Scientists agree that alcohol is toxic and that chronic alcohol abuse can damage all organs - including the brain - to various degrees. There is less agreement, however, on whether or how much neurodegeneration is triggered by alcohol's toxicity during alcohol consumption or by the hyperexcitability caused by withdrawal from alcohol. A study in the April issue of Alcoholism: Clinical & Experimental Research uses rodents to examine what effects just a few days of the equivalent of binge drinking can have on neuronal function.
"Most studies of alcohol-induced brain damage have looked at humans who have been alcoholic for decades or rats treated with alcohol for six to 18 months," said Fulton T. Crews, Director of the Center for Alcohol Studies at the University of North Carolina and corresponding author for the study. "Our study shows significant damage in several regions of the brain after only four days, that it occurs during intoxication, and that the process is similar to a dark-cell degeneration that is primarily necrotic." Necrosis refers to the pathologic death of cells or a portion of tissue or organ due to irreversible damage.
Male Sprague-Dawley rats (n=120) were surgically implanted with intragastric catheters. Experimental rats (n= 80) were given alcohol at a rate equivalent to binge drinking, every eight hours for four consecutive days. Doses were based on their estimated blood alcohol levels. Control rats (n=40) were given an alcohol-free yet calorie-equivalent diet at the same rate. Several histological methods - such as amino cupric silver staining, fluoro-Jade B staining, hematoxylin and eosin staining, and transmission electron microscopy - were used to track the course, time points, and specific changes that occurred in conjunction with the alcohol intake. Some rats were sacrificed at two days, some at four days, and some after four days of alcohol and three days of withdrawal.
"This study shows significant damage in the olfactory bulb after just 2 days of heavy drinking," said Crews, "which is a short period of time relative to the decades of drinking that alcoholics do, and may be an important early process in the progression from experimentation with alcohol to addiction. In addition, the major current hypothesis regarding alcohol-induced brain damage suggests that damage occurs during withdrawal. All of these studies, however, were done in vitro (in an artificial environment). Our findings, which are in vivo (in the living body), indicate that alcohol-induced brain damage occurs during intoxication."
"In the rat," explained Michael A. Collins, professor of biochemistry at Loyola University Chicago, "which on one level is a 'walking nose,' the overall damage to the olfactory pathway is quite significant. The olfactory neurons in the bulb are some of the few neurons that are always turning over, dying and regenerating. One guess is that the repetitively elevated alcohol levels are pushing more of these neurons 'over the edge,' but apparently in a necrotic fashion."
Collins said that drinking patterns may specify the nature of neuropathology that occurs and the brain regions and neurons where it occurs. "The short-term binge pattern in these studies," he said, "which affords periodically high blood and brain alcohol levels, seems to damage the olfactory cortical regions quite selectively. In other models in which lower alcohol levels are sustained for several months - more akin to the primary type of alcohol abuse in countries like France and Spain - rodents show significant loss of brain neurons in regions evidently not affected in the brief binge-drinking model used here, for example, the cerebellum and the frontal cortex."
Collins added that even though chronic alcohol abuse damages all organs to greater or lesser degrees, most attention has been paid to liver damage, largely because it is easier for doctors to detect and measure, and can eventually lead to liver-failure death. However, he added, "a study of relatively young alcoholics published some time ago in the British journal Lancet showed that indicators of relatively permanent cognitive damage, measured by neuropsychological tests, actually showed up earlier than clinical signs of liver damage. Sadly, when the brain - the limbic cortex and dentate gyrus of the hippocampus, in this case - loses its excitable cells, for all practical purposes they are gone for good. In the day-to-day life of an alcoholic, this means a decreased ability to learn, to recall, to make decisions, and perhaps to sense and appreciate life in its fullest."
According to some estimates, said Collins, alcohol abuse in the United States is perhaps the third or fourth most common cause of brain damage, and may be even higher in other countries. "Given this," he said, "it is surprising that the mechanisms of brain neuronal degeneration due to a widely abused neurotoxicant are so understudied and therefore still somewhat obscure. Certainly this has implications for a college student contemplating a weekend of binge drinking. Seriously, though, it is possible that neuronal degeneration after a couple of days of heavy intoxication in the rat might translate to the human drinker who is not even a chronic alcohol abuser. There is no firm proof of this at present, and we would need brain imaging to determine whether acute short-term binge drinking in people could be permanently deleterious to olfactory or other neurons."
Funding for this Addiction Science Made Easy project is provided by the Addiction Technology Transfer Center National Office, under the cooperative agreement from the Center for Substance Abuse Treatment of SAMHSA.
Articles were written based on the following published research:
Obernier, J.A., Bouldin, T.W., & Crews, F.T. (2002, April). Binge ethanol exposure in adult rats causes necrotic cell death. Alcoholism: Clinical & Experimental Research, 26(4).
Hosted at A2