NPC transplantation rescues sci‑driven cAMP/EPAC2 alterations, leading to neuroprotection and microglial modulation

This study investigates the therapeutic mechanisms of neural progenitor cell (NPC) transplantation for spinal cord injury (SCI) in rats. It focuses on how NPCs affect gene expression and signaling pathways, particularly the cAMP pathway, which is crucial for nerve regeneration. The research found that SCI causes significant changes in gene expression, including downregulation of cAMP signaling components. NPC transplantation can reverse these changes, promoting a more favorable environment for nerve recovery. The study also explored the role of EPAC2, a protein involved in the cAMP pathway. Inhibiting EPAC2 appears to counteract some of the beneficial effects of NPC transplantation, suggesting its importance in the recovery process.

• 1
  SCI induces robust transcriptional dysregulation affecting nearly 20,000 genes, with significant downregulation of cAMP signaling components.
• 2
  NPC transplantation normalizes the expression of a large proportion of SCI-affected genes, including rescuing the expression of cAMP signaling genes like EPAC2.
• 3
  Inhibition of EPAC2 downstream signaling reverses NPC-mediated effects, increasing scar area, polarizing microglia into an inflammatory phenotype, and increasing the gap between NeuN+ cells across the lesion.