Neurotrophic agents in fibrin glue mediate adult dorsal root regeneration into spinal cord

OBJECTIVE: The aim of the present study was to determine whether neurotroph ic factors (NTFs) exogenously administered in fibrin glue assisted cut dors al root axons of adult rats to regenerate into the spinal cord. METHODS: Rats received intraspinal implants of fibrin glue containing neuro trophin-3, brain-derived NTF, ciliary NTF, or Dulbecco's modified Eagle's m edium (control) into left dorsal quadrant cavities aspirated in the lumbar enlargement. The transected L5 dorsal root stump was placed at the bottom o f the lesion cavity and was secured between the fibrin glue and the spinal cord. Regenerated dorsal root axons were subsequently labeled with immunohi stochemical methods to demonstrate those that contained calcitonin gene-rel ated peptide. RESULTS: Calcitonin gene-related peptide-immunoreactive dorsal root axons r egenerated across the dorsal root-spinal cord interface of rats with fibrin glue containing neurotrophin-3, brain-derived NTF, or ciliary NTF, entered the spinal cord, and frequently arborized within clusters of motoneuronal cell bodies. Only a few axons regenerated into the spinal cord of animals w ith fibrin glue implants that lacked NTF, and their growth within the spina l cord was extremely limited. The results of quantitative studies confirmed these observations. CONCLUSION: Our results indicate that neurotrophin-3, brain-derived NTF, an d ciliary NTF enhance dorsal root regeneration into spinal cord and that fi brin glue is an effective medium for intraspinal delivery of NTF. This meth od of delivering NTF may therefore provide a strategy for restoring injured spinal reflex arcs.