Surprising Cause Found of Spinal Cord Injury

It is the first time that high levels of ATP have been identified as a cause of bodily injury. The findings were reported in the August issue of Nature Medicine.

Researchers from the University of Rochester Medical Center (NY, USA; www.rochester.edu) found that excess ATP damages motor neurons, whose death in the spinal cord results in paralysis. When the researchers blocked ATP's effects on neurons, the rats with damaged spinal cords recovered most of their function, walking and climbing nearly as well as healthy rats. This finding offers promise mainly to people who have just had a spinal cord injury, but not for those whose injury is more than a day old.

"This is an unusual way of looking at spinal cord injury,” explained Maiken Nedergaard, M.D., Ph.D., a professor of neurosurgery at the University of Rochester, who led the study. "Much of the focus of research has been on trying to regrow portions of the spinal cord. We're trying to stop the damage up front.”

The researchers used the same technology that underlies the enzyme luciferase to convert ATP to the glow it uses to light up. Dr. Nedergaard's team used the same enzyme to study the levels of ATP around the site of spinal cord injury, recording a very bright signal there for several hours. Although low levels of ATP provide a quick way for cells to communicate, Dr. Nedergaard said that levels found in the spinal cord were hundreds of times more higher than normal. The glut of ATP overstimulates neurons and causes them to die from metabolic stress.

The reason why neurons in the spinal cord are so susceptible to ATP is because of a molecule known as "the death receptor.” Also called P2X7, this receptor plays a role in regulating the deaths of immune cells such as macrophages. ATP uses this receptor to latch onto neurons and send them the flood of signals that causes their deaths. Dr. Nedergaard's team discovered that P2X7 is carried in abundance by neurons in the spinal cord.

The source of the ATP that kills the neurons gave researchers another surprise. Star-shaped cells called astrocytes, long thought to be simply passive support cells for neurons in the nervous system, produce the high levels of ATP. Scientists are beginning to believe that astrocytes also play a vital role in human health by nourishing neurons, supplying them with chemicals they need, and vacuuming up excess chemicals in order to keep the signals of neurons crisp.

"For a long time, astrocytes were thought of simply as the housekeepers of the brain, feeding the neurons and regulating their environment,” said Dr. Nedergaard. "But astrocytes are much more active than we have thought. It appears that sometimes astrocytes even give out the instructions telling neurons what to do. It's very likely they play an important role in many human diseases.”



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