Role of erythropoietin in the brain

Abstract

Multi-tissue erythropoietin receptor (EPO-R) expression provides for erythropoietin (EPO) activity beyond its known regulation of red blood cell production. This review highlights the role of EPO and EPO-R in brain development and neuroprotection. EPO-R brain expression includes neural progenitor cells (NPC), neurons, glial cells and endothelial cells. EPO is produced in brain in a hypoxia sensitive manner, stimulates NPC proliferation and differentiation, and neuron survival, and contributes to ischemic preconditioning. Mice lacking EPO or EPO-R exhibit increased neural cell apoptosis during development before embryonic death due to severe anemia. EPO administration provides neural protection in animal models of brain ischemia and trauma, reducing the extent of injury and damage. EPO stimulation of endothelial cells contributes to neuroprotection and is of particular importance since only low levels of EPO appear to cross the blood-brain barrier when administered at high dose intravenously. The therapeutic potential of EPO for brain ischemia/trauma and neurodegenerative diseases has shown promise in early clinical trial and awaits further validation.

Effects of recombinant human erythropoietin on neuropathic pain and cerebral expressions of cytokines and nuclear factor-kappa B

“…22 NF-kB activation during nerve injury can upregulate some downstream antiapoptotic and neuroprotective genes. 25,26 Digicaylioglu and Lipton 25 have reported that neuronal EPO-receptors activated the neuroprotective signalling pathway via Janus Kinase-2 (JAK2), and NF-kB. Liu et al 27 have observed a modest activation of NF-kB in rhEPO group before ischemia-reperfusion in myocardium and contributed this to the protective effects of rhEPO pretreatment.…”

SIRT1 deficiency compromises mouse embryonic stem cell hematopoietic differentiation, and embryonic and adult hematopoiesis in the mouse

“…44 Epo, generally considered an erythropoietic growth factor, is also a potent prosurvival factor that protects developing stem and progenitor cells in a variety of organs. 45 Renal Epo gene expression differs between SIRT1 ϩ/Ϫ and SIRT1 ϩ/ϩ mice exposed to 6% O 2 , while both groups of mice have similar amounts of renal Epo mRNA under ambient O 2 . 44 Similarly, our data showed that hematopoietic progenitor colony formation from adult mice significantly differed between SIRT1 ϩ/ϩ and SIRT1 ϩ/Ϫ mice under 5% O 2 , while both groups of mice had similar numbers under normoxia.…”

Therapeutic Potential of Erythropoietin and its Structural or Functional Variants in the Nervous System

“…7,8 Expression of EPO and its receptors in the nervous system, as well as its multifaceted protective actions in cell culture and animal models (e.g., induction of anti-apoptotic, anti-oxidant and anti-inflammatory signaling in neurons, glial and cerebrovascular endothelial cells, stimulation of angiogenesis, and neurogenesis), have been reported extensively and reviewed in detail elsewhere. [7][8][9][10][11][12][13][14][15][16][17] Therefore, this review will focus on 1) preclinical work published on EPO variants and 2) clinical studies in neuropsychiatric disease performed with EPO.…”