title: A Drosophila model of closed head traumatic brain injury.
abstract: Traumatic brain injury (TBI) is a substantial health issue worldwide, yet the mechanisms responsible for its complex spectrum of pathologies remains largely unknown. To investigate the mechanisms underlying TBI pathologies, we developed a model of TBI in Drosophila melanogaster. The model allows us to take advantage of the wealth of experimental tools available in flies. Closed head TBI was inflicted with a mechanical device that subjects flies to rapid acceleration and deceleration. Similar to humans with TBI, flies with TBI exhibited temporary incapacitation, ataxia, activation of the innate immune response, neurodegeneration, and death. Our data indicate that TBI results in death shortly after a primary injury only if the injury exceeds a certain threshold and that age and genetic background, but not sex, substantially affect this threshold. Furthermore, this threshold also appears to be dependent on the same cellular and molecular mechanisms that control normal longevity. This study demonstrates the potential of flies for providing key insights into human TBI that may ultimately provide unique opportunities for therapeutic intervention.
authors.affiliation: Department of Cell and Regenerative Biology, School of Medicine and Public Health, and Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI 53706.
authors.forename: Rebeccah J
authors.initials: RJ
authors.lastname: Katzenberger
authors.forename: Carin A
authors.initials: CA
authors.lastname: Loewen
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Wassarman
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Petersen
authors.forename: Barry
authors.initials: B
authors.lastname: Ganetzky
authors.forename: David A
authors.initials: DA
authors.lastname: Wassarman
mesh_terms: D000054:Acceleration / Q000009:adverse effects*; D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000276:immunology; D001930:Brain Injuries / Q000473:pathology*; D004195:Disease Models, Animal; D004331:Drosophila melanogaster; D005260:Female; D007113:Immunity, Innate / Q000502:physiology*; D008136:Longevity / Q000502:physiology*; D008297:Male; D060888:Real-Time Polymerase Chain Reaction; D012737:Sex Factors
chemical_list: D023181:Antimicrobial Cationic Peptides
keywords: chronic traumatic encephalopathy; concussion; insect