Remodeling of axonal connections contributes to recovery in an animal model of multiple sclerosis

Martin Kerschensteiner, Florence M. Bareyre, Bigna S. Buddeberg, Doron Merkler, Christine Stadelmann, Wolfgang Brück, Thomas Misgeld, Martin E. Schwab

Research output: Contribution to journalArticlepeer-review

120 Scopus citations

Abstract

In multiple sclerosis (MS), inflammation in the central nervous system (CNS) leads to damage of axons and myelin. Early during the clinical course, patients can compensate this damage, but little is known about the changes that underlie this improvement of neurological function. To study axonal changes that may contribute to recovery, we made use of an animal model of MS, which allows us to target inflammatory lesions to the corticospinal tract (CST), a major descending motor pathway. We demonstrate that axons remodel at multiple levels in response to a single neuroinflammatory lesion as follows: (a) surrounding the lesion, local interneurons show regenerative sprouting; (b) above the lesion, descending CST axons extend new collaterals that establish a "detour" circuit to the lumbar target area, whereas below the lesion, spared CST axons increase their terminal branching; and (c) in the motor cortex, the distribution of projection neurons is remodeled, and new neurons are recruited to the cortical motor pool. Behavioral tests directly show the importance of these changes for recovery. This paper provides evidence for a highly plastic response of the motor system to a single neuroinflammatory lesion. This framework will help to understand the endogenous repair capacity of the CNS and to develop therapeutic strategies to support it.

Original languageEnglish
Pages (from-to)1027-1038
Number of pages12
JournalJournal of Experimental Medicine
Volume200
Issue number8
DOIs
StatePublished - 18 Oct 2004
Externally publishedYes

Keywords

  • Axons
  • Demyelinating autoimmune disease
  • Nerve regeneration
  • Pyramidal tracts
  • Spinal cord

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