Using zebrafish for pre-clinical brain haemorrhage research

Student thesis: Phd


Intracerebral haemorrhage (ICH) is a devastating condition with limited treatment options, accounting for 49% of 6.5 million annual stroke deaths worldwide, and over half of all disability adjusted life years lost to stroke. Current understanding of pathophysiology is incomplete, partly due to limitations of the existing pre-clinical models of spontaneous disease. Here we show that zebrafish larvae can be used to model spontaneous ICH and exhibit comparable pathological outcomes to human condition, therefore offering an alternative model for pre-clinical study for ICH. Zebrafish larvae are associated with several practical advantages including high fecundity, optical translucency and non-protected status prior to 5 days post fertilisation. Through live, non-invasive imaging of transgenic fluorescent reporter lines and behavioural assessment we can quantify pathological outcomes and neuroinflammation following ICH. Using these assessable outcomes we can quantify improvement after ICH with targeted drug treatment, to ameliorate primary injury and secondary neuroinflammatory responses. Due to the spontaneous nature of blood vessel rupture in this model we can investigate the relationship between clinically relevant risk factors and ICH in zebrafish. In this study we show that the zebrafish larvae represent a novel model for pre-clinical ICH investigation that is appropriate for use in medium throughput drug screening. The zebrafish larval model has potential to reduce the number of protected animals used in pre-clinical ICH investigation and to support the advancement of the stroke field with practical translatable outcomes to directly benefit patients in the clinic.
Date of Award1 Aug 2020
Original languageEnglish
Awarding Institution
  • The University of Manchester
SupervisorStuart Allan (Supervisor), Paul Kasher (Supervisor) & Adrian Parry-Jones (Supervisor)


  • stroke
  • zebrafish
  • brain haemorrhage
  • ICH
  • NC3Rs
  • neuroinflammation

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