Riluzole improves functional recovery after acute spinal cord injury in rats and may be associated with changes in spinal microglia/macrophages polarization

Spinal cord injury (SCI) triggers pronounced inflammatory responses that are accompanied by neuronal disruption and functional deficits. SCI treatment remains an unmet clinical need. Emerging evidence suggests that riluzole may exert a neuroprotective effect due to its anti-inflammatory properties. However, details of the underlying mechanisms remain poorly defined. The polarization of microglial/macrophages has an important role in neuroinflammation. Here, we examined whether riluzole can exert a neuroprotective effect after acute SCI, and whether this effect is associated with changes in microglia/macrophages polarization. Riluzole (4 mg/kg) or vehicle were injected intraperitoneally (i.p.) in female rats immediately following SCI and repeated for 7 consecutive days (b.i.d.). Compared with vehicle treatment, riluzole-treated SCI rats showed significant higher locomotor scores (Basso, Beattie, and Bresnahan score, Inclined Plane test score, n= 18/group). Riluzole-treated rats also developed smaller spinal cavities, showed higher levels of myelin basic protein (MBP) and neurofilament (NF)200 immunoreactivities, and lower levels of proinflammatory cytokines in the spinal cord at 7 days post-SCI. Immunofluorescence study revealed more CD206(+) cells and less iNOS(+) cells in the injured spinal cord of riluzole-treated SCI rats, as compared to vehicle control. Using real-time PCR, we found that riluzole upregulated the mRNA levels of M2 markers, but downregulated that of M1 markers, as compared to the vehicle treatment. Current findings suggest that systemic administration of riluzole after acute SCI facilitated motor function recovery and inhibited inflammatory responses, which may be associated with polarization of M2 microglia/macrophages.