MRI identification of white matter reorganization enhanced by erythropoietin treatment in a rat model of focal ischemia.
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.
Li
Lian
L
Department of Neurology, Henry Ford Hospital, Detroit, Mich. 48202, USA.
Jiang
Quan
Q
Ding
Guangliang
G
Zhang
Li
L
Zhang
Zheng Gang
ZG
Li
Qingjiang
Q
Panda
Swayamprava
S
Kapke
Alissa
A
Lu
Mei
M
Ewing
James R
JR
Chopp
Michael
M
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
D011994:Recombinant Proteins; D004921:Erythropoietin