Publicaciones

Research Letters: Retinoic Acid-Loaded Nanoparticles Promote Neurovascular Protection in Stroke

Machado-Pereira M, Grayston A, Garcia-Gabilondo M et al. Stroke. 2023 Apr;54(4):e149-e151. doi: 10.1161/STROKEAHA.122.041839. Epub 2023 Mar 13. PMID: 36912140

https://pubmed.ncbi.nlm.nih.gov/36912140/

Funding: Supported by Portuguese Platform of BioImaging, POCI-01-0145-FEDER-022122; FCT, UID/Multi/00709/2013, SFRH/BD/137440/2018, ISCIII, FI17/00073; PTDC/BTM- SAL/5174/2020, EXPL/BTM-ORG/1348/2021; INTER-REG Atlantic Area (EAPA_791/2018_ NEUROATLANTIC Project), INTER-REG V A España Portugal (POCTEP; 0624_2IQBIONEURO_6_E), European Regional Development Fund; SLT017/20/000197 from AGAUR; RICORS-Stroke Network from ISCIII (RD21/0006/0007); IF/00178/2015/CP1300/CT0001; PERIS-SLT017/20/000197 (Generalitat Catalunya).

Circulating extracellular vesicles promote recovery in a preclinical model of intracerebral hemorrhage

Laso-García F, Casado-Fernández L, Piniella D et al. Mol Ther Nucleic Acids. 2023 Mar 21;32:247-262. doi: 10.1016/j.omtn.2023.03.006. eCollection 2023 Jun 13. PMID: 37090418

https://pubmed.ncbi.nlm.nih.gov/37090418/

Abstract: Circulating extracellular vesicles (EVs) are proposed to participate in enhancing pathways of recovery after stroke through paracrine signaling. To verify this hypothesis in a proof-ofconcept study, blood-derived allogenic EVs from rats and xenogenic EVs from humans who experienced spontaneous good recovery after an intracerebral hemorrhage (ICH) were administered intravenously to rats at 24 h after a subcortical ICH. At 28 days, both treatments improved the motor function assessment scales score, showed greater fiber preservation in the perilesional zone (diffusion tensor-fractional anisotropy MRI), increased immunofluorescence markers of myelin (MOG), and decreased astrocyte markers (GFAP) compared with controls. Comparison of the protein cargo of circulating EVs at 28 days from animals with good vs. poor recovery showed down expression of immune system activation pathways (CO4, KLKB1, PROC, FA9, and C1QA) and of restorative processes such as axon guidance (RAC1), myelination (MBP), and synaptic vesicle trafficking (SYN1), which is in line with better tissue preservation. Up-expression of PCSK9 (neuron differentiation) in xenogenic EVs-treated animals suggests
enhancement of repair pathways. In conclusion, the administration of blood-derived EVs improved recovery after ICH. These findings open a new and promising opportunity for
further development of restorative therapies to improve the outcomes after an ICH.

Funding: The experimental animal model study was approved by the Ethics Committee for Research in Animals at the La Paz University Hospital and authorized by the Madrid Regional Government. Animal care and experimental procedures were designed in accordance with our medical school’s Ethical Committee for the Care and Use of Animals
in Research (Ref. PROEX 159/17) according to the Spanish (RD 1201/ 2005 and RD53/2013) and EU (86/609/CEE, 2003/65/CE, and 2010/ 63/EU) rules. This work was supported by Instituto de Salud Carlos III (ISCIII) and co-funded by the European Union (European Regional Development Fund -FEDER) under grant PI17/01922 and PI20/00243; Invictus plus network under grant RD16/0019/0005; RICORS network under grant RD21/0006/0012; Miguel Servet under grant CP15/00069 and CPII20/00002 to M.G.-F. and CP20/00024 to L.O.-O.; Sara Borrell under grant CD19/00033 to M.P.-M., CD20/00112 to M.d.P.C.-V. and CD21/00059 to J.A.-O.; Ministerio de Universidades, Plan de Recuperación, Transformación y Resiliencia, Universidad Autónoma de Madrid under grant CA1/RSUE/2021-00753 to D.P.-A.; and the Spanish Ministry of Health-ISCIII under grant FI18/00026 to F.L.-G. and FI17/00188 to M.C.G.-d.F.

