Project ID NS-MH2024_28


Co Supervisor 1A Institute of Psychiatry, Psychology & Neuroscience, School of Neuroscience, Wolfson Centre for Age-Related DiseasesWebsite

Co Supervisor 1B Institute of Psychiatry, Psychology & Neuroscience, School of Neuroscience, Wolfson Centre for Age-Related DiseasesWebsite

Investigating how perinatal asphyxia affects myelination and epileptogenesis

Perinatal asphyxia is a critical condition that occurs when there is a lack of oxygen supply to the foetus or newborn during the perinatal period. It can lead to severe neurological complications caused by impaired myelination and epileptogenesis. Understanding the mechanisms underlying this pathology is crucial for developing targeted therapeutic strategies.

We have evidence that oligodendrocytes, which are the cells that generate myelin to speed nerve conduction in the brain, express TRP channels that (1) become overactivated during ischaemia (Hamilton et al., Nature, 2016); (2) cause demyelination (Giacco et al., Glia, 2023); and (3) increase seizure propensity (Giacco et al., unpublished).

This PhD project aims to use a range of cutting-edge techniques to investigate this mechanism in rodent models of perinatal asphyxia and human tissue obtained from elective terminations and surgeries. The latter provides a unique translational aspect to the project. Specifically, the student will:

Year 1:
•Obtain a Home Office Personal Licence to generate a rodent model of perinatal asphyxia:
measure O2 concentrations in vivo (in collaboration with Catherine Hall at Sussex Uni).
• Learn patch-clamping, electron microscopy, western blotting, compound action potential recording and immunohistochemistry (IHC) to study cell function and cell death occurring in vivo during and after asphyxia.

Year 2:
• Set up experiments to study human foetal and paediatric tissue with patch-clamping, culturing and IHC techniques.
• Investigate the mechanisms leading to cell death during oxygen and glucose deprivation in organotypic slice experiments made from rodent and human tissue.

Year 3:
• Test whether block of candidate pathological pathways prevents OPC and myelin damage and promotes remyelination in vivo and ex vivo.

The Ahmed (MB/PhD, MA (Cantab), FRCS (SN)) and Hamilton-Whitaker Labs have a great track record of generating high-impact results and publications, and in training PhD students and would provide the support and platform needed to obtain the PhD.

Representative Publications

Hamilton NB, Kolodziejczyk K, Kougioumtzidou E, Attwell D. 2016. Proton-gated Ca2+-permeable TRP channels damage myelin in conditions mimicking ischaemia. Nature doi: 10.1038/nature16519.

Giacco V, Flower G, Artamonova M, Hunter J, Padilla Requerey A, Hamilton N.B.+ (2023) Transient receptor potential Ankyrin-1 (TRPA1) agonists suppress myelination and induce demyelination in organotypic cortical slices. Glia. 2023. doi: 10.1002/glia.24347;

Lajoso, W., Flower, G., Giacco, V., Kaul, A., La Mache, C., Br?ban, A., Roxas, A., Hamilton N.B.+ (2021) Transient Receptor Potential Ankyrin-1 (TRPA1) Block Protects against Loss of White Matter Function during Ischaemia in the Mouse Optic Nerve. Pharmaceuticals.. doi: 10.3390/ph14090909.

Age-Dependent Changes in Synaptic NMDA Receptor Composition in Adult Human Cortical Neurons. Chrysia M. Pegasiou… Aminul Ahmed, 2020. Cerebral Cortex. doi: 10.1093/cercor/bhaa052.

Sonic Hedgehog Signaling Promotes Peri-Lesion Cell Proliferation and Functional Improvement after Cortical Contusion Injury. Ashley K. Pringle,… Aminul Ahmed. 2021. Neurotrauma Reports.;

Hypothermia in Traumatic Brain Injury. Ahmed AI, Bullock MR, Dietrich WD. 2016. Neurosurg Clin N Am. doi: 10.1016/