Affiliations: Department of Neuroscience, Karolinska Institutet,
S-171 77 Stockholm, Tulane University, New Orleans, USA | Experimental Traumatology, Swedish Defense Research
Agency (FOI), Department of Neuroscience, Karolinska Institutet, S-171 77
Stockholm, Sweden
Note: [] Corresponding author: Johan Widenfalk, Dept. of Neuroscience,
Karolinska Institutet, S-171 77 Stockholm, Sweden. Tel.: +46 8 52486653; Fax:
+46 8 52486088; E-mail: johan.widenfalk@neuro.ki.se
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.
