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Post-Stroke Longitudinal Imaging & Behavioural Change in Rodent Models

Dementia and cognitive impairment are becoming increasingly recognised as major complications occurring in patients post-stroke and are associated with higher rates of mortality, institutionalisation and greater healthcare costs.

Aims

Examine the trajectory of cognitive dysfunction and corresponding changes in brain volume occurring in rodents subjected to stroke.

Quantify protein accumulation occurring at sites of remote volume change post-stroke

This project, which forms part of a larger collaboration between leading Florey neuroscientists and clinicians, aims to characterise the trajectory and mechanisms of post-stroke cognitive dysfunction

Using rodent models of the stroke, and cutting edge technologies, our goal is to develop new therapies for this devastating that will improve quality of life in stroke survivors.

Methods: 

We will employ two complementary approaches to model ischaemic stroke in rats and mice (Jackman Meth Mol Biol, 2010). In C57Bl/6 mice, transient occlusion of the proximal MCA (MCAO) will be induced using the intraluminal filament technique, while the endothelin-1 (ET-1) model of stroke will be used in Wistar rats to induce localised lesions in specific regions of the brain. The degree of acute cerebral infarction, as well as progressive changes in regional brain volume and the development of selective neuronal degeneration in remote brain regions will be evaluated using MRI at various time points up to twelve months post-stroke. Immunohistological techniques will also be employed to assess selective neuronal degeneration in more depth, as well as the spatiotemporal profile of various dementia-related proteins (e.g. Tau, TDP-43). To assess cognitive function post-stroke, both rats and mice subjected to experimental stroke will be assessed using the rodent touchscreen cognitive assays (Bussey et al., Neuropharmacology, 2012; Nithianantharajah et al., Nat Neurosci, 2013) – a recently developed innovative method for modelling complex higher order cognitive functions in rodent models.

Progress:

Middle cerebral artery occlusion (MCAO) stroke surgeries in mice, including MRI scans commenced July 2016.

Focal cortical endothelin-1 (ET-1) stroke surgery in rats and MRI scans will commence in early November 2016.

Evaluation of post-stroke cognitive deficits using touchscreen technology will commence in October 2016.

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