Emerging strategies to promote improved functional outcome after peripheral nerve injury

Abstract

Purpose: To present a general review of experimental strategies used to improve functional outcome after peripheral nerve injury. In order to understand the mechanisms behind the strategies, the process of nerve healing after injury is described briefly and each strategy is described in its context. Since the functional outcome is not solely determined by nerve regeneration but by a number of different factors, we have also chosen to cover many other important topics.

Methods: Literature review.

Results: Review article.

Conclusions: Functional outcome after peripheral nerve injury is often poor and sometimes associated with neuropathic pain. Therapeutic intervention can be carried out at different levels and we attempt to place the different strategies and target molecules, in the context of the nerve healing process. The most obvious interventions are perhaps to minimize cell death and enhance regeneration across the lesion gap. Others, which are more difficult, may be to limit neuropathic pain, improve target finding and cortical reorganization, counteract effects of prolonged denervation/axotomy, and reduce electrical conduction block at the scar formation. Although clinical outcome is often poor at present, recent preclinical research provides several promising approaches and new target molecules for therapeutic intervention, such as neurotrophic factor (GDNF and ARTN) treatment of neuropathic pain, manipulation of the small Rho GTPases (Rac, Rho, Cdc42, Tc10), lipid raft manipulation, gene silencing with DNA enzyme and siRNA. In addition, recent research involving high throughput screening of gene expression (microarray) after nerve injury encourages the discoveries of new possible target molecules.