Erythropoietin Reduces Neurodegeneration and Long-Term Memory Deficits Following Sevoflurane Exposure in Neonatal Rats.

Abstract

Exposure to general anesthetics induces neural apoptosis and degeneration in the immature neonatal brain. Erythropoietin (EPO) has been shown to protect neonatal animals against hypoxic-ischemic injury and general anesthesia-induced developmental neurotoxicity. However, preventive strategy caused by EPO against neurotoxicity due to general anesthesia is still uncertain. This study examined the effects of EPO administration on brain cytology and cognitive function in adolescent rats exposed to 3% sevoflurane as neonates. Seven-day-old rats received intraperitoneal saline (EPO 0U group) or EPO (60, 120, or 600U) 30min before exposure to 3% sevoflurane with 21% oxygen for 4h. The rats only received 21% oxygen without EPO and sevoflurane as the sham group. The Morris water maze task was performed time-dependently among the groups, 3weeks post-anesthesia exposure. Escape latency and % quadrant in the EPO 600U group were significantly reduced and increased, respectively, compared with those in the EPO 0U group 6weeks post-exposure. In addition, freezing time in response to the conditioned stimulus and the number of NeuN-positive cells in the hippocampal CA1 region were significantly increased in the EPO 120 and 600U groups than in the EPO 0U group 6weeks after exposure. Moreover, the statistical parameter mapping of positive cell density was increased in the EPO-treated rats. These results support the observations that pretreatment with EPO reduced long-term cognitive deficits and neuronal degeneration in cortex and hippocampus induced by sevoflurane exposure with low oxygen concentration in neonatal rats.