Effects of erythropoietin on posttraumatic place learning in fimbria-fornix transected rats after a 30-day postoperative pause.

Human recombinant erythropoietin (EPO) has been shown to exert neuroprotective effects following both vascular and mechanical brain injury. Previously, we showed that behavioral symptoms associated with mechanical lesions of the hippocampus are nearly abolished due to EPO treatment. In these studies, the EPO administration took place simultaneously with the infliction of brain injury and the rehabilitation training started 6-7 days postoperatively. In the present study, we tested whether the therapeutic effect of EPO on the acquisition of an allocentric eight-arm radial maze spatial task also manifests itself if the rehabilitative training is postponed. Postoperatively, the animals were left without any specific stimulation for 30 days. The current results show an improved behavioral performance of the EPO-treated lesioned group relative to the saline-treated lesioned group, and confirm EPO's therapeutic effect even in case of postponed rehabilitation. However, compared to the control group, the EPO-treated lesioned group demonstrated an impaired task acquisition. All subjects eventually recovered functionally. Subsequently, the animals were given behavioral challenges during which the cue constellation in the room was changed. The challenges revealed that, although the EPO-treated lesion group had achieved the same level of task proficiency as the control group, the cognitive mechanisms mediating the task performance in the EPO-treated lesion group (as well as in the saline-treated lesion group) were dissimilar from those mediating the task in the control group. Both the EPO-treated and the saline-treated lesion group demonstrated an increased dependency on the original cue configuration.