Neuroprotection with Erythropoietin Administration Following Controlled Cortical Impact Injury in Rats

Cherian, Leela; Goodman, Clay; Robertson, Claudia S.

doi:10.1124/jpet.107.119628

Cited by 99 publications

(85 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…More specifically, administration of EPO also represents a viable option for the prevention of retinal cell injury during glaucoma [29]. Systemic application of EPO also can improve functional outcome and reduce cell loss during spinal cord injury [30,31], cerebral edema, [32], cortical trauma [33], and epileptic activity [34,35].…”

Section: Neurodegeneration Inflammatory Cell Activation and Epomentioning

confidence: 99%

Raves and risks for erythropoietin

Maiese

Chong²,

Shang³

2008

Cytokine & Growth Factor Reviews

125

View full text Add to dashboard Cite

Global use of erythropoietin (EPO) continues to increase as a proven agent for the treatment of anemia. Yet, EPO is no longer believed to have exclusive biological activity in the hematopoietic system and is now considered applicable for a variety of disorders such as diabetes, Alzheimer's disease, and cardiovascular disease. Treatment with EPO is considered to be robust and can prevent metabolic compromise, neuronal and vascular degeneration, and inflammatory cell activation. On the converse side, observations that EPO administration is not without risk have fueled controversy. Here we present recent advances that have elucidated a number of novel cellular pathways governed by EPO to open new therapeutic avenues for this agent and avert its potential deleterious effects. Keywordsangiogenesis; cardiac; diabetes; erythropoietin; neurodegeneration Historical Background for ErythropoietinInitially termed "hemopoietine", erythropoietin (EPO) became evident as a factor that could stimulate new red blood cell development through the pioneering studies of Carnot and Deflandre in 1906 [1]. This team of investigators demonstrated that plasma removed from rabbits following a bleeding stimulus that was later injected into control untreated rabbits would lead to the development of immature red blood cells, or reticulocytosis. A number of other investigators followed these studies that demonstrated similar findings that plasma from animals that were bled would yield a significant reticulocytosis. Interestingly, more elegant experiments later demonstrated that a rise in hemoglobin levels with reticulocytosis occurred in parabiotic rats when only one partner was exposed to hypoxia, illustrating that depressed oxygen tensions could stimulate EPO production. Eventually, human EPO protein was purified that paved the way for the cloning of the EPO gene and the development of recombinant EPO for clinical use [2,3]. *Corresponding Author: Kenneth Maiese, MD, Department of Neurology, 8C-1 UHC, Wayne State University School of Medicine, 4201 St. Antoine, Detroit,; email: aa2088@wayne.edu, kmaiese@med.wayne.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. The production and secretion of the mature EPO also relies upon the integrity of the N-and O-linked chains. The EPO gene is located on chromosome 7, exists as a single copy in a 5.4 kb region of the genomic DNA, and encodes a polypeptide chain containing 193 amino acids. During the production and secretion of EPO, a 166 amino acid peptide is initially generated following the cleavage of a 27 amino acid hydrophobic secretory leader ...

show abstract

Section: Neurodegeneration Inflammatory Cell Activation and Epomentioning

confidence: 99%

Raves and risks for erythropoietin

Maiese

Chong²,

Shang³

2008

Cytokine & Growth Factor Reviews

125

View full text Add to dashboard Cite

show abstract

“…In addition, administration of EPO also represents a viable option for the prevention of retinal cell injury during glaucoma (Tsai, et al, 2007). Systemic application of EPO also can improve functional outcome and reduce cell loss during spinal cord injury (King, et al, 2007, Okutan, et al, 2007, traumatic cerebral edema (Verdonck, et al, 2007), cortical trauma (Cherian, et al, 2007), and epileptic activity (Mikati, et al, 2007, Nadam, et al, 2007.…”

