Chinese Medicine And Rehabilitation Assessment Of Children With Cerebral Palsy And Related Syndromes In Molecular Biology Mechanism,

Cerebral palsy(CP) is most commonly seen inborn brain disorder syndrome of childen or happened in children's perinatal period.The main symptom of the CP is centrocinesia disorder and abnormal gesture.It is often accompanied by mental retardation and vision disorder,acoustic disorder,speech disorder and epilepsy. The distinctive curative effect of TCM therapy is always be interested by the researchers.It is the most important point of the TCM theory system that determination of treatment based on differentiation of symptoms and signs. Therefore,we start from the theoretical research,and through clinical and experimental studies on the characteristics of Chinese syndromes and the mechanisms of molecular biology research about the motor dysfunction caused by CP,in order to give better play to the Chinese medicine treatment,and lay the foundation for Differential Treatment of the motor dysfunction of CP.1.Theoretical StudyWe study the motor dysfunction caused by CP based on the theory of endogenous liver wind of TCM.The abnormal gesture and muscular tension and involuntary movement are expressions of the liver wind,which is caused by asthenia of both the spleen and kidney.Modern medicine discovers,the exitotoxicity by the Glu is one of the important neurological mechanism of the CP. The dynamic balance of these two transmitters relates to the normal function of the NS,which is concerned with the function of liver of TCM.We can treat the motor dysfunction of CP from invigorate the kidney and the spleen.Through the therapy of "nourishing the kidney is adopted to treat yin deficiency in the liver and kidney" and "reinforcing the spleen to restrain the abnormal function of the liver", we can extinguish the liver wind and elevate the motor function of the CP.2 Clinical StudiesThe main symptom of the CP is centrocinesia disorder and abnormal gesture. It is often accompanied by mental retardation and vision disorder,acoustic disorder,speech disorder and epilepsy.In this part we observed the Chinese Syndromes of CP,combining with the evaluation of the gross motor function,the intelligence quotient,and the gait analysis,and conducted a relevance study between the Chinese syndromes and these evaluations.The key elements are as follows:2.1 The study on the characteristics of Chinese Syndromes of the children of CPWe selected 90 children of CP,whose age were from 4 to 12 years old.We found that deficiency syndrome accompanied with excess syndrome were always appeared in the children of CP.we concluded the ten of the most Chinese Syndromes appeared.The deficient syndromes were deficiency of kidney-essence, deficiency of spleen-Qi,deficiency of kidney-yin,deficiency of lung-QI,and deficiency of liver-Yin,the sthenia syndromes were blood stasis,gastric heat, stagnation of qi of the stomach intestine and mental confusion due to phlegm.The tendency is the frequency of the deficiency syndromes was higher,and accompanied with the sthenia syndromes,such as phlegm,blood stasis,moist,heat, stagnation of the qi,and so on.2.2 Related research on gross motor function evaluation and Chinese syndromes of CPWe selected 90 children of CP,whose age were from 4 to 12 years old and evaluated them with the GMFM scale and GMFCS scale.The result showed there is no obvious difference between the children of the spastic cerebral palsy and athetosis cerebral palsy in GMFM score and GMFCS score.But through the deeper research,we found the motor function of lower limb of athetosis CP is better than spastic CP,and the motor function of upper limb of spastic CP is better than athetosis CP.There is negative correlation between the gross motor function and the Chinese syndrome,the syndrome of deficiency of kidney-essence, deficiency of spleen-Qi,endogenous liver wind and deficiency of kidney-yin were intimate with the gross motor functional disturbance of CP.2.3 A study of the gait character of spastic cerebral palsyForty children with spastic cerebral palsy and forty healthy children with normal walking ability were involved in this research.Footscan 7 gait analysis system was used to measure foot initial touchdown part,the ratio of different part touchdown phase to single supporting phase,the degree of strephenopodia and strephexopodia in different part.Two groups' characteristic parameters were analyzed by statistics method.Differences were found in foot first touchdown part between two groups.The phenomenon that toes or metatarsus or whole foot first touch the earth was found in children with spastic cerebral palsy.The ratio of anterior foot and middle foot touchdown phase to single supporting phase were higher than normal children.In spastic cerebral palsy group the phenomenon of strephexopodia was more serious than strephenopodia during anterior foot touchdown phase.Conclusion:Lots of children with spastic cerebral palsy were suffering longtime compression pain and strephexopodia with anterior foot,active rectification must be perform during rehabilitation care.2.4 The study of the gait character and the TCM mechanism of which in the children of CPWe selected 50 children of CP and 40 normal children.The gait analysis was carried out and the research of the linear correlation between the gait underlying parameters and The Chinese syndrome was progressed.We found that,in the children of CP,the step length is shorter,step frequency and gait speed is lower than the normal children.The excursion frequency of the resultant centre from planta pressure curve is higher,the included angle between the foot axis and the proceed direction is bigger than the normal children.These were caused by the abnormal gesture and disability of the balance in children of CP.We also found that the Chinese syndromes of deficiency of kidney-essence,deficiency of kidney-yin,deficiency of spleen-qi,mental confusion due to phlegm,blood