LFA-1: A potential key player in microglia-mediated neuroprotection against oxygen-glucose deprivation in vitro.
For the last 38 years, all neuroprotective agents for patients with ischemic stroke have failed in clinical trials. The innate immune system, particularly microglia, is a much-discussed target for neuroprotective agents. Promising results for neuroprotection by inhibition of integrins with drugs suc...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0314020 |
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| author | Robin Jansen Marc Pawlitzki Michael Gliem Sven G Meuth Stefanie Schreiber Michael-W Görtler Jens Neumann |
| author_facet | Robin Jansen Marc Pawlitzki Michael Gliem Sven G Meuth Stefanie Schreiber Michael-W Görtler Jens Neumann |
| author_sort | Robin Jansen |
| collection | DOAJ |
| description | For the last 38 years, all neuroprotective agents for patients with ischemic stroke have failed in clinical trials. The innate immune system, particularly microglia, is a much-discussed target for neuroprotective agents. Promising results for neuroprotection by inhibition of integrins with drugs such as natalizumab in animal stroke models have not been translated into clinical practice. Our present study reveals the relevance of a β2 integrin, lymphocyte function-associated antigen-1 (LFA-1), as a potential key player in protecting neuronal cell death after oxygen-glucose deprivation in organotypic hippocampal cell cultures. In addition, we identified microglial cells as effector cells for LFA-1-mediated neuroprotection. The counterpart of LFA-1 on microglia is unclear, but we show strong expression of ICAM-5 in hippocampal neurons, suggesting a critical role for direct crosstalk between microglia and neurons for neuronal survival under oxygen-glucose deprivation. The enigma of neuroprotection after ischemic stroke remains to be solved, and our findings highlight the continuing importance and lack of understanding of integrin-mediated pathways after ischemic stroke and the need for further intensive research. |
| format | Article |
| id | doaj-art-d78f19483934458eba8b92b5d3307dda |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-d78f19483934458eba8b92b5d3307dda2025-01-17T05:31:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01201e031402010.1371/journal.pone.0314020LFA-1: A potential key player in microglia-mediated neuroprotection against oxygen-glucose deprivation in vitro.Robin JansenMarc PawlitzkiMichael GliemSven G MeuthStefanie SchreiberMichael-W GörtlerJens NeumannFor the last 38 years, all neuroprotective agents for patients with ischemic stroke have failed in clinical trials. The innate immune system, particularly microglia, is a much-discussed target for neuroprotective agents. Promising results for neuroprotection by inhibition of integrins with drugs such as natalizumab in animal stroke models have not been translated into clinical practice. Our present study reveals the relevance of a β2 integrin, lymphocyte function-associated antigen-1 (LFA-1), as a potential key player in protecting neuronal cell death after oxygen-glucose deprivation in organotypic hippocampal cell cultures. In addition, we identified microglial cells as effector cells for LFA-1-mediated neuroprotection. The counterpart of LFA-1 on microglia is unclear, but we show strong expression of ICAM-5 in hippocampal neurons, suggesting a critical role for direct crosstalk between microglia and neurons for neuronal survival under oxygen-glucose deprivation. The enigma of neuroprotection after ischemic stroke remains to be solved, and our findings highlight the continuing importance and lack of understanding of integrin-mediated pathways after ischemic stroke and the need for further intensive research.https://doi.org/10.1371/journal.pone.0314020 |
| spellingShingle | Robin Jansen Marc Pawlitzki Michael Gliem Sven G Meuth Stefanie Schreiber Michael-W Görtler Jens Neumann LFA-1: A potential key player in microglia-mediated neuroprotection against oxygen-glucose deprivation in vitro. PLoS ONE |
| title | LFA-1: A potential key player in microglia-mediated neuroprotection against oxygen-glucose deprivation in vitro. |
| title_full | LFA-1: A potential key player in microglia-mediated neuroprotection against oxygen-glucose deprivation in vitro. |
| title_fullStr | LFA-1: A potential key player in microglia-mediated neuroprotection against oxygen-glucose deprivation in vitro. |
| title_full_unstemmed | LFA-1: A potential key player in microglia-mediated neuroprotection against oxygen-glucose deprivation in vitro. |
| title_short | LFA-1: A potential key player in microglia-mediated neuroprotection against oxygen-glucose deprivation in vitro. |
| title_sort | lfa 1 a potential key player in microglia mediated neuroprotection against oxygen glucose deprivation in vitro |
| url | https://doi.org/10.1371/journal.pone.0314020 |
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