Sustained Delivery of Activated Rho GTPases and BDNF Promotes Axon Growth in CSPG-Rich Regions Following Spinal Cord Injury

Spinal cord injuries often lead to permanent loss of function due to physical trauma and secondary events like the deposition of chondroitin sulfate proteoglycans (CSPGs), which inhibit axon regeneration. The study explores whether delivering activated Rho GTPases (Cdc42 and Rac1) and Brain-Derived Neurotrophic Factor (BDNF) to the injury site can reduce CSPG-mediated inhibition and promote axon regeneration. An in situ gelling hydrogel system was used to deliver CA-Rho GTPases or BDNF, which served to physically bridge the lesion and allow the local, slow release of the proteins.

• 1
  Treatment with BDNF, CA-Cdc42, or CA-Rac1 reduced the number of GFAP-positive astrocytes, as well as CSPG deposition, at the interface of the implanted hydrogel and host tissue.
• 2
  Neurofilament 160kDa positively stained axons traversed the glial scar extensively, entering the hydrogel-filled cavity in the treatments with BDNF and CA-Rho GTPases.
• 3
  The treated animals had a higher percentage of axons from the corticospinal tract that traversed the CSPG-rich regions located proximal to the lesion site.