Cognitive Impairment And Frontal Lobe Injury In Rats With Obstructive Sleep Apnea Syndrome

Objective:To explore the relationship between cognitive impairment and frontal lobe injury in rats with obstructive sleep apnea syndrome.Methods:Selected male rats were 3-months-old and with a similar weight(mean,2000±10 g)were assigned to the model group(n=30)and the control group(n=30).The rats in the OSAS model group were injected with 0.1 ml sodium hyaluronate solution into the upper respiratory tract at the junction between the hard and soft palate.After OSAS model was established in the experimental group,they were divided into the 2-week experiment group,the 4-week experiment group,and the 6-week experiment group(10 rats each in each group)according to the length of continued feeding(2 weeks,4 weeks,and 6 weeks).The control group was fed under normal conditions and also divided into the 2-week control group,the 4-week control group,and the 6-week control group(10 rats in each group)according to the length of continued feeding(2 weeks,4 weeks,and 6 weeks).The model and normal rats were compared using tests of Morris Water Maze.Western blot was used to detect the expression of ERK1/2、Bcl2 and NogoA.The tissue sections were stained by hematoxylin eosin(HE)and immunohistochemically(IHC).Results:1.Morris water maze test:(1)The results of training test:The time-to-event AFT model showed significant differences between 2、4、6 week’s OSAS rats over all swims on the everyday,p<0.001,as summarized in Table 1,Table 2,Table 3and Figure2.The figure2 shows a consistent trend of lower probability of reaching the platform over time for the OSAS group in comparison with the control group.It also shows the expected trend in increased probability of finding the platform over time both over multiple swims per day and between days.And showed significant differences between OSAS and control group on the same week,p<0.001.In addition,the mean escape latency of 6 week’s OSAS group was significantly increased compared with that of the control group.(2)For OSAS rat the fraction of time spent in each quadrant is approximately similar leading to a uniform distribution whereas for control rat the time spent in the target quadrant is significantly higher leading to a non-uniform distribution.And showed significant differences between OSAS and control group on the same week,p<0.05.Constraints on ml(leftmost column)indicate that control rats favor the target quadrant.2.Western Blot results:The expression of ERK1/2、Bcl2 and NogoA protein in the frontal cortex in the experimental group was lower than that in the control group at the same point,the differences were statistically significant(p<0.05).3.HE staining revealed that rats in control group had clear layers of brain tissue structures,stained evenly and with a regular cell shape,compared with rats in OSAS group.Astrocytes were considered to be of the pale glial nuclei showing a vesicular nucleus with at least one basophilic nucleolus were visible.In 2w’s OSAS group,the right cortical pyramidal layer astrocytes is mild vacuolation of internal capsule and major rami.And the left frontal cortex showed cortical laminar oedema with vacuolation,irregular arrangement,disorganization,rods of the nerve cells were identified,astrocyte activation and reactive gliosis,abundant astrocyte(Figure 5).These evidence shows that the histopathological change of frontal cortex is astrocyte hyperplastic inflammatory response.4.The result of IHC showed compared with the control group at each time point,the microglia cells in other OSAS groups increased and some of them were deep stained except in the right OSAS group at 6 weeks.The morphological changes showed that the positive cells in the right frontal cortex of OSAS increased at 2、4 weeks(p<0.05)。There were more positive cells in the left frontal cortex of OSAS at 2、4、6 weeks,and the differences were statistically significant(p<0.05).Conclusion:1.OSAS rats were complicated with cognitive dysfunction;2.Cognitive dysfunction was associated with frontal cortex injury in OSAS rats;3.The activation of microglia and astrocytes in the frontal cortex of OSAS rats may be leading to cognitive dysfunction.4.Cognitive dysfunction in OSAS rats may be associated with decreased NogoA protein in the frontal cortex;5.Cognitive impairment in the frontal cortex of OSAS rats is associated with the apoptosis pathway of ERK1/2-Bcl2.6.A new statistical method to analyze Morris Water Maze data using R code.