Inhibiting Rho kinase 2 reduces memory dysfunction in adult rats exposed to sevoflurane at postnatal days 7-9.

The aim of the present study was to investigate the roles of Rho protein A (RhoA) and Rho kinases 2 (ROCK2) in the memory dysfunction of adult rats exposed to sevoflurane at postnatal days 7-9 (P7-9). One-week-old Sprague-Dawley rats were divided into four groups known as C, S1, S3 and F. Rats in the S1 (2 h at P7) and S3 groups (2 h/day at P7-9) were exposed to sevoflurane. The rats in the F group were treated with the ROCK2 inhibitor and subsequent sevoflurane exposure (2 h/day at P7-9). The rats in the C group received no sevoflurane. The protein levels of RhoA, ROCK2 and cleaved caspase-3 (Cl-Csp3) in the adult hippocampus were assessed by western blot analysis. Learning and memory of rats at postnatal 45-50 days (P45-50) were detected by the Morris water maze (MWM) test. During the training of MWM, the latency and distance of rats in the S3 group were significantly longer than that of the C group (P<0.05, respectively). In the probe test, the percentages of time and distance in the target quadrant for the S3 group were evidently less than that of the C group (P<0.05). There was no significant difference in the behaviors between the C and S1 groups (P>0.05, respectively). Corresponding to the behavioral changes, the levels of RhoA, ROCK2 and Cl-Csp3 in the hippocampus of the S3 group significantly increased, compared to that of the C and S1 groups (P<0.05). Additionally, the ROCK2 inhibitor clearly decreased ROCK2 and Cl-Csp3 expression and shortened the latency during the training (P<0.05, P46-49 respectively) and probe test (P<0.05) in the F group, compared to that of the S3 group. Compared to the C group, the expression of RhoA, ROCK2 and Cl-Csp3 in the hippocampus of the S1 group had no significant difference (P>0.05). Multiple inhalation of sevoflurane can induce neurotoxicity and memory dysfunction. RhoA and ROCK2 played important roles in the impairment of learning and memory of adults rats exposed to sevoflurane at the postnatal early stage.