Chronic ethanol increases systemic TLR3 agonist-induced neuroinflammation and neurodegeneration.
- Authors
- Qin, Liya; Crews, Fulton T
- Year
- 2012
- Journal
- Journal of neuroinflammation
- PMID
- 22709825
- DOI
- 10.1186/1742-2094-9-130
- PMCID
- PMC3412752
BACKGROUND: Increasing evidence links systemic inflammation to neuroinflammation and neurodegeneration. We previously found that systemic endotoxin, a TLR4 agonist or TNFα, increased blood TNFα that entered the brain activating microglia and persistent neuroinflammation. Further, we found that models of ethanol binge drinking sensitized blood and brain proinflammatory responses. We hypothesized that blood cytokines contribute to the magnitude of neuroinflammation and that ethanol primes proinflammatory responses. Here, we investigate the effects of chronic ethanol on neuroinflammation and neurodegeneration triggered by toll-like receptor 3 (TLR3) agonist poly I:C. METHODS: Polyinosine-polycytidylic acid (poly I:C) was used to induce inflammatory responses when sensitized with D-galactosamine (D-GalN). Male C57BL/6 mice were treated with water or ethanol (5 g/kg/day, i.g., 10 days) or poly I:C (250 μg/kg, i.p.) alone or sequentially 24 hours after ethanol exposure. Cytokines, chemokines, microglial morphology, NADPH oxidase (NOX), reactive oxygen species (ROS), high-mobility group box 1 (HMGB1), TLR3 and cell death markers were examined using real-time PCR, ELISA, immunohistochemistry and hydroethidine histochemistry. RESULTS: Poly I:C increased blood and brain TNFα that peaked at three hours. Blood levels returned within one day, whereas brain levels remained elevated for at least three days. Escalating blood and brain proinflammatory responses were found with ethanol, poly I:C, and ethanol-poly I:C treatment. Ethanol pretreatment potentiated poly I:C-induced brain TNFα (345%), IL-1β (331%), IL-6 (255%), and MCP-1(190%). Increased levels of brain cytokines coincided with increased microglial activation, NOX gp91phox, superoxide and markers of neurodegeneration (activated caspase-3 and Fluoro-Jade B). Ethanol potentiation of poly I:C was associated with ethanol-increased expression of TLR3 and endogenous agonist HMGB1 in the brain. Minocycline and naltrexone blocked microglial activation and neurodegeneration. CONCLUSIONS: Chronic ethanol potentiates poly I:C blood and brain proinflammatory responses. Poly I:C neuroinflammation persists after systemic responses subside. Increases in blood TNFα, IL-1β, IL-6, and MCP-1 parallel brain responses consistent with blood cytokines contributing to the magnitude of neuroinflammation. Ethanol potentiation of TLR3 agonist responses is consistent with priming microglia-monocytes and increased NOX, ROS, HMGB1-TLR3 and markers of neurodegeneration. These studies indicate that TLR3 agonists increase blood cytokines that contribute to neurodegeneration and that ethanol binge drinking potentiates these responses.
TLR3 agonist poly I:C induction of TNFα in mouse serum and brain. Levels of proinflammatory cytokine TNFα were determined following a single poly I:C (250 μg/kg, i.p.) and d-galactosamine (D-GalN, 20 mg/kg, i.p.) injection into C57BL/6 mice. At the time points indicated, mice were sacrificed and brain extracts and sera prepared as described in methods. Note both brain and serum TNFα peaked at three hours. Interestingly, blood (serum) TNFα declined to control level by 24 hours whereas brain TNFα level remained elevated at about half the peak level for at least 72 hours. The results shown are the means ± SEM of two experiments performed with seven mice per time point. *P <0.05, **P <0.01, compared to the corresponding vehicle controls.
Activated Fluoro-Jade B in brain. (A) Brain sections were stained with Fluoro-Jade B, a marker of cell death, and quantitated in cortex and dentate gyrus. The Fluoro-Jade B fluorescence in cortex and dentate gyrus was increased by ethanol, poly I:C and sequential ethanol-poly I:C. The results are the means ± SEM of two independent experiments performed with seven mice per group. **P <0.01, compared with vehicle control. ##P <0.01, compared with poly I:C. (B) Confocal microscopy images of cortex (upper panels) and dentate gyrus (lower panels) in ethanol-poly I:C group. Immunolabeling was visualized by using Alexa Fluor 488 and 555. Confocal microscopy indicates that Fluoro-Jade B in green (left panels) are NeuN positive in red (middle panels), as shown in the merged images (right panels) with arrows indicating yellow co-labeling. Scale bar, 30 μm.
Minocycline and naltrexone block microglial activation.(A) Quantification of activated Iba1 + IR cells in cortex. Ethanol, poly I:C and ethanol-poly I:C treatment groups show increased microglial activation. Minocycline and naltrexone decreased ethanol-poly I:C-activated Iba1 + IR cells. (C, control; E, ethanol; P, poly I:C; EP, ethanol-poly I:C; EPM, ethanol-poly I:C-minocycline; EPN, ethanol-poly I:C-naltrexone.). (B) Representative images from vehicle control (C), ethanol-poly I:C (EP), ethanol-poly I:C-minocycline (EPM) and ethanol-poly I:C-naltrexone (EPN) groups in cortex. In control, EPM and EPN groups, most microglia are in a resting state: small cell bodies with thin, highly ramified processes. In the EP-treated group, microglia are activated: large cell bodies, irregular shape and intensified Iba1 staining. **P <0.01, compared with control group. ##P <0.01, compared with poly I:C group. $$P <0.01, compared with ethanol-poly I:C group. Scale bar, 200 μm.
Minocycline and naltrexone blunt ethanol-poly I:C-induced caspase-3 + IR. (A) Brain sections were stained with polyclonal cleave caspase-3 (Asp175) antibody. Immunolabeling was visualized by using nickel-enhanced 3,3′-diaminobenzidinne (DAB) as described in the methods. The number of caspase-3 + IR cells in cortex was significantly increased in ethanol, poly I:C and ethanol-poly I:C treatment groups. Minocycline and naltrexone reduced ethanol-poly I:C-induced caspase-3 expression. (C, control; E, ethanol; P, poly I:C; EP, ethanol-poly I:C; EPM, ethanol-poly I:C-minocycline; EPN, ethanol-poly I:C-naltrexone). (B) Images are representative of vehicle control (C), ethanol-poly I:C (EP), ethanol-poly I:C-minocycline (EPM) and ethanol-poly I:C-naltrexone (EPN) groups in cortex. Scale bar, 50 μm. *P <0.05, **P <0.01, compared with vehicle control. ##P <0.01, compared with poly I:C. $$P <0.01, compared with ethanol-poly I:C.
