Serum Amyloid A1/Toll-Like Receptor-4 Axis, an Important Link between Inflammation and Outcome of TBI Patients

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Farré Alins, Víctor and Palomino Antolín, Alejandra and Narros Fernández, Paloma and López Rodríguez, Ana Belén and Decouty Pérez, Céline and Muñoz Montero, Alicia and Zamorano Fernández, Jorge and Mansilla Fernández, Beatriz and Giner García, Javier and García Feijoo, Pablo and Sáez Alegre, Miguel and Palpán Flores, Alexis J. and Roda Frade, José María and Carabias, Cristina S. and Rosa, Juliana M. and Civantos Martín, Belén and Yus Teruel, Santiago and Gandía, Luis and Lagares Gomez-Abascal, Alfonso and Hernández García, Borja J. and Egea, Javier (2021) Serum Amyloid A1/Toll-Like Receptor-4 Axis, an Important Link between Inflammation and Outcome of TBI Patients. Biomedicines, 9 (6). p. 599. ISSN 2227-9059

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Official URL: https://doi.org/10.3390/biomedicines9060599




Abstract

Traumatic brain injury (TBI) is one of the leading causes of mortality and disability worldwide without any validated biomarker or set of biomarkers to help the diagnosis and evaluation of the evolution/prognosis of TBI patients. To achieve this aim, a deeper knowledge of the biochemical and pathophysiological processes triggered after the trauma is essential. Here, we identified the serum amyloid A1 protein-Toll-like receptor 4 (SAA1-TLR4) axis as an important link between inflammation and the outcome of TBI patients. Using serum and mRNA from white blood cells (WBC) of TBI patients, we found a positive correlation between serum SAA1 levels and injury severity, as well as with the 6-month outcome of TBI patients. SAA1 levels also correlate with the presence of TLR4 mRNA in WBC. In vitro, we found that SAA1 contributes to inflammation via TLR4 activation that releases inflammatory cytokines, which in turn increases SAA1 levels, establishing a positive proinflammatory loop. In vivo, post-TBI treatment with the TLR4-antagonist TAK242 reduces SAA1 levels, improves neurobehavioral outcome, and prevents blood–brain barrier disruption. Our data support further evaluation of (i) post-TBI treatment in the presence of TLR4 inhibition for limiting TBI-induced damage and (ii) SAA1-TLR4 as a biomarker of injury progression in TBI patients.


Item Type:Article
Uncontrolled Keywords:traumatic brain injury; neuroinflammation; prognosis; biomarkers; immunomodulation
Subjects:Medical sciences > Medicine > Neurosciences
ID Code:69646
Deposited On:03 Feb 2022 17:32
Last Modified:04 Feb 2022 08:09

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