title: Ventricular expansion in wild-type Wistar rats after alcohol exposure by vapor chamber.
abstract: 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.
authors.affiliation: Neuroscience Program, SRI International, Menlo Park, California, USA.
authors.forename: Adolf
authors.initials: A
authors.lastname: Pfefferbaum
authors.forename: Natalie M
authors.initials: NM
authors.lastname: Zahr
authors.forename: Dirk
authors.initials: D
authors.lastname: Mayer
authors.forename: Shara
authors.initials: S
authors.lastname: Vinco
authors.forename: Juan
authors.initials: J
authors.lastname: Orduna
authors.forename: Torsten
authors.initials: T
authors.lastname: Rohlfing
authors.forename: Edith V
authors.initials: EV
authors.lastname: Sullivan
mesh_terms: 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
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol
references.citation: Alcohol Health Res World. 1995;19(4):321-324
references.pmid: 31798057
references.citation: Alcohol Alcohol. 1997 Mar-Apr;32(2):161-72
references.pmid: 9105510
references.citation: Brain Res. 1998 Apr 27;791(1-2):347-51
references.pmid: 9593988
references.citation: Alcohol Clin Exp Res. 2000 Apr;24(4):465-75
references.pmid: 10798582
references.citation: Neuroimage. 2007 Feb 1;34(3):879-87
references.pmid: 17127079
references.citation: Alcohol Clin Exp Res. 2004 Nov;28(11):1676-82
references.pmid: 15547454
references.citation: Neurology. 2003 Dec 23;61(12):1716-9
references.pmid: 14694035
references.citation: Alcohol Clin Exp Res. 1990 Dec;14(6):878-86
references.pmid: 2088124
references.citation: Alcohol Clin Exp Res. 2002 Mar;26(3):400-6
references.pmid: 11923595
references.citation: Alcohol Clin Exp Res. 2006 Oct;30(10):1678-92
references.pmid: 17010135
references.citation: Alcohol Clin Exp Res. 2003 Sep;27(9):1409-19
references.pmid: 14506401
references.citation: Alcohol Clin Exp Res. 1997 May;21(3):521-9
references.pmid: 9161613
references.citation: Alcohol Clin Exp Res. 2006 Jul;30(7):1248-61
references.pmid: 16792573
references.citation: Neuropsychol Rev. 2007 Sep;17(3):239-57
references.pmid: 17874302
references.citation: Alcohol Res Health. 2000;24(2):105-13
references.pmid: 11199277
references.citation: Alcohol Clin Exp Res. 1995 Feb;19(1):110-22
references.pmid: 7771636
references.citation: Psychiatry Res. 2006 Mar 31;146(2):157-70
references.pmid: 16500088
references.citation: Psychopharmacology (Berl). 2005 Oct;181(4):688-96
references.pmid: 16001125
references.citation: Alcohol Clin Exp Res. 2002 Apr;26(4):558-64
references.pmid: 11981133
references.citation: Alcohol Clin Exp Res. 1997 Apr;21(2):311-7
references.pmid: 9113269
references.citation: Arch Gen Psychiatry. 1998 Oct;55(10):905-12
references.pmid: 9783561
references.citation: Arch Gen Psychiatry. 2000 Sep;57(9):894-902
references.pmid: 10986553
references.citation: Neuroimage. 2004 May;22(1):381-6
references.pmid: 15110030
references.citation: Neuropsychology. 2000 Jul;14(3):341-52
references.pmid: 10928737
references.citation: Arch Gen Psychiatry. 1999 Apr;56(4):356-63
references.pmid: 10197833
references.citation: Addict Biol. 2006 Sep;11(3-4):270-88
references.pmid: 16961759
references.citation: Alcohol. 2005 Jan;35(1):19-26
references.pmid: 15922134
references.citation: Behav Brain Res. 2001 Mar 15;119(2):167-77
references.pmid: 11165332
references.citation: Am J Psychiatry. 2003 Jun;160(6):1110-6
references.pmid: 12777269
references.citation: Alcohol Alcohol. 1997 Jul-Aug;32(4):463-70
references.pmid: 9269854
references.citation: Alcohol Clin Exp Res. 1991 Jun;15(3):418-27
references.pmid: 1877728
references.citation: Drug Alcohol Depend. 1979 Jan-Mar;4(1-2):45-60
references.pmid: 41697
references.citation: Neuropsychopharmacology. 2000 Jun;22(6):581-94
references.pmid: 10788758
references.citation: Psychopharmacology (Berl). 2005 Aug;180(4):583-94
references.pmid: 15834536
references.citation: IEEE Trans Inf Technol Biomed. 2003 Mar;7(1):16-25
references.pmid: 12670015
references.citation: Alcohol Alcohol. 2002 Nov-Dec;37(6):513-21
references.pmid: 12414541
references.citation: Crit Rev Neurobiol. 1998;12(4):339-69
references.pmid: 10348615
references.citation: MAGMA. 2000 Jun;10(2):131-46
references.pmid: 10873203
references.citation: Magn Reson Imaging. 1995;13(4):555-61
references.pmid: 7674851
references.citation: Alcohol Alcohol. 2000 Jan;35(1):35-43
references.pmid: 10684774
references.citation: Alcohol Clin Exp Res. 2000 Jan;24(1):110-22
references.pmid: 10656200
references.citation: Neuroimage. 2004 Apr;21(4):1585-95
references.pmid: 15050582
references.citation: Neurobiol Aging. 2006 Jul;27(7):994-1009
references.pmid: 15964101
references.citation: Pharmacol Biochem Behav. 2004 Nov;79(3):439-50
references.pmid: 15582015
references.citation: Alcohol Clin Exp Res. 2006 Jul;30(7):1234-47
references.pmid: 16792572
references.citation: Alcohol Clin Exp Res. 1992 Dec;16(6):1078-89
references.pmid: 1471762
references.citation: Alcohol Clin Exp Res. 1993 Dec;17(6):1301-8
references.pmid: 8116846
references.citation: Alcohol Clin Exp Res. 1996 Nov;20(8):1489-95
references.pmid: 8947329
references.citation: Alcohol Clin Exp Res. 2004 Oct;28(10):1549-56
references.pmid: 15597088
references.citation: J Magn Reson Imaging. 2004 Nov;20(5):779-85
references.pmid: 15503335