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Pathogenesis of tissue injury in MS lesions
1Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic Foundation, OH 44195, USA. trappb@cesmtp.ccf.org
Abstract:
Multiple sclerosis (MS) is an inflammatory disease of the central nervous system. The primary pathological target in multiple sclerosis is myelin. Most MS patients follow a relapsing-remitting (RR-MS) course for 10 to 15 years that transforms into a chronic or secondary progressive disease (SP-MS). This review summarizes studies from our laboratory that implicate activated microglia and astrocytes in early stages of myelin destruction in MS brain. In addition, we review evidence that indicates that axonal transection is a major pathological process in multiple sclerosis. Our data support the hypothesis that neurological disability in RR-MS is due to inflammatory demyelination while axonal loss plays a significant role in the irreversible neurological decline in SP-MS. Further elucidation of the pathological targets and pathological mechanisms of tissue destruction in MS brain will help identify new therapeutics.
Insights
Multiple sclerosis involves central nervous system inflammation, primarily targeting myelin. Activated immune cells like microglia and astrocytes contribute to myelin destruction, while axonal loss drives irreversible disability in progressive stages.
Area of Science:
- Neuroimmunology
- Neuropathology
Background:
- Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system.
- Myelin, the protective sheath around nerve fibers, is the primary pathological target in MS.
- MS typically progresses from a relapsing-remitting (RR-MS) course to a secondary progressive (SP-MS) phase.
Purpose of the Study:
- To review laboratory studies implicating activated microglia and astrocytes in early myelin destruction in MS.
- To examine evidence supporting axonal transection as a key pathological process in MS.
- To differentiate pathological mechanisms underlying disability in RR-MS versus SP-MS.
Main Methods:
- Review of laboratory studies focusing on MS neuropathology.
- Analysis of pathological findings in MS brain tissue.
- Correlation of pathological processes with clinical disease progression.
Main Results:
- Activated microglia and astrocytes are implicated in the early stages of myelin destruction in MS.
- Axonal transection is identified as a significant pathological mechanism in MS.
- Inflammatory demyelination contributes to neurological disability in RR-MS.
- Axonal loss is a major factor in the irreversible neurological decline seen in SP-MS.
Conclusions:
- Understanding the specific pathological targets and mechanisms in MS is crucial for developing effective therapeutics.
- Differentiating the roles of demyelination and axonal loss in MS progression can inform targeted treatment strategies.