The Effect Of Neuroprotection Of Different Transplanting Time Of Human Umbilical Cord Blood Mononuclear Cells On The Newborn Rat With Hypoxic Ischemic Brain Damage

Neonatal Hypoxic ischemic encephalopathy(Hypoxic- ischemic encephalopathyy, HIE) refers to the neonatal brain lesions caused by a lack of oxygen or ischemia in the perinatal period, HIE is a common cause which can lead neonatal death and severe neurological dysfunction, including mental retardation retardation, cerebral palsy, visual disorders, epilepsy and other permanent neurological disability. Severely affecting the overall quality of life of children. Pregnant women during pregnancy middle-late strong uterine contractions, placental abruption, and production of oxygen can lead to the fetus intrauterine asphyxia or production. Acute fetal distress can occur in prenatal fetal intrauterine asphyxia, intrapartum anoxia suffocate and respiratory depression asphyxia at any time in the postpartum period, leading to the occurrence of HIE. In full-term newborns, the incidence of HIE was 1 to 3 cases per 1000 newborns, the incidence is higher in premature infants. Children with HIE can cause direct death, the survivors are still can left permanent neurological disability, seriously affect the overall quality of life of children, a heavy burden on individuals, families and society,, the serious influence to our country people’s physical and mental health, the overall national economic development and social stability.So far, the treatment of HIE mainly includes nutrition support treatment in the acute phase of brain cells therapy and postnatal rehabilitation training, but these treatments cannot promote the regeneration of the nerve cells, prevention of the occurrence of neurological sequelae.So, although with rapid development of the perinatology and rehabilitation medicine in recent decades, the mortality and the incidence of cerebral palsy of HIE has no obvious change.In recent years, mesenchymal stem cells(MSCs) transplantation as a new treatment have received wide attention, and also brought bright future in the treatment of HIE.MSCs originate from mesoderm with similar shape to fibroblasts, widely exists in a variety of tissues, such as the bone marrow, umbilical cord blood, adipose body. MSCs are a progenitor cells,they can not only have the potential of self-renewal, and can be also divided into garment for all kinds of tissue cells, Under certain conditions,they can differentiate into a variety of tissues and cells.The broad differentiation potential and low immunogenicity of MSCs make it a hot research topic in the field of medicine and biology in recent years, providing a new method for neonatal HIE, stroke,cerebral palsy, spinal cord injuryand neurodegenerative diseases.Human umbilical Cord Blood Mononuclear Cells(Human Cord Blood Mononuclear Cells, HCMNCs) contains rich hematopoietic stem Cells and mesenchymal stem Cells, etc. Human umbilical cord blood mononuclear cells have many advantages and it is easy to collect, and can be got in the children immediately after childbirth; It has no no trauma for children and is not restricted by ethics. Therefore, HCMNCs is becoming a hot spot in recent research.In recent years, although the study of stem cell transplantation for the treatment of HIE is abundant, but the specific migration time and way remain to illuminate. There is still no common conclusion, especially in terms of the timing of the transplant in domestic and foreign research. The purpose of this study is to research different transplanting time on the long-term effect of neurobehavioral function of rats after HIBD and synaptic ultrastructure changes through the nose transplant of HCMNCs.Therefore, research on the following:The effect of neuroprotection of different transplanting time of human umbilical cord blood mononuclear cells on the newborn rat with hypoxic ischemic brain damage Objective To explore the effect of neurobehavioral function development and brain tissue damage of different transplanting time of human umbilical cord blood mononuclear cells on the newborn rat with hypoxic ischemic brain damage. Method Total of 100 7-day-old neonatal Sprague-Dawley rats were divided into five groups randomly. Modified newborn rat model was combined hypoxic and ischemic brain damage which described by Rice was used. After HIBD 24 h, HIBD+24h HCMNC s groups were injectied by intranasal with 0.5×10 6 HCMNCs( in 50 ul 0.9% Na Cl), HIBD+ 24 h Na Cl groups were injectied by intranasal with the equal Na Cl,after HIBD 72 h, HIBD+ 72 h HCMNCs groups were injectied by intranasal with 0.5×10 6 HCMNCs( in 50 ul 0.9% Na Cl),and HIBD+ 72 h Na Cl groups were injectied by intranasal with the equal Na Cl. early nervous reflex and the Morris water maze were used to evaluate nervous behavioral function,and the brain MRI,score of the gross morphologic appearance and electron microscope to evaluate brain damage recovery. Result There were no difference between HIBD+ 24 h Na Cl groups and HIBD+ 72 h Na Cl groups,P >0.05. Compared with HIBD+ 24 h Na Cl groups and HIBD+ 72 h Na Cl groups, In Morris Water Maze, the HIBD+ 24 h HCMNCs groups and HIBD+72h HCMNCs groups showed the Cliff aversion [(16.93±6.67) vs.(23.51±6.88)、(12.56±5.25) vs.(22.25±5.59)] and and negative geotaxis reflex time[(19.16±5.53) vs.(24.84±5.45)、(14.76±5.86) vs.(23.55±5.61)]on postnatal 14 days were significantly reduced, P<0.05;The escape latency was shorter[(26.34±5.89) vs.(32.82±8.73)、(21.32±8.22) vs.(34.86±7.67)],the swimming distance was shorter[(12.73±3.15) vs.(15.41±2.72)、(10.76±3.02) vs.(14.93±3.63)],P<0.05; The damage of brain volume [(32.22±8.10) vs.(39.49±11.88)、(26.02±6.28) vs.(38.68±10.01)]was reduced, P<0.05; The score of the gross morphologic appearance was reduced[(1.89±1.04) vs(1.61±0.92)、(2.61±1.62) vs.(2.74±1.42)];The synaptic cleft was more narrowed [(21.40±2.05) vs.(22.68±2.24)、(20.14±1.52) vs.(22.65±2.23)],P<0.05.Compared with control groups, All the results of groups ware significantly increased except of the synaptic cleft in HIBD+72h HCMNCs groups. Conclusion Human UCBMC intranasal transplantation significantly promoted recovery of injured brain cells and neurobehavioral function development especially in HIBD+72h HCMNCs groups.