Long-term results of enriched environment and erythropoietin after hypobaric hypoxia in rats.

After global cerebral hypoxia, many patients are severely disabled even after intensive neurorehabilitation. Secondary mechanisms of brain injury as a result of biochemical and physiological events occur within a period of hours to months, and provide a window of opportunity for therapeutic intervention. Erythropoietin (EPO) has been shown to be neuroprotective in the brain subjected to a variety of injuries. Fifty-nine 3-month-old male Wistar rats were randomly distributed to experimental groups with respect to the housing (enriched environment - EE, standard housing - SH), to hypoxia exposure, and to EPO treatment. An acute mountain sickness model was used as a hypobaric hypoxia simulating an altitude of 8000 m. One half of the animals received erythropoietin injections, while the others were injected saline. Spatial memory was tested in a Morris water maze (MWM). The escape latency and the path length were measured. Better spatial learning in MWM was only seen in the group that received erythropoietin together with enriched environment. EPO administration itself had no influence on spatial memory. The results were very similar for both latencies and path lengths. These results support the idea that after brain injuries, the recovery can be potentiated by EPO administration combined with neurorehabilitation.