Figure 8.

A, B) Effect of AX115 on the pathways downstream of PLA₂ after SCI. A) Western blots of spinal cord tissue taken 3 and 7 d after SCI. B) Western blot analysis of spinal cord tissue taken 3 d after SCI (n=3/time point) shows that in mice treated with AX115, cPLA₂ GIVA is increased ∼60% as compared to vehicle-treated mice, while iPLA₂ GVIA and sPLA₂ GIIA showed no change. At the same time point, COX-2 and mPGEs-1 were increased >2-fold in mice treated with AX115. Similar results were also observed at 7 dpi (data not shown). No changes were found in the expression of 5-LOX, and HPGDS. No changes were found in iPLA2, sPLA₂, 5-LOX, or HPGDS at 7 dpi either (data not shown). These results suggest that AX115 appears to have an effect on the cPLA2, COX-2, prostaglandin E pathway. EP1 receptor expression showed a delayed increase of ∼50% at 7 dpi in mice treated with AX115, but no differences were detected at 3 dpi. No changes in expression were seen in EP2 and EP4. C, D) Treatment with SC51089, an EP1 antagonist, significantly reduced the beneficial effects of AX115 on locomotor recovery starting from d 7 onwards, as seen with the BMS analysis (C), and from d 10 onwards in the BMS subscores (D) (vehicle n=9; AX115 n=7; AX115 + SC51089 n=7). *P < 0.05.