title: MRI identification of white matter reorganization enhanced by erythropoietin treatment in a rat model of focal ischemia.
abstract: OBJECTIVE
  The objectives of the present study were to: (1) noninvasively identify white matter reorganization and monitor its progress within 6 weeks after the onset of stroke; and (2) quantitatively investigate the effect of recombinant human erythropoietin treatment on this structural change using in vivo measurement of diffusion anisotropy.
  
  
  METHODS
  Male Wistar rats were subjected to middle cerebral artery occlusion and treated with recombinant human erythropoietin intraperitoneally at a dose of 5000 U/kg of body weight (n=11) or the same volume of saline (n=7) daily for 7 days starting 24 hours after middle cerebral artery occlusion. MRI measurements of T2- and diffusion-weighted images and cerebral blood flow were performed and neurological severity score was assessed at 1 day and weekly for 6 weeks after middle cerebral artery occlusion. Luxol fast blue and Bielschowsky staining were used to demonstrate myelin and axons, respectively.
  
  
  RESULTS
  White matter reorganization occurred along the ischemic lesion boundary after stroke. The region of white matter reorganization seen on the tissue slice coincided with the elevated area on the fractional anisotropy map, which can be accurately identified. The increase in elevated fractional anisotropy pixels corresponded with progress of white matter reorganization and was associated with improvement of neurological function. Treatment with recombinant human erythropoietin after stroke significantly enhanced white matter reorganization, restored local cerebral blood flow, and expedited functional recovery.
  
  
  CONCLUSIONS
  White matter reorganization can be detected by fractional anisotropy. Elevated fractional anisotropy pixels may be a good MRI index to stage white matter remodeling and predict functional outcome.
authors.affiliation: Department of Neurology, Henry Ford Hospital, Detroit, Mich. 48202, USA.
authors.forename: Lian
authors.initials: L
authors.lastname: Li
authors.forename: Quan
authors.initials: Q
authors.lastname: Jiang
authors.forename: Guangliang
authors.initials: G
authors.lastname: Ding
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Zheng Gang
authors.initials: ZG
authors.lastname: Zhang
authors.forename: Qingjiang
authors.initials: Q
authors.lastname: Li
authors.forename: Swayamprava
authors.initials: S
authors.lastname: Panda
authors.forename: Alissa
authors.initials: A
authors.lastname: Kapke
authors.forename: Mei
authors.initials: M
authors.lastname: Lu
authors.forename: James R
authors.initials: JR
authors.lastname: Ewing
authors.forename: Michael
authors.initials: M
authors.lastname: Chopp
mesh_terms: D000818:Animals; D016880:Anisotropy; D001369:Axons / Q000473:pathology; D001921:Brain / Q000473:pathology*; D038524:Diffusion Magnetic Resonance Imaging; D004921:Erythropoietin / Q000627:therapeutic use*; D006651:Histocytochemistry; D006801:Humans; D007091:Image Processing, Computer-Assisted; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D009186:Myelin Sheath / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D020127:Recovery of Function
chemical_list: D011994:Recombinant Proteins; D004921:Erythropoietin