bims-blobar 2025-08-31 papers

bims-blobar

Biomed News

on Blood brain barrier repair

Issue of 2025–08–31
twenty-six papers selected by
Nicolas Rebergue

Endothelial mitochondria in the blood-brain barrier.
Bezafibrate improves mitochondrial function, blood-brain barrier integrity, and social deficits in models of 22q11.2 deletion syndrome.
Partial eNOS Deficiency Results in Greater Levels of Vascular Inflammation and BBB Disruption in Response to Chronic Mild Hypoxia.
Phased blood-brain barrier disruption in ischaemic stroke: implications for therapy?
PACAP mitigates traumatic brain injury progression via ELF3/ZO-1 axis-mediated blood-brain barrier repair.
Nitro-oleic acid activation of endothelial PPARγ signaling pathway alleviates neurovascular injury and improves functional outcomes in ischemic stroke.
Human iPSC-Derived Astrocyte-Endothelial Cell and Neuron-Endothelial Cell Co-culture Models of the Blood-Brain Barrier to Study the Impact of Ischemic Stroke in Vitro.
Dexmedetomidine attenuates postoperative delirium by activating Nrf2 to reduce oxidative stress and blood-brain barrier disruption.
Bridging regional neurovascular unit heterogeneity and cognitive function: a review.
Myelin basic protein and occludin may be the biomarkers to diagnose leukoaraiosis and cognitive dysfunction.
[Dynamics of permeability of the blood-brain barrier after FUS thalamotomy according to contrast-enhanced MRI].
A multi-pore model of the blood-brain barrier tight junction strands recapitulates the permeability features of wild-type and mutant claudin-5.
Breakdown of blood-brain barrier, astrocytic endfeet swelling, and abnormal behaviors by blockade of TROY signaling in TROY-Fc transgenic mice.
The heart-brain crosstalk in age related cardiovascular and neurodegenerative diseases.
High-throughput drug screening to investigate blood-brain barrier permeability in vitro with a focus on breast cancer chemotherapeutic agents.
Interaction of coexposure to inorganic arsenic and manganese: Tight junction injury of the blood-brain barrier and the relationship between oxidative stress and inflammatory cytokines in glial cells.
Synergistic Neuroprotection of Artesunate and Tetramethylpyrazine in Ischemic Stroke, Mechanisms of Blood-Brain Barrier Preservation.
Shear Conditioning Promotes Microvascular Endothelial Barrier Resilience in a Human BBB-on-a-Chip Model of Systemic Inflammation Leading to Astrogliosis.
Flecainide mediated sodium channel blockade enhances blood brain barrier integrity and promotes neuroprotection in neuroinflammation.
Blocking SKI-1 to rescue the blood-brain barrier and improve stroke recovery.
Review of the Role of TRAF7 in Brain Endothelial Integrity and Cerebrovascular Aging.
Total flavonoids of Dracocephalum moldavica L. alleviate cognitive impairment via TNF-α/NF-κB p65 signaling pathway in vascular dementia rats.
Intravenously injected hPSC-derived pericytes for Alzheimer's disease: neuroprotection and vascular repair via extracellular vesicles.
Editorial: Endo- and transcytotic pathways at the brain barriers.
Quercetin promotes angiogenesis and protects the blood-spinal cord barrier structure after spinal cord injury by targeting the PI3K/Akt signaling pathway.
G3BP1 maintains endothelial barrier integrity through dual mechanisms: direct stabilization of junction protein mRNAs and suppression of the inflammatory MYD88-ARNO-ARF6 pathway.

Fluids Barriers CNS. 2025 Aug 25. 22(1): 88

Endothelial mitochondria in the blood-brain barrier.

Yunwei Shao, Lingling Mai, Ruogu Qiao, Yi Liang, Yuying Jiao, Judith Homburg, Zhenfu Jiang, Laiyu Song.

  The blood-brain barrier (BBB) is a highly selective interface between the peripheral circulation and the central nervous system (CNS), crucial for maintaining brain homeostasis. Disruptions to the BBB, such as increased permeability or structural damage, can lead to neurological damage. Mitochondria, the primary energy producers within endothelial cells, play a key role in the function of the BBB by maintaining its integrity and low permeability. This review first outlines the structural components of the BBB, then examines the role of mitochondria in endothelial cells under physiological conditions. We further focus on alterations in mitochondrial function during pathological states, discussing their impact on BBB stability. Briefly, this review explores the involvement of mitochondria in BBB endothelial cells in both physiological processes and the pathological progression of neurological diseases, while proposing potential therapeutic directions for treating CNS disorders.

Keywords:  Blood-brain barrier; Endothelial cells; Mitochondria; Nervous system

DOI:  https://doi.org/10.1186/s12987-025-00699-w
Sci Transl Med. 2025 08 20. 17(812): eads2116

Bezafibrate improves mitochondrial function, blood-brain barrier integrity, and social deficits in models of 22q11.2 deletion syndrome.

Alexis M Crockett, Maria C Vélez Colόn, Hania Kebir, Frances M Smith, Daniel M Iascone, Brianna Ciesielski, Sergei Koshkin, Andrew D Patterson, Adam J Rossano, Amita Sehgal, Stewart A Anderson, Jorge Ivan Alvarez.

Maintenance of blood-brain barrier (BBB) integrity is critical to optimal brain function, and its impairment has been linked to multiple neurological disorders. A notable feature of the BBB is its elevated mitochondrial content compared with peripheral endothelial cells, although the functional implications of this phenomenon are unclear. Here, we studied BBB mitochondrial function in the context of 22q11.2 deletion syndrome (22qDS), a condition associated with a highly increased risk for neuropsychiatric disease. Because the 22q11.2 deletion includes six mitochondrial genes, and because we have previously identified BBB impairment in 22qDS, we addressed the hypothesis that mitochondrial deficits contribute to BBB dysfunction and affect behavior in this condition. We report mitochondrial impairment in human induced pluripotent stem cell (iPSC)-derived brain microvascular endothelial cells (iBMECs) from people with 22qDS and in BBB endothelial cells from a mouse model of 22qDS. We found that treatment with bezafibrate, an activator of mitochondrial biogenesis, attenuates mitochondrial deficits and enhances BBB function in both the iBMECs and a mouse model of 22qDS. This treatment also corrects social memory in the mouse model, a deficit previously associated with BBB dysfunction. Given that BBB integrity correlated with social memory performance, our findings suggest that mitochondrial dysfunction in the BBB influences barrier integrity and behavior.

