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Neurons grown from embryonic stem cells restore function in paralyzed rats

roups of paralyzed rats. Each group received a different combination of treatments. Some groups received injections of a drug called rolipram under the skin before and after the transplants. Rolipram, a drug approved to treat depression, helps to counteract axon-inhibiting signals from myelin. Some animals also received transplants of neural stem cells that secreted the nerve growth factor GDNF into the sciatic nerve (the sciatic nerve extends from the spine down the back of the hind leg). GDNF causes axons to grow toward it.

Three months after the transplants, the investigators examined the rats for signs that the stem cell-derived neurons had survived and integrated with the nervous system. The rats that had received the full cocktail of treatments ?transplanted motor neurons, rolipram, dbcAMP, and GDNF-secreting neural stem cells in the sciatic nerve ?had several hundred transplant-derived axons extending into the peripheral nervous system, more than in any other group. The axons in these animals reached all the way to the gastrocnemius muscle in the lower leg and formed functional connections, called synapses, with the muscle. The rats showed an increase in the number of functioning motor neurons and an approximately 50 percent improvement in hind limb grip strength by 4 months after transplantation. In contrast, none of the rats given other combinations of treatments recovered lost function.

"We found that we needed a combination of all of the treatments in order to restore function," Dr. Kerr says.

Follow-up experiments with GDNF treatment on only one side of the body showed that, by 6 months after treatment, 75 percent of rats given the full combination of treatments regained the ability to bear weight on the GDNF-treated limbs and to take steps and push away with the foot on that side of the body.

"This research represents significant progress," says David Owens, Ph.D., the NINDS program director for the grant that funded t
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Source:NIH/National Institute of Neurological Disorders and Stroke


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