Identifying a potential role of immune cells in gadolinium deposition within the brain
Abstract Background Gadolinium (Gd) deposition in the brain was observed in patients with history of gadolinium-based contrast agent (GBCA) administration. However, the exact mechanism behind this deposition remains unclear, especially given that an intact blood-brain barrier (BBB) is considered imp...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-07-01
|
| Series: | Fluids and Barriers of the CNS |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12987-025-00674-5 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849225969625202688 |
|---|---|
| author | Dixy Parakkattel Nico Ruprecht Peter Broekmann Sarah Guimbal Chiara Stüdle Sasha Soldati Johannes T. Heverhagen Britta Engelhardt Hendrik von Tengg-Kobligk |
| author_facet | Dixy Parakkattel Nico Ruprecht Peter Broekmann Sarah Guimbal Chiara Stüdle Sasha Soldati Johannes T. Heverhagen Britta Engelhardt Hendrik von Tengg-Kobligk |
| author_sort | Dixy Parakkattel |
| collection | DOAJ |
| description | Abstract Background Gadolinium (Gd) deposition in the brain was observed in patients with history of gadolinium-based contrast agent (GBCA) administration. However, the exact mechanism behind this deposition remains unclear, especially given that an intact blood-brain barrier (BBB) is considered impermeable to GBCA. In this study, we propose that immune cells might play a role in facilitating GBCA entry into the brain despite an intact BBB. Methods Gadoterate meglumine, gadoteridol, gadobutrol and gadodiamide were investigated as GBCAs. Immune cells from human donor buffy coats were isolated, incubated with the GBCA and used in the experiments. Gd associated with the immune cells were measured using single-cell inductively coupled mass spectrometry (SC-ICP-MS). Flow cytometry analysis was performed to characterise the adhesion molecule expression profile on the immune cells and binding assay was employed to check the binding of Gd treated immune cells with endothelial ligands in static conditions. An in vitro model of the human BBB that prevents free diffusion of GBCA across was further used to observe immune cell behaviour at the BBB under physiological flow, in vitro. Results Our findings confirm that various immune cells, including CD4+ T cells, CD8+ T cells, monocytes, NK cells and B cells are capable of taking up the different GBCAs. Furthermore, we demonstrate that GBCA loading does not impair immune cell interaction with the endothelial ligands required for successful extravasation across the BBB under static conditions. Most importantly, we show that T cells and monocytes, loaded with the different contrast agents, extravasated across an in vitro BBB model under physiological flow conditions in a comparable manner to non GBCA loaded cells. Conclusions Taken together, our in vitro observations show that immune cells can transport GBCA across the BBB and could lead to permanent deposition of Gd in the brain. |
| format | Article |
| id | doaj-art-24de5419aa5147edaa799c204ac7d582 |
| institution | Kabale University |
| issn | 2045-8118 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Fluids and Barriers of the CNS |
| spelling | doaj-art-24de5419aa5147edaa799c204ac7d5822025-08-24T11:46:28ZengBMCFluids and Barriers of the CNS2045-81182025-07-0122111610.1186/s12987-025-00674-5Identifying a potential role of immune cells in gadolinium deposition within the brainDixy Parakkattel0Nico Ruprecht1Peter Broekmann2Sarah Guimbal3Chiara Stüdle4Sasha Soldati5Johannes T. Heverhagen6Britta Engelhardt7Hendrik von Tengg-Kobligk8Department of Diagnostic, Interventional and Pediatric Radiology, Inselspital, University of BernDepartment of Diagnostic, Interventional and Pediatric Radiology, Inselspital, University of BernDepartment of Chemistry, Biochemistry and Pharmaceutical Sciences, University of BernTheodor Kocher Institute, University of BernTheodor Kocher Institute, University of BernTheodor Kocher Institute, University of BernDepartment of Diagnostic, Interventional and Pediatric Radiology, Inselspital, University of BernTheodor Kocher Institute, University