颅脑创伤代谢组学和早期 Ru360 治疗后的线粒体影响。
Traumatic brain injury metabolome and mitochondrial impact after early stage Ru360 treatment.
机构信息
Department of Radiology, Rutgers New Jersey Medical School, Administrative Complex Building 5 (ADMC5), 30 Bergen Street Room 575, Newark, NJ 07101, USA.
Department of Pharmacology, Physiology & Neuroscience, Rutgers New Jersey Medical School, MSB-H-512, 185 S. Orange Ave, Newark, NJ 07103, USA; Molecular, Cell and Systems Biology, University of California Riverside, Spieth 1308, 3401 Watkins Drive, Riverside, CA 92521, USA.
出版信息
Mitochondrion. 2021 Mar;57:192-204. doi: 10.1016/j.mito.2021.01.003. Epub 2021 Jan 21.
Abstract
Ru360, a mitochondrial Ca uptake inhibitor, was tested in a unilateral fluid percussion TBI model in developing rats (P31). Vehicle and Ru360 treated TBI rats underwent sensorimotor behavioral monitoring between 24 and 72 h, thereafter which 185 brain metabolites were analyzed postmortem using LC/MS. Ru360 treatment after TBI improved sensorimotor behavioral recovery, upregulated glycolytic and pentose phosphate pathways, mitigated oxidative stress and prevented NAD depletion across both hemispheres. While neural viability improved ipsilaterally, it reduced contralaterally. Ru360 treatment, overall, had a global impact with most benefit near the strongest injury impact areas, while perturbing mitochondrial oxidative energetics in the milder TBI impact areas.
摘要
Ru360 是一种线粒体钙摄取抑制剂，在发育中的大鼠（P31）单侧液压冲击性脑损伤模型中进行了测试。在 24 至 72 小时之间，对接受载体和 Ru360 处理的 TBI 大鼠进行了感觉运动行为监测，此后使用 LC/MS 对死后的 185 种大脑代谢物进行了分析。TBI 后 Ru360 的治疗改善了感觉运动行为的恢复，上调了糖酵解和戊糖磷酸途径，减轻了氧化应激并防止了两侧半球的 NAD 耗竭。虽然同侧的神经活力得到了改善，但对侧的神经活力却降低了。总体而言，Ru360 的治疗具有全局影响，在最强的损伤影响区域附近具有最大的益处，而在较轻的 TBI 影响区域则扰乱了线粒体氧化能量代谢。
相似文献
1
Traumatic brain injury metabolome and mitochondrial impact after early stage Ru360 treatment.颅脑创伤代谢组学和早期 Ru360 治疗后的线粒体影响。
Mitochondrion. 2021 Mar;57:192-204. doi: 10.1016/j.mito.2021.01.003. Epub 2021 Jan 21.
2
Beneficial Effects of Kaempferol after Developmental Traumatic Brain Injury Is through Protection of Mitochondrial Function, Oxidative Metabolism, and Neural Viability.山奈酚对发育期创伤性脑损伤的有益作用是通过保护线粒体功能、氧化代谢和神经活力实现的。
J Neurotrauma. 2019 Apr 15;36(8):1264-1278. doi: 10.1089/neu.2018.6100. Epub 2019 Jan 8.
3
Early behavioral and metabolomic change after mild to moderate traumatic brain injury in the developing brain.发育脑中小至中度创伤性脑损伤后的早期行为和代谢组学变化。
Neurochem Int. 2018 Nov;120:75-86. doi: 10.1016/j.neuint.2018.08.003. Epub 2018 Aug 9.
4
Role of mitochondrial calcium uniporter-mediated Ca and iron accumulation in traumatic brain injury.线粒体钙单向转运体介导线粒体钙和铁积累在创伤性脑损伤中的作用。
J Cell Mol Med. 2019 Apr;23(4):2995-3009. doi: 10.1111/jcmm.14206. Epub 2019 Feb 12.
