Drosophila model of closed head traumatic brain injury

• Published in: Proceedings of the National Academy of Sciences - PNAS 2013-10, Vol.110 (44), p.E4152-E4159
• Main Authors: Katzenberger, Rebeccah J, Loewen, Carin A, Wassarman, Douglas R, Petersen, Andrew J, Ganetzky, Barry, Wassarman, David A
• Format: Article
• Language: English
• Subjects: Acceleration - adverse effects; Age Factors; Analysis of Variance; Animals; Antimicrobial Cationic Peptides - genetics; Antimicrobial Cationic Peptides - immunology; Biological Sciences; Brain damage; Brain Injuries - pathology; Disease Models, Animal; Drosophila melanogaster; Female; Immunity, Innate - physiology; Insects; Longevity - physiology; Male; Medical research; Mortality; Neurology; PNAS Plus; Real-Time Polymerase Chain Reaction; Sex Factors
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1316895110

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.