MRI identification of white matter reorganization enhanced by erythropoietin treatment in a rat model of focal ischemia
Open accessAbstract
Background and Purpose— 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.
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Stroke induces anterograde Wallerian degeneration of pyramidal tract axons, with degree depending on severity of ischaemic insult.
“Stroke induces anterograde Wallerian degeneration of pyramidal tract axons, the degree of which depends on the severity of the ischaemic insult (figure 1).19,21,22”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [21]
Axonal fibre tracts reorganise along the infarct rim after stroke.
“Subsequently, axonal fibre tracts reorganise along the infarct rim.21,23”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [21]
The efficacy of neurorestorative therapies does not depend on successful reperfusion of ischaemic brain tissue, unlike neuroprotection.
“By sharp contrast with neuroprotection, the efficacy of neuro restorative therapies does not depend on the successful reperfusion of ischaemic brain tissue.11,12,15,17,21”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [21]
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- Authors
- Li, L., Jiang, Q., Ding, G., Zhang, L., Zhang, Z. G., Li, Q., Panda, S., Kapke, A., Lu, M., Ewing, J. R., & Chopp, M.
- Affiliations
- Henry Ford Health (US)
- From the Departments of Neurology (L.L., Q.J., G.D., L.Z., Z.G.Z., Q.L., S.P., J.R.E., M.C.) and Biostatistics and Research Epidemiology (A.K., M.L.), Henry Ford Hospital, Detroit, Mich; and the Department of Physics (M.C.), Oakland University, Rochester, Mich.
- Venue
- Stroke
- Published
- 2009-03
- Volume
- 40
- Issue
- 3
- Pages
- 936-941
- ISSN
- 0039-2499 (ISSN-L)
- 1524-4628
- PMC
- PMC2730918
- OpenAlex
- W2072741548
- Cited by
- 67
- References
- 32
- Citations by year
- 2021: 2 · 2020: 6 · 2019: 1 · 2018: 2 · 2017: 4 · 2016: 5 · 2015: 7 · 2014: 4 · 2013: 7 · 2012: 7
- FWCI
- 7.30
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Stroke (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL 64766, R01HL064766)
- National Cancer Institute (R01CA135329)
- National Institute of Neurological Disorders and Stroke (P01NS23393, R01NS062832, P01NS023393, P01NS42345, P50NS023393, R01 NS48349, R01NS043324, R01 NS 38292, R01NS048349, P01NS042345, R01NS038292, R01 NS 43324)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Keywords
- white matter reorganization, erythropoietin, focal cerebral ischemia, middle cerebral artery occlusion, diffusion anisotropy, fractional anisotropy, diffusion-weighted imaging, stroke recovery, cerebral blood flow, myelin, axons, white matter remodeling
- MeSH terms
- Animals, Axons, Brain, Ischemic Attack, Transient, Erythropoietin, Histocytochemistry, Humans, Image Processing, Computer-Assisted, Male, Myelin Sheath, Recombinant Proteins, Anisotropy, Rats, Wistar, Recovery of Function, Infarction, Middle Cerebral Artery, Diffusion Magnetic Resonance Imaging, Rats
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