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Review
. 2014 Oct;51(4):481-8.
doi: 10.1016/j.pediatrneurol.2014.06.008. Epub 2014 Jun 24.

Erythropoietin: emerging role of erythropoietin in neonatal neuroprotection

Vijayeta Rangarajan  1 , Sandra E Juul  2
Affiliations
Review

Erythropoietin: emerging role of erythropoietin in neonatal neuroprotection

Vijayeta Rangarajan et al. Pediatr Neurol. 2014 Oct.

Abstract

Background: In the last two decades, there has been considerable evolution in understanding the role of erythropoietin in neuroprotection. Erythropoietin has both paracrine and autocrine functions in the brain. Erythropoietin binding results in neurogenesis, oligodendrogenesis, and angiogenesis. Erythropoietin and its receptor are upregulated by exposure to hypoxia and proinflammatory cytokines after brain injury. While erythropoietin aids in recovery of locally injured neuronal cells, it provides negative feedback to glial cells in the penumbra, thereby limiting extension of injury. This forms the rationale for use of recombinant erythropoietin and erythropoietin mimetics in neonatal and adult injury models of stroke, traumatic brain injury, spinal cord injury, intracerebral hemorrhage, and neonatal hypoxic ischemia.

Method: Review of published literature (Pubmed, Medline, and Google scholar).

Results: Preclinical neuroprotective data are reviewed, and the rationale for proceeding to clinical trials is discussed. Results from phase I/II trials are presented, as are updates on ongoing and upcoming clinical trials of erythropoietin neuroprotection in neonatal populations.

Conclusions: The scientific rationale and preclinical data for erythropoietin neuroprotection are promising. Phase II and III clinical trials are currently in process to determine the safety and efficacy of neuroprotective dosing of erythropoietin for extreme prematurity and hypoxic-ischemic encephalopathy in neonates.

Keywords: brain; cytokine; erythropoietin; hypoxic-ischemic encephalopathy; neuroprotection; prematurity.

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Figures

Figure 1
Figure 1
Neuroprotective effects of Epo in brain following hypoxic-ischemic injury. Brain injury increases local astrogliosis and microglial cell activation. Astrocytes produce Epo, which enhances neurogenesis and oligodendrogenesis, while decreasing local inflammation. It also stimulates angiogenesis through local endothelial cells.
See this image and copyright information in PMC

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