bims-blobar Biomed News
on Blood brain barrier repair
Issue of 2025–10–12
nine papers selected by
Nicolas Rebergue
  1. Expression of Concern for: "Mechanisms of Osteopontin-Induced Stabilization of Blood-Brain Barrier Disruption After Subarachnoid Hemorrhage in Rats".
  2. Methyl-beta-cyclodextrin and myriocin alleviate blood-brain barrier impairment in septic rats.
  3. Amplifying blood brain barrier injury: Neuroinflammation propagates cerebral microbleed cascades in cerebral small vessel disease, driving dementia.
  4. Effects of Irrigation With Normal Saline on Traumatic Brain Injury Combined With Seawater Immersion in Rats.
  5. Correction to "Improved Antiglioblastoma Activity and BBB Permeability by Conjugation of Paclitaxel to a Cell-Penetrative MMP-2-Cleavable Peptide".
  6. Engineered neural stem cell vesicles activating Wnt promote blood-brain barrier repair after cerebral haemorrhage.
  7. Bispecific self-assembled peptides as supra-growth factors for preventing endotheliopathy and improving survival of traumatic brain injury in mice.
  8. BECLIN-1/BECN1 at the barrier: a gatekeeper of epithelial and endothelial homeostasis.
  9. Alzheimer Disease, Vascular Disease, and Blood-Brain Barrier Permeability Biomarkers in Middle-Aged Adults.
  1. Stroke. 2025 Oct 09.
    Expression of Concern for: "Mechanisms of Osteopontin-Induced Stabilization of Blood-Brain Barrier Disruption After Subarachnoid Hemorrhage in Rats".
      
    DOI:  https://doi.org/10.1161/STR.0000000000000510
  2. Histochem Cell Biol. 2025 Oct 08. 163(1): 95
    Methyl-beta-cyclodextrin and myriocin alleviate blood-brain barrier impairment in septic rats.
    Uğur Akcan, Haşim Bakbak, Ecem Ayvaz, Müge Atış, Canan Uğur Yılmaz, Nurcan Orhan, Tuğba Kotil, Nadir Arıcan, Bülent Ahıshalı, Mehmet Kaya.
      In this study, the effect of targeting plasma membranes by depleting cholesterol and inhibiting sphingolipid synthesis using methyl-beta-cyclodextrin (MβCD) and myriocin, respectively, on blood-brain barrier (BBB) integrity was investigated in rats under septic conditions induced by cecal ligation and puncture (CLP). Horseradish peroxidase (HRP) and Evans blue (EB) tracers were used to assess BBB permeability. Caveolin (Cav)-1, claudin-3 and -5, and glucose transporter (Glut)-1 expression was assessed using immunofluorescence staining. In septic rats, MβCD or myriocin significantly attenuated the increased BBB permeability to both tracers. Upon MβCD administration, Cav-1 immunoreactivity decreased in the cerebral cortex; however, it increased markedly in the hippocampus in CLP-operated animals. MβCD and myriocin treatments to septic rats increased claudin-3 immunoreactivity in brain regions, and the difference reached statistical significance with the former treatment. In septic rats, claudin-5 immunoreactivity in brain regions was significantly decreased by MβCD and increased by myriocin. In CLP-operated animals, MβCD and myriocin treatments increased Glut-1 immunoreactivity in the brain regions, with the differences reaching statistical significance in the cerebral cortex and hippocampus by the former, while in only the cerebral cortex by the latter treatment. In conclusion, our results suggest that altering lipid profiles of plasma membranes by MβCD and myriocin can alleviate BBB disruption in septic conditions and, hence, may account for a novel therapeutic modality.
    Keywords:  Blood–brain barrier; Methyl-beta-cyclodextrin; Myriocin; Sepsis
    DOI:  https://doi.org/10.1007/s00418-025-02421-1
  3. Exp Neurol. 2025 Oct 02. pii: S0014-4886(25)00350-4. [Epub ahead of print]395 115485
    Amplifying blood brain barrier injury: Neuroinflammation propagates cerebral microbleed cascades in cerebral small vessel disease, driving dementia.
    Mengxin Wang, Mofan Li, Haowen Yuan, Yang Sun, Yongyue Zhang, Weiguang Zhang, Xiaolong Liang, Shumin Wang.
