Ventricular expansion in wild-type Wistar rats after alcohol exposure by vapor chamber.
BACKGROUND
Structural magnetic resonance imaging (MRI) reveals widespread brain damage manifest as tissue shrinkage and complementary ventriculomegaly in human alcoholism. For an animal model to parallel the human condition, high alcohol exposure should produce similar radiologically detectable neuropathology. Our previous structural MRI study demonstrated only modest brain dysmorphology of the alcohol-preferring (P) rat with average blood alcohol levels(BALs) of 125 mg/dl achieved with voluntary consumption. Here, we tested the hypothesis that wild-type Wistar rats, exposed to vaporized alcohol ensuring higher BALs than typically achieved with voluntary consumption in rodents, would model MRI findings in the brains of humans with chronic alcoholism.


METHODS
The longitudinal effects of vaporized alcohol exposure on the brains of 10 wild-type Wistar rats compared with 10 sibling controls were investigated with structural MRI, conducted before (MRI 1) and after (MRI 2) 16 of alcohol exposure and after an additional 8 weeks at a higher concentration of alcohol (MRI 3).


RESULTS
Two rats in the alcohol group died prior to MRI 2. The remaining vapor-exposed rats(n = 8) achieved BALs of 293 mg/dl by MRI 2 and 445 mg/dl by MRI 3. Whereas the controls gained 17% of their body weight from MRI 1 to MRI 3, the alcohol-exposed group lost 6%.MRI, quantified with atlas-based parcellation, revealed a profile of significant ventricular expansion,after alcohol vapor exposure, in 9 contiguous slices, extending from the dorsolateral to ventrolateral ventricles. In particular, from MRI 1 to MRI 2, this ventricular volume expanded by an average of 6.5% in the controls and by 27.1% in the alcohol-exposed rats but only an additional 1.5% in controls and 2.4% in alcohol-exposed rats from MRI 2 to MRI 3. The midsagittal volume of the full anterior-to-posterior extent of the corpus callosum grew between the first 2 MRIs in both groups followed by regression in the alcohol group by MRI 3. Although group differences were statistically significant, among animals there was substantial variability of the effects of alcohol exposure on brain morphology; some animals showed profound effects, whereas others were essentially unaffected.


CONCLUSIONS
The ventricular dilatation and callosal shrinkage produced in wild-type rats following involuntary alcohol exposure yielded a modestly successful model of neurodysmorphology phenotypes of human alcoholism. As is the case for the human condition, however, in which some individuals express greater alcoholism-related neuropathology than others, some rats maybe more susceptible than others to extreme alcohol exposure.
Pfefferbaum
Adolf
A
Neuroscience Program, SRI International, Menlo Park, California, USA.
Zahr
Natalie M
NM
Mayer
Dirk
D
Vinco
Shara
S
Orduna
Juan
J
Rohlfing
Torsten
T
Sullivan
Edith V
EV
D000280:Administration, Inhalation; D000437:Alcoholism / Q000473:pathology; D000818:Animals; D001835:Body Weight; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D002552:Cerebral Ventricles / Q000187:drug effects* / Q000473:pathology*; D003337:Corpus Callosum / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D005260:Female; D008279:Magnetic Resonance Imaging; D008297:Male; D009330:Nebulizers and Vaporizers; D051381:Rats; D017208:Rats, Wistar
D002492:Central Nervous System Depressants; D000431:Ethanol
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