Therapeutic Sleep for Traumatic Brain Injury

To test the therapeutic effect of correcting sleep impairments caused by TBI, we developed and validated a Drosophila head-specific model for TBI where well-controlled, non-penetrating strikes are directly delivered to the head of unanesthetized flies. This assay recapitulates many TBI phenotypes, including increased mortality, decreased and fragmented sleep, impaired motor control and increased neuronal cell death. Using glial TRAP-seq, we detected substantial changes in gene expression, including a strong upregulation of the innate immune response as well as several wake-promoting genes. To test the in vivo functional role of these changes, we examined TBI-dependent behavior and lethality in mutants of the master immune regulator NF-B and found that while lethality effects were still evident, changes in sleep and motor function were abolished, suggesting that TBI-induced changes in sleep are due to the immune response, rather than the injury.