dTBI: A paradigm for closed-head injury in Drosophila

Abstract

Drosophila models have been instrumental in providing insights into molecular mechanisms of neurodegeneration, that are applicable to human disease. We have recently described a model of controlled head injury to flies, which remarkably parallels many of the physiological responses of humans to traumatic brain injury (TBI). This protocol describes the construction, calibration and use the of the Drosophila TBI (dTBI) device, a platform that employs a piezoelectric actuator to reproducibly deliver a force, which briefly compresses the fly head against a metal surface. The extent of head compression can be specified, allowing the operator to set different thresholds of injury. Using readily available components and tools, the device can be assembled and calibrated within two days, for a total cost of ~$700. The dTBI device can be used to harness the power of Drosophila genetics and perform large-scale genetic or pharmacological screens, using a 7-day post-injury survival curve to identify modifiers of injury.

Dynamic neural and glial responses of a head-specific model for traumatic brain injury inDrosophila

“…The dTBI device was assembled, calibrated, and tested in the laboratory (SI Appendix, Fig. S1A) (75). The main components of the device are readily available and include a piezoelectric actuator (q220-a4-203yb; piezo.com), an Arduino microcontroller-based system (digikey.com, 1050-1024-ND; A000066, Arduino), and a power amplifier (EVB-304; piezo.com).…”

“…All data associated with the manuscript are provided within the manuscript; additional detailed information that is required to assemble and use the dTBI device is publicly accessible at Protocol Exchange (http://dx. doi.org/10.21203/rs.3.pex-949/v1) (75).…”

Drosophila melanogaster as a model to study age and sex differences in brain injury and neurodegeneration after mild head trauma

“…Loss of highwire, a protein involved in Wallerian degeneration, which was first studied within the fly, is protective against cell death and degeneration following head injury exposure (Hill et al, 2020). Additional Drosophila TBI models have been developed, including those that can deliver head-specific impacts (Barekat et al, 2016;Sun and Chen, 2017;Saikumar et al, 2020;Behnke et al, 2021;van Alphen et al, 2022;Figure 1B). A summary of different Drosophila TBI models and the key findings from research using these models is provided in Supplementary Table 1.…”

“…These models have also been extensively covered by other reviews (Shah et al, 2019;Buhlman et al, 2021;Aggarwal et al, 2022). It should be noted that studies using Drosophila TBI models have recapitulated several key aspects of trauma found in humans and other preclinical models of trauma, including acute stress responses such as oxidative stress and lysosomal activity, progressive neurodegeneration, neuronal hyperexcitability, and glial-specific responses (Barekat et al, 2016;Sun and Chen, 2017;Saikumar et al, 2020;Behnke et al, 2021;van Alphen et al, 2022). The short lifespan of fruit flies also enables the lifelong monitoring of brain deficits elicited by early exposure to mild head traumatic impacts (Behnke et al, 2021).…”

“…They also found that aging exacerbated injury-induced neurodegeneration in the flies that survived 14 days following injury. The piezo-electric actuator model (Saikumar et al, 2020 has been utilized to examine chronic time-points (up to 28 days after injury) in which chronic activation of the immune system promotes neurodegeneration after injury at a young age. In a similar vein, Behnke et al (2021) examined the lifelong sensorimotor behaviors and brain structure after the flies receive mild head trauma at young age (3 day), and found that immediate elevation of neuronal activity contributes to chronic neurodegeneration.…”