Pathogenesis of axonal and neuronal damage in multiple sclerosis. Neurology 68(22 Suppl 3):S22-S31

Department of Neuroscience, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Neurology (Impact Factor: 8.29). 06/2007; 68(22 Suppl 3):S22-31; discussion S43-54. DOI: 10.1212/01.wnl.0000275229.13012.32
Source: PubMed


Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the CNS. Approximately 2 million people worldwide have MS, with females outnumbering males 2:1. Because of its high prevalence, MS is the leading cause of nontraumatic neurologic disability in young adults in the United States and Europe. Axon loss is the major cause of irreversible disability in patients with MS. Axon damage, including transection of the axon, begins early in MS and correlates with inflammatory activity. Several mechanisms lead to axon loss, including inflammatory secretions, loss of myelin-derived support, disruption of axonal ion concentrations, energy failure, and Ca(2+) accumulation. Therapeutic interventions directed toward each of these mechanisms need to be tested for their efficacy in enhancing axon survival and, ultimately, their ability to delay progression of neurologic disability in patients with MS.

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Available from: Ranjan Dutta, Mar 24, 2015
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    • "We also showed that ACTH stimulated OPC proliferation and induced OL to elaborate larger and more dense membrane sheets (Benjamins et al., 2014). It is increasingly clear that damage to axons/neurons is important in the pathogenesis of MS in all stages of the disease (Ferguson et al., 1997; Trapp et al., 1998; Dutta and Trapp, 2007; Lassmann, 2013; Mahad et al., 2015). While some axonal and neuronal loss may result from changes in function in demyelinated axons (Dutta and Trapp, 2011; Criste et al., 2014), some damage and neuronal loss may be caused by direct effects of mediators of excitotoxicity and inflammation (Lisak et al., 2012; Lassmann, 2014a, 2014b). "
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    • "As far as myelin sheath is concerned, we have supposed that this aerobic metabolism supports the axonal energy demand [24]. This would be consistent with the hypothesis that myelin sheath plays an as yet unidentified trophic role [25] considering that myelin loss in demyelinating diseases leads to an axonal degeneration, the cause of the most severe symptoms in these pathologies [26]. "
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    • "rosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) (Delisle and Carpenter, 1984; Hori and Carpenter, 1994; Takahashi et al., 1997; Trapp et al., 1998; Dickson et al., 1999; Mattila et al., 1999; Swann et al., 2000; Goel et al., 2003; Pavlidis et al., 2003; Saito et al., 2003; Dutta and Trapp, 2007 "
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