stasis can cause the balance founction of the gait descend.Through the analysis of the mechanism,we believe asthenia of both the spleen and kidney is the basic reason which caused endogenous liver wind,and the dysfunction of these three organs can caused the blood stasis and phlegmatic hygrosis.Under the effect of all these Chinese syndrome,the balance of the body was broken-down,and abnormal gaits were appeared.2.5 Related research on intellectual evaluation,gross motor function evaluation and Chinese syndromes of CPWe selected 90 children of CP,whose age were from 4 to 12 years old,and evaluated their intelligence by WIPSI.The result showed that the IQ of the athetosis CP is better than the spastic CP.There is positive correlation between the IQ and the GMFCS score of the the spastic CP,and no correlation of the athetosis CP.We also found that the children who have the syndromes of blood stasis, phlegmatic hygrosis and mental confusion due to phlegm always displaied as midrange or serious dysgnosia.3.Experimental StudiesIntrauterine infection is one of the most important high risk factor causing CP, which can make fetal distress in uterus and lead to HIE,and CP is the appearance and continuator following fetal distress in uterus and HIE.In this part,We evaluated the neuroethology changes through establishing animal models of CP. We use immunohistochemistry and fluorescence quantitative PCR methods to observe the changes of rats Glu/GABA receptors and mRNA in Cortex of frontal lobe,and use different Chinese herbs to intervene for animal models in order to investigate their roles in medicine mechanisms.Main content and the results are as follows:3.1 Establishing rat model of sports fatigueIn this study,we established CP animal model by LPS peritoneal injection leading to intrauterine infection.The neuroethology evaluations were proceeded on the neonate rat.The evaluation included voluntary movement evaluation, muscular tension evaluation,muscle power evaluation,gesture evaluation and involuntary movement evaluation,these were looked on as the sieve standard of the CP animal model.The result showed,the sieved CP rats were appeared as reaction clumsy,voluntary movement decreasing,abnormal gesture and motor stability decreasing,and some of the CP rats occurred thrill and hyperspasmia. These appearances were consistent with the neuroethological characters of CP.We proceeded HE drum dyeing on the brain section of the CP rats,the result showed that the brain damage were consistent with the pathological changes of CP.3.2 Assessing the ethology changes of the CP rats under the effect of the Chinese herb medicines intervening on.In this part we use neuroethological examination,which included slopes reflect experiment,suspension experiment,Tarlov score,Ashworth score,to observe the changes of the motor function of the CP rats and the effect of the Chinese herb medicines "Large Wind-Expelling Decoction" and "Bu Zhong Yi Qi soup".The result showed that as the rats of "Bu Zhong Yi Qi soup" group,whose voluntary movement score and gesture score and animal force increasing, muscular tension descending,and still had involuntary movements.As the rats of "Large Wind-Expelling Decoction" group,whose voluntary movement score and gesture score and animal force increasing,muscular tension descending,and had no involuntary movements.We can make the conclusion through the therapy of "reinforce the spleen to restrain the abnormal function of the liver",the agonist muscle force can be elevated,and oppose the antagonistic muscle,and improve the gesture or voluntary movement.Through the therapy of "nourishing the kidney is adopted to treat yin deficiency in the liver and kidney",the abnormal state of muscle spasm and involuntary movement can be improved. 3.3 changes of expression of Glu/GABA receptors and the mRNA in the Cortex of frontal Iobe of the CP ratsThe imbalance of the transmitters Glu/GABA was one of the important factor which lead to exitotoxicity in CNS.In this part,we selected Glu receptor NMDAR1,NMDAR2B and GABA receptor GABABR1 as the target,through immunohistochemistry and fluorescence quantitative PCR methods,we observed the changes of rats GLU/GABA receptors and mRNA in Cortex of frontal lobe, and analysised the effect of Chinese herb medicines.The result showed,compared with normal control group,the CP model group's NR1,NR2B receptors upgraded and GABABR1 receptor descended and the mRNA of NR1,NR2B,GABABR1 receptors were all up-regulation.Both"Large Wind-Expelling Decoction" and "Bu Zhong Yi Qi soup" could down regulate expression of the NMDA receptors from the level of proteinum and gene."Large Wind-Expelling Decoction" could up-regulate expression of the GABA receptors from proteinum level and gene level.4.SummaryAccording to the literatures study,we research on syndrome characteristics and mechanisms of molecular biology of the motor dysfunction caused by CP.In theoretical study,we start from the etiology,pathogenesis through the in-depth excavation of the liver's function,and explain the motor dysfunction of CP from the theory of endogenous liver wind.In clinical studies,we observed Chinese syndrome of CP,combining with rehabilitation assessments,we studied the relevance of Chinese syndromes and gross motor functions,intelligence quotient, gait characters.In the experimental studies,we established rat model of CP,and assessed neuroethological ability of the animal model.Then we use immunohistochemistry and fluorescence quantitative PCR methods systematically observaed the changes of subunit receptors of Glu/GABA in the expression of mRNA and protein levels.At the same time,we use different Chinese herbs intervening animal models in order to investigate the role of drug mechanisms and the model's characteristics of Chinese Syndrome.All the studies give a good play to the characteristics of Chinese medicine treatment and lay the foundation for studying differential treatment of motor dysfunction of CP.