NEUROPROTECTIVE EFFECTS OF ETHYL PYRUVATE ON ENERGY METABOLISM OF RAT BRAIN AFTER ISCHEMIA: A 31P-NMR STUDY

丙酮酸乙酯对缺血后大鼠脑能量代谢的神经保护作用：31P-NMR 研究

• 批准号: 17591639
• 负责人: KITANO Takaaki
• 金额: $ 1.28万
• 依托单位: Oita University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591639/
• 关键词: 31P-NMR; ethyl pyruvate; ischemia; phosphocreatine; Brain slices; fluorocitrate; Ethyl Pyruvate; ^<31>P-NMR; Ischemic reperfusion injury; Brain Slices

Introduction : Pyruvate is not only an intermediary metabolite of energy metabolism but also a neuro-protectant as a potent antioxidant and free radical scavenger. It was reported that administration of pyruvate improved cerebral metabolic and functional status during hemorrhagic shock and reduced neuronal death after cerebral ischemia.Neuroprotective effects of ethyl pyruvate (EP), a stable and lipophilic derivative of pyruvate, on energy metabolism of rat brain exposed to ischemia were investigated by phosphorous nuclear magnetic resonance (^<31>P-NMR) spectroscopy.Methods : Brain slices prepared from a male Wistar rat (6 week-old) were incubated in standard artificial cerebrospinal fluid (ACSF) with 2mM EP or ACSF only (control) at 25℃. The brain slices were exposed to ischemia by halting the perfusion for 1 hr. Recovery of the levels of high-energy phosphates, phosphocreatine (PCr), after reperfusion were measured by ^<31>P-NMR.Results : Recovery of the level of PCr after ischemia was significantly greater when EP was present in ACSF than in its absence (78.2 ± 3.3% vs 60.8 ± 1.9%, respectively; p = 0.001). EP was less effective when it was administered only during the recovery period (71.9 ± 4.6%; p = 0.059). When the brain slices were treated with 1001μM fluorocitrate (FC), a selective glial poison, PCr level was decreased to 92.0 ± 3.3% of the untreated level. In neuron-rich brain slices pretreated with FC, difference in recovery of the PCr level after ischemia was not detected (69.8 ± 6.4% vs 70.0 ± 4.5%; p = 0.66).Conclusions : These results indicated that EP is neuroprotective against ischemia when administered before the ischemic exposure. Our results also showed that EP did not show significant neuroprotective effects in neuron-rich slices pretreated with FC. It was suggested that the administration of EP before ischemia and the presence of glial cells are required for EP to exert neuroprotective effects.

简介：丙酮酸不仅是能量代谢的中间代谢产物，而且作为一种强有力的抗氧化剂和自由基清除剂，也是一种神经保护剂。丙酮酸乙酯（ethyl pyruvate，EP）是丙酮酸的一种亲脂性衍生物，应用磷核磁共振（~ 1 P-NMR）技术研究了EP对脑缺血大鼠能量代谢的保护作用<31>。将从雄性Wistar大鼠（6周龄）制备的脑切片在25℃下在含有2 mM EP或仅含有ACSF（对照）的标准人工脑脊液（ACSF）中孵育。结果<31>：在ACSF中加入EP后，缺血后PCr水平的恢复明显高于不加EP时的恢复（分别为78.2 ± 3.3%和60.8 ± 1.9%; p = 0.001）。EP仅在恢复期给药时的有效性较低（71.9 ± 4.6%; p = 0.059）。用1001μM氟柠檬酸（FC）处理脑片后，PCr水平下降至未处理水平的92.0 ± 3.3%。在用FC预处理的富含神经元的脑切片中，未检测到缺血后PCr水平恢复的差异（69.8 ± 6.4%对70.0 ± 4.5%; p = 0.66）。结论：这些结果表明，当在缺血暴露前施用EP时，对缺血具有神经保护作用。我们的研究结果还表明，EP没有表现出显着的神经元丰富的切片预处理与FC的神经保护作用。提示脑缺血前给予EP及脑内胶质细胞的存在是EP发挥神经保护作用的必要条件。

项目成果

Gamma knife radiosurgery targeting protocols for the experiments with small animals

• DOI: 10.1159/000099071
• 发表时间: 2007-01-01
• 期刊: STEREOTACTIC AND FUNCTIONAL NEUROSURGERY
• 影响因子: 1.7
• 作者: Tokumaru, Osamu;Hayashi, Motohiro;Kouyama, Nobuo
• 通讯作者: Kouyama, Nobuo

Effects of gamma ray irradiation on energy metabolism in the rat brain : a ^<31>P nuclear magnetic resonance study.

伽马射线照射对大鼠脑能量代谢的影响：^ 31 P核磁共振研究。

• 发表时间: 2006
• 期刊: J Neurosurg 105(Suppl)
• 作者: Tokumaru O;Kitano T;Takei H;Ogata K;Kawazato H;Yasuda A;Nisimaru N;Yokoi I
• 通讯作者: Yokoi I

Effects of gamma ray irradiation on energy metabolism in the rat brain : a 31P nuclear magnetic resonance study.

伽马射线照射对大鼠脑能量代谢的影响：31P 核磁共振研究。

• 发表时间: 2006
• 期刊: J Neurosurg (Suppl) 105
• 作者: Tokumaru 0;Kitano T;Takei H;Ogata K Kawazato H;Yasuda A;Nisimaru N;Yokoi I.
• 通讯作者: Yokoi I.