Proton MR spectroscopic studies of chronic alcohol exposure on the rat brain

Abstract

Purpose: To better understand the long-term pathophysiologic mechanisms of alcoholism-related organic brain damage by serially assessing brain metabolites in chronically exposed rats using both in vivo magnetic resonance spectroscopy (MRS) and high-resolution nuclear magnetic resonance (NMR) from brain extracts. Materials and Methods:The alcoholic regimen was continued up to 60 weeks. In vivo proton MRS studies were performed at 200 MHz using a small animal imaging/spectrometer. In vitro rat brain extracts were also examined using a 500 MHz vertical bore magnet. Comparison measurements were also obtained in an age-matched control group. Results:In vivo results showed that there is a significant increase in the Cho/NAA ratio in the chronic alcohol-exposed group that reached a maximum around 16 weeks. After 44 weeks of alcohol exposure, Cho/NAA in the alcohol group decreased significantly from its maximum value to a value that was significantly lower than those from the control groups. Brain extract studies demonstrated that PC and GPC were the main components responsible for the observed in vivo spectral changes after 16 and 60 weeks of alcohol consumption, respectively. Conclusion:The fluctuation of choline-containing metabolites during alcohol intoxication could explain sometimes seemingly conflicting and confusing results from MRS studies in human and animal studies in which the duration of alcohol consumption and amount are varied widely.

Recreational alcohol use induces changes in the concentrations of choline-containing compounds and total creatine in the brain: a 1H MRS study of healthy subjects

“…This finding is in agreement with results from an animal study by Lee et al [58], in which an initially increasing tCho/tNAA signal was observed in alcohol-exposed rats. The increasing tCho/tNAA signal reached a maximum after approximately 16 weeks but eventually, after 44 weeks of alcohol exposure, the tCho/tNAA signal was lower than in the control group.…”

In Vivo Quantification of Ethanol Kinetics in Rat Brain

“…A longitudinal study of Sprague-Dawley rats chronically exposed to alcohol, however, showed an increase in the Cho/NAA ratio, peaking at about 16 weeks, followed by a decrease after 44 weeks of chronic alcohol exposure (Lee et al, 2003). Follow-up HPLC studies of tissue indicated that the alcohol-related metabolite ratio changes were possibly attributable to change in Cho rather than NAA.…”

Manifestations of early brain recovery associated with abstinence from alcoholism

“…Similarly, lowered levels of choline have been detected (Jagannathan et al, 1996;Seitz et al, 1999;Bloomer et al, 2004;Viola et al, 2004;Ende et al, 2005;Mason et al, 2006), although this finding seems even more ambiguous (Schweinsburg et al, 2000(Schweinsburg et al, , 2001(Schweinsburg et al, , 2003 and dependent on localization (Bendszus et al, 2001;Parks et al, 2002). Shifts between different choline containing compounds may contribute to these heterogeneous results (Lee et al, 2003). Spectroscopic elevations of inositol compounds (Schweinsburg et al, 2000(Schweinsburg et al, , 2001Viola et al, 2004) due to alcohol toxicity and deviations of other metabolites such as g-aminobutyric acid (Behar et al, 1999), glutamate, and glutamine have been reported but as yet these are still conflicting (Seitz et al, 1999;Braunova et al, 2000;Parks et al, 2002;Meyerhoff et al, 2004), related to comorbidities such as nicotine abuse (Mason et al, 2006), medical complications such as hepatic failure (Mesisca and Ross, quoted in Mason et al, 2005) or just the timepoint studied (Mason et al, 2003) and mostly difficult to detect reliably at conventional field strength and with appropriate signalto-noise (S/N) ratios.…”