Dexmedetomidine Attenuates Isoflurane-induced Neurocognitive Impairment in Neonatal Rats
Dexmedetomidine Attenuates Isoflurane-induced Neurocognitive Impairment in Neonatal Rats
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DOI：
10.1097/aln.0b013e31819daedd
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发表时间：
2009-05-01
期刊：
影响因子：
8.8
通讯作者：
Maze, Mervyn
中科院分区：
文献类型：
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作者：
Sanders, Robert D.;Xu, Jing;Maze, Mervyn
背景：神经细胞凋亡是由麻醉剂对年轻人的管理。为.肾上腺素能受体信号在发育过程中起营养作用，并在几种神经元损伤的环境中具有神经保护作用，作者研究了右旋美托咪啶是否可以提供对异氟烷诱导的injuries.Methods的功能保护：异氟烷诱导的损伤在出生后第7天大鼠的器官型海马切片培养物中通过6小时暴露于0.75%的异氟烷（含或不含右旋美托咪啶）而在体外或体内引起。在体内，α 2肾上腺素受体拮抗剂阿替美唑用于鉴定右旋美托咪定神经保护是否涉及α肾上腺素受体活化。γ-氨基丁酸A型拮抗剂，gabazine，也被添加到异氟烷存在下的器官型海马切片培养。使用切割的caspase-3免疫组织化学评估细胞凋亡。认知功能进行了评估，在体内出生后第40天使用恐惧conditioning.Results：在体内右美托咪定剂量依赖性地防止异氟烷诱导的海马，丘脑和皮质损伤，这种神经保护与阿替美唑治疗衰减。虽然麻醉治疗不影响短期记忆的获得，异氟烷确实诱导长期记忆障碍。这种神经认知缺陷是通过管理右美托咪定，这也抑制了异氟烷诱导的caspase-3的表达在器官型海马切片培养在体外，但是，gabazine没有修改这种neuropapoptosis.Conclusion：右美托咪定衰减异氟烷诱导的损伤在发育中的大脑，提供神经认知保护。异氟烷诱导的体外损伤似乎不依赖于γ-氨基丁酸A型受体的激活。如果异氟烷诱导的神经细胞凋亡被证明是一个临床问题，右美托咪定给药可能是预防异氟烷诱导的神经毒性的重要辅助措施。
Background: Neuroapoptosis is induced by the administration of anesthetic agents to the young. As a. adrenoceptor signaling plays a trophic role during development and is neuroprotective in several settings of neuronal injury, the authors investigated whether dexmedetomidine could provide functional protection against isoflurane-induced injury.Methods: Isoflurane-induced injury was provoked in organotypic hippocampal slice cultures in vitro or in vivo in postnatal day 7 rats by a 6-h exposure to 0.75% isoflurane with or without dexmedetomidine. In vivo, the alpha(2) adrenoceptor antagonist atipamezole was used to identify if dexmedetomidine neuroprotection involved a, adrenoceptor activation. The gamma-amino-butyric-acid type A antagonist, gabazine, was also added to the organotypic hippocampal slice cultures in the presence of isoflurane. Apoptosis was assessed using cleaved caspase-3 immunohistochemistry. Cognitive function was assessed in vivo on postnatal day 40 using fear conditioning.Results: In vivo dexmedetomidine dose-dependently prevented isoflurane-induced injury in the hippocampus, thalamus, and cortex; this neuroprotection was attenuated by treatment with atipamezole. Although anesthetic treatment did not affect the acquisition of short-term memory, isoflurane did induce long-term memory impairment. This neurocognitive deficit was prevented by administration of dexmedetomidine, which also inhibited isoflurane-induced caspase-3 expression in organotypic hippocampal slice cultures in vitro; however, gabazine did not modify this neuroapoptosis.Conclusion: Dexmedetomidine attenuates isoflurane-induced injury in the developing brain, providing neurocognitive protection. Isoflurane-induced injury in vitro appears to be independent of activation of the gamma-amino-butyric-acid type A receptor. If isoflurane-induced neuroapoptosis proves to be a clinical problem, administration of dexmedetomidine may be an important adjunct to prevent isoflurane-induced neurotoxicity.