Comparative Lipid Profiling Reveals the Differential Response of Distinct Lipid Subclasses in Blast and Blunt-Induced Mild Traumatic Brain Injury

Head trauma from blast exposure is a growing health concern, particularly among active military personnel, and is considered the signature injury of the Gulf War. However, it remains elusive whether fundamental differences exist between blast-related Traumatic Brain Injuries (TBI) and TBI due to other mechanisms. Considering the importance of lipid metabolism associated with neuronal membrane integrity and its compromise during TBI, we sought to find changes in lipidomic profiling during blast or blunt (Stereotaxically Controlled Contusison-SCC)mediated TBI. In the current study, we have developed the mild TBI (mTBI) model of blast (130 +/- 10 kPa) and SCC (1.5 mm dorsal-ventral) on C57BL/6 mice, followed by the serum collection on days 1 and 7. Lipidomics was performed via ultra-high performance liquid chromatography (UHPLC) quadrupole time-of-flight mass spectrometry (qTOF-MS). Additionally, neurobehavioral outcomes were estimated using a revised neurobehavioral severity score for mice (mNSS-R) and an open field test (OFT). The study found that blast-exposed group exhibited more lipid dysregulation, as evidenced by a higher number of significant lipids and associated pathways at both time points. However, the comparative investigation further reveals eight significantly common lipids that can characterize the mTBI regardless of the manner of induction (blast or blunt). Besides, modulated neurobehavioral, locomotor and anxiety functions were also observed post-mTBI. The study illustrates the distinct systemic lipid metabolism intended to preserve the brain's lipid homeostasis post-mTBI. This approach may provide novel insights into lipid metabolism and identification of individual lipid species that aids in understanding the pathophysiology of mTBI.