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Mitochondrial damage and histotoxic hypoxia: a pathway of tissue injury in inflammatory brain disease?

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Abstract

The immunological mechanisms leading to tissue damage in inflammatory brain diseases are heterogeneous and complex. They may involve direct cytotoxicity of T lymphocytes, specific antibodies and activated effector cells, such as macrophages and microglia. Here we describe that in certain inflammatory brain lesions a pattern of tissue injury is present, which closely reflects that found in hypoxic conditions of the central nervous system. Certain inflammatory mediators, in particular reactive oxygen and nitrogen species, are able to mediate mitochondrial dysfunction, and we suggest that these inflammatory mediators, when excessively liberated, can result in a state of histotoxic hypoxia. This mechanism may play a major role in multiple sclerosis, not only explaining the lesions formed in a subtype of patients with acute and relapsing course, but also being involved in the formation of diffuse “neurodegenerative” lesions in chronic progressive forms of the disease.

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Acknowledgement:

This study was funded by the Fonds zur Förderung der wissenschaftlichen Forschung (Austria; P 16063-B02).

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Aboul-Enein, F., Lassmann, H. Mitochondrial damage and histotoxic hypoxia: a pathway of tissue injury in inflammatory brain disease?. Acta Neuropathol 109, 49–55 (2005). https://doi.org/10.1007/s00401-004-0954-8

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  • DOI: https://doi.org/10.1007/s00401-004-0954-8

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