Regenerating the Spinal Cord

Article excerpt

Researchers are moving systematically toward the distant goal of restoring movement to patients whose damaged central nervous system leaves them paralyzed.

More than three decades ago, as I was embarking on a research career studying limb regeneration in salamanders, I read an article about a young athlete who had broken his neck in a trampoline accident, leaving him a quadriplegic. He was engaged to be married. With no hope for recovery, he did a brave and unselfish thing. He called off the engagement to give his fiancee a chance at a normal life.

I had seen limb regeneration as a tool for investigating how cells organize themselves into tissue patterns and had had no interest in potential medical applications from limb regeneration research. Reading this article broadened my horizons, impressing me with the need for linking studies of the basic biology of regeneration to the development of regenerative therapies, especially for nervous system cells. At the time, it was believed that the human spinal cord had no capacity for regenerating itself, so the notion of medical intervention to reverse total paralysis was viewed as science fiction at best. Like other "impossibles," however, this one too has crumbled under the advances of scientific research.

Statistics compiled by the National Spinal Cord Injury Statistical Center at the University of Alabama, Birmingham, indicate that up to 230,000 persons in the United States are living with spinal cord injury (SCI) caused by trauma. Of the 10,000 new cases each year, 80 percent are males. Most cord injuries are due to compression of the spinal cord by pieces of broken vertebrae, leading to partial or complete paralysis.

The U.S. health-care costs of SCI exceed $8 billion per year and $1.5 million per patient over a lifetime, but even greater is the cost in personal freedom and quality of life. Thus, one goal of medical neuroscience is to diminish or reverse the paralysis caused by SCI. Designing successful therapies requires an understanding of the structure and function of the spinal cord (see "Our Complex Nervous System" on p. xxx), the molecular environment produced by injury, and the influences of the injury environment on spinal cord cells.

Injury events

Spinal cord injury that destroys substantial numbers of neurons and/or axons causes sensory deprivation and paralysis below the level of injury, followed by muscle atrophy and spasticity. The higher the level of injury along the spinal cord, the more body segments will be paralyzed and sensory deprived. This is why injuries in the cervical (neck) portion of the cord are devastating, because all sensory and motor connections below the neck are interrupted. The descending motor nerves passing through the neck carry signals that modulate the activity of the autonomic nervous system (which lies outside the vertebral column). Thus, interrupting the descending motor nerves not only disrupts movement of the limbs but causes disturbances in such autonomic functions as regulation of blood pressure, heart rate, and temperature.

Trauma to the spinal cord induces a cascade of events:

* First, blood vessels rupture, depriving the injured area of blood flow and hence of oxygen and glucose (the major sugar used as fuel by cells). As blood leaks into the wound from damaged vessels, it clots. In addition, excess fluid from the leak causes the cord to swell, further compressing the tissue and killing many neurons and glial cells outright.

* Second, undamaged neurons become overexcited, releasing excess amounts of a neurotransmitter that triggers the opening of membrane channels for calcium entry into a cell. Thus otherwise undamaged neurons can be damaged by a toxic influx of calcium.

* Third, the insulating myelin from both dead and surviving axons breaks down, and oligodendrocytes, the cells that normally wrap axons with organized myelin, instead secrete individual myelin proteins and other molecules into the lesion that inhibit axon growth. …