UNASSIGNED: Astrocytes are key players in the pathology of @entity15 and can assume beneficial and detrimental roles during lesion development. The triggers and timing of the different astroglial responses in @entity697 remain unclear. Astrocytes in acute @entity15 have been shown previously to contain myelin debris, although its significance has not been examined. We hypothesized that myelin phagocytosis by astrocytes is an early event during lesion formation and leads to astroglial immune responses. We examined @entity15 and other central nervous system pathologies with @entity17 , namely, progressive multifocal @entity62 , @entity8431 and subacute @entity1188 . In all conditions, we found that myelin debris was present in most astrocytes at sites of acute myelin breakdown, indicating that astroglial myelin phagocytosis is an early and prominent feature. Functionally, myelin debris was taken up by astrocytes through receptor-mediated endocytosis and resulted in astroglial NF-kB activation and secretion of chemokines. These in vitro results in @entity35 were validated in @entity1 disease where myelin-positive @entity1184 astrocytes showed increased nuclear localization of NF-kB and elevated chemokine expression compared to myelin-negative, reactive astrocytes. Thus, our data suggest that myelin uptake is an early response of astrocytes in diseases with @entity17 that results in recruitment of immune cells. This first line response of astrocytes to @entity17 may exert beneficial or detrimental effects on the lesion pathology, depending on the inflammatory context. Modulating this response might be of therapeutic relevance in @entity15 and other demyelinating conditions.

Myelin phagocytosis by astrocytes after XXXX promotes lesion pathology.

@entity1 :: ('9606', 'Species') :: ['human'] @entity17 :: ('MESH:D003711', 'Disease') :: ['prominent myelin injury', 'myelin injury'] @entity697 :: ('MESH:D000208', 'Disease') :: ['acute lesions'] @entity1184 :: ('MESH:D006984', 'Disease') :: ['hypertrophic'] @entity8431 :: ('MESH:D007966', 'Disease') :: ['metachromatic leukodystrophy'] @entity1188 :: ('MESH:D007238', 'Disease') :: ['infarct'] @entity35 :: ('10116', 'Species') :: ['rats'] @entity62 :: ('MESH:D056784', 'Disease') :: ['leukoencephalopathy'] @entity15 :: ('MESH:D009103', 'Disease') :: ['multiple sclerosis lesions', 'multiple sclerosis']
@entity17 :: (MESH:D003711,Disease) :: ['myelin damage']
