MA (Oxon), MA (Cantab), MBBS (Lond)
Guarantors of Brain Entry Research Fellow
- Core Training Psychiatrist, Oxford Deanery
I am a Guarantors of Brain-sponsored Clinical Research Fellow working in the Vladyslav Vyazovskiy Group.
Globally, stroke is a leading cause of adult disability. Thrombolysis with alteplase has revolutionised acute management of ischaemic stroke. However, its time window as an effective treatment is relatively short. In ischaemic stroke, relatively small differences in brain temperature critically determine the extent of neuronal injury.
Torpor is a fully-reversible state of regulated metabolic suppression, and represents a unique adaptive response to extreme environmental conditions. Torpid animals are unique in that they can survive extremely low body temperatures; the inevitable deleterious changes that occur in organs are fully reversed on emergence from torpor, via endogenous mechanisms that are yet to be fully characterised.
Torpor occurs spontaneously in several mammalian species, but has also been successfully pharmacologically induced in facultative heterotherms such as laboratory mice (e.g. using via fasting and via intraperitoneal injection of 5’ AMP). There is an increasing and well-publicised drive to develop safe and efficacious methods of inducing torpor in humans both by the medical community (as a way of achieving neuroprotective hypothermia for ischaemic stroke, cardiac arrest, and neonatal hypoxemia), and by multinational space-agencies such as NASA and ESA (for sending astronauts on long distance space missions).
However, the impact of induced torpor on brain activity and function is unclear. Neurohistochemical evidence in Arctic ground squirrels suggests that during natural torpor there is drastic but reversible loss of synaptic connectivity in the brain. It is unclear whether loss of synaptic connectivity occurs during induced torpor or, more importantly, whether it is reversible. Since irreversible loss of synaptic connectivity would likely have a deleterious effect on cognitive function, it would be essential to investigate this in a genetically-tractable facultative heterothermic species such as the laboratory mouse, before induced torpor can safely be trialled in humans.
Therefore, my project is to investigate the consequences of induced torpor on brain activity, synaptic connectivity and behaviour in the laboratory mouse. To do this, I will use a combination of electrophysiological techniques (e.g. chronic electroencephalography in freely-moving mice) and behavioural tests (in collaboration with Prof. David Bannerman, Department of Experimental Psychology).