Chapter 2: Translating Animal Research to Humans with Spinal Cord Injury

Objectives

Introduction

When attempting to understand the mechanisms underlying central nervous system (CNS) compensation after spinal cord injury, animal models have many advantages. Among other issues, humans with spinal cord injury (SCI) frequently have damage to structures other than the spinal cord that may confound the results of an experimental intervention. Humans may have associated conditions (e.g., traumatic brain injury), additional physical damage (damage to peripheral nerve, muscle, joints, etc.), trauma that makes it difficult to assess the extent and stability of the lesion (partial sparing of descending tracts, temporary demyelinization that partly recovers, etc.), as well as issues related to psychological responses to injury and the influence of social and environmental factors. It is for these reasons and others that using animal models is valuable. Using animal models allows researchers to separate the complex problem of SCI into simpler parts that they can study one aspect at a time. While some may consider this approach to be too reductionist, the great conservation of basic anatomy and physiology across species (including humans) has, since the late 1980s, allowed scientists to improve the locomotor recovery of individuals with SCI based on evidence obtained from animal models, for example, using weight-supported treadmill training. While in many areas of spinal cord injury research it remains to be seen whether the new discoveries are directly applicable to humans, locomotor function is one area in which evidence from animal models has already lead to the development of valuable new technologies such as robotics and spinal cord stimulation. For this reason, this chapter will use evidence from studies of locomotion in animal models of SCI as the basis for the discussion of translational studies.

The Basics of the Neural Control of Locomotion

When observing an able-bodied individual walking across a room, the movement appears to be fluid and effortless. To achieve this graceful displacement of the whole body, many different components of the central nervous system must be activated and coordinated to precisely time dozens of interacting muscles across a multiarticular system that is inherently unstable.

Animal models of locomotor control have allowed scientists to identify two important principles describing the neural control of walking: (1) control is distributed across the CNS, and (2) control is hierarchical. The walking movement can be decomposed into several elements, summarized here under two categories: