Effects of Current Medical Therapies on Reparative and Neuroprotective Functions in Multiple Sclerosis

  • Jack P. Antel
  • Veronique E. Miron


Multiple sclerosis (MS) is most frequently clinically characterized by an initial relapsing–remitting phase that evolves into a secondary progressive course; these phases can also be ongoing concurrently. Each of these clinical disease aspects reflects distinctive pathologic substrates, each of which may require its own therapeutic strategies. The pathologic correlate of clinical relapses is the development of new demyelinating lesions within the CNS that feature an inflammatory infiltrate comprised of cells of the adaptive (lymphocytes) and innate (myeloid cells) systems that have transgressed the blood–brain barrier (BBB) and/or the subarachnoid space/brain barrier (Kivisakk et al. 2003). Axonal transections are a further feature of the acute lesions (Trapp et al. 1998). Magnetic resonance imaging (MRI) studies indicate that multiple such lesions can occur without apparent clinical symptoms (Engell 1989). Recovery from relapses reflects the combined effects of multiple factors including resolution of inflammation, axonal adaptation to demyelination, remyelination, and cerebral reorganization. The pathologic correlates of the later progressive disease phase are even more complex involving changes both within initial lesions and in normal appearing white matter (NAWM) (Fu et al. 1998). Intralesional changes include further loss of oligodendrocytes (OLs) and axons, enhanced gliosis, and apparent failure of remyelination. Such lesions are dominated by innate immune cells (microglia/macrophages) rather than lymphocytes (Revesz et al. 1994). Observed changes in NAWM include continued decrease in axonal density and activated glial cells (microglia, astrocytes). There is also an apparent increase of lesions within the gray matter over time characterized by loss of neurons and demyelination without marked inflammation (Kidd et al. 1999). Ongoing remyelination is more apparent in recent rather than more chronic lesions and may be more prevalent in gray matter than in white matter lesions (Prineas and Connell 1979; Raine and Wu 1993; Stadelmann and Bruck 2008). Disease progression is thus likely to involve variable contributions by ongoing tissue injury, degeneration of previously injured OLs and neurons, and failure to initiate or sustain repair mechanisms (Table 9.1).


Multiple Sclerosis Experimental Autoimmune Encephalomyelitis Multiple Sclerosis Patient Glatiramer Acetate Normal Appear White Matter 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Neuroimmunology Unit, Montreal Neurological InstituteMcGill UniversityMontrealCanada
  2. 2.Scottish Centre for Regenerative MedicineThe University of EdinburghEdinburghUK

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