Fly model of traumatic brain injury untangles factors tied to mortality
Each year, emergency departments in the US treat almost 700,000 people for traumatic brain injury (TBI). The outcome depends largely on the severity and location of the injury, but these aren’t the only factors. Age also plays a role, with children often recovering more fully than do adults. The patient’s diet following the injury may also have an impact. Using a fruit fly model of TBI, research published in the December issue of G3 examined the contributions of these factors to TBI mortality.
Much of the damage caused by TBI doesn’t occur during the primary injury: secondary injury—which is caused by inflammation, overactivation of certain receptors, and other contributors—also affects TBI outcomes. The authors had previously demonstrated in flies that the severity of secondary injuries depends on age at the time of injury and diet following the injury, with younger age and no food predicting better outcomes. In the present work, the authors compared different strains of flies and found that the mortality rate following TBI was affected by age and diet in some strains but not in others. This suggests that genetic background is an important factor in this model of TBI, which agrees with evidence from severe human TBI cases that variants in several genes influence mortality. Some of these variants also act in an age-dependent fashion.
The researchers also conclude that age and diet affect mortality through independent mechanisms, since mortality in some strains was affected by diet but not age and in others it was affected by age but not diet. And interestingly, these separate pathways seem to act synergistically—in flies susceptible to the damaging effects of advanced age and post-injury feeding, the combination of the two factors increased mortality to a greater extent than the sum of the individual effects.
The researchers also found gene expression changes consistent with activation of the innate immune system after TBI, some of which depended on age and diet, although they aren’t able to say with certainty that the injuries to the head and not to the rest of the body caused the change. The procedure the researchers used to induce TBI undoubtedly causes damage to tissues other than the brain, and since the authors tested whole flies rather than just fly heads, they can’t firmly conclude that the changes in gene expression occurred in the brain. By further testing these results in flies and other animals, it might be possible to design better protocols—perhaps even genotype-based—for post-TBI care.
Katzenberger, R.; Ganetzky, B.; Wassarman, D. Age and Diet Affect Genetically Separable Secondary Injuries that Cause Acute Mortality Following Traumatic Brain Injury in Drosophila.
G3, 6(12), 4151-4166.