Activated microglia in primary MS lesions: defenders or aggressors?

Regions of myelinated normal-appearing white matter in clinically early cases of MS show activated parenchymal microglia, with evidence of the beginnings of endocytosis and lysis of the myelin sheath. Whether these cells act as scavengers and restorers of already-damaged tissue, or play an essential primary and aggressive role in myelin lysis and pathogenesis of the MS plaque, is unclear. This review describes the various events observed in these primordial MS lesions in recent studies using immunocytochemistry, magnetic resonance spectroscopy and gene-activation analysis. Despite the various controversial mechanisms proposed to explain the findings, all seem to require the presence of an as-yet undiscovered primary provoking antigen, which is most probably being processed internally by immune systems of the central nervous system. Events taking place in the primordial MS lesion do not seem to be directed by a primary autoimmune attack; they are more suggestive of processes particularly associated with bacterial antigen response.