Examinando por Autor "Bravo-Ferrer, Isabel"

Mostrando 1 - 2 de 2

Lack of the aryl hydrocarbon receptor accelerates aging in mice
(Wiley, 2019-09-06) Bravo-Ferrer, Isabel; Cuartero, María Isabel; Medina, Violeta; Ahedo-Quero, Dalia; Peña-Martínez, Carolina; Pérez-Ruíz, Alberto; Fernández-Valle, María Encarnación; Hernández-Sánchez, Catalina; Fernández-Salguero, Pedro; Lizasoain, Ignacio; Moro, Maria Ángeles
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor, largely known for its role in xenobiotic metabolism and detoxification as well as its crucial role as a regulator of inflammation. Here, we have compared a cohort wild-type and AhR-null mice along aging to study the relationship between this receptor and age-associated inflammation, termed as “inflammaging,” both at a systemic and the CNS level. Our results show that AhR deficiency is associated with a premature aged phenotype, characterized by early inflammaging, as shown by an increase in plasma cytokines levels. The absence of AhR also promotes the appearance of brain aging anatomic features, such as the loss of the white matter integrity. In addition, AhR2/2 mice present an earlier spatial memory impairment and an enhanced astrogliosis in the hippocampus when comparedwith their age-matchedAhR+/+ controls. Importantly,we have found that AhR protein levels decrease with age in this brain structure, strongly suggesting a link between AhR and aging.
Pharmacological Modulation of Neutrophil Extracellular Traps Reverses Thrombotic Stroke tPA (Tissue-Type Plasminogen Activator) Resistance
(2019-07-16) Peña-Martínez, Carolina; Durán-Laforet, Violeta; García-Culebras, Alicia; Ostos, Fernando; Hernández-Jiménez, Macarena; Bravo-Ferrer, Isabel; Pérez-Ruiz, Alberto; Ballenilla, Federico; Díaz-Guzmán, Jaime; Pradillo, Jesús; Lizasoain, Ignacio; Moro, María
Background and Purpose—Recanalization of the occluded artery is a primary goal in stroke treatment. Unfortunately, endovascular treatment is not always available, and tPA (tissue-type plasminogen activator) therapy is limited by its narrow therapeutic window; importantly, the rate of early arterial recanalization after tPA administration is low, especially for platelet-rich thrombi. The mechanisms for this tPA resistance are not well known. Since neutrophil extracellular traps (NETs) have been implicated in this setting, our aim was to study whether NET pharmacological modulation can reverse tPA resistance and the role of TLR4 (Toll-like receptor 4), previously related to NET formation, in thrombosis. Methods—To this goal, we have used a mouse photothrombotic stroke model, which produces a fibrin-free thrombus composed primarily of aggregated platelets and thrombi obtained from human stroke patients. Results—Our results demonstrate that (1) administration of DNase-I, which promotes NETs lysis, but not of tPA, recanalizes the occluded vessel improving photothrombotic stroke outcome; (2) a preventive treatment with Cl-amidine, impeding NET formation, completely precludes thrombotic occlusion; (3) platelet TLR4 mediates NET formation after photothrombotic stroke; and (4) ex vivo fresh platelet-rich thrombi from ischemic stroke patients are effectively lysed by DNase-I. Conclusions—Hence, our data open new avenues for recanalization of platelet-rich thrombi after stroke, especially to overcome tPA resistance.