Further to be considered are the effects of combined insults as a link between sublethal injury and subsequent OL cell death. As an example, we have previously shown that adenovirus-mediated induction in human adult OLs of low levels of p53, a transcription factor that regulates apoptosis and can be detected in OLs in actively demyelinating MS lesions, renders these cells susceptible to subsequent FasL- and TRAIL-medicated killing45. P53 can be induced by multiple stress stimuli, including inflammatory cytokines/inflammation and ischemia/hypoxia. As observed in OPCs in MS lesions46, it is tempting to speculate that cellular senescence may play a role in regulating OL responses, as senescent cells are resistant to cell death; this postulate remains to be investigated.
