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.
Highlights
For most patients with acute ischemic stroke, limited therapeutic options exist beyond 8 h after the onset of stroke
Composite Neurological Scores, the primary behavioral endpoint, varied according to treatment
Contralateral forelimb placing deficits were clearly present at 60 min after middle cerebral artery occlusion (MCAo) in all groups
Summary
For most patients with acute ischemic stroke, limited therapeutic options exist beyond 8 h after the onset of stroke. Human chorionic gonadotropin (hCG), like other neurotrophic factors (Craig et al, 1996; Shingo et al, 2001; Kolb et al, 2007), promotes proliferation of endogenous neural stem cells. The current study builds directly on a prior report by Kolb et al (2007), who found improved behavioral outcome and reduced infarct volume with delayed administration of intraventricular epidermal growth factor followed by EPO (Kolb et al, 2007) in rats with experimental stroke. We decided first to use hCG to promote proliferation and use EPO to promote survival and differentiation of new progenitors This treatment paradigm (hCG followed by EPO) was initiated 24 h after experimental stroke, which has increased human translational potential
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have