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Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

Neural Regeneration Research 2025年第6期20卷 1644-1664页

作者： Gabriela Seplovich Yazan Bouchi juan Pablo de Rivero Vaccari jennifer C.Munoz Pareja Andrew Reisner Laura Blackwell Yehia Mechref kevin k.Wang j.Adrian Tyndall Binu Tharakan Firas kobeissy Department of Surgery Morehouse School of MedicineAtlantaGAUSA Department of Neurobiology Center for NeurotraumaMultiomics&Biomarkers(CNMB)Neuroscience InstituteMorehouse School of MedicineAtlantaGAUSA Department of Neurological Surgery and the Miami Project to Cure Paralysis University of Miami Miller School of MedicineMiamiFLUSA Division of Pediatric Critical Care Department of PediatricsUniversity of Miami Miller School of MedicineMiamiFLUSA Department of Pediatrics Emory UniversityAtlantaGAUSA Department of Neurosurgery Children’s Healthcare of AtlantaAtlantaGAUSA Department of Chemistry and Biochemistry Texas Tech UniversityLubbockTXUSA Morehouse School of Medicine AtlantaGAUSA

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

关键词： Alzheimer's disease caspase-1 chronic traumatic encephalopathy inflammasomes neurodegeneration neuroinflammation NLRP1 NLRP3 pyroptosis tauopathy traumatic brain injury

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Cyclic loading of marble:Correlating the attenuation of the electric and acoustic activities and highlighting criticality indices in terms of natural time

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International journal of Mining Science and Technology 2025年第2期35卷 159-174页

作者： Dimos Triantis Ilias Stavrakas Ermioni D.Pasiou Stavros k.kourkoulis University of West Attica Department of Electrical&Electronics EngineeringElectronic Devices and Materials LaboratoryAncient Olive Grove CampusAthens 12244Greece National Technical University of Athens School of Applied Mathematical and Physical SciencesDepartment of MechanicsLaboratory for Testing and MaterialsAthens 15773Greece

The attenuation of the acoustic activity in marble specimens under uniaxial compressive loadingunloading loops is quantified in juxtaposition to that of the electric *** parallel,the existence of"pre-failure indiceso"warning about entrance into a critical stage,that of impending fracture,is *** acoustic activity is quantified in terms of the normalized number of acoustic hits,their average rate of production and their cumulative energy,and,the cumulative counts and their average rate of *** electric activity is studied in terms of the pressure stimulated currents and the electric charge *** analysis revealed that the acoustic and electric activities are linearly correlated to each other,suggesting that they are different manifestations of the same damage *** addition,kaiser's effect,governing the acoustic activity,is found to govern,also,the electric ***,it is concluded that entrance into the critical stage is safely predicted by means of a simple criterion,based on the evolution of the average rate of change of the normalized cumulative counts in the natural time *** predictions are almost identical with those of the criterion based on the "varianceo" and the "entropies" of the time series of acoustic events in this domain.

关键词： Marble cyclic loading Acoustic emissions kaiser's effect Pressure stimulated currents Criticality indices Natural time

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Temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries on magnetic resonance imaging

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Neural Regeneration Research 2025年第11期20卷 3144-3150页

作者： Holly Flyger Samantha j.Holdsworth Alistair j.Gunn Laura Bennet Hamid Abbasi Mātai Medical Research Institute Tairāwhiti GisborneNew Zealand Department of Anatomy&Medical Imaging Faculty of Medical and Health SciencesThe University of AucklandAucklandNew Zealand Center for Brain Research The University of AucklandAucklandNew Zealand Auckland Bioengineering Institute The University of AucklandAucklandNew Zealand

Moderate to severe perinatal hypoxic-ischemic encephalopathy occurs in~1 to 3/1000 live births in high-income countries and is associated with a significant risk of death or neurodevelopmental *** assessment is important to help identify highrisk infants,to help families,and to support appropriate interventions.A wide range of monitoring tools is available to assess changes over time,including urine and blood biomarkers,neurological examination,and *** present,magnetic resonance imaging is unique as although it is expensive and not suited to monitoring the early evolution of hypoxic-ischemic encephalopathy by a week of life it can provide direct insight into the anatomical changes in the brain after hypoxic-ischemic encephalopathy and so offers strong prognostic information on the long-term outcome after hypoxic-ischemic *** review investigated the temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries,with a particular emphasis on exploring the correlation between the prognostic implications of magnetic resonance imaging scans in the first week of life and their relationship to long-term outcome prediction,particularly for infants treated with therapeutic hypothermia.A comprehensive literature search,from 2016 to 2024,identified 20 pertinent *** review highlights that while the optimal timing of magnetic resonance imaging scans is not clear,overall,it suggests that magnetic resonance imaging within the first week of life provides strong prognostic *** challenges limit the timing consistency,particularly the need for intensive care and clinical ***,although most reports examined the prognostic value of scans taken between 4 and 10 days after birth,there is evidence from small numbers of cases that,at times,brain injury may continue to evolve for weeks after *** suggests that in the future it will be important to explore a wider range of times after hypo

