The role of astrocytes in neuroinflammation

Concurrent with the changing view of MS, evidence of axon-glia and glia-glia networking and communication emerged. These data emphasize the existence and importance of cross-talk and interdependence between the cellular CNS elements, namely astrocytes, microglia, oligodendroglia and nerve cell bodies and axons. A picture of an immensely complex interrelated and constantly communicating multi-dimensional network emerges in which change or damage to one element will inevitably be transmitted throughout the whole system.

Our electron microscopy studies have clearly demonstrated the occurrence of widespread axonal damage and significant astrocyte hypertrophy before large-scale parenchymal invasion of inflammatory cells, particularly T cells and before widespread demyelination. These observations are of particular interest, because the contribution of astrocytes to neuroinflammation is poorly understood and is generally viewed as being secondary to that of microglia.

Further to the above, we have compared astrocytic responses between NOD/Lt and C57Bl/6 variants by quantitative confocal microscopy and quantitative western blotting. These studies demonstrated opposing responses between the two variants, with gradually increasing astrocytic response in NOD/Lt mice with increasing inflammatory infiltration, but a diminishing response in C57Bl/6 mice.