Schematic summary and hypothetical mechanisms of neuroinflammation and neurodegeneration. (Lower left) Chronic ethanol treatment potentiates poly I:C increases serum TNFα IL-1β, IL-6 and MCP-1 protein. These proteins in the blood enter the brain through transport systems or other mechanisms as described in the discussion (upper left). In brain these proinflammatory cytokines activate microglia. Ethanol can also directly activate NF-κB transcription. Activated microglia amplify the brain neuroinflammatory response through at least three potential mechanisms. Loop 1 represents microglial synthesis and release of cytokines that activate transcription factor NF-κB to synthesize and release more inflammatory cytokines, which further activates the microglia, producing more proinflammatory signals. Loop 2 involves activation of NADPH oxidase (NOX) in microglia that produces reactive oxygen species that activate transcription factor NF-κB to synthesize and release more inflammatory cytokines. Loop 3 involves HMGB1, a TLR activator, and TLR3 on microglia that stimulates NF-κB and microglial activation. Cytokine, glutamate and/or ethanol release of HMGB1 that can activate multiple TLR receptors on microglia. Our findings of ethanol increased HMGB1 and TLR3 expression in brain support a role for loop 3 in microglial activation. Together, these amplify proinflammatory responses that spread from microglia to neurons (upper right). Neuronal expression of NOX increases oxidative stress leading to neuronal death. Minocycline and naltrexone block microglial activation and blunt neuronal death. These studies suggest that blood proinflammatory signals contribute to neuroinflammation and neurodegeneration that can be prevented by blocking microglial proinflammatory activation
Effect of chronic ethanol treatment on poly I:C-induced blood and brain TNFα and IL-1β. As described in the methods, male C57BL/6 mice were treated intragastrically with ethanol (5 g/kg, i.g. daily for 10 days) and 24 hours after the last dose of ethanol treatment injected intraperitoneally with poly I:C (250 μg/kg) plus D-GalN (20 mg/kg). Brains were collected three hours after poly I:C injection for all groups, that is, ethanol alone is 27 hours after the last dose of ethanol. The levels of serum TNFα and IL-1β protein and brain TNFα and IL-1β mRNA and protein were measured by real-time PCR and ELISA. (A) Poly I:C treatment increased serum TNFα protein and brain TNFα mRNA and protein. Ethanol treatment did not alter serum TNFα protein, but increased brain TNFα mRNA and protein. Ethanol exposure potentiated poly I:C-induced serum TNFα protein as well as brain TNFα mRNA and protein. (B) Poly I:C treatment increased serum IL-1β protein and brain IL-1β mRNA and protein. Ethanol alone had no significant effect. Ethanol pretreatment potentiated poly I:C-induced serum IL-1β protein and brain IL-1β gene expression and protein synthesis. The results are the means ± SEM in two independent experiments with seven animals per group. *P <0.05, **P <0.01, compared with the vehicle control group. #P <0.05, compared with the corresponding poly I:C treated group.
Effect of chronic ethanol treatment on poly I:C-induced blood and brain IL-6 and MCP-1. As described in the methods, male C57BL/6 mice were treated intragastrically with ethanol (5 g/kg, i.g. daily for 10 days) and 24 hours after the last dose of ethanol treatment injected intraperitoneally with poly I:C (250 μg/kg) plus D-GalN (20 mg/kg). Brains were collected three hours after poly I:C injection for all groups, that is, ethanol alone is 27 hours after the last dose of ethanol. (A) Ethanol or poly I:C alone treatment increased serum IL-6 protein and brain IL-6 mRNA and protein. Sequential ethanol-poly I:C treatment significantly augmented the blood and brain levels of IL-6. (B) Ethanol or poly I:C alone treatment increased serum MCP-1 protein and brain MCP-1 mRNA and protein. Ethanol pretreatment potentiated poly I:C-induced serum MCP-1 protein and brain MCP-1 gene expression and protein synthesis. The results are the means ± SEM in two independent experiments with seven animals per group. *P <0.05, **P <0.01, compared with the vehicle control group. #P <0.05, compared with the corresponding poly I:C treated group.
Immunocytochemical analysis of microglia. Mice were treated as described above. (A) Levels of immunoreactive density of Iba1, a marker of microglia, in cortex and hippocampal dentate gyrus were quantified using BioQuant image analysis software and presented as mean ± SEM in pixel/mm2. Ethanol alone, poly I:C alone and ethanol-poly I:C treated groups all show increased Iba1 + IR in both brain regions. (B) Representative images of Iba1 + IR cells in cortex and dentate gyrus from control and ethanol-poly I:C-treated groups. In water control group, microglia showed a resting morphological shape. In either ethanol or poly I:C alone-treated groups, some of the microglia are enlarged (images not shown). Iba1 + IR cells in EtOH-poly I:C-treated mouse brains have increased cell size, irregular shape, and intensified Iba1 staining consistent with morphological changes in activated microglia. Scale bar, 200 μm.
Induction of NOX-NADPH oxidase subunit gp91phoxexpression. Male C57BL/6 mice were treated with ethanol, poly I:C, ethanol-poly I:C as indicated in methods. (A) gp91phox gene expression was determined by real-time PCR three hours after poly I:C treatment. Note chronic ethanol pretreatment increased brain poly I:C-induced gp91phox mRNA by 2.7-fold. (B) NADPH oxidase subunit gp91phox + IR in cortex and dentate gyrus (DG). Sections were stained with monoclonal mouse gp91phox antibody and quantified by BioQuant image analysis system. NADPH oxidase subunit gp91phox + IR was increased in cortex about 6 fold by ethanol and 14 fold by poly I:C and in DG about 5 fold by ethanol and 10 fold by poly I:C. Pretreatment of ethanol significantly enhanced poly I:C-induced gp91phox + IR in both cortex and DG. (C) The images shown are representative of gp91phox + IR cells from cortex (left) and dentate gyrus (right) for control (upper images) and ethanol-poly I:C groups (lower images). *P <0.05, **P <0.01, compared with the vehicle control mice. #P <0.05, ##P <0.01, compared with poly I:C-treated mice. Scale bar, 200 μm.
Confocal microscopy with cell specific markers finds neuronal and microglial expression of NADPH oxidase subunit gp91phox. Brain sections from ethanol-poly I:C-treated mice were double-labeled for gp91phox in green with neuronal marker MAP-2, microglial marker Iba1, or astroglial marker GFAP in red. Co-labeling was investigated using a Leica SP2 LCS confocal microscope with associated software. The representative images shown are from dentate gyrus of mice treated with ethanol-poly I:C. The left panel of pictures shows gp91phox + IR. The middle panel shows cell specific markers, for example, neuronal MAP-2 (upper panel), microglial Iba1 (middle) and astrocyte GFAP (lower panel) pictures. Merged images are to the right. Merged yellow indicates red and green are combined and likely co-localized within the marked cell. Merged pictures on the right with enlarged cells suggest that gp91phox + IR is expressed in MAP-2 neurons (yellow) and Iba1 microglia (yellow), but not in astrocytes. Scale bar, 30 μm; inset 5 μm.
Superoxide formation and oxidative stress in brain. Mice were injected with hydroethidine (dihydroethidium, 10 mg/kg, i.p.) 2.5 hours after poly I:C treatment and brains harvested 30 minutes later, frozen and sectioned (15 μm thickness) as described in the methods. The oxidation product, ethidium, is formed from dihydroethidium by superoxide resulting in ethidium accumulation within cells producing superoxide. Ethidium is detected as red nuclei by fluorescence microscopy. The level of fluorescence intensity of ethidium-positive cells was quantified by BioQuant image analysis software. (A) Quantitation of ethidium fluorescence indicates ethanol, poly I:C and ethanol + poly I:C treatment significantly increases O2- and O2--derived oxidant production in cortex. (B) Representative images of ethidium fluorescence. Ethanol and poly I:C alone increased O2- and O2--derived oxidant production compared with vehicle control. Ethanol pretreatment significantly potentiated poly I:C-induced O2- and O2--derived oxidant production. **P <0.01, compared with vehicle control group. ##P <0.01 compared with poly I:C group. Scale bar, 200 μm.
