Can a continuous trail of growth signals help injured spinal nerves grow past a scar?

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Delivering neurotrophic factors to spinal cord injury (SCI) sites promotes axon growth into the lesions, but not beyond them. Researchers tested whether sustained growth factor gradients extending beyond SCI regions could promote significant axonal bridging into and beyond lesions.

In a controlled experiment, adult rats underwent C3 spinal cord lesions that transected ascending dorsal column sensory axons. Autologous bone marrow stromal cells were grafted into the lesions to provide a cellular bridge for growth into the injured region. At the same time, lentiviral vectors expressing neurotrophin-3 (NT-3), or green fluorescent protein (GFP) as a control, were injected into the host spinal cord rostral to the lesion—toward the head—to promote axon extension beyond the graft and lesion.

Four weeks later, ELISA detected NT-3 gradients beyond the lesion in animals that received NT-3-expressing lentiviral vectors. Average NT-3 levels were highest near the rostral vector injection site.

Significantly more ascending sensory axons extended into tissue rostral to the lesion in animals injected with NT-3 vectors than in those injected with GFP vectors, but only when the zone of NT-3 vector transduction extended continuously from the injection site to the graft. Any gap in NT-3 expression between the graft and rostral tissue resulted in axon bridging failure.

Despite bridging beyond the lesion, regenerating axons did not continue growing over very long distances, even with a continuing growth factor gradient beyond the lesion. The findings indicate that a localized, continuous NT-3 gradient can enable axonal bridging beyond the glial scar, but a trophic stimulus alone cannot sustain longer-distance growth.