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Beyond wrecking a wall:revisiting the concept of blood–brain barrier breakdown in ischemic stroke

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Neural Regeneration Research 2025年第7期20卷 1944-1956页

作者： Julia Castillo-gonzález Elena gonzález-Rey institute of Parasitology and Biomedicine Lopez-Neyra(iPBLN) CSICPT SaludGranadaSpain

The blood–brain barrier constitutes a dynamic and interactive boundary separating the central nervous system and the peripheral *** tightly modulates the ion transport and nutrient influx,while restricting the entry of harmful factors,and selectively limiting the migration of immune cells,thereby maintaining brain *** the well-established association between blood–brain barrier disruption and most neurodegenerative/neuroinflammatory diseases,much remains unknown about the factors influencing its physiology and the mechanisms underlying its ***,the role of blood–brain barrier breakdown in the translational failure underlying therapies for brain disorders is just starting to be *** review aims to revisit this concept of“blood–brain barrier breakdown,”delving into the most controversial aspects,prevalent challenges,and knowledge gaps concerning the lack of blood–brain barrier *** moving beyond the oversimplistic dichotomy of an“open”/“bad”or a“closed”/“good”barrier,our objective is to provide a more comprehensive insight into blood–brain barrier dynamics,to identify novel targets and/or therapeutic approaches aimed at mitigating blood–brain barrier ***,in this review,we advocate for considering the diverse time-and location-dependent alterations in the blood–brain barrier,which go beyond tight-junction disruption or brain endothelial cell breakdown,illustrated through the dynamics of ischemic stroke as a case *** this exploration,we seek to underscore the complexity of blood–brain barrier dysfunction and its implications for the pathogenesis and therapy of brain diseases.

关键词： blood–brain barrier disruption drug delivery ischemic stroke neuroinflammation tight-junctions

Targeting harmful effects of non-excitatory amino acids as an alternative therapeutic strategy to reduce ischemic damage

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Neural Regeneration Research 2025年第9期20卷 2454-2463页

作者： Victoria Jiménez Carretero irisÁlvarez-Merz Jorge hernández-Campano Sergei A.Kirov Jesús M.hernández-Guijo Department of Pharmacology and Therapeutic School of MedicineUniv.Autónoma de MadridMadridSpain Ramón y Cajal institute for Health Research(iRYCiS) Neurobiology-Research ServiceHospital Ramón y CajalMadridSpain institute of Neurobiology Faculty of Mathematics and Natural SciencesHeinrich Heine University DüsseldorfDüsseldorfGermany Department of Neuroscience and Regenerative Medicine&Department of Neurosurgery Medical College of Georgia at Augusta UniversityAugustaGAUSA

The involvement of the excitatory amino acids glutamate and aspartate in ce rebral ischemia and excitotoxicity is ***,the role of non-excitatory amino acids in brain damage following a stroke or brain trauma remains largely *** release of amino acids by necrotic cells in the ischemic core may contribute to the expansion of the *** findings indicated that the reversible loss of field excitato ry postsynaptic potentials caused by transient hypoxia became irreversible when exposed to a mixture of just four non-excitatory amino acids(L-alanine,glycine,L-glutamine,and L-serine)at their plasma *** amino acids induce swelling in the somas of neurons and astrocytes during hypoxia,along with permanent dendritic damage mediated by N-methyl-D-aspartate *** N-methyl-D-aspartate receptors prevented neuronal damage in the presence of these amino acids during *** is likely that astroglial swelling caused by the accumulation of these amino acids via the alanine-serine-cysteine transporter 2 exchanger and system N transporters activates volume-regulated anion channels,leading to the release of excitotoxins and subsequent neuronal damage through N-methyl-D-aspartate receptor ***,previously unrecognized mechanisms involving non-excitatory amino acids may contribute to the progression and expansion of brain injury in neurological emergencies such as stroke and traumatic brain *** these pathways co uld highlight new therapeutic targets to mitigate brain injury.

