Effects Of Isoflurane On Memory And Expression Of NMDAR2B And GABAR1 In The Brain Of Aged Rats

Postoperative cognitive dysfunction is recognized as a central nervous system complications with cognitive function degradation following the general anesthesia and surgery,especially in the elderly.Its clinical manifestation mainly include personality changes,memory impairment and sociality decline.POCD can prolong hospital stay,increase the mortality and affect the quality of life of postoperative elderly patients seriously.The objective of this study was to explore the different concentrations and inhalation duration time of isoflurane on cognitive dysfunction in aged rats and the effects of the expression of NMDAR2 B and GABAR1 in different brain regions.One hundred aged male rats were randomly divided into control group(group C,20 rats),isoflurance group(group S,80 rats).The rats in each group were treated with the water maze experiment for five days to make them develop stable memory.Control groups received air at room tempreture.Test groups were divided into four groups: group S1(1.5%-2h),group S2(2.5%-2h),group S3(1.5%-4h),group S4(2.5%-4h)according to isoflurane concentration and inhalation duration time.Each group was equally divided into two groups and Morris water maze test would be done at 1 day and 7 days after isoflurane inhalation.Then the right temporal lobe and hippocampus were gathered and the mRNA transcription and protein expression of GABAR1 and NMDAR2 B were detected by RT-PCR and Immunofluorescence technique.We found that the times of crossing the platform of the rats in group S one day after isoflurane inhaltion significantly decreased compared with the control rats and the higher of the concentration,the longer of the duration time,the more extent cognitive function declined.The escape latent period of therats in groups S prolonged accompanied with isoflurane concentration rising and inhalation duration time adding.While,at 7days after isoflurane inhalation,the spatial memory ability of group S4 decreased compared with control group and the other test groups.There is no significant difference between control group and the other test groups(S1,S2,S3).The results of immunofluorescence and RT-PCR showed that the level of expression and transcription of GABAR1 in hippocampus and temporal lope of the rats in group S increased compared with the rats in control group at one day after isoflurane inhalation.And this trend was accompanied with isoflurane concentration rising and inhalation duration time adding.At 7days after isoflurane inhalation,there was no significant difference among group S1,S2,S3 and group control on the expression and transcription of GABAR1.While,the level of expression and transcription of group S4 increased significantly.The results of immunofluorescence and RT-PCR also showed that the level of expression and transcription of NMDAR2 B in hippocampus and temporal lope of the rats in group S decreased compared with the rats in control group at one day after isoflurane inhalation.And this trend accompanied with isoflurane concentration rising and inhalation duration time adding.Seven days later,there was no significant difference between group C and group S(except for group S4).The level of expression and transcription of group S4 decreased significantly.Via this experiment,It could draw a conclusion as follows:1.Continuous inhalation of isoflurane does cause short-term learning and memory damage in aged rats,and this damage may continue for a long time with higher concentration and longer duration time of inhalation.2.Up-regulation of GABAR1 and down-regulation of NMDAR2 B are related with the changes of spatial memory ability caused by isoflurane.3.Isoflurane inhalation not only change the expression of related proteins in hippocampus,but also in temprol lope.We hypothesized that postoperative cognitive dysfunction is the participation of multilobes of thebrain and brain regions.