期刊
ANESTHESIOLOGY
卷 110, 期 4, 页码 862-868出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/ALN.0b013e31819b5eab
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资金
- NICHD NIH HHS [R01 HD052664, R37 HD037100-11, HD37100, R37 HD037100, R37 HD037100-10] Funding Source: Medline
- NIDA NIH HHS [R01 DA005072-19, R01 DA005072, R01 DA005072-18, DA05072] Funding Source: Medline
- NIMH NIH HHS [T32 MH014677-30, T32 MH014677, T32 MH014677-29, T32MH14677] Funding Source: Medline
Background: Ethanol and anesthetic drugs trigger neuroapoptosis in the developing mouse brain. Recently, it was found that ethanol-induced neuroapoptosis is preceded by suppressed phosphorylation of extracellular signal-regulated protein kinase (ERK), and lithium counteracts both the phosphorylated ERK suppressant action and ethanol-induced neuroapoptosis. The current study was undertaken to address the following questions. (1) Do ketamine and propofol mimic ethanol in suppressing ERK phosphorylation? (2) If they do, does lithium prevent this suppressant action and also prevent these anesthetic drugs from triggering neuroapoptosis? Method: Postnatal day 5 mice were treated with propofol, ketamine, lithium, a combination of propofol or ketamine with lithium or saline, and their brains were prepared for Western blot analysis or histology. For Western blot, cytosolic lysates of caudate putamen were analyzed for expression of phosphorylated ERK and phosphorylated serine/threonine-specific protein kinase. For histology, brains were stained immunohistochemically with antibodies to activated caspase-3, and the density of activated caspase-3 positive cells was determined. Results: Ketamine and propofol suppressed phosphorylated ERK, and lithium counteracted both the phosphorylated ERK suppressant action and neuroapoptotic action of these anesthetic drugs. Conclusion: If further testing finds lithium to be safe for use in pediatric/obstetric medicine, administration of a single dose of lithium before anesthesia induction may be a suitable means of mitigating the risk of anesthesia-induced developmental neuroapoptosis.
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