The changes in neurotrophic properties of the peripheral nerves extracts following blocking of BDNF activity

Abstract

Objectives: Retinal ganglion cells (RGCs) of adult rats are unable to regenerate their axons after optic nerve injury and soon after they enter the pathway of apoptosis. They may, however, survive and regenerate new axons in response to application of specific peripheral nerve extracts that presumably contain a range of neurotrophic substances. One of the recognized substances of proven neurotrophic activity is brain-derived neurotrophic factor (BDNF).We have investigated whether blocking the BDNF activity in post-microsomal fractions obtained from 7 day pre-degenerated peripheral nerves would affect its neurotrophic properties towards RGCs after optic nerve transection in adult rats.Methods: Autologous connective tissue chambers sutured to the distal end of transected optic nerve served as active substances containers.Surviving RGCs were visualized using Dil. The number of myelinated outgrowing fibers within the chambers was evaluated in histologic sections.Results: BDNF and 7 day pre-degenerated nerve extracts, and also extracts with blocked BDNF activity, enhanced RGC fibers outgrowth.The regeneration was significantly weaker in the control group. Blocking the BDNF activity in the 7 day pre-degenerated peripheral nerve extract reduced its neurotrophic effects but the differences were insignificant in comparison with non-blocked extracts.Discussion: The regeneration intensities in groups receiving 7 day pre-degenerated peripheral nerve extracts (PD7) and BDNF were comparable. The number of surviving cells was higher in the PD7 group and there were more regenerating fibers in the BDNF group, which may be explained by the strong BDNF effect on axonal collateralization and sprouting.