About four years into her dissertation research, University neuroscience student Lois Kehl’s investigation into pain-transmitting neurons took a surprising turn.
In the study published in today’s Science magazine, Kehl and her co-researchers found cervical spinal cord tissue taken from young rats could generate functioning new neurons in a specially-prepared culture system, a fluid which contains substances that support cell growth. Many people believe regeneration of neurons is key to effective treatment of spinal cord injuries. While acknowledging their findings are a necessary step toward that end, Kehl, now a research associate in the School of Dentistry, cautioned against false hope.
“It will take the work of many laboratories a number of years to achieve that goal,” she said.
Neurons, also known as nerve cells, can receive and transmit nervous impulses. The human spinal cord consists of a bundle of nerve cells and fibers. Together with the brain, it is part of the central nervous system. Nerve cells in the spinal cord communicate senses and carry the brain’s messages to other parts of the human body. In spinal cord injuries, this two-way transmission is interrupted, resulting in complete or partial loss of sensory and motor functions in parts of the human body.
Unlike nerve cells in the peripheral nervous system, neurons in the spinal cord can seldom recover from serious damage. Until recently, scientists believed the spinal cord in mammals lost neuron-production capacity before birth. The University study defied this conviction.
Kehl and co-researchers made cultures of nerve tissue from the cervical spinal cord of 15- and 16-day-old rats to study nerve cells that are important to pain transmission. But they soon observed through microscope the apparent proliferation of neurons. Treating the tissue with antibodies that would distinguish neurons from other types of cells, the researchers counted the neurons in each culture and found their numbers had mushroomed from hundreds to tens of thousands within two weeks.
After a review of previous literature, Kehl and her colleagues came to believe that theirs was the first study in which pre-existing neurons were preserved in the culture as new ones came into being. It was also one of the few studies that regenerated neurons in nerve tissue from postnatal mammalian spinal cords.
In 1996, a group of Canadian scientists led by Samuel Weiss successfully generated new neurons from precursor cells, which are immature cells that might evolve into other types of nervous system cells. Weiss and his colleagues used spinal cord tissue from older rats but eliminated existing neurons at the beginning of the experiment.
Kehl said the Canadians failed to point out the new neurons were functional — producing action potentials which are a form of electrical impulses unique to working neurons. The University study therefore constituted an extension of the earlier work by demonstrating for the first time that newly-generated neurons function like normal nerve cells.
In some projects sponsored by the National Institute of Neurological Disorders and Stroke, scientists succeeded in transplanting fetal spinal cord tissue from rats into postnatal rat spinal cord to sustain damaged neurons for a limited period of time.
Trauma from accidents, gunshots and falls, as well as diseases such as polio, spina bifida and Friedreich’s Ataxia, can inflict spinal cord injuries. The institute estimates that approximately 10,000 new incidents occur each year. A total of about 200,000 Americans are severely disabled with spinal cord damages, roughly two-thirds of whom are under the age of 30.
Scientists have tried various methods to rehabilitate patients with spinal cord injuries, including implanting electrodes connected to a microcomputer. But for many, the hope of recovery is next to none.
Like scientists elsewhere, who have regenerated neurons either from fetal or postnatal tissues, Kehl and her colleagues are trying to single out the specific component of their culture system which stimulated the generation of new neurons. “Then one could imagine taking tissue from the central nervous system and putting it in a culture and allowing it to regenerate and then putting it back,” said University Professor of Pharmacology George Wilcox, who was Kehl’s academic advisor.
“But that’s a long way to go,” he quickly pointed out. “So it’s important to keep the therapeutic implications (of this study) to a minimum. Many other studies need to be done before there is a clinical application.”