[Acute injury to ce.rebral function produced by isoflurane anesthesia given at different time interval in neonatal rats]

Objective:To investigate effects of isoflurane anesthesia of different time interval on acute injury of brain function in neonatal rats with consistent total time of isoflurane anesthesia. Methods:Seven-day neonatal Sprague-Dawley (SD) rats were randomly divided into normal control group (breathe the air), continuous anesthesia group (a single 6-hour exposure to 1.5% isoflurane), and intermittent anesthesia 1 day and 3 days groups (three times of 2-hour exposure to anesthesia with an interval of 1 day or 3 days), 12 rats in each group. The ratio of male to female was 5:7. They underwent the test of learning and memory in the radial arm maze (RAM) 21 days after birth, twice a day for 4 days. The number of entry into wrong arms, number of repeated errors, number of total arm entries, and time for completing the task were recorded for evaluation of effect of neonatal isoflurane on cognitive behavior in rats. Results:① Compared with normal control group, the percentage of number of errors > 3 in anesthesia of 3-day interval group was significantly decreased (33.3% vs. 46.9%, P < 0.05), the percentages of repeated errors > 0 and total arm entries > 8 were significantly increased (33.3% vs. 18.8%, 27.1% vs. 13.5%, both P < 0.05), but there were no statistically significant difference in the percentage of mistake number > 3 between continuous anesthesia group, interval anesthesia 1-day group and the normal control group (44.8%, 44.8% vs. 46.9%), the percentages of number of repeated mistake > 0 and total arm entries > 8 in above three groups were slightly increased as compared with those of normal control group (27.1%, 22.9% vs. 18.8%, 20.8%, 21.9% vs. 13.5%, all P > 0.05). No statistical differences in completing the task among normal control group, continuous anesthesia group, interval anesthesia 1 day and 3 days groups were found (minutes: 1.32±0.91, 1.54±1.05, 1.46±0.86, 1.38±0.79, all P > 0.05). ② It was found by gender analysis that the percentages number of repeated errors > 0 and total arm entries > 8 were significantly lower in female rats than those in the male rats only in normal control group (5.0% vs. 28.6%, P < 0.01; 5.0% vs. 19.6%, P < 0.05). There was no obvious gender difference in exposed groups. ③ Compared between groups of female rats, the percentages of repeated mistake > 0 in continuous anesthesia group, interval anesthesia 1 day and 3 days groups (25.0%, 25.0%, 30.0% vs. 5.0%, P < 0.05 or P < 0.01) and the percentage of total arm entries > 8 in interval anesthesia 1 day and 3 days groups were significantly higher than that of normal control group (22.5%, 25.0% vs. 5.0%, both P < 0.05). No significant difference about the RAM task in male rats of all the four groups was found. Conclusions:Different time interval of neonatal isoflurane exposure may develop certain degree of acute brain injury in rats, characterized by cognitive function. Prolongation of the interval time significantly enhanced long-term memory in rats. Multiple neonatal exposures to isoflurane were associated with greater cognitive impairment than a single exposure. In addition, isoflurane can significantly increase cognitional functional disorder in the female, not in the male rats.