%0 Journal Article
%T Clusters of activated microglia in normal-appearing white matter show signs of innate immune activation
%A Jack van Horssen
%A Shailender Singh
%A Susanne van der Pol
%A Markus Kipp
%A Jamie L Lim
%A Laura Peferoen
%A Wouter Gerritsen
%A Evert-Jan Kooi
%A Maarten E Witte
%A Jeroen J Geurts
%A Helga E de Vries
%A Regina Peferoen-Baert
%A Peter J van den Elsen
%A Paul van der Valk
%A Sandra Amor
%J Journal of Neuroinflammation
%D 2012
%I BioMed Central
%R 10.1186/1742-2094-9-156
%X Here, we document the frequency of preactive lesions and their association with distinct white matter lesions in a cohort of 21 MS patients. Immunohistochemistry was used to gain further insight into the cellular and molecular composition of preactive lesions.Preactive lesions were observed in a majority of MS patients (67%) irrespective of disease duration, gender or subtype of disease. Microglial clusters were predominantly observed in the vicinity of active demyelinating lesions and are not associated with T cell infiltrates, axonal alterations, activated astrocytes or blood¨Cbrain barrier disruption. Microglia in preactive lesions consistently express interleukin-10 and TNF-¦Á, but not interleukin-4, whereas matrix metalloproteases-2 and £¿9 are virtually absent in microglial nodules. Interestingly, key subunits of the free-radical-generating enzyme NADPH oxidase-2 were abundantly expressed in microglial clusters.The high frequency of preactive lesions suggests that it is unlikely that most of them will progress into full-blown demyelinating lesions. Preactive lesions are not associated with blood¨Cbrain barrier disruption, suggesting that an intrinsic trigger of innate immune activation, rather than extrinsic factors crossing a damaged blood¨Cbrain barrier, induces the formation of clusters of activated microglia.
%K Multiple sclerosis
%K Microglial cells
%K Preactive lesion
%K Immune activation
%K Lesion development
%U http://www.jneuroinflammation.com/content/9/1/156/abstract