Sevoflurane preconditioning against focal cerebral ischemia: Inhibition of apoptosis in the face of transient improvement of neurological outcome

Background: Preconditioning the brain with volatile anesthetics seems to be a viable option for reducing ischemic cerebral injury. However, it is uncertain whether this preconditioning effect extends over a longer period of time. The purpose of this study was to determine if sevoflurane preconditioning offers durable neuroprotection against cerebral ischemia. Methods: Rats (Sprague-Dawley) were randomly allocated to two groups: nonpreconditioned control group (n =3D 44) and preconditioned group (n =3D 45) exposed to 2.7 vol% sevoflurane (45 min) 60 min before surgery. Animals in both groups were anesthetized with 3.0vol% sevoflurane and subjected to transient middle cerebral artery occlusion. After 60 min of awake focal ischemia, the filament was removed. Functional neurologic outcome (range 0-18; 0 =3D no deficit), cerebral infarct size (Nissl staining), and apoptosis (Terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick-end labeling; cleaved caspase-3 staining) were evaluated at 3, 7, and 14 days after ischemia. Results: Sevoflurane preconditioning significantly improved functional outcome and reduced infarct volume (109 +/- 43 vs. 148 +/- 56 mm3) 3 days after ischemia compared to the control group. However, after 7- and 14-day recovery periods, no significant differences were observed between groups. The number of apoptotic cells was significantly lower in the preconditioned group than in the control group after 3- and 7-day recovery periods. Fourteen days after ischemia, no differences were observed between groups. Conclusion: In this model of transient focal cerebral ischemia, sevoflurane preconditioning induced effective but transient neuroprotective effects. Sevoflurane preconditioning also decreased ischemia-induced apoptosis in a more sustained way because it was observed up to 7 days after injury. (C) 2009 American Society of Anesthesiologists, Inc