Intelligence-Based Recommendation System for Critical Stroke Management in Intensive Care Units

García Terriza, L.; Risco-Martín, J.; Ayala, J. and Roselló, G. BIOINFORMATICS 2023, ISBN 978-989-758-631-6; ISSN 2184-4305, pages 131-138. DOI: 10.5220/0011621000003414

https://www.scitepress.org/Papers/2023/116210/116210.pdf

Abstract: This work presents an integrated recommendation system capable of providing support in healthcare critical environments such as Intensive Care Units or Stroke Care Units using Machine Learning techniques. The system can manage several patients by reading monitoring hemodynamic data in real-time, presenting current death risk probability, and showing recommendations that would reduce such probability and, in some cases, avoid death. This system introduces a novel method to produce recommendations based on genetic models and supervised machine learning. The interface is built upon a web application where clinicians can evaluate recommendations and straightforwardly provide feedback.

Funding: This research has been funded by Instituto de Salud Carlos III (RICORS-RD21/0006/0009) and cofinanced with FEDER Funds and/or from the European funds of the Recovery, Transformation and Resilience Plan and by NextGenerationEU. This work is also supported by Spanish Ministry of Science and Innovation under project PID2019-110866RB-I00.

Cross-talk between energy and redox metabolism in astrocyte-neuron functional cooperation

Almeida A, Jimenez-Blasco D, Bolaños JP. Essays Biochem. 2023 Mar 3;67(1):17-26. doi: 10.1042/EBC20220075. PMID: 36805653

https://pubmed.ncbi.nlm.nih.gov/36805653/

Abstract: Astrocytes show unique anatomical, morphological, and metabolic features to take up substrates from the blood and metabolize them for local delivery to active synapses to sustain neuron function. In the present review, we specifically focus on key molecular aspects of energy and redox metabolism that facilitate this astrocyte-neuronal coupling in a controlled manner. Basal glycolysis is co-ordinated by the anaphase-promoting complex/cyclosome (APC/C)-Cdh1, a ubiquitin ligase that targets the proglycolytic enzyme 6-phosphofructokinase-2,6-bisphosphastate-3 (PFKFB3) for degradation. APC/C-Cdh1 activity is more robust in neurons than in astrocytes, which determine that PFKFB3 abundance and glycolytic rate are weaker in neurons. The low PFKFB3 activity in neurons facilitates glucose-6-phosphate oxidation via the pentose-phosphate pathway, which promotes antioxidant protection. Conversely, the high PFKFB3 activity in astrocytes allows the production and release of glycolytic lactate, which is taken up by neurons that use it as an oxidizable substrate. Importantly, the mitochondrial respiratory chain is tighter assembled in neurons than in astrocytes, thus the bioenergetic efficiency of mitochondria is higher in neurons. Because of this, the production of reactive oxygen species (mROS) by mitochondrial complex I is very low in neurons and very high in astrocytes. Such a naturally occurring high abundance of mROS in astrocytes physiologically determines a specific transcriptional fingerprint that contributes to sustaining cognitive performance. We conclude that the energy and redoxmetabolism of astrocytes must complementarily match that of neurons to regulate brain function and animal welfare.

Funding: This work was supported by the Agencia Estatal de Investigacion [grant numbers ´ PID2019-105699RB-I00/AEI/10.13039/501100011033, PDC2021-121013-I00, RED2018-102576-T (to J.P.B.)]; Plan Nacional de Drogas [grant number 2020I028 (to J.P.B.)]; Instituto de Salud Carlos III [grant numbers PI21/00727, RD21/0006/0005
cofunded by the European Union (to A.A.)]; and Junta de Castilla y Leon [grant number CS/151P20 cofunded by P.O. FEDER (to ´ A.A.)]; Apoyo Regional a la Competitividad Empresarial, [grant number ICE 04/18/LE/0017 (to J.P.B.)]; and Escalera de Excelencia [grant number CLU-2017-03 (to J.P.B. and A.A.)]. D.J.B. is a recipient of a Juan de la Cierva-Incorporacion contract [grant number ´ IJC2020-044230-I].