نبذة مختصرة : 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.
Competing Interests: Michael Gliem: Speaking fees from Novartis and Pfizer. Mark Pawlitzki received honoraria for lecturing and travel expenses for attending meetings from Alexion, ArgenX, Bayer Health Care, Biogen, Hexal, Merck Serono, Novartis, Sanofi-Aventis and Teva. His research is funded by the by ArgenX, Biogen, Hexal and Novartis. Sven Meuth receives honoraria for lecturing, and travel expenses for attending meetings from Academy 2, Argenx, Alexion, Almirall, Amicus Therapeutics Germany, Bayer Health Care, Biogen, BioNtech, BMS, Celgene, Datamed, Demecan, Desitin, Diamed, Diaplan, DIU Dresden, DPmed, Gen Medicine and Healthcare products, Genzyme, Hexal AG, Impulze GmbH, Janssen Cilag, KW Medipoint, MedDay Pharmaceuticals, Merck Serono, Neuropoint, Novartis, Novo Nordisk, ONO Pharma, Oxford PharmaGenesis, Roche, Sanofi-Aventis, Springer Medizin Verlag, Chugai Pharma, QuintilesIMS, Teva, Wings for Life international and Xcenda. His research is funded by the German Ministry for Education and Research (BMBF), Bundesinstitut für Risikobewertung (BfR), Deutsche Forschungsgemeinschaft (DFG), Else Kröner Fresenius Foundation, Gemeinsamer Bundesausschuss (G-BA), German Academic Exchange Service, Hertie Foundation, Interdisciplinary Center for Clinical Studies (IZKF) Muenster, German Foundation Neurology and Alexion, Almirall, Amicus Therapeutics Germany, Biogen, Diamed, DGM e.v., Fresenius Medical Care, Genzyme, Gesellschaft von Freunden und Förderern der Heinrich-Heine-Universität Düsseldorf e.V., HERZ Burgdorf, Merck Serono, Novartis, ONO Pharma, Roche, and Teva. This does not alter our adherence to PLOS ONE policies on sharing data and materials
(Copyright: © 2025 Jansen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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