关键词： cell swelling N-methyl-D-aspartate receptor non-excitatory amino acids stroke synaptic transmission

Dendritic spine degeneration:a primary mechanism in the aging process

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Neural Regeneration Research 2025年第6期20卷 1696-1698页

作者： gonzalo Flores Leonardo Aguilar-hernández Fernado García-Dolores Humberto Nicolini Andrea Judith Vázquez-hernández Hiram Tendilla-Beltrán instituto de Fisiología Benemérita Universidad Autónoma de Puebla(BUAP)PueblaMexico instituto de Ciencias Forenses(iNCiFO) Tribunal Superior de Justicia de la Ciudad de México(TSJCDMX).Mexico CityMexico instituto Nacional de Medicina Genómica(iNMEGEN) Mexico CityMexico

Recent reports suggest that aging is not solely a physiological process in living beings;instead, it should be considered a pathological process or disease(Amorim et al., 2022). Consequently, this process involves a wide range of factors, spanning from genetic to environmental factors, and even includes the gut microbiome(GM)(Mayer et al., 2022). All these processes coincide at some point in the inflammatory process, oxidative stress, and apoptosis, at different degrees in various organs and systems that constitute a living organism(Mayer et al., 2022;Aguilarhernández et al., 2023).

关键词： aging process stress

impacts of Pi3K/protein kinase B pathway activation in reactive astrocytes: from detrimental effects to protective functions

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Neural Regeneration Research 2025年第4期20卷 1031-1041页

作者： Ramón Pérez-Núñez María Fernanda gonzález Ana María Avalos Lisette Leyton Cellular Communication Laboratory Programa de Biología Celular y MolecularCenter for Studies on ExerciseMetabolism and Cancer(CEMC)Instituto de Ciencias Biomédicas(ICBM)Facultad de MedicinaUniversidad de ChileSantiagoChile Advanced Center for Chronic Diseases(ACCDiS) Faculty of Chemical and Pharmaceutical Sciences&Faculty of MedicineUniversidad de ChileSantiagoChile instituto de Ciencias Biomédicas Facultad de Ciencias de la SaludUniversidad Autónoma de ChileSantiagoChile

Astrocytes are the most abundant type of glial cell in the central nervous *** injury and inflammation,astrocytes become reactive and undergo morphological and functional *** on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,***,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and *** analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their *** actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune *** phosphoinositide 3-kinase(Pi3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo *** astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory ***,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their *** highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the Pi3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/Pi3K/AKT/connexin 43,and Notch/Pi3K/AKT *** targeting the inactivation of the Pi3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial *** dual function of the Pi3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function *** review emphasizes the importance of employing astrocyte-exclusive models to underst

关键词： inflammation integrins neuroprotective neurotoxic phosphatidylinositol 3-kinase reactive astrocytes signal transduction Thy-1(CD90)

The ecological scale mediates whether trees experience drought legacies in radial growth

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Forest Ecosystems 2023年第3期10卷 298-306页

作者： Héctor hernández-Alonso Jaime Madrigal-gonzález Fernando Silla Area of Ecology Faculty of BiologyUniversidad de SalamancaE-37007SalamancaSpain iuFOR-EiFAB Campus de SoriaUniversidad de ValladolidE-42004SoriaSpain

