Department of Anaesthesiology, University of Virginia, Charlottesville, VA, USA.
Br J Anaesth. 2013 Jun;110 Suppl 1(Suppl 1):i47-52. doi: 10.1093/bja/aet073. Epub 2013 Apr 24.
Exposure to general anaesthesia during critical stages of brain development results in long-lasting cognitive impairment. Co-administration of protective agents could minimize the detrimental effects of anaesthesia. Co-administration of R(+)pramipexole (PPX), a synthetic aminobenzothiazol derivative that restores mitochondrial integrity, prevents anaesthesia-induced mitochondrial and neuronal damage and prevents early development of cognitive impairment. Here, we determine the protective effects of PPX into late adulthood in male and female rats.
Postnatal day 7 rats of both sexes were exposed to mock anaesthesia or combined midazolam, nitrous oxide, and isoflurane anaesthesia for 6 h with or without PPX. Cognitive abilities were assessed between 5 and 7 months of age using Morris water maze spatial navigation tasks.
Examination of spatial reference memory revealed that female, but not male, neonatal rats exposed to anaesthesia showed slowing of acquisition rates, which was significantly improved with PPX treatment. Examination of memory retention revealed that both male and female anaesthesia-treated rats have impaired memory retention performance compared with sham controls. Co-treatment with PPX resulted in improvement in memory retention in both sexes.
PPX provides long-lasting protection against cognitive impairment known to occur when very young animals are exposed to anaesthesia during the peak of brain development. Anaesthesia-induced cognitive impairment appears to be sex-specific with females being more vulnerable than males, suggesting that they could benefit more from early prevention.
在大脑发育的关键阶段暴露于全身麻醉会导致长期认知障碍。联合使用保护剂可以最大程度地减少麻醉的有害影响。联合使用 R(+)普拉克索（PPX），一种恢复线粒体完整性的合成氨基苯并噻唑衍生物，可以预防麻醉诱导的线粒体和神经元损伤，并预防认知障碍的早期发展。在这里，我们确定了 PPX 在雄性和雌性大鼠成年后期的保护作用。
出生后 7 天的雄性和雌性大鼠接受模拟麻醉或咪达唑仑、氧化亚氮和异氟烷联合麻醉 6 小时，同时给予或不给予 PPX。在 5 至 7 个月大时，使用 Morris 水迷宫空间导航任务评估认知能力。
对空间参考记忆的检查表明，接受麻醉的雌性但不是雄性新生大鼠的获得速度明显减慢，而 PPX 治疗可显著改善。对记忆保留的检查表明，与假手术对照组相比，接受麻醉的雄性和雌性大鼠的记忆保留性能均受损。用 PPX 共同治疗可改善两性的记忆保留。
PPX 可提供针对认知障碍的长期保护，当非常年幼的动物在大脑发育高峰期接受麻醉时，已知会发生这种障碍。麻醉诱导的认知障碍似乎具有性别特异性，雌性比雄性更易受影响，这表明它们可能从早期预防中获益更多。
