Using zebrafish larval models to study brain injury, locomotor and neuroinflammatory outcomes following intracerebral haemorrhage

摘要: Intracerebral haemorrhage (ICH) is a devastating condition with limited treatment options, and current understanding of pathophysiology incomplete. Spontaneous cerebral bleeding characteristic the human that has proven difficult to recapitulate in existing pre-clinical rodent models. Zebrafish larvae are frequently used as vertebrate disease models associated several advantages, including high fecundity, optical translucency non-protected status prior 5 days post-fertilisation. Furthermore, other groups have shown zebrafish can exhibit spontaneous ICH. The aim this study was investigate whether such be utilised pathological consequences brain, context ICH research. Here, we compared genetic (bubblehead) chemically inducible (atorvastatin) larval studied subsequent processes. Through live, non-invasive imaging transgenic fluorescent reporter lines behavioural assessment quantified brain injury, locomotor function neuroinflammation following We show both comparable timing, frequency location. results increased cell death persistent deficit. Additionally, haemorrhaged observed significant increase macrophage recruitment site injury. Live vivo allowed us track active macrophage-based phagocytosis dying cells 24 hours after haemorrhage. Morphological analyses quantification indicated an overall activation occurs brain. Our shows larvae, induces quantifiable phenotypic outcomes mimic key features hope methodology will enable community adopt model alternative rodents, supporting future throughput drug screening complementary approach elucidating crucial mechanisms pathophysiology.