title: Combinatorial therapy with neurotrophins and cAMP promotes axonal regeneration beyond sites of spinal cord injury.
abstract: Previous attempts to promote regeneration after spinal cord injury have succeeded in stimulating axonal growth into or around lesion sites but rarely beyond them. We tested whether a combinatorial approach of stimulating the neuronal cell body with cAMP and the injured axon with neurotrophins would propel axonal growth into and beyond sites of spinal cord injury. A preconditioning stimulus to sensory neuronal cell bodies was delivered by injecting cAMP into the L4 dorsal root ganglion, and a postinjury stimulus to the injured axon was administered by injecting neurotrophin-3 (NT-3) within and beyond a cervical spinal cord lesion site grafted with autologous bone marrow stromal cells. One to 3 months later, long-projecting dorsal-column sensory axons regenerated into and beyond the lesion. Regeneration beyond the lesion did not occur after treatment with cAMP or NT-3 alone. Thus, clear axonal regeneration beyond spinal cord injury sites can be achieved by combinatorial approaches that stimulate both the neuronal soma and the axon, representing a major advance in strategies to enhance spinal cord repair.
authors.affiliation: Department of Neurosciences, University of California at San Diego, La Jolla, California 92093-0626, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Lu
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.forename: Leonard L
authors.initials: LL
authors.lastname: Jones
authors.forename: Marie T
authors.initials: MT
authors.lastname: Filbin
authors.forename: Mark H
authors.initials: MH
authors.lastname: Tuszynski
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000502:physiology; D016026:Bone Marrow Transplantation; D003994:Bucladesine / Q000008:administration & dosage / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004341:Drug Evaluation; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D005260:Female; D005727:Ganglia, Spinal; D015552:Injections, Intralesional; D009416:Nerve Regeneration / Q000187:drug effects*; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D020933:Neurotrophin 3 / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D011916:Rats, Inbred F344; D013119:Spinal Cord Injuries / Q000188:drug therapy*; D017154:Stromal Cells / Q000637:transplantation; D014182:Transplantation, Autologous
chemical_list: D020933:Neurotrophin 3; D003994:Bucladesine