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

Autor:	Farré-Alins V; Molecular Neuroinflammation and Neuronal Plasticity Research Laboratory, Research Unit, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria-Hospital Universitario de la Princesa, 28009 Madrid, Spain.; Instituto Teófilo Hernando, Departamento de Farmacología y Terapéutica, Facultad de Medicina, UAM, 28029 Madrid, Spain., Palomino-Antolín A; Molecular Neuroinflammation and Neuronal Plasticity Research Laboratory, Research Unit, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria-Hospital Universitario de la Princesa, 28009 Madrid, Spain.; Instituto Teófilo Hernando, Departamento de Farmacología y Terapéutica, Facultad de Medicina, UAM, 28029 Madrid, Spain., Narros-Fernández P; Molecular Neuroinflammation and Neuronal Plasticity Research Laboratory, Research Unit, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria-Hospital Universitario de la Princesa, 28009 Madrid, Spain.; Instituto Teófilo Hernando, Departamento de Farmacología y Terapéutica, Facultad de Medicina, UAM, 28029 Madrid, Spain., Lopez-Rodriguez AB; Molecular Neuroinflammation and Neuronal Plasticity Research Laboratory, Research Unit, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria-Hospital Universitario de la Princesa, 28009 Madrid, Spain.; Instituto Teófilo Hernando, Departamento de Farmacología y Terapéutica, Facultad de Medicina, UAM, 28029 Madrid, Spain., Decouty-Perez C; Molecular Neuroinflammation and Neuronal Plasticity Research Laboratory, Research Unit, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria-Hospital Universitario de la Princesa, 28009 Madrid, Spain.; Instituto Teófilo Hernando, Departamento de Farmacología y Terapéutica, Facultad de Medicina, UAM, 28029 Madrid, Spain., Muñoz-Montero A; Instituto Teófilo Hernando, Departamento de Farmacología y Terapéutica, Facultad de Medicina, UAM, 28029 Madrid, Spain., Zamorano-Fernández J; Servicio de Neurocirugía, Hospital Universitario La Paz, 28046 Madrid, Spain., Mansilla-Fernández B; Servicio de Neurocirugía, Hospital Universitario La Paz, 28046 Madrid, Spain., Giner-García J; Servicio de Neurocirugía, Hospital Universitario La Paz, 28046 Madrid, Spain., García-Feijoo P; Servicio de Neurocirugía, Hospital Universitario La Paz, 28046 Madrid, Spain., Sáez-Alegre M; Servicio de Neurocirugía, Hospital Universitario La Paz, 28046 Madrid, Spain., Palpán-Flores AJ; Servicio de Neurocirugía, Hospital Universitario La Paz, 28046 Madrid, Spain., Roda-Frade JM; Servicio de Neurocirugía, Hospital Universitario La Paz, 28046 Madrid, Spain., Carabias CS; Servicio de Neurocirugía, Hospital Universitario 12 de Octubre, imas12, Universidad Complutense de Madrid, 28041 Madrid, Spain., Rosa JM; Molecular Neuroinflammation and Neuronal Plasticity Research Laboratory, Research Unit, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria-Hospital Universitario de la Princesa, 28009 Madrid, Spain., Civantos-Martín B; Servicio de Medicina Intensiva, Hospital Universitario La Paz, 28046 Madrid, Spain., Yus-Teruel S; Servicio de Medicina Intensiva, Hospital Universitario La Paz, 28046 Madrid, Spain., Gandía L; Instituto Teófilo Hernando, Departamento de Farmacología y Terapéutica, Facultad de Medicina, UAM, 28029 Madrid, Spain., Lagares A; Servicio de Neurocirugía, Hospital Universitario 12 de Octubre, imas12, Universidad Complutense de Madrid, 28041 Madrid, Spain., Hernández-García BJ; Servicio de Neurocirugía, Hospital Universitario La Paz, 28046 Madrid, Spain., Egea J; Molecular Neuroinflammation and Neuronal Plasticity Research Laboratory, Research Unit, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria-Hospital Universitario de la Princesa, 28009 Madrid, Spain.; Instituto Teófilo Hernando, Departamento de Farmacología y Terapéutica, Facultad de Medicina, UAM, 28029 Madrid, Spain.
Jazyk:	angličtina
Zdroj:	Biomedicines [Biomedicines] 2021 May 25; Vol. 9 (6). Date of Electronic Publication: 2021 May 25.
DOI:	10.3390/biomedicines9060599
Abstrakt:	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.
Databáze:	MEDLINE
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