Poly(I:C) promotes TNFa/TNFR1-dependent oligodendrocyte death in mixed glial cultures

Steelman, Andrew J; Li, Jianrong

Previous studies have demonstrated that lipopolysaccharide (LPS) and subsequent activation of TLR4 is capable of inducing oligodendrocyte death in vivo as well as in vitro [17] and that this cell death is dependent on both TNFα production [24] and TNFR1 signaling [25] . The stimulation of mixed glial cultures with LPS provides a relevant model with which to study certain CNS white matter pathology brought on by gram-negative bacteria, which are thought to contribute to periventricular leukomalacia, a major cause of cerebral palsy. However, the use of LPS in vitro may not accurately reflect inflammatory responses of glial cells during a viral infection; particularly since the pattern recognition receptors that recognize LPS and poly(I:C) are distinct and unequally distributed in parenchymal cells [15] . Direct viral infection of glial cultures provides a relevant tool to model CNS viral-induced pathogenesis and/or tropism. However, infection of CNS-derived cultures with live virus often makes it difficult to separate virusinduced cytopathic effect (i.e. cell lysis) from bystander effects of activated glia.