N-acetylaspartate reduction as a measure of injury severity and mitochondrial dysfunction following diffuse traumatic brain injury
N-acetylaspartate reduction as a measure of injury severity and mitochondrial dysfunction following diffuse traumatic brain injury
复制标题
DOI：
10.1089/08977150152693683
复制
发表时间：
2001-10-01
影响因子：
4.2
通讯作者：
Vagnozzi, R
中科院分区：
文献类型：
--
作者：
Signoretti, S;Marmarou, A;Vagnozzi, R
N-乙酰天冬氨酸 (NAA) 被认为是一种神经元特异性代谢物，其减少是神经元损失的标志。本研究的目的是评估不同级别的创伤性脑损伤 (TBI) 中 NAA 变化的时间过程，以及能量代谢物 (ATP) 的紊乱。由于 NAA 是由线粒体合成的，因此推测 NAA 的变化会跟随 ATP 的变化。冲击加速模型用于产生三个等级的 TBI。 Sprague-Dawley 大鼠被分为以下四组：假手术对照组（n = 12）；中度 TBI（n = 36）；严重 TBI (n = 36)；以及严重 TBI 伴有缺氧低血压 (n = 16)。在受伤后1分钟到120小时的不同时间点处死动物，并对大脑进行处理以进行NAA和ATP的高效液相色谱(HPLC)分析。中度 TBI 后，NAA 在 6 小时逐渐减少 35%，在 15 小时减少 46%，同时 ATP 减少 57% 和 45%。 120 小时 NAA 自发恢复至基线的 86%，同时 ATP 也恢复。在严重的TBI中，NAA突然下降并且没有恢复，在48小时时显示出临界下降（60%）。 ATP减少了70%并且也没有恢复。二次损伤时 NAA 和 ATP 下降最大（48 小时分别为 80% 和 90%）。这些数据表明，在弥漫性 TBI 后 48 小时，NAA 的减少根据损伤的严重程度进行分级。如果损伤程度为中度并且不伴有继发性损伤，NAA 就会恢复。 NAA 和 ATP 之间高度相似的时间过程和相关性支持 NAA 减少与能量损伤相关的观点。
N-Acetylaspartate (NAA) is considered a neuron-specific metabolite and its reduction a marker of neuronal loss. The objective of this study was to evaluate the time course of NAA changes in varying grades of traumatic brain injury (TBI), in concert with the disturbance of energy metabolites (ATP). Since NAA is synthesized by the mitochondria, it was hypothesized that changes in NAA would follow ATP. The impact acceleration model was used to produce three grades of TBI. Sprague-Dawley rats were divided into the following four-groups: sham control (n = 12); moderate TBI (n = 36); severe TBI (n = 36); and severe TBI coupled with hypoxia-hypotension (n = 16). Animals were sacrificed at different time points ranging from I min to 120 h postinjury, and the brain was processed for high-performance liquid chromatography (HPLC) analysis of NAA and ATP. After moderate TBI, NAA reduced gradually by 35% at 6 h and 46% at 15 h, accompanied by a 57% and 45% reduction in ATP. A spontaneous recovery of NAA to 86% of baseline at 120 h was paralleled by a restoration in ATP. In severe TBI, NAA fell suddenly and did not recover, showing critical reduction (60%) at 48 h. ATP was reduced by 70% and also did not recover. Maximum NAA and ATP decrease occurred with secondary insult (80% and 90%, respectively, at 48 h). These data show that, at 48 h post diffuse TBI, reduction of NAA is graded according to the severity of insult. NAA recovers if the degree of injury is moderate and not accompanied by secondary insult. The highly similar time course and correlation between NAA and ATP supports the notion that NAA reduction is related to energetic impairment.