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Carbon Monoxide's Two-Pronged Attack
30 August 2004 (All day)
Researchers now understand why up to 40% of people poisoned with carbon monoxide mysteriously develop permanent brain damage weeks later. Changes to a protein found throughout the brain trigger a disastrous immune response. This knowledge could lead to new treatments for this common type of poisoning.
Carbon monoxide is an odorless, colorless gas, and more people die each year from inhaling it than from any other poison. Carbon monoxide sticks to oxygen-toting hemoglobin molecules inside blood cells much better than oxygen molecules do, which means the blood can't ferry oxygen to the brain and other organs. Doctors treat patients with pure oxygen and can remove carbon monoxide from the bloodstream within hours, but many people still develop permanent brain damage similar to Parkinson's disease. Until now, doctors couldn't explain why or how.
Through experiments with rats, Stephen Thom, an emergency-medicine physician at the University of Pennsylvania in Philadelphia, and his team tracked biochemical changes in the brain after carbon monoxide exposure. They found that when carbon monoxide deprives the brain of oxygen, a common protein in the insulating sheaths around neurons--myelin basic protein (MBP)--becomes altered. The chemically modified MBP then triggers immune responses throughout the brain. But the immune system doesn't know when to stop. After clearing away much of the altered MBP within a few weeks, immune cells continue to fight against normal MBP, "creating the potential risk of permanent, ongoing brain damage," says Thom.
To confirm that MBP is at the heart of the delayed brain damage, the team engineered a group of rats incapable of developing antibodies against MBP and exposed them to carbon monoxide. None of the rats developed delayed brain damage, and they performed normally in a maze test designed to measure cognitive and motor skills, the team reports online this week in the Proceedings of the National Academy of Sciences. Thom now hopes to investigate the possibility of preventing permanent brain damage through the use of immunosuppressant drugs.
The study is a tour de force, says Lindell Weaver, a critical-care physician at the University of Utah in Salt Lake City. He adds that the findings could have implications for treating other diseases and injuries that deprive the brain of oxygen.