DOI: https://doi.org/10.1126/scitranslmed.ads2116
Int J Mol Sci. 2025 Aug 15. pii: 7902. [Epub ahead of print]26(16):

Partial eNOS Deficiency Results in Greater Levels of Vascular Inflammation and BBB Disruption in Response to Chronic Mild Hypoxia.

Arjun Sapkota, Sebok K Halder, Saifudeen Ismael, Gregory J Bix, Richard Milner.

  Blood-brain barrier (BBB) deterioration with increasing age is an important factor contributing to vascular dementia. Previous studies show that endothelial nitric oxide synthase (eNOS) facilitates vascular endothelial growth factor-mediated angiogenesis and increased vascular permeability. In contrast, recent work has shown that aged hemi-deficient hemizygous eNOS+/- mice manifest BBB disruption in association with increased incidence of thromboembolic events in the brain. To unravel whether eNOS contributes to or protects against hypoxia-induced cerebrovascular damage, we compared chronic mild hypoxia (CMH)-induced cerebrovascular angiogenic remodeling and BBB breakdown in aged (20 months old) eNOS+/- and wild-type (WT) mice. This revealed that CMH strongly enhanced eNOS expression in cerebral blood vessels with much lower levels in eNOS+/- mice. eNOS hemi-deficiency resulted in greater CMH-induced BBB disruption, but unexpectedly, had no effect on endothelial proliferation. eNOS+/- mice also displayed enhanced endothelial expression of the endothelial activation markers MECA-32, VCAM-1, and β3 integrin in cerebral blood vessels, indicating greater vascular inflammation, and this correlated with increased levels of microglial activation and demyelination. Taken together, our results support the concept that eNOS plays an important protective function in the aged brain by suppressing endothelial activation and maintaining cerebrovascular health.

Keywords:  aging; blood vessels; blood–brain barrier (BBB) integrity; brain; chronic mild hypoxia; endothelial nitric oxide synthase (eNOS); microglia

DOI:  https://doi.org/10.3390/ijms26167902
Fluids Barriers CNS. 2025 Aug 27. 22(1): 90

Phased blood-brain barrier disruption in ischaemic stroke: implications for therapy?

Alissia Blase, Costanza Giovene di Girasole, Laura Benjamin, Patric Turowski.

  Cerebrovascular disease, which primarily affects the brain's blood vessels, remains a major global cause of death and disability. Among its clinical manifestations, ischaemic stroke is by far the most common. Prolonged oedema due to blood vessel leakage is detrimental to the delicate neuronal environment throughout the ischaemic and reperfusion phase and contributes to the mortality, morbidity, and disabilities associated with this devastating condition. Under physiological conditions, an intact blood-brain barrier (BBB) protects and regulates solute and cell transit in and out of the central nervous system. Indeed, dysfunction of this formidable cerebrovascular regulator has been functionally linked to adverse outcomes in stroke. While our knowledge of the underlying mechanism is incomplete, increasing evidence, particularly from studies using models of rodents exposed to middle cerebral artery occlusion (MCAO), supports a biphasic breakdown of the BBB in ischemic stroke. However, debate persists regarding the precise mechanisms of BBB dysfunction. Understanding this pathobiology is essential for developing targeted interventions to improve clinical outcomes in stroke patients. In this review, we provide a summary of the structure and function of the BBB as well as the cellular and molecular determinants of leakage pathways present in pathological conditions, and evaluate medical strategies aimed at reducing BBB disruption in stroke. We also discuss the potential for selectively targeting specific phases of BBB leakage.

Keywords:  Blood-brain barrier; Caveolae; Endothelial cell; Ischaemic stroke; Reperfusion; Tight junctions

DOI:  https://doi.org/10.1186/s12987-025-00701-5
Psychoneuroendocrinology. 2025 Aug 06. pii: S0306-4530(25)00296-3. [Epub ahead of print]180 107573

PACAP mitigates traumatic brain injury progression via ELF3/ZO-1 axis-mediated blood-brain barrier repair.

Liping Bai, Zhiming Guan, Jianwen Zhang, Zhigan Lv, Yinglei Duan, Shouyuan Tian.

  Traumatic brain injury (TBI) often leads to significant damage to the blood-brain barrier (BBB), contributing to the progression of neurological dysfunction and exacerbating inflammatory responses. BBB disruption is a critical factor in TBI pathology, as it facilitates neuroinflammation and edema, thereby worsening brain injury. For the first time, this study investigates the neuroprotective role of Human Pituitary Adenylate Cyclase Activating Peptide (PACAP) in mitigating the progression of TBI by addressing BBB dysfunction. Using a murine TBI model, the research demonstrates a significant reduction in PACAP levels in both serum and cortical tissues post-injury. Administration of PACAP was found to ameliorate neurological deficits, as evidenced by improved modified Neurological Severity Scores (mNSS) and enhanced motor coordination. Furthermore, PACAP treatment attenuated neutrophil infiltration and pro-inflammatory cytokine secretion, including TNF-α and IL-6, while reducing endothelial inflammation markers VCAM-1 and ICAM-1. PACAP also preserved BBB integrity by decreasing brain water content and Evans blue dye extravasation, alongside upregulating tight junction protein ZO-1. In vitro studies on human brain microvascular endothelial cells (HBMVECs) corroborated these findings, showing PACAP's efficacy in reducing endothelial permeability and enhancing transendothelial electrical resistance (TEER). The protective effects were mediated through the upregulation of ELF3, as its silencing negated PACAP's benefits. Collectively, these findings underscore PACAP's potential as a therapeutic agent in TBI management by fortifying BBB integrity and curtailing inflammatory responses.

Keywords:  BBB integrity; ELF3; Pituitary Adenylate Cyclase Activating Peptide (PACAP); Traumatic brain injury; ZO-1

DOI:  https://doi.org/10.1016/j.psyneuen.2025.107573
Brain Pathol. 2025 Aug 23. e70037

Nitro-oleic acid activation of endothelial PPARγ signaling pathway alleviates neurovascular injury and improves functional outcomes in ischemic stroke.

Tianqing Xiong, Na Qiu, Andrew Ni, Xiaotao Xu, Ping Sun, Shun Li, Ke-Jie Yin.

