Georgetown studies find that delaying treatment of spinal cord injury may aid in recovery

December 01, 2001

Researchers at Georgetown University Medical Center have found that rats whose spinal cords had been severed recovered more fully when treatment was delayed until two to four weeks after the spinal cord injury. This unexpected, seemingly counterintuitive finding contradicts the idea that treatment must take place as quickly as possible to be effective. The study is being published in the December 1 issue of the Journal of Neuroscience.

The treatment the rats received consisted of transplanting spinal cord tissue from fetal rats--in conjunction with neurotrophins (substances made by the body that encourage nerves to grow)--into the gap where the spinal cord had been severed. Earlier studies by a team of scientists led by Barbara Bregman, PhD, professor and chair of neuroscience at Georgetown University, have shown that this combination increases the growth of nerve fibers after spinal cord injury. The most recent study, which was also led by Bregman, is the first to show that delaying this treatment by two to four weeks may be even more effective than immediate treatment.

"The intent of our experiment was to determine whether increased growth of nerve fibers contributed to the recovery of motor function," Bregman said. "We tested immediate and delayed treatment. Much to our surprise we found that delayed treatment was more effective."

The study involved four groups of rats whose spinal cords had all been completely severed. In the first group, researchers transplanted the fetal tissue into the lesion site immediately after the spinal cord had been severed. In the second group, researchers transplanted the fetal tissue two weeks after the spinal cord severance. The third group received the fetal tissue four weeks after severance, and the fourth was a control group that received no fetal tissue grafts.

The animals that received tissue grafts also received either saline (as a control), or one of two types of neurotrophins. The fetal tissue is thought to create a "highway" at the lesion point that provides a substance for the new nerve fibers to grow through, and neurotrophins have been shown to boost the capacity of nerve cells to generate new axons (long branches extending from nerve cells that transmit impulses from one nerve cell to another).

The researchers found that delaying the treatment by two to four weeks resulted in increased regrowth of nerve cell fibers. The addition of the neurotrophins to the fetal tissue grafts was key to recovery; the animals that received both tissue transplants and neurotrophins experienced significantly greater recovery than those that received the tissue grafts alone. Another surprising finding was that these rats experienced nerve regrowth in both "white matter" (tissue that contains nerve fibers coated by a fatty white substance called myelin) and in "gray matter" (tissue that does not contain myelin). This was surprising because previous research has shown that the presence of myelin may interfere with axon growth.

"These findings suggest that the time window for intervention may be far greater than we had originally thought, and that the neurons of the central nervous system with long-standing injuries may be able to reinitiate growth, leading to improvement in motor function," Bregman said.

"The research described in Dr. Bregman's latest article is very exciting," said Susan Howley, executive vice president and director of research of the Christopher Reeve Paralysis Foundation, on whose scientific advisory council Bregman serves. "The fact that limb function could actually be improved by delaying treatment gives us a whole new way to think about spinal cord injury. The window of opportunity for treating these injuries could be much wider than we previously thought."
The Georgetown research was supported in part by the National Institute of Neurological Disorders and Stroke (NINDS), a component of the National Institutes of Health.

According to statistics published by the National Spinal Cord Statistical Center, disabling spinal-cord injuries are suffered every year by 11,000 Americans, most of them young and active.

Georgetown University Medical Center

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