Año: 2022

Evaluation and Characterization of Post-Stroke Lung Damage in a Murine Model of Cerebral Ischemia

Faura J, Ramiro L, Simats A, Ma F, Penalba A, Gasull T, Rosell A, Montaner J, Bustamante A. Int J Mol Sci. 2022 Jul 22;23(15):8093. doi: 10.3390/ijms23158093. PMID: 35897671

https://pubmed.ncbi.nlm.nih.gov/35897671/

Abstract: After stroke and other brain injuries, there is a high incidence of respiratory complications such as pneumonia or acute lung injury. The molecular mechanisms that drive the brain-lung interaction post-stroke have not yet been elucidated. We performed transient middle cerebral artery occlusion (MCAO) and sham surgery on C57BL/6J mice and collected bronchoalveolar lavage fluid (BALF), serum, brain, and lung homogenate samples 24 h after surgery. A 92 proteins-panel developed by Olink Proteomics® was used to analyze the content in BALF and lung homogenates. MCAO animals had higher protein concentration levels in BALF than sham-controls, but these levels did not correlate with the infarct volume. No alteration in alveolar-capillary barrier permeability was observed. A total of 12 and 14 proteins were differentially expressed between the groups (FDR < 0.1)
in BALF and lung tissue homogenates, respectively. Of those, HGF, TGF-α, and CCL2 were identified as the most relevant to this study. Their protein expression patterns were verified by ELISA. This study confirmed that post-stroke lung damage was not associated with increased lung permeability or cerebral ischemia severity. Furthermore, the dysregulation of HGF, TGF-α, and CCL2 in BALF and lung tissue after ischemia could play an important role in the molecular mechanisms underlying stroke-induced lung damage.

This project received funding from: Instituto de Salud Carlos III (ISCIII) [PI17/02130, PI21/00939], co-financed by the European Regional Development Fund (FEDER), from the Fundació La Marató de TV3 [201706]. The participating centers take part into RICORS-ICTUS network [RD21/0006/0024, RD21/0006/0007, RD21/0006/0015] from Instituto de Salud Carlos III (ISCIII)
[PI17/02130, PI21/00939], co-financed by the European Regional Development Fund (FEDER). The funders had no role in designing or executing this study

Development of a Score to Predict the Paroxysmal Atrial Fibrillation in Stroke Patients: The Screening for Atrial Fibrillation Scale

Amaya Pascasio L, Quesada López M, García-Torrecillas JM, Arjona-Padillo A, Martínez Sánchez P. Front Neurol. 2022 Jun 28;13:900582. doi: 10.3389/fneur.2022.900582. eCollection 2022. PMID: 35837230
Conclusion: Screening for atrial fibrillation scale (SAFE) is a novel and simple strategy for selecting ischemic stroke patients at higher risk of having AF who can benefit from a
more thorough etiological evaluation. External validation of SAFE in a multicenter study, with a larger number of patients, is warranted.
FUNDING: The investigators were granted funds by the Carlos III Institute of Health (RICORS-ICTUS and RD21/0006/0010).

Preclinical Characterization of Antioxidant Quinolyl Nitrone QN23 as a New Candidate for the Treatment of Ischemic Stroke

Martínez-Alonso E, Escobar-Peso A, Aliena-Valero A, Torregrosa G et al. Antioxidants (Basel). 2022 Jun 16;11(6):1186. doi: 10.3390/antiox11061186. PMID: 35740081

https://pubmed.ncbi.nlm.nih.gov/35740081/

Abstract: Nitrones are encouraging drug candidates for the treatment of oxidative stress-driven diseases such as acute ischemic stroke (AIS). In a previous study, we found a promising quinolylnitrone, QN23, which exerted a neuroprotective effect in neuronal cell cultures subjected to oxygen–glucose deprivation and in experimental models of cerebral ischemia. In this paper, we update the biological and pharmacological characterization of QN23. We describe the suitability of intravenous administration of QN23 to induce neuroprotection in transitory four-vessel occlusion (4VO) and middle cerebral artery occlusion (tMCAO) experimental models of brain ischemia by assessing neuronal
death, apoptosis induction, and infarct area, as well as neurofunctional outcomes. QN23 significantly decreased the neuronal death and apoptosis induced by the ischemic episode in a dose-dependent manner and showed a therapeutic effect when administered up to 3 h after post-ischemic reperfusion onset, effects that remained 11 weeks after the ischemic episode. In addition, QN23 significantly reduced infarct volume, thus recovering the motor function in a tMCAO model. Remarkably, we assessed the antioxidant activity of QN23 in vivo using dihydroethidium as a molecular probe for radical species. Finally, we describe QN23 pharmacokinetic parameters. All these resul

Funding: This work was supported by the Instituto de Salud Carlos III and co-financed by the European Development Regional Fund (FEDER) through grants PI18/00255, RD16/0019/0006,and RD21/0006/0019 to J.M. and A.A., and RD16/0019/0008 and RD21/0 006/0014 to J.B.S.; the MINECO grant SAF2015-65586-R to J.M.-C.; and the Comunidad de Madrid Neurocentro project B2017/BMD-3760 to D.G.-N.