Mitochondrial defects in acute multiple sclerosis lesions

TLDR

Multiple sclerosis is a chronic inflammatory disease that forms demyelinating plaques, and certain acute lesions resembling white matter stroke suggest a hypoxia‑like injury potentially driven by distinct immune mechanisms. The study aimed to assess mitochondrial respiratory chain proteins in active acute MS lesions and white matter stroke via immunohistochemistry. Immunohistochemistry was used to examine mitochondrial respiratory chain proteins in active lesions from acute multiple sclerosis and white matter stroke. Pattern III MS lesions show complex IV (COX) defects in oligodendrocytes, astrocytes, and axons, whereas Pattern II lesions do not, indicating that hypoxia‑like injury in Pattern III may stem from mitochondrial impairment.

Abstract

Multiple sclerosis is a chronic inflammatory disease, which leads to focal plaques of demyelination and tissue injury in the CNS. The structural and immunopathological patterns of demyelination suggest that different immune mechanisms may be involved in tissue damage. In a subtype of lesions, which are mainly found in patients with acute fulminant multiple sclerosis with Balo's type concentric sclerosis and in a subset of early relapsing remitting multiple sclerosis, the initial myelin changes closely resemble those seen in white matter stroke (WMS), suggesting a hypoxia-like tissue injury. Since mitochondrial injury may be involved in the pathogenesis of such lesions, we analysed a number of mitochondrial respiratory chain proteins in active lesions from acute multiple sclerosis and from WMS using immunohistochemistry. Functionally important defects of mitochondrial respiratory chain complex IV [cytochrome c oxidase (COX)] including its catalytic component (COX-I) are present in Pattern III but not in Pattern II multiple sclerosis lesions. The lack of immunohistochemically detected COX-I is apparent in oligodendrocytes, hypertrophied astrocytes and axons, but not in microglia. The profile of immunohistochemically detected mitochondrial respiratory chain complex subunits differs between multiple sclerosis and WMS. The findings suggest that hypoxia-like tissue injury in Pattern III multiple sclerosis lesions may be due to mitochondrial impairment.