Department of Biomedical Science, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE, C1A 4P3, Canada.
Neurosci Res. 2011 Apr;69(4):299-307. doi: 10.1016/j.neures.2010.12.011. Epub 2010 Dec 24.
Lipoic acid (LA) is a naturally occurring compound and dietary supplement with powerful antioxidant properties. Although LA is neuroprotective in models of stroke, little is known about the cellular mechanisms by which it confers protection during the early stages of ischemia. Here, using a rat model of permanent middle cerebral artery occlusion (MCAO), we demonstrated that administration of LA 30 min prior to stroke, reduces infarct volume in a dose dependent manner. Whole-cell patch clamp techniques in rat brain slices were used to determine if LA causes any electrophysiological alterations in either healthy neurons or neurons exposed to oxygen and glucose deprivation (OGD). In healthy neurons, LA (0.005 mg/ml and 0.05 mg/ml) did not significantly change resting membrane potential, threshold or frequency of action potentials or synaptic transmission, as determined by amplitude of excitatory post synaptic currents (EPSCs). Similarly, in neurons exposed to OGD, LA did not alter the time course to loss of EPSCs. However, there was a significant delay the onset of anoxic depolarization as well as in the time course of the depolarization. Next, intracellular calcium (Ca(2+)) levels were monitored in isolated neurons using fura-2. Pretreatment with 0.005 mg/ml and 0.05 mg/ml LA for 30 min and 6 h did not significantly alter resting Ca(2+) levels or Ca(2+) response to glutamate (250 μM). However, pretreatment with 0.5 mg/ml LA for 6 h significantly increased resting Ca(2+) levels and significantly decreased the Ca(2+) response to glutamate. In summary, these findings suggest that LA does not affect neuronal physiology under normal conditions, but can protect cells from an ischemic event.
硫辛酸（LA）是一种天然存在的化合物和膳食补充剂，具有强大的抗氧化特性。尽管 LA 在中风模型中具有神经保护作用，但对于它在缺血早期阶段提供保护的细胞机制知之甚少。在这里，我们使用永久性大脑中动脉闭塞（MCAO）大鼠模型证明，在中风前 30 分钟给予 LA 可剂量依赖性地减少梗死体积。在大鼠脑片中使用全细胞膜片钳技术，以确定 LA 是否会导致健康神经元或暴露于缺氧和葡萄糖剥夺（OGD）的神经元发生任何电生理改变。在健康神经元中，LA（0.005 mg/ml 和 0.05 mg/ml）不会显著改变静息膜电位、阈值或动作电位频率或突触传递，这是通过兴奋性突触后电流（EPSC）的幅度确定的。同样，在暴露于 OGD 的神经元中，LA 不会改变 EPSC 丧失的时程。然而，缺氧去极化的起始以及去极化的时程有明显的延迟。接下来，使用 fura-2 在分离神经元中监测细胞内钙（Ca（2+））水平。用 0.005 mg/ml 和 0.05 mg/ml LA 预处理 30 分钟和 6 小时不会显著改变静息 Ca（2+）水平或谷氨酸（250 μM）的 Ca（2+）反应。然而，用 0.5 mg/ml LA 预处理 6 小时会显著增加静息 Ca（2+）水平并显著降低谷氨酸的 Ca（2+）反应。总之，这些发现表明 LA 在正常条件下不会影响神经元生理学，但可以保护细胞免受缺血事件的影响。