Ethanol increases TLR3 and HMGB1 expression. Chronic ethanol treatment of C57BL/6 mice (5 g/kg, i.g., daily for 10 days) increased mRNA and protein expression (+IR) of brain TLR3 and HMGB1. (A) Quantitation of TLR3 mRNA and TLR3 + IR. (A-a) Level of brain TLR3 mRNA 27 hours following the last dose of ethanol treatment was measured using real-time PCR as described in the methods. Ethanol exposure significantly increased brain TLR3 mRNA. (A-b) TLR3 + IR cells were counted in mouse cortex after TLR3 immunostaining. Ethanol significantly increased the number of TLR3 + IR cells. (A-c) Representative images of immunohistochemical staining for TLR3 in the cortex of control and ethanol-treated mice. (B) Quantitation of HMGB1 mRNA and HMGB1 + IR. (B-a) HMGB1 mRNA was measured by real-time PCR in which ethanol increased by about 2 fold. (B-b) Quantitative evaluation of HMGB1 + IR. The number of HMGB1 + IR cells was increased about 2 fold. (B-c) The representative images of immunohistochemical staining for HMGB1 in the cortex of control and ethanol-treated mice. *P <0.05, **P <0.01, compared with water control group. Scale bar, 50 μm.
Activated caspase-3 + IR in brain. Brain sections were stained with polyclonal cleave caspase-3 (Asp175) antibody, a marker of cell death. (A) Quantitation of caspase-3 + IR in cortex. The number of caspase-3 + IR cells in cortex was increased by ethanol, poly I:C and sequential ethanol-poly I:C. (B) Quantitation of caspase-3 + IR in hippocampal dentate gyrus. The number of caspase-3 + IR cells in dentate gyrus was increased by ethanol, poly I:C and sequential ethanol-poly I:C. The results are the means ± SEM of two independent experiments performed with seven mice per group. *P <0.05, **P <0.01, compared with vehicle control. ##P <0.01, compared with poly I:C. (C and D) Representative images of caspase-3 + IR in cortex (C) and dentate gyrus (D) in vehicle control and ethanol-poly I:C groups. Scale bar, 200 μm. To determine if caspase-3 + IR was within neurons, brain sections were double-stained with NeuN (a neuronal marker). (E) Confocal microscopy images of cortex (upper panels) and dentate gyrus (lower panels) in ethanol-poly I:C group. Immunolabeling was visualized by using Alexa Fluor 488 and 555. Confocal microscopy indicates that caspase-3 + IR cells in green (left panels) are NeuN positive in red (middle panels), as shown in the merged images (right panels) with arrows indicating yellow co-labeling of caspase-3 and NeuN. Insets are higher magnification of the merged images. Scale bar, 30 μm; inset 5 μm.
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| Citation | PMID | DOI | Status |
|---|---|---|---|
| AgrawalRGHewetsonAGeorgeCMSyapinPJBergesonSEMinocycline reduces ethanol drinkingBrain Behav Immun2011Suppl 1S165S1692139700510.1016/j.bbi.2011.03.002PMC3098317 | — | — | — |
| AlexopoulouLHoltACMedzhitovRFlavellRARecognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3Nature200141373273810.1038/3509956011607032 | — | — | — |
| Alfonso-LoechesSPascual-LucasMBlancoAMSanchez-VeraIGuerriCPivotal role of TLR4 receptors in alcohol-induced neuroinflammation and brain damageJ Neurosci2010308285829510.1523/JNEUROSCI.0976-10.201020554880PMC6634595 | — | — | — |
| BanksWAEricksonMAThe blood–brain barrier and immune function and dysfunctionNeurobiol Dis201037263210.1016/j.nbd.2009.07.03119664708 | — | — | — |
| BindokasVPJordanJLeeCCMillerRJSuperoxide production in rat hippocampal neurons: selective imaging with hydroethidineJ Neurosci19961613241336877828410.1523/JNEUROSCI.16-04-01324.1996PMC6578569 | — | — | — |
| BlancoAMVallesSLPascualMGuerriCInvolvement of TLR4/type I IL-1 receptor signaling in the induction of inflammatory mediators and cell death induced by ethanol in cultured astrocytesJ Immunol2005175689368991627234810.4049/jimmunol.175.10.6893 | — | — | — |
| BlednovYABenavidezJMGeilCPerraSMorikawaHHarrisRAActivation of inflammatory signaling by lipopolysaccharide produces a prolonged increase of voluntary alcohol intake in miceBrain Behav Immun2011Suppl 1S92S1052126619410.1016/j.bbi.2011.01.008PMC3098320 | — | — | — |
| BlednovYAPonomarevIGeilCBergesonSKoobGFHarrisRANeuroimmune regulation of alcohol consumption: behavioral validation of genes obtained from genomic studiesAddict Biol201211081202130994710.1111/j.1369-1600.2010.00284.xPMC3117922 | — | — | — |
| BlockMLZeccaLHongJSMicroglia-mediated neurotoxicity: uncovering the molecular mechanismsNat Rev Neurosci20078576910.1038/nrn203817180163 | — | — | — |
| BsibsiMRavidRGvericDvan NoortJMBroad expression of Toll-like receptors in the human central nervous systemJ Neuropathol Exp Neurol200261101310211243071810.1093/jnen/61.11.1013 | — | — | — |
| CarpentierPABegolkaWSOlsonJKElhofyAKarpusWJMillerSDDifferential activation of astrocytes by innate and adaptive immune stimuliGlia20054936037410.1002/glia.2011715538753 | — | — | — |
| CartyMBowieAGEvaluating the role of Toll-like receptors in diseases of the central nervous systemBiochem Pharmacol20118182583710.1016/j.bcp.2011.01.00321241665 | — | — | — |
| ChenCJChenJHChenSYLiaoSLRaungSLUpregulation of RANTES gene expression in neuroglia by Japanese encephalitis virus infectionJ Virol200478121071211910.1128/JVI.78.22.12107-12119.200415507597PMC525064 | — | — | — |
| ChenWJParnellSEWestJRNeonatal alcohol and nicotine exposure limits brain growth and depletes cerebellar Purkinje cellsAlcohol199815334110.1016/S0741-8329(97)00084-09426835 | — | — | — |
| CrewsFTNixonKMechanisms of neurodegeneration and regeneration in alcoholismAlcohol Alcohol2009441151271894095910.1093/alcalc/agn079PMC2948812 | — | — | — |
| CrewsFTNixonKWilkieMEExercise reverses ethanol inhibition of neural stem cell proliferationAlcohol20043363711535317410.1016/j.alcohol.2004.04.005 | — | — | — |
| CrewsFTZouJQinLInduction of innate immune genes in brain create the neurobiology of addictionBrain Behav Immun2011Suppl 1S4S122140214310.1016/j.bbi.2011.03.003PMC3552373 | — | — | — |
| DejagerLLibertCTumor necrosis factor alpha mediates the lethal hepatotoxic effects of poly(I:C) in D-galactosamine-sensitized miceCytokine200842556110.1016/j.cyto.2008.01.01418331798 | — | — | — |
| DoyleSEO’ConnellRVaidyaSAChowEKYeeKChengGToll-like receptor 3 mediates a more potent antiviral response than Toll-like receptor 4J Immunol2003170356535711264661810.4049/jimmunol.170.7.3565 | — | — | — |
