819b73e079c6394ed4135dbfedb29356 pmc_9138236.pdf 7ac01b1827e1da1a08669e8850a39a441cb3c5ab pmc_9138236.pdf d408a57fbdefa15a433da90fee00b0f28f4f335190f006dc561e8278f63be964 pmc_9138236.pdf Title: Vascular Endothelial Growth Factor as a Potential Biomarker of Neuroinflammation and Frontal Cognitive Impairment in Patients with Alcohol Use Disorder Subject: (1) Background: Alcohol Use Disorder (AUD) is associated with functional disruption of several brain structures that may trigger cognitive dysfunction. One of the mechanisms of alcohol-associated cognitive impairment has been proposed to arise from its direct impact on the immune system, which culminates in the release of cytokines and chemokines which can eventually reach the brain. Alcohol can also disrupt the blood–brain barrier, facilitating the penetration of pro-inflammatory molecules throughout vascular endothelial growth factor A (VEGFA). Thus, alcohol-induced alterations in chemokines and VEGFA might contribute to the neuroinflammation and cognitive impairment associated with AUD. (2) Methods: The present cross-sectional study investigates whether patients with AUD (n = 86) present cognitive disability associated to alterations in plasma concentration of SDF-1, fractalkine, eotaxin, MCP-1, MIP-1 and VEGFA when compared to control subjects (n = 51). (3) Results: The analysis indicated that SDF-1 and MCP-1 concentrations were higher in AUD patients than in controls. Concentrations of VEGFA were higher in AUD patients with severe frontal deficits, and the score of frontal lobe functions was negatively correlated with VEGFA and fractalkine. Acute alcohol effects on VEGFA plasma levels in healthy volunteers demonstrated the induction of VEGFA release by heavy alcohol drinking. VEGFA was positively correlated with pro-inflammatory chemokines in AUD patients with frontal cognitive impairment. (4) Conclusions: we propose VEGFA/chemokine monitoring as biomarkers of potential cognitive impairment in AUD patients. Keywords: alcohol use disorders; addiction; VEGFA; blood–brain barrier; chemokines; fractalkine; neuroinflammation; cognitive dysfunction; neurodegeneration; dementia Author: Nerea Requena-Ocaña, María Flores-Lopez, Esther Papaseit, Nuria García-Marchena, Juan Jesús Ruiz, Jesús Ortega-Pinazo, Antonia Serrano, Francisco Javier Pavón-Morón, Magí Farré, Juan Suarez, Fernando Rodríguez de Fonseca and Pedro Araos Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Apr 21 02:28:49 2022 CEST ModDate: Thu Apr 21 02:41:44 2022 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 19 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2385559 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- DIMMOC+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 ODUQCM+VnURWPalladioL 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PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Recruitment and Screening of Participants Destination: subsection.2.1 Item: Title: Ethical Statement Destination: subsection.2.2 Item: Title: Psychiatric and Neuropsychological Evaluation Destination: subsection.2.3 Item: Title: Obtaining Plasma Samples Destination: subsection.2.4 Item: Title: Multiplexed Bead Immunoassay Destination: subsection.2.5 Item: Title: Statistical Analysis Destination: subsection.2.6 Item: Title: Results Destination: section.3 Children: Item: Title: Sociodemographic Characteristics Destination: subsection.3.1 Item: Title: Alcohol-Related Variables in AUD Group Destination: subsection.3.2 Item: Title: Plasma Concentrations of VEGFA and Chemokines in Abstinent AUD Patients Destination: subsection.3.3 Item: Title: Plasma Concentrations of VEGFA and Chemokines in Abstinent AUD Patients with Frontal Cognitive Impairment Destination: subsection.3.4 Item: Title: Correlation Analyses between Frontal Cognition and Plasma Concentrations of VEGFA and Chemokines in AUD Patients Destination: subsection.3.5 Item: Title: Correlation Analyses between Plasma Concentrations of VEGFA and Chemokines in AUD Patients with and without Mild Cognitive Impairment Destination: subsection.3.6 Item: Title: Differential Profiles Associated with VEGFA and Chemokines in AUD Patients with Frontal Cognitive Impairment Destination: subsection.3.7 Item: Title: Plasma Concentrations of VEGFA and Chemokines in Comorbid Medical, Psychiatric Medication and Substance Use Problems in AUD Patients Destination: subsection.3.8 Item: Title: Time Course of Plasma Concentrations of VEGFA after an Acute Administration of Alcohol (100 g) in Healthy Male Volunteers Destination: subsection.3.9 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions, Limitations, and Future Perspectives Destination: section.5 Item: Title: References Destination: section.5 Info: Title: Vascular Endothelial Growth Factor as a Potential Biomarker of Neuroinflammation and Frontal Cognitive Impairment in Patients with Alcohol Use Disorder Author: Nerea Requena-Ocaña, María Flores-Lopez, Esther Papaseit, Nuria García-Marchena, Juan Jesús Ruiz, Jesús Ortega-Pinazo, Antonia Serrano, Francisco Javier Pavón-Morón, Magí Farré, Juan Suarez, Fernando Rodríguez de Fonseca and Pedro Araos Subject: (1) Background: Alcohol Use Disorder (AUD) is associated with functional disruption of several brain structures that may trigger cognitive dysfunction. One of the mechanisms of alcohol-associated cognitive impairment has been proposed to arise from its direct impact on the immune system, which culminates in the release of cytokines and chemokines which can eventually reach the brain. Alcohol can also disrupt the blood brain barrier, facilitating the penetration of pro-inflammatory molecules throughout vascular endothelial growth factor A (VEGFA). Thus, alcohol-induced alterations in chemokines and VEGFA might contribute to the neuroinflammation and cognitive impairment associated with AUD. (2) Methods: The present cross-sectional study investigates whether patients with AUD (n = 86) present cognitive disability associated to alterations in plasma concentration of SDF-1, fractalkine, eotaxin, MCP-1, MIP-1 and VEGFA when compared to control subjects (n = 51). (3) Results: The analysis indicated that SDF-1 and MCP-1 concentrations were higher in AUD patients than in controls. Concentrations of VEGFA were higher in AUD patients with severe frontal deficits, and the score of frontal lobe functions was negatively correlated with VEGFA and fractalkine. Acute alcohol effects on VEGFA plasma levels in healthy volunteers demonstrated the induction of VEGFA release by heavy alcohol drinking. VEGFA was positively correlated with pro-inflammatory chemokines in AUD patients with frontal cognitive impairment. (4) Conclusions: we propose VEGFA/chemokine monitoring as biomarkers of potential cognitive impairment in AUD patients. 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