October 18, 2004

UCSD Medical Researchers Use Brain Cell Transplants
To Correct Muscle Spasms After Aneurysm Surgery

By Sue Pondrom

Transplantation of human brain cells corrected involuntary muscle spasms in rats with ischemic spinal cord injury, according to research published online October 12 and in print October 19, 2004 in the European Journal of Neurosciences by investigators at the University of California, San Diego (UCSD) School of Medicine.

Ischemic spinal cord injury, caused by reduced blood flow to the spinal cord, occurs in 20 to 40 percent of the several hundred patients each year in the U.S. who undergo surgery to repair an aneurysm, or sac-like widening of the aorta, the main artery that leaves the heart. A subpopulation of patients with ischemic spinal cord injury develop a prominent muscle spasticity, or jerkiness of the legs and lower body, due to the irreversible loss of specialized spinal cord cells that control local motor function.

During a 12-week period in which the animals were followed, the UCSD team found that rats receiving the brain, or neuronal cell transplants displayed a progressive recovery of motor function and a decrease in spasticity in the lower extremities over a period of several weeks following the injections. Fifty percent of the animals experienced a significant improvement in motor function. In contrast, the “control” rats that did not receive transplants exhibited no improvement in motor function or spasticity. A post-mortem study of the animals showed a robust growth of neurons and an increase in neurotransmitters in the spinal cords of rats that received the transplanted neuronal cells.

“These findings provide conclusive evidence that transplantation of well defined human neuronal cells into a specific region of the spinal cord can be an effective treatment for spasticity in cases of ischemic spinal cord injury,” said the study’s lead author, Martin Marsala, M.D., UCSD associate professor of anesthesiology.

“While we believe the transplantation may relieve spasticity in victims of traumatic spinal cord injury, as well, it won’t help those patients recover voluntary movement,” he added.

Current treatment for debilitating muscle spasticity is continuous systemic or spinal drug treatments using implanted pumps. These approaches display limited efficacy with accompanying side effects and eventual drug tolerance.

The ischemic spinal cord injury that occurs during surgery is usually due to clamping of the blood flow to the spinal cord, to permit repairs of the aorta, Marsala said. The loss of specialized spinal cord neurons called spinal inhibitory neurons is irreversible and the resulting spasticity often worsens over time as more neurons are lost.

In addition to Marsala, authors of the paper included Tony Yaksh, Ph.D. and Osamu Kakinohana, Ph.D., UCSD Department of Anesthesiology; and Zoltan Tomori and Dasa Cizkova, Slovak Academy of Sciences, Slovakia. The study was funded by the National Institutes of Health.

Media Contact: Sue Pondrom (619) 543-6163