| Fernandez-LizarbeSPascualMGuerriCCritical role of TLR4 response in the activation of microglia induced by ethanolJ Immunol20091834733474410.4049/jimmunol.080359019752239 | — | — | — |
| FinchCEMorganTESystemic inflammation, infection, ApoE alleles, and Alzheimer disease: a position paperCurr Alzheimer Res2007418518910.2174/15672050778036225417430245 | — | — | — |
| GarbuttJCEfficacy and tolerability of naltrexone in the management of alcohol dependenceCurr Pharm Des2010162091209710.2174/13816121079151645920482515 | — | — | — |
| GargADNowisDGolabJVandenabeelePKryskoDVAgostinisPImmunogenic cell death, DAMPs and anticancer therapeutics: an emerging amalgamationBiochim Biophys Acta2010180553711972011310.1016/j.bbcan.2009.08.003 | — | — | — |
| GlassCKSaijoKWinnerBMarchettoMCGageFHMechanisms underlying inflammation in neurodegenerationCell201014091893410.1016/j.cell.2010.02.01620303880PMC2873093 | — | — | — |
| Guha-ThakurtaNMajdeJAEarly induction of proinflammatory cytokine and type I interferon mRNAs following Newcastle disease virus, poly [rI:rC], or low-dose LPS challenge of the mouseJ Interferon Cytokine Res19971719720410.1089/jir.1997.17.1979142648 | — | — | — |
| GuLOkadaYClintonSKGerardCSukhovaGKLibbyPRollinsBJAbsence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptor-deficient miceMol Cell1998227528110.1016/S1097-2765(00)80139-29734366 | — | — | — |
| GundersenHJBendtsenTFKorboLMarcussenNMollerANielsenKNyengaardJRPakkenbergBSorensenFBVesterbyAWestMJSome new, simple and efficient stereological methods and their use in pathological research and diagnosisAPMIS19889637939410.1111/j.1699-0463.1988.tb05320.x3288247 | — | — | — |
| HarperCThe neuropathology of alcohol-related brain damageAlcohol Alcohol2009441361401914779810.1093/alcalc/agn102 | — | — | — |
| HeJCrewsFTIncreased MCP-1 and microglia in various regions of the human alcoholic brainExp Neurol200821034935810.1016/j.expneurol.2007.11.01718190912PMC2346541 | — | — | — |
| HuangWTangYLiLHMGB1, a potent proinflammatory cytokine in sepsisCytokine20105111912610.1016/j.cyto.2010.02.02120347329 | — | — | — |
| HutchinsonMRShavitYGracePMRiceKCMaierSFWatkinsLRExploring the neuroimmunopharmacology of opioids: an integrative review of mechanisms of central immune signaling and their implications for opioid analgesiaPharmacol Rev20116377281010.1124/pr.110.00413521752874PMC3141878 | — | — | — |
| HutchinsonMRZhangYBrownKCoatsBDShridharMSholarPWPatelSJCrysdaleNYHarrisonJAMaierSFRiceKCWatkinsLRNon-stereoselective reversal of neuropathic pain by naloxone and naltrexone: involvement of toll-like receptor 4 (TLR4)Eur J Neurosci200828202910.1111/j.1460-9568.2008.06321.x18662331PMC2588470 | — | — | — |
| JiangWSunRWeiHTianZToll-like receptor 3 ligand attenuates LPS-induced liver injury by down-regulation of toll-like receptor 4 expression on macrophagesProc Natl Acad Sci USA2005102170771708210.1073/pnas.050457010216287979PMC1287976 | — | — | — |
| KielianTMicroglia and chemokines in infectious diseases of the nervous system: views and reviewsFront Biosci2004973275010.2741/126614766404 | — | — | — |
| LiuJLewohlJMHarrisRAIyerVRDoddPRRandallPKMayfieldRDPatterns of gene expression in the frontal cortex discriminate alcoholic from nonalcoholic individualsNeuropsychopharmacology2006311574158210.1038/sj.npp.130094716292326 | — | — | — |
| LiuJYangARKellyTPucheAEsogaCJuneHLElnabawiAMerchenthalerISieghartWSr JuneHLAurelianLBinge alcohol drinking is associated with GABAA alpha2-regulated Toll-like receptor 4 (TLR4) expression in the central amygdalaProc Natl Acad Sci U SA20111084465447010.1073/pnas.1019020108PMC306022421368176 | — | — | — |
| LiuYQinLWilsonBWuXQianLGranholmACCrewsFTHongJSEndotoxin induces a delayed loss of TH-IR neurons in substantia nigra and motor behavioral deficitsNeurotoxicology20082986487010.1016/j.neuro.2008.02.01418471886PMC2762082 | — | — | — |
| MandrekarPCatalanoDSzaboGInhibition of lipopolysaccharide-mediated NFkappaB activation by ethanol in human monocytesInt Immunol1999111781179010.1093/intimm/11.11.178110545482 | — | — | — |
| MarosoMBalossoSRavizzaTLiuJAronicaEIyerAMRossettiCMolteniMCasalgrandiMManfrediAABianchiMEVezzaniAToll-like receptor 4 and high-mobility group box-1 are involved in ictogenesis and can be targeted to reduce seizuresNat Med20101641341910.1038/nm.212720348922 | — | — | — |
| McClainJAMorrisSADeenyMAMarshallSAHayesDMKiserZMNixonKAdolescent binge alcohol exposure induces long-lasting partial activation of microgliaBrain Behav Immun2011Suppl 1S120S1282126233910.1016/j.bbi.2011.01.006PMC3098298 | — | — | — |
| NelsonSKollsJKAlcohol, host defence and societyNat Rev Immunol2002220520910.1038/nri74411913071 | — | — | — |
| NguyenMDJulienJPRivestSInnate immunity: the missing link in neuroprotection and neurodegeneration?Nat Rev Neurosci2002321622710.1038/nrn75211994753 | — | — | — |
| OlsonJKMillerSDMicroglia initiate central nervous system innate and adaptive immune responses through multiple TLRsJ Immunol2004173391639241535614010.4049/jimmunol.173.6.3916 | — | — | — |
| ParkCLeeSChoIHLeeHKKimDChoiSYOhSBParkKKimJSLeeSJTLR3-mediated signal induces proinflammatory cytokine and chemokine gene expression in astrocytes: differential signaling mechanisms of TLR3-induced IP-10 and IL-8 gene expressionGlia20065324825610.1002/glia.2027816265667 | — | — | — |
| PlaneJMShenYPleasureDEDengWProspects for minocycline neuroprotectionArch Neurol2010671442144810.1001/archneurol.2010.19120697034PMC3127230 | — | — | — |
| PruettSBFanRZhengQAcute ethanol administration profoundly alters poly I:C-induced cytokine expression in mice by a mechanism that is not dependent on corticosteroneLife Sci2003721825183910.1016/S0024-3205(02)02507-912586220 | — | — | — |
| QinLCrewsFTNADPH oxidase and reactive oxygen species contribute to alcohol-induced microglial activation and neurodegenerationJ Neuroinflammation20129510.1186/1742-2094-9-522240163PMC3271961 | — | — | — |
| QinLHeJHanesRNPluzarevOHongJSCrewsFTIncreased systemic and brain cytokine production and neuroinflammation by endotoxin following ethanol treatmentJ Neuroinflammation200851010.1186/1742-2094-5-1018348728PMC2373291 | — | — | — |
| QinLLiuYWangTWeiSJBlockMLWilsonBLiuBHongJSNADPH oxidase mediates lipopolysaccharide-induced neurotoxicity and proinflammatory gene expression in activated microgliaJ Biol Chem2004279141514211457835310.1074/jbc.M307657200 | — | — | — |
