The effects of time window on the long-term neuroprotection of sevoflurane postconditioning on neonatal rats with hypoxic/ischemic brain injury

Objective To evaluate the effects of time window on long-term neuroprotection of sevoflurane postconditioning on neonatal rats with hypoxic/ischemic(H/I) brain injury. Methods Two hundred and forty 7-days-old SD rats, weighing 13-17 g, (male/female ratio, 1∶1), were randomly divided into 6 groups(n=40) using a random number table: sham operation group(group Sham), H/I injury group(group H/I), according to the time of postconditioning, 0 h(group P0), 3 h(group P3), 6 h(group P6), 12 h(group P12). To establish H/I brain injury model in neonatal rats, the left common carotid artery ligation was carried out, and then the rats were exposed to 8% O2+92% N2 at 37 ℃ for 2 h in group H/I, P0, P3, P6 and P12. The rats of group P0, P3, P6, P12 inhaled 2% sevoflurane for 30 min at 0, 3, 6, 12 h after the H/I model was established. At 7 d after the model was established, the mortality was recorded in the rats. The survival rats were weighed and then sacrificed. The brains were removed and the right and left cerebral hemispheres were weighed separately, and the ratio between left/right cerebral hemispheres was calculated. The density of normal neurons in the hippocampal CA1 region of the left cerebral hemispheres were measured. In another experiment, the function of cognitive and memory were assessed in adolescence (28 d after H/I) using Morris water maze. Results There was no significant difference in the mortality among the five groups (P> 0.05). Compared with group sham, the density of normal neurons in the hippocampal CA1 region in the left cerebral hemispheres, weight of left cerebral hemispheres, and ratio between left/right cerebral hemispheres were significantly decreased, and left brain injury was more severe in group H/I and the postconditioned groups (P 0.05). The measurement results coincided with the results of Morris water maze: compared with group H/I, the escape latency longations were decreased significantly and crossing platform times were increased in group P0, P3 and P6(P 0.05). Conclusions 2% sevoflurane postconditioning within 6 h was most effective on attenuating neonatal rats' H/I brain injury, and the protection is long-term and can improve learning and memory function during adolescence. Key words: Time window; Sevoflurane; Postconditioning; Newborn rats; Hypoxic/ischemic brain injury; Cerebral protection