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Sevoflurane Causes Long‐lasting Dendritic Spine Head Enlargement without Lasting Effect on Neuritic Extension

Early postnatal anesthesia causes long‐lasting learning and memory impairment in rodents, however, the underlying mechanisms remain largely unknown. We tested a hypothesis that clinically relevant concentrations of the volatile anesthetic sevoflurane alters morphology in developing mouse hippocampal neurons. Mouse fetal day 16 hippocampal neurons were cultured in Neurobasal medium for 7 days in vitro (DIV) prior to a single (4 hour) exposure to 3% sevoflurane in 95% air/5% CO2 or control condition (95% air/5% CO2). Neurons were immediately fixed in 4% paraformaldehyde or cultured for 14 more days prior to staining for filamentous (F)‐actin using Alexa Fluor555‐Phalloidin, or actin‐binding drebrin. Proximal and distal dendritic segments were randomly selected for analysis. Sevoflurane induced acute significant decreases in mean dendritic filopodial length (n=49), compared to control DIV7 neurons (n=105; P < 0.00001). The effect was completely prevented by Y27632 (10 µM), a selective Rho kinase inhibitor consistent with a RhoA/Rho kinase‐mediated mechanism of F‐actin depolymerization. Sevoflurane‐treated neurons recovered to control mean filopodial length by DIV14. On the other hand, early spine enlargement persisted until DIV14 in sevoflurane‐treated neurons (0.83 µm vs 0.61 µm, P = 0.0001, n= 52) associated with significantly (P = 0.047) increased F‐actin concentration. Drebrin immunoreactive spines showed similar results. Sevoflurane‐treated neurons (DIV21) had a higher proportion of large spines (> 8 μm) (18% vs 10%; P = 0.053) compared to control neurons. These data suggest sevoflurane differentially affects F‐actin pools in spine head and neck.