title: Effects of posttraumatic carbamylated erythropoietin therapy on reducing lesion volume and hippocampal cell loss, enhancing angiogenesis and neurogenesis, and improving functional outcome in rats following traumatic brain injury.
abstract: OBJECTIVE
  Carbamylated erythropoietin (CEPO) is a modified erythropoietin molecule that does not affect hematocrit. In this study, the authors compared the efficacy of a single dose with a triple dose of CEPO treatment for traumatic brain injury (TBI) in rats.
  
  
  METHODS
  Traumatic brain injury was induced by controlled cortical impact over the left parietal cortex. Carbamylated erythropoietin (50 μg/kg) was administered intraperitoneally in rats with TBI at 6 hours (CEPO × 1) or at 6, 24, and 48 hours (CEPO × 3) postinjury. Neurological function was assessed using a modified neurological severity score and foot fault and Morris water maze tests. Animals were killed 35 days after injury, and brain sections were stained for immunohistochemical analysis to assess lesion volume, cell loss, cell proliferation, angiogenesis, and neurogenesis after CEPO treatment.
  
  
  RESULTS
  Compared with the vehicle treatment, single treatment of CEPO (6 hours) significantly reduced lesion volume and hippocampal cell loss, enhanced angiogenesis and neurogenesis in the injured cortex and hippocampus, and significantly improved sensorimotor functional recovery and spatial learning in rats after TBI. Importantly, triple dosing of CEPO (6, 24, and 48 hours) further reduced lesion volume and improved functional recovery and neurogenesis compared with the CEPO × 1 group.
  
  
  CONCLUSIONS
  The authors' results indicate that CEPO has considerable therapeutic potential in TBI and related pathologies and furthermore that repeated dosing in the subacute phase might have important pharmacological relevance.
authors.affiliation: Department of Neurosurgery, Henry Ford Health System, Detroit, Michigan 48202, USA. nsxye@neuro.hfh.edu
authors.forename: Ye
authors.initials: Y
authors.lastname: Xiong
authors.forename: Asim
authors.initials: A
authors.lastname: Mahmood
authors.forename: Yanlu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yuling
authors.initials: Y
authors.lastname: Meng
authors.forename: Zheng Gang
authors.initials: ZG
authors.lastname: Zhang
authors.forename: Changsheng
authors.initials: C
authors.lastname: Qu
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Sager
authors.forename: Michael
authors.initials: M
authors.lastname: Chopp
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002452:Cell Count; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D007858:Learning / Q000187:drug effects / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D055495:Neurogenesis / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D010296:Parietal Lobe / Q000187:drug effects / Q000293:injuries / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
chemical_list: C488171:carbamylated erythropoietin; D004921:Erythropoietin