Erythropoietin Improves Place Learning in an 8-Arm Radial Maze in Fimbria-Fornix Transected Rats

Abstract

Systemically administered human recombinant erythropoietin (EPO) may have the potential to reduce the cognitive and behavioral symptoms of mechanical brain injury. In a series of studies, we address this possibility. We previously found that EPO given to fimbriafornix transected rats at the moment of injury could substantially improve the posttraumatic acquisition of an allocentric place learning task when such a task is administered in a water maze. Due to the clinical importance of such results, it is important to scrutinize whether the therapeutic effect of EPO is specific to the experimental setup of our original experiments or generalizes across test situations. Consequently, here we studied the effects of similarly administered EPO in fimbria-fornix transected and control operated rats, respectively, evaluating the posttraumatic behavioral/cognitive abilities in an allocentric place learning task administered in an 8-arm radial maze. The administration of EPO to the hippocampally injured rats was associated with a virtually complete elimination of the otherwise severe behavioral impairment caused by fimbria-fornix transection. In contrast, EPO had no detectable effect on the task acquisition of non-lesioned animals. The results of the present study confirm our previous demonstration of EPO's ability to reduce or eliminate the behavioral/cognitive consequences of mechanical injury to the hippocampus, while adding the important observation that such a therapeutic effect is not restricted to the specific experimental setup previously studied.