Modulation of Both Intrinsic and Extrinsic Factors Additively Promotes Rewiring of Corticospinal Circuits after Spinal Cord Injury

Spinal cord injuries often result in motor deficits due to damage to the corticospinal tract, a critical pathway for voluntary movements. The regeneration of corticospinal tract axons is crucial for restoring motor function; however, the intrinsic ability of axons to regrow and the presence of inhibitory molecules limit this regeneration. This study investigates whether suppressing extrinsic inhibitory cues by deleting Rho, and enhancing the intrinsic pathway by deleting Pten, can enable axon regrowth and rewiring of the corticospinal tract after spinal cord injury. The findings indicate that simultaneously eliminating extrinsic and intrinsic signaling pathways additively promotes axon sprouting and rewiring of corticospinal circuits, suggesting a potential molecular approach to reconstruct motor pathways after spinal cord injury.

• 1
  Genetic deletion of RhoA and RhoC suppresses axon retraction or dieback after spinal cord injury.
• 2
  Pten deletion increases regrowth of corticospinal axons into the lesion core.
• 3
  Deletion of both RhoA and Pten additively promotes rewiring of corticospinal circuits connecting the cerebral cortex, spinal cord, and hindlimb muscles.