The Effects Of Motor Training Beginning At Different Time To The Cognitive Function And Hippocampal Plasticity Of Experimental Cerebral Hemorrhage In Rats

Object: This paper mainly explored the effects of motor training beginning at different time to the cognitive function and hippocampal plasticity of experimental cerebral hemorrhage in rats,to provide guidance for clinical patients about when to begin to motor training after intracerebral hemorrhage.Methods: 1.The methods of molding and intervention: we made the model of experimental cerebral hemorrhage in rats by injecting collagenase of Ⅰtype into the caudate nucleus of rats.On the contrary,we injected the same volume of normal saline into the caudate nucleus of rats in the sham-operated group.We adopted Modified Neurological Severity Score(mNSS)and micro PET/CT to evaluate the models,if the score ≥8.5 and PET/CT examination prompted there was a hematoma,the model was successful.The rats were divided into 24 hours(24 h)group,3 day(3 d)group and 7 day(7 d)group depending on the different starting time of motor training after the success of the molding,each group was trained for 3 weeks,the total time of training were 3 weeks,and the sham-operated group and the model group were not given any treatment.2.Index detection:(1)Conducted Y-maze test and passive avoidance reaction test to each group of rats to detect the ability of learning and memory after the end of training;(2)Observed the histopathological changes of cerebral tissue around the hematoma in cerebral hemorrhage rats by HE staining method;(3)Detected the expression of brain derived neurotrophic factor(BDNF)and interleukin 10(IL-10)in hippocampal CA3 area around the hematoma in cerebral hemorrhage rats by immunohistochemical staining method,in the average optical density value(optical density OD);(4)Detected the expression of bax mRNA and bcl-2 mRNA in hippocampal CA3 area around the hematoma in cerebral hemorrhage rats by RT-PCR method,in grayscale value.3.Statistical processing: Statistical analysis was performed with IBM SPSS Statistics 17.0 software and all the data was indicated in the form of Mean±standard deviation(?x±s).p<0.05 was statistically significant.One-way analysis of variance(one-way ANOVA)and SLD-t test were used to compare the average optical density value of IL-10 and BDNF between the five groups.The correlation test was undertaken with the linear correlation analysis.Results:1.The scores of learning ability of motor training groups were lower than the model group,the times that 24 h group、3d group、7d group need respectively to succeed were 74.25±10.10,66.25±9.88,77.50±10.88 in Y-maze test,and the model group need 104.92±12.25(p<0.05).There is no significant difference between 24 h group and 7d group,but the scores of the two groups were higher than 3d group in Y-maze test.The scores of memory ability of motor training groups is higher than the model group,step-through latency of 24 h group、3d group、7d group respectively were 268.7s,283.1s,242.3s,and the model group’s was 132.8s(p<0.05).There was no significant difference between 24 h group and 3d group(p>0.05),but the scores of the two groups were higher than 7d group in passive avoidance reaction test(p<0.05).2.HE staining: the model group and the motor training groups had typical pathological changes compare with sham-operated group.The caudate nucleus of rats in the sham-operated group had uniform structure and dyeing,and there was no abnormal glial cell proliferation and angiogenesis.The profiles of the cells were complete and clear,and had plenty of plasma,the nucleus was centered.The absorption of hematoma in the model group rats was incomplete,the organization around the hematoma was loose,and could see the uneven distribution of cavitation and blood vessels and glial cells hyperplasia.The absorption of hematoma in the 24 h group was relatively completely,the surrounding tissue loose degree was slightly improved compared with the model group,and the blood vessels and glial cells hyperplasia significantly,but still could see the uneven distribution of cavitation.The absorption of hematoma in the 3d and 7d group was more completely compared with the 24 h group,the surrounding tissue loose degree was obviously improved,the cavitation decreased significantly,blood vessels and glial cells hyperplasia almost the same.3.The expression of BDNF and IL-10:(1)The expression of BDNF in hippocampal CA3 area around the hematoma in cerebral hemorrhage rats in the sham-operated group was very low,the expression of BDNF in the model group and the motor training groups were higher than the sham-operated group(p<0.05);the expression of BDNF in the motor training groups were higher than the model group(p<0.05);there was no significant difference between the 24 h group and the 3d group(p>0.05),but the expression of BDNF in 24 h group and 3d group were higher than 7d group(p<0.05);(2)The expression of IL-10 in hippocampal CA3 area around the hematoma in cerebral hemorrhage rats in the sham-operated group was very low,the expression of IL-10 in the model group and the motor training groups were higher than the sham-operated group(p<0.05);the expression of IL-10 in the motor training groups were higher than the model group(p<0.05);there was no significant difference between the 24 h group and the 7d group(p>0.05),but the expression of IL-10 in 24 h group and 7d group were lowerr than 3d group(p<0.05);4.The expression of bax mRNA、bcl-2 mRNA:(1)The expression of bax mRNA in the model group and the motor training groups were higher than sham-operated group(p<0.05),the model groups increased more obviously(p<0.05).The 7d group had the highest expression of bax mRNA in the motor training groups(p<0.05),and there was no significant difference between 24 h group and 7d group(p>0.05).(2)The expression of bcl-2 mRNA in the model group and the motor training groups were higher than sham-operated group(p<0.05),the motor training groups increased more obviously(p<0.05).The 3d group had the highest expression of bcl-2 mRNA in the motor training groups,the second was the 24 h group,and the last was 7d group(p<0.05).(3)bcl-2 mRNA /bax mRNA:the bcl-2 mRNA /bax mRNA ratio of bcl-2 mRNA /bax mRNA was higher than sham-operated group and model group,all have significant difference(p<0.05),and there is no significant difference between sham-operated group and model group(p>0.05);The 3d group had the highest bcl-2 mRNA /bax mRNA ratio in the motor training groups,the second was the 24 h group,and the last was 7d group,all have significant difference(p<0.05).Conclusion:1.the collagenase injection method is a good choice to make the model of experimental cerebral hemorrhage in rats.2.Motor training can effectively improve the cognitive functions of cerebral hemorrhage in rats,that beginning to motor training 3 days after cerebral hemorrhage has the most beneficial on cognitive function;3.Motor training could promote the expression of BDNF、IL-10 and bcl-2 mRNA,reduce the expression of bax mRNA in hippocampal CA3 area around the hematoma in cerebral hemorrhage rats,to inhibit neuronal apoptosis by anti-inflammatory,this kind of change may be one of the mechanism of motor training to improve cognitive function.