  Nitro-oleic acid (OA-NO2) is an endogenous peroxisome proliferator-activated receptor-γ (PPARγ) ligand and can activate this receptor under both physiological and pathological conditions. In this study, we explore the role and molecular mechanisms of OA-NO2 in maintaining blood-brain barrier (BBB) integrity and enhancing neurovascular function during ischemic stroke, with a particular emphasis on the activation of endothelial PPARγ signaling pathways. Endothelial cell-selective PPARγ conditional knockout (EC-PPARγ cKO) and wild-type (WT) mice underwent 1 h middle cerebral artery occlusion (MCAO) with 1-7 days of reperfusion. Mice were treated with oleic acid (OA) or OA-NO2 (5 mg/kg) via tail vein 2 h after MCAO. Neurobehavioral deficits were assessed on days 3, 5, and 7 after MCAO. Neuroinflammation and BBB function were assessed on days 1 or 2 after MCAO by immunohistochemistry, RT-qPCR, or Western blot analysis. Compared to OA controls, intravenous administration of OA-NO2 led to reduced BBB leakage in ischemic brains, as indicated by a significant decrease in the extravasation of BBB tracers. This reduction in BBB leakage was also almost abolished in the EC-PPARγ cKO mice. Furthermore, OA-NO2 treatment reduced brain infarction in stroke mice, but this protective effect was completely reversed in the EC-PPARγ cKO mice. Interestingly, OA-NO2 treatment promoted a shift towards an anti-inflammatory microglial phenotype (M2) in the peri-infarct regions of WT mice, but not in EC-PPARγ cKO mice. Mechanistically, OA-NO2 increased levels of major endothelial tight junction proteins in WT mice but not in EC-PPARγ cKO mice following ischemic stroke. These findings suggest that OA-NO2 activation of endothelial PPARγ signaling cascade attenuates neurovascular injury after ischemic stroke.

Keywords:  OA‐NO2; blood–brain barrier; cerebral inflammation; endothelial PPARγ; ischemic stroke

DOI:  https://doi.org/10.1111/bpa.70037
Methods Mol Biol. 2025 ;2956 53-64

Human iPSC-Derived Astrocyte-Endothelial Cell and Neuron-Endothelial Cell Co-culture Models of the Blood-Brain Barrier to Study the Impact of Ischemic Stroke in Vitro.

Nausheen Syeara, Yash Mehta, Vardan T Karamyan, Abraham Al-Ahmad.

  The role of the blood-brain barrier (BBB) in pathogenic mechanisms of neurodegenerative disorders, including stroke, is well recognized. In vitro BBB models offer opportunities to recapitulate aspects of the disease using different cell types, extracellular matrices, and soluble factors to study the biology of the disease and the role of the BBB. This chapter describes the rigorous protocols and our schemes to successfully establish human-induced pluripotent stem cell-derived astrocyte-endothelial cell and neuron-endothelial cell co-culture models to study the impact of ischemia-reoxygenation for in vitro stroke studies.

Keywords:  Astrocytes; Blood; Brain barrier; Endothelial cells; Induced pluripotent stem cells; Neurons

DOI:  https://doi.org/10.1007/978-1-0716-4706-6_5
Brain Res Bull. 2025 Aug 24. pii: S0361-9230(25)00335-1. [Epub ahead of print]230 111523

Dexmedetomidine attenuates postoperative delirium by activating Nrf2 to reduce oxidative stress and blood-brain barrier disruption.

Tengchen Feng, Jie Yao, Yanlin Chen, Jiayi Wang, Ying Zhu, Zhiming Lan, Xuhua Huo, Yeming Wang, Jingui Gao.

   BACKGROUND: Postoperative delirium (POD), characterized by cognitive dysfunction, is a prevalent and severe complication following surgery. The blood-brain barrier (BBB) is crucial in maintaining central nervous system (CNS) homeostasis, and its disruption is associated with POD. Dexmedetomidine (DEX), an α2-adrenergic receptor agonist, potentially reduces POD incidence by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, which regulates antioxidant responses and alleviates BBB damage.
METHODS: This study used transcriptomic analysis to identify differentially expressed genes in patients with POD and explored the therapeutic targets of DEX. In vitro experiments using HCMEC/D3 cells and an in vivo mouse model of POD were conducted to assess the effects of DEX on BBB integrity and neuroinflammation. Western blotting, flow cytometry, and ELISA were used to evaluate protein expression, apoptosis, and cytokine levels, respectively. Behavioral tests (open-field and Y-maze tests) were performed to assess cognitive function in mice.
RESULTS: Bioinformatics analysis revealed Nrf2 as a key target of DEX. DEX treatment significantly increased Nrf2 expression and alleviated oxidative stress and neuroinflammation in HCMEC/D3 cells. In the POD mouse model, DEX improved cognitive function, evidenced by enhanced performance in behavioral tests. DEX also upregulated Nrf2 expression in the mouse brain tissue and reduced serum inflammatory. Furthermore, DEX preserved BBB integrity by upregulating tight junction proteins, which was reversed by the Nrf2 inhibitor, ML385.
CONCLUSIONS: DEX ameliorates POD by activating Nrf2, thereby reducing oxidative stress and inflammation, and maintaining BBB integrity. These findings suggest DEX is a potential therapeutic agent for POD, highlighting the Nrf2 pathway as a novel target for treatment strategies.

Keywords:  Blood-brain barrier; Dexmedetomidine; Nrf2; Oxidative Stress; Postoperative delirium

DOI:  https://doi.org/10.1016/j.brainresbull.2025.111523
Fluids Barriers CNS. 2025 Aug 20. 22(1): 85

Bridging regional neurovascular unit heterogeneity and cognitive function: a review.

Amalia Tsintzou, Roseline Poirier, Rania Harati, Almira Kustubayeva, Clemence Disdier, Rifat Hamoudi, Aloïse Mabondzo.

  The blood-brain barrier (BBB) is a critical central nervous system interface that tightly regulates the exchange of substances between the blood circulation and the brain parenchyma. The BBB, glia, mural cells and neurons form the neurovascular unit (NVU), which modulates cerebral homeostasis. Traditionally considered a uniform and selective barrier, emerging research has unveiled significant heterogeneity in BBB properties across various brain structures. This review synthesizes current knowledge of the heterogeneity of the NVU elements of different brain structures. The structural and functional differences of the endothelial cells, glial cells, and neurons of different brain structures are pinpointed. Finally, BBB heterogeneity and its link to cognition in physiology and pathology are discussed. Understanding such relationships could help effectively target and cure neurological diseases.

