Vink R, McIntosh T K, Rhomhanyi R, Faden A I
Department of Chemistry and Biochemistry, James Cook University, Townsville, Australia.
J Neurosci. 1990 Nov;10(11):3524-30. doi: 10.1523/JNEUROSCI.10-11-03524.1990.
Treatment of CNS trauma with the opiate antagonist naloxone improves outcome, though the mechanisms of action remain speculative. Nalmefene is another opiate-receptor antagonist, but it has substantially greater potency and duration of action than naloxone. It also has increased activity at kappa opiate receptors and has recently been shown to limit histological changes and neurological dysfunction after traumatic spinal cord injury. The present study examined the effects of treatment with nalmefene on outcome after fluid-percussion-induced traumatic brain injury in rats, using magnetic resonance spectroscopy to monitor acute metabolic changes and behavioral tests to determine chronic neurological recovery. Single-dose treatment with nalmefene (100 micrograms/kg, i.v.) at 30 min after trauma significantly improved (p less than 0.05) neurological outcome (up to 4 weeks) as compared to saline-treated controls. Early changes in intracellular free-magnesium concentration, adenosine diphosphate concentration, and cytosolic phosphorylation potential were all significantly improved by nalmefene treatment, reflecting improved bioenergetic state. We suggest that the ability of nalmefene to improve cellular bioenergetics after trauma may in part account for the neuroprotective effects of this and related compounds.
使用阿片类拮抗剂纳洛酮治疗中枢神经系统创伤可改善预后，但其作用机制仍存在推测性。纳美芬是另一种阿片受体拮抗剂，但其效力和作用持续时间比纳洛酮大得多。它在κ阿片受体上的活性也有所增加，最近已被证明可限制创伤性脊髓损伤后的组织学变化和神经功能障碍。本研究使用磁共振波谱监测急性代谢变化，并通过行为测试确定慢性神经功能恢复情况，研究了纳美芬治疗对大鼠液体冲击诱导的创伤性脑损伤后预后的影响。与生理盐水处理的对照组相比，创伤后30分钟给予纳美芬单剂量治疗（100微克/千克，静脉注射）显著改善了（p<0.05）神经功能预后（长达4周）。纳美芬治疗显著改善了细胞内游离镁浓度、二磷酸腺苷浓度和胞质磷酸化电位的早期变化，反映了生物能量状态的改善。我们认为，纳美芬改善创伤后细胞生物能量学的能力可能部分解释了该化合物及相关化合物的神经保护作用。