| QinLWuXBlockMLLiuYBreeseGRHongJSKnappDJCrewsFTSystemic LPS causes chronic neuroinflammation and progressive neurodegenerationGlia20075545346210.1002/glia.2046717203472PMC2871685 | — | — | — |
| ReFStromingerJLIL-10 released by concomitant TLR2 stimulation blocks the induction of a subset of Th1 cytokines that are specifically induced by TLR4 or TLR3 in human dendritic cellsJ Immunol2004173754875551558588210.4049/jimmunol.173.12.7548 | — | — | — |
| SchulzODieboldSSChenMNaslundTINolteMAAlexopoulouLAzumaYTFlavellRALiljestromPReis e SousaCToll-like receptor 3 promotes cross-priming to virus-infected cellsNature200543388789210.1038/nature0332615711573 | — | — | — |
| ScumpiaPOKellyKMReevesWHStevensBRDouble-stranded RNA signals antiviral and inflammatory programs and dysfunctional glutamate transport in TLR3-expressing astrocytesGlia20055215316210.1002/glia.2023415920723 | — | — | — |
| SimsGPRoweDCRietdijkSTHerbstRCoyleAJHMGB1 and RAGE in inflammation and cancerAnnu Rev Immunol20102836738810.1146/annurev.immunol.021908.13260320192808 | — | — | — |
| SivoriSFalcoMDella ChiesaMCarlomagnoSVitaleMMorettaLMorettaACpG and double-stranded RNA trigger human NK cells by Toll-like receptors: induction of cytokine release and cytotoxicity against tumors and dendritic cellsProc Natl Acad Sci U S A2004101101161012110.1073/pnas.040374410115218108PMC454174 | — | — | — |
| TangSCArumugamTVXuXChengAMughalMRJoDGLathiaJDSilerDAChigurupatiSOuyangXMagnusTCamandolaSMattsonMPPivotal role for neuronal Toll-like receptors in ischemic brain injury and functional deficitsProc Natl Acad Sci USA2007104137981380310.1073/pnas.070255310417693552PMC1959462 | — | — | — |
| WangQZhouHGaoHChenSHChuCHWilsonBHongJSNaloxone inhibits immune cell function by suppressing superoxide production through a direct interaction with gp91phox subunit of NADPH oxidaseJ Neuroinflammation201293210.1186/1742-2094-9-3222340895PMC3305409 | — | — | — |
| WestMJGundersenHJUnbiased stereological estimation of the number of neurons in the human hippocampusJ Comp Neurol199029612210.1002/cne.9029601022358525 | — | — | — |
| WuDCTeismannPTieuKVilaMJackson-LewisVIschiropoulosHPrzedborskiSNADPH oxidase mediates oxidative stress in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson’s diseaseProc Natl Acad Sci USA20031006145615010.1073/pnas.093723910012721370PMC156340 | — | — | — |
| WuYLousbergELMoldenhauerLMHayballJDRobertsonSACollerJKWatkinsLRSomogyiAAHutchinsonMRAttenuation of microglial and IL-1 signaling protects mice from acute alcohol-induced sedation and/or motor impairmentBrain Behav Immun2011Suppl 1S155S1642127684810.1016/j.bbi.2011.01.012 | — | — | — |
| YanaiHBanTWangZChoiMKKawamuraTNegishiHNakasatoMLuYHangaiSKoshibaRSavitskyDRonfaniLAkiraSBianchiMEHondaKTamuraTKodamaTTaniguchiTHMGB proteins function as universal sentinels for nucleic-acid-mediated innate immune responsesNature20094629910310.1038/nature0851219890330 | — | — | — |
| ZouJCrewsFCREB and NF-kappaB transcription factors regulate sensitivity to excitotoxic and oxidative stress induced neuronal cell deathCell Mol Neurobiol2006263854051663389110.1007/s10571-006-9045-9PMC11520752 | — | — | — |
| ZouJCrewsFInduction of innate immune gene expression cascades in brain slice cultures by ethanol: key role of NF-kappaB and proinflammatory cytokinesAlcohol Clin Exp Res20103477778910.1111/j.1530-0277.2010.01150.x20201932 | — | — | — |
In this knowledge base
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Microglia Promote Neurodegeneration and Hyperkatifeia during Withdrawal and Abstinence from Binge Alcohol. | McNair EM et al. | — | 2026 | → |
| Modulatory effects of GLT-1 enhancer, MC-100093, on neuroinflammatory factors in mesocorticolimbic brain regions of female P rats exposed chronically to ethanol. | Bhowmik KK et al. | — | 2026 | → |
| Adolescent binge alcohol exposure accelerates Alzheimer's disease-associated basal forebrain neuropathology through proinflammatory HMGB1 signaling. | Fisher RP et al. | — | 2025 | → |
| Binge ethanol consumption can be attenuated by systemic administration of minocycline and is associated with enhanced neuroinflammation in the central amygdala. | Schrank S et al. | — | 2025 | → |
| Excessive Alcohol Use as a Risk Factor for Alzheimer's Disease: Epidemiological and Preclinical Evidence. | Anton PE et al. | — | 2025 | → |
| Impact of adolescent ethanol binge on serotonin signaling and pain sensitivity post-withdrawal. | Feller AJ et al. | — | 2025 | → |
| Impact of Neuroimmune System Activation by Adolescent Binge Alcohol Exposure on Adult Neurobiology. | Macht V et al. | — | 2025 | → |
| Modulation of TNFα-driven neuroinflammation by Gardenin A: insights from <i>in vitro</i>, <i>in vivo</i>, and <i>in silico</i> studies. | Chadha P et al. | — | 2025 | → |
| Neural Inflammation in Thoracic Dorsal Root Ganglia Mediates Cardiopulmonary Spinal Afferent Sensitization in Chronic Heart Failure | Hong J et al. | — | 2025 | — |
| Adolescent intermittent ethanol (AIE) sensitized fever in male Sprague Dawley rats exposed to poly I:C in adulthood. | Gano A et al. | — | 2024 | → |
| Alcohol, HMGB1, and Innate Immune Signaling in the Brain. | Crews FT et al. | — | 2024 | → |
| Association between cytokines and suicidality in patients with psychosis: A multicentre longitudinal analysis. | Hoprekstad GE et al. | — | 2024 | → |
| Binge ethanol exposure in advanced age elevates neuroinflammation and early indicators of neurodegeneration and cognitive impairment in female mice. | Anton PE et al. | — | 2024 | → |
| cGAS/STING signaling pathway-mediated microglial activation in the PFC underlies chronic ethanol exposure-induced anxiety-like behaviors in mice. | Zhao W et al. | — | 2024 | → |
| Effects of novel GLT-1 modulator, MC-100093, on neuroinflammatory and neurotrophic biomarkers in mesocorticolimbic brain regions of male alcohol preferring rats exposed chronically to ethanol. | Travaglianti S et al. | — | 2024 | → |
| Epigenetic regulation of microglia and neurons by proinflammatory signaling following adolescent intermittent ethanol (AIE) exposure and in human AUD. | Crews FT et al. | — | 2024 | → |
| Knockdown of Tlr3 in dorsal striatum reduces ethanol consumption and acute functional tolerance in male mice. | Dilly GA et al. | — | 2024 | → |
| Mesenchymal stem cells as a promising therapy for alcohol use disorder. | Gallardo J et al. | — | 2024 | → |
| Postinjury Alcohol Use Is Associated With Prolonged Recovery After Concussion in NCAA Athletes. | Chang RC et al. | — | 2024 | → |