Keywords:  Astrocytes; Cognition; Microglia; Neurons; Neurovascular unit heterogeneity; Pericytes

DOI:  https://doi.org/10.1186/s12987-025-00697-y
Sci Rep. 2025 Aug 27. 15(1): 31547

Myelin basic protein and occludin may be the biomarkers to diagnose leukoaraiosis and cognitive dysfunction.

Yingping Chen, Hua Li, Junliang Lin, Huanjian Huang, Yingying Cao, Hong Zhou.

  Leukoaraiosis (LA) can lead to a range of clinical symptoms, with cognitive dysfunction being the most prominent. However, the biomarkers that could assist in the early diagnosis of LA and predict disease progression are lacking. Myelin basic protein (MBP), a key component of the myelin sheath, and Occludin (OCLN), a critical tight junction protein maintaining blood-brain barrier (BBB) integrity, are released into circulation upon white matter and BBB damage, making them promising candidate biomarkers. Clinical data and blood samples were collected from 99 healthy individuals and 99 patients with LA. The levels of myelin basic protein (MBP) and occludin (OCLN) in peripheral blood were measured in both groups, and the correlation between these proteins and clinical features was analyzed. The levels of MBP and OCLN in the peripheral blood of the LA group were significantly elevated compared to those of the control group. The MBP and OCLN possessed outstanding diagnostic accuracy. Importantly, MBP level showed a positive correlation with the severity of LA, and a significant correlation was observed between MBP and cognitive function. MBP and OCLN may serve as biomarkers for LA, with MBP showing potential value in diagnosing LA-associated cognitive dysfunction.

Keywords:  Cognitive function; Leukoaraiosis; Myelin basic protein; Occludin; White matter

DOI:  https://doi.org/10.1038/s41598-025-17617-7
Zh Vopr Neirokhir Im N N Burdenko. 2025 ;89(4): 51-60

[Dynamics of permeability of the blood-brain barrier after FUS thalamotomy according to contrast-enhanced MRI].

M B Dolgushin, K A Prischepina, M Yu Martynov, I S Gumin, E A Katunina, I V Senko, R T Tairova, A V Dvoryanchikov.

   OBJECTIVE: To study the dynamics of permeability of the blood-brain barrier (BBB) after focused ultrasound (FUS) thalamotomy in patients with tremor of different origin through visualization phenomena, assessment of the tendency of contrast accumulation level change at MRI in coagulation necrosis focus over different time intervals.
MATERIAL AND METHODS: The study included 10 patients (8 - with Parkinson's disease, 2 - with essential tremor). MRI of the brain was performed before the procedure, MRI of the brain with contrast enhancement («Gadobutrol») was carried out after 2 and 24 hours, 1, 3, 6 and 12 months from FUS thalamotomy. The volume and nature of contrast accumulation in the impact area were evaluated.
RESULTS: Observations show that the performance of FUS thalamotomy leads to a temporary impairment of the BBB permeability. This is confirmed by the data of dynamic accumulation of contrast substance in MRI in the area of coagulation necrosis.
CONCLUSION: The analysis of the dynamic changes of volume and patterns of accumulation of contrast substance in MRI in the area of coagulation necrosis after FUS thalamotomy was performed during the study. The obtained data demonstrate almost complete absence of contrast enhancement 24 hours after intervention, that may indicate a partial restoration of the structural-functional integrity of BBB after its transient disruption in the early postoperative period.

Keywords:  FUS; Parkinson’s disease; blood-brain barrier; essential tremor; focused ultrasound; magnetic resonance imaging; thalamotomy; tremor

DOI:  https://doi.org/10.17116/neiro20258904151
Protein Sci. 2025 Sep;34(9): e70271

A multi-pore model of the blood-brain barrier tight junction strands recapitulates the permeability features of wild-type and mutant claudin-5.

Alessandro Berselli, Giulio Alberini, Linda Cerioni, Fabio Benfenati, Luca Maragliano.

  In the blood-brain barrier (BBB), endothelial cells are joined by tight junctions (TJs), multi-protein assemblies that seal the paracellular space and restrict molecular transport. Among the BBB TJ proteins, Claudin-5 (Cldn15) is the most abundant one. Structural models for claudin complexes, first introduced for channel-forming, selectively permeable claudins, comprise protomers arranged to form paracellular pores that regulate transport by electrostatic and/or steric effects arising from pore-lining residues. With limited exceptions, computational studies explored oligomers of only a few subunits, while TJs are formed by extended polymeric strands. Here, we employ multi-microsecond all-atom molecular dynamics and free-energy (FE) calculations to study two distinct models of TJ-forming Cldn15 complexes, called multi-Pore I and multi-Pore II, each comprising 16 protomers arranged around three adjacent pores. FE calculations of water and ions permeation reveal that, in both models, ion transport is hindered by FE barriers higher than in single pores. Moreover, only the multi-Pore I model captures the Cldn15 G60R variant's effect, making it anion-permeable. The results provide insights into Cldn15 structure and function and validate a structural model of BBB TJs useful for studying barrier impairment in brain diseases and for developing therapeutic approaches.

Keywords:  blood brain barrier; claudin‐5; claudin‐based paracellular models; free‐energy calculations; molecular dynamics; paracellular proteins; protein–protein complexes; structural modeling; tight junctions

DOI:  https://doi.org/10.1002/pro.70271
Brain Behav Immun. 2025 Aug 18. pii: S0889-1591(25)00318-6. [Epub ahead of print]130 106083

Breakdown of blood-brain barrier, astrocytic endfeet swelling, and abnormal behaviors by blockade of TROY signaling in TROY-Fc transgenic mice.

Tadasuke Komori, Tomoko Hisaoka, Emi Kuriyama, Mizuki Kajimoto, Naoyuki Nakao, Toshio Kitamura, Yoshihiro Morikawa.

