Setting the stage for functional repair of spinal cord injuries: a cast of thousands

Abstract

Here we review mechanisms and molecules that necessitate protection and oppose axonal growth in the injured spinal cord, representing not only a cast of villains but also a company of therapeutic targets, many of which have yet to be fully exploited. We next discuss recent progress in the fields of bridging, overcoming conduction block and rehabilitation after spinal cord injury (SCI), where several treatments in each category have entered the spotlight, and some are being tested clinically. Finally, studies that combine treatments targeting different aspects of SCI are reviewed. Although experiments applying some treatments in combination have been completed, auditions for each part in the much-sought combination therapy are ongoing, and performers must demonstrate robust anatomical regeneration and/or significant return of function in animal models before being considered for a lead role.Spinal Cord (2005) 43, 134-161.

International spinal research trust research strategy. III: A discussion document

“…Thus, spinal injuries comprise a primary zone of direct injury plus a zone of secondary injury, and neuroprotective strategies that either reduce or prevent the spread of secondary damage are likely to result in greater recovery of function. [3][4][5] Many of the mechanisms responsible for these secondary processes remain unknown. Thus, further understanding of the detailed molecular and cellular mechanisms involved in early trauma and cell death, inflammation and glial scarring is vital to provide direction for the rational development of therapeutics to minimise secondary damage and enhance function following injury.…”

“…4 Encourage the use of genetically modified animals (eg knockout and transgenic animals) in established SCI models to gain additional insights into the key molecular and cellular components of SCI and its repair HC1. 5 Fund research into the significance of demyelination and remyelination in SCI and repair HC1. 6 Fund research to establish a large-animal model of SCI in order to harness the sophisticated electrophysiological capabilities available for this species HC1.…”

“…Work should eventually be confirmed in a large-animal model with well developed, higher cortical modulation of behaviour HC2. 5 Fund work (experimental, literature review and crossdisciplinary discussion fora) that correlates measurement systems used in animal models and in humans HC2. 6 Fund research that aims to establish an integrated package of baseline data in SCI patients, including comprehensive, sensitive and detailed characterisations of the state of spinal cord damage, synaptic connectivity and residual function HC2.…”

“…4 Consider promoting SCI (if an appropriately robust clinical trial can be developed and tested) as a surrogate for evaluating treatments for allied neurological applications, as a means of accessing additional support and potential treatments HC3. 5 Explore options for sharing with other medical charities, especially in the neurosciences, additional staff to manage clinical trial activities on a day-to-day basis HC3. 6 Establish links with other organisations to share knowledge and establish common standards of clinical and ethical practice, including open access to databases HC3.…”

Clinical canine spinal cord injury provides an opportunity to examine the issues in translating laboratory techniques into practical therapy

“…[1][2][3][4][5] These interventions can be subdivided into those that exert effects through putative neuroprotective, 6 regenerative 7-9 or plasticity-inducing 10,11 mechanisms, many of which have been substantiated through further in vivo, or in vitro, experiments. However, although an intervention might show great promise by alleviating the effects of SCI in an experimental animal model, there are many differences between experimental SCI in rodent models and the clinical injuries that occur in human patients.…”