Involvement of neuronal nitric oxide synthase in cognitive impairment in isoflurane-treated rats.

The underlying causes of post-operative cognitive dysfunction (POCD) in elderly patients remain to be elucidated. In order to explore possible contributory mechanisms, we tested the effects of isoflurane anesthesia on (i) expression of hippocampal neuronal nitric oxide synthase (nNOS) and (ii) the relationship of changes in nNOS expression to cognitive dysfunction in isoflurane-treated aged rats. Our results indicate that isoflurane treatment leads to significant changes in correct reactions (F=28.35, p<0.001), initiative avoidances (F=29.33, p<0.001), and total reaction time (TRT) (F=6.99, p<0.05) of treated rats in the Y-maze test. Isoflurane-treated rats had fewer correct reactions and initiative avoidances in the Y-maze test 24 and 48 h after 2 h of isoflurane anesthesia compared with control group rats (p<0.05). TRTs to complete 20 trials of the Y-maze test increased significantly 48 h after 2 h anesthesia. The number of nNOS-positive hippocampal neurons decreased 24 h after anesthesia, corresponding to an increased mean immunostaining grey-scale value. These data show that isoflurane causes a transient decrease in expression of hippocampal nNOS in aged rats during early post-anesthesia stages, and that the transient decrease of nNOS is closely correlated with cognitive impairment in isoflurane-treated aged rats.