  An orphan receptor of tumor necrosis factor receptor superfamily (TNFRSF), TROY (TNFRSF19), forms the receptor complex with Nogo-66 receptor/LINGO-1 and DR6 in neurons and cerebral endothelial cells, respectively. Although TROY is expressed in astrocytes of the brain under normal conditions, its function is still unknown. Here, we demonstrated that TROY was strongly expressed in astrocytes rather than in neurons and endothelial cells in the adult mouse brain under normal conditions. Recombinant soluble form of the extracellular domain (ECD) of mouse TROY (sTROY) bound to megalencephalic leukoencephalopathy with subcortical cysts 1 (Mlc1)-positive astrocytes, endfeet of which were surrounding large vessels, in the adult mouse brain. These findings suggest the presence of an unidentified ligand that directly binds to TROY in such astrocytes. To antagonize TROY ligand(s) in vivo, we generated transgenic (Tg) mice overexpressing a chimeric protein consisting of the ECD of mouse TROY and the Fc domain of human immunoglobulin G1 (TROY-Fc). Adult TROY-Fc Tg mice showed the enhanced permeability of the blood-brain barrier (BBB), which is consistent with TROY-deficient mice, and swollen astrocytic endfeet. The expressions of tight junction proteins (claudin-5, claudin-12, occludin, and zonula occludens-1) and src-suppressed C-kinase substrate (SSeCKS) were reduced in adult Tg mice, whereas aquaporin-4 (AQP4) expression was increased. In postnatal Tg mice, the expressions of vascular endothelial growth factor and AQP4 were increased in TROY-Fc Tg mice, whereas angiopoietin-1 and SSeCKS were reduced. There was no significant change in the expression of endogenous TROY in postnatal and adult Tg mice. Behavioral tests revealed that TROY-Fc Tg mice exhibited a reduction in exploratory motivation and an enhancement of responses to stress. Thus, the signaling mediated by unidentified TROY ligand(s)-TROY interaction may be essential for proper neuronal function through the maintenance of intact BBB.

Keywords:  Astrocytes; Behavior; Blood-brain barrier; Endfoot; Ig-Fc fusion protein; TROY; Transgenic mice; Tumor necrosis factor receptor superfamily

DOI:  https://doi.org/10.1016/j.bbi.2025.106083
Fluids Barriers CNS. 2025 Aug 26. 22(1): 89

The heart-brain crosstalk in age related cardiovascular and neurodegenerative diseases.

Muhammad Ahmad Fahim, Yao Yao, Srinivas M Tipparaju, Wanling Xuan.

  Aging is a major risk factor for both cardiovascular and neurodegenerative diseases. The bidirectional communication between the heart and brain, commonly referred to as heart-brain crosstalk, is increasingly disrupted with age. In this review, we summarize current evidence linking cardiovascular and neurodegenerative disorders, particularly in the context of aging. We also discuss the underlying mechanisms responsible for the heart-brain crosstalk, including blood-brain barrier breakdown, vascular dysfunction, nervous system alterations, inflammation, and endocrine dysregulation, which may explain the frequent co-occurrence of dysfunction in both organs during aging. Understanding these interconnections provides critical insights into the pathophysiology of age-related diseases and highlights potential therapeutic targets to preserve both heart and brain health in the aging population.

Keywords:  Aging; Blood-brain barrier; Neuroinflammation; Vascular dysfunction

DOI:  https://doi.org/10.1186/s12987-025-00700-6
Front Drug Deliv. 2024 ;4 1331126

High-throughput drug screening to investigate blood-brain barrier permeability in vitro with a focus on breast cancer chemotherapeutic agents.

Carolin J Curtaz, Sophia Wucherpfennig, Emad Al-Masnaea, Saskia-Laureen Herbert, Achim Wöckel, Patrick Meybohm, Malgorzata Burek.

  Therapy of cerebral diseases such as brain metastatic breast cancer is still challenging. Due to the blood-brain barrier (BBB), a tight barrier that protects the brain and prevents the passage of many drugs, therapeutically sufficient drug concentrations in the brain are often not achieved. Therefore, methods and drugs to manipulate the BBB permeability are required. Here we used high-throughput screening (HTS) to identify chemicals that may increase BBB permeability. Human BBB in vitro model derived from hematopoietic CD34+ stem cells (differentiated to brain-like endothelial cells, BLECs) was used. BLECs were seeded on 96-well plates coated with biotinylated gelatin, treated with respective chemicals for 24 h followed by addition of FITC-avidin for permeability estimation. Selected substances were further tested in vitro on BLECs. Cell viability, gene and protein expression were measured using CellTiter-Glo®, qPCR and Western blot, respectively. From 1,278 compounds, we identified 175 substances that cause at least a 50 percent increase in BBB permeability. Two substances from the substance classes used in breast cancer therapy, GW2974 (tyrosine kinase inhibitor) and 4-amino-1,8-naphthalimide (ANI) (PARP inhibitor), were analyzed in more detail. ANI was nontoxic to BLECs, while GW2974 decreased or increased viability depending on the concentration used. Both compounds significantly increased BBB permeability and altered protein and mRNA expression in BLECs. Influencing the BBB permeability in patients with brain metastases could increase the response rate to systemic therapy. Using HTS, we were able to accurately and quickly identify compounds that increase BBB permeability and show that using this type of screening method can be applied to endothelial paracellular permeability testing.

Keywords:  4-amino-1,8-naphthalimide; GW2974; blood-brain barrier; high-throughput drug screening; in vitro models; metastatic breast cancer

DOI:  https://doi.org/10.3389/fddev.2024.1331126
PLoS One. 2025 ;20(8): e0330287

Interaction of coexposure to inorganic arsenic and manganese: Tight junction injury of the blood-brain barrier and the relationship between oxidative stress and inflammatory cytokines in glial cells.

Toshiaki Hitomi, Hiroko Okuda, Ayako Takata, Hiroshi Yamauchi.

Coexposure to inorganic arsenic (iAs) and manganese (Mn) may exacerbate cognitive dysfunction caused by iAs alone. In this study, we investigated the cytotoxicity of coexposure to iAs and Mn in glial cells and the expression and correlation between oxidative stress and inflammatory cytokines. Additionally, we assessed tight junction (TJ) injury using a rat in vitro blood-brain barrier (BBB) model. In glial cells, coexposure to iAs and Mn increased cytotoxicity compared to single exposure, suggesting a likely additive effect. iAs exposure significantly increased the expression of antioxidant stress markers, including nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), relative to Mn exposure. Notably, HO-1 expression was further elevated under coexposure conditions, indicating a potential synergistic effect. Regarding inflammatory cytokines, expression of C-C motif chemokine ligand 2 (MCP-1) and interleukin-6 (IL-6) was slightly higher in the iAs exposure compared to Mn exposure. A synergistic effect was observed in the Mn concentration-dependent increase in IL-6 under coexposure. A significant positive correlation was found between Nrf2 or HO-1 and inflammatory cytokines (MCP-1 and IL-6) (p < 0.001), suggesting an interaction between oxidative stress and inflammatory cytokines. The BBB TJ injury was evaluated by measuring the transendothelial electrical resistance values and the Claudin-5 and zonula occludens-1. The results showed expression in iAs exposure but not in Mn exposure. Furthermore, Mn did not affect iAs-induced TJ injury. In conclusion, our findings demonstrate that coexposure to iAs and Mn exerts synergistic effects on oxidative stress and inflammatory cytokines in glial cells. These joint effects may increase the risk of neurotoxicity compared to single-iAs or Mn exposure.

