whether release of noradrenaline and ATP from nerves is normal or augmented using electrochemical and electrophysiological techniques. We will compare the responses with those in normal arteries, those in arteries whose nerves have been silenced by removing all connections from the spinal cord and those in arteries that have lost all their nerve supply. This will enable us to identify whether the mechanisms for release of transmitter substances are modified and whether the arterial muscle is hypersensitive to these substances. The results will help in the design of safer treatment for these potentially lethal emergencies in spinal patients.Read moreRead less
Mechanisms Regulating Nutrient Induced Motor Patterns In The Isolated Small Intestine
Funder
National Health and Medical Research Council
Funding Amount
$427,750.00
Summary
The movements of the small intestine are essential for the digestion and absorption of a meal and consist of two basic patterns during a 3-4 hour period after a meal. These are mixing (or segmentation) and propulsion (or peristalsis). Although it is the subject of ongoing study, much is known about the basic mechanisms that control propulsion, largely because this behaviour is readily seen in isolated segments of gut so it is possible to undertake highly controlled experiments to identify the va ....The movements of the small intestine are essential for the digestion and absorption of a meal and consist of two basic patterns during a 3-4 hour period after a meal. These are mixing (or segmentation) and propulsion (or peristalsis). Although it is the subject of ongoing study, much is known about the basic mechanisms that control propulsion, largely because this behaviour is readily seen in isolated segments of gut so it is possible to undertake highly controlled experiments to identify the various cellular components of the system. By contrast, mixing has only been reliably seen in intact animals making studies of the detailed mechanisms responsible for this behaviour much more difficult. What is known is that the composition of a meal controls the relative amount of mixing and propulsion seen at any location along the small intestine. We have recently identified a pattern of contractions in isolated small intestine (duodenum and-or jejunum) that is induced by the presence of a nutrient in the intestine and appears very similar to the mixing behaviour seen in the intact animal. We have shown that this pattern depends on the activity of nerve cells including those that excite the gut muscle and that it depends on the activity of a hormone released from the lining of the gut wall by fats and other nutrients. The aims of this proposal are to identify how nutrients interact to produce this pattern of contractions, the relative roles of specific types of nerve cells and the sites at which the local hormones released by nutrients act. This is important because increasing the proportion of mixing to propulsion enhances the absorption of nutrient from a meal, so if the mechanisms that initiate mixing behaviour can be regulated in a predictable way by specific nutrient, absorption can be enhanced in various malabsorption syndromes.Read moreRead less
The Role Of Prostaglandins In The Control Of Intestinal Motility In Physiological And Experimental Inflammatory States.
Funder
National Health and Medical Research Council
Funding Amount
$316,209.00
Summary
Many intestinal disorders are due to inflammations of unknown origin, associated with pain, diarrhoea or constipation. How this occurs is not known. The movements of the intestine are due to the contractions and relaxations of the muscular wall, which are controlled by a network of nerve cells, a kind of a brain in the gut. In inflammatory conditions, a multitude of chemical substances are produced by the sick gut. Among these substances are the prostaglandins that are responsible for increasing ....Many intestinal disorders are due to inflammations of unknown origin, associated with pain, diarrhoea or constipation. How this occurs is not known. The movements of the intestine are due to the contractions and relaxations of the muscular wall, which are controlled by a network of nerve cells, a kind of a brain in the gut. In inflammatory conditions, a multitude of chemical substances are produced by the sick gut. Among these substances are the prostaglandins that are responsible for increasing pain from inflamed parts. However, the gut makes prostaglandins even when there is no inflammation, although it is not clear what do these substances do in the normal intestine. During disease, prostaglandins are made in much larger amounts. If we can establish what they do normally we may be able to establish how they work in disease. Therefore our projects is in two parts. First, we will investigate how prostaglandins normally affect the working of the nerves and muscle controlling intestinal movement. In the second part we will reveal the role of these substances during mild inflammation induced in some laboratory animals to mimic human diseases. All experiments will be carried out on intestines removed from these experimental animals after they are killed humanely. This enables us to study how the experimentally induced diseases affect gut function, especially movement. We will use a method, that has recently been developed in our laboratory, to transform video recordings of gut movements into computer-generated maps. From these pictures, we can see patterns of movement that are too subtle to detect by just watching the videos. We will end our project by establishing if and when prostaglandins are responsible for producing the abnormal intestinal movements seen in disease. This will give clinicians a better basis to develop new drugs against gut disorders.Read moreRead less