Lithium protects against anesthesia-induced developmental neuroapoptosis.
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?


METHODS
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.


CONCLUSIONS
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.
Straiko
Megan M W
MM
Department of Psychiatry, Washington University in St. Louis School of Medicine, St. Louis, Missouri 63110, USA.
Young
Chainllie
C
Cattano
Davide
D
Creeley
Catherine E
CE
Wang
Haihui
H
Smith
Derek J
DJ
Johnson
Stephen A
SA
Li
Erin S
ES
Olney
John W
JW
D018686:Anesthetics, Intravenous / Q000633:toxicity; D000818:Animals; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000196:embryology / Q000473:pathology; D053148:Caspase 3 / Q000187:drug effects; D007649:Ketamine / Q000633:toxicity; D016651:Lithium Carbonate / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects; D048052:Mitogen-Activated Protein Kinase 3 / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D015742:Propofol / Q000633:toxicity; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects; D011897:Random Allocation; D016896:Treatment Outcome
D018686:Anesthetics, Intravenous; D014150:Antipsychotic Agents; D016651:Lithium Carbonate; D007649:Ketamine; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D053148:Caspase 3; D015742:Propofol