Traumatic brain injury (TBI) is often complicated by long-lasting disabilities, including
headache,
fatigue,
insomnia, hyperactivity, and cognitive deficits. In a previous study in mice, we showed that persistent non-goal-directed hyperactivity is a characteristic post-TBI behavior that was associated with low levels of
endocannabinoids in the perilesional cortex. We now analyzed lipidome patterns in the brain and plasma in TBI versus
sham mice in association with key behavioral parameters and
endocannabinoids. Lipidome profiles in the plasma and subcortical ipsilateral and contralateral brain were astonishingly equal in
sham and TBI mice, but the ipsilateral perilesional cortex revealed a strong increase in neutral
lipids represented by 30 species of
triacylglycerols (TGs) of different chain lengths and saturation. The accumulation of TG was localized predominantly to perilesional border cells as revealed by
Oil Red O staining. In addition, hexosylceramides (HexCer) and
phosphatidylethanolamines (PE and
ether-linked PE-O) were reduced. They are precursors of
gangliosides and
endocannabinoids, respectively. High TG, low HexCer, and low PE/PE-O showed a linear association with non-goal-directed nighttime hyperactivity but not with the loss of avoidance memory. The analyses suggest that TG overload and HexCer and PE deficiencies contributed to behavioral dimensions of post-TBI psychopathology.