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Lower motor neuron loss in multiple sclerosis and experimental autoimmune encephalomyelitis

Vogt, Johannes, Paul, Friedemann, Aktas, Orhan, Müller‐Wielsch, Kathrin, Dörr, Jan, Dörr, Susanne, Bharathi, B. Suman, Glumm, Robert, Schmitz, Christoph, Steinbusch, Harry, Raine, Cedric S., Tsokos, Michael, Nitsch, Robert, Zipp, Frauke·2009·Annals of Neurology
DOI 10.1002/ana.21719
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Abstract

Objective: Multiple sclerosis (MS) is considered a chronic inflammatory and demyelinating disease of the central nervous system. Evidence that axonal and neuronal pathology contributes to the disease is accumulating, however, the distribution of neuronal injury as well as the underlying mechanisms have not yet been fully clarified. Here, we investigated the role of neuronal cell loss in MS and its animal model, experimental autoimmune encephalomyelitis (EAE). Methods: We performed electrophysiological investigations in MS patients, including assessment of compound muscle action potentials and motor unit numbers and quantified neuronal cell loss in human MS samples and different EAE models by high‐precision stereology. Results: Both electrophysiological and morphological analyses indicated a massive loss of lower motor neurons in MS patients. We regularly found dying spinal motor neurons surrounded by CD3+ (CD4+ as well as CD8+) T cells expressing tumor necrosis factor–related apoptosis‐inducing ligand (TRAIL). We observed a similar degree of damage and immune attack in different variants of EAE; the lower motor neurons were preserved in adoptive transfer EAE induced with TRAIL‐deficient T lymphocytes. Interpretation: Our study indicates that damage to lower motor neurons and TRAIL‐mediated inflammatory neurodegeneration in the spinal cord contribute to MS pathology. Ann Neurol 2009;66:310–332

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Research works printed but not linked: 33

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Metadata

Authors
Vogt, J., Paul, F., Aktas, O., Müller‐Wielsch, K., Dörr, J., Dörr, S., Bharathi, B. S., Glumm, R., Schmitz, C., Steinbusch, H., Raine, C. S., Tsokos, M., Nitsch, R., & Zipp, F.
Venue
Annals of Neurology
Publisher
Wiley
Published
2009-09
Volume
66
Issue
3
Pages
310-322
ISSN
  • 0364-5134
  • 1531-8249
DOI
10.1002/ana.21719
Cited by
157
References
6
Language
en
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)

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CoChat. (2026). Citation check: Lower motor neuron loss in multiple sclerosis and experimental autoimmune encephalomyelitis. https://app.cochat.ai/papers/10.1002/ana.21719
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Vogt, J., Paul, F., Aktas, O., Müller‐Wielsch, K., Dörr, J., Dörr, S., Bharathi, B. S., Glumm, R., Schmitz, C., Steinbusch, H., Raine, C. S., Tsokos, M., Nitsch, R., & Zipp, F. (2009). Lower motor neuron loss in multiple sclerosis and experimental autoimmune encephalomyelitis. Annals of Neurology. https://doi.org/10.1002/ana.21719