关键词： magnetic resonance imaging neonatal hypoxic-ischemic encephalopathy neurodevelopmental outcomes prognostic biomarkers in neuroimaging scan timing therapeutic hypothermia

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Two-plasmon-decay instability stimulated by dual laser beams in inertial confinement fusion

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Matter and Radiation at Extremes 2025年第1期10卷 48-56页

作者： C.-W.Lian Y.ji R.Yan j.Li L.-F.Wang Y.-k.Ding j.Zheng Department of Modern Mechanics University of Science and Technology of ChinaHefeiAnhui 230026China Collaborative Innovation Center of IFSA Shanghai Jiao Tong UniversityShanghai 200240China Department of Plasma Physics and Fusion Engineering University of Science and Technology of ChinaHefei 230026China Institute of Applied Physics and Computational Mathematics Beijing 100088China

Two-plasmon-decay instability(TPD)poses a critical target preheating risk in direct-drive inertial confinement *** this paper,TPD collectively driven by dual laser beams consisting of a normal-incidence laser beam(Beam-N)and a large-angle-incidence laser beam(Beam-L)is investigated via particle-in-cell *** is found that significant TPD growth can develop in this regime at previously unexpected low laser intensities if the intensity of Beam-L exceeds the large-angle-incidence *** beams contribute to the growth of TPD in a“seed-amplification”manner in which the absolute instability driven by Beam-L provides the seeds that are convectively amplified by Beam-N,making TPD energetically important and causing significant pump depletion and hot-electron generation.

关键词： laser pump decay

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Gene therapy for spinal muscular atrophy:perspectives on the possibility of optimizing SMN1 delivery to correct all neurological and systemic perturbations

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Neural Regeneration Research 2025年第7期20卷 2011-2012页

作者： Sharon j.Brown Rafael j.Yáñez-Muñoz Heidi R.Fuller School of Pharmacy and Bioengineering Keele UniversityKeeleUK Wolfson Center for Inherited Neuromuscular Disease TORCH BuildingRJAH Orthopaedic HospitalOswestryUK *** Center of Gene and Cell TherapyDepartment of Biological SciencesSchool of Life Sciences and the EnvironmentRoyal Holloway University of LondonEghamUK

Spinal muscular atrophy(SMA)is a genetic condition that results in selective lower motor neuron loss with concomitant muscle weakness and *** genetic cause of SMA was understood in 1995 when loss or impairment of the survival motor neuron 1(SMN1)gene was identified as the main contributing factor(Lefebvre et al.,1995).This,in combination with the discovery that humans have a“back-up”gene,SMN2,which can produce low levels(approximately 10%)of the full-length functional SMN protein,has led to the generation of SMA-specific gene *** was traditionally classified according to age of symptom onset and developmental milestones achieved,with life expectancy and severity varying between ***,SMN2 copy number is used as a proxy for the prediction of disease severity,with higher SMN2 copy number typically being associated with reduced severity of SMA,although this relationship is not absolute:some individuals with low SMN2 copy number have less severe SMA phenotypes and vice ***,the etiology of SMA is further complicated by other factors,such as non-typical nucleotide variants and SMN2-independent modifiers of disease severity.

关键词： atrophy traditionally absolute

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Laser interaction with undercritical foams of different spatial structures

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Matter and Radiation at Extremes 2025年第1期10卷 39-47页

作者： j.Limpouch V.Tikhonchuk O.Renner Sh.Agarwal T.Burian j.Cervenka j.Dostál R.Dudzák D.Ettel A.Gintrand L.Hudec L.juha O.klimo M.krupka M.krus T.Lastovicka R.Liska W.Nazarov S.k.Singh M.Šilhavík S.Weber Faculty of Nuclear Science and Physical Engineering Czech Technical University in Prague11519 PragueCzech Republic The Extreme Light Infrastructure ERIC ELI-Beamlines FacilityZa Radnicí83525241 DolníBrezanyCzech Republic Centre Lasers Intenses et Applications University of Bordeaux-CNRS-CEA351 Cours de la Liberation33405 TalenceFrance Institute of Physics Czech Academy of SciencesNa Slovance 1999/218200 PragueCzech Republic Institute of Plasma Physics Czech Academy of Sciences18200 PragueCzech Republic Faculty of Mathematics and Physics Charles University12116 PragueCzech Republic Faculty of Mechatronics Informatics and Interdisciplinary StudiesTechnical University of Liberec46117 LiberecCzech Republic Independent Foam Target Supplier St.AndrewsFifeScotland