of BernDepartment of Diagnostic, Interventional and Pediatric Radiology, Inselspital, University of BernAbstract Background Gadolinium (Gd) deposition in the brain was observed in patients with history of gadolinium-based contrast agent (GBCA) administration. However, the exact mechanism behind this deposition remains unclear, especially given that an intact blood-brain barrier (BBB) is considered impermeable to GBCA. In this study, we propose that immune cells might play a role in facilitating GBCA entry into the brain despite an intact BBB. Methods Gadoterate meglumine, gadoteridol, gadobutrol and gadodiamide were investigated as GBCAs. Immune cells from human donor buffy coats were isolated, incubated with the GBCA and used in the experiments. Gd associated with the immune cells were measured using single-cell inductively coupled mass spectrometry (SC-ICP-MS). Flow cytometry analysis was performed to characterise the adhesion molecule expression profile on the immune cells and binding assay was employed to check the binding of Gd treated immune cells with endothelial ligands in static conditions. An in vitro model of the human BBB that prevents free diffusion of GBCA across was further used to observe immune cell behaviour at the BBB under physiological flow, in vitro. Results Our findings confirm that various immune cells, including CD4+ T cells, CD8+ T cells, monocytes, NK cells and B cells are capable of taking up the different GBCAs. Furthermore, we demonstrate that GBCA loading does not impair immune cell interaction with the endothelial ligands required for successful extravasation across the BBB under static conditions. Most importantly, we show that T cells and monocytes, loaded with the different contrast agents, extravasated across an in vitro BBB model under physiological flow conditions in a comparable manner to non GBCA loaded cells. Conclusions Taken together, our in vitro observations show that immune cells can transport GBCA across the BBB and could lead to permanent deposition of Gd in the brain.https://doi.org/10.1186/s12987-025-00674-5Gadolinium-based contrast agentsImmune cell migrationBlood-brain barrier |
| spellingShingle | Dixy Parakkattel Nico Ruprecht Peter Broekmann Sarah Guimbal Chiara Stüdle Sasha Soldati Johannes T. Heverhagen Britta Engelhardt Hendrik von Tengg-Kobligk Identifying a potential role of immune cells in gadolinium deposition within the brain Fluids and Barriers of the CNS Gadolinium-based contrast agents Immune cell migration Blood-brain barrier |
| title | Identifying a potential role of immune cells in gadolinium deposition within the brain |
| title_full | Identifying a potential role of immune cells in gadolinium deposition within the brain |
| title_fullStr | Identifying a potential role of immune cells in gadolinium deposition within the brain |
| title_full_unstemmed | Identifying a potential role of immune cells in gadolinium deposition within the brain |
| title_short | Identifying a potential role of immune cells in gadolinium deposition within the brain |
| title_sort | identifying a potential role of immune cells in gadolinium deposition within the brain |
| topic | Gadolinium-based contrast agents Immune cell migration Blood-brain barrier |
| url | https://doi.org/10.1186/s12987-025-00674-5 |
| work_keys_str_mv | AT dixyparakkattel identifyingapotentialroleofimmunecellsingadoliniumdepositionwithinthebrain AT nicoruprecht identifyingapotentialroleofimmunecellsingadoliniumdepositionwithinthebrain AT peterbroekmann identifyingapotentialroleofimmunecellsingadoliniumdepositionwithinthebrain AT sarahguimbal identifyingapotentialroleofimmunecellsingadoliniumdepositionwithinthebrain AT chiarastudle identifyingapotentialroleofimmunecellsingadoliniumdepositionwithinthebrain AT sashasoldati identifyingapotentialroleofimmunecellsingadoliniumdepositionwithinthebrain AT johannestheverhagen identifyingapotentialroleofimmunecellsingadoliniumdepositionwithinthebrain AT brittaengelhardt identifyingapotentialroleofimmunecellsingadoliniumdepositionwithinthebrain AT hendrikvontenggkobligk identifyingapotentialroleofimmunecellsingadoliniumdepositionwithinthebrain |