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

Abstract

The aim of the present study was to determine whether neurotrophic factors (NTFs) exogenously administered in fibrin glue assisted cut dorsal root axons of adult rats to regenerate into the spinal cord. Rats received intraspinal implants of fibrin glue containing neurotrophin-3, brain-derived NTF, ciliary NTF, or Dulbecco's modified Eagle's medium (control) into left dorsal quadrant cavities aspirated in the lumbar enlargement. The transected L5 dorsal root stump was placed at the bottom of the lesion cavity and was secured between the fibrin glue and the spinal cord. Regenerated dorsal root axons were subsequently labeled with immunohistochemical methods to demonstrate those that contained calcitonin gene-related peptide. Calcitonin gene-related peptide-immunoreactive dorsal root axons regenerated 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 with fibrin glue implants that lacked NTF, and their growth within the spinal cord was extremely limited. The results of quantitative studies confirmed these observations. Our results indicate that neurotrophin-3, brain-derived NTF, and ciliary NTF enhance dorsal root regeneration into spinal cord and that fibrin glue is an effective medium for intraspinal delivery of NTF. This method of delivering NTF may therefore provide a strategy for restoring injured spinal reflex arcs.