Conclusion
This study indicates that FFA improves functional recovery, in part, due to the following reasons: (1) it inhibits the expression of Trpm4 to reduce the secondary hemorrhage; and (2) it inhibits the expression of MMP-2 and MMP-9 to block BSCB disruption. Thus, the results of our study suggest that FFA may represent a potential therapeutic agent for promoting functional recovery.
Methods
Using a moderate contusion injury model at T10 of the spinal cord, flufenamic acid (FFA) was injected intraperitoneally 1 h after SCI and then continuously once per day for one week.
Results
Trpm4 expression is highly up-regulated in capillaries 1 d after SCI. Treatment with flufenamic acid (FFA) inhibited Trpm4 expression, secondary hemorrhage, and capillary fragmentation and promoted angiogenesis. In addition, FFA significantly inhibited the expression of MMP-2 and MMP-9 at 1 d after SCI and significantly attenuated BSCB disruption at 1 d and 3 d after injury. Furthermore, we found that FFA decreased the hemorrhage- and BSCB disruption-induced activation of microglia/macrophages and was associated with smaller lesions, decreased cavity formation, better myelin preservation and less reactive gliosis. Finally, FFA protected motor neurons and improved locomotor functions after SCI.