| Detrimental Effects of Alcohol-Induced Inflammation on Brain Health: From Neurogenesis to Neurodegeneration. | Anand SK et al. | — | 2023 | → |
| Differential Effects of Nicotine, Alcohol, and Coexposure on Neuroimmune-Related Protein and Gene Expression in Corticolimbic Brain Regions of Rats. | Randall CA et al. | — | 2023 | → |
| Healthy lifestyles and wellbeing reduce neuroinflammation and prevent neurodegenerative and psychiatric disorders. | Kip E et al. | — | 2023 | → |
| HMGB1 is a promising therapeutic target for asthma. | Zhao Y et al. | — | 2023 | → |
| Sclerostin, vascular risk factors, and brain atrophy in excessive drinkers. | MartÃn-González C et al. | — | 2023 | → |
| Targeting Persistent Changes in Neuroimmune and Epigenetic Signaling in Adolescent Drinking to Treat Alcohol Use Disorder in Adulthood. | Crews FT et al. | — | 2023 | → |
| The effects of lipopolysaccharide exposure on social interaction, cytokine expression, and alcohol consumption in male and female mice. | Decker Ramirez EB et al. | — | 2023 | → |
| The Influence of Arsenic Co-Exposure in a Model of Alcohol-Induced Neurodegeneration in C57BL/6J Mice. | Sides TR et al. | — | 2023 | → |
| The neuroimmune system - Where aging and excess alcohol intersect. | Carlson ER et al. | — | 2023 | → |
| Adolescent Binge Alcohol Enhances Early Alzheimer's Disease Pathology in Adulthood Through Proinflammatory Neuroimmune Activation. | Barnett A et al. | — | 2022 | → |
| Animal Models for Neuroinflammation and Potential Treatment Methods. | Tamura Y et al. | — | 2022 | → |
| Anti-inflammatory drugs prevent memory and hippocampal plasticity deficits following initial binge-like alcohol exposure in adolescent male rats. | Deschamps C et al. | — | 2022 | → |
| Attenuation of the levels of pro-inflammatory cytokines prevents depressive-like behavior during ethanol withdrawal in mice. | Fraga-Junior EB et al. | — | 2022 | → |
| Cholinergic and Neuroimmune Signaling Interact to Impact Adult Hippocampal Neurogenesis and Alcohol Pathology Across Development. | Macht VA et al. | — | 2022 | → |
| Increased alcohol self-administration following repeated Toll-like receptor 3 agonist treatment in male and female rats. | Lovelock DF et al. | — | 2022 | → |
| Inflammatory Markers in Substance Use and Mood Disorders: A Neuroimaging Perspective. | Agarwal K et al. | — | 2022 | → |
| Innate immune activation: Parallels in alcohol use disorder and Alzheimer's disease. | Ramos A et al. | — | 2022 | → |
| Prevention and mitigation of alcohol-induced neuroinflammation by <i>Lactobacillus plantarum</i> by an EGF receptor-dependent mechanism. | Shukla PK et al. | — | 2022 | → |
| Prevention of glutamate excitotoxicity in lateral habenula alleviates ethanol withdrawal-induced somatic and behavioral effects in ethanol dependent mice. | Gakare SG et al. | — | 2022 | → |
| Sex differences in stress-induced alcohol intake: a review of preclinical studies focused on amygdala and inflammatory pathways. | Mineur YS et al. | — | 2022 | → |
| The Role of High Mobility Group Box 1 (HMGB1) in Neurodegeneration: A Systematic Review. | Ikram FZ et al. | — | 2022 | → |
| The Toll-like receptor 7 agonist imiquimod increases ethanol self-administration and induces expression of Toll-like receptor related genes. | Lovelock DF et al. | — | 2022 | → |
| Transcriptional and Epigenetic Regulation of Monocyte and Macrophage Dysfunction by Chronic Alcohol Consumption. | Malherbe DC et al. | — | 2022 | → |
| Translational Structural and Functional Signatures of Chronic Alcohol Effects in Mice. | Degiorgis L et al. | — | 2022 | → |
| Aberrant neurogenesis and late onset suppression of synaptic plasticity as well as sustained neuroinflammation in the hippocampal dentate gyrus after developmental exposure to ethanol in rats. | Takahashi Y et al. | — | 2021 | → |
| Acute ethanol exposure rapidly alters cerebellar and cortical microglial physiology. | Stowell RD et al. | — | 2021 | → |
| A Multimodal Neuroprosthetic Interface to Record, Modulate and Classify Electrophysiological Biomarkers Relevant to Neuropsychiatric Disorders. | Habelt B et al. | — | 2021 | → |
| Brain-derived neurotrophic factor among patients with alcoholism. | MartÃn-González C et al. | — | 2021 | → |
| Combined and sequential effects of alcohol and methamphetamine in animal models. | Stafford AM et al. | — | 2021 | → |
| Curcumin Can be Acts as Effective agent for Prevent or Treatment of Alcohol-induced Toxicity in Hepatocytes: An Illustrated Mechanistic Review. | Salehi E et al. | — | 2021 | → |
| Deletion of Tlr3 reduces acute tolerance to alcohol and alcohol consumption in the intermittent access procedure in male mice. | Blednov YA et al. | — | 2021 | → |
| Dynamics of microglia and dendritic spines in early adolescent cortex after developmental alcohol exposure. | Wong EL et al. | — | 2021 | → |
| Glial cells as influencers and maladaptive consequences of alcohol use disorders. | Marshall SA | — | 2021 | → |
| Ibudilast attenuates alcohol cue-elicited frontostriatal functional connectivity in alcohol use disorder. | Burnette EM et al. | — | 2021 | → |
| Increased Toll-like Receptor-MyD88-NFκB-Proinflammatory neuroimmune signaling in the orbitofrontal cortex of humans with alcohol use disorder. | Vetreno RP et al. | — | 2021 | → |
| Microbiome and substances of abuse. | Salavrakos M et al. | — | 2021 | → |
| Sudden cessation of fluoxetine before alcohol drinking reinstatement alters microglial morphology and TLR4/inflammatory neuroadaptation in the rat brain. | Aranda J et al. | — | 2021 | → |
| TRAIL Mediates Neuronal Death in AUD: A Link between Neuroinflammation and Neurodegeneration. | Qin L et al. | — | 2021 | → |
| Aberrations in peripheral inflammatory cytokine levels in substance use disorders: a meta-analysis of 74 studies. | Wei ZX et al. | — | 2020 | → |
| Alcohol exposure-induced neurovascular inflammatory priming impacts ischemic stroke and is linked with brain perivascular macrophages. | Drieu A et al. | — | 2020 | → |
| Ampicillin/Sulbactam Treatment Modulates NMDA Receptor NR2B Subunit and Attenuates Neuroinflammation and Alcohol Intake in Male High Alcohol Drinking Rats. | Alasmari F et al. | — | 2020 | → |
| Chronic ethanol exposure induces neuroinflammation in H4 cells through TLR3 / NF-κB pathway and anxiety-like behavior in male C57BL/6 mice. | Wang X et al. | — | 2020 | → |
