In vivo metabolic imaging of Traumatic Brain Injury.
In vivo metabolic imaging of Traumatic Brain Injury.
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DOI：
10.1038/s41598-017-17758-4
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发表时间：
2017-12-13
影响因子：
4.6
通讯作者：
Chaumeil MM
中科院分区：
文献类型：
--
作者：
Guglielmetti C;Chou A;Krukowski K;Najac C;Feng X;Riparip LK;Rosi S;Chaumeil MM
创伤性脑损伤（TBI）后，脑能量代谢发生复杂变化。迄今为止，允许代谢评估的方法是高度侵入性的，限制了我们对与TBI发病机制相关的代谢损伤的理解。我们研究了超极化（HP）[1- 13 C]丙酮酸盐的13 C MRSI（一种非侵入性代谢成像方法）是否可以检测控制性皮质损伤（CCI）小鼠（n = 57）的代谢变化。我们的研究结果表明，HP [1- 13 C]乳酸-丙酮酸比在损伤后的急性（12/24小时）和亚急性（7天）时间点在损伤的皮质中增加，与丙酮酸脱氢酶（PDH）活性降低一致，表明氧化磷酸化途径受损。然后，我们使用集落刺激因子-1受体抑制剂PLX 5622在CCI之前和之后耗尽脑驻留小胶质细胞，以确认HP [1- 13 C]乳酸-丙酮酸比率的调节与小胶质细胞活化有关。尽管CCI，HP [1- 13 C]乳酸-丙酮酸比在损伤后7天的小胶质细胞耗尽的动物的损伤皮质保持不变，与对侧半球相比，和PDH活性不受影响。总之，我们的研究结果表明，HP [1- 13 C]丙酮酸具有很大的潜力，在体内非侵入性检测脑代谢后TBI，提供了一种新的工具，以监测治疗靶向TBI后小胶质细胞/巨噬细胞活化的效果。
Complex alterations in cerebral energetic metabolism arise after traumatic brain injury (TBI). To date, methods allowing for metabolic evaluation are highly invasive, limiting our understanding of metabolic impairments associated with TBI pathogenesis. We investigated whether 13C MRSI of hyperpolarized (HP) [1-13C] pyruvate, a non-invasive metabolic imaging method, could detect metabolic changes in controlled cortical injury (CCI) mice (n = 57). Our results show that HP [1-13C] lactate-to-pyruvate ratios were increased in the injured cortex at acute (12/24 hours) and sub-acute (7 days) time points after injury, in line with decreased pyruvate dehydrogenase (PDH) activity, suggesting impairment of the oxidative phosphorylation pathway. We then used the colony-stimulating factor-1 receptor inhibitor PLX5622 to deplete brain resident microglia prior to and after CCI, in order to confirm that modulations of HP [1-13C] lactate-to-pyruvate ratios were linked to microglial activation. Despite CCI, the HP [1-13C] lactate-to-pyruvate ratio at the injury cortex of microglia-depleted animals at 7 days post-injury remained unchanged compared to contralateral hemisphere, and PDH activity was not affected. Altogether, our results demonstrate that HP [1-13C] pyruvate has great potential for in vivo non-invasive detection of cerebral metabolism post-TBI, providing a new tool to monitor the effect of therapies targeting microglia/macrophages activation after TBI.
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影响因子：
4.3
作者：
Carpenter KL;Jalloh I;Hutchinson PJ
通讯作者：
Hutchinson PJ
影响因子：
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Guglielmetti C;Veraart J;Roelant E;Mai Z;Daans J;Van Audekerke J;Naeyaert M;Vanhoutte G;Delgado Y Palacios R;Praet J;Fieremans E;Ponsaerts P;Sijbers J;Van der Linden A;Verhoye M
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Verhoye M
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Daniels, Charlie J.;McLean, Mary A.;Gallagher, Ferdia A.
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Gallagher, Ferdia A.
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影响因子：
9.3
作者：
Feng X;Jopson TD;Paladini MS;Liu S;West BL;Gupta N;Rosi S
通讯作者：
Rosi S
影响因子：
4.8
作者：
Kurhanewicz, John;Vigneron, Daniel B.;Malloy, Craig R.
通讯作者：
Malloy, Craig R.