DOI: https://doi.org/10.1371/journal.pone.0330287
Int J Mol Sci. 2025 Aug 18. pii: 7979. [Epub ahead of print]26(16):

Synergistic Neuroprotection of Artesunate and Tetramethylpyrazine in Ischemic Stroke, Mechanisms of Blood-Brain Barrier Preservation.

Yan Liang, Shuoqiu Deng, Yu Li, Shuiqing Qu, Chengcheng Liu, Luqi Wang, Lina Chen, Tuo Liu, Yujie Li.

  Artesunate (AS) and tetramethylpyrazine (TMP) have been proven to have therapeutic potential in ischemic stroke. Nevertheless, their synergistic treatment mechanisms and effectiveness remain unclear. A rat MCAO model was induced, and AS, combined with TMP, was administered intranasally to rats once a day for 3 days. The neurological severity scores, TTC staining, and H&E staining were implemented to analyze tissue injuries. Evans blue staining and immunohistochemistry of ZO-1, occludin, MMP-9, and TIMP-1 were implemented to evaluate the integrity of the blood-brain barrier (BBB). ELISA was used to detect the expression levels of inflammatory factors TNF-α and IL-10. TUNEL staining and the protein expression of Bax and Bcl-2 were used to evaluate the apoptosis of brain tissue cells. The core targets were predicted by network pharmacology and verified by the OGD/R cell model and siRNA in vitro. Results showed that nasal administration of AS and TMP significantly ameliorated ischemic-stroke-induced neurological dysfunction, BBB disruption, and cortical neuronal apoptosis. The protective mechanisms mainly included adjusting the expression and ratio of tight junction proteins TIMP-1 and MMP-9 in brain tissue, regulating the HIF-1α-VEGF pathway, and anti-inflammatory effects. This study provides experimental support for the further development and application of AS and TMP nasal combinations and provides the foundation for expanding the practical-application value of artemisinin and its derivatives.

Keywords:  BBB; MMP9; TIMP1; artesunate; ischemic stroke; tetramethylpyrazine

DOI:  https://doi.org/10.3390/ijms26167979
Adv Sci (Weinh). 2025 Aug 27. e08271

Shear Conditioning Promotes Microvascular Endothelial Barrier Resilience in a Human BBB-on-a-Chip Model of Systemic Inflammation Leading to Astrogliosis.

Kaihua Chen, Isabelle M Linares, Michelle A Trempel, Alexis M Feidler, Dinindu De Silva, Sami Farajollahi, Jordan Jones, Julia Kuebel, Pelin Kasap, Britta Engelhardt, Jonathan Flax, Vinay V Abhyankar, Richard E Waugh, Harris A Gelbard, Niccolo Terrando, James L McGrath.

  The blood-brain barrier (BBB) maintains cerebral homeostasis and protects the central nervous system (CNS) during systemic inflammation. Advanced in vitro models integrating circulation, a functional BBB, and reactive glial cells are essential for studying the link between peripheral inflammation and neuroinflammation. Fluid shear stress, a key hemodynamic parameter, strengthens microvascular barriers. This study examines endothelial shear conditioning on barrier function in a fluidic µSiM-BBB (Microphysiological System featuring a Silicon Membrane -BBB). hiPSC-derived brain microvascular endothelial cell monocultures are conditioned with 0.5 Pa shear stress for 48 h. Shear conditioning lowers baseline permeability, increases glycocalyx production, and reduces responses to inflammatory challenges, including barrier breakdown, ICAM-1 upregulation, and neutrophil transmigration. Shear conditioning produces a resilient barrier function against a low-dose inflammatory challenge (10 pg mL-1 TNF-α/IL1-β/INF-γ) but a high-dose challenge (50 pg mL-1) disrupts the barrier. Adding astrocytes as neuroinflammatory "sensors" reveals that a high-dose inflammatory challenge activates astrocytes but only in combination with fibrinogen-a plasma protein known to trigger astrogliosis in multiple neurological conditions. This study highlights the utility of fluidic-enabled µSiM-BBB for investigating acute peripheral inflammation and brain injury relationships, serving as a foundation for more advanced models, including more cells of the neurovascular unit and brain parenchyma.

Keywords:  astrogliosis; barrier resilience; fluid shear stress; human BBB‐on‐a‐chip

DOI:  https://doi.org/10.1002/advs.202508271
Sci Rep. 2025 Aug 23. 15(1): 31032

Flecainide mediated sodium channel blockade enhances blood brain barrier integrity and promotes neuroprotection in neuroinflammation.

Mustafa Sindi, Diana Klees, Vera Dobelmann, Paul Disse, Hanne Weigel, Stefanie Lichtenberg, Rebekka Ricci, Leonie Thewes, Gülsüm Deniz-Köseoglu, Christina Hecker, Thomas Müntefering, Andrea Issberner, Joel Gruchot, Hans-Peter Hartung, Tobias Ruck, Carsten Berndt, Thomas Kurz, Holger Stark, Patrick Küry, Britta Engelhardt, Ruth Lyck, Sven G Meuth, Michael Dietrich, Philipp Albrecht.

