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Recent trends in erythropoietin-mediated neuroprotection
Ronald J McPherson1, Sandra E Juul
1Department of Pediatrics, University of Washington, Seattle, WA 98195, USA.
Insights
Erythropoietin shows promise for treating neonatal brain injury and may prevent neurodevelopmental issues like ADHD. Early treatment with recombinant erythropoietin offers neuroprotection against hypoxic-ischemic brain injury.
Area of Science:
- Neuroscience
- Neonatal Medicine
- Pharmacology
Background:
- Neonatal brain injury from extreme prematurity and perinatal asphyxia leads to severe neurodevelopmental deficits.
- Conditions include cerebral palsy, intellectual disability, and attention deficit hyperactivity disorder (ADHD).
- Erythropoietin (EPO) is a cytokine with demonstrated neuroprotective potential.
Purpose of the Study:
- To review the evidence for erythropoietin as a neuroprotectant in neonatal brain injury.
- To explore EPO's potential in preventing or treating ADHD in extremely premature infants.
- To address concerns regarding EPO's impact on retinopathy of prematurity.
Main Methods:
- Systemic administration of high-dose recombinant erythropoietin.
- Analysis of EPO's blood-brain barrier penetration and neuroprotective mechanisms.
- Review of existing literature on EPO's efficacy and safety in neonatal populations.
Main Results:
- Erythropoietin crosses the blood-brain barrier and protects against hypoxic-ischemic brain injury.
- EPO specifically protects dopaminergic neurons, suggesting a role in treating ADHD.
- Evidence supports EPO's promise in reducing neonatal brain injury.
Conclusions:
- Early erythropoietin treatment may reduce or prevent neonatal brain injury and associated neurodevelopmental complications.
- EPO's neuroprotective effects, particularly on dopaminergic neurons, indicate potential for ADHD treatment.
- Further research is needed to balance EPO's benefits against risks like retinopathy of prematurity.
Abstract:
Fifteen years of evidence have established that the cytokine erythropoietin offers promise as a treatment for brain injury. In particular, neonatal brain injury may be reduced or prevented by early treatment with recombinant erythropoietin. Extreme prematurity and perinatal asphyxia are common conditions associated with poor neurodevelopmental outcomes including cerebral palsy, mental retardation, hearing or visual impairment, and attention deficit hyperactivity disorder. When high doses of erythropoietin are administered systemically, a small proportion crosses the blood-brain barrier and can protect against hypoxic-ischemic brain injury. In addition to other protective effects, erythropoietin can specifically protect dopaminergic neurons. Since reduced dopamine neurotransmission contributes to attention deficit hyperactivity disorder, this condition may be amenable to erythropoietin treatment. This review focuses on the potential application of erythropoietin as a neuroprotectant with regard to neurologic complications of extreme prematurity, including attention deficit hyperactivity disorder. Recent concerns that early erythropoietin might exacerbate the pathologic neovascularization associated with retinopathy of prematurity are addressed.
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