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Beyond Animal Research
By Kristie Sullivan, M.P.H.
Spinal Cord Injury Experiments on Animals
Every year, approximately 10,000 people in the United States suffer some sort of spinal cord injury; many thereafter are confined to wheelchairs and forced to adapt to a host of medical challenges.1 Decreased activity can lead to bone and muscle loss, weight gain, cardiovascular disease, diabetes mellitus, and circulatory dysfunction. Others experience idiopathic pain sensations, muscle spasticity, and pressure ulcers on the skin. Finally, most have functional difficulties with the digestive, excretory, and reproductive systems.
Unfortunately, the tragic results of spinal cord injuries (SCI) are in fact two-fold. In an effort to help people with SCI, many researchers are attempting to create animal “models” of injured humans. Over the past few decades, much effort and expense has been spent creating sophisticated impaction devices and other injury techniques designed to eliminate variability and deliver a reproducible spinally injured animal. Every year, thousands of animals are given spinal cord injuries through blunt trauma, loss of blood flow, or surgical transection, then treated or dissected in hopes that a cure will be found.
Some of these projects have seemed to bear fruit—at first. Scientists have managed to re-grow damaged neural tissue in the spinal cords of rats,2-4 see cats with completely cut spinal cords walk again, determine detailed information about neural connectivity in macaques,5 and prevent secondary damage to neural tissue after injury.6 Thousands of animals have been injured and evaluated.
Unfortunately, and perhaps predictably, not one of these experiments has actually led to a cure or effective treatment for human spinal cord injury. Out of nearly two dozen therapies suggested to be effective in non-human animals,7 only one (methylprednisolone) proved helpful to injured humans.8 Even the effectiveness of methylprednisolone is now being called into serious question by practicing clinicians.
Perhaps the most salient reasons for this failure are related to anatomy—each species has a unique spinal orientation, movement kinetics, and neural anatomy. Furthermore, every human spinal injury comes with its own set of physical, neurochemical, and histological pathologies that cannot be properly duplicated in a laboratory setting.
On the other hand, human research methods have produced promising results, and others are worth a closer look. Here’s a sampling:
- A group of London researchers found that damage to spinal cord neurons in cell culture was prevented by inhibiting a specific nuclear enzyme apparently involved in peroxynitrite-induced cell damage after injury.9
- A procedure to create human motoneuron cell lines in culture was developed in 2000.10 Researchers found the cloned neurons displayed normal neuronal processes, including immunoreactivity and action potential firing, and researchers were also able to coax clonal precursor cells into multiple types of spinal cord neurons.10
- Non-invasive imaging techniques, such as PET, SPECT, and fMRI, as well as more invasive cerebrospinal fluid studies, can be used to visualize neural pathology at various time points after injury and monitor the effects of experimental therapies. By studying neuromuscular connections in both uninjured and spinal cord-injured patients, University of Miami School of Medicine scientists have found mechanisms in the spinal cord that are responsible for coordinating opposing muscle movements.11
- In Miami, researchers are collaborating on the Human Spinal Cord Injury Model project. This project is studying spinal cord injured patients, both pre- and post-mortem, to build a more realistic understanding of human spinal cord injury. Post-mortem spinal cord tissue can be compared to MRIs to determine histopathological changes in cells and tissues.12,13
Researchers, clinicians, and patients alike agree that a more directed effort to establish human clinical research projects is needed. While success in restoring functional endpoints has been realized in a number of areas,14-23 more investment in this avenue of research is needed. Only then will true success be realized.
Kristie Sullivan, M.P.H., is a PCRM research analyst.
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