5
Inhibition of the mitochondrial calcium uniporter by the oxo-bridged dinuclear ruthenium amine complex (Ru360) prevents from irreversible injury in postischemic rat heart.氧桥联双核钌胺配合物（Ru360）对线粒体钙单向转运体的抑制作用可防止缺血后大鼠心脏发生不可逆损伤。
FEBS J. 2005 Jul;272(13):3477-88. doi: 10.1111/j.1742-4658.2005.04771.x.
6
Post-Injury Administration of Mitochondrial Uncouplers Increases Tissue Sparing and Improves Behavioral Outcome following Traumatic Brain Injury in Rodents.线粒体解偶联剂在损伤后给药可减少啮齿动物创伤性脑损伤后的组织损伤并改善行为结果。
J Neurotrauma. 2007 May;24(5):798-811. doi: 10.1089/neu.2006.3673.
7
Mitochondrial uncoupling prodrug improves tissue sparing, cognitive outcome, and mitochondrial bioenergetics after traumatic brain injury in male mice.线粒体解偶联前药可改善雄性小鼠创伤性脑损伤后的组织保护、认知结果和线粒体生物能学。
J Neurosci Res. 2018 Oct;96(10):1677-1688. doi: 10.1002/jnr.24271. Epub 2018 Jul 31.
8
Synaptic and nonsynaptic mitochondria demonstrate a different degree of calcium-induced mitochondrial dysfunction.突触和非突触线粒体表现出不同程度的钙诱导的线粒体功能障碍。
Life Sci. 2012 May 22;90(19-20):808-14. doi: 10.1016/j.lfs.2012.04.004. Epub 2012 Apr 14.
9
Oxygen-bridged dinuclear ruthenium amine complex specifically inhibits Ca2+ uptake into mitochondria in vitro and in situ in single cardiac myocytes.氧桥联双核钌胺配合物在体外和单个心肌细胞原位均能特异性抑制Ca2+摄入线粒体。
J Biol Chem. 1998 Apr 24;273(17):10223-31. doi: 10.1074/jbc.273.17.10223.
10
Cardiac responses to β-adrenoceptor stimulation is partly dependent on mitochondrial calcium uniporter activity.心脏对β-肾上腺素能受体刺激的反应部分依赖于线粒体钙单向转运体的活性。
Br J Pharmacol. 2014 Sep;171(18):4207-21. doi: 10.1111/bph.12684. Epub 2014 Jul 1.
引用本文的文献
1
Mitochondrial dysfunction and NLRP3 inflammasome activation in drug-resistant epilepsy: emerging insights and mitochondrial-targeted therapeutic strategies.耐药性癫痫中的线粒体功能障碍与NLRP3炎性小体激活：新见解及线粒体靶向治疗策略
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jul 23. doi: 10.1007/s00210-025-04468-2.
2
Mitochondria: the hidden engines of traumatic brain injury-driven neurodegeneration.线粒体：创伤性脑损伤所致神经退行性变的隐匿引擎
Front Cell Neurosci. 2025 May 9;19:1570596. doi: 10.3389/fncel.2025.1570596. eCollection 2025.
3
Targeting mitochondrial quality control: new therapeutic strategies for major diseases.靶向线粒体质量控制：重大疾病的新治疗策略。
Mil Med Res. 2024 Aug 21;11(1):59. doi: 10.1186/s40779-024-00556-1.
4
From spreading depolarization to blood-brain barrier dysfunction: navigating traumatic brain injury for novel diagnosis and therapy.从扩散性去极化到血脑屏障功能障碍：探索创伤性脑损伤的新诊断和治疗方法。
Nat Rev Neurol. 2024 Jul;20(7):408-425. doi: 10.1038/s41582-024-00973-9. Epub 2024 Jun 17.
5
Fundamental Neurochemistry Review: Microglial immunometabolism in traumatic brain injury.基础神经化学评论：创伤性脑损伤中的小胶质细胞免疫代谢。
J Neurochem. 2023 Oct;167(2):129-153. doi: 10.1111/jnc.15959. Epub 2023 Sep 27.
