This award aims to replace the use of mice in intracerebral haemorrhage brain regeneration studies by using a transgenic larval zebrafish model.
Intracerebral haemorrhages are the most severe type of stroke and have high mortality and morbidity rates, often resulting in death or disability. Research is currently ongoing into how the brain regenerates after a haemorrhage and how to increase this regenerative capacity. Mice are often used to model a haemorrhage through an invasive procedure where collagenase is injected into the brain to induce bleeding and the following brain regeneration is analysed. In her NC3Rs funded PhD, Dr Siobhan Crilly developed a larval zebrafish model that spontaneously develops a haemorrhage as an alternative model system. The larval zebrafish used are less than five days of age (before they begin independently feeding) and are therefore not protected under the UK legislation on the protection of animals used in research. Based on current thinking, at this early stage the embryos are not considered capable of suffering and they therefore provide a partial replacement for the use of other animals.
Siobhan undertook an extensive characterisation of the larval zebrafish model during her PhD studies, demonstrating evidence of brain damage and subsequent regeneration. During her Fellowship, Siobhan will apply the model to investigate the immune and neuronal cellular response during regeneration. The aim of this is to demonstrate the utility of the model and increase buy-in from the mammalian model stroke community. Siobhan will develop skills in cell culture, fluorescence microscopy, and transcriptomic and proteomic analysis.
Bone, M, Malik, M and Crilly S. (2023). Identifying applications of virtual reality to benefit the stroke translational pipeline. Brain and Neuroscience Advances 2023(7). doi:10.1177/23982128231182506
Crilly, S, McMahon E & Kasher, P (2022). Zebrafish for modeling stroke and their applicability for drug discovery and development. Expert Opinion on Drug Discovery 17(6): 559-68. doi: 10.1080/17460441.2022.2072828