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Contributed by Barry Ganetzky, September 6, 2013 (sent for review August 6, 2013)
Significance
Traumatic brain injury (TBI) occurs when a strong jolt to the head causes damage to brain cells, resulting in immediate and long-term consequences including physical, behavioral, and cognitive problems. Despite the importance of TBI as a major health issue, our understanding of the underlying cellular and molecular mechanisms is limited. To unravel these mechanisms, we have developed a model of TBI in the fruit fly, Drosophila melanogaster, where we can apply many powerful experimental tools. The main features of human TBI also occur in flies, suggesting that the underlying mechanisms are conserved. Our studies demonstrate the value of a fly model for understanding the consequences of TBI and may ultimately enable development of therapies for their prevention and treatment.
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.
Footnotes
- ↵1To whom correspondence may be addressed. E-mail: ganetzky{at}wisc.edu or dawassarman{at}wisc.edu.
Author contributions: R.J.K., A.J.P., B.G., and D.A.W. designed research; R.J.K., C.A.L., D.R.W., A.J.P., and D.A.W. performed research; D.A.W. contributed new reagents/analytic tools; R.J.K., C.A.L., B.G., and D.A.W. analyzed data; and R.J.K., C.A.L., B.G., and D.A.W. wrote the paper.
The authors declare no conflict of interest.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1316895110/-/DCSupplemental.
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