title: Beneficial Effect of Erythropoietin Short Peptide on Acute Traumatic Brain Injury.
abstract: 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 full-length 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.
authors.affiliation: Neurology Service, VA Medical Center of East Orange, East Orange, NJ, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Neurology Service, VA Medical Center of East Orange, East Orange, NJ, USA.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Kang
authors.affiliation: Neurology Service, VA Medical Center of East Orange, East Orange, NJ, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Marchese
authors.affiliation: Neurology Service, VA Medical Center of East Orange, East Orange, NJ, USA.
authors.forename: Esther
authors.initials: E
authors.lastname: Rodriguez
authors.affiliation: Neurology Service, VA Medical Center of East Orange, East Orange, NJ, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.affiliation: Neurology Service, VA Medical Center of East Orange, East Orange, NJ, USA.
authors.forename: Xintong
authors.initials: X
authors.lastname: Li
authors.affiliation: Neurology Service, VA Medical Center of East Orange, East Orange, NJ, USA.|Department of Neurology and Neurosciences, Rutgers New Jersey Medical School, Newark, NJ, USA.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Maeda
authors.affiliation: Neurology Service, VA Medical Center of East Orange, East Orange, NJ, USA. dowlinpc@njms.rutgers.edu.|Department of Neurology and Neurosciences, Rutgers New Jersey Medical School, Newark, NJ, USA. dowlinpc@njms.rutgers.edu.
authors.forename: Peter
authors.initials: P
authors.lastname: Dowling
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000473:pathology; D000070642:Brain Injuries, Traumatic / Q000188:drug therapy* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D004921:Erythropoietin / Q000627:therapeutic use*; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000627:therapeutic use*
chemical_list: D018696:Neuroprotective Agents; D010446:Peptide Fragments; C000613468:erythropoietin (28-46); D004921:Erythropoietin
keywords: Erythropoietin; Neuroprotection; Small peptide therapy; Traumatic brain injury