Early behavioral and metabolomic change after mild to moderate traumatic brain injury in the developing brain.
Early behavioral and metabolomic change after mild to moderate traumatic brain injury in the developing brain.
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DOI：
10.1016/j.neuint.2018.08.003
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发表时间：
2018-11
影响因子：
4.2
通讯作者：
Kannurpatti SS
中科院分区：
文献类型：
--
作者：
Chitturi J;Li Y;Santhakumar V;Kannurpatti SS
由于发育中大脑的内在差异，发育性创伤性脑损伤(TBI)的病理生理学是独特的。脑发育早期(P13至P30)的能量代谢研究表明，急性氧化能量代谢在颅脑损伤后24小时内下降，通常在48小时后恢复。然而，在青春期的后期观察到明显的神经变性和神经功能连通性改变。由于继发性神经变性在大鼠脑损伤后第一周最为突出，我们推测亚急性脑损伤代谢体可能含有神经变性的预测性标记物。在p31岁的雄性SD大鼠中，在轻到中等强度的TBI后72小时检测了SHAM和TBI代谢体。在伤后24、48和72小时评估感觉运动行为，然后在死后72小时取脑进行代谢组学检测。在损伤侧(同侧)半球，广泛的脑损伤引起的代谢改变以相对较高的强度发生。代谢紊乱的强度与感觉运动行为缺陷的程度相关。脑损伤后72小时的N-乙酰-天冬氨酸(NAA)水平预测脑损伤后7天神经变性的程度。多变量非靶向方法的结果清楚地区分了脑损伤引起的代谢变化。在脑损伤后72小时，氨基酸、脂肪酸和能量代谢等几条通路继续受到影响，这些通路的共同作用可能决定了脑损伤后早期的整体病理反应，包括神经退行性变。
Pathophysiology of developmental traumatic brain injury (TBI) is unique due to intrinsic differences in the developing brain. Energy metabolic studies of the brain during early development (P13 to P30) have indicated acute oxidative energy metabolic decreases below 24 hours after TBI, which generally recovered by 48 hours. However, marked neurodegeneration and altered neural functional connectivity have been observed at later stages into adolescence. As secondary neurodegeneration is most prominent during the first week after TBI in the rat model, we hypothesized that the subacute TBI-metabolome may contain predictive markers of neurodegeneration. Sham and TBI metabolomes were examined at 72 hours after a mild to moderate intensity TBI in male Sprague-Dawley rats aged P31. Sensorimotor behavior was assessed at 24, 48 and 72 hours after injury, followed by 72-hour postmortem brain removal for metabolomics using Liquid Chromatography/Mass Spectrometry (LCMS) measurement. Broad TBI-induced metabolomic shifts occurred with relatively higher intensity in the injury-lateralized (ipsilateral) hemisphere. Intensity of metabolomic perturbation correlated with the extent of sensorimotor behavioral deficit. N-acetyl-aspartate (NAA) levels at 72 hours after TBI, predicted the extent of neurodegeneration assessed histochemically 7-days post TBI. Results from the multivariate untargeted approach clearly distinguished metabolomic shifts induced by TBI. Several pathways including amino acid, fatty acid and energy metabolism continued to be affected at 72 hours after TBI, whose collective effects may determine the overall pathological response after TBI in early development including neurodegeneration.
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