Proton Magnetic Resonance Spectroscopy Lactate/N-Acetylaspartate Within 48 h Predicts Cell Death Following Varied Neuroprotective Interventions in a Piglet Model of Hypoxia-Ischemia With and Without Inflammation-Sensitization.
Proton Magnetic Resonance Spectroscopy Lactate/N-Acetylaspartate Within 48 h Predicts Cell Death Following Varied Neuroprotective Interventions in a Piglet Model of Hypoxia-Ischemia With and Without Inflammation-Sensitization.
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DOI：
10.3389/fneur.2020.00883
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发表时间：
2020
影响因子：
3.4
通讯作者：
Robertson NJ
中科院分区：
文献类型：
--
作者：
Pang R;Martinello KA;Meehan C;Avdic-Belltheus A;Lingam I;Sokolska M;Mutshiya T;Bainbridge A;Golay X;Robertson NJ
尽管进行了低温治疗，新生儿脑病幸存者的不良后果发生率仍然很高。需要早期替代结果测量来加快神经保护试验的转化。通过质子 (1H) 磁共振波谱 (MRS) 获得的丘脑乳酸 (Lac)/N-乙酰天冬氨酸 (NAA) 峰面积比可准确预测 2 年神经发育结果。我们评估了在接受各种神经保护干预后的仔猪模型中损伤后 24-48 小时获得的 MR 生物标志物与细胞死亡和神经炎症之间的关系。纳入了 67 头患有缺氧缺血、单纯缺氧或脂多糖 (LPS) 致敏的仔猪，神经保护干预措施包括治疗性低温、褪黑激素和镁。在 24 小时和 48 小时采集 MRS 和弥散加权成像 (DWI)。 48小时时，实验终止，并评估免疫组织化学。 Lac/NAA 与总体细胞死亡 [末端脱氧核苷酸转移酶 dUTP 缺口末端标记 (TUNEL)] [平均 Lac/NAA 基底节和丘脑 (BGT) 体素 r = 0.722，白质 (WM) 体素 r = 0.784，p < 0.01] 和小胶质细胞激活 [离子钙结合接头分子 1] 之间存在相关性(Iba1)] (BGT r = -0.786，WM r = -0.632，p < 0.01)。与 caspase 依赖性细胞凋亡标记物 [裂解的 caspase 3 (CC3)] 的相关性较低 (BGT r = -0.636，WM r = -0.495，p < 0.01)。 DWI 和 TUNEL 之间的关系不太稳健（平均扩散率 BGT r = -0.615，分数各向异性 BGT r = 0.523）。总体而言，Lac/NAA 与细胞死亡和小胶质细胞激活的相关性最好。这些数据与临床研究一致，证明 Lac/NAA 作为新生儿脑病 (NE) 结果预测因子的优越性，并支持其在临床前和临床神经保护研究中的使用。
Despite therapeutic hypothermia, survivors of neonatal encephalopathy have high rates of adverse outcome. Early surrogate outcome measures are needed to speed up the translation of neuroprotection trials. Thalamic lactate (Lac)/N-acetylaspartate (NAA) peak area ratio acquired with proton (1H) magnetic resonance spectroscopy (MRS) accurately predicts 2-year neurodevelopmental outcome. We assessed the relationship between MR biomarkers acquired at 24–48 h following injury with cell death and neuroinflammation in a piglet model following various neuroprotective interventions. Sixty-seven piglets with hypoxia–ischemia, hypoxia alone, or lipopolysaccharide (LPS) sensitization were included, and neuroprotective interventions were therapeutic hypothermia, melatonin, and magnesium. MRS and diffusion-weighted imaging (DWI) were acquired at 24 and 48 h. At 48 h, experiments were terminated, and immunohistochemistry was assessed. There was a correlation between Lac/NAA and overall cell death [terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)] [mean Lac/NAA basal ganglia and thalamus (BGT) voxel r = 0.722, white matter (WM) voxel r = 0.784, p < 0.01] and microglial activation [ionized calcium-binding adapter molecule 1 (Iba1)] (BGT r = −0.786, WM r = −0.632, p < 0.01). Correlation with marker of caspase-dependent apoptosis [cleaved caspase 3 (CC3)] was lower (BGT r = −0.636, WM r = −0.495, p < 0.01). Relation between DWI and TUNEL was less robust (mean diffusivity BGT r = −0.615, fractional anisotropy BGT r = 0.523). Overall, Lac/NAA correlated best with cell death and microglial activation. These data align with clinical studies demonstrating Lac/NAA superiority as an outcome predictor in neonatal encephalopathy (NE) and support its use in preclinical and clinical neuroprotection studies.
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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：
3.4
作者：
Eklind, S;Mallard, C;Hagberg, H
通讯作者：
Hagberg, H
影响因子：
8.3
作者：
Ito, D;Tanaka, K;Fukuuchi, Y
通讯作者：
Fukuuchi, Y
影响因子：
3.3
作者：
Choi, Changho;Coupland, Nicholas J.;Allen, Peter S.
通讯作者：
Allen, Peter S.
影响因子：
5.6
作者：
Charriaut-Marlangue C;Besson VC;Baud O
通讯作者：
Baud O