The interaction of high-power laser pulses with undercritical foams produced by different techniques but with the same average density is studied at the PALS laser *** spatial-temporal evolution of X-ray emission is observed using an X-ray streak camera,electron and ion temperatures are measured by X-ray spectroscopy,and hot-electron production is characterized by monochromatic X-ray *** of a femtosecond laser probe pulse through foams is observed in the near and far *** spite of large differences in pore size and foam structure,the velocity of ionization front propagation is quite similar for all the foams studied and is slower than that in a homogeneous material of the same average *** ion temperature in the plasma behind the ionization front is a few times higher than the electron ***-electron production in plastic foams with small pores is strongly suppressed compared with that in solid targets,whereas in foams produced by additive manufacturing,it is significantly increased to the level observed in bare copper foil targets.

关键词： temperature. interaction critical

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LHAASO detection of very-high-energy γ-ray emission surrounding PSR j0248+6021

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Science China(Physics,Mechanics & Astronomy) 2025年

作者： Zhen Cao F.Aharonian Axikegu Y.X.Bai Y.W.Bao D.Bastieri X.j.Bi Y.j.Bi W.Bian A.V.Bukevich Q.Cao W.Y.Cao Zhe Cao j.Chang j.F.Chang A.M.Chen E.S.Chen H.X.Chen Liang Chen Lin Chen Long Chen M.j.Chen M.L.Chen Q.H.Chen S.Chen S.H.Chen S.Z.Chen T.L.Chen Y.Chen N.Cheng Y.D.Cheng M.C.Chu M.Y.Cui S.W.Cui X.H.Cui Y.D.Cui B.Z.Dai H.L.Dai Z.G.Dai Danzengluobu X.Q.Dong k.k.Duan j.H.Fan Y.Z.Fan j.Fang j.H.Fang k.Fang C.F.Feng H.Feng L.Feng S.H.Feng X.T.Feng Y.Feng Y.L.Feng S.Gabici B.Gao C.D.Gao Q.Gao W.Gao W.k.Gao M.M.Ge T.T.Ge L.S.Geng G.Giacinti G.H.Gong Q.B.Gou M.H.Gu F.L.Guo j.Guo X.L.Guo Y.Q.Guo Y.Y.Guo Y.A.Han O.A.Hannuksela M.Hasan H.H.He H.N.He j.Y.He Y.He Y.k.Hor B.W.Hou C.Hou X.Hou H.B.Hu Q.Hu S.C.Hu C.Huang D.H.Huang T.Q.Huang W.j.Huang X.T.Huang X.Y.Huang Y.Huang Y.Y.Huang X.L.ji H.Y.jia k.jia H.B.jiang k.jiang X.W.jiang Z.j.jiang M.jin M.M.kang I.karpikov D.khangulyan D.kuleshov k.kurinov B.B.Li C.M.Li Cheng Li Cong Li D.Li F.Li H.B.Li H.C.Li jian Li jie Li k.Li S.D.Li W.L.Li W.L.Li X.R.Li Xin Li Y.Z.Li Zhe Li Zhuo Li E.W.Liang Y.F.Liang S.j.Lin B.Liu C.Liu D.Liu D.B.Liu H.Liu H.D.Liu j.Liu j.L.Liu M.Y.Liu R.Y.Liu S.M.Liu W.Liu Y.Liu Y.N.Liu Q.Luo Y.Luo H.k.Lv B.Q.Ma L.L.Ma X.H.Ma j.R.Mao Z.Min W.Mitthumsiri H.j.Mu Y.C.Nan A.Neronov k.C.Y.Ng L.j.Ou P.Pattarakijwanich Z.Y.Pei j.C.Qi M.Y.Qi B.Q.Qiao j.j.Qin A.Raza D.Ruffolo A.Sáiz M.Saeed D.Semikoz L.Shao O.Shchegolev X.D.Sheng F.W.Shu H.C.Song Yu.V.Stenkin V.Stepanov Y.Su D.X.Sun Q.N.Sun X.N.Sun Z.B.Sun j.Takata P.H.T.Tam Q.W.Tang R.Tang Z.B.Tang W.W.Tian L.H.Wan C.Wang C.B.Wang G.W.Wang H.G.Wang H.H.Wang j.C.Wang kai Wang kai Wang L.P.Wang L.Y.Wang P.H.Wang R.Wang W.Wang X.G.Wang X.Y.Wang Y.Wang Y.D.Wang Y.j.Wang Z.H.Wang Z.X.Wang Zhen Wang Zheng Wang D.M.Wei j.j.Wei Y.j.Wei T.Wen C.Y.Wu H.R.Wu Q.W.Wu S.Wu X.F.Wu Y.S.Wu S.Q.Xi j.Xia G.M.Xiang D.X.Xiao G.Xiao Y.L.Xin Y.Xing D.R.Xiong Z.Xiong D.L.Xu R.F.Xu R.X.Xu W.L.Xu L.Xue D.H.Yan j.Z.Yan T.Yan