Pellmar T C
Department of Physiology, Armed Forces Radiobiology Research Institute, Bethesda, MD 20889-5603, USA.
J Neurosci Methods. 1995 Jun;59(1):93-8. doi: 10.1016/0165-0270(94)00198-p.
To understand the neuropathological roles of free radicals we investigate their actions in a model neuronal system, the hippocampal brain slice. Free radicals can be generated through a number of methods: hydrogen peroxide to produce hydroxyl radicals, dihydroxyfumarate to generate superoxide and ionizing radiation producing a variety of radical species. We find that free radicals have a number of profound effects in this system, which can be prevented by free-radical scavengers and antioxidants. With exposure to free radicals, the ability to generate spikes and synaptic efficacy are impaired. Decreased spike generating ability is correlated with lipid peroxidation. No change in membrane potential, membrane resistance, or many of the potassium currents can account for the effect on spike generation. Protein oxidation is likely to underlie synaptic damage. Both inhibitory and excitatory synaptic potentials are reduced by free-radical exposure. Presynaptic mechanisms are implicated. Lower concentrations of radicals prevent the maintenance of long-term potentiation, perhaps through oxidation of the NMDA receptor. The actions of the free radicals are often reversible because of the presence of repair mechanisms, such as glutathione, in hippocampal slices. The brain slice preparation has allowed us to begin to understand the electrophysiological and biochemical consequences of free-radical exposure.
为了解自由基的神经病理学作用，我们在一个模型神经元系统——海马脑片中研究它们的作用。自由基可通过多种方法产生：用过氧化氢产生羟基自由基，用二羟基富马酸产生超氧阴离子，以及用电离辐射产生多种自由基。我们发现自由基在这个系统中具有多种深远影响，自由基清除剂和抗氧化剂可预防这些影响。暴露于自由基时，产生动作电位的能力和突触效能会受损。动作电位产生能力的下降与脂质过氧化有关。膜电位、膜电阻或许多钾电流的变化均不能解释对动作电位产生的影响。蛋白质氧化可能是突触损伤的基础。自由基暴露会使抑制性和兴奋性突触电位均降低。这涉及突触前机制。较低浓度的自由基可能通过氧化NMDA受体而阻止长时程增强的维持。由于海马脑片中存在诸如谷胱甘肽等修复机制，自由基的作用通常是可逆的。脑片制备使我们能够开始了解自由基暴露的电生理和生化后果。
