improves transmission of signals. The treated rats also grew back many more nerve fibers than untreated rats or rats that received only one or two of the therapies. The regenerated nerve fibers included many that carry the nerve-signaling chemical serotonin, which is important for locomotion.

Rats that received the triple therapy had much better locomotion and coordination 8 weeks after treatment than control rats.

"The behavioral improvements in the rats receiving the triple therapy are dramatically better than those reported previously using Schwann cell bridges or cAMP strategies in spinal cord-injured animals," says Naomi Kleitman, Ph.D., the NINDS program director for spinal cord injury research. Previous studies using Schwann cells found that nerve fibers from cells above the injury could travel onto the Schwann cell bridge, but they did not leave the bridge, she explains. The triple therapy "punches the cells into overdrive and helps them get off the bridge."

The therapies tested in this study were selected for their likely feasibility in humans, Dr. Kleitman adds. Rolipram has already been tested in clinical trials for other disorders, and Schwann cells can be grown from patients' own peripheral nerves.

The researchers are now planning follow-up studies to confirm their results and to try to learn more about how the triple therapy works, Dr. Bunge says. Their studies might also lead to the development of better drugs to prevent the breakdown of cAMP, she adds.

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Contact: Natalie Frazin or Paul Girolami
301-496-5924
NIH/National Institute of Neurological Disorders and Stroke
23-May-2004

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