Neurorestorative effect of erythropoietin and environmental enrichment in the early stage of stroke recovery

Abstract

The purpose of this study was to investigate whether erythropoietin (EPO) and environmental enrichment (EE) after hypoxic ischemic insult can prevent brain damage, improve neuronal plasticity, and reduce sensorimotor deficits and whether the combination of EPO and EE has a synergistic effect. Sixty Sprague-Dawley rats were used for this study. The rats were divided into three groups: middle cerebral artery occlusion (MCAO) without treatment, MACO + EPO, and MCAO + EPO + EE. For the behavior test, the foot-fault test and measurement of the crossing time in the parallel bars were used. Infarct volume measurement, Neuronal nuclei (NeuN) immunohistochemistry, western blot of the synaptophysin (SYP), and Growth-Associated protein 43 (GAP-43) were used. On postoperative days (POD) at 1 week and 4 weeks, group of EPO and EE increased the recovery as seen in the behavior test. The infarct volume of the EPO group was 32.4%, the EPO + EE group was 28.5%, and the control group was 44.0% on POD 4 weeks. The SYP and GAP-43 expression showed an increase in the EPO and EPO + EE group compared with the MCAO group. EPO and EPO + EE treatment creates a neurorestorative effect, improved neural plasticity, and reduced sensorimotor deficits. But the synergistic effect of the combination of EPO and EE was significantly not proved. In the results of this study, we suggest that EPO and EE treatment may offer a neruorestoration, which can improve the functional brain disturbance of stroke patients.