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Sustained delivery of activated Rho GTPases and BDNF promotes axon growth in CSPG-rich regions following spinal cord injury.

Publication ,  Journal Article
Jain, A; McKeon, RJ; Brady-Kalnay, SM; Bellamkonda, RV
Published in: PloS one
January 2011

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.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.Local delivery of CA-Cdc42, CA-Rac1, and BDNF may have a significant therapeutic role in overcoming CSPG-mediated regenerative failure after SCI.

Duke Scholars

Published In

PloS one

DOI

EISSN

1932-6203

ISSN

1932-6203

Publication Date

January 2011

Volume

6

Issue

1

Start / End Page

e16135

Related Subject Headings

  • rho GTP-Binding Proteins
  • rac1 GTP-Binding Protein
  • cdc42 GTP-Binding Protein
  • Spinal Cord Regeneration
  • Spinal Cord Injuries
  • Rats
  • General Science & Technology
  • Chondroitin Sulfate Proteoglycans
  • Brain-Derived Neurotrophic Factor
  • Axons
 

Citation

APA
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MLA
NLM
Jain, A., McKeon, R. J., Brady-Kalnay, S. M., & Bellamkonda, R. V. (2011). Sustained delivery of activated Rho GTPases and BDNF promotes axon growth in CSPG-rich regions following spinal cord injury. PloS One, 6(1), e16135. https://doi.org/10.1371/journal.pone.0016135
Jain, Anjana, Robert J. McKeon, Susann M. Brady-Kalnay, and Ravi V. Bellamkonda. “Sustained delivery of activated Rho GTPases and BDNF promotes axon growth in CSPG-rich regions following spinal cord injury.PloS One 6, no. 1 (January 2011): e16135. https://doi.org/10.1371/journal.pone.0016135.
Jain A, McKeon RJ, Brady-Kalnay SM, Bellamkonda RV. Sustained delivery of activated Rho GTPases and BDNF promotes axon growth in CSPG-rich regions following spinal cord injury. PloS one. 2011 Jan;6(1):e16135.
Jain, Anjana, et al. “Sustained delivery of activated Rho GTPases and BDNF promotes axon growth in CSPG-rich regions following spinal cord injury.PloS One, vol. 6, no. 1, Jan. 2011, p. e16135. Epmc, doi:10.1371/journal.pone.0016135.
Jain A, McKeon RJ, Brady-Kalnay SM, Bellamkonda RV. Sustained delivery of activated Rho GTPases and BDNF promotes axon growth in CSPG-rich regions following spinal cord injury. PloS one. 2011 Jan;6(1):e16135.

Published In

PloS one

DOI

EISSN

1932-6203

ISSN

1932-6203

Publication Date

January 2011

Volume

6

Issue

1

Start / End Page

e16135

Related Subject Headings

  • rho GTP-Binding Proteins
  • rac1 GTP-Binding Protein
  • cdc42 GTP-Binding Protein
  • Spinal Cord Regeneration
  • Spinal Cord Injuries
  • Rats
  • General Science & Technology
  • Chondroitin Sulfate Proteoglycans
  • Brain-Derived Neurotrophic Factor
  • Axons