Publicaciones: julio 2022

Postischemic Neuroprotection of Aminoethoxydiphenyl Borate Associates Shortening of Peri-Infarct Depolarizations

Fernández-Serra R, Martínez-Alonso E, Alcázar A, Chioua M, Marco-Contelles J, Martínez-Murillo R, Ramos M, Guinea GV, González-Nieto D. Int J Mol Sci. 2022 Jul 4;23(13):7449. doi: 10.3390/ijms23137449.PMID: 35806455
Abstract: Brain stroke is a highly prevalent pathology and a main cause of disability among older adults. If not promptly treated with recanalization therapies, primary and secondary mechanisms of injury contribute to an increase in the lesion, enhancing neurological deficits. Targeting excitotoxicity and oxidative stress are very promising approaches, but only a few compounds have reached the clinic with relatively good positive outcomes. The exploration of novel targets might overcome the lack of clinical translation of previous efficient preclinical neuroprotective treatments. In this study, we examined the neuroprotective properties of 2-aminoethoxydiphenyl borate (2-APB), a molecule that interferes with intracellular calcium dynamics by the antagonization of several channels and receptors. In a permanent model of cerebral ischemia, we showed that 2-APB reduces the extent of the damage and preserves the functionality of the cortical territory, as evaluated by somatosensory evoked potentials (SSEPs). While in this permanent ischemia model, the neuroprotective effect exerted by the antioxidant scavenger cholesteronitrone F2 was associated with a reduction in reactive oxygen species (ROS) and better neuronal survival in the penumbra, 2-APB did not modify the inflammatory response or decrease the content of ROS and was mostly associated with a shortening of peri-infarct depolarizations, which translated into better cerebral blood perfusion in the penumbra. Our study highlights the potential of 2-APB to target spreading depolarization events and their associated inverse hemodynamic changes, which mainly contribute to extension of the area of lesion in cerebrovascular pathologies.
Funding: This research was funded by the Ministerio de Economía y Competitividad Grants MAT2016-79832-R (to G.V.G. and D.G.-N.) and SAF2015-65586-R (to J.M.-C.), ISCIII and FEDER grant RD21/0006/0019 (to A.A.), Ministerio de Ciencia e Innovación grant PID2020-116403RB-I00 funded by MCIN/AEI/10.13039/501100011033 (to D.G.-N.) and funds from the regional government of Madrid: Neurocentro-B2017/BMD-3760 (to G.V.G., R.M.-M. and D.G.-N.) and IND2018/BMD-9804 (to G.V.G.).

A Polygenic Risk Score Based on a Cardioembolic Stroke Multitrait Analysis Improves a Clinical Prediction Model for This Stroke Subtype

Palà E, Bustamante A, Pagola J, Juega J, Francisco-Pascual J, Penalba A et al. Front Cardiovasc Med. 2022 Jul 4;9:908053. doi: 10.3389/fcvm.2022.908053. eCollection 2022. PMID: 35859587

https://pubmed.ncbi.nlm.nih.gov/35859587/

Results: We found and replicated eleven loci associated with CES. Eight were novel loci. Seven of them had been previously associated with AF, namely, CAV1, ESR2, GORAB, IGF1R, NEURL1, WIPF1, and ZEB2. KIAA1755 locus had never been associated with CES/AF, leading its index variant to a missense change (R1045W). The PRS generated has been significantly associated with CES improving discrimination and patient reclassification of a model with age, sex, and hypertension.

J. Cárcel-Márquez has received funding through an AGAUR Contract (Agència de Gestió d’Ajuts Universitaris i de Recerca; FI_DGR 2019, grant number 2020FI_B1 00157) co-financed with Fons Social Europeu (FSE) (https://agaur.gencat.cat). From Instituto de Salud Carlos III: E. Muiño is funded by a Río Hortega Contract (CM18/00198), M. Lledós is funded by a PFIS Contract (Contratos Predoctorales de Formación en Investigación en Salud, FI19/00309), C. Gallego-Fabrega is supported by a Sara Borrell Contract (CD20/00043) and Fondo Europeo de Desarrollo Regional (ISCIII-FEDER), T. Sobrino (CPII17/00027), and F. Campos (CPII19/00020) are recipients of research contracts from the Miguel Servet Program (https://www.isciii.es). This study has been funded by Instituto de Salud Carlos III PI15/01978, PI17/02089, PI18-01338, and RICORS-ICTUS RD21/0006/0006 (Instituto deSalud Carlos III), by Marató TV3 support of the Epigenesis study (https://www.ccma.cat/tv3/marato/), by the Fundació  Docència i Recerca FMT grant for the Epigenesis project(https://www.mutuaterrassa.com), by Eranet-Neuron of the biostroke project (AC19/00106) (https://www.neuron-eranet. eu), by Boehringer Ingelheim of the SEDMAN Study (https:// www.boehringer-ingelheim.it), and GCAT Cession Research Project PI-2018-01 (http://www.gcatbiobank.org). GCAT was funded by Acción de Dinamización del ISCIII-MINECO and the Ministry of Health of the Generalitat of Catalunya (ADE 10/00026); and have additional suport by the Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR) (2017-SGR 529).