Regeneration after Spinal Cord Injury: A Review on the Crucial Aspects of V2a Interneurons

Spinal cord injuries (SCI) are extremely difficult to treat due to the limited capacity for neural regeneration across the injury site. However, V2a interneurons have been a point of interest in SCI research over the last decade, as they have been shown to contribute to the promotion of neuroplasticity after injury. These excitatory interneurons contain either long or short projections that are effective at driving rhythmic motor firing. By possessing ipsilateral, contralateral, or propriospinal projections, subtypes of V2a interneurons expressing the visual system homeobox-2 (Vsx-2) gene have been shown to extend their projections past the site of injury and restore injured spinal circuits that contribute to the respiration and right-left coordination. Moreover, Vsx-2/Zfhx3-expressing V2a interneurons in the midthoracic region of the spinal cord are a point of interest due to their unique ability to extend long projections caudally past the injury site and into the lumbar region, which resulted in substantial improvement in hind limb function after SCI in mice. Here, we collectively summarize the origin, subtypes, and the role Vsx-2 V2a interneurons play after SCI. We further describe the various techniques utilized to promote the accumulation and growth of these interneurons across or around the site of injury, effectively rewiring motor networks to contribute to functional recovery.