title: Sustained delivery of activated Rho GTPases and BDNF promotes axon growth in CSPG-rich regions following spinal cord injury.
abstract: BACKGROUND
  Spinal cord injury (SCI) often results in permanent functional loss. This physical trauma leads to secondary events, such as the deposition of inhibitory chondroitin sulfate proteoglycan (CSPG) within astroglial scar tissue at the lesion.
  
  
  RESULTS
  We examined whether local delivery of constitutively active (CA) Rho GTPases, Cdc42 and Rac1 to the lesion site alleviated CSPG-mediated inhibition of regenerating axons. A dorsal over-hemisection lesion was created in the rat spinal cord and the resulting cavity was conformally filled with an in situ gelling hydrogel combined with lipid microtubes that slowly released constitutively active (CA) Cdc42, Rac1, or Brain-derived neurotrophic factor (BDNF). 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. Neurofilament 160kDa positively stained axons traversed the glial scar extensively, entering the hydrogel-filled cavity in the treatments with BDNF and CA-Rho GTPases. 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.
  
  
  CONCLUSIONS
  Local delivery of CA-Cdc42, CA-Rac1, and BDNF may have a significant therapeutic role in overcoming CSPG-mediated regenerative failure after SCI.
authors.affiliation: Neurological Biomaterials and Therapeutics, Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology/Emory University, Atlanta, Georgia, United States of America.
authors.forename: Anjana
authors.initials: A
authors.lastname: Jain
authors.forename: Robert J
authors.initials: RJ
authors.lastname: McKeon
authors.forename: Susann M
authors.initials: SM
authors.lastname: Brady-Kalnay
authors.forename: Ravi V
authors.initials: RV
authors.lastname: Bellamkonda
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects*; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage* / Q000627:therapeutic use; D011508:Chondroitin Sulfate Proteoglycans / Q000502:physiology*; D051381:Rats; D013119:Spinal Cord Injuries / Q000628:therapy*; D058630:Spinal Cord Regeneration / Q000187:drug effects*; D020764:cdc42 GTP-Binding Protein / Q000008:administration & dosage; D020830:rac1 GTP-Binding Protein / Q000008:administration & dosage; D020741:rho GTP-Binding Proteins / Q000008:administration & dosage* / Q000378:metabolism / Q000627:therapeutic use
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D011508:Chondroitin Sulfate Proteoglycans; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins