ArticleProceedings of the National Academy of Sciences of the United States of America2009
Optimal neuroprotection by erythropoietin requires elevated expression of its receptor in neurons.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 98 citations in OpenAlex.
- Erythropoietin in amyotrophic lateral sclerosis: a multicentre, randomised, double blind, placebo controlled, phase III study.Journal of neurology, neurosurgery, and psychiatry · 2015Trial
- Brain Delivery of Antibody-Derived Biologicals for Alzheimer's Disease: An Updated Narrative Review.Antibodies (Basel, Switzerland) · 2026Review
- Neuroprotective properties of erythropoietin (Epo) and its receptor (EpoR) in open spinal dysraphism (OSD): an investigation of EpoR expression in a rat OSD model, along with in vitro studies on the neuroprotective effects of Epo on rat spinal cord-derived neural progenitor cells.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2025Article
- Acute carbamoylated erythropoietin reduces social stress-induced anxiety and depression-related behaviors.Neuropharmacology · 2025Article
- Brain-infiltrated monocyte macrophages in a rat model of temporal lobe epilepsy: revisiting the pro-inflammatory paradigm.Frontiers in immunology · 2025Article
- Expression of erythropoietin receptor protein in the mouse hippocampus in response to normobaric hypoxia.Heliyon · 2024Article
- The cytokine receptor CRLF3 is a human neuroprotective EV-3 (Epo) receptor.Frontiers in molecular neuroscience · 2023Article
- Summary of drug therapy to treat cognitive impairment-induced obstructive sleep apnea.Frontiers in cellular neuroscience · 2023Review
- Cerebral Oxygen Delivery and Consumption in Brain-Injured Patients.Journal of personalized medicine · 2022Review
- Respiratory dysfunction in two rodent models of chronic epilepsy and acute seizures and its link with the brainstem serotonin system.Scientific reports · 2022Article
- Revealing the Modular Similarities and Differences Among Alzheimer's Disease, Vascular Dementia, and Parkinson's Disease in Genomic Networks.Neuromolecular medicine · 2022Article
- The Effect of Erythropoietin and Its Derivatives on Ischemic Stroke Therapy: A Comprehensive Review.Frontiers in pharmacology · 2022Review
- Locust Hemolymph Conveys Erythropoietin-Like CytoprotectionFrontiers in physiology · 2021Article
- Insights into Potential Targets for Therapeutic Intervention in Epilepsy.International journal of molecular sciences · 2020Review
- Endogenous erythropoietin signaling regulates migration and laminar positioning of upper-layer neurons in the developing neocortex.Development (Cambridge, England) · 2020Article
- Genetic compensation byCell cycle (Georgetown, Tex.) · 2019Article
- Sirtuin 1 Regulates Mitochondrial Biogenesis and Provides an Endogenous Neuroprotective Mechanism Against Seizure-Induced Neuronal Cell Death in the Hippocampus Following Status Epilepticus.International journal of molecular sciences · 2019Article
- Neuroprotective Agents in the Intensive Care Unit: -Neuroprotective Agents in ICU.Journal of pharmacopuncture · 2018Review
- Brain Penetrating Bifunctional Erythropoietin-Transferrin Receptor Antibody Fusion Protein for Alzheimer's Disease.Molecular pharmaceutics · 2018Article
- Article
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Erythropoietin receptor (EpoR) binding mediates neuroprotection by endogenous Epo or by exogenous recombinant human (rh)Epo. The level of EpoR gene expression may determine tissue responsiveness to Epo. Thus, harnessing the neuroprotective power of Epo requires an understanding of the Epo-EpoR system and its regulation. We tested the hypothesis that neuronal expression of EpoR is required to achieve optimal neuroprotection by Epo. The ventral limbic region (VLR) in the rat brain was used because we determined that its neurons express minimal EpoR under basal conditions, and they are highly sensitive to excitotoxic damage, such as occurs with pilocarpine-induced status epilepticus (Pilo-SE). We report that (i) EpoR expression is significantly elevated in nearly all VLR neurons when rats are subjected to 3 moderate hypoxic exposures, with each separated by a 4-day interval; (ii) synergistic induction of EpoR expression is achieved in the dorsal hippocampus and neocortex by the combination of hypoxia and exposure to an enriched environment, with minimal increased expression by either treatment alone; and (iii) rhEpo administered after Pilo-SE cannot rescue neurons in the VLR, unless neuronal induction of EpoR is elicited by hypoxia before Pilo-SE. This study thus demonstrates using environmental manipulations in normal rodents, the strict requirement for induction of EpoR expression in brain neurons to achieve optimal neuroprotection. Our results indicate that regulation of EpoR gene expression may facilitate the neuroprotective potential of rhEpo.
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