Delayed Repeated Injections of Erythropoietin Improve Neurobehavioural Deficits Caused By Ischemic Stroke

Abstract

Background and purpose: This study was undertaken to reveal the effects of delayed and repeated injection of erythropoietin(EPO) on neurobehavioural deficits caused by ischemic stroke.

Methods: Two hundred ischemic stroke model rats were divided into four groups: 1) control(S-S, n=60), 2) single injection(E-S, n=60), 3) repeated injection(E-E, n=40) 4) delayed repeated injection (S-E,n=40) groups. Neurobehavioural functions were assessed for 43 days in 40 rats from each group. To investigate the mechanisms of recombinant human EPO (rhEPO) effects, 20 rats each from the S-S and E-S groups were sacrificed at 22h after the initial injection; all other rats were sacrificed at 43 days.

Results: When compared with the S-S group, neurobehavioural functions were significantly improved in the E-E, E-S, and S-E groups, in that order. The beneficial effects of acute treatment with rhEPO were associated with an increase in survival signals and decreased in infarct volume and death signals. The beneficial effects of delayed repeated treatment with rhEPO were associated with an increase in endogenous neural stem cells.

Conclusions: These findings suggest that delayed repeated treatment with rhEPO has beneficial effects in ischemic stroke, although acute treatment with rhEPO is much more effective.