No effective strategy exists to treat the well-recognized, devastating impact of Traumatic Brain Injury (TBI) and Chronic Traumatic Encephalopathy (CTE) which is the brain degeneration likely caused by repeated head trauma. The goals of this project were: 1) To study the effects of single and recurrent TBI (rTBI) on Drosophila melanogaster’s: a) Life span b) Response to sedatives and c)Behavioral responses to light and gravity; 2) To determine whether therapeutic hypothermia or the intentional lowering of body temperature can mitigate the deleterious effects of TBI.

Five experimental groups were created: 1) Control; 2) Single TBI or concussion; 3) Concussion + hypothermia; 4) Recurrent TBI; 5) Recurrent TBI + hypothermia. A “high-impact trauma” (HIT) device was built, which used a spring-based mechanism to propel flies against the wall of a vial, causing mechanical damage to the brain. Hypothermia groups were cooled to 15⁰ C for 3 minutes, after each inflicted TBI.  Group differences were analyzed with chi-square tests for the categorical variables and with ANOVA tests for the continuous variables.

Survival curve analysis showed that recurrent TBI can decrease Drosophila lifespan and hypothermia diminished this impact. Average sedation time for Control vs. Concussion vs. Concussion + hypothermia was 78 vs. 52 vs. 61 seconds(P<.0001). Similarly, rTBI vs. rTBI/hypothermia groups took 43 vs. 59 seconds (P<.0001). Concussed flies preferred dark environments compared with control flies (Risk Ratio 3.3, P<.01) while flies who were concussed and cooled had a Risk Ratio of 2.7 (P<.01). Flies with CTE were almost 4 times likely to prefer the dark environment but only 3 times as likely if they were cooled, compared to controls. Geotaxis was significantly affected by rTBI only and yet less so if CTE flies were cooled.

Hypothermia successfully mitigated many deleterious effects of TBI in Drosophila and may represent a promising breakthrough in the treatment of human TBI.