Transplantation of bone marrow mesenchymal stem cells promotes learning and memory functional recovery and reduces hippocampal damage in rats with alcohol-associated dementia.

Abstract

Chronic ethanol exposure leads to permanent damage to the central nervous system and produces cognitive deficits such as learning and memory impairment. The present study was designed to explore the therapeutic effect of bone marrow mesenchymal stem cells (BMMSCs) on a rat model of alcohol-associated dementia (AAD). Bone marrow mesenchymal stem cells were prelabeled with 4',6-diamidino-2-phenylindole and directly transplanted into the hippocampus of AAD rats, an important site of alcohol effects that lead to cognitive deficits. The therapeutic effect of BMMSCs was evaluated by observing Morris water maze behavior, hippocampus morphology, and neuronal apoptosis. Still, the activities of antioxidant enzymes including total superoxide dismutase and glutathione peroxidase in rat hippocampus were measured, and the expression of brain-derived neurotrophic factor in rat hippocampus was also detected by the method of immunohistochemistry. Transplantation of BMMSCs directly into the hippocampus significantly improved the learning and memory function of AAD rats and prevented alcohol-induced hippocampal damages. Moreover, BMMSC transplantation inhibited neuron cell apoptosis and increased the activity of total superoxide dismutase in the hippocampus. Moreover, transplantation of BMMSCs improved the protein level of brain-derived neurotrophic factor in the hippocampus in parallel with behavioral and histologic recovery for AAD rats. The findings indicate that the functional benefit observed in the BMMSC-grafted AAD rats is caused by the reduction of oxidative damage and the production of trophic factors by BMMSCs. Bone marrow mesenchymal stem-cell transplantation may be a useful and feasible method for clinical treatment of alcohol-induced brain injuries.