| Chronic Voluntary Binge Ethanol Consumption Causes Sex-Specific Differences in Microglial Signaling Pathways and Withdrawal-associated Behaviors in Mice. | Rath M et al. | — | 2020 | → |
| Combined Effects of Repetitive Mild Traumatic Brain Injury and Alcohol Drinking on the Neuroinflammatory Cytokine Response and Cognitive Behavioral Outcomes. | Hoffman J et al. | — | 2020 | → |
| Impact of High Fat Diet and Ethanol Consumption on Neurocircuitry Regulating Emotional Processing and Metabolic Function. | Coker CR et al. | — | 2020 | → |
| Inbred Substrain Differences Influence Neuroimmune Response and Drinking Behavior. | Warden AS et al. | — | 2020 | → |
| [Involvement of TOLL-like receptors in the neuroimmunology of alcoholism]. | Airapetov MI et al. | — | 2020 | → |
| Microglial depletion and repopulation in brain slice culture normalizes sensitized proinflammatory signaling. | Coleman LG et al. | — | 2020 | → |
| Neurological consequences of COVID-19: what have we learned and where do we go from here? | Jarrahi A et al. | — | 2020 | → |
| Prospective Study Examining the Effects of Extreme Drinking on Brain Structure in Emerging Adults. | Hua JPY et al. | — | 2020 | → |
| Tumour Necrosis Factor in Neuroplasticity, Neurogenesis and Alcohol Use Disorder. | Alvarez Cooper I et al. | — | 2020 | → |
| A comparison of hippocampal microglial responses in aged and young rodents following dependent and non-dependent binge drinking. | Grifasi IR et al. | — | 2019 | → |
| Aging with alcohol-related brain damage: Critical brain circuits associated with cognitive dysfunction. | Nunes PT et al. | — | 2019 | → |
| Alcohol and Cocaine Exposure Modulates ABCB1 and ABCG2 Transporters in Male Alcohol-Preferring Rats. | Hammad AM et al. | — | 2019 | → |
| A Pivotal Role for Thiamine Deficiency in the Expression of Neuroinflammation Markers in Models of Alcohol-Related Brain Damage. | Toledo Nunes P et al. | — | 2019 | → |
| ApoA-I Mimetic Peptide Reduces Vascular and White Matter Damage After Stroke in Type-2 Diabetic Mice. | Wang X et al. | — | 2019 | → |
| Characterization of the Hippocampal Neuroimmune Response to Binge-Like Ethanol Consumption in the Drinking in the Dark Model. | Grifasi IR et al. | — | 2019 | → |
| Early life alcohol exposure primes hypothalamic microglia to later-life hypersensitivity to immune stress: possible epigenetic mechanism. | Chastain LG et al. | — | 2019 | → |
| Ethanol induces interferon expression in neurons via TRAIL: role of astrocyte-to-neuron signaling. | Lawrimore CJ et al. | — | 2019 | → |
| Ethanol Induction of Innate Immune Signals Across BV2 Microglia and SH-SY5Y Neuroblastoma Involves Induction of IL-4 and IL-13. | Lawrimore CJ et al. | — | 2019 | → |
| Exercise-driven restoration of the alcohol-damaged brain. | West RK et al. | — | 2019 | → |
| Glial gene networks associated with alcohol dependence. | Erickson EK et al. | — | 2019 | → |
| Glial mechanisms underlying substance use disorders. | Linker KE et al. | — | 2019 | → |
| Innate Immunity and Alcohol. | Kany S et al. | — | 2019 | → |
| Its complicated: The relationship between alcohol and microglia in the search for novel pharmacotherapeutic targets for alcohol use disorders. | Melbourne JK et al. | — | 2019 | → |
| Multiorgan Development of Oxidative and Nitrosative Stress in LPS-Induced Endotoxemia in C57Bl/6 Mice: DHE-Based <i>In Vivo</i> Approach. | Proniewski B et al. | — | 2019 | → |
| Neuroimmune signaling in alcohol use disorder. | Erickson EK et al. | — | 2019 | → |
| The Cortical Neuroimmune Regulator TANK Affects Emotional Processing and Enhances Alcohol Drinking: A Translational Study. | Müller CP et al. | — | 2019 | → |
| The Toll-Like Receptor 3 Agonist Poly(I:C) Induces Rapid and Lasting Changes in Gene Expression Related to Glutamatergic Function and Increases Ethanol Self-Administration in Rats. | Randall PA et al. | — | 2019 | → |
| Toll-like receptor 3 activation increases voluntary alcohol intake in C57BL/6J male mice. | Warden AS et al. | — | 2019 | → |
| Toll-like receptor 3 dynamics in female C57BL/6J mice: Regulation of alcohol intake. | Warden AS et al. | — | 2019 | → |
| Developmental alcohol exposure impairs synaptic plasticity without overtly altering microglial function in mouse visual cortex. | Wong EL et al. | — | 2018 | → |
| HMGB1/IL-1β complexes regulate neuroimmune responses in alcoholism. | Coleman LG et al. | — | 2018 | → |
| Innate Immune Signaling and Alcohol Use Disorders. | Coleman LG et al. | — | 2018 | → |
| Methamphetamine-Induced Brain Injury and Alcohol Drinking. | Blaker AL et al. | — | 2018 | → |
| Microglia and alcohol meet at the crossroads: Microglia as critical modulators of alcohol neurotoxicity. | Henriques JF et al. | — | 2018 | → |
| Microglial-specific transcriptome changes following chronic alcohol consumption. | McCarthy GM et al. | — | 2018 | → |
| Peripheral TNFα elevations in abstinent alcoholics are associated with hepatitis C infection. | Zahr NM | — | 2018 | → |
| Soluble Klotho and Brain Atrophy in Alcoholism. | González-Reimers E et al. | — | 2018 | → |
| The role of the orbitofrontal cortex in alcohol use, abuse, and dependence. | Moorman DE | — | 2018 | → |
| TLR7-let-7 Signaling Contributes to Ethanol-Induced Hepatic Inflammatory Response in Mice and in Alcoholic Hepatitis. | Massey VL et al. | — | 2018 | → |
| Alcohol, aging, and innate immunity. | Boule LA et al. | — | 2017 | → |
| Alcohol and Stress Activation of Microglia and Neurons: Brain Regional Effects. | Walter TJ et al. | — | 2017 | → |
| A role for the peripheral immune system in the development of alcohol use disorders? | de Timary P et al. | — | 2017 | → |
| Binge ethanol in adulthood exacerbates negative outcomes following juvenile traumatic brain injury. | Karelina K et al. | — | 2017 | → |
| Elevated microRNA-129-5p level ameliorates neuroinflammation and blood-spinal cord barrier damage after ischemia-reperfusion by inhibiting HMGB1 and the TLR3-cytokine pathway. | Li XQ et al. | — | 2017 | → |
| Ethanol Consumption in Mice Lacking CD14, TLR2, TLR4, or MyD88. | Blednov YA et al. | — | 2017 | → |
| Ethanol, TLR3, and TLR4 Agonists Have Unique Innate Immune Responses in Neuron-Like SH-SY5Y and Microglia-Like BV2. | Lawrimore CJ et al. | — | 2017 | → |
| Investigation of Sex Differences in the Microglial Response to Binge Ethanol and Exercise. | Barton EA et al. | — | 2017 | → |
| Microglia Gone Rogue: Impacts on Psychiatric Disorders across the Lifespan. | Tay TL et al. | — | 2017 | → |
