Dose-dependent influence of sevoflurane anesthesia on neuronal survival and cognitive outcome after transient forebrain ischemia in Sprague-Dawley rats.

ABSTRACT

BACKGROUND: Volatile anesthetics reduce postischemic neurohistopathological injury and improve neurological outcome in various animal models. However, the isoflurane concentrations above 1 minimum alveolar concentration (MAC) have been associated with reduced neuronal survival and impaired functional outcome. The aim of this study was to evaluate if 1.8 MAC sevoflurane alters postischemic neuronal survival and neurologic outcome compared with 0.45 MAC sevoflurane. METHODS: In this study, 20 fasted male Sprague-Dawley rats were randomly assigned to treatment groups with 1 or 4 vol.% sevoflurane end-tidal concentration. Cerebral ischemia was induced by bilateral carotid artery occlusion and hemorrhagic hypotension (BCAO). The cognitive outcome was assessed after 7 days using the object recognition test. Animals were then re-anesthetized and brains were removed for neurohistopathological analysis of the hippocampus (CA1) and cortex using hematoxylin-eosin staining. RESULTS: Physiologic parameters were not different between both the treatment groups. The number of viable neurons (median [Q1, Q3]) in the CA1 region on postischemic day 7 was increased after high-dose sevoflurane compared with low-dose sevoflurane (1645 [453, 1825] vs. 3222 [2920, 3993] neurons/ROI, P < 0.05). Results of the object recognition test were not different between both the treatment groups. CONCLUSIONS: Postischemic neuronal survival was increased with 1.8 MAC compared with 0.45 MAC sevoflurane. Therefore, experimental models of cerebral ischemia should account for neuroprotective effects of sevoflurane with increasing concentrations. To ensure minimal interference of sevoflurane on neuronal survival, a low inspired concentration should be used and fluctuations in the depth of anesthesia should be limited.