Imaging to understand neurological diseases

The cells that help control signals within the brain to ensure a balance between its energy demand and supply are being investigated by researchers whose findings could have significant implications for many brain diseases.

Imaging to UnderstandDr Clare Howarth, a Wellcome Trust and Royal Society Sir Henry Dale Fellow, is investigating the cells and signalling pathways involved in regulating the amount of energy brought to the brain by blood in the form of oxygen and the simple sugar, glucose.

“When neurons need more energy, they send a message to the blood vessels. However, the biological mechanisms behind this are not fully understood,” said Dr Howarth, who has recently joined Sheffield’s Neurovascular and Neuroimaging Research Group, international leaders in the fields of neurovascular coupling and preclinical neuroimaging research.

“My research looks at the cells and molecules which control this signalling process. In conditions such as stroke and ageing, and in many neurodegenerative diseases such as Alzheimer’s disease, the matching of neural energy demand and energy supply by the blood may be dysfunctional.”

Dr Jason Berwick, a Reader in Neurophysiology and the group’s leader, said: “It’s great to have Clare join us, she fits perfectly with what we are doing. She is helping the group extend the scope of its research to include the ageing process.”

Using state-of-the-art imaging equipment, Dr Howarth is now exploring whether the brain’s blood flow can still meet the energy requirements of the active brain in conditions where the communication between neurons and blood vessels is altered. She said her new project – The role of astrocytes in neurovascular coupling in health and ageing – will determine which signals stimulate increased blood flow to active parts of the brain, and focus on what happens in conditions where this signalling process is disrupted.

Her colleague, Dr Chris Martin, is also researching the role that blood plays in brain function. “Over 1.5 pints of blood flow through your brain every minute. Getting this delivered to those areas that need it, when they need it, is a remarkable feat of biological logistics,” said Dr Martin, a Royal Society University Research Fellow. “This is a really exciting area of science to work in right now. There is suddenly a much wider recognition that even small disturbances of brain blood flow regulation could have big implications for not only brain health, but also our ability to use brain imaging techniques in humans to understand brain function, and dysfunction.”

“This is a really exciting area of science to work in right now, as it seems likely that what we can currently achieve with these tools is merely the tip of the iceberg," says Dr Chris Martin.

This is a really exciting area of science to work in right now. There is suddenly a much wider recognition that even small disturbances of brain blood flow regulation could have big implications for not only brain health, but also our ability to use brain imaging techniques in humans to understand brain function, and dysfunction.

Dr Chris Martin

The group is based in the Department of Psychology, but collaborates with many other research teams across the University of Sheffield. “There is increasing opportunity for us to connect our work with that going on in other groups,” said Dr Martin. “For instance, we have recently launched the Neuroimaging in Cardiovascular Disease (NICAD) Network, which links our work to that going on in the Sheffield Institute for Translational Neuroscience (SITraN) and the Department of Infection, Immunity and Cardiovascular Disease. The focus of this network is to investigate how cardiovascular risk factors impact upon brain blood flow regulation using a range of neuroimaging techniques.”

The group has attracted more than £10 million in research funding over recent years – including support from the Medical Research Council, Alzheimer’s Research UK, Wellcome Trust, the British Academy, the Leverhulme Trust, the Royal Society, the Biotechnology and Biological Sciences Research Council (BBSRC) and Engineering and Physical Sciences Research Council (EPSRC). In one of Dr Jason Berwick’s latest projects, funded by Epilepsy Research UK, he is investigating how epileptic seizures can start in a small part of the brain before quickly spreading to others.

“Finding where seizures begin in the brain and how they spread is important so that patients that aren’t helped by medication can be treated in other ways, for instance using surgery. Using our specialised imaging techniques, we have found that stimulating the whiskers in a rat can make seizures that start in different parts of the brain spread more easily to those areas that receive information from the whiskers,” he said. “This might suggest that areas which are receiving sensory input are more vulnerable to incoming seizure activity. We want to learn how, and measure the changes in the way brain cells work and are fed by blood during the spread of seizures. This knowledge could help to improve treatments that control and prevent seizures.”

 

Sheffield's neurovascular and neuroimaging research group

Sheffield's Neurovascular and Neuroimaging Research Group within the Department of Psychology is recognised as an international leader in the fields of neurovascular coupling and preclinical neuroimaging research. The group has secured over £10M of research funding over the last 5 years (>£5M as PIs), whilst publishing in leading international journals. Their facilities and expertise enable them to investigate neurovascular function from the level of individual cells up to whole brain.

Healthy brain function is critically dependent upon the rapid, local and dynamic regulation of blood supply according to the metabolic demand of neurons. Whilst this ‘neurovascular coupling’ is well established as the mechanism underpinning non-invasive brain imaging techniques such as functional MRI, disruption of this mechanism is increasingly recognised as a key factor in many of the most prevalent neurological diseases.

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