Time restricted feeding alters the behavioural and physiological outcomes to repeated mild traumatic brain injury in male and female rats

Mild traumatic brain injury (mTBI) research has had limited success translating treatments from preclinical models to clinical application for concussion. One major factor that has been overlooked is the near 24-hour availability of food, both for experimental nocturnal rodents and patients suffering from mTBI. Here, we characterised the impact of food restriction limited to either the inactive (day) or the active phase (night), on repetitive mTBI (RmTBI) - induced outcomes in male and female rats. We found that active phase fed rats consumed more food, had increased body weight, and reduced brain weights. Behaviourally, active phase feeding increased motor coordination deficits and caused changes to thermal nociceptive processing following RmTBI. Hypothalamic transcriptomic analysis revealed minor changes in response to RmTBI, and genes associated with oxytocin-vasopressin regulation in response to inactive phase, but not active phase feeding. These transcript changes were absent in females, where the overall effect of RmTBI was minor. Prefrontal cortex lipidomics revealed an increase in sphingomyelin synthesis following injury and marked sex differences in response to feeding. Of the lipids that changed and overlapped between the prefrontal cortex and serum, dihydroceramides, sphingomyelins, and hexosylceramides, were higher in the serum but lower in the prefrontal cortex. Together, these results demonstrate that feeding time alters outcomes to RmTBI, independent of the hypothalamic transcriptome, and injury-specific lipids may serve as useful biomarkers in RmTBI diagnosis.