Determining the Threshold for Alcohol-Induced Brain Damage: New Evidence with Gliosis Markers
Version of Record online: 24 JAN 2013
Copyright © 2013 by the Research Society on Alcoholism
Alcoholism: Clinical and Experimental Research
Volume 37, Issue 3, pages 425–434, March 2013
How to Cite
Hayes, D. M., Deeny, M. A., Shaner, C. A. and Nixon, K. (2013), Determining the Threshold for Alcohol-Induced Brain Damage: New Evidence with Gliosis Markers. Alcoholism: Clinical and Experimental Research, 37: 425–434. doi: 10.1111/j.1530-0277.2012.01955.x
- Issue online: 28 FEB 2013
- Version of Record online: 24 JAN 2013
- Manuscript Accepted: 26 JUL 2012
- Manuscript Received: 12 OCT 2011
- National Institute on Alcohol Abuse and Alcoholism. Grant Number: R01AA016959
- National Institute on Drug Abuse. Grant Number: T32DA007304
Chronic intake of ethanol (EtOH) has been linked to serious health consequences such as cardiac and liver problems, cognitive impairments, and brain damage. Alcohol's detrimental effects depend upon the dose, duration, and pattern of exposure with binge drinking as one of the most common, but most damaging, patterns of intake. Little is known about the threshold of the damaging effects of alcohol. Therefore, these experiments sought to determine a threshold for brain damage using various markers of neurodegeneration.
Adult male Sprague–Dawley rats were administered nutritionally complete liquid diet containing either EtOH (25% w/v) or isocaloric dextrose every 8 hours for either 1 (mean dose, 13.4 ± 0.3 g/kg/d; mean blood EtOH concentration (BEC), 336.2 ± 18.8 mg/dl) or 2 days (mean dose, 10.9 ± 0.3 g/kg/d; mean BEC, 369.8 ± 18.1 mg/dl). On the basis of a known time course of various neurodegeneration-associated events, rats were perfused transcardially immediately following, 2 days after, or 7 days post EtOH exposure. To label actively dividing cells, some animals were injected with BromodeoxyUridine (BrdU) 2 hours prior to perfusion. Tissue was then analyzed for the presence of BrdU (cell proliferation), FluoroJade B (degenerative neurons), and vimentin (reactive astrogliosis) immunoreactivity.
One or 2 days of EtOH exposure failed to alter cell proliferation at any of the time points analyzed. However, significant 2- to 9-fold increases in neuronal degeneration in limbic cortex and clear evidence of reactive gliosis as indicated by a 2- to 8-fold upregulation in vimentin immunoreactivity in the hippocampus were observed following as little as 1 day of binge EtOH exposure.
These results indicate that as little as 1 day (24 hours) of high BEC, binge-like EtOH exposure is enough to elicit signs of alcohol-induced brain damage in adult rats. Further, reactive gliosis may be a more sensitive marker of alcohol-induced damage in the hippocampus.