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Herwerth M, Kalluri SR, Srivastava R, et al. In vivo imaging reveals rapid astrocyte depletion and axon damage in a model of neuromyelitis optica-related pathology. Ann Neurol. 2016;79(5):794-805doi: 10.1002/ana.24630.
Herwerth, M., Kalluri, S. R., Srivastava, R., Kleele, T., Kenet, S., Illes, Z., Merkler, D., Bennett, J. L., Misgeld, T., & Hemmer, B. (2016). In vivo imaging reveals rapid astrocyte depletion and axon damage in a model of neuromyelitis optica-related pathology. Annals of neurology, 79(5), 794-805. https://doi.org/10.1002/ana.24630
Herwerth, Marina, et al. "In vivo imaging reveals rapid astrocyte depletion and axon damage in a model of neuromyelitis optica-related pathology." Annals of neurology vol. 79,5 (2016): 794-805. doi: https://doi.org/10.1002/ana.24630
Herwerth M, Kalluri SR, Srivastava R, Kleele T, Kenet S, Illes Z, Merkler D, Bennett JL, Misgeld T, Hemmer B. In vivo imaging reveals rapid astrocyte depletion and axon damage in a model of neuromyelitis optica-related pathology. Ann Neurol. 2016 May;79(5):794-805. doi: 10.1002/ana.24630. Epub 2016 Apr 18. PMID: 26946517; PMCID: PMC5021140.
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Ann Neurol. 2016 May;79(5):794-805. doi: 10.1002/ana.24630. Epub 2016 Apr 18.

In vivo imaging reveals rapid astrocyte depletion and axon damage in a model of neuromyelitis optica-related pathology.

Annals of neurology

Marina Herwerth, Sudhakar Reddy Kalluri, Rajneesh Srivastava, Tatjana Kleele, Selin Kenet, Zsolt Illes, Doron Merkler, Jeffrey L Bennett, Thomas Misgeld, Bernhard Hemmer

Affiliations

  1. Department of Neurology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
  2. Institute of Neuronal Cell Biology, Technical University of Munich, Munich, Germany.
  3. Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
  4. Department of Neurology, Division of Clinical and Experimental Neuroimmunology, University of Pecs, Pecs, Hungary.
  5. Department of Neurology and Institute of Clinical Research, Odense University Hospital, University of Southern Denmark, Odense, Denmark.
  6. Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
  7. Division of Clinical Pathology, Geneva University Hospital, Geneva, Switzerland.
  8. Department of Neuropathology, University Medical Center, Göttingen, Germany.
  9. Departments of Neurology and Ophthalmology, Program in Neuroscience, University of Colorado Denver School of Medicine, Aurora, CO.
  10. German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
  11. Center of Integrated Protein Science (CIPSM), Munich, Germany.
  12. equal contributing senior authors.

PMID: 26946517 PMCID: PMC5021140 DOI: 10.1002/ana.24630

Abstract

OBJECTIVE: Neuromyelitis optica (NMO) is an autoimmune disease of the central nervous system, which resembles multiple sclerosis (MS). NMO differs from MS, however, in the distribution and histology of neuroinflammatory lesions and shows a more aggressive clinical course. Moreover, the majority of NMO patients carry immunoglobulin G autoantibodies against aquaporin-4 (AQP4), an astrocytic water channel. Antibodies against AQP4 can damage astrocytes by complement, but NMO histopathology also shows demyelination, and - importantly-axon injury, which may determine permanent deficits following NMO relapses. The dynamics of astrocyte injury in NMO and the mechanisms by which toxicity spreads to axons are not understood.

METHODS: Here, we establish in vivo imaging of the spinal cord, one of the main sites of NMO pathology, as a powerful tool to study the formation of experimental NMO-related lesions caused by human AQP4 antibodies in mice.

RESULTS: We found that human AQP4 antibodies caused acute astrocyte depletion with initial oligodendrocyte survival. Within 2 hours of antibody application, we observed secondary axon injury in the form of progressive swellings. Astrocyte toxicity and axon damage were dependent on AQP4 antibody titer and complement, specifically C1q.

INTERPRETATION: In vivo imaging of the spinal cord reveals the swift development of NMO-related acute axon injury after AQP4 antibody-mediated astrocyte depletion. This approach will be useful in studying the mechanisms underlying the spread of NMO pathology beyond astrocytes, as well as in evaluating potential neuroprotective interventions. Ann Neurol 2016;79:794-805.

© 2016 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.

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