Chemokine associations with blood cerebrospinal fluid (CSF) barrier permeability and delirium
Delirium is a highly prevalent neuropsychiatric syndrome characterised by acute and fluctuating impairments in attention and cognition. Mechanisms driving delirium are poorly understood but it has been suggested that blood cytokines and chemokines cross the blood brain barrier during delirium, direc...
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Elsevier
2025-02-01
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| Series: | Brain, Behavior, & Immunity - Health |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666354624001984 |
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| author | Paul Denver Lucas Tortorelli Karen Hov Jens Petter Berg Lasse M. Giil Arshed Nazmi Ana Lopez-Rodriguez Daire Healy Carol Murray Robyn Barry Leiv Otto Watne Colm Cunningham |
| author_facet | Paul Denver Lucas Tortorelli Karen Hov Jens Petter Berg Lasse M. Giil Arshed Nazmi Ana Lopez-Rodriguez Daire Healy Carol Murray Robyn Barry Leiv Otto Watne Colm Cunningham |
| author_sort | Paul Denver |
| collection | DOAJ |
| description | Delirium is a highly prevalent neuropsychiatric syndrome characterised by acute and fluctuating impairments in attention and cognition. Mechanisms driving delirium are poorly understood but it has been suggested that blood cytokines and chemokines cross the blood brain barrier during delirium, directly impairing brain function. It is not known whether these molecules reach higher brain levels when the blood cerebrospinal fluid barrier (BCSFB) is impaired. Here, in human hip-fracture patients, we tested the influence of BCSFB integrity on CSF levels of chemokines and assessed their association with delirium. CSF levels of IP-10, eotaxin, eotaxin 3 and TARC showed weak to moderate correlations with BCSFB permeability, as measured by the Qalbumin ratio, while MCP1, IL-8, MIP1α and MIP1β showed no significant correlation. Chemokines were not associated with delirium in univariate analysis or when stratified on dementia status, but exploratory analyses showed that elevated Eotaxin (CCL11) and MIP1α (CCL3) were associated with prevalent delirium. Modelling acute systemic inflammation, we used bacterial LPS (250 μg/kg) or sterile laparotomy surgery in mice to demonstrate de novo synthesis of chemokines at the choroid plexus (CP) and microvasculature. Gene expression data showed CP-enriched expression of Il1b, Tnfa, Cxcl1 and Ccl3 in both models and immunohistochemistry showed cytokine and chemokine synthesis in CP stromal (IL-1β, CCL2/MCP1) or epithelial cells (CXCL10/IP-10) cells and at the microvasculature. Larger studies are required to confirm these human findings on chemokine associations with BCSFB permeability and prevalent delirium. Preclinical studies are warranted to determine whether chemokines might play a role in the pathophysiology of delirium. |
| format | Article |
| id | doaj-art-73ddad099ab3495bb781bfdfebcbad31 |
| institution | Kabale University |
| issn | 2666-3546 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain, Behavior, & Immunity - Health |
| spelling | doaj-art-73ddad099ab3495bb781bfdfebcbad312025-01-26T05:05:00ZengElsevierBrain, Behavior, & Immunity - Health2666-35462025-02-0143100920Chemokine associations with blood cerebrospinal fluid (CSF) barrier permeability and deliriumPaul Denver0Lucas Tortorelli1Karen Hov2Jens Petter Berg3Lasse M. Giil4Arshed Nazmi5Ana Lopez-Rodriguez6Daire Healy7Carol Murray8Robyn Barry9Leiv Otto Watne10Colm Cunningham11School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute & Trinity College Institute of Neuroscience, Trinity College Dublin, Pearse Street, Dublin 2, IrelandSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute & Trinity College Institute of Neuroscience, Trinity College Dublin, Pearse Street, Dublin 2, IrelandOslo Delirium Research Group, Department of Geriatric Medicine, Akershus University Hospital, Lørenskog, NorwayInstitute of Clinical Medicine, University of Oslo, NorwayDepartment of Clinical Science, University of Bergen, 5020, Bergen, NorwaySchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute & Trinity College Institute of Neuroscience, Trinity College Dublin, Pearse