Brain Advance Access published online on February 7, 2005
Brain, doi:10.1093/brain/awh417
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Veterinary Medicine, University of Cambridge, UK
* To whom correspondence should be addressed. Summary A major challenge in multiple sclerosis research is to understand the cause or causes of remyelination failure and to devise ways of ameliorating its consequences. This requires appropriate experimental models. Although there are many models of acute demyelination, at present there are few suitable models of chronic demyelination. The taiep rat is a myelin mutant that shows progressive myelin loss and, by 1 year of age, its CNS tissue has many features of chronic areas of demyelination in multiple sclerosis: chronically demyelinated axons present in an astrocytic environment in the absence of acute inflammation. Using the taiep rat and a combination of X-irradiation and cell transplantation, it has been possible to address a number of questions concerning remyelination failure in chronic multiple sclerosis lesions, such as whether chronically demyelinated axons have undergone changes that render them refractory to remyelination and why remyelination is absent when oligodendrocyte progenitor cells (OPCs) are present. Our experiments show that (i) transplanted OPCs will not populate OPC-containing areas of chronic demyelination; (ii) myelination competent OPCs can repopulate OPC-depleted chronically demyelinated astrocytosed tissue, but this repopulation does not result in remyelination--closely resembling the situation found in some multiple sclerosis plaques; and (iii) the induction of acute inflammation in this non-remyelinating situation results in remyelination. Thus, we can conclude that axonal changes induced by chronic demyelination are unlikely to contribute to remyelination failure in multiple sclerosis. Rather, remyelination fails either because OPCs fail to repopulate areas of demyelination or because if OPCs are present they are unable to generate remyelinating oligodendrocytes owing to the presence of inhibitory factors and/or a lack of the stimuli required to activate these cells to generate remyelinating oligodendrocytes. This non-remyelinating situation can be transformed to a remyelinating one by the induction of acute inflammation.
Received October 15, 2004
Revised January 4, 2005
Accepted January 5, 2005
Article
Inflammation stimulates remyelination in areas of chronic demyelination
W. F. Blakemore, E-mail: wfb1000{at}cam.ac.uk
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  V. Skihar, C. Silva, A. Chojnacki, A. Doring, W. B. Stallcup, S. Weiss, and V. W. Yong Promoting oligodendrogenesis and myelin repair using the multiple sclerosis medication glatiramer acetate PNAS, October 20, 2009; 106(42): 17992 - 17997. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Baer, Y. A. Syed, S. U. Kang, D. Mitteregger, R. Vig, C. ffrench-Constant, R. J. M. Franklin, F. Altmann, G. Lubec, and M. R. Kotter Myelin-mediated inhibition of oligodendrocyte precursor differentiation can be overcome by pharmacological modulation of Fyn-RhoA and protein kinase C signalling Brain, February 1, 2009; 132(2): 465 - 481. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. E. Buckley, P. Goldsmith, and R. J. M. Franklin Zebrafish myelination: a transparent model for remyelination? Dis. Model. Mech., November 1, 2008; 1(4-5): 221 - 228. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A Wilkins and N Scolding Protecting axons in multiple sclerosis Multiple Sclerosis, September 1, 2008; 14(8): 1013 - 1025. [Abstract] [PDF]
|
|
|
|
|
|
M. Dubois-Dalcq, A. Williams, C. Stadelmann, B. Stankoff, B. Zalc, and C. Lubetzki From fish to man: understanding endogenous remyelination in central nervous system demyelinating diseases Brain, July 1, 2008; 131(7): 1686 - 1700. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Chandran, D. Hunt, A. Joannides, C. Zhao, A. Compston, and R. J.M Franklin Myelin repair: the role of stem and precursor cells in multiple sclerosis Phil Trans R Soc B, January 12, 2008; 363(1489): 171 - 183. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Williams, G. Piaton, M.-S. Aigrot, A. Belhadi, M. Theaudin, F. Petermann, J.-L. Thomas, B. Zalc, and C. Lubetzki Semaphorin 3A and 3F: key players in myelin repair in multiple sclerosis? Brain, October 1, 2007; 130(10): 2554 - 2565. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V Tepavcevic and W.F Blakemore Glial grafting for demyelinating disease Phil Trans R Soc B, September 29, 2005; 360(1461): 1775 - 1795. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Friese and L. Fugger Autoreactive CD8+ T cells in multiple sclerosis: a new target for therapy? Brain, August 1, 2005; 128(8): 1747 - 1763. [Abstract] [Full Text] [PDF]
|
|