| Microglial depletion alters the brain neuroimmune response to acute binge ethanol withdrawal. | Walter TJ et al. | — | 2017 | → |
| Microglial-derived miRNA let-7 and HMGB1 contribute to ethanol-induced neurotoxicity via TLR7. | Coleman LG et al. | — | 2017 | → |
| Modulation of Binge-like Ethanol Consumption by IL-10 Signaling in the Basolateral Amygdala. | Marshall SA et al. | — | 2017 | → |
| Multi-modal MRI classifiers identify excessive alcohol consumption and treatment effects in the brain. | Cosa A et al. | — | 2017 | → |
| N-acetylcysteine Prevents Alcohol Related Neuroinflammation in Rats. | Schneider R et al. | — | 2017 | → |
| New Implications for the Melanocortin System in Alcohol Drinking Behavior in Adolescents: The Glial Dysfunction Hypothesis. | Orellana JA et al. | — | 2017 | → |
| The role of neuroimmune signaling in alcoholism. | Crews FT et al. | — | 2017 | → |
| What the Spectrum of Microglial Functions Can Teach us About Fetal Alcohol Spectrum Disorder. | Wong EL et al. | — | 2017 | → |
| Alcohol-Induced Molecular Dysregulation in Human Embryonic Stem Cell-Derived Neural Precursor Cells. | Kim YY et al. | — | 2016 | → |
| Anthropogenic pollutants may increase the incidence of neurodegenerative disease in an aging population. | Bondy SC | — | 2016 | → |
| Ethanol-Induced TLR4/NLRP3 Neuroinflammatory Response in Microglial Cells Promotes Leukocyte Infiltration Across the BBB. | Alfonso-Loeches S et al. | — | 2016 | → |
| IL-1 receptor signaling in the basolateral amygdala modulates binge-like ethanol consumption in male C57BL/6J mice. | Marshall SA et al. | — | 2016 | → |
| Inflammatory responses to alcohol in the CNS: nuclear receptors as potential therapeutics for alcohol-induced neuropathologies. | Kane CJ et al. | — | 2016 | → |
| Prior Binge Ethanol Exposure Potentiates the Microglial Response in a Model of Alcohol-Induced Neurodegeneration. | Marshall SA et al. | — | 2016 | → |
| The neuroimmune transcriptome and alcohol dependence: potential for targeted therapies. | Warden A et al. | — | 2016 | → |
| Transgenic mice with increased astrocyte expression of IL-6 show altered effects of acute ethanol on synaptic function. | Hernandez RV et al. | — | 2016 | → |
| Brain pathways to recovery from alcohol dependence. | Cui C et al. | — | 2015 | → |
| Cytokines and chemokines as biomarkers of ethanol-induced neuroinflammation and anxiety-related behavior: role of TLR4 and TLR2. | Pascual M et al. | — | 2015 | → |
| Microglia-Induced Maladaptive Plasticity Can Be Modulated by Neuropeptides In Vivo. | Morara S et al. | — | 2015 | → |
| Neuroimmune Function and the Consequences of Alcohol Exposure. | Crews FT et al. | — | 2015 | → |
| Novel candidate genes for alcoholism--transcriptomic analysis of prefrontal medial cortex, hippocampus and nucleus accumbens of Warsaw alcohol-preferring and non-preferring rats. | Stankiewicz AM et al. | — | 2015 | → |
| SjCa8, a calcium-binding protein from Schistosoma japonicum, inhibits cell migration and suppresses nitric oxide release of RAW264.7 macrophages. | Liu J et al. | — | 2015 | → |
| Current hypotheses on the mechanisms of alcoholism. | Vetreno RP et al. | — | 2014 | → |
| Effect of repeated alcohol exposure during the third trimester-equivalent on messenger RNA levels for interleukin-1β, chemokine (C-C motif) ligand 2, and interleukin 10 in the developing rat brain after injection of lipopolysaccharide. | Topper LA et al. | — | 2014 | → |
| Effects of ceftriaxone on systemic and central expression of anti- and pro-inflammatory cytokines in alcohol-preferring (P) rats exposed to ethanol. | Rao PS et al. | — | 2014 | → |
| Fetal alcohol spectrum disorders and neuroimmune changes. | Drew PD et al. | — | 2014 | → |
| Focal thalamic degeneration from ethanol and thiamine deficiency is associated with neuroimmune gene induction, microglial activation, and lack of monocarboxylic acid transporters. | Qin L et al. | — | 2014 | → |
| HIV-1 and alcohol: interactions in the central nervous system. | Silverstein PS et al. | — | 2014 | → |
| Intoxication- and withdrawal-dependent expression of central and peripheral cytokines following initial ethanol exposure. | Doremus-Fitzwater TL et al. | — | 2014 | → |
| Minocycline mitigates motor impairments and cortical neuronal loss induced by focal ischemia in rats chronically exposed to ethanol during adolescence. | Oliveira GB et al. | — | 2014 | → |
| Neuroimmune basis of alcoholic brain damage. | Crews FT et al. | — | 2014 | → |
| Opportunities for the development of neuroimmune therapies in addiction. | Ray LA et al. | — | 2014 | → |
| Phospholipase A2, oxidative stress, and neurodegeneration in binge ethanol-treated organotypic slice cultures of developing rat brain. | Moon KH et al. | — | 2014 | → |
| Proteome of brain glia: the molecular basis of diverse glial phenotypes. | Jha MK et al. | — | 2014 | → |
| Release of neuronal HMGB1 by ethanol through decreased HDAC activity activates brain neuroimmune signaling. | Zou JY et al. | — | 2014 | → |
| Role of microglia in ethanol-induced neurodegenerative disease: Pathological and behavioral dysfunction at different developmental stages. | Yang JY et al. | — | 2014 | → |
| Role of microglia in regulation of ethanol neurotoxic action. | Chastain LG et al. | — | 2014 | → |
| High mobility group box 1/Toll-like receptor danger signaling increases brain neuroimmune activation in alcohol dependence. | Crews FT et al. | — | 2013 | → |
| Intranasal delivery of plasma and platelet growth factors using PRGF-Endoret system enhances neurogenesis in a mouse model of Alzheimer's disease. | Anitua E et al. | — | 2013 | → |
| Microglial activation is not equivalent to neuroinflammation in alcohol-induced neurodegeneration: The importance of microglia phenotype. | Marshall SA et al. | — | 2013 | → |
| NADPH oxidase and aging drive microglial activation, oxidative stress, and dopaminergic neurodegeneration following systemic LPS administration. | Qin L et al. | — | 2013 | → |
| Neuroimmune signaling: a key component of alcohol abuse. | Mayfield J et al. | — | 2013 | → |
| Reversed scototaxis during withdrawal after daily-moderate, but not weekly-binge, administration of ethanol in zebrafish. | Holcombe A et al. | — | 2013 | → |
| Stress-response pathways are altered in the hippocampus of chronic alcoholics. | McClintick JN et al. | — | 2013 | → |