The impact of lag effects produced by disturbances on primary production has been a major concern among ecologists during the last *** and extreme climatic events are imposing drastic reductions in radial growth of trees as evidenced in tree-rings series Dendrochronological samples are obtained at tree level but analyzed at an aggregated scale(i.e.,mean chronologies),although aggregating tree-ring chronology on a regional scale may reduce the possibility of studying the variability of individual tree response to drought,by amplifying the average population ***,we conducted experimental research in which 370 trees of 5 species were analyzed to assess the potential statistical and scaling issues that may occur when using regressionbased methods to analyze ecosystem responses to *** legacy effects were quantified using individual and aggregated ***,lag effects were validated using confidence and prediction intervals to identify values falling outside the certainty of the climate-growth model individual scale legacy effects contrasted with confidence intervals were commonly distributed across species but were scarce when compared with prediction *** analysis of aggregated scale legacies detected significant growth reductions when validated using prediction intervals;however,individual scale legacy lag effects were not *** finding directly contrasts the results obtained when using an aggregated *** results provide empirical evidence on how aggregating ecological data to infer processes that emerge from an individual scale can lead to distorted *** therefore encourage the use of individual based statistical and ecological procedures to analyze tree rings as a means of further understanding the ecosystem responses to disturbances.

关键词： Legacy effects Drought disturbances Tree growth Tree-ring width Dendrochronology individual scale Mountainous forests

Tribological performance of tributylmethylammonium bis(trifluoromethylsulfonyl)amide as neat lubricant and as an additive in a polar oil

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Friction 2019年第3期7卷 282-288页

作者： Rubén gonzález Diego RAMOS David BLANCO Alfonso FERNández-gonzález Jose L.ViESCA Mark HADFiELD Antolin hernández BATTEZ Department of Marine Science and Technology University of OviedoAsturias 33203Spain Department of Construction and Manufacturing Engineering University of OviedoAsturias 33203Spain Department of Physical and Analytical Chemistry University of OviedoAsturias 33006Spain Department of Design and Engineering Bournemouth UniversityPoole BH12 5BBUK

The ionic liquid(iL) tributylmethylammonium bis(trifluoromethylsulfonyl)amide([N4441][NTf2]) was used as neat lubricant and as an additive(1.5 wt%) in a polar oil to study its friction and wear reducing *** tests were completed for 90 minutes at room temperature and 100 °C in a reciprocating configuration at loads of 30 and 70 N,10 Hz-frequency,and 4 mm stroke *** volume was measured by confocal microscopy and the surface-iL interaction determined by *** main findings were that neat iL showed the best tribological behavior;the iL-containing mixture behaved similar to the base oil regarding friction,however outperformed the antiwear behavior of the base oil under higher temperature;surface-iL chemical interaction was found mainly at 100 °C.

关键词： ionic liquid additive friction wear polar oil

Synthesis of activated carbons from black sapote seeds,characterization and application in the elimination of heavy metals and textile dyes

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Chinese Journal of Chemical Engineering 2020年第2期28卷 613-623页

作者： Alejandra Alicia Peláez-Cid Vincent Romero-hernández Ana María Herrera-gonzález Alejandro Bautista-hernández Oscar Coreno-Alonso Facultad de ingeniería Benemérita Universidad Autónoma de PueblaMexico instituto de Ciencias Básicas e ingeniería Universidad Autónoma del Estado de HidalgoMexico División de ingenierías Universidad de GuanajuatoMexico

Many different techniques may be used to remove industrial pollutants from wastewater. Adsorption using activated carbon has been reported to be an effective method. This work proposes the use of a vegetable residue(black sapote seeds) as a raw material for its synthesis. These carbons were chemically activated using phosphoric acid and carbonized at 673 and 873 K. Adsorption isotherms were constructed for the textile dyes on the carbons, and this data was treated using Langmuir’s equation to quantitatively describe the adsorption process. The synthesized carbons were characterized using FTiR, EA, SEM, Nitrogen adsorption(specific surface areas of 879 and 652 m2·g-1), and their points of zero charge(2.1 and 2.3). it was possible to adsorb both heavy metals and textile dyes present in aqueous solutions and wastewaters using these activated carbons. Heavy metals were adsorbed almost completely by both carbons. Cationic dyes where adsorbed(58–59.8 mg·g-1) in greater amounts compared to anionic dyes(10–58.8 mg·g-1). The amount of anionic dyes adsorbed increased almost 30% by changing the pH of the solutions. One of the carbons was thermally regenerated on three occasions without losing its adsorption capacity and it was proved in a flow system.

