Methylprednisolone (MP) can be used to treat a variety of neurological disorders involving white matter injury, including multiple sclerosis, acute disseminated encephalomyelitis, and spinal cord injury (SCI). presence or absence of RU486. Eight days after SCI, MP significantly increased oligodendrocytes (CC-1 immunoreactive cells) following SCI, but neuronal IWP-2 kinase activity assay (NeuN immunoreactive cells) number remained unchanged; RU486 reversed this protective effect. MP also inhibited SCI-induced decreases in Bcl-xL and caspase-3 activation. Consistent with these findings, the volume of demyelination, assessed by Luxol Fast Blue staining, was attenuated by MP and reversed by RU486. These results suggest that MP selectively inhibits oligodendrocyte but not neuronal cell death via a receptor-mediated action, and may be a mechanism for its limited protective effect following SCI. gene has several GRE consensus sequences in the promoter region (Gascoyne et al., 2003), suggesting a potential mechanism for its induction by MP in oligodendrocytes. Despite the expression of glucocorticoid receptors in neurons (Fuxe et al., 1985a; Fuxe et al., 1985b), MP did not exert protective effects on cortical neurons studies, MP did not induce Bcl-xL expression in neurons, while it was induced in oligodendrocytes. These findings suggest that MP’s cell-type-specific activities may be mediated by downstream signaling events, which are likely to be different in neurons vs. oligodendrocytes. Although RU486 was first developed as a specific glucocorticoid antagonist (Teutsch et al., 1981), subsequent characterization revealed several other activities. RU486 binds to but weakly activates GR avidly, offering it agonist/antagonist properties (Bourgeois et al., 1984). Furthermore, RU486 antagonizes the progesterone receptor (Teutsch et al., 1981; Philibert, 1984), which may be the basis because of its contraceptive activity. Inside our research, we discovered that RU486 antagonized MP’s defensive actions in oligodendrocytes treated with STP or em in vivo /em . Although MP isn’t FDA-approved for make use of in severe SCI, it really is commonly found in this placing predicated on the outcomes of many randomized controlled studies (Bracken et al., 1990; Bracken et al., 1997). Nevertheless, many possess questioned the efficacy of MP because of its marginal effects and criticisms of study design and interpretation (Nesathurai, 1998; Coleman et al., 2000; Hurlbert, 2000; Sayer et al., 2006). Moreover, there is concern that MP may have detrimental effects that may outweigh its marginal clinical benefits (Nesathurai, 1998; Sayer et al., 2006). There may still IWP-2 kinase activity assay be power in understanding mechanisms of MP’s protective effects with hopes of developing interventions that promote protective effects, while minimizing adverse effects. That MP is usually selectively protective for oligodendrocytes is usually intuitively appealing, as its clinical indications involve several CNS disorders involving WM injury. Despite its marginal efficacy in SCI, MP is the mainstay of IWP-2 kinase activity assay therapy for a variety of demyelinating disorders, including multiple sclerosis and acute disseminated encephalomyelitis. Demyelination following SCI is thought to play an important role in disability, and has been proposed to be an important target for therapeutic intervention (for review, see McDonald and Belegu, 2006). Though current opinion favors an anti-oxidant or Rabbit Polyclonal to Src anti-inflammatory mechanism, based on our study we raise the possibility that MP’s mechanisms of action may also involve IWP-2 kinase activity assay direct anti-apoptotic activity in oligodendrocytes. This novel mechanism may have implications for MP’s use in other disorders involving white matter injury. Acknowledgements This work was supported by NIH NINDS R01 NS40525, NS48283, P01 NS32636 (JML), and R01 NS40162 (JX). Technical assistance was provided by the In Vivo Animal Model Core from the Hope Center for Neurological Disorders..