Section: Immune Function and The Nervous Systemmentioning

confidence: 99%

Erythropoietin and Oxidative Stress

Maiese

Chong

Hou

et al. 2008

CNR

110

113

View full text Add to dashboard Cite

Unmitigated oxidative stress can lead to diminished cellular longevity, accelerated aging, and accumulated toxic effects for an organism. Current investigations further suggest the significant disadvantages that can occur with cellular oxidative stress that can lead to clinical disability in a number of disorders, such as myocardial infarction, dementia, stroke, and diabetes. New therapeutic strategies are therefore sought that can be directed toward ameliorating the toxic effects of oxidative stress. Here we discuss the exciting potential of the growth factor and cytokine erythropoietin for the treatment of diseases such as cardiac ischemia, vascular injury, neurodegeneration, and diabetes through the modulation of cellular oxidative stress. Erythropoietin controls a variety of signal transduction pathways during oxidative stress that can involve Janus-tyrosine kinase 2, protein kinase B, signal transducer and activator of transcription pathways, Wnt proteins, mammalian forkhead transcription factors, caspases, and nuclear factor κB. Yet, the biological effects of erythropoietin may not always be beneficial and may be poor tolerated in a number of clinical scenarios, necessitating further basic and clinical investigations that emphasize the elucidation of the signal transduction pathways controlled by erythropoietin to direct both successful and safe clinical care. KeywordsAlzheimer's disease; Akt; angiogenesis; apoptosis; cancer; cardiac; caspases; diabetes; endothelial; erythropoietin; forkhead; FoxO; GSK-3β; inflammation; mitochondria; NF-κB; renal; STATs; Wnt OXIDATIVE STRESSInitial work in pathways that can lead to oxidative stress by early investigators observed that increased metabolic rates could be detrimental to animals in an elevated oxygen environment. More current studies point to the potential aging mechanisms and accumulated toxic effects for an organism that are tied to oxidative stress (Maiese, et al., 2008a NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript in organisms, or at least the rate of oxygen consumption in organisms, has intrigued several investigators. Pearl proposed that increased exposure to oxygen through an increased metabolic rate could lead to a shortened life span (Pearl, 1928). Subsequent work by multiple investigators has furthered this hypothesis by demonstrating that increased metabolic rates could be detrimental to animals in an elevated oxygen environment . When one moves to more current work, oxygen free radicals and mitochondrial DNA mutations have become associated with oxidative stress injury, aging mechanisms, and accumulated toxicity for an organism (Yui and Matsuura, 2006).Oxygen free radicals can be generated in elevated quantities during the reduction of oxygen and subsequently lead to cell injury and apoptosis. Oxidative stress occurs as a result of the development of reactive oxygen species that consist of oxygen free radicals and other chemical entities. These agents can involve superoxide free radicals, hydrogen peroxide, sin...

show abstract

“…Whole EPO has received considerable attention over the last decade, owing to reports of its possible neuroprotective and neuroregenerative properties following central nervous system (CNS) injury, including middle cerebral artery occlusion, focal ischemia, subarachnoid hemorrhage, and TBI [2][3][4][5][6]. In several studies, EPO demonstrated efficacy in animal models of stroke and TBI [7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Beneficial Effect of Erythropoietin Short Peptide on Acute Traumatic Brain Injury

et al. 2016

View full text Add to dashboard Cite

There is currently no effective medical treatment for traumatic brain injury (TBI). Beyond the immediate physical damage caused by the initial impact, additional damage evolves due to the inflammatory response that follows brain injury. Here we show that therapy with JM4, a low molecular weight 19-amino acid nonhematopoietic erythropoietin (EPO) peptidyl fragment, containing amino acids 28-46 derived from the first loop of EPO, markedly reduces acute brain injury. Mice underwent controlled cortical injury and received either whole molecule EPO, JM4, or sham-treatment with phosphate-buffered saline. Animals treated with JM4 peptide exhibited a large decrease in number of dead neural cells and a marked reduction in lesion size at both 3 and 8 days postinjury. Therapy with JM4 also led to improved functional recovery and we observed a treatment window for JM4 peptide that remained open for at least 9 h postinjury. The fulllength EPO molecule was divided into a series of 6 contiguous peptide segments; the JM4-containing segment and the adjoining downstream region contained the bulk of the death attenuating effects seen with intact EPO molecule following TBI. These findings indicate that the JM4 molecule substantially blocks cell death and brain injury following acute brain trauma and, as such, presents an excellent opportunity to explore the therapeutic potential of a small-peptide EPO derivative in the medical treatment of TBI.

show abstract

Neuroprotection with Erythropoietin Administration Following Controlled Cortical Impact Injury in Rats

Cited by 99 publications

References 39 publications

Raves and risks for erythropoietin

Raves and risks for erythropoietin

Erythropoietin and Oxidative Stress

Beneficial Effect of Erythropoietin Short Peptide on Acute Traumatic Brain Injury

Contact Info

Product

Resources

About