  Multiple Sclerosis (MS), an autoimmune disorder, is characterized by severe neuroinflammation, leading to demyelination and neuronal damage in the CNS, resulting in significant clinical impairment. MS progression involves complex pathological processes like immune cell invasion and cytokine-mediated recruitment to the CNS. Experimental autoimmune encephalomyelitis (EAE), widely used as a model for MS, despite its translational limitations, has been crucial for identifying effective treatments. Recent studies have shown that sodium channel (NaV) blockers and monoamine oxidase- (MAO) B inhibitors can alleviate symptoms of EAE and optic neuritis (ON), but their mode of action remains partially unclear. To evaluate the effects and understand the action mechanism of NaV blockers and MAO-B inhibitors (rasagiline, safinamide, flecainide and phenytoin) in neurological conditions, various techniques were used, including optical coherence tomography (OCT), optomotor response measurement (OMR), flow cytometry, histological evaluations, Evans blue assay, blood-brain barrier (BBB) permeability assay, western blot, proliferations assay, and gene expression analyses. The study found that the primary therapeutic effect comes from inhibiting the NaV 1.5 sodium channel, not MAO-B inhibition. Flecainide, a NaV 1.5 channel blocker, significantly reduced EAE disability scores, mitigated neurodegeneration, preserved visual function, and restricted immune cell migration into the CNS. Importantly, blocking the NaV 1.5 channel had an effect on the BBB, limiting lymphocyte entry into the CNS. This research highlights sodium channel blockers' potential in treating EAE. The findings demonstrate induced neuroprotection and reduced disease progression, suggesting a novel therapeutic approach. Crucially, it reveals for the first time that NaV 1.5 channel blockade leads to neuroprotection primarily by affecting the BBB, a key factor in controlling immune cell migration, thus addressing a critical aspect of neuroinflammation.

Keywords:  Blood-brain-barrier; EAE; Flecainide; MAO-B inhibition; Multiple sclerosis; Neuroprotection; Rasagiline; Safinamide; Sodium-channel blocking

DOI:  https://doi.org/10.1038/s41598-025-15430-w
Nat Cardiovasc Res. 2025 Aug 26.

Blocking SKI-1 to rescue the blood-brain barrier and improve stroke recovery.

Ken Arai, Masafumi Ihara.

DOI: https://doi.org/10.1038/s44161-025-00683-5
Life (Basel). 2025 Aug 12. pii: 1280. [Epub ahead of print]15(8):

Review of the Role of TRAF7 in Brain Endothelial Integrity and Cerebrovascular Aging.

Jennifer Ihuoma, Sherwin Tavakol, Sharon Negri, Cade Ballard, Khanh Phan, Albert Orock, Zeke Reyff, Madison Milan, Eva Troyano-Rodriguez, Rakesh Rudraboina, Anna Csiszar, Anthony C Johnson, Ian F Dunn, Stefano Tarantini.

  Tumor necrosis factor (TNF) receptor-associated factor 7 (TRAF7) is a signal transducer in the TNF receptor superfamily. TRAF7 is unique among its superfamily in that it does not contain a TRAF-C domain but does contain WD-40 domains. TRAF7 interacts with mitogen-activated protein kinases (MAPK), which are known regulators of inflammation and shear stress response. Notably, these molecular interactions have profound implications for the function of brain endothelial cells (ECs), which are pivotal for sustaining the integrity of the blood-brain barrier (BBB), orchestrating neurovascular coupling (NVC), and modulating the vascular architecture. By directly influencing MAPK signaling pathways, particularly the shear stress-responsive MAPK kinase kinase 3 (MEKK3)-MAPK kinase 5 (MEK5)-extracellular-regulated protein kinase 5 (ERK5) cascade, TRAF7 contributes to vascular homeostasis, as exemplified by its role in phosphorylating ERK5. Such molecular events underpin the capacity of brain ECs to regulate substance exchange, adjust blood flow in response to neural activity, and maintain efficient cerebral perfusion, all of which are essential for preserving brain health and cognitive performance. By synthesizing the current evidence regarding TRAF7's molecular functions and its impact on brain endothelial integrity, cerebrovascular aging, and exploring implications for therapeutic strategies targeting vascular dysfunction in the aging brain, this review fills a crucial gap in the literature. Given the limited number of original studies directly addressing these contexts, the review will integrate broader insights from related literature to provide a foundational overview for future research in this developing field. The culmination of this literature will provide a rationale for the development of novel TRAF7-targeted therapies to restore vascular integrity in the context of aging, which could maintain cognitive health. Although TRAF7 has been implicated in regulating endothelial permeability during inflammation, its precise functions in brain ECs and the subsequent effects on cerebrovascular structure and cognitive function remain to be fully elucidated.

Keywords:  ERK5; MAPK; MEK5; TRAF7 protein; aging; cerebrovascular health; cognitive dementia; endothelial cell; tumor necrosis factor; vascular fragility

DOI:  https://doi.org/10.3390/life15081280
Front Pharmacol. 2025 ;16 1640272

Total flavonoids of Dracocephalum moldavica L. alleviate cognitive impairment via TNF-α/NF-κB p65 signaling pathway in vascular dementia rats.

Shangjia Ma, Jianxin Jia, Lie Wu, Kai Tian, Lu Wang, Hua Li, Jiayu Lv, Dewang Gao, Zhanjun Yang, Xia Guo.

   Objective: This study aims to elucidate the neuroprotective effects and underlying mechanisms of total flavonoids of Dracocephalum moldavica L. (TFDM) in VaD by using network pharmacology and in vivo validation.
Methods: The network pharmacology was used to explore the mechanism of TFDM to improve VaD. A rat model of VaD was established using permanent bilateral common carotid artery occlusion (2VO). The Morris water maze test assessed spatial learning and memory capacities. Nissl staining was used to examine the neuronal damage. Western blot and Immunofluorescence analysis was employed to evaluate protein levels of factors associated with neuroinflammation, blood-brain barrier integrity, and angiogenesis.
Results: The network pharmacology suggests TFDM may combat VaD through TNF-α/NF-κB p65 signaling pathways. TFDM treatment may attenuate memory deficits associated with 2VO and reduce neuronal damage. TFDM improved blood-brain barrier integrity and promoted angiogenesis by downregulating MMP-9 and upregulating ZO-1 and VEGFA. Moreover, TFDM exhibited anti-inflammatory properties by inhibiting TNF-α and NF-κB p65 production, thereby mitigating the neuroinflammatory response in VaD rats.
Conclusion: TFDM demonstrated significant improvement in cognitive function in VaD rats. This improvement was attributed to the multifaceted effects, including the improvement of blood-brain barrier integrity, promotion of angiogenesis, and reduction of neuroinflammation. These findings suggest that TFDM may represent a promising therapeutic approach for VaD management.

Keywords:  TNF-α/NF-κB p65 signaling pathway; blood-brain barrier; network pharmacology; neuroinflammation; total flavonoids of Dracocephalum moldavica L.; vascular dementia

DOI:  https://doi.org/10.3389/fphar.2025.1640272
Mol Ther. 2025 Aug 19. pii: S1525-0016(25)00653-7. [Epub ahead of print]

Intravenously injected hPSC-derived pericytes for Alzheimer's disease: neuroprotection and vascular repair via extracellular vesicles.