       OBJECTIVE: As an important cause of cognitive impairment, Cerebral Small Vessel Disease (CSVD) is characterized by structural and functional abnormalities of the Blood-Brain Barrier (BBB). To explore the association between impaired integrity of the blood-brain barrier and decline in cognitive ability, and to clarify the specific dynamic pathological and physiological changes of the model, the alterations in synaptic plasticity, as well as the specific impact of blood-brain barrier damage on neuronal function.
    METHODS: In this study, Ultrasound-Targeted Microbubble Destruction (UTMD) technology was innovatively used to construct an animal model of CSVD. Multi-dimensional evidence such as MRI, ultrasound super resolution microvascular imaging (USRMI), molecular biology, behavior, and transcriptome sequencing was used for research.
    RESULTS: This model accurately recapitulates the typical features of CSVD such as cerebral microbleeds, microinfarcts, and enlarged perivascular space, and reveals the molecular cascade mechanism of BBB damage triggering cognitive impairment. Studies have found that neuroinflammation induced by BBB leakage inhibits neuronal synaptic plasticity, in which the abnormal activation of microglia is the key node leading to the reduction of neuronal dendritic spine density and neural network dysfunction. Transcriptome sequencing results further confirmed that the activation of multiple signaling pathways promoted the occurrence of cognitive impairment in CSVD rats. This study provides a logical chain of "BBB damage, neuroinflammation, and synaptic dysfunction" for CSVD-related cognitive impairment, provides experimental evidence that BBB damage is the core mechanism of CSVD disease.
    INTERPRETATION: These findings not only deepen the systematic understanding of the pathogenesis of CSVD, but also provide new animal models and potential therapeutic targets for translational medicine research.
    Keywords:  Blood brain barrier; Cerebral small vessel disease; Cognitive function; Microbleed; Microglia; Neuroinflammation
    DOI:  https://doi.org/10.1016/j.expneurol.2025.115485
  4. J Surg Res. 2025 Oct 09. pii: S0022-4804(25)00569-4. [Epub ahead of print]
    Effects of Irrigation With Normal Saline on Traumatic Brain Injury Combined With Seawater Immersion in Rats.
    Yang Yang, Li Chen, Pengwei Hou, Xia Yu, Tianshun Feng, Yuhui Chen, Yongjun Xu, Shousen Wang.
       INTRODUCTION: With the integrated development of the global economy, various economic activities in marine environments are also expanding, along with the number of offshore employees. However, the increased risk of accidental falling and collisions at sea may lead to traumatic brain injury (TBI) accompanied by seawater immersion (SI). The high permeability and alkalinity of seawater increase the risk of TBI and damage to the blood-brain barrier (BBB), which can indirectly result in excessive neuroinflammation, brain edema, and neuronal cell death.
    METHODS: A well-characterized rat model of TBI + SI induced by controlled cortical impact combined with SI was established. After successful modeling, three different concentrations of sodium chloride (NaCl) solutions were used to irrigate the wound site to assess the effects on rats with early TBI complicated with SI.
    RESULTS: The results showed that irrigation with 0.9% NaCl (normal saline [NS]) significantly reduced neurological dysfunction, reduced brain edema, and inhibited neuroinflammatory response in rats with TBI combined with SI. However, irrigation with 3% NaCl (3% hypertonic saline) aggravated the injury, whereas 0.45% NaCl (half-NS) had no obvious improvement. Irrigation with NS can neutralize the high alkalinity of seawater and prevent further damage to the BBB. Irrigation with NS caused fewer morphological changes to the neuronal mitochondria and prevented further damage, suggesting that NS was the most suitable rinse solution.
    CONCLUSIONS: SI can cause damage to the BBB, neuroinflammation, and neuronal cell death after TBI. Restoration of the injured BBB is a promising strategy for the treatment of TBI combined with SI.
    Keywords:  Blood–brain barrier; Inflammation; Seawater immersion; Traumatic brain injury
    DOI:  https://doi.org/10.1016/j.jss.2025.09.017
  5. Adv Sci (Weinh). 2025 Oct 05. e10150
    Correction to "Improved Antiglioblastoma Activity and BBB Permeability by Conjugation of Paclitaxel to a Cell-Penetrative MMP-2-Cleavable Peptide".
      
    DOI:  https://doi.org/10.1002/advs.202510150
  6. Brain. 2025 Oct 08. pii: awaf381. [Epub ahead of print]
    Engineered neural stem cell vesicles activating Wnt promote blood-brain barrier repair after cerebral haemorrhage.
