A Mild Traumatic Brain Injury in Mice Produces Lasting Deficits in Brain Metabolism.
A Mild Traumatic Brain Injury in Mice Produces Lasting Deficits in Brain Metabolism.
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DOI：
10.1089/neu.2018.5663
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发表时间：
2018-10-15
影响因子：
4.2
通讯作者：
Bachstetter AD
中科院分区：
文献类型：
--
作者：
Lyons DN;Vekaria H;Macheda T;Bakshi V;Powell DK;Gold BT;Lin AL;Sullivan PG;Bachstetter AD
创伤性脑损伤（TBI）后的最初几分钟到几天内，代谢解偶联已得到充分表征，但脑损伤后数周数月的线粒体生物能量学却定义不明确，尤其是在轻度TBI之后。我们假设闭合性颅脑损伤（CHI）在损伤后一个月会与线粒体生物能量学缺陷相关。在成年C57Bl/6J小鼠损伤后一个月，发现状态III（三磷酸腺苷产生）和状态V（复合物 - I）驱动的线粒体呼吸显著降低。突触线粒体的分离表明状态III和状态V的缺陷主要在神经元。受伤小鼠在损伤后一个月在记忆回忆方面存在时间上一致的缺陷。使用7特斯拉的质子磁共振波谱（1H MRS），我们发现磷酸肌酸、N - 乙酰天冬氨酸和总胆碱显著减少。我们还通过伪连续动脉自旋标记磁共振序列测量发现脑血流存在区域差异，包括低灌注和高灌注。我们的研究结果强调了与CHI相关的线粒体生物能量学的慢性缺陷，这可能为轻度TBI后的神经修复提供一种新方法。MRS为评估旨在改善线粒体生物能量学的候选治疗方法的疗效提供了一种潜在的生物标志物。
Metabolic uncoupling has been well-characterized during the first minutes-to-days after a traumatic brain injury (TBI), yet mitochondrial bioenergetics during the weeks-to-months after a brain injury is poorly defined, particularly after a mild TBI. We hypothesized that a closed head injury (CHI) would be associated with deficits in mitochondrial bioenergetics at one month after the injury. A significant decrease in state-III (adenosine triphosphate production) and state-V (complex-I) driven mitochondrial respiration was found at one month post-injury in adult C57Bl/6J mice. Isolation of synaptic mitochondria demonstrated that the deficit in state-III and state-V was primarily neuronal. Injured mice had a temporally consistent deficit in memory recall at one month post-injury. Using proton magnetic resonance spectroscopy (1H MRS) at 7-Tesla, we found significant decreases in phosphocreatine, N-Acetylaspartic acid, and total choline. We also found regional variations in cerebral blood flow, including both hypo- and hyperperfusion, as measured by a pseudocontinuous arterial spin labeling MR sequence. Our results highlight a chronic deficit in mitochondrial bioenergetics associated with a CHI that may lead toward a novel approach for neurorestoration after a mild TBI. MRS provides a potential biomarker for assessing the efficacy of candidate treatments targeted at improving mitochondrial bioenergetics.
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DOI：
10.1038/jcbfm.2012.114
发表时间：
2012-12
期刊：
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.2
作者：
George, Elijah O.;Roys, Steve;Gullapalli, Rao P.
通讯作者：
Gullapalli, Rao P.
影响因子：
4.1
作者：
Martin, NA;Patwardhan, RV;Becker, DP
通讯作者：
Becker, DP
影响因子：
4.2
作者：
Kulbe, Jacqueline R.;Hill, Rachel L.;Hall, Edward D.
通讯作者：
Hall, Edward D.
影响因子：
3.3
作者：
Deelchand, Dinesh K.;Adanyeguh, Isaac M.;Emir, Uzay E.;Nguyen, Tra-My;Valabregue, Romain;Henry, Pierre-Gilles;Mochel, Fanny;Oez, Guelin
通讯作者：
Oez, Guelin