Brain injury and recovery following binge ethanol: evidence from in vivo magnetic resonance spectroscopy

Abstract

Background: The binge-drinking model in rodents using intragastric injections of ethanol (EtOH) for 4 days results in argyrophilic corticolimbic tissue classically interpreted as indicating irreversible neuronal degeneration. However, recent findings suggest that acquired argyrophilia can also identify injured neurons that have the potential to recover. The current in vivo magnetic resonance (MR) imaging and spectroscopy study was conducted to test the hypothesis that binge EtOH exposure would injure but not cause the death of neurons as previously ascertained postmortem.

Methods: After baseline MR scanning, 11 of 19 rats received a loading dose of 5 g/kg EtOH via oral gavage, then a maximum of 3 g/kg every 8 hours for 4 days, for a total average cumulative EtOH dose of 43 +/- 1.2 g/kg and average blood alcohol levels of 258 +/- 12 mg/dL. All animals were scanned after 4 days of gavage (post-gavage scan) with EtOH (EtOH group) or dextrose (control [Con] group) and again after 7 days of abstinence from EtOH (recovery scan).

Results: Tissue shrinkage at the post-gavage scan was reflected by significantly increased lateral ventricular volume in the EtOH group compared with the Con group. At the post-gavage scan, the EtOH group had lower dorsal hippocampal N-acetylaspartate and total creatine and higher choline-containing compounds than the Con group. At the recovery scan, neither ventricular volume nor metabolite levels differentiated the groups.

Conclusions: Rapid recovery of ventricular volume and metabolite levels with removal of the causative agent argues for transient rather than permanent effects of a single EtOH binge episode in rats.

Figure 1

Structural, group averaged computed T2-images showing example slices from Con and EtOH treated animals demonstrating increased ventricular volume in the EtOH animal at the post-gavage scan.

Figure 2

Quantification of ventricular volume (mean ± SE) at the 3 scan points (i.e., baseline, post-gavage, and recovery).

Figure 3

a) Axial (left), coronal (top right), and sagittal (bottom right) views of a rat brain demonstrating voxel placement^*. b) Averaged spectra of the Con group (n=8, dashed, red) and EtOH group (n=11, solid, blue) at the 3 scan points. Note the EtOH peak visible in the post-gavage spectra of the EtOH group. ^*see text for details on structures included in voxel.

Figure 4

Water-referenced metabolite levels in the dorsal hippocampal voxel at baseline, post-gavage, and recovery scans. * p<.05. Error bars represent standard errors.

Figure 5

Correlation between Cho and EtOH levels at the post-gavage scan as quantified using MRS.