Philadelphia, PA - Later this fall, emergency-medicine physicians enter into what they call the “CO season” - a time when faulty furnaces and other mechanical mishaps lead to a spike in cases of carbon monoxide (CO) poisoning. CO poisoning is the leading cause of injury and death by poisoning worldwide, with about 40,000 people treated in the U.S. annually. Brain damage occurs - days to weeks later - in half of the patients with a serious case of CO poisoning.
The physiological causes of this delayed decline were not well understood until now. A team led by Stephen R. Thom, MD, PhD, Professor of Emergency Medicine and Chief of Hyperbaric Medicine, at the University of Pennsylvania School of Medicine, report this week online in the Proceedings of the National Academies of Sciences that CO causes profound changes in myelin basic protein (MBP) - a major protein constituent of myelin, the protective sheath surrounding neurons. Using an animal model, they showed that the CO-induced changes in MBP set into motion an autoimmune response in which lymphocytes, triggered to eliminate altered MBP, continue to attack normal MBP.
Specifically, the researchers found that by-products of CO metabolism in the brain alter the charge and structure of MBP. “These changes in MBP have also been demonstrated in multiple sclerosis, which is why we paralleled the study along those lines,” says Thom.
To link acute CO poisoning to long-term brain injury, the team conducted tests on normal versus CO-poisoned rats, comparing their abilities to navigate and memorize a maze. "CO poisoned rats don't learn," said Thom. "But if you render their immune systems tolerant to altered MBP, by feeding them normal MBP before CO poisoning and thereby short-circuiting the lymphocyte response, the rats learn normally."
Thom says that overall this work suggests that the 50 percent or more of patients who develop brain damage following severe CO poisoning may do so, in large part, due to an autoimmune reaction. The body simply does not know when to stop attacking what it now views as an invader. “This opens up a lot of possibilities, such as treatment with immunosuppressant agents, in conjunction with standard hyperbaric oxygen therapy,” he says. “Until our study elucidated this immune response, we had no motivation to think along those lines.”
Penn colleagues on the paper are: Veena M. Bhopale, Donald Fisher, Jie Zhang, and Phyllis Gimotty. This study was funded by the National Institutes of Health.
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