Therapeutic effects of various methods of MSC transplantation on cerebral resuscitation following cardiac arrest in rats.

Abstract

In the present study, mesenchymal stem cells (MSCs) were transplanted into the brain of rats following cardiopulmonary resuscitation (CPR) by three different methods: Direct stereotaxic injection into the lateral cerebral ventricle (LV), intra-carotid administration (A), and femoral venous infusion (V). The three different methods were compared by observing the effects of MSCs on neurological function following global cerebral hypoxia-ischemia, in order to determine the optimum method for MSC transplantation. MSCs were transplanted in groups A, V and LV following the restoration of spontaneous circulation. Neurological deficit scale scores were higher in the transplantation groups, as compared with the control group. Neuronal damage, brain water content and serum levels of S100 calcium-binding protein B were reduced in the hippo-campus and temporal cortex of the transplantation groups, as compared with the control rats following resuscitation. MSCs were able to migrate inside the brain tissue following transplantation, and were predominantly distributed in the hippocampus and temporal cortex where the neurons were vulnerable during global cerebral ischemia. These results suggest that transplantation of MSCs may notably improve neurological function following CPR in a rat model. Of the three different methods of MSC transplantation tested in the present study, LV induced the highest concentration of MSCs in brain areas vulnerable to global cerebral ischemia, and therefore, produced the best neurological outcome.