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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

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)

Impact of Shaft Stiffness on Inertial Response of Fixed Speed Wind Turbines

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电力系统自动化 2012年第8期36卷 191-197页

作者： Francisco gonzlez-LONGATT Faculty of Engineering and Computing Coventry UniversityCoventry CV1 5FBUnited Kingdom

Future power system faces several challenges,one of them is the high penetration level of intermittent wind power generation,providing small or even no inertial response and being not contributing to the frequency *** effect of shaft stiffness on inertial response of fixed speed wind turbines is *** different drive-train models based on the multi-body system are *** small-signal analysis demonstrates no significant differences between models in terms of electro-mechanical eigen-values for increasing shaft *** natural resonance frequency of drive-train torsion modes shows slightly different values between damped and undamped models,but no significant differences are found in the number-mass ***-domain simulations show the changes in the active power contribution of a wind farm based on a fixed speed wind turbine during the system frequency *** changes in the kinetic energy during the dynamic process are calculated and their contribution to the inertia constant is small and *** largest contribution of the kinetic energy is provided at the beginning of the system frequency disturbance to reduce the rate of the frequency change,it is positive for the frequency stability.

关键词：风力发电机刚度模型惯性风力涡轮机频率稳定性轴定速传动系统

Tolerance of Chrysantemum maximum to heavy metals:The potential for its use in the revegetation of tailings heaps

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Journal of Environmental Sciences 2013年第2期25卷 367-375页

作者： Ma.del Carmen A.gonzlez-Chvez Rogelio Carrillo-gonzlez Colegio de Postgraduados Programa de EdafologíaCarr.Mxico-Texcocokm 36.5MontecilloTexcoco estado de Mxico 56230Mxico

To find if ornamental plants are applicable to the remediation of metal-polluted areas, the tolerance of chrysanthemum plants （Chysanthemum maximum） var. Shasta to different metals under hydroponic conditions was studied. Their responses as influenced by the mycorrhizal fungus Glomus mosseae （Nicol. ＆ Gerd.） Gerdemann ＆ Trappe BEG25 on substrates containing mine residues were also investigated. Our results showed that chrysanthemum is a metal-tolerant plant under hydroponic conditions, plants behaving as Pb-excluders, whereas Cd, Cu and Ni were accumulated in roots. Low accumulation in flowers was observed for Cd and Cu but it was concentration-dependent. Ni and Pb were not translocated to flowers. Shoot biomass was not significantly affected by the different rates of mine residue addition for both mycorrhizal and non-mycorrhizal plants. Mycorrhizal plants accumulated less Pb and Cu in both shoots and roots than non-mycorrhizal plants. Chysanthemum could be a prospective plant for revegetation of tailings and the use of inoculation may decrease plant metal accumulation in polluted soils.

关键词： mine residues ornamental plants phytostabilization urban remediation

Disaster Risk Governance as Assemblage: The Chilean Framework of the 1985 San Antonio Earthquake

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International Journal of Disaster Risk Science 2022年第6期13卷 878-889页

作者： Daniela P.gonzález Architecture and Urban Studies Pontifcal Catholic University of Chile7520245 SantiagoChile

The purpose of this article is to analyze disaster risk governance through assemblage theory, identifying how-during the altered political context of a military regime with a centralized disaster risk management as in the case of Chile in 1985-new actors emerge during the disaster response phase as a de/reterritorialization effect that is influenced by their agencies and relationships, disfiguring the edges of the assemblage. Based on this conceptualization, it is possible to investigate the interactions between the different actors, their power relations, and their reconfigurations in the governance exercise. For this purpose, we reviewed the response phase of the 1985 San Antonio earthquake that affected the central zone of Chile, where strategic functions, institutions, and forms of power are *** describe and visualize the actors during the response phase in the disaster risk governance framework, a map of actors was developed that identifies the existing relationships and their different weights. The central scale proved to be dominant and occupied a political space that was transfigured by its overrepresentation-enforced by allies such as the banking system and business associations-enhancing a neoliberal agenda. The leaps in scale from the central scale to the local scale cancel agency of the last, destabilizing its capacity to deal with the effects of the earthquake and isolating it from the decision-making processes. Consequently,delays in providing aid demonstrate that authoritarian governments do not provide better management in the disaster response phase.

关键词： Assemblage Chile Disaster response phase Disaster risk governance San Antonio earthquake

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

Progesterone for the treatment of central nervous system disorders: the many signaling roads for a single molecule

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Neural Regeneration Research 2020年第10期15卷 1846-1847页

作者： Susana Laura gonzález Universidad de Buenos Aires Facultad de Medicina Departamento de Bioquímica Humana Buenos Aires Laboratorio de Nocicepción y Dolor Neuropático Instituto de Biología y Medicina Experimental

Central nervous system(CNS)injuries and neurodegenerative diseases show a broad spectrum of common pathophysiological processes,including oxidative stress,neuroinflammation,excitotoxicity,demyelination and neurotransmission *** the past decades,valuable experimental investigations have helped to clarify the role and timing of these multiple molecular and cellular mechanisms in each of these particular disorders,which usually overlap and critically contribute to long-term ***,up to now,no definite cures or effective disease-modifying therapies are available for any of these *** has led to an active search of novel therapeutic approaches,including the repositioning of existing drugs for new indications,as a valid approach to promptly move candidate molecules to clinical trials.

关键词： injuries disorders drugs

Thrombin activation and liver inflammation in advanced hepatitis C virus infection

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World Journal of Gastroenterology 2016年第18期22卷 4427-4437页

作者： Emilio gonzález-Reimers Geraldine Quintero-Platt Candelaria Martín-gonzález Onán Pérez-Hernández Lucía romero-Acevedo Francisco Santolaria-Fernández Servicio de Medicina Interna Hospital Universitario de Canarias Universidad de La Laguna

Hepatitis C virus(HCV) infection is associated with increased thrombotic risk. Several mechanisms are involved including direct endothelial damage by the HCV virus, with activation of tissue factor, altered fibrinolysis and increased platelet aggregation and activation. In advanced stages, chronic HCV infection may evolve to liver cirrhosis, a condition in which alterations in the portal microcirculation may also ultimately lead to thrombin activation, platelet aggregation, and clot formation. Therefore in advanced HCV liver disease there is an increased prevalence of thrombotic phenomena in portal vein radicles. Increased thrombin formation may activate hepatic stellate cells and promote liver fibrosis. In addition, ischemic changes derived from vascular occlusion by microthrombi favor the so called parenchymal extinction, a process that promotes collapse of hepatocytes and the formation of gross fibrous tracts. These reasons may explain why advanced HCV infection may evolve more rapidly to end-stage liver disease than other forms of cirrhosis.

关键词： Coagulation Liver cirrhosis Hepatitis C virus Fibrogenesis Parenchymal extinction Portal thrombosis Protein C

Effects of fire history on animal communities:a systematic review

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Ecological Processes 2022年第1期11卷 248-258页

作者： Tania Marisol gonzález Juan David gonzález‑Trujillo Alberto Muñoz Dolors Armenteras Laboratorio de Ecología del Paisaje y Modelación de Ecosistemas ECOL‑MOD Departamento de BiologíaFacultad de CienciasUniversidad Nacional de ColombiaEdificio 421111321 BogotáColombia Departamento de Biología Facultad de CienciasUniversidad Nacional de ColombiaEdificio 421111321 BogotáColombia Departamento de Didáctica de Ciencias Experimentales Sociales y MatemáticasFacultad de EducaciónUniversidad Complutense de Madrid28040 MadridSpain CREAF 08193 Cerdanyola del VallèsCataloniaSpain

Fire is a natural agent with a paramount role in ecosystem functioning and biodiversity ***,it can also act as a negative force against many *** some knowledge of the interactions of fire and vegetation,there is no clear understanding of how different components of fire regimes(i.e.,severity,history,or frequency)influence known patterns of animal ***,we performed a systematic review on the global responses of arthropods,birds,mammals,reptiles,and amphibians to different fire ***,we focused on assessing how fire severity,history,and frequency modulate the effect of fire on the richness and abundance of faunal *** conducted a systematic review of 566 papers retrieved from the Scopus *** also scrutinized all the documents included in the meta‑analysis of Pastro et al.(Pastro et *** Ecol Biogeogr 23:1146–1156,2014).Our selection criteria excluded studies without data on species richness or *** also excluded studies without adequate controls and those without information about the fire regime of the study *** careful examination,we used data from 162 studies to perform a quantitative meta‑*** the 162 studies meeting our selection criteria,nearly 60%of the studies are from North America,25%from Australia,11%from Europe,and 4%from the *** to the ecological role of fire,90%of the studies were carried out in fire‑dependent ecosystems(i.e.,conifer forests,natural savannas,pastures).Finally,40%of the studies analyzed birds,22%mammals,and 20%*** meta‑analysis of the available evidence indicates that fire history is an important modulator of animal richness and *** negative or positive,animal responses depended on the time since the last fire *** that short‑term studies may not capture such a long‑term effect on fauna,this translates to more challenges at implementing fire management *** or not we can

关键词： Amphibians Arthropods Birds Fire regime components Mammals Reptiles