Dexmedetomidine Attenuates Isoflurane-induced Neurocognitive Impairment in Neonatal Rats

被引:455
作者
Sanders, Robert D.
Xu, Jing [3 ]
Shu, Yi [1 ]
Januszewski, Adam [1 ]
Halder, Sunil [2 ]
Fidalgo, Antonio [1 ]
Sun, Pamela [1 ]
Hossain, Mahmuda [1 ]
Ma, Daqing [1 ]
Maze, Mervyn [1 ,4 ]
机构
[1] Univ London Imperial Coll Sci Technol & Med, Dept Anaesthet Intens Care & Pain Med, Chelsea & Westminster Hosp, London SW10 9NH, England
[2] Reading Gen Hosp, Dept Anaesthet, Reading, Berks, England
[3] Gongli Hosp, Dept Anesthesiol, Shanghai, Peoples R China
[4] Abbott Labs, Abbott Pk, IL 60064 USA
关键词
NEURONAL CELL-DEATH; METHYL-D-ASPARTATE; APOPTOTIC NEURODEGENERATION; IN-VIVO; GENERAL-ANESTHESIA; RECEPTOR BLOCKADE; CONTEXTUAL FEAR; NERVOUS-TISSUE; BRAIN; XENON;
D O I
10.1097/ALN.0b013e31819daedd
中图分类号
R614 [麻醉学];
学科分类号
100217 ;
摘要
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.
引用
收藏
页码:1077 / 1085
页数:9
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