A novel neurotrophic therapeutic strategy for experimental stroke

Abstract

Human chorionic gonadotropin (hCG) promotes proliferation of endogenous neural stem cells, and erythropoietin (EPO) promotes differentiation of these cells into neural stem cells. The current study examined effects of sequential administration of these two compounds, initiated 24 h after stroke. At that time, rats were randomized into four treatment groups: hCG+EPO (3 IM doses hCG over 5 days, followed by 3 IV doses EPO over 3 days), hCG+Saline using the same schedule, Saline+EPO using the same schedule, or neither drug (Saline+Saline). The primary endpoint was the composite neurological score, measured 11 times, from 1 h until 12 weeks post-insult. The neurological score was different across treatment groups (p<0.03). Pairwise testing of groups found that the hCG+EPO group had significantly better behavior at 6/10 post-stroke time points as compared to Saline+Saline. The differences observed when comparing the two-drug group with placebo were less apparent when comparing either of the one-drug groups with placebo. The two one-drug treatment arms did not significantly differ at any time point. Treatment with hCG+EPO significantly reduced total lesion volume by 82-89% compared to the other three treatment groups. The current therapeutic strategy improved behavioral outcome and reduced lesion volume with a time window of 24 h after the onset of stroke. The results from these experiments provide new insight into the effects of these two growth factors on stroke in rats, and could suggest a potential for translation into human stroke studies.