Comparing Brain and Blood Lipidome Changes following Single and Repetitive Mild Traumatic Brain Injury in Rats.

Comparing Brain and Blood Lipidome Changes following Single and Repetitive Mild Traumatic Brain Injury in Rats.
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DOI:
10.1021/acschemneuro.3c00603
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发表时间:
2024-01-17
影响因子:
5
通讯作者:
Laplaca, Michelle C.
Laplaca, Michelle C.
中科院分区:
医学3区
文献类型:
--
作者:
Pulliam, Alexis N.;Gier, Eric C.;Gaul, David A.;Moore, Samuel G.;Fernandez, Facundo M.;Laplaca, Michelle C.

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创伤性脑损伤(TBI)是美国和全球的一个主要健康问题,导致残疾和长期的神经系统问题。TBI后的脂质失调尚未得到充分研究,更好地了解脂质周转和降解可能指向新的生物标志物候选者和治疗靶点。在这里,我们使用数据驱动的发现方法研究了大脑和血液中重叠的脂质组变化,以了解轻度TBI(mTBI)后大脑和血清室中的脂质变化以及大脑脂质向外周血的潜在流出。在单次和重复闭合头部撞击后,通过超高效液相色谱-质谱法(UHPLC-MS)在正离子和负离子模式下分析雄性和雌性Sprague-Dawley大鼠的皮质和血清。使用内部数据词典识别数据集中的重叠脂质,以研究脂质类别变化。基于MS的脂质谱显示血清室的总体变化增加,而脑脂质主要显示变化减少。有趣的是,在单一和重复性损伤后,脑和血液隔室中的鞘脂类有显著的改变,这可能表明脑鞘脂在TBI后流出到血液中。遗传算法用于预测面板选择,以高灵敏度和特异性对损伤和对照样本进行分类。这些重叠的脂质组主要映射到甘油磷脂代谢途径,Benjamini-Hochberg校正的q值小于0.05。总的来说,这些结果详细说明了脑和血液室中mTBI后重叠的脂质组变化,增加了我们对TBI相关脂质失调的理解,同时确定了新的生物标志物候选者。
Traumatic brain injury (TBI) is a major health concern in the United States and globally, contributing to disability and long-term neurological problems. Lipid dysregulation after TBI is underexplored, and a better understanding of lipid turnover and degradation could point to novel biomarker candidates and therapeutic targets. Here, we investigated overlapping lipidome changes in the brain and blood using a data-driven discovery approach to understand lipid alterations in the brain and serum compartments acutely following mild TBI (mTBI) and the potential efflux of brain lipids to peripheral blood. The cortices and sera from male and female Sprague–Dawley rats were analyzed via ultra-high performance liquid chromatography–mass spectrometry (UHPLC-MS) in both positive and negative ion modes following single and repetitive closed head impacts. The overlapping lipids in the data sets were identified with an in-house data dictionary for investigating lipid class changes. MS-based lipid profiling revealed overall increased changes in the serum compartment, while the brain lipids primarily showed decreased changes. Interestingly, there were prominent alterations in the sphingolipid class in the brain and blood compartments after single and repetitive injury, which may suggest efflux of brain sphingolipids into the blood after TBI. Genetic algorithms were used for predictive panel selection to classify injured and control samples with high sensitivity and specificity. These overlapping lipid panels primarily mapped to the glycerophospholipid metabolism pathway with Benjamini–Hochberg adjusted q-values less than 0.05. Collectively, these results detail overlapping lipidome changes following mTBI in the brain and blood compartments, increasing our understanding of TBI-related lipid dysregulation while identifying novel biomarker candidates.
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