In Stroke, the Immune System Turns Traitor
Discovery may help minimize brain damage
Strokes strike suddenly, but they can wreak damage for hours, even when doctors step in and restore blood flow with clot-busting drugs. Scientists have been at a loss to explain much of the continued deterioration--until now.
Researchers now say that some of the delayed injury is caused by the immune system running amok. Cardiologist David Pinsky of Columbia University School of Medicine and colleagues have discovered that neurons in distress coat themselves with proteins that switch on the complement system, a primitive immune-signaling system that triggers white blood cells to invade. "It's like activating a bunch of cluster bombs in the region," says Pinsky. "Not only can it target dead cells but bystander cells in the area get injured as well." In the rest of the body, killing injured cells and microbial invaders speeds healing and allows healthier tissues to regenerate. But in the brain, such an assault can permanently destroy neurons and other brain tissue that regenerate poorly, if at all.
A second immune-system response also exacerbates stroke damage. When deprived of oxygen, blood vessel walls break out in sticky selectin molecules, which help capture passing platelets and circulating white blood cells, or leukocytes. The platelets and leukocytes clog blood vessels and restrict flow. The leukocytes also migrate through blood vessel walls and unload a toxic arsenal of free radicals, enzymes, and acids.
Engineered defense. To reduce this damage, the researchers bioengineered a molecule to both halt complement action and maintain circulation. The scientists chose a molecule called sCR1, known to suppress the complement cascade, and studded it with carbohydrates that would bind to the selectins on oxygen-starved blood vessels. They found that up to 23 hours after an experimentally induced stroke, mice given the modified sCR1 enjoyed better neural function and more blood flow to stroke areas than those given plain sCR1 or left untreated. The researchers reported their results in last week's Science.
If the therapy proves successful in humans, it could slash the time elapsed between stroke and treatment, where minutes can spell the difference between recovery and permanent disability. Clot-dissolving drugs require a time-consuming CT scan before they are administered, in order to ensure that the drugs won't cause bleeding into the brain. Preliminary experiments suggest that hybrid sCR1 can be given immediately without increasing the risk of hemorrhaging.
Pinsky says the technique might also be used after heart attacks or organ transplant operations, when low oxygen levels spark the complement reaction. The researchers plan to confirm their results in other animals before testing the therapy on humans.
This story appears in the August 2, 1999 print edition of U.S. News & World Report.