The Role Of Maternal Expousure To Propofol During Late Gestation Period In Sprague-dawley Offspring Rat’s Learning And Memory Dysfunction And The Expression Of BDNF In Hippocampal Area

Objective: To study the effect of propofol on learning and memory function in Sprague-Dawley rat offsprings after propofol anesthesia in maternal rats during the third trimester, and we observe the expression of brain derived neurotrophic factor(BDNF) in hippocampus, in order to interpret the mechanisms underlying the influence of propofol on learning and memory in offspring rats.Methods: According to the random number table, thirty healthy SD rats, aged 7 weeks, were randomly divided into three groups: propofol anesthesia for 4h(group Pro4); propofol anesthesia for 8 h(group Pro8) and Control group(group C). On the 18 th day after pregnancy, rats in group Pro4 as well as group Pro8 were injected intravenously with propofol 20 mg/kg via cauda vein for induction, and then maintained with 20mg/kg/h for 4h or 8h, respectively. Rats in group C were injected with the same amount of saline for comparison. 30 days after birth, the offsprings produced by each female rats were randomly divided into agonist subgroups(Pro4D, Pro8 D, CD subgroups) and agonist solvent subgroups(Pro4N, Pro8 N, CN subgroups). 2h before each Morris water maze test, rat offspings in the agonist subgroups were injected with 7, 8-DHF intraperitoneally(5 mg/kg), while those in the agonist solvent subgroups were just treated with an equal volume of solvent. The second day after the end of the water maze test, offsprings were sacrificed and the brains were immediately removed. By using real-time PCR, the expression levels of both BDNF and tropomyosin receptor kinase B(Trk B) in hippocampal tissues were analyzed.Result:(1) The escape latency of the offsprings in solvent subgroups(Pro4N, Pro8N), was significantly longer than that in group CN(P<0.05). In addition, the escape latency of the offsprings in Trk B agonist subgroups(Pro4D, Pro8D), was also significantly longer than that in group CD(P<0.05). The time that offsprings, in solvent subgroup(Pro8N), spent in traveling the second quadrant of the water maze and the number they tried to cross the platform, was significantly shorter or less than that in group CN(P<0.05), but longer or greater than that in group Pro4N(P<0.05). Moreover, the escape latency was shorter in the solvent subgroup(Pro8N) than that in group Pro4N(P<0.05). Compared with group Pro4 D, the escape latency of the offsprings in the Trk B agonist subgroups(Pro8D) as shorter, and the time they used for passing the second quadrant and the number they tried for crossing the platform was longer or greater(P<0.05). Then, when compared to those in the solvent subgroups(CN, Pro4 N, Pro8N), the escape latency was shorter, and the time or number offsprings spent on water maze test was longer or greater in Trk B agonist subgroups(CD, Pro4 D, Pro8D)(P<0.05), respectively.(2) RT-PCR results: comparing the BDNF together with Trk B expression levels in hippocampus in the solvent subgroups, we found that the levels in offsprings born after their mothers infused with propofol in the late phase of pregnancy(group Pro4 N and Pro8N) reduced significantly when compared with group CN(P < 0.05). Similarly, the BDNF and Trk B expression levels in agonist solvent subgroups such as group Pro4 D and Pro8 D also decreased compared to those in group CD(P < 0.05). However, the expression levels of BDNF and Trk B were significantly higher in all of the agonist subgroups(group CD, Pro4 D, Pro8D) than those in solvent subgroups(group Pro4 N, Pro8 N, CN)(P < 0.05).(3) Immunohistochemical results: compared with group CN in solvent subgroups, the number of BDNF/Trk B positive cells was less in group Pro4 N and Pro8 N, along with staining shallowed. Meanwhile, the BDNF/Trk B positive cells decreased in group Pro4 D and Pro8 D and the dye of cells became lighter when compared to group CD. But the number of BDNF/Trk B positive cells was greater and the staining was deeper in the agonist subgroups than in the solvent subgroups.Conclusion:Infusion with propofol in maternal rats during the late phase of pregnancy may lead to the impairment of learning and memory function in the offsprings with time-effect relationship. Besides, the BDNF expression level in the hippocampus reduced in offspring rats, such changes may related with the inhibition of the expression of Trk B. Thus, we speculated that propofol anesthesia during the third trimester may damage offsprings’ learning and memory function via “BDNF-Trk B” pathway, but the exact role of this pathway remains to be further investigated.