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.
Mitochondrion. 2021 Mar;57:192-204. doi: 10.1016/j.mito.2021.01.003. Epub 2021 Jan 21.
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.
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。
