A larval zebrafish model of traumatic brain injury: optimizing the dose of neurotrauma for discovery of treatments and aetiology.

Traumatic brain injuries (TBI) are diverse with heterogeneous injury pathologies, which creates challenges for the clinical treatment and prevention of secondary pathologies such as post-traumatic epilepsy and subsequent dementias. To develop pharmacological strategies that treat TBI and prevent complications, animal models must capture the spectrum of TBI severity to better understand pathophysiological events that occur during and after injury. To address such issues, we improved upon our recent larval zebrafish TBI paradigm emphasizing titrating to different injury levels. We observed coordination between an increase in injury level and clinically relevant injury phenotypes including post-traumatic seizures (PTS) and tau aggregation. This preclinical TBI model is simple to implement, allows dosing of injury levels to model diverse pathologies, and can be scaled to medium- or high-throughput screening.