Inhibition of COX 2 protects white matter excitotoxic death in spinal cord slice cultures The former findings are consistent having a position for COX 2 contributing for the loss of oligodendrocytes in demyeli nating lesions. 1 way during which oligodendrocytes will be lost in demyelinating ailment is by means of GluR mediated excitotoxic death. Oligodendrocytes express GluRs and therefore are vulnerable to excitotoxic death. Even further, inhibitors of GluRs can reduce demyelination inside the EAE model of MS. In order to test no matter if COX two inhibitors could defend white matter oligodendrocytes against excitotoxic death, an in vitro spinal cord slice cul ture program was employed. This program retains neuro anatom ical relationships and permits the examination of compounds which include COX two inhibitors that could guard towards excitotoxic death.
selelck kinase inhibitor As viewed in Figure 3, the GluR agonist Kainic Acid produces a robust induc tion of white matter cell death as indicated from the appear ance of marker for cell death activated caspase three. This marker for cell death has become observed in excitotoxic death of oligodendrocytes. Having said that, addition on the COX 2 inhibitor NS398 created higher than a two fold reduction within the quantity of activated caspase three in white matter. COX 2 inhibitors also diminished a similar quantity of KA induced gray matter excitotoxicity. This consequence in gray matter is steady with other reports displaying that inhibition of COX two protects against neu ronal excitotoxic death. GluR induced expression of COX two in purified dispersed oligodendrocyte cultures The prior effects are consistent by using a role for COX 2 in oligodendrocyte death. Nevertheless, the preceding experi ments with spinal cord slice cultures don’t distinguish no matter if the protective effects of COX two inhibitors are directed selleck chemical in direction of oligodendrocytes or mediated by way of other cell styles.
To be able to examine the direct effects on oligodendrocytes we applied a cell culture process with dis persed oligodendrocytes purified from submit natal mice. This program has two distinctive strengths. The primary advantage is the fact that the direct results of COX 2 inhibitors on oligodendrocyte viability will be examined independent of other cell varieties. Yet another advantage is the fact that these effects can also be examined for oligodendro cyte precursor cells in undifferentiated cultures. The lat ter is very important to infer likely implications on oligodendrocyte precursor cells that contribute to remy elination. In neurons, activation of GluRs induces COX 2 expres sion which may contribute to excitotoxic neuronal death. In an effort to decide regardless of whether a comparable result of GluR activation occurs for oligodendrocytes, dispersed cultures have been taken care of with sub lethal doses of KA along with the quantity of COX two expression examined by immunofluo rescent confocal microscopy.