Investigating recovery after a spontaneous intracerebral haemorrhage in zebrafish larvae

Intracerebral haemorrhage (ICH) is a debilitating stroke subtype with high morbidity and mortality rates. For survivors, rehabilitation is a long process, and with no available therapeutics to limit the immediate pathophysiology of the haemorrhage, recovery is dependent on individual neuroplasticity. We have previously shown that zebrafish larvae can be used to model spontaneous brain haemorrhage. Zebrafish exhibit innate recovery mechanisms and are often used as a model system for investigation into regeneration after injury, including injury to the nervous system. Here, we investigate the spontaneous and immediate recovery in zebrafish larvae following an ICH at 2 days post fertilisation, during pre-protected stages and over the first 3 weeks of life.

We have shown that following the onset of bleed at ~2 days post fertilisation zebrafish are capable of clearing the haematoma through the ventricles. Brain cell damage associated with ICH is resolved within 48 hours, and this recovery is associated with survival rates equal to wildtype and non-haemorrhaged sibling control animals. Larvae express more nestin-positive neural progenitor cells 24 hours after injury when the most damage is observed, and through mass spectrometry analysis we have determined that these cells are highly proliferative and may specially differentiate into oligodendrocytes. This study provides an insight into the haematoma resolution processes in a live, intact organism, and may suggest potential therapeutic approaches to support the recovery of ICH patients.