An inexpensive method for modeling TBI in flies at different levels of severity

Saikumar J, Kim J, Byrns CN, Hemphill M, Meaney DF, Bonini NM. Inducing different severities of traumatic brain injury in Drosophila using a piezoelectric actuator. Nat Protoc. 2020 Dec 4. doi: 10.1038/s41596-020-00415-y. Epub ahead of print. PMID: 33277631.

Abstract:

"Drosophila models have been instrumental in providing insights into molecular mechanisms of neurodegeneration, with wide application to human disease. The brain degeneration associated with traumatic brain injury (TBI) has been modeled in Drosophila using devices that inflict trauma on multiple parts of the fly body, including the head. However, the injuries produced by these models are not specific in location and are inconsistent between individual animals. We have recently developed a device that can be used to inflict controlled head injury to flies, resulting in physiological responses that are remarkably similar to those observed in humans with TBI. This protocol describes the construction, calibration and use of the Drosophila TBI (dTBI) device, a platform that employs a piezoelectric actuator to reproducibly deliver a force in order to briefly compress the fly head against a metal surface. The extent of head compression can be controlled through an electrical circuit, allowing the operator to set different levels of injury. The entire device can be assembled and calibrated in under a week. The device components and the necessary electrical tools are readily available and cost ~$800. The dTBI device can be used to harness the power of Drosophila genetics and perform large-scale genetic or pharmacological screens, using a 7-d post-injury survival curve to identify modifiers of injury."

Study using a Drosophila model of traumatic brain injury suggests link to mitochondrial activity

Sen A, Gurdziel K, Liu J, Qu W, Nuga OO, Burl RB, Hüttemann M, Pique-Regi R, Ruden DM. Smooth, an hnRNP-L Homolog, Might Decrease Mitochondrial Metabolism by Post-Transcriptional Regulation of Isocitrate Dehydrogenase (Idh) and Other Metabolic Genes in the Sub-Acute Phase of Traumatic Brain Injury. Front Genet. 2017 Nov 15;8:175. PMID: 29187863; PMCID: PMC5694756.

From the abstract: "Traumatic brain injury (TBI) can cause persistent pathological alteration of neurons. ... To investigate the underlying genetic and molecular basis of TBI, we subjected w1118 Drosophila melanogaster to mild closed head trauma and found that mitochondrial activity is reduced in the brains of these flies 24 h after inflicting trauma. To determine the transcriptomic changes after mild TBI, we collected fly heads 24 h after inflicting trauma, and performed RNA-seq analyses. ... Based on these results, we propose a model in which TBI temporarily decreases mitochondrial activity in the brain 24 h after inflicting trauma ... We further propose that decreasing metabolism after TBI in such a manner is a protective mechanism that gives the brain time to repair cellular damage induced by TBI."

Learning from a fly model of traumatic brain injury

Katzenberger RJ, Chtarbanova S, Rimkus SA, Fischer JA, Kaur G, Seppala JM, Swanson LC, Zajac JE, Ganetzky B, Wassarman DA. Death following traumatic brain injury in Drosophila is associated with intestinal barrier dysfunction. Elife.2015 Mar 5;4. PMID: 25742603; PMCID: PMC4377547.

From the abstract: "Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Unfavorable TBI outcomes result from primary mechanical injuries to the brain and ensuing secondary non-mechanical injuries that are not limited to the brain. Our genome-wide association study of Drosophila melanogaster revealed that the probability of death following TBI is associated with single nucleotide polymorphisms in genes involved in tissue barrier function and glucose homeostasis. We found that TBI causes intestinal and blood-brain barrier dysfunction and that intestinal barrier dysfunction is highly correlated with the probability of death. ..."

Video methods: modeling TBI in the fly

Katzenberger RJ, Loewen CA, Bockstruck RT, Woods MA, Ganetzky B, Wassarman DA. A Method to Inflict Closed Head Traumatic Brain Injury in Drosophila. J Vis Exp. 2015 Jun 30;(100):e52905. doi: 10.3791/52905. Erratum in: J Vis Exp. 2015;(101):e5744. Ganetky, Barry [corrected to Ganetzky, Barry]. PMID: 26168076.

From the abstract: "Traumatic brain injury (TBI) affects millions of people each year, causing impairment of physical, cognitive, and behavioral functions and death. Studies using Drosophila have contributed important breakthroughs in understanding neurological processes. Thus, with the goal of understanding the cellular and molecular basis of TBI pathologies in humans, we developed the High Impact Trauma (HIT) device to inflict closed head TBI in flies. ... the HIT device can be used to perform large-scale genetic screens to understand the genetic basis of TBI pathologies."

Fly as a model for study of head trauma

Katzenberger RJ, Loewen CA, Wassarman DR, Petersen AJ, Ganetzky B, Wassarman DA. A Drosophila model of closed head traumatic brain injury. Proc Natl Acad Sci U S A. 2013 Oct 29;110(44):E4152-9. doi: 10.1073/pnas.1316895110. PMID: 24127584; PMCID: PMC3816429.