Combining Peripheral Nerve Grafts and Chondroitinase Promotes Functional Axonal Regeneration in the Chronically Injured Spinal Cord
Veronica J. Tom, * Harra R. Sandrow-Feinberg, * Kassi Miller, Lauren Santi, Theresa Connors, Michel A. Lemay, and John D. Houlé
Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129
Correspondence should be addressed to Dr. John D. Houlé, Department of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129. Email: jhoule@drexelmed.edu
Because there currently is no treatment for spinal cord injury, most patients are living with long-standing injuries. Therefore, strategies aimed at promoting restoration of function to the chronically injured spinal cord have high therapeutic value. For successful regeneration, long-injured axons must overcome their poor intrinsic growth potential as well as the inhibitory environment of the glial scar established around the lesion site. Acutely injured axons that regenerate into growth-permissive peripheral nerve grafts (PNGs) reenter host tissue to mediate functional recovery if the distal graft–host interface is treated with chondroitinase ABC (ChABC) to cleave inhibitory chondroitin sulfate proteoglycans in the scar matrix. To determine whether a similar strategy is effective for a chronic injury, we combined grafting of a peripheral nerve into a highly relevant, chronic, cervical contusion site with ChABC treatment of the glial scar and glial cell line-derived neurotrophic factor (GDNF) stimulation of long-injured axons. We tested this combination in two grafting paradigms: (1) a peripheral nerve that was grafted to span a chronic injury site or (2) a PNG that bridged a chronic contusion site with a second, more distal injury site. Unlike GDNF–PBS treatment, GDNF–ChABC treatment facilitated axons to exit the PNG into host tissue and promoted some functional recovery. Electrical stimulation of axons in the peripheral nerve bridge induced c-Fos expression in host neurons, indicative of synaptic contact by regenerating fibers. Thus, our data demonstrate, for the first time, that administering ChABC to a distal graft interface allows for functional axonal regeneration by chronically injured neurons.
Received July 28, 2009; revised Oct. 2, 2009; accepted Oct. 14, 2009.
Correspondence should be addressed to Dr. John D. Houlé, Department of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129. Email: jhoule@drexelmed.edu
Chondroitinase Promotes Functional Axonal Regeneration SCI
-
Christopher
- Posts: 845
- Joined: Wed Jun 18, 2003 10:09 pm
- Injury Description, Date, extent, surgical intervention etc: Date of Injury: 12/15/02
Level of Injury:
-dominant side C5, C6, & C7 avulsed. C8 & T1 stretched & crushed
BPI Related Surgeries:
-2 Intercostal nerves grafted to Biceps muscle,
-Free-Gracilis muscle transfer to Biceps Region innervated with 2 Intercostal nerves grafts.
-2 Sural nerves harvested from both Calves for nerve grafting.
-Partial Ulnar nerve grafted to Long Triceps.
-Uninjured C7 Hemi-Contralateral cross-over to Deltoid muscle.
-Wrist flexor tendon transfer to middle, ring, & pinky finger extensors.
Surgical medical facility:
Brachial Plexus Clinic at The Mayo Clinic, Rochester MN
(all surgeries successful)
"Do what you can, with what you have, where you are."
~Theodore Roosevelt - Location: Los Angeles, California USA
Chondroitinase Promotes Functional Axonal Regeneration SCI
http://www.jneurosci.org/cgi/content/ab ... 881?ck=nck