Acceleration in the rate of CNS remyelination in lysolecithin-induced demyelination

Kevin D. Pavelko, B. G M Van Engelen, Moses Rodriguez

Research output: Contribution to journalArticle

115 Citations (Scopus)

Abstract

One important therapeutic goal during CNS injury from trauma or demyelinating diseases such as multiple sclerosis is to develop methods to promote remyelination. We tested the hypothesis that spontaneous remyelination in the toxic nonimmune model of lysolecithin-induced demyelination can be enhanced by manipulating the inflammatory response. In PBS-treated SJL/J mice, the number of remyelinating axons per square millimeter of lesion area increased significantly 3 and 5 weeks after lysolecithin injection in the spinal cord. However, methylprednisolone or a monoclonal antibody (mAb), SCH94.03, developed for its ability to promote remyelination in the Theiler's virus murine model of demyelination, further increased the number of remyelinating axons per lesion area at 3 weeks by a factor of 2.6 and 1.9, respectively, but did not increase the ratio of myelin sheath thickness to axon diameter or the number of cells incorporating tritiated thymidine in the lesion. After 3 weeks, the number of remyelinating axons in the methylprednisolone or mAb SCH94.03 treatment groups was similar to the spontaneous remyelination in the 5 week PBS control-treated group, indicating that these treatments promoted remyelination by increasing its rate rather than its-extent. To address a mechanism for promoting remyelination, through an effect on scavenger function, we assessed morphometrically the number of macrophages in lesions after methylprednisolone and mAb SCH94.03 treatment. Methylprenisolone reduced the number of macrophages, but SCH94.03 did not, although both enhanced remyelination. This study supports the hypothesis that even in toxic nonprimary immune demyelination, manipulating the inflammatory response is a benefit in myelin repair.

Original languageEnglish (US)
Pages (from-to)2498-2505
Number of pages8
JournalJournal of Neuroscience
Volume18
Issue number7
StatePublished - Apr 1 1998

Fingerprint

Lysophosphatidylcholines
Demyelinating Diseases
Axons
Methylprednisolone
Poisons
Myelin Sheath
Macrophages
Theilovirus
Wounds and Injuries
Therapeutics
Thymidine
Multiple Sclerosis
Spinal Cord
Cell Count
Control Groups
Injections
SCH94.03 monoclonal antibody

Keywords

  • Autoantibodies
  • CNS
  • Corticoste roids
  • Demyelination
  • Immunoglobulin
  • Injury
  • Lysolecithin
  • Remyelination

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Pavelko, K. D., Van Engelen, B. G. M., & Rodriguez, M. (1998). Acceleration in the rate of CNS remyelination in lysolecithin-induced demyelination. Journal of Neuroscience, 18(7), 2498-2505.

Acceleration in the rate of CNS remyelination in lysolecithin-induced demyelination. / Pavelko, Kevin D.; Van Engelen, B. G M; Rodriguez, Moses.

In: Journal of Neuroscience, Vol. 18, No. 7, 01.04.1998, p. 2498-2505.

Research output: Contribution to journalArticle

Pavelko, KD, Van Engelen, BGM & Rodriguez, M 1998, 'Acceleration in the rate of CNS remyelination in lysolecithin-induced demyelination', Journal of Neuroscience, vol. 18, no. 7, pp. 2498-2505.
Pavelko KD, Van Engelen BGM, Rodriguez M. Acceleration in the rate of CNS remyelination in lysolecithin-induced demyelination. Journal of Neuroscience. 1998 Apr 1;18(7):2498-2505.
Pavelko, Kevin D. ; Van Engelen, B. G M ; Rodriguez, Moses. / Acceleration in the rate of CNS remyelination in lysolecithin-induced demyelination. In: Journal of Neuroscience. 1998 ; Vol. 18, No. 7. pp. 2498-2505.
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