The volatile anesthetic isoflurane is neuroprotective when administered just before or concurrent with brain ischemia. In hippocampal slice cultures, isoflurane administered concurrently with OGD reduces cell death in CA1, CA3 and dentate neurons by >75% (Anesthesiol., 96:189, 2002). In the heart, isoflurane pre-conditioning (a bout of anesthetic administration <1hr before ischemia) reduces myocardial injury during subsequent ischemia, but a phenomenon similar to classic ischemic preconditioning with isoflurane has not been described in the brain. In cortical neurons in mice and in organotypic hippocampal slice cultures from rats, isoflurane increases intracellular calcium concentration, activates MAPK p42/44 (ERK), pC-JUN, MKK3/6 and Raf, events possibly linked to neuroprotective gene expression (Fahlman, C.S. SFN Abstract, 2003). Therefore, in organotypic hippcampal cultures, we determined whether isoflurane (2% vapor in 95%O2/5%CO2 for 2 hrs at 37 C) 24 hours before a one hour period of oxygen-glucose d...