title: Effects of erythropoietin on reducing brain damage and improving functional outcome after traumatic brain injury in mice.
abstract: OBJECTIVE
  This study was designed to investigate the beneficial effects of recombinant human erythropoietin (rhEPO) treatment of traumatic brain injury (TBI) in mice.
  
  
  METHODS
  Adult male C57BL/6 mice were divided into 3 groups: 1) the saline group (TBI and saline [13 mice]); 2) EPO group (TBI and rhEPO [12]); and 3) sham group (sham and rhEPO [8]). Traumatic brain injury was induced by controlled cortical impact. Bromodeoxyuridine (100 mg/kg) was injected daily for 10 days, starting 1 day after injury, for labeling proliferating cells. Recombinant human erythropoietin was administered intraperitoneally at 6 hours and at 3 and 7 days post-TBI (5000 U/kg body weight, total dosage 15,000 U/kg). Neurological function was assessed using the Morris water maze and footfault tests. Animals were killed 35 days after injury, and brain sections were stained for immunohistochemical evaluation.
  
  
  RESULTS
  Traumatic brain injury caused tissue loss in the cortex and cell loss in the dentate gyrus (DG) as well as impairment of sensorimotor function (footfault testing) and spatial learning (Morris water maze). Traumatic brain injury alone stimulated cell proliferation and angiogenesis. Compared with saline treatment, rhEPO significantly reduced lesion volume in the cortex and cell loss in the DG after TBI and substantially improved recovery of sensorimotor function and spatial learning performance. It enhanced neurogenesis in the injured cortex and the DG.
  
  
  CONCLUSIONS
  Recombinant human erythropoietin initiated 6 hours post-TBI provided neuroprotection by decreasing lesion volume and cell loss as well as neurorestoration by enhancing neurogenesis, subsequently improving sensorimotor and spatial learning function. It is a promising neuroprotective and neurorestorative agent for TBI and warrants further investigation.
authors.affiliation: Department of Neurosurgery, Henry Ford Health System, Detroit, Michigan 48202, USA.
authors.forename: Ye
authors.initials: Y
authors.lastname: Xiong
authors.forename: Dunyue
authors.initials: D
authors.lastname: Lu
authors.forename: Changsheng
authors.initials: C
authors.lastname: Qu
authors.forename: Anton
authors.initials: A
authors.lastname: Goussev
authors.forename: Timothy
authors.initials: T
authors.lastname: Schallert
authors.forename: Asim
authors.initials: A
authors.lastname: Mahmood
authors.forename: Michael
authors.initials: M
authors.lastname: Chopp