关键词： Activated carbons Black sapote seeds Heavy metal adsorption Textile dye adsorption Wastewater treatment

New insights into Wnt signaling alterations in amyotrophic lateral sclerosis: a potential therapeutic target?

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Neural Regeneration Research 2020年第9期15卷 1580-1589页

作者： Carlos gonzález-Fernández Pau gonzález Francisco Javier Rodríguez Laboratory of Molecular Neurology Hospital Nacional de Parapléjicos (HNP)

Amyotrophic lateral sclerosis is a fatal neurodegenerative disorder characterized by upper and lower motor neuron degeneration, which leads to progressive paralysis of skeletal muscles and, ultimately, respiratory failure between 2–5 years after symptom onset. Unfortunately, currently accepted treatments for amyotrophic lateral sclerosis are extremely scarce and only provide modest benefit. As a consequence, a great effort is being done by the scientific community in order to achieve a better understanding of the different molecular and cellular processes that influence the progression and/or outcome of this neuropathological condition and, therefore, unravel new potential targets for therapeutic intervention. interestingly, a growing number of experimental evidences have recently shown that, besides its well-known physiological roles in the developing and adult central nervous system, the Wnt family of proteins is involved in different neuropathologica conditions, including amyotrophic lateral sclerosis. These proteins are able to modulate, at least, three different signaling pathways, usually known as canonical(β-catenin dependent) and non-canonical(β-catenin independent) signaling pathways. in the present review, we aim to provide a general overview of the current knowledge that supports the relationship between the Wnt family of proteins and its associated signaling pathways and amyotrophic lateral sclerosis pathology, as well as their possible mechanisms of action. Altogether, the currently available knowledge suggests that Wnt signaling modulation might be a promising therapeutic approach to ameliorate the histopathological and functional deficits associated to amyotrophic lateral sclerosis, and thus improve the progression and outcome of this neuropathology.

关键词： ALS astrocytes Frizzled human microglia motor neuron neurodegeneration neuroinflammation spinal cord Wnt

A building energy models calibration methodology based on inverse modelling approach

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Building Simulation 2022年第11期15卷 1883-1898页

作者： Vicente Gutiérrez gonzález Carlos Fernández Bandera installations construction and structuresSchool of ArchitectureUniversity of NavarraCampus UniversitarioPamplona31009NavarraSpain

Nowadays,building energy models(BEMs)are widely used,particularly in the assessment of energy consumption in buildings to address the potential savings that can be *** realisation of a dynamic energy model based on high-fidelity physics(white-box models)requires a tuning process to fit the model to reality,due to many uncertainties *** some research trends try to reduce this performance gap by modulating different types of experimental parameters such as:capacitances or *** EnergyPlus simulation software,in its latest versions,has implemented an object:HybridModel:Zone that calculates the infiltration and internal mass of buildings using an inverse modelling approach that employs only the measured indoor temperature data to invert the heat balance equation for the zone under *** main objective of this paper is to reduce the execution time and uncertainties in the development of quality energy models by generating a new calibration methodology that implements this *** uses,as a starting point,a research created by the authors of this study,which was empirically and comparatively validated against the energy models developed by the participants in Annex *** is also worth highlighting the empirical validation of the HybridModel:Zone object,since it was activated in all scenarios where its execution is possible:periods of seven days or more of free oscillation and periods in which the building is under *** findings are *** data generated with the new methodology,if compared with those produced by the baseline model,improve their resemblance to the real ones by 22.9%.While those of its predecessor did it by 15.6%.For this study,the two dwellings foreseen in Annex 58 of the iEA ECB project have been modelled and their real monitoring data have been used.

关键词： internal thermal mass energy simulation EnergyPlus inverse model Annex 58 infiltration