Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/16281
Título
Neutrophil β1 adrenoceptor blockade blunts stroke-associated neuroinflammation.
Autor(es)
Clemente-Moragón, Agustín | Oliver, Eduardo CNIC | Calle, Daniel | Cusso, Lorena CNIC | Gomez, Monica CNIC | Pradillo, Jesús M | Castejón, Raquel | Rallón, Norma | Benito, José M | Fernández-Ferro, José C | Carneado-Ruíz, Joaquín | Moro, María A | Sanchez-Gonzalez, Javier CNIC | Fuster, Valentín | Cortes-Canteli, Marta CNIC | Desco, Manuel CNIC | Ibáñez, Borja CNIC
Fecha de publicación
2023-02
Cita
Br J Pharmacol. 2023 Feb;180(4):459-478
Idioma
Inglés
Tipo de documento
research article
Resumen
BACKGROUND AND PURPOSE
Reperfusion therapy is the standard of care for ischaemic stroke; however, there is a need to identify new therapeutic targets able to ameliorate cerebral damage. Neutrophil β1 adrenoceptors (β1AR) have been linked to neutrophil migration during exacerbated inflammation. Given the central role of neutrophils in cerebral damage during stroke, we hypothesize that β1AR blockade will improve stroke outcomes.
EXPERIMENTAL APPROACH
Rats were subjected to middle cerebral artery occlusion-reperfusion to evaluate the effect on stroke of the selective β1AR blocker metoprolol (12.5 mg·kg-1 ) when injected i.v. 10 min before reperfusion.
KEY RESULTS
Magnetic resonance imaging and histopathology analysis showed that pre-reperfusion i.v. metoprolol reduced infarct size. This effect was accompanied by reduced cytotoxic oedema at 24 h and vasogenic oedema at 7 days. Metoprolol-treated rats showed reduced brain neutrophil infiltration and those which infiltrated displayed a high proportion of anti-inflammatory phenotype (N2, YM1+ ). Additional inflammatory models demonstrated that metoprolol specifically blocked neutrophil migration via β1AR and excluded a significant effect on the glia compartment. Consistently, metoprolol did not protect the brain in neutrophil-depleted rats upon stroke. In patients suffering an ischaemic stroke, β1AR blockade by metoprolol reduced circulating neutrophil-platelet co-aggregates.
CONCLUSIONS AND IMPLICATIONS
Our findings describe that β1AR blockade ameliorates cerebral damage by targeting neutrophils, identifying a novel therapeutic target to improve outcomes in patients with stroke. This therapeutic strategy is in the earliest stages of the translational pathway and should be further explored.
MESH
Brain Ischemia | Stroke | Ischemic Stroke | Rats | Animals | Metoprolol | Neutrophils | Neuroinflammatory Diseases | Receptors, Adrenergic
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- Nombre:
- Neutrophil beta_1_Br J Pharmac ...
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