Ying Liu, Zhiyuan Ning, Qingyuan Dai, Xinkai Zhang, Yibing Xiao, Zhan Zhang, Daji Guo, Junhua Chen, Yi Li, Weiqiang Li, Songhua Xiao, Yamei Tang.

Intravenously injected human pluripotent stem cell (hPSC)-derived pericytes and their extracellular vesicles (EVs) represent promising therapeutic strategies for neurological diseases. Our study aimed to investigate the effects and mechanisms of intravenous transplantation for treating Alzheimer's disease (AD), with a focus on elucidating the critical role of EV-related mechanisms. We generated pericytes (hPSC-CNC PCs) from hPSC derived cranial neural crest (CNC) and employed 12-month-old 5xFAD mice as an advanced stage AD model. We investigated memory function, intracerebral β-amyloid (Aβ) deposition, blood-brain barrier (BBB) permeability, neuronal morphology, and associated protein expressions in mice to determine the therapeutic effects of intravenous administration of hPSC-CNC PCs or EVs. MiRNA sequencing was conducted to identify potential downstream pathways. We found that intravenous administration of hPSC-CNC PCs improved memory function of aged AD mice, concurrently reducing pathological deposits and BBB leakage, and enhancing neurofunctional outcomes via EVs. Furthermore, miRNA-486-5p in EVs might potentially promote neurovascular repair through various mechanisms. Our results demonstrated that EVs from hPSC-CNC PCs exert protective effects against AD.

DOI: https://doi.org/10.1016/j.ymthe.2025.08.024
Front Drug Deliv. 2024 ;4 1415104

Editorial: Endo- and transcytotic pathways at the brain barriers.

Michelle A Erickson, Morten S Nielsen.



Keywords:  antibodies; biologics; bispecific antibodies; blood-brain barrier; endocytosis; insulin; transcytosis; transferrin receptor

DOI:  https://doi.org/10.3389/fddev.2024.1415104
J Transl Med. 2025 Aug 25. 23(1): 958

Quercetin promotes angiogenesis and protects the blood-spinal cord barrier structure after spinal cord injury by targeting the PI3K/Akt signaling pathway.

Xinfang Liu, Xuhua Liu, Sidong Luo, Di Chen, Jinbo Lin, Man Xiong, Lei Yang, Kaifan Li, Dawei Sun, Lina Wei, Sheng Luo, Yeyang Wang.

   BACKGROUND: Revascularization and reconstruction of the blood-spinal cord barrier (BSCB) following spinal cord injury (SCI) play crucial roles in supplying essential nutrients and fostering a supportive microenvironment for neural network reconstruction. Thus, facilitating vascular regeneration and maintaining BSCB integrity are key therapeutic targets for functional recovery post-SCI.
METHODS: Ischemia-induced pathological alterations in spinal cord microvascular endothelial cells were modeled in vitro using oxygen-glucose deprivation/reperfusion (OGD/R)-exposed bEnd.3 cells to assess whether QCT protects endothelial cells and enhances their angiogenic capacity. Subsequently, motor function, histopathological morphology, vascular density, and BSCB integrity were evaluated in rats with SCI to examine the therapeutic efficacy of QCT. A network pharmacology approach was employed to predict the potential pharmacological mechanisms of QCT in the treatment of SCI, followed by experimental validation.
RESULTS: QCT enhanced survival, tube formation, and migration of bEnd.3 cells following OGD/R exposure in vitro. In the rat SCI model, QCT demonstrated beneficial effects on vascular regeneration and BSCB integrity, contributing to improved functional recovery. The PI3K/Akt signaling pathway was investigated to elucidate the underlying molecular mechanisms.
CONCLUSIONS: These findings suggest that QCT can promote the regeneration of blood vessels in the injured spinal cord and protect the structure of the BSCB by activating the PI3K/Akt signaling pathway, thereby enhancing the neurological function of rats following SCI.

Keywords:  Angiogenesis; Blood-spinal cord barrier; Endothelial cells; PI3K/Akt pathway; Quercetin; Spinal cord injury

DOI:  https://doi.org/10.1186/s12967-025-06973-7
Angiogenesis. 2025 Aug 25. 28(4): 46

G3BP1 maintains endothelial barrier integrity through dual mechanisms: direct stabilization of junction protein mRNAs and suppression of the inflammatory MYD88-ARNO-ARF6 pathway.

Weiyue Sun, Haoran Wu, Yuxi He, Huiqiao Chen, Yuanhui Meng, Guofang Tang, Jinshun Zhu, Zhengwang Wen, Hui Zhang, Rongzhou Wu, Guowei Wu, Chunxiang Zhang, Maoping Chu, Bin Wen.

  Vascular permeability, crucial for organ function, relies on the endothelial barrier formed by intercellular junctions (AJs, TJs). However, mechanisms regulating these junctions and maintaining endothelial barrier integrity are incompletely understood. Here, we investigate the RNA-binding protein G3BP1's role in endothelial barrier integrity using G3bp1 knockout mice and G3BP1-deficient human endothelial cells. We found that G3BP1 loss compromised barrier function, leading to reduced AJ and TJ protein levels and increased vascular permeability, particularly under LPS-induced inflammatory conditions. Mechanistically, G3BP1 exerts dual post-transcriptional control: it directly binds to and stabilizes mRNAs of key AJ proteins (VE-cadherin, p120), ensuring their sustained expression. Concurrently, G3BP1 binds MYD88 mRNA and promotes its decay, thereby suppressing the pro-permeability MYD88-ARNO-ARF6 signaling cascade, particularly during inflammation. Pharmacological or genetic inhibition of this pathway, or VE-cadherin overexpression, partially rescued barrier defects in G3BP1-deficient models, with combined interventions showing enhanced restoration under inflammatory conditions. Our findings reveal that G3BP1 maintains vascular barrier integrity through dual post-transcriptional control: stabilizing key AJ mRNA and suppressing inflammatory signaling via MYD88 mRNA decay. Targeting G3BP1 may offer a therapeutic strategy for vascular permeability disorders.

Keywords:  Adherens junctions (AJs); Endothelial barrier integrity; G3BP1; MYD88-ARNO-ARF6 signaling pathway; RNA-binding proteins; Vascular permeability

DOI:  https://doi.org/10.1007/s10456-025-09993-5