There are estimated to be more than 100,000 people in the UK living with the effects of a spinal cord injury, and around 4,700 new spinal cord injuries every year.
One of the most common impairments after spinal cord injury (SCI) is impairment in urinary function. This is highly debilitating and has been highlighted as a priority by those living with SCI.
In this project, Professor Rob Brownstone and team will address a key gap in our knowledge of the neural circuits that control bladder function and how these circuits change following spinal cord injury. This will provide foundational knowledge to underpin the development of effective therapies.
The bladder is a relatively simple organ that expands to store urine and contracts to empty it when we choose. People with SCI often lose bladder control due to a condition called ‘neurogenic bladder’. Those affected have reduced awareness of their bladder being full, and reflexes can cause it to empty involuntarily. Bladders also tend to become overactive, meaning that they may contract frequently, with little or no warning. As a result, many people with SCI rely on catheters to manage their bladder.
Regaining bladder control is consistently highlighted as a major concern for those with SCI. Existing treatments, such as medications and electrical stimulation, can help to some extent but don't fully restore function, and often cause side effects.
A major obstacle to the development of new, more effective treatments is our limited understanding of the intricate neural circuits of the spinal cord - circuits that coordinate the contractions of various muscles to store urine and to empty the bladder. We also lack a clear understanding of how these circuits change following SCI. Professor Brownstone and team propose to address this knowledge gap to identify new treatment approaches.
The process of emptying the bladder is controlled by a combination of brain and spinal cord neurons working together. A group of neurons in the brainstem generates a bladder-emptying (voiding) ‘command’ that is then interpreted by neuronal circuits in the lower spinal cord to coordinate activation of the bladder and sphincter muscles. When the voiding command initiates urinary function, these muscles are activated and inactivated in a coordinated matter to empty the bladder.
After SCI, however, both the brainstem control and the spinal cord coordination are lost, leading to urine retention and a need to catheterise the bladder. At first, the sphincter muscles remain permanently contracted, thus preventing voiding of the bladder. Later, this continuous contraction is relieved by unknown mechanisms, but normal, coordinated voiding does not return.
To understand which neurons are involved in normal urinary function, and how these cells adapt following SCI, the team will study how these nerve circuits work in mice and how they change after SCI. They will use a range of techniques to map out the neurons involved.
Interestingly, mice can regain some of their bladder function within several weeks of SCI. Thus, the team will use their tools to focus on two important timeframes: the early phase right after the injury, and a later phase when the mice have started to recover some bladder function. By comparing these two phases, the team hopes to reveal how the circuits adapt and change during the initial shock of the injury and when some recovery is observed.
This project will provide a detailed characterisation of the neurons involved in normal bladder control, how they change after SCI, and how they adapt to the new state of the nervous system at later stages. The identification of cellular and circuit dysfunction will provide foundational knowledge to develop new therapies aimed at these specific targets. Such therapies could include, for example, genetic therapies and nerve stimulation.
The project team comprises three scientists. Professor Rob Brownstone is the Brain Research UK Chair of Neurosurgery at UCL Queen Square Institute of Neurology, and is a neurosurgeon-scientist, with expertise in neural circuits and the spinal cord.
On this project he is working with Professor Marco Beato and Dr Görkem Özyurt, neuroscientists who bring complementary skills and expertise, to successfully complete the intricate experiments involved in this project.
Acquired brain and spinal cord injury (including stroke) is one of our current research priorities, reflecting the large unmet need in this area. Our aim is to fund research to advance understanding of how to promote repair of the brain and spinal cord following injury.
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