Multiple models of TBI in Drosophila yield common and unique genetic, physiological, behavioral outcomes

Traumatic brain injury is a significant public health problem, but the complex pathology of TBI has posed a barrier to a molecular understanding of the root causes of post-TBI sequelae. Fruit fly models of TBI offer opportunities to conduct high throughput screens for genes affecting multiple outcomes of TBI. This review provides a primer on fly traumatic injury paradigms, a summary of findings made in fly TBI models, and recommendations for future areas of TBI research amenable to the fly model. Using the whole-animal and head-specific TBI paradigms available in Drosophila, researchers have identified changes in acute mortality and median lifespan, reduction in locomotor function, immune activation, remodeling of metabolic functions and sleep, and acceleration of neurodegenerative phenotypes. Fly TBI models also show effects of age, diet, and sex on injury outcomes. Drosophila genetic tools offer unique advantages for high throughput screening, and fly screens have identified genes that affect acute mortality after injury. Further standardization of fly TBI paradigms will advance the field and allow discovery of genes and biochemical pathways that affect TBI outcomes across species and accelerate the development of evidence-based treatments for TBI survivors.