Dhariwal Seema, Maan Kiran, Baghel Ruchi, Sharma Apoorva, Kumari Megha, Aleem Mohd, Manda Kailash, Trivedi Richa, Rana Poonam
Traumatic Brain Injury & Metabolomics Department, DRDO, Institute of Nuclear Medicine and Allied Sciences (INMAS), S. K Mazumdar Road, Timarpur, New Delhi 110054, India.
Traumatic Brain Injury & Metabolomics Department, DRDO, Institute of Nuclear Medicine and Allied Sciences (INMAS), S. K Mazumdar Road, Timarpur, New Delhi 110054, India.
Exp Neurol. 2025 Mar;385:115141. doi: 10.1016/j.expneurol.2025.115141. Epub 2025 Jan 7.
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.
爆炸暴露导致的头部创伤日益引起人们对健康的关注,尤其是在现役军人中,并且被认为是海湾战争的标志性损伤。然而,与爆炸相关的创伤性脑损伤(TBI)和其他机制导致的TBI之间是否存在根本差异仍不明确。考虑到脂质代谢与神经元膜完整性相关的重要性及其在TBI期间受到的损害,我们试图找出爆炸或钝性(立体定向控制挫伤-SCC)介导的TBI过程中脂质组学特征的变化。在本研究中,我们在C57BL/6小鼠上建立了爆炸(130±10kPa)和SCC(背腹1.5mm)的轻度TBI(mTBI)模型,然后在第1天和第7天采集血清。通过超高效液相色谱(UHPLC)四极杆飞行时间质谱(qTOF-MS)进行脂质组学分析。此外,使用修订后的小鼠神经行为严重程度评分(mNSS-R)和旷场试验(OFT)评估神经行为结果。研究发现,爆炸暴露组表现出更多的脂质失调,两个时间点均有更多数量的显著脂质和相关通路证明了这一点。然而,比较研究进一步揭示了八种显著常见的脂质,无论诱导方式(爆炸或钝性)如何,这些脂质都可以表征mTBI。此外,在mTBI后还观察到神经行为、运动和焦虑功能的调节。该研究说明了旨在维持mTBI后脑脂质稳态的独特全身脂质代谢。这种方法可能为脂质代谢以及有助于理解mTBI病理生理学的单个脂质种类的鉴定提供新的见解。