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