Impact of bacterial translocation in stroke outcome. Soluble CD14 as early clinical marker and effect of TLR4

Granados-Martinez, C.; Alfageme-Lopez, N.; Diaz-Benito, B.; Moraga, A.; Sevillano-Fernandez, D.; Alou-Cervera, L.; Fernandez-Valle, M. E.; Castejon-Ferrer, D.; Calleja-Castano, P.; Moro, M. A.; Hernandez-Jimenez, M.; Lizasoain, I.; Pradillo, J. M.

doi:10.1101/2024.12.30.630676

bioRxiv · 10.1101/2024.12.30.630676

Impact of bacterial translocation in stroke outcome. Soluble CD14 as early clinical marker and effect of TLR4

Granados-Martinez, C.·Alfageme-Lopez, N.·Diaz-Benito, B.·Moraga, A.·Sevillano-Fernandez, D.·Alou-Cervera, L.·Fernandez-Valle, M. E.·Castejon-Ferrer, D.·Calleja-Castano, P.·Moro, M. A.·Hernandez-Jimenez, M.·Lizasoain, I.·Pradillo, J. M.

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Abstract

Bacterial infections are among the most common complications in stroke patients. While some factors triggering these infections are well established, bacterial translocation (BT) from the intestine to other organs represents another significant factor to consider. In our study, we observed a high percentage of animals with intestinal barrier dysfunction (GBD) and BT following stroke, with typical intestinal bacteria even detected in the lungs. Moreover, this process not only exacerbates peripheral/central inflammation but also increases lesion size. In this context, our data in stroke patients demonstrate the presence of GBD, associated with elevated levels of soluble CD14 as a marker, and its strong correlation with neurological status, infarct volume, and the development of infections. Finally, our findings highlight the neuroprotective effects of the absence or pharmacological inhibition of TLR4 using ApTOLL, which not only reduces infarct volume and inflammation but also mitigates GBD/BT processes following experimental stroke.

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Granados-Martinez, C., Alfageme-Lopez, N., Diaz-Benito, B., Moraga, A., Sevillano-Fernandez, D., Alou-Cervera, L., Fernandez-Valle, M. E., Castejon-Ferrer, D., Calleja-Castano, P., Moro, M. A., Hernandez-Jimenez, M., Lizasoain, I., Pradillo, J. M.. 2024-12-31. Impact of bacterial translocation in stroke outcome. Soluble CD14 as early clinical marker and effect of TLR4. https://doi.org/10.1101/2024.12.30.630676

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