Enhancing and regulating neurite outgrowth.

Numerous agents have demonstrated the potential to enhance neuronal repair following spinal cord or peripheral nerve injury using neurite outgrowth as a biomarker for axonal extension in primary cell cultures and neuronal cell lines. This article provides an assessment of the dose-response features of chemically induced neuronal outgrowth in a broad range of experimental models during normal developmental processes, following chemically induced neuronal damage or processes that simulate such damage. These findings indicate that endogenous and exogenous agents, independent of biological model, stimulate central and peripheral nervous system neuronal outgrowths in a biphasic manner consistent with the quantitative features of the hormetic dose-response model. These findings have important clinical implications as they define the plasticity of neurite outgrowth stimulatory responses with respect to the magnitude of enhancement and width of the possible therapeutic zone. The findings also display an essential role for hormetic dose-response relationships in normal neuronal-based developmental and tissue repair processes.