Hall E D
Central Nervous System Diseases Research Unit, Upjohn Company, Kalamazoo, Michigan.
J Neurosurg. 1992 Jan;76(1):13-22. doi: 10.3171/jns.1992.76.1.0013.
A 24-hour intensive intravenous dosing regimen with the glucocorticoid steroid methylprednisolone has recently been shown to be effective in enhancing neurological recovery in spinal cord-injured patients when initiated within 8 hours after injury. The state of knowledge concerning the neuroprotective pharmacology of methylprednisolone, including mechanism(s) of action, dosing requirements, and time-action considerations is reviewed, as are the results of studies with high doses in experimental and clinical head injury, subarachnoid hemorrhage, and cerebral ischemia. A primary neuroprotective mechanism of action in each of these cases is hypothesized to involve the ability of high doses of methylprednisolone to inhibit oxygen free radical-induced lipid peroxidation, although additional mechanisms may contribute. Unresolved issues are also addressed, including the therapeutic window, optimum duration of treatment, and rational combination with other neuroprotective agents. A newer methylprednisolone pro-drug with improved solution stability is discussed, together with a brief consideration of novel nonglucocorticoid steroids that surpass methylprednisolone's lipid antioxidant effects without unwanted glucocorticoid properties.
最近有研究表明，对于脊髓损伤患者，在受伤后8小时内开始使用糖皮质激素甲泼尼龙进行24小时强化静脉给药方案，可有效促进神经功能恢复。本文综述了有关甲泼尼龙神经保护药理学的知识状况，包括作用机制、给药要求和时效关系等，还介绍了高剂量甲泼尼龙在实验性和临床性头部损伤、蛛网膜下腔出血及脑缺血研究中的结果。假设在上述每种情况下，主要的神经保护作用机制都涉及高剂量甲泼尼龙抑制氧自由基诱导的脂质过氧化的能力，不过可能还有其他机制起作用。文中还讨论了尚未解决的问题，包括治疗窗、最佳治疗持续时间以及与其他神经保护剂的合理联合使用。此外，还讨论了一种溶液稳定性有所改善的新型甲泼尼龙前体药物，并简要提及了一些新型非糖皮质激素甾体，它们具有超过甲泼尼龙的脂质抗氧化作用且无不良糖皮质激素特性。
