Three main laboratory strategies are currently used to treat a damaged spinal cord. The first, neuroprotection, is to protect what is left and minimize further damage. Second, especially for incomplete injuries, the strategy includes remyelination or making the most of what remains. Repair is the third strategy, which includes restoring communication, axonal regeneration, and reconnection, often by cell transplantation or pharmacological intervention.

Spinal Cord Research in Animals

Spinal cord research in humans is difficult and in some cases impossible. There is no ability to biopsy tissue, imaging is limited, and studies cannot be done on large groups of people with similar pathology. The only way to investigate spinal cord injury, Barnett said, is to use animal models or primary cells from animal tissue.

An example of an animal model of a spinal cord lesion is a wire knife lesion, generated by inserting the knife into the dorsal column and pulling up a piece of tissue. Barnett noted that this method is clean, accurate, and consistent, resulting in a cavity and glial scarring that mimics human spinal cord injury. By tracing regenerating axons using fluorescent labeling techniques, Barnett has observed that while many axons enter and fill the lesion site, they have limited ability to grow through the lesion, and few exit and find their target. This, Barnett explained, is the major problem with many of the spinal cord injury repair therapies.

One aspect of spinal cord injury that researchers want to mimic is the glial scar. A useful model would have a lesion surrounded by reactive astrocytes that express molecules of interest; axons would be inhibited from entering or exiting the scar and would become demyelinated; and there would be activated microglia.

Several disadvantages to rat models of spinal cord injury include the need for large numbers of animals, the severity of the procedure, and the distress and discomfort to the animals, Barnett said. Additionally, there is a long time frame for results and the experiments are expensive and time consuming. To address this, Barnett is working to replace animals in her experiments.

Replacing Animals with Cell Culture

Barnett described her in vitro model of spinal cord injury in which disassociated embryonic spinal cord cells from rats are layered on top of an astrocyte monolayer derived from embryonic tissue (Sorensen et al., 2008). Growth in culture over time leads to complex axonal/glial interactions resulting in myelinated neurons. This system allows for the study of contact



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