Drugs that block N-methyl-d-aspartate glutamate receptors or that promote gamma-aminobutyric acid type A inhibition trigger neuroapoptosis in the developing rodent brain. Propofol reportedly interacts with both gamma-aminobutyric acid type A and N-methyl-d-aspartate glutamate receptors, but has not been adequately evaluated for its ability to induce developmental neuroapoptosis. Here we determined that the intraperitoneal (i.p.) dose of propofol required to induce a surgical plane of anesthesia in the infant mouse is 200 mg/kg. We then administered graduated doses of propofol (25-300 mg/kg i.p.) and found that doses >or=50 mg/kg induce a significant neuroapoptosis response. We conclude that propofol induces neuroapoptosis at 1/4 the dose required for surgical anesthesia.

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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 present 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 and lithium or saline and their brains 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 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 prior to anesthesia induction may be a suitable means of mitigating the risk of anesthesia-induced developmental neuroapoptosis.

Diabetes may be a risk factor for unsuccessful preparation of donor tissue for DMEK. We recommend caution in the use of diabetic tissue for DMEK graft preparation. Further study is needed to identify what subset of diabetic donors is at risk for unsuccessful DMEK graft preparation.

Tissue prestripped by an eye bank technician can be safely used for DMEK surgery. SF6 gas for prolonged tissue support may reduce the rebubble rate in DMEK, with no apparent acute toxic effect. An unrecognized upside-down graft was the primary cause of graft failure in this series. Upside-down grafts may be eliminated by the use of donor tissue premarked by the eye bank with an S orientation stamp.