C.W.Yang C.Y.Yang F.Yang F.F.Yang L.L.Yang M.j.Yang R.Z.Yang W.X.Yang Y.H.Yao Z.G.Yao L.Q.Yin N.Yin X.H.You Z.Y.You Y.H Southwest jiaotong University School of Astronomy and Space Science Nanjing University Center for Astrophysics Guangzhou University Tsung-Dao Lee Institute & School of Physics and Astronomy Shanghai jiao Tong University Institute for Nuclear Research of Russian Academy of Sciences Hebei Normal University University of Science and Technology of China LHAASO Collaboration State key Laboratory of Particle Detection and Electronics key Laboratory of Dark Matter and Space Astronomy & key Laboratory of Radio Astronomy Purple Mountain Observatory Chinese Academy of Sciences Research Center for Astronomical Computing Zhejiang Laboratory key Laboratory for Research in Galaxies and Cosmology Shanghai Astronomical Observatory Chinese Academy of Sciences School of Physics and Astronomy key Laboratory of Particle Astrophysics & Experimental Physics Division & Computing Center Yunnan University key Laboratory of Cosmic Rays (Tibet University) Ministry of Education Department of Physics The Chinese University of Hong kong key Laboratory of Radio Astronomy and Technology National Astronomical Observatories Chinese Academy of Sciences School of Physics and Astronomy (Zhuhai) & School of Physics (Guangzhou) & Sino-French Institute of Nuclear Engineering and Technology (Zhuhai) Sun Yat-sen University Institute of High Energy Physics Institute of Frontier and Interdisciplinary Science Shandong University APC Université Paris Cité CNRS/IN2P3 CEA/IRFU Observatoire de Paris Department of Engineering Physics & Department of Astronomy Tsinghua University School of Physics and Microelectronics Chinese Academy of Sciences Zhengzhou University Yunnan Observatories Chinese Academy of Sciences China Center of Advanced Science and Technology College of Physics Sichuan University School of Physics Peking University Guangxi key Laboratory for Relativistic Astrophysics School of Physical Science and Technology University of Chinese Academy of Sciences Guangxi University Department of Physics Faculty of Science Mahidol University Moscow Institute

We report the detection of an extended very-high-energy(VHE) γ-ray source coincident with the location of middle-aged(62.4 kyr) pulsar PSR j0248+6021, by using the LHAASO-WCDA data of live 796 d and LHAASO-kM2A data of live 1216d. A significant excess of γ-ray induced showers is observed both by WCDA in energy bands of 1-25 Te V and kM2A in energy bands of >25 TeV with 7.3σ and 13.5σ, respectively. The best-fit position derived through WCDA data is R.A. = 42.06°± 0.12°and Dec. = 60.24°± 0.13°with an extension of 0.69°±0.15°and that of the kM2A data is R.A.= 42.29°± 0.13°and Dec. =60.38°± 0.07°with an extension of 0.37°±0.07°. No clear extended multiwavelength counterpart of this LHAASO source has been found from the radio band to the GeV band. The most plausible explanation of the VHE γ-ray emission is the inverse Compton process of highly relativistic electrons and positrons injected by the pulsar. These electrons/positrons are hypothesized to be either confined within the pulsar wind nebula or to have already escaped into the interstellar medium, forming a pulsar halo.

