The Therapeutic Effects Of Different Route Of MSCs Transplantations In Cerebral Resuscitation After Cardiac Arrest In The Rats

Cardiovascular disease is the world’s leading cause of death and can cause cardiacarrest which is one of the important factors threatening people’s health. Thus it is aserious health issue that cannot be ignored. Although out-of-hospital cardiac arrestpatients can finally restore spontaneous circulation, they will have dysfunctionalneurologic outcome as neuronal apoptosis has been triggered especially in the morevulnerable parts of the brain due to hypoxia-ischemia after cardiac arrest and CPR.Therefore, reducing neuronal damage and recovering neurologic function by effectivecerebral resuscitation is now an important area and issue in Emergency Medicineresearch.Mesenchymal stem cells (MSCs) are stromal cells found in a wide range of adulttissues including the bone marrow, which are distinct from the hematopoietic lineage.They are multipotent cells which have the capacity for self renewal and todifferentiate into derivatives depending on their specific source tissue. Studies showthat MSCs have the capacity to differentiate into Neural-like cells or a neuronal-likephenotype during in vitro culture. In models of middle cerebral artery occlusion(MCAO), the transplanted MSCs can migrate to the brain damaged tissue and savethe neurons in ischemic penumbra, induce MSC-mediated neural functional recovery.At present, only a few researches have done in MSCs transplantation for treatingglobal cerebral ischemia which specially due to cardiac arrest. However, all of themhave indicated that MSCs transplantation significantly improve neurological outcome. In this study,4’,6-diamidino-2-phenylindole (DAPI) labeled mesenchymal stemcells are transplanted in the rats by directly stereotaxic injection into lateral cerebralventricle, intra-carotid administration and femoral venous infusion. Then, observe themigration features of the MCSs in the ventricle and the effects they contribute incerebral edema, neuronal apoptosis and function. Investigate the therapeutic effects ofdifferent route of MSCs transplantations in cerebral resuscitation after cardiac arrestin the rats.ObjectivesTransplant MSCs inside the brain of the rats after CPR by three different ways:directly stereotaxic injection into lateral cerebral ventricle, intra-carotidadministration and femoral venous infusion. Compare the three different ways oftransplantation by observing the effects of MSCs in repairing neurologic functionafter the global cerebral hypoxia-ischemia in the rats, then find out the optimum wayof transplanting MSCs.Material and MethodsEstablish the global cerebral ischemia after cardiac arrest induced by asphyxia inrats model. Thirty-two Sprague-Dawley rats with body weight of300-400wererandomly divided into four groups: control group in which only CPR have beenapplied, group A is transplantation of MSCs by intra-carotid administration, group Vis transplantation of MSCs by femoral venous infusion, Group LV is transplantationof MSCs by directly stereotaxic injection into lateral cerebral ventricle. One hour afterROSC, MSCs will be transplanted in group A, V and LV, the total number of MSCstransplanted for each group was approximately1×106. The distribution and migrationof MSCs in the brain were observed and the neurological status after ROSC wasassessed by neurological deficit scale scores (NDSS) and adhesive tape removal test.Pathological examination of hippocampus and temporal cortex, brain water content,Serum levels of S100B were recorded in3d and7d after ROSC. Results1. In3d after ROSC, the labeled MSCs were observed in group A, V and LV byfluorescence microscopy, they were mainly distributed in hippocampus and temporalcortex. Group LV had more number of MSCs than group A and V (P<0.05), whilethere was no statistically significant difference between group A and group V.2. There was no statistically significant difference in NDSS among all four groupsin the first day after ROSC. However, NDSS were higher in the three transplantationgroups than the control group (P<0.05) in3d and7d after ROSC. And NDSS washigher in Group LV than group A and group V (P<0.05), while there was nostatistically significant difference between group A and group V.3. The time of adhesive tape removal test in the three transplantation groups wasshorter than the control group (P<0.05), and group LV need shorter time than group Aand group V (P<0.05), while there was no statistically significant difference betweengroup A and group V.4. Neuronal damages could be found in hippocampus and temporal cortex of the ratsafter resuscitation. The number of neurons damaged of hippocampus and temporalcortex in the transplantation groups was much lesser than in the control group(P<0.01), and group LV was lesser than group A and group V (P<0.01), while therewas no statistically significant difference between group A and group V.5. In brain water content, the transplantation groups were lower than the controlgroup (P<0.01), group LV was lower than group A and group V (P<0.05), while therewas no statistically significant difference between group A and group V in any timeintervals.6. Serum level of S100B of the transplantation groups was lower than the controlgroup in every time intervals. In3d after ROSC, the level of S100B of group LV waslower than group A and group V (P<0.05), while there was no statistically significant difference between group A and group V. In7d after ROSC, there was no statisticallysignificant difference among group LV, group A and group V.Conclusion1. MSCs could migrate inside the brain tissue after transplantation by directlystereotaxic injection into lateral cerebral ventricle or intra-carotid administration orfemoral venous infusion, MSCs mainly distributed in hippocampus and temporalcortex where the neurons were very vulnerable during global cerebral ischemia.2. MSCs transplantation could improve neurologic function significantly after CPRin rat model.3. Among these three different ways of MSCs transplantation, stereotaxic injectioninto lateral cerebral ventricle could make the vulnerable parts of the brain duringglobal cerebral ischemia had the highest concentration of MSCs, and the bestneurological outcome.