Lack of Synergistic Outcomes with Roflumilast Combined with Levetiracetam or Adipose Stem Cell Secretome After Spinal Cord Injury

Abstract

The Spinal Cord Injury (SCI) pathophysiology is highly complex, contributing to a poor prognosis and lack of effective treatments. Previously, we demonstrated that Roflumilast (Rof), leads to functional recovery when tested in a SCI contusion model. However, it is unlikely that Rof treatment on its own could fully restore the spinal cord. Therefore, our objective was to scrutinize the synergistic effects of combining Rof with neuroprotective approaches. Herein we tested two therapies, firstly, Rof combined with Levetiracetam (Lev), and in a second phase, the complementary interplay between Rof and Adipose Stem Cells secretome (Sec). We induced SCI using a weight drop trauma model at the T8 level. Functional recovery was assessed according to the Basso, Beattie, and Bresnahan scale, Activity Box Test, Motor Swimming Test, and Von Frei test. Results indicate that the unilateral use of Rof, Lev, or Sec was effective in promoting functional recovery. However, the combination of Rof + Lev or Rof + Sec did not lead to an improvement in functional outcomes when compared to standalone treatments. Moreover, the combination of Rof + Sec actually led to worst functional outcome than the single treatments. Further studies are needed to find a combinatorial treatment that can lead to superior therapeutic effects with potential clinical application.