Expression And Significance Of Neurotrophic Factors In The Therapy Of Bone Marrow Mesenchymal Stem Cells To Newborn Rats With Severe Hypoxic Ischemic Brain Damage

Objective:To study the expression changes of nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) and neurotrophin-3(NT-3), glia cell line-derived neurotrophic factor (GDNF) in the process of bone marrow mesenchymal stem cells (BM-MSCs) therapy to newborn rats with severe hypoxic ischemic brain damage and relationship with improvement of neurofunction. To compare the impact of umbilical cord-derived mesenchymal stem cell (MSC) transplantation on the motor functions of identical twins with cerebral palsy (CP) and to explore the correlation between the efficacy and hereditary factorsMethods:The rat models of severe hypoxic ischemic brain damage through the right common carotid artery ligation+oxygen deficit(number=60)were divided into stem cell treatment group(MSC group, number=20), the operation control group(NS group, number=20)and blank control group(BC group, number=20) randomly.We transplanted BM-MSCs cultured and amplified in vitro into cerebrospinal fluid of model rats through cisterna magna.To assess the rats, movement with modified Neurological Severity Scores (mNSS) in3day,7day,14day and21day after transplantation.NS group used the same volume of normal saline instead of BM-MSCs and mNSS evaluation time and method is the same with MSC group.BC group established the model with no transplantation and mNSS evaluation time and method is the same with MSC group.Examine the expression of NGF, BDNF, NT-3and GDNF collected from rats, cerebrospinal fluid in3day,7day,14day and21day after transplantation.Results:There is significant difference in mNSS scores of MSC group and NS group in7day,14day and21day after transplantation(P<0.05). And BC group has a variation only in21day after transplantation(P<0.05).And there is apparent increase in the expression of neurotrophic factors of MSC group in3day,7day,14day and21day after transplantation by cerebrospinal fluid detection(P<0.05). Eight pairs (16individuals) of identical twins with CP were recruited and received allogenic umbilical cord-derived MSC transplantation by subarachnoid injection. The gross motor function measure (GMFM) and the fine motor function measure (FMFM) were performed before and one and six months after the treatment to compare the results of individuals before and after the therapy.Conclusion:BM-MSCs can promote recovery of neurological function in brain injury rats. NGF、NT-3、BDNF and GDNF play an important role in the process of the recovery of neural function,but the specific mechanism needs further research, motor function improvements in the GMFM between identical twins were closely correlated, but improvements between twin pairs were not correlated. We hypothesized that hereditary factors contribute to the mechanisms of umbilical cord-derived MSC transplantation in the motor function improvement in children with CP.