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The effect of dementia and aging on the functional and hemodynamic response of the brain


Project Description

The neuro-vascular unit and the hemodynamic response regulate how the blood supply in our brain meets the metabolic demand of neuronal activity. There is evidence that this control mechanism degenerates with age and is also impaired in dementia. However, the basic mechanisms underlying this decreased performance in neurovascular coupling are poorly understood. We have developed an in vivo multi photon imaging approach that allows us to investigate the hemodynamic response to sensory stimulation with high spatial and temporal resolution. We can analyse the spatio-temporal properties of vasodilation as well as the effect that activity has on the neuronal function of the brain tissue. In this study we propose to compare the neural activity and hemodynamic response in animal models of dementia at several stages of the disease.

We hope to identify through this research which parameters in the complex hemodynamic response have the biggest contribution to the degeneration with dementia and also old age. This might also lead to the development of imaging based biomarkers for early detection of changes in the brain before clinical symptoms of dementia are detected.

Training/techniques to be provided:
The student will be trained in several in vivo skills including surgical preparation, animal anaesthesia, animal handling and maintenance (Schiessl/Lawrence/Allan). The candidate will be trained using the functional brain imaging setup as well as electrophysiological recordings (Schiessl). The student will be trained to prepare the brain tissue for several histological and immuno-histochemical markers (Lawrence/Allan). The candidate will be trained in modern mathematical approaches for the analysis of functional brain imaging data (Schiessl). The student will be trained in experimental design and how to organise research with different subject cohorts (Schiessl/Lawrence/Allan).

Entry Requirements:
Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area / subject. Candidates with experience in in-vivo neuroscience and immune-histochemistry are encouraged to apply.

For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit http://www.internationalphd.manchester.ac.uk

Funding Notes

Applications are invited from self-funded students. This project has a Band 3 fee. Details of our different fee bands can be found on our website (View Website). For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (View Website).

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

References

1. ZS. Al-Ahmady, D Jasim, SS Ahmad, R Wong, M Haley, G Coutts, I Schiessl, SM. Allan, K Kostarelos. Selective Liposomal Transport Through Blood Brain Barrier Disruption in Ischaemic Stroke Reveals Two Distinct Therapeutic Opportunities. Doi: http://dx.doi.org/10.1101/570234 bioRxiv preprint first posted online Mar. 9, 2019

2. Haley, M., Krishnan, S., Burrows, D., de Hogg, L., Thakrar, J., Schiessl, I., Allan, S. & Lawrence, C. B. (2017) “Acute high-fat feeding leads to disruptions in glucose homeostasis and worsens stroke outcome.” J Cereb Blood Flow Metab Nov 19
3. Bray, N., Burrows, F. E., Jones , M., Berwick , J., Allan, S. & Schiessl, I., (2016) “Decreased Haemodynamic Response and Decoupling of Cortical Gamma Band Activity and Tissue Oxygen Perfusion after Striatal Interleukin-1 Injection”, J. Neuroinflammation, Aug 24;13(1):195

4. Burrows, F., Haley, M., Scott, E., Coutts, G., Lawrence, C., Allan, S. & Schiessl, I. (2016) “Systemic Inflammation Affects Reperfusion Following Transient Cerebral Ischaemia.” Experimental Neurology. 277, p. 252-60 9 p.

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