This study was designed to investigate whether isoflurane, a commonly used volatile anesthetic with neuroprotective property, reduces alpha-amino-3-hydroxy-5-methyl-4-isoxazol propionic acid (AMPA)-induced neurotoxicity in a concentration- and time (when isoflurane was applied in relation to the AMPA exposure)-dependent manner. Cerebellar slices from postnatal 10-14-day-old rats were exposed to 30 microM AMPA for 30 min followed by a 120-min AMPA-free recovery period at 37 degrees C. This protocol resulted in dark cell degeneration (DCD) in the majority of Purkinje neurons (60.8+/-6.9%). Fewer Purkinje neurons (31.6+/-5.2%) had edematous damage (ED) characters. Application of isoflurane (1, 2, or 3%) during both the AMPA exposure and recovery periods significantly increased the percentage of morphologically normal Purkinje neurons (neurons without DCD or ED changes) but the effects were apparently not dose-dependent. Isoflurane (3%) applied before, during or after the AMPA exposure period also significantly increased the percentage of morphologically normal Purkinje neurons. These isoflurane-induced increases in the percentage of morphologically normal Purkinje neurons were mainly due to fewer cells with DCD changes. Isoflurane decreased AMPA-induced ED significantly only when isoflurane (1 or 2%) was present during both the AMPA exposure and recovery periods. Isoflurane applied before, during or after the AMPA exposure period did not significantly affect the percentage of cells with ED changes. These results suggest that isoflurane time-dependently but not concentration-dependently reduce AMPA-induced neurotoxicity. These effects may be one mechanism for the isoflurane-induced neuroprotection demonstrated in previous studies.
Copyright 2002 Elsevier Science B.V.