Intrathecal delivery of BDNF to the lumbar spinal cord modulates lumbar interneurons activity in a feline model of spinal cord injury.

Abstract

Objective.In the present study, we examined the correlations between the recovery of stepping obtained with intrathecal brain derived neurotrophic factor (BDNF) delivery to the lumbar spinal cord and the firing of the lumbar spinal interneurons in a feline model of spinal cord injury (SCI).Approach. In-vivoextracellular recordings of spinal neurons were conducted using two 64-channel microelectrode arrays inserted in the intermediate zone of the L3-L7 segments of cats spinalized at the T11-T12 level that received either saline or BDNF delivered intrathecally to the lumbar cisterna via an implanted minipump. Interneuronal activity was explored in terms of averaged neuronal firing properties and in terms of spike train interactions.Main results.With respect to averaged neuronal firing properties, we observed a significant increase in firing frequency in BNDF-treated animals and a similar distribution of the units' preferred phase of firing relative to the step cycle between the groups. With respect to spike train interactions, we observed higher synchrony of firing in BDNF-treated animals as well as less dependency on the unit's past firing.Significance.Studies conducted in feline models of complete SCI show a gradual recovery of hindlimb stepping after intensive treadmill training. Similarly, delivery of neurotrophins such as BDNF or neurotrophin-3 to the injury site via cellular transplant or via implantable mini-pump to the lumbar cisterna has been shown to promote recovery of locomotor behavior in the absence of locomotor training. The results from this study suggest that BDNF treatment sets the overall population in a state of high excitability, which along with higher synchrony and ensemble-dependent behavior, allows for the proper integration of cutaneous and proprioceptive input resulting in treadmill locomotor recovery after SCI.