Immune response to spinal cord injury may worsen damage
A new study by neuroscientists at the Ohio State University Medical Center may have solved the mystery. It was found that antibodies may actually get worse and spread the damage to the spinal cord.
The first antibodies attach to nerve cells and other elements of the nervous system, then the other components of the immune system to attack cells and by antibodies labeled substances, like infectious agents or foreign material.
“Our results suggest that inhibiting or depleting B cells, cells that produce antibodies, can promote healing and reduce long-term effects of spinal cord injury,” says study leader Phillip G. Popovich, professor of neuroscience and molecular virology, immunology and medical genetics and director of the Center for brain and spinal cord repair.
“They may also help explain why the central nervous system does not repair itself effectively and why others are often impaired spinal cord injuries.
The animal study was published online by the Journal of Clinical Investigation.
Earlier work by Popovich and colleagues showed that B cells are activated as part of an immune response in general after a spinal cord injury, and accumulate around the injury of the spinal cord and begin producing antibodies.
For this study, Popovich, the first author Daniel P. Ankeny, and research associate Zhen Guan, used mice that were anesthetized and given a moderately severe spinal injury that mimics a contusion type of spinal injury in humans.
A group of injured mice with normal immune systems, antibody-producing cell B. A second group of mice was identical to the first except that lacked B cells, and therefore did not produce antibodies.
Nine weeks after spinal cord injury, the researchers compared the two groups.
They found that, on average, the area of spinal cord injury in mice without antibodies was 30 percent lower than the damaged area in the mice with antibodies.
They found that B cells and antibodies had accumulated around the spinal cord of normal mice but not in the other group, and that the antibodies were attached to the damaged areas of the spinal cord.
They also found substantially higher levels of antibodies in the bloodstream of the normal group after spinal cord injury that were present before the injury.
To determine whether these antibodies could on their own damage to the spinal cord, researchers purified the blood of the injured mice and microinjection in one side of the spinal cord of normal mice unharmed.
Within 48 hours, the hind leg on the side of the injection was halted, and remained partially after one week. The animals also showed that loss of neurons and other damage to the spinal cord.
“This was one of the most amazing, remarkable aspects of the study, the fact that antibodies of a wounded animal can activate an immune response that damages tissue in a healthy animal,” says Ankeny, research scientist in molecular virology, immunology and medical genetics.
“These experiments essentially show that antibodies have the potential to do for themselves spinal injuries worse.”
The researchers speculate that because antibodies are produced systemically, but also can damage other tissues. Popovich said that, along with paralysis, individuals with spinal cord injury may also have systemic problems, such as chronic bladder problems.
These are usually attributed to chronic catheterization and loss of bladder control, he says. “But that does not explain the changes that also occur in the kidneys. It may be that the antibodies target antigens in the kidney and cause kidney damage.
The same may be true in the sexual organs. “The male sterility is a significant problem in men with spinal injuries,” he says, “and there is no explanation why this happens.”
Source: Ohio State University Medical Center
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