Effects of isoflurane on spatial learning, memory and nNOS expression in the hippocampus of the aged rats

Objective: To investigate the effects of isoflurane on both spatial learning and memory and nNOS expression in the hippocampal CA1 subfield of the aged rats. Methods: Twenty -month -old Sprague -Dawley (SD) male rats (n =36/group) were included in this study. Based on the duration of anesthesia as well as the time-point of behavioral testing post-anesthesia, the aged rats were randomly divided into 6 groups (n =6/group) as follows: control group (no MWM testing, no anesthesia, just hippocampal sections processed); training group (no anesthesia, just MWM testing); isoflurane 2 h/2 d, 2 h/2 week, 4 h/2 d, 4 h/2 week groups in which the aged rats were exposed to 1.2% isoflurane for two or four hours and were tested with MWM at two days or two weeks after isoflurane administered, respectively. Following MWM behavioral testing, animals were killed and hippocampal sections were processed for nNOS expression in the CA1 subfield via immunohistochemistry. Results: Isoflurane exposure induced spatial memory deficits in aged rats since the escape latency increased significantly (P 0.05). Especially, four hours exposure to isoflurane resulted in more severe spatial memory impairment relative to two hours exposure. Moreover, this impairment occurred up to two weeks following the anesthesia (P 0.05). The training groups exhibited a remarkable increase in nNOS expression in the hippocampal CA1 subfield relative to control, non-treated rats (P 0.05). Exposure to isoflurane inhibited nNOS expression, and this inhibition increased with increasing exposure duration, and that could last for a relative long time (two weeks). Conclusion: The inhalational anesthetic-isoflurane may impair the spatial learning and memory induced by inhibiting nNOS expression in hippocampal CA1 region of the aged rats.