    Tianwen Li, Peng Wang, Fengshi Li, Kezhu Chen, Jingyu Yu, Chencheng Ma, Xiao Fan, Junjie Zhong, Qisheng Tang, Xiaoming Wang, Guangchao Ji, Tongming Zhu, Jianhong Zhu.
      The blood-brain barrier (BBB), a highly specialized neurovascular structure indispensable for preserving cerebral homeostasis, exhibits significant impairment across diverse neurological pathologies; however, its therapeutic targeting persists as a formidable challenge due to the inherent complexity of its multicellular architecture and dynamic regulatory networks. Although the Wnt/β-catenin signaling pathway orchestrates the development and maintenance of the BBB, the clinical translation of Wnt-based interventions remains elusive. We fabricated functionalized extracellular vesicles derived from neural stem cells (EVs-WK) by loading them with an engineered BBB-tropic ligand, Wnt7a-K190A, using electroporation. The therapeutic benefits of EVs-WK for BBB protection and repair were subsequently interrogated through comprehensive in vitro and in vivo analyses. In vitro mechanistic studies demonstrated that EVs-WK had three main effects: they enhanced BBB integrity, promoted synaptogenesis through β-catenin-mediated reinforcement, and significantly attenuated neurotoxic activation of astrocytes. Cross-species validation using humanized EVs (hEVs-WK) confirmed the conserved therapeutic efficacy of this approach, as shown by the mitigation of LPS-induced barrier dysfunction and downregulation of inflammatory pathways. In murine intracerebral hemorrhage (ICH) models, administering EVs-WK significantly reduced hematoma expansion and accelerated motor recovery. This modular EV platform combines BBB restoration with neurovascular unit repair, thus overcoming critical translational barriers in neurological therapeutics through targeted-controlled activation of Wnt signaling.
    Keywords:  Wnt activation; blood–brain barrier; extracellular vesicles; intracerebral haemorrhage; neural stem cell
    DOI:  https://doi.org/10.1093/brain/awaf381
  7. J Nanobiotechnology. 2025 Oct 09. 23(1): 632
    Bispecific self-assembled peptides as supra-growth factors for preventing endotheliopathy and improving survival of traumatic brain injury in mice.
    Yichi Zhang, Lanxing Wang, Dandan Li, Xingyao Sun, Zijian Zhou, Ying Zhang, Linan Jiao, Shuhong Yang, Yafan Liu, Tianrui Ma, Hao Zhang, Lujia Tang, Kaifeng Pang, Pengbo Zhao, Muyan Xu, Jie Li, Jianning Zhang, Zhimou Yang, Jie Gao, Zilong Zhao.
      Traumatic brain injury (TBI) causes endothelial injury (endotheliopathy), which contributes to a cascade of adverse events, including cerebral hemorrhage, edema and acute lung injury (ALI), and leads to poor clinical outcomes. Protecting endothelial integrity and targeting cerebral endothelium is therefore critical for preventing secondary cerebral injuries from TBI. However, effective treatment strategies in the clinic remain lacking. Here, we report a nanofiber of bispecific self-assembled peptide (BsSA) as a supra-growth factor that possesses multiple functions, such as binding to the blood‒brain barrier (BBB) and dual growth factor activity. BsSA protects TBI mice by binding to the BBB through Insulin-like growth factor 1 receptor (IGF-1R) and insulin receptor (IR) and ameliorating endothelial injury by activating the IGF-1R/IR signaling pathway. Specifically, this protection is achieved by promoting endothelial cell proliferation and survival and mitigating oxidative stress. Exogenous BsSA, as a therapeutic agent, prevented mice with TBI from developing brain and pulmonary endotheliopathy and improved their outcomes. This study identified BsSA as a potential therapeutic agent to reduce TBI-induced endotheliopathy, brain edema, and lung injury and improve TBI outcomes.
    Keywords:  Drug delivery; Endotheliopathy; Nanoscale materials; Self-assembled peptides; Traumatic brain injury
    DOI:  https://doi.org/10.1186/s12951-025-03713-3
  8. Autophagy Rep. 2025 ;4(1): 2566129
    BECLIN-1/BECN1 at the barrier: a gatekeeper of epithelial and endothelial homeostasis.
    Juliani Juliani, Walter D Fairlie, Erinna F Lee.
      Epithelial and endothelial barriers are essential for tissue homeostasis, protecting the body from environmental insults while regulating selective transport. The integrity of these barriers relies on dynamic intercellular junctions whose composition and organization are constantly remodeled in response to stress and physiological cues. Autophagy and endocytic trafficking are key intracellular pathways that maintain junