Milestones in Spinal Cord Injury Research.
Finding a cure for Spinal injury paralysis
1981
Albert Aguayo proves that axons in the rat could regrow in the central nervous system (CNS) through a peripheral nerve graft. However, once on the other side of the graft, back in the hostile CNS environment, the regenerating axons stop almost immediately.
1969
Regeneration research gets a huge boost when Geoffrey Raisman shows electron microscopic proof that new synapses (connections) form in the adult rat brain after injury. It had always been thought that the CNS was "hard wired" and lacked plasticity (the ability to adapt following trauma). Raisman's work shows that the CNS actually could "reorganize" itself after injury and form new connections.
1951
Nobel Prize winner Rita Levi-Montalcini, and Viktor Hamburger, discover a nerve growth factor (NGF). NGF is needed for the survival of nerves, enhanced regeneration in lower animals and the "rescue" of certain nerve cells in mammalian brains after injury.
World War II
Individuals begin to survive the initial stages of spinal cord injury with the advent of neurosurgery and bacteria-killing drugs that control formerly fatal lung, bladder and skin infections.
Sir Ludwig Guttmann pioneers a centralized rehabilitation approach to SCI individuals. His Stoke Mandeville Hospital in England becomes a model for the worldwide development of SCI centers.
1890
Santiago Ramón y Cajal, the father of modern neuroscience, describes the nervous system and its individual nerve cells. He reports that although mammalian CNS nerves try to regenerate, they do not get far. He blames their failure to regrow on the hostile environment of the CNS.
1830's
Anatomist Theodor Schwann finds evidence of rabbit sciatic
regeneration below a cut nerve. The peripheral nervous system cells that make the myelin
wrapping around axons are named Schwann cells in his honor. These cells, transplanted to
the damaged spinal cord, are eventually thought to help repair nerves whose wrapping has
been lost due to injury.
2500 B.C.
Spinal cord injury is described as "an ailment not to be treated" - found on an Egyptian surgical papyrus.
Source: American Paralysis Association.
Reference: Maddox, Sam. The Quest for a Cure:
Restoring Function After Spinal Cord Injury. Paralyzed Veterans of America.
Washington, D.C.: 1993.
APACURE
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The following are key events in the diagnosis of spinal cord injury paralysis and the search for a cure:2006 In a research project published in the Journal of Neuroscience,the Drexel University College of Medicine in Philadelphia led by Professor of Neurobiology and Anatomy John Houle has observed in Laboratory experiments how a nerve taken from a lab animal and transplanted across spinal cord injury combined with a enzyme digestion of scar material can lead to a regeneration of the injured nerve tissue and lead to recovery of limb movements. The milestone of this lab demonstration is that the process is equally applicable to animals that are newly injured as well as in animals with long-term injuries because of the ability to use the implanted nerve bridge to direct regeneration towards a specific target area in the spinal cord.
The next follow up of this experiment will be to test the ability of that specific enzyme, chondroitinase, to modify scar tissue, reducing its normal inhibitory nature and facilitating growth beyond the implanted nerve bridge.
Dr. Houle: “This study represents a major milestone in the battle to return spinal cord injury patients to a state of mobility, however there is still a lot of work to be done to adapt this procedure to human use.”
1996 Lars Olson of the Karolinska Institute reports for the
first time having achieved "true functional recovery" of a severed adult rat
spinal cord. Olson and colleagues used a five-step strategy, including implanted
peripheral nerve bridges stabilized by using fibrin glue mixed with fibroblast growth
factor. (Scientists caution that the procedure was successfully done on only a few animals
and none recovered the ability to walk. These experiments will have to be replicated in
other laboratories around the world. Science News, Vol. 150; July 27, 1996.) 1995 The American Paralysis Association Consortium on Spinal
Cord Injury is organized to help stimulate research on repair of the chronically damaged
spinal cord. The APA Consortium focuses on three objectives: a) characterizing the injured
and uninjured cords at the cellular and molecular levels; b) identifying ways to promote
recovery of nerve cell function and axon regrowth; and c) investigating strategies to
replace nerve cells destroyed by the injury. The collaboration pools the expertise and
scientific tools of a number of neuroscientists and focuses them strategically and
cohesively on the problem of chronic spinal cord injury. 1994 Fred Gage reports that skin cells, genetically engineered to secrete growth factors and neurotransmitters, cause massive regeneration of sensory nerve cells in the spinal cord. Genetically engineered cells with growth factors believed to cause regeneration of movement controlling cells are now being tested. Wise Young organizes the first multi center, animal spinal cord injury (SCI) study using a standardized rodent model, treatment protocols and behavioral recovery scale to test drug therapies, to identify viable SCI treatments and reduce the average 11-year wait for FDA approval. Martin Schwab reports dramatic regrowth of nerves in partially severed rat spinal cords after treatment with a combination of the antibody IN-1 and the growth-promoting factor NT-3. 1992 First human clinical trials of the nerve-boosting drug 4-aminopyridine (4-AP) are held. 4-AP allows nerve signals to pass along axons which have lost their "insulation wrapping" due to injury. These early trials show that in some chronically paralyzed patients, 4-AP can increase the ability of axons to conduct signals and thus restore some lost function after injury. 1990
"Decade of the Brain" declared by the United States Congress. Martin Schwab induces nerve regeneration in the rat spinal cord by blocking damaging proteins with an antibody called IN-1. With this treatment, regenerating axons grow about 11 millimeters; without treatment, they do not grow even one millimeter. The first effective treatment for acute SCI is identified. Clinical Trials show that neurological recovery in Human spinal cord injuries improves by an average 20% if large doses of the steroid methylprednisolone (MP) are administered within eight hours of injury. 1988 Martin Schwab discovers two myelin-associated proteins that inhibit growth in the damaged mammalian spinal cord, a revolutionary finding. Until now, it was believed that the cord's inability to regenerate was due only to the absence of nerve growth factors. |