Street, Dublin 2, IrelandSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute & Trinity College Institute of Neuroscience, Trinity College Dublin, Pearse Street, Dublin 2, IrelandSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute & Trinity College Institute of Neuroscience, Trinity College Dublin, Pearse Street, Dublin 2, IrelandSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute & Trinity College Institute of Neuroscience, Trinity College Dublin, Pearse Street, Dublin 2, IrelandSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute & Trinity College Institute of Neuroscience, Trinity College Dublin, Pearse Street, Dublin 2, IrelandOslo Delirium Research Group, Department of Geriatric Medicine, Akershus University Hospital, Lørenskog, Norway; Institute of Clinical Medicine, University of Oslo, NorwaySchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute & Trinity College Institute of Neuroscience, Trinity College Dublin, Pearse Street, Dublin 2, Ireland; Corresponding author.Delirium is a highly prevalent neuropsychiatric syndrome characterised by acute and fluctuating impairments in attention and cognition. Mechanisms driving delirium are poorly understood but it has been suggested that blood cytokines and chemokines cross the blood brain barrier during delirium, directly impairing brain function. It is not known whether these molecules reach higher brain levels when the blood cerebrospinal fluid barrier (BCSFB) is impaired. Here, in human hip-fracture patients, we tested the influence of BCSFB integrity on CSF levels of chemokines and assessed their association with delirium. CSF levels of IP-10, eotaxin, eotaxin 3 and TARC showed weak to moderate correlations with BCSFB permeability, as measured by the Qalbumin ratio, while MCP1, IL-8, MIP1α and MIP1β showed no significant correlation. Chemokines were not associated with delirium in univariate analysis or when stratified on dementia status, but exploratory analyses showed that elevated Eotaxin (CCL11) and MIP1α (CCL3) were associated with prevalent delirium. Modelling acute systemic inflammation, we used bacterial LPS (250 μg/kg) or sterile laparotomy surgery in mice to demonstrate de novo synthesis of chemokines at the choroid plexus (CP) and microvasculature. Gene expression data showed CP-enriched expression of Il1b, Tnfa, Cxcl1 and Ccl3 in both models and immunohistochemistry showed cytokine and chemokine synthesis in CP stromal (IL-1β, CCL2/MCP1) or epithelial cells (CXCL10/IP-10) cells and at the microvasculature. Larger studies are required to confirm these human findings on chemokine associations with BCSFB permeability and prevalent delirium. Preclinical studies are warranted to determine whether chemokines might play a role in the pathophysiology of delirium.http://www.sciencedirect.com/science/article/pii/S2666354624001984DeliriumChemokinesCSFSystemic inflammationBlood brain barrierBlood CSF barrier |
| spellingShingle | Paul Denver Lucas Tortorelli Karen Hov Jens Petter Berg Lasse M. Giil Arshed Nazmi Ana Lopez-Rodriguez Daire Healy Carol Murray Robyn Barry Leiv Otto Watne Colm Cunningham Chemokine associations with blood cerebrospinal fluid (CSF) barrier permeability and delirium Brain, Behavior, & Immunity - Health Delirium Chemokines CSF Systemic inflammation Blood brain barrier Blood CSF barrier |
| title | Chemokine associations with blood cerebrospinal fluid (CSF) barrier permeability and delirium |
| title_full | Chemokine associations with blood cerebrospinal fluid (CSF) barrier permeability and delirium |
| title_fullStr | Chemokine associations with blood cerebrospinal fluid (CSF) barrier permeability and delirium |
| title_full_unstemmed | Chemokine associations with blood cerebrospinal fluid (CSF) barrier permeability and delirium |
| title_short | Chemokine associations with blood cerebrospinal fluid (CSF) barrier permeability and delirium |
| title_sort | chemokine associations with blood cerebrospinal fluid csf barrier permeability and delirium |
| topic | Delirium Chemokines CSF Systemic inflammation Blood brain barrier Blood CSF barrier |
| url | http://www.sciencedirect.com/science/article/pii/S2666354624001984 |
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