6
Ru360 Alleviates Postoperative Cognitive Dysfunction in Aged Mice by Inhibiting MCU-Mediated Mitochondrial Dysfunction.Ru360通过抑制MCU介导的线粒体功能障碍减轻老年小鼠术后认知功能障碍。
Neuropsychiatr Dis Treat. 2023 Jul 4;19:1531-1542. doi: 10.2147/NDT.S409568. eCollection 2023.
7
Rescuing mitochondria in traumatic brain injury and intracerebral hemorrhages - A potential therapeutic approach.创伤性脑损伤和脑出血中挽救线粒体 - 一种潜在的治疗方法。
Neurochem Int. 2021 Nov;150:105192. doi: 10.1016/j.neuint.2021.105192. Epub 2021 Sep 22.
本文引用的文献
1
The mitochondrial calcium uniporter is crucial for the generation of fast cortical network rhythms.线粒体钙单向转运蛋白对于快速皮质网络节律的产生至关重要。
J Cereb Blood Flow Metab. 2020 Nov;40(11):2225-2239. doi: 10.1177/0271678X19887777. Epub 2019 Nov 13.
2
Consolidated Biochemical Profile of Subacute Stage Traumatic Brain Injury in Early Development.早期发育阶段亚急性创伤性脑损伤的综合生化特征
Front Neurosci. 2019 May 3;13:431. doi: 10.3389/fnins.2019.00431. eCollection 2019.
3
Beneficial Effects of Kaempferol after Developmental Traumatic Brain Injury Is through Protection of Mitochondrial Function, Oxidative Metabolism, and Neural Viability.山奈酚对发育期创伤性脑损伤的有益作用是通过保护线粒体功能、氧化代谢和神经活力实现的。
J Neurotrauma. 2019 Apr 15;36(8):1264-1278. doi: 10.1089/neu.2018.6100. Epub 2019 Jan 8.
4
Early behavioral and metabolomic change after mild to moderate traumatic brain injury in the developing brain.发育脑中小至中度创伤性脑损伤后的早期行为和代谢组学变化。
Neurochem Int. 2018 Nov;120:75-86. doi: 10.1016/j.neuint.2018.08.003. Epub 2018 Aug 9.
5
Alterations of Parenchymal Microstructure, Neuronal Connectivity, and Cerebrovascular Resistance at Adolescence after Mild-to-Moderate Traumatic Brain Injury in Early Development.发育期轻度至中度创伤性脑损伤后青少年脑实质微观结构、神经元连接和脑血管阻力的改变。
J Neurotrauma. 2019 Feb 15;36(4):601-608. doi: 10.1089/neu.2018.5741. Epub 2018 Aug 13.
6
Glucose metabolism in pediatric traumatic brain injury.小儿创伤性脑损伤中的葡萄糖代谢
Childs Nerv Syst. 2017 Oct;33(10):1711-1718. doi: 10.1007/s00381-017-3518-7. Epub 2017 Sep 6.
7
L-Carnitine and Acetyl-L-carnitine Roles and Neuroprotection in Developing Brain.左旋肉碱和乙酰左旋肉碱在发育中大脑的作用及神经保护
Neurochem Res. 2017 Jun;42(6):1661-1675. doi: 10.1007/s11064-017-2288-7. Epub 2017 May 16.
8
Mitochondrial calcium homeostasis: Implications for neurovascular and neurometabolic coupling.线粒体钙稳态：对神经血管和神经代谢偶联的影响。
J Cereb Blood Flow Metab. 2017 Feb;37(2):381-395. doi: 10.1177/0271678X16680637. Epub 2016 Nov 24.
9
Antioxidant Mechanism of Betaine without Free Radical Scavenging Ability.无自由基清除能力的甜菜碱的抗氧化机制。
J Agric Food Chem. 2016 Oct 26;64(42):7921-7930. doi: 10.1021/acs.jafc.6b03592. Epub 2016 Oct 12.
10
Biosynthesis of glycerol phosphate is associated with long-term potentiation in hippocampal neurons.磷酸甘油的生物合成与海马神经元的长期增强作用相关。
Metabolomics. 2016;12:133. doi: 10.1007/s11306-016-1083-9. Epub 2016 Jul 23.
Zotero 插件