Understanding the basic biology of anaesthetic-induced cognitive decline

The deadline for 2012 Doctoral College Studentships has now passed.

The Brighton Doctoral College is pleased to welcome applications from self-funded or externally sponsored students for programmes of research in this or a closely related area, beginning from September 2012. Applications are welcome from students wishing to study full time or part time, and applications are welcome from students in employment who have the support of their employers.

• Based in the Faculty of Science and Engineering
• Supervisors:  Dr Mark Yeoman;  Dr Bhavik Patel.

Application deadline

The university cannot guarantee that students can start at their requested date unless deadlines are met.

• UK/EU students: The deadline for the university to receive applications for an entry date of October is the 1 August, for January entry it is the 1 November and for May it is the 1 March.
• International students: The deadline for the university to receive applications for an entry date of October is the 1 June, for January entry it is the 1 September and for May it is the 1 January.

Apply now.

50 years ago surgery was considered hazardous for patients aged 55 years and older, with many older patients who underwent general anaesthesia suffering from post-operative cognitive decline (POCD).

Based on this work many elderly patients were denied much needed operations. Despite improvements in both surgical and anaesthetic techniques, the risks of POCD still remain significant, with decline lasting a few days to a few months or, in the worst circumstances, causing permanent changes in personality. 

The risk factors for POCD are currently unclear but are likely to be multi-factorial. One possible cause is exposure to the anaesthetic itself. Previous work using human neuronal cell lines has shown that physiological concentrations of anaesthetics such as isoflurane and halothane are capable of disrupting Ca²⁺ homeostasis in aged neurones.  Very similar changes appear to occur as a consequence of normal brain ageing. Alterations in Ca²⁺ homeostasis seen during ageing may be due to alterations in the redox potential of the cell although the effects of anaesthetics on redox state are currently unclear. Ca²⁺ is an extremely important second messenger molecule that is crucial for regulating transmitter release, and is intimately involved in the molecular changes that occur in our neurones during learning and memory. Disruptions to normal Ca²⁺ signalling therefore have the potential to disrupt learning and memory formation. In addition, persistently high levels of Ca²⁺ can cause neuronal cell death through apoptosis, affecting the ability of the CNS to function. Anaesthetics such as desflurane, servoflurane and propafol have markedly lesser effects on Ca²⁺ homeostasis while still being effective anaesthetic agents, suggesting that this disruption is unlikely to be an important part of these drugs’ ability to cause anaesthesia.

The student will utilise a unique top-down systems level approach to more fully understand the effects of anaesthetics on learning and memory and the changes that occur with increasing age. This will be based on a study of the pond snail; Lymnaea stagnalis as a model to further understand the direct effects of anaesthetics on the functioning of key neurones that have previously been shown to be involved in learning and memory formation (see Fig).  The principal outcome of the research will be to improve the quality of life for older people.  Understanding how the effects of anaesthetics change with increasing age will identify potential new targets which may lead to alterations in anaesthesia techniques or the design of novel compounds by the Pharmaceutical Industry to protect against POCD and help maintain independence in the older person.

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