Study Finds Soldiers Exposed to Sarin in Persian Gulf

12/22/2002

From: Steve Robinson of the National Gulf War Resource Center, 301-996-8450 E-mail: srobinson@ngwrc.org WASHINGTON, Dec. 22 -- Exposure to sarin nerve gas in concentrations too low to produce immediate symptoms causes irreversible brain damage in laboratory rats, according to a new study by researchers at the University of New Mexico, Albuquerque, and the U.S. Army Medical Research Institute of Chemical Defense, Aberdeen, Md. The new findings, published in three scientific articles in the peer-reviewed journal Toxicology and Applied Pharmacology, supplies the final missing piece of the puzzle that connects nerve gas exposure in the 1991 Gulf War to the collection of disabling symptoms known as Gulf War illness. In its September 2000 report, Gulf War and Health, Volume 1: Depleted Uranium, Sarin, Pyridostigmine Bromide, and Vaccines, an expert committee of the Institute of Medicine found that exposure to low-level sarin in concentrations sufficient to cause immediate symptoms can produce long-term brain injury with symptoms identical to those of Gulf War illness. The committee stopped short of attributing the veterans' illness to low-level sarin, however, because they found insufficient evidence proving that exposure to low-level sarin in concentrations below the level that would cause immediate symptoms can produce long-term brain injury. The committee recommended that further laboratory research in animals be undertaken to address this final link. In the new study researchers administered very low doses of sarin to laboratory rats for one hour per day for 1, 5 or 10 days, while observing the rats for signs of immediate effects on breathing, body temperature, activity level and body weight. The experiment was repeated in additional rats living in a high temperature environment. Half the rats in each experiment were sacrificed and tested for evidence of brain cell damage one day after the exposures ended, looking for immediate brain effects, and the other half were sacrificed and tested 30 days later for delayed, long-term effects. The study found that none of the sarin-exposed rats had immediate symptoms of nerve gas effects or brain changes at one day after the exposures were ended. However, at 30 days after the end of the exposures, the brains of the rats in all the sarin-exposed groups had marked signs of brain cell damage. The degree of brain cell damage was proportional to the dose of sarin given and was increased by living in the hot environment. The measure of brain cell damage used in the study was the loss of so-called muscarinic-1 (M1) cholinergic receptors. These are active sites on the surface of brain cells that normally allow the brain neurotransmitter acetylcholine to bind in transmitting brain signals. Loss of M1 cholinergic receptors would cause the brain cells not to respond normally to signals, resulting in symptoms. "Our results indicate that rats exposed to low levels of sarin, particularly under heat-stress conditions, sustain alterations in muscarinic receptor sites in critical areas of the brain and that most of these alterations appeared long after the exposure occurred," the study's authors concluded. "Repeated exposures to levels of sarin that would not be noticed clinically resulted in delayed development of brain alterations that could be associated with memory loss and cognitive dysfunction." The brain cell damage in the rats was found only in certain regions of the brain, most notably in the basal ganglia (also called the "striatum" by researchers), as well as in the frontal cortex, the olfactory tubercle and the anterior nucleus. The basal ganglia are vital deep brain structures that were found to be damaged in ill Gulf War veterans in a 2000 brain imaging study by researchers at the University of Texas Southwestern Medical Center in Dallas. Subsequently, that finding was replicated by brain imaging scientists at the University of California at San Francisco and the San Francisco VA Medical Center. "The bottom line is, now we have the evidence the IOM committee needed to draw a connection between low-level sarin and Gulf War illness," concluded Steve Robinson, director of the National Gulf War Resource Center. "It is urgent that the IOM committee evaluate the new evidence and revise their conclusions. This will allow the Secretary of Veterans Affairs to assure current troops that if they get wounded by nerve gas in Iraq next year, the VA system with take care of them." At the Society of Neuroscience meeting in Washington in late November, other researchers from the U.S. Army Medical Research Institute of Chemical Defense presented additional evidence of long-term brain damage in laboratory animals from low-level sarin and possible potentiation of the damage by pyridostigmine bromide, the active ingredient in anti-nerve gas tablets given to U.S. troops in the 1991 Gulf War. All of these new studies appear to corroborate the findings of studies reported in the early 1990s by researchers at the Indian Defense Research and Development agency, who first studied long-term effects of repeated low-level sarin exposure in laboratory animals. Additional evidence of the link in humans includes epidemiological surveys from the University of Texas Southwestern and the VA Central Office linking self-reported nerve gas exposure to Gulf War illness; the development of similar symptoms by survivors of the 1995 sarin attacks in the Tokyo and Matsumoto subways; and evidence of an increased susceptibility to nerve gas damage from a genetically determined deficiency of the paraoxonase enzyme in ill Gulf War veterans, reported by several research groups. Prior research over the past 20 years has shown that brain cells in the basal ganglia and other deep brain structures are particularly susceptible to damage by chemical warfare nerve agents. The U.S. Army Medical Research and Materiel Command funded the new study.