Metabolomics Research Facility, Division of Behavioral Neuroscience, Institute of Nuclear Medicine and Allied Sciences, Delhi, India.
Center for Injury Biomechanics, Materials and Medicine (CIBM3), Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ, 07102-1982, USA.
Metabolomics. 2020 Mar 12;16(3):39. doi: 10.1007/s11306-020-1649-4.
Blast-induced neurotrauma (BINT) has been recognized as the common mode of traumatic brain injury amongst military and civilian personnel due to an increased insurgent activity domestically and abroad. Previous studies from this laboratory have identified three major pathological events following BINT which include blood brain barrier disruption the earliest event, followed by oxidative stress and neuroinflammation as secondary events occurring a few hours following blast.
Our recent studies have also identified an increase in oxidative stress mediated by the activation of superoxide producing enzyme NADPH oxidase (NOX) in different brain regions at varying levels with neurons displaying higher oxidative stress (NOX activation) compared to any other neural cell. Since neurons have higher energy demands in brain and are more prone to oxidative damage, this study evaluated the effect of oxidative stress on blast-blast induced changes in metabolomics profiles in different brain regions.
Animals were exposed to mild/moderate blast injury (180 kPa) and examined the metabolites of energy metabolism, amino acid metabolism as well as the profiles of plasma membrane metabolites in different brain regions at different time points (24 h, 3 day and 7 day) after blast using H NMR spectroscopy. Effect of apocynin, an inhibitor of superoxide producing enzyme NADPH oxidase on cerebral metabalomics profiles was also examined.
Several metabolomic profile changes were observed in frontal cortex and hippocampus with concomitant decrease in energy metabolism. In addition, glutamate/glutamine and other amino acid metabolism as well as metabolites involved in plasma membrane integrity were also altered. Hippocampus appears metabolically more vulnerable than the frontal cortex. A post-treatment of animals with apocynin, an inhibitor of NOX activation significantly prevented the changes in metabolite profiles.
Together these studies indicate that blast injury reduces both cerebral energy and neurotransmitter amino acid metabolism and that oxidative stress contributes to these processes. Thus, strategies aimed at reducing oxidative stress can have a therapeutic benefit in mitigating metabolic changes following BINT.
爆炸引起的神经创伤（BINT）已被认为是国内外由于叛乱活动增加而导致军事和民用人员创伤性脑损伤的常见模式。本实验室的先前研究已经确定了 BINT 后的三个主要病理事件，包括最早发生的血脑屏障破坏，其次是氧化应激和神经炎症，这是在爆炸后几个小时发生的继发性事件。
我们最近的研究还发现，氧化应激通过超氧化物产生酶 NADPH 氧化酶（NOX）的激活而增加，在不同的脑区以不同的水平发生，神经元显示出比任何其他神经细胞更高的氧化应激（NOX 激活）。由于神经元在大脑中具有更高的能量需求并且更容易受到氧化损伤，因此该研究评估了氧化应激对不同脑区爆炸诱导的代谢组学谱变化的影响。
动物暴露于轻度/中度爆炸伤（180 kPa），并使用 H NMR 光谱法在爆炸后不同时间点（24 小时、3 天和 7 天）检查不同脑区的能量代谢物、氨基酸代谢物以及质膜代谢物的代谢物谱。还检查了超氧化物产生酶 NADPH 氧化酶抑制剂 apocynin 对大脑代谢组学谱的影响。
在前额皮质和海马体中观察到几种代谢组学谱变化，同时伴有能量代谢减少。此外，谷氨酸/谷氨酰胺和其他氨基酸代谢物以及参与质膜完整性的代谢物也发生了改变。海马体在代谢上比前额皮质更脆弱。用 apocynin（NOX 激活抑制剂）对动物进行后处理可显著防止代谢物谱的变化。
这些研究表明，爆炸伤会降低大脑的能量和神经递质氨基酸代谢，氧化应激会导致这些过程发生。因此，旨在降低氧化应激的策略可以在减轻 BINT 后代谢变化方面具有治疗益处。
