Erythropoietin EPO

EPO is considered one of the most promising stroke therapeutic agents. The mechanistic pathways by which EPO provides its neuroprotective effects remain to be fully elucidated; however, it is hypothesized that they involve an EPO receptor distinct from that activated in erythropoiesis. EPO has pleiotropic effects: it has been shown to cross the blood-brain barrier, protect against ischemia-reperfusion injury by inhibiting apoptosis and hypoxia, and enhance angiogenesis. When directly administered into the brain, EPO reduces neurologic dysfunction in rodent models of stroke, and reduces infarct volumes by 75% when administered systemically up to 3 hours after arterial occlusion. In a small (n = 40), randomized, double-blind, placebo-controlled trial of EPO administered intravenously between 2 hours and 40 minutes and 7 hours and 55 minutes after stroke symptom onset, the agent was found to be safe, and treatment correlated with a reduction in NIHSS

score between baseline and day 30 after stroke. Furthermore, there was a strong trend toward functional improvement as measured by mRS and BI (Fig. 5.2) and infarct reduction on brain MRI, as well as a significant reduction in the neuronal injury marker S100beta in the EPO arm 30 days after infarct.

FIGURE 5.2 Clinical outcome of patients in the double-blind, proof-of-concept trial evaluating EPO in acute stroke. (a) Barthel Index (rhEPO vs. placebo, p < 0.05). (b) Modified Rankin Scale (rhEPO vs. placebo, p < 0.07) on day 30. Dead patients received the worst possible score. Evolution of lesion size of patients in the efficacy trial of Albumin in acute stroke. ((a-1) and DWI and (a-2) FLAIR.) (Reprinted with permission from reference 50.)

FIGURE 5.2 Clinical outcome of patients in the double-blind, proof-of-concept trial evaluating EPO in acute stroke. (a) Barthel Index (rhEPO vs. placebo, p < 0.05). (b) Modified Rankin Scale (rhEPO vs. placebo, p < 0.07) on day 30. Dead patients received the worst possible score. Evolution of lesion size of patients in the efficacy trial of Albumin in acute stroke. ((a-1) and DWI and (a-2) FLAIR.) (Reprinted with permission from reference 50.)

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