Study Finds Carbon Monoxide can Trigger Brain-Damage Attack by Immune System

JAMA, October 6, 2004—Vol. 292, No. 13

Tracy Hampton, PhD

CARBON MONOXIDE'S REPUTATION as a stealth toxin goes be­yond its odorless, colorless properties. The gas can also surrepti­tiously cause delayed permanent brain damage, an effect that scientists have been unable to explain.  But now they are no longer in the dark. A new study reveals that the dam­age arises from over activation of im­mune cells that attack proteins that help insulate nerves.

The findings were published in the September 1 online issue of the Pro­ceedings of the National Academy of Science (vvvvw.pnas.org).

ONE-TWO PUNCH

Annually in the United Stales, about 40,000 individuals are treated for car­bon monoxide poisoning, the leading agent of injury and death by poison­ing worldwide.  The gas' initial effect on the body is a result of its high affinity for hemo­globin.  This causes hypoxic stress, and affected patients are generally treated with oxygen. 

Stephen Thorn, MD, PhD, of the University of Pennsylvania in Phila­delphia, has been studying carbon monoxide’s second effect—permanent brain damage, which can become evi­dent between 4 days and 3 weeks fol­lowing exposure. Thorn and col­leagues have found that this effect occurs because carbon monoxide exposure modifies myelin basic protein, found in the insulating cells around neurons.  "It turns out that the altered myelin basic protein is now recognized by the body as an invader or a foreign sub­stance," said Thorn. "The big surprise in our findings vas that once the immune system is turned on, the lymphocytes also recognize normal myelin basic pro­tein as abnormal.  As these immune cells continue to lash out against normal myelin basic protein, permanent brain damage can result.  Thorn and the research learn carne to their conclusions when they found that rats engineered to be incapable of mounting an immune response against myelin basic protein did not develop brain damage following carbon monoxide exposure. These rats also performed normally in a maze test that mea­sures cognitive and motor function.  Control rats did not fare as well. Their brain cells exhibited measur­able biochemical damage and the ani­mals performed poorly in the maze test.  "We think that that's also a clinical correlate—that is to say, patients who suffer serious carbon monoxide poi­soning and don't get early treatment, they have perhaps as much as a 50% chance of suffering what is called de­layed neurological sequelae." said Thorn. "So it's a clinically very important problem," one that can result in im­paired learning and concentration prob­lems, he said.

POTENTIAL THERAPIES?

The study's findings suggest potential therapies. "One of the next steps is to go back to the animal model and say, now that we have this pathway figured out, what can we what can we do to disturb it," said Thorn. Obvious candidates an immunosuppressants. It they prove effective in ani­mal studies, then "we rather quickly could be going to clinical trials to see if we can do something for patients," said Thorn. D

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This ties in well with the fact that an active immune system will stimulate healing response, which in turn results in the build up of plaque—see above article.--JK