title: Exogenous BDNF enhances the integration of chronically injured axons that regenerate through a peripheral nerve grafted into a chondroitinase-treated spinal cord injury site.
abstract: Although axons lose some of their intrinsic capacity for growth after their developmental period, some axons retain the potential for regrowth after injury. When provided with a growth-promoting substrate such as a peripheral nerve graft (PNG), severed axons regenerate into and through the graft; however, they stop when they reach the glial scar at the distal graft-host interface that is rich with inhibitory chondroitin sulfate proteoglycans. We previously showed that treatment of a spinal cord injury site with chondroitinase (ChABC) allows axons within the graft to traverse the scar and reinnervate spinal cord, where they form functional synapses. While this improvement in outgrowth was significant, it still represented only a small percentage (<20%) of axons compared to the total number of axons that regenerated into the PNG. Here we tested whether providing exogenous brain-derived neurotrophic factor (BDNF) via lentivirus in tissue distal to the PNG would augment regeneration beyond a ChABC-treated glial interface. We found that ChABC treatment alone promoted axonal regeneration but combining ChABC with BDNF-lentivirus did not increase the number of axons that regenerated back into spinal cord. Combining BDNF with ChABC did increase the number of spinal cord neurons that were trans-synaptically activated during electrical stimulation of the graft, as indicated by c-Fos expression, suggesting that BDNF overexpression improved the functional significance of axons that did reinnervate distal spinal cord tissue.
authors.affiliation: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA. vtom@drexelmed.edu
authors.forename: Veronica J
authors.initials: VJ
authors.lastname: Tom
authors.forename: Harra R
authors.initials: HR
authors.lastname: Sandrow-Feinberg
authors.forename: Kassi
authors.initials: K
authors.lastname: Miller
authors.forename: Cheryl
authors.initials: C
authors.lastname: Domitrovich
authors.forename: Julien
authors.initials: J
authors.lastname: Bouyer
authors.forename: Victoria
authors.initials: V
authors.lastname: Zhukareva
authors.forename: Michelle C
authors.initials: MC
authors.lastname: Klaw
authors.forename: Michel A
authors.initials: MA
authors.lastname: Lemay
authors.forename: John D
authors.initials: JD
authors.lastname: Houlé
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D019765:Chondroitin ABC Lyase / Q000627:therapeutic use*; D004558:Electric Stimulation; D005260:Female; D005822:Genetic Vectors; D016086:Lentivirus / Q000235:genetics; D008124:Locomotion / Q000187:drug effects; D009416:Nerve Regeneration / Q000187:drug effects*; D009457:Neuroglia / Q000502:physiology; D010525:Peripheral Nerves / Q000187:drug effects* / Q000637:transplantation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000096:biosynthesis; D013119:Spinal Cord Injuries / Q000188:drug therapy*; D013569:Synapses / Q000502:physiology; D016138:Walking
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D020813:Receptor, trkB; D019765:Chondroitin ABC Lyase