Zhang R, Shohami E, Beit-Yannai E, Bass R, Trembovler V, Samuni A
Department of Molecular Biology, Faculty of Medicine, The Hebrew University, Jerusalem, Israel.
Free Radic Biol Med. 1998 Jan 15;24(2):332-40. doi: 10.1016/s0891-5849(97)00267-0.
Reactive oxygen-derived species were previously implicated in mediation of post-traumatic brain damage; however, the efficacy of traditional antioxidants in preventing/reversing the damage is sometimes limited. The present work focused on the mechanisms underlying the neuroprotective activity of cell permeable, nontoxic, antioxidants, namely stable nitroxide radicals in an experimental model of rat closed-head injury. Brain damage was induced by the weight-drop method and the clinical status was evaluated according to a neurological severity score at 1 h and 24 h, where the difference between these scores reflects the extent of recovery. The metal chelator deferoxamine as well as three nitroxide derivatives, differing in hydrophilicity and charge, and one hydroxylamine (a reduced nitroxide) facilitated the clinical recovery and decreased the brain edema. The nitroxides, but neither the hydroxylamine nor deferoxamine, protected the integrity of the blood-brain barrier. Superoxide dismutase also improved the clinical recovery but did not affect brain edema or the blood-brain barrier. The results suggest that by switching back and forth between themselves, the nitroxide and hydroxylamine act catalytically as self-replenishing antioxidants, and protect brain tissue by terminating radical-chain reactions, oxidizing deleterious metal ions, and by removal of intracellular superoxide.
活性氧衍生的物质先前被认为参与创伤性脑损伤的介导过程；然而，传统抗氧化剂在预防/逆转损伤方面的功效有时是有限的。目前的工作聚焦于细胞可渗透、无毒的抗氧化剂（即稳定的氮氧自由基）在大鼠闭合性颅脑损伤实验模型中的神经保护活性的潜在机制。通过重物下落法诱导脑损伤，并在1小时和24小时时根据神经严重程度评分评估临床状态，这些评分之间的差异反映恢复程度。金属螯合剂去铁胺以及三种在亲水性和电荷方面不同的氮氧衍生物和一种羟胺（还原的氮氧自由基）促进了临床恢复并减轻了脑水肿。氮氧自由基保护了血脑屏障的完整性，但羟胺和去铁胺均未起到这种作用。超氧化物歧化酶也改善了临床恢复，但未影响脑水肿或血脑屏障。结果表明，氮氧自由基和羟胺通过相互转换，作为自我补充的抗氧化剂起催化作用，并通过终止自由基链反应、氧化有害金属离子以及清除细胞内超氧化物来保护脑组织。
