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  • ReceivedNov 29, 2019
  • AcceptedMar 28, 2020
  • PublishedMay 26, 2020

Abstract

Alcohol use disorder (AUD) is a global health concern associated with several comorbidities. Various health problems related to AUD, such as cognitive deficits, have been linked to neuroinflammation. Alcohol use has been associated with changes in neuroimmune activity, although current literature has yielded mixed results. For example, markers of gliosis, including translocator protein 18-kDa (TSPO), pro-inflammatory cytokines, glutamate (Glu), and myo-inositol (mI), are disrupted in the alcohol-dependent brain. Further, neuroinflammatory-related phenomena including membrane turnover, blood brain barrier (BBB) permeability, and adenosine release have also shown alterations in AUD. However, current literature remains inconclusive about the directionality of these changes. Both in vivo and in vitro studies have provided insight on the relationship between alcohol use and neuroinflammatory processes, suggesting considerable treatment potential for alcohol use disorder and its inflammatory comorbidities. Here, we review current neuroimaging literature assessing the impacts of alcohol use on neuroimmune activity in the brain.


Acknowledgment

This work was supported by National Institute on Alcohol Abuse and Alcoholism (Grant No. Y1AA-3009). We thank Yang HU for his valuable support in text formatting and reference management.


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  • Table 1  

    Table 1Direct and indirect indicators of neuroinflammation in AUD

    Marker Imaging methodRegionsFindings
    Gliosis
    18-kDA Human PET ([$^{11}$C]PBR28)Averaged across regions; cerebellum; hippocampus$^{\rm~ns}$; striatum$^{\rm~ns}$AUD textless HV [21]
    HippocampusAUD textless HV [22]
    Whole brain, GM, WM, hippocampus, and thalamusAUD textless HV$^{\#}$. neg corr. between cholesterol and PBR binding [23]
    Baboon PET ([$^{18}$F]DPA714)Whole brainBinge textgreater non-binge; sustained TSPO increase after 7 to 12 months [20]
    Rat PET ([$^{11}$C]PBR28)n/aNo significant differences [19]
    Cytokines DSC-MRIThalamus and frontal GM and WMAlcohol-caused increase in CBF in social drinkers [24]
    DSC-MRIAveraged across WM regionsAlcohol-caused increase in CBV in social drinkers [24]
    Glutamate MRSFrontal WMGlu neg corr. with drinking severity & “loss of control" [25]
    ACCAUD textless HV when presented with cues [26]
    Primary visual cortexAUD textless HV in early abstinence (Glx) [27]
    Bilateral medial frontal cortex AUD textless HV in early abstinence [28]
    ACCAUD textless HV in early abstinence [29]
    ACCAUD textgreater HV ([Glu] & [Glu]/[Cr]) [30,31]
    Nucleus accumbensAUD textgreater HV [45]
    Myo-inositol MRSStriatumAUD textgreater HV (in patients with HIV) [32]
    Parietal GMHeavy drinkers textgreater light drinkers [33]
    Averaged across parietal and frontal WMAUD textgreater HV [34]
    Right thalamus, ACCAUD textgreater HV [35]
    Membrane Turnover
    Choline MRSVisual cortexIncrease during heavy drinking ([Cho]/[Cr]) [27]
    Parietal GMHeavy drinkers textgreater light drinkers [33]
    CerebellumAUD textless HV, may or may not recover over time [36,37]
    ACCAUD textless HV [30]
    Left prefrontal cortexAUD textless HV [38]
    Frontal WM, cerebellar cortex, and cerebellar vermisAUD textless HV, recovers after 3 months [39]
    BBB
    Permeability
    Gadolinium-chelates CE-MRITemporal cortexEthanol induced BBB degradation [40]
    Altered water distributionBilateral frontal and temporal WM; AUD-C+AUD-R textgreater HV [41]
    Bilateral parietal regions, fornix and thalamus
    Adenosine Release
    Acetate$^{\dag}$ PET([$^{11}$C]Acetate)Cerebellum and thalamusIntoxication increases acetate uptake [42]
    ASL-MRIMedial thalamusAcetate increase in CBF [43,44]
    Right orbitofrontal, medial prefrontal, and cingulate cortex, and hippocampus; superior/inferior frontal gyri and bilateral ACCAlcohol increase in CBF [43,44]

    Note

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