Effect of lactate therapy upon cognitive deficits after traumatic brain injury in the rat
Effect of lactate therapy upon cognitive deficits after traumatic brain injury in the rat
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DOI：
10.1007/s00701-007-1241-y
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发表时间：
2007-09-01
影响因子：
2.4
通讯作者：
Bullock, M. R.
中科院分区：
文献类型：
--
作者：
Holloway, R.;Zhou, Z.;Bullock, M. R.
背景资料。以往的研究表明，静脉注射乳酸治疗可以改善大鼠创伤性脑损伤后的脑神经化学、三磷酸腺苷(ATP)的生成和预后。在本研究中，我们检测了：(1)四种L乳酸浓度，以确定颅脑损伤后认知功能的最佳治疗剂量；(2)脑损伤后三磷酸腺苷的产生，以L乳酸浓度为最佳剂量；(3)L乳酸浓度最高时可能产生的乳酸酸中毒。左侧大脑半球液压冲击伤后30min，分别静脉滴注L乳酸盐10、28、100、280 mM(每组各10只)，每次0.65ml/h，持续3h，假手术组和对照组均注射生理盐水。在伤后11-15天，用Morris水迷宫(MWM)测试大鼠的认知功能。实验分为假手术组、损伤+生理盐水组、损伤+最适乳酸剂量组(n=4/组)。此外，接受280 mM L乳酸盐的一组(n=5)和接受生理盐水输注的一组(n=3)的动脉血压变量和血压也被监测。在MWM测试中，只有L乳酸盐100 mM处理的损伤动物的认知功能障碍与生理盐水处理的损伤动物相比有显著减少(pn0.05)。在ATP研究中，未经治疗的损伤动物同侧皮质中的ATP水平下降了53%，而100 mM乳酸处理的动物下降了28%。(P<0.05)。静脉滴注280 mM L乳酸盐无乳酸中毒发生。本研究表明，静脉滴注100 mM L乳酸可提供改善大鼠脑损伤后认知功能损害的最佳底物浓度，其机制可能与三磷酸腺苷的再生有关。
Background. In previous studies, it has been shown that intravenous lactate therapy can improve brain neurochemistry, adenosine triphosphate (ATP) generation and outcome after traumatic brain injury (TBI) in rats. In this study, we examined: (1) four L-lactate concentrations to determine the optimal therapeutic dose post TBI in terms of cognitive function; (2) ATP production after TBI for the L-lactate concentration found to be the optimal dose; (3) the possible production of lactic acidosis with the highest L-lactate concentration tested.Methods. Thirty minutes following a fluid percussion injury (FPI) over the left cerebral hemisphere, the animals received an intravenous infusion of 10, 28, 100, or 280mM L-lactate (n = 10 for each group) for 3h at a rate of 0.65ml/h. Shams and control injured animals received a saline infusion. At 11-15 days post injury, cognitive deficits were examined using the Morris Water Maze (MWM) test. Three groups of rats were used for ATP analysis: shams, injured + saline infusion, and injury + the optimal lactate dose as determined by the MWM (n = 4/group). Additionally, a group receiving 280mM L-lactate (n = 5) and one receiving a saline infusion (n = 3) were monitored for arterial blood variables and blood pressures.Findings. In the MWM test, only the 100mM L-lactate-treated injured animals showed a significant reduction in cognitive deficits when compared to saline-treated injured animals (p n 0.05). In the ATP study, injured animals without treatment had a 53% reduction in ATP level in the ipsilateral cortex, while animals with 100mM lactate treatment had a 28% reduction. (p n 0.05). No lactic acidosis was induced by the intravenous infusion of 280mM L-lactate.Conclusions. This study indicates that the intravenous infusion of 100mM L-lactate provided the optimal concentration of the substrate to ameliorate cognitive impairment, probably via the regeneration of ATP following TBI in rats.