| Objective: To establish an animal model of white matter injury(WMD)in neonatal rats,and to investigate the effects of human umbilical cord mesenchymal stem cells(HUC-MSCs)transplantation through nasal mucosa or lateral ventricle within 24 hours after modeling.Methods: 80 2-day-old(P2d)SD rats were randomly divided into WMD group(n = 56)and control group(n = 24).Control group: no intervention.The white matter injury model was established in the WMD group.At 7 days after modeling,8 SD rats were randomly selected from the control group and the WMD group,and TTC staining was performed to calculate the ischemic necrosis area of brain tissue and verify the model.The WMD group was randomly divided into a model group,a nasal mucosa transplantation group,and a lateral ventricle transplantation group according to different treatments,with 16 rats in each group.The model group did not receive any intervention after modeling.In the nasal mucosa transplantation group,HUC-MSCs were transplanted through the nose at 24 hours after modeling.HUC-MSCs were transplanted into the lateral ventricle 24 hours after modeling.At different time points after modeling,righting reflex test,negative geotaxis test,suspension test and Morris water maze test were performed to observe the changes of movement and memory of SD rats.On the 7th and 14 th day after modeling,8 rats from each group were randomly selected for HE staining to observe the pathological changes of the periventricular tissue.TUNEL assay was used to observe the apoptosis of nerve cells on the 14 th day after modeling and the number of apoptosis cells was calculated.Results: 1)TTC staining showed that the brain injury area of the model group was significantly larger than that of the control group,and the difference was statistically significant(P < 0.05),indicating that the neonatal WMD model was successfully established.2)In the short-term behavioral test,compared with the model group,the nasal mucosa transplantation group and lateral ventricle transplantation group had significantly shorter time of righting reflex and negative geotaxis test and significantly longer time of suspension test(P < 0.05 or P < 0.01).Morris water maze test showed that compared with the model group,the time of stay in the target quadrant of the nasal mucosa transplantation group and the lateral ventricle transplantation group was significantly increased,and the number of crossing the platform of the lateral ventricle transplantation group was significantly higher than that of the nasal mucosa transplantation group(P<0.05),suggesting that the learning and memory abilities of SD rats in this group were significantly improved.3)After HE staining,the brain tissue of the model group showed obvious interstitial edema,obvious widening of some small blood vessel spaces,and patchy cell necrosis areas,especially in the left brain.Compared with the model group,the lateral ventricle transplantation group and the nasal mucosa transplantation group showed relatively regular cell arrangement and smaller apoptotic areas.4)TUNEL assay showed that the number of apoptotic cells in nasal mucosa transplantation group and lateral ventricle transplantation group was less than that in model group(P<0.05).There was no significant difference in the number of apoptotic cells between the lateral ventricle transplantation group and the nasal mucosa transplantation group(P> 05),indicating that HUC-MSCs transplantation through different routes can reduce cell apoptosis in brain tissue,and there is no significant difference in the degree of reducing apoptosis between nasal mucosa transplantation and lateral ventricle transplantation.Conclusion: Both nasal and lateral ventricular transplantation of HUC-MSCs can play a neuroprotective role,improve neurobehavioral function and reduce brain tissue cell apoptosis,and the effect of lateral ventricular transplantation on improving behavior and cognitive ability in SD rats with WMD is stronger than that of nasal mucosal transplantation. |
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