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 Stoick, M.P.H., is a PCRM research analyst.
References:
1. Reyes O, Sosa I, Kuffler DP Neuroprotection of spinal neurons
against blunt trauma and ischemia. P R Health Sci J 2003;22(3):277-86.
2. Li Y and Raisman G. Schwann cells induce sprouting in motor and
sensory axons in the adult rat spinal cord. J Neurosci 1994;14:4050-63.
3. Richardson PM, Issa VMK, Aguayo AJ. Regeneration of long spinal
axons in the rat. J Neurocytology 1984;13:165-82.
4. Li WWY, Yew DTW, Chuah MI, Leung PC, Tsang DSC. Axonal sprouting
in the hemisected adult rat spinal cord. Neurosci 1994;61(1):133-9.
5. Galea MP and Darian-Smith I. Multiple corticospinal neuron populations
in the macaque monkey are specified by their unique cortical origins,
spinal terminations, and connections. Cereb Cortex 1994;4:166-94.
6. Yu CG, Jimenez O, Marcillo AE, Weider B, Bangerter K, Dietrich
WD, Castro S, Yezierski RP. Beneficial effects of modest systemic
hypothermia on locomotor function and histopathological damage following
contusion-induced spinal cord injury in rats. J Neurosurg 2000;93(1
Suppl):85-93.
7. Maiman D. Symposium on spinal cord injury models: Introduction.
J Am Paraplegia Soc 1988;11:23-25.
8. Dobkin BH and Havton LA. Basic advances and new avenues in therapy
of spinal cord injury. Annu Rev Med 2004;55:255-82.
9. Scott GS, C Szabo, DC Hooper. Poly(ADP-ribose) polymerase activity
contributes to peroxynitrite induced spinal cord neuronal cell death
in vitro. J Neurotrauma 2004;21(9):1255-63
10. Li R, S Thode, N Richard, J Pardinas, MS Rao, DW Sah. Motoneuron
differentiation of immortalized human spinal cord cell lines. J
Neurosci Res 2000;59(3):342-52.
11. Perez MA, EC Field-Fote. Impaired posture-dependent modulation
of disynaptic reciprocal Ia inhibition in individuals with incomplete
spinal cord injury. Neurosci Lett 2003;341(3):225-8.
12. Emery E, P Aldana, MB Bunge, W Puckett, A Srinivasan, RW Keane,
J Bethea, AD Levi. Apoptosis after traumatic human spinal cord injury.
J Neurosurg 1998; 89(6):911-20.
13. Bruce JH, MD Norenberg, S Kraydieh, W Puckett, A Marcillo, D
Dietrich. Schwannosis: role of gliosis and proteoglycan in human
spinal cord injury. J Neurotrauma 2000;17(9):781-8.
14. Herman, R, J He, S D’Luzansky, W Willis, S. Dilli. Spinal
cord stimulation facilitates functional walking in a chronic incomplete
spinal cord injured. Spinal Cord 2002;40(2):65-8.
15. Carhart MR, J He, R Herman, S D’Luzansky, WT Willis. Epidural
spinal-cord stimulation facilitates recovery of function walking
following incomplete spinal-cord injury. IEEE Trans Neural Syst
Rehabil Eng 2004;12(1):32-42.
16. Widerstrom-Noga EG and DC Turk. Types and effectiveness of treatments
used by people with chronic pain associated with spinal cord injuries:
influence of pain and psychosocial characteristics. Spinal Cord
2003;41(11):600-9.
17. Nance PW, J Bugaresti, K Shellenberger, W Sheremata, A Martinez-Arizala.
Efficacy and safety of tizanidine in the treatment of spasticity
in patients with spinal cord injury. North American tizandine study
group. Neurology 1994;44(11 Suppl 9):S44-51.
18. Mathew KM, G Ravichandran, K May, K Morsley. The biophyschosocial
model and spinal cord injury. Spinal Cord 2001;39(12):644-9.
19. Raghavan P, WA Raza, YS Ahmed, MA Chamberlain. Prevalence of
pressure sores in a community sample of spinal injury patients.
Clin Rehabil 2003;17(8):879-84.
20. Sprigle S, M Linden, D McKenna, K Davis, B Riordan. Clinical
skin temperature measurement to predict incipient pressure ulcers.
Adv Skin Wound Care 2001;14(3):133-7.
21. Moussavi RM, HM Garza, SG Eisele, G Rodriguez, DH Rintala. Serum
levels of vitamins A, C, and E in persons with chronic spinal cord
injury living in the community. Arch Phys Med Rehabil 2003;84(7):1061-7.
22. Korsten MA, NR Fajardo, AS Rosman, GH Creasey, AM Spungen, WA
Bauman. Difficulty with evacuation after spinal cord injury: Colonic
motility during sleep and effects of abdominal wall stimulation.
J Rehabil Res Dev 2004;41(1):95-100.
23. Creasey GH, JH Grill, M Korsten, U HS, R Betz, R Anderson, J
Walter, Implanted Neuroprosthesis Research group. An implantable
neuroprosthesis for restoring bladder and bowel control to patients
with spinal cord injuries: a multicenter trial. Arch Phys Med Rehabil
2001;82(11):1512-9.
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