Use of GDNF-Releasing Nanofiber Nerve Guide Conduits for the Repair of Conus Medullaris/Cauda Equina Injury in the Non-Human Primate. Annual Report September 30, 2012-September 29, 2013.

摘要

The present study is evaluating a surgical approach for repair of conus medullaris/cauda equina injury in rhesus macaques using a biodegradable bridging graft that releasing the trophic factor, GDNF. All subjects have been entered into the study. All subjects have also undergone pre-surgical testing, including magnetic resonance imaging, pain behavioral testing, urodynamic recordings, electromyography of external anal sphincter, and locomotor testing. All subjects have also undergone surgery with 5 subjects in each group undergoing either 1) unilateral L6-S3 ventral root avulsion (VRA) injury, 2) L6-S3 VRA injury followed by replantation into the spinal cord using a peripheral nerve bridging graft, 3) L6-S3 VRA injury followed by root replantation into the spinal cord using a GDNF-releasing nerve guide channel as bridging graft, or 4) L6-S3 VRA injury followed by root replantation into the spinal cord using an empty (control) nerve guide channel as bridging graft. The surgery was tolerated well and subjects underwent additional, longitudinal functional assessments using locomotor testing, urodynamic recordings, electromyography of the pelvic floor, and pain behavioral testing. At 18 months after the surgery, a final set of imaging and functional assessments are obtained, following by termination of the study and harvesting of spinal cord and nerve root tissues for anatomical studies. A subset of subjects are still undergoing evaluations. Preliminary studies of subjects undergoing VRA injury and root repair show that the intercostal nerve is well innervated by regenerating axons. In a first subject undergoing post-operative morphological evaluation of GDNF-releasing nerve guide channels, it is shown that regenerating fibers are also capable of entering the graft.