Responses of the nerve cell body to axotomy.

Abstract

Peripheral nerve injury causes retrograde changes in the damaged neurons, which are beneficial to axonal regeneration. Better understanding of the mechanisms of induction and mediation of these conditioning responses would help to design strategies to invoke stronger regenerative responses in neurons in situations when these responses are inadequate. Relevant literature is reviewed. Experimental preparations that measure the influence of peripheral axotomy on regeneration in the central axons of primary sensory neurons are useful to examine mechanisms of conditioning neurons. Despite 4 decades of speculation, the nature of the damage signals from injured nerves that initiate axonal signals to the nerve cell body remains elusive. Members of the family of neuropoietic cytokines are clearly implicated, but what induces them is unknown. Multiple changes in gene regulation in axotomized neurons have been described, and dozens of growth-associated genes have been identified: neurotrophic factors, transcription factors, molecules participating in axonal transport, and molecules active in the growth cone. The mechanisms of interaction of a few regeneration-associated molecules with the signaling cascades that lead to actin and tubulin remodeling at the growth cone are understood in some detail. In animals, viral gene therapy to deliver regeneration-associated genes to neurons or other local measures to induce these genes can improve regeneration. A few pharmacological agents, administered systemically, have small beneficial effects on axonal regeneration. Advances in laboratory research have provided knowledge of cell body responses to axotomy with clinical relevance.