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Transient Axonal Injury in the Absence of Demyelination: A Correlate of Clinical Disease in Acute Experimental Autoimmune Encephalomyelitis

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Abstract

Axonal degeneration contributes to the transient and permanent neurological deficits seen in multiple sclerosis, an inflammatory disease of the central nervous system. To study the immunological mechanisms causing axonal degeneration, we induced experimental autoimmune encephalomyelitis (EAE) in wildtype Lewis rats and Lewis rats with a slowly progressive myelin degeneration due to proteolipid protein (PLP) overexpression. EAE was triggered either by the transfer of encephalitogenic T-cells alone or by the co-transfer of T-cells with demyelinating antibodies. Inducible nitric oxide synthase (iNOS) expression in perivascular macrophages was associated with a transient functional disturbance of axons, reflected by the focal and reversible accumulation of amyloid precursor protein. Clinical disease correlated with the numbers of APP positive axon spheroids. Demyelination was associated with a further increase of iNOS expression in macrophages and with a higher degree of axonal injury. Our studies suggest that nitric oxide and its metabolites contribute to axonal pathology and possibly also to subsequent neurological dysfunction in EAE.

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Abbreviations

MOG:

Myelin oligodendrocyte glycoprotein

α-MOG:

Anti-MOG antibodies

APP:

Amyloid precursor protein

CNP:

2′3′-cyclic nucleotide 3′ phosphodiesterase

EAE:

Experimental autoimmune encephalomyelitis

GFAP:

Glial fibrillary acidic protein

MBP:

Myelin basic protein

NS:

Normal serum

NT:

Nitrotyrosine

PFA:

Paraformaldehyde

PLP:

Proteolipid protein

Tg:

Transgenics

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Acknowledgments

This work was supported by the FWF (project P16047-B02) and the European commission (QLG3-CT-2002-00612). The authors wish to thank Ulrike Köck, Angela Kury, and Marianne Leiszer for the excellent technical assistance.

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Authors and Affiliations

  1. Department of Neuroimmunology, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, 1090, Vienna, Austria

    Fahmy Aboul-Enein, Peter Weiser, Hans Lassmann & Monika Bradl

  2. Institute of Neurology, Medical University of Vienna, AKH 4J, Währinger Gürtel 18-20, 1097, Vienna, Austria

    Romana Höftberger

Authors
  1. Fahmy Aboul-Enein
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  2. Peter Weiser
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  3. Romana Höftberger
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  4. Hans Lassmann
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Correspondence to Fahmy Aboul-Enein.

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Aboul-Enein, F., Weiser, P., Höftberger, R. et al. Transient Axonal Injury in the Absence of Demyelination: A Correlate of Clinical Disease in Acute Experimental Autoimmune Encephalomyelitis. Acta Neuropathol 111, 539–547 (2006). https://doi.org/10.1007/s00401-006-0047-y

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  • DOI: https://doi.org/10.1007/s00401-006-0047-y

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