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Real-world cost-effectiveness of targeted temperature management in out-of-hospital cardiac arrest survivors: results from an academic medical center

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World journal of Emergency Medicine 2025年第1期16卷 28-34页

作者： Wachira Wongtanasarasin Daniel k.Nishijima Wanrudee Isaranuwatchai jeff rey S.Hoch Department of Emergency Medicine Faculty of MedicineChiang Mai UniversityChiang Mai 50200Thailand Department of Emergency Medicine University of California Davis School of MedicineSacramento 95817USA Health Intervention and Technology Assessment Program Ministry of Public HealthBangkok 11000Thailand Institute of Health Policy Management and EvaluationUniversity of TorontoToronto M5T 3M6Canada Division of Health Policy and Management Department of Public Health SciencesUniversity of California Davis School of MedicineSacramento 95817USA Center for Healthcare Policy and Research University of California Davis School of MedicineSacramento 95817USA

BACkGROUND: Targeted temperature management(TTM) is a common therapeutic intervention, yet its cost-effectiveness remains uncertain. This study aimed to evaluate the real-world cost-effectiveness of TTM compared with that of conventional care in adult out-of-hospital cardiac arrest(OHCA) survivors using clinical patient-level ***: We conducted a retrospective cohort study at an academic medical center in the USA to assess the cost-effectiveness of TTM in adult non-traumatic OHCA survivors between 1 january, 2019 and 30 june, 2023. The primary outcome was survival to hospital discharge. Incremental cost-effectiveness ratios(ICERs) were calculated and compared with various decision makers' willingness to pay. Cost-effectiveness acceptability curves were utilized to evaluate the economic attractiveness of TTM. Uncertainty about the incremental cost and effect was explored with a 95% confidence ***: Among 925 non-traumatic OHCA survivors, only 30(3%) received TTM. After adjusting for potential confounders, the TTM group did not demonstrate a significantly lower cost(delta cost-$5,141, 95% confidence interval [95% CI]: $-35,347 to $25,065, P=0.79) and higher survival to hospital discharge(delta effect 6%, 95% CI:-11% to 23%, P=0.41). Additionally, a 95% confidence ellipse indicated uncertainty reflected by evidence that the true value of the ICER could be in any of the quadrants of the cost-effectiveness ***: Although TTM did not demonstrate a clear survival benefit in this study, its potential cost-effectiveness warrants further investigation with larger sample sizes. These findings highlight the need for additional research to optimize TTM use in OHCA care and inform resource allocation decisions.

关键词： Out-of-hospital cardiac arrest Targeted temperature management Cost-effectiveness Survival Real-world data

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Women in visual neural regeneration research

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Neural Regeneration Research 2025年第2期20卷 489-490页

作者： Tonia S.Rex David j.Calkins Vanderbilt Eye Institute Vanderbilt University Medical CenterNashvilleTNUSA

The year 2024 marks the 60^(th)anniversary of Title IX and 25 years since the New York Times revealed bias against female faculty members at the Massachusetts Institute of *** take an opportunity here to examine the state of gender bias in a relatively new yet already prominent field,neural regeneration in the visual system,for which there is a well-defined context useful for this *** National Eye Institute(NEI)provided the first round of research funding for its Audacious Goals Initiative(AGI)on visual neural regeneration in 2013 and the last round in ***,we focus on this *** sources included PubMed,the National Science Foundation(NSF),the NEI,the Blue Ridge Institute for Medical Research and data from the major professional organization for eye and vision research,the Association for Research in Vision and Ophthalmology(ARVO).

关键词： neural visual Times

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Generation of brain vascular heterogeneity:recent advances from the perspective of angiogenesis

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Neural Regeneration Research 2025年第7期20卷 2013-2014页

作者： Nathanael j.Lee Ryota L.Matsuoka Department of Neurosciences Lerner Research InstituteCleveland ClinicClevelandOHUSA Department of Molecular Medicine Cleveland Clinic Lerner College of MedicineCase Western Reserve UniversityClevelandOHUSA

Heterogeneous proper t i es of vascular endothelial cells in the brain:The brain displays large energy dynamics and consumption,and this high level of metabolic demands is fulfilled by a continuous supply of glucose and oxygen through its vascular *** vasculature consists of highly divergent blood vessel branches,giving rise to a dense network of capillaries that supply blood to all cells across the *** elaborated vascular network is thought to develop via angiogenesis,a process in which new blood vessels grow from pre-existing *** capillaries exhibit organotypic features distinct from other tissues and are formed primarily by two major endothelial cell(EC)types:those that form the semi-permeable blood-brain barrier(BBB)and those that develop highly permeable pores known as fenestrae(Matsuoka et al.,2022).The structural and functional differences between BBB and fenestrated vascular ECs represent a fundamental feature of brain vasculature and form the foundation for both brain function and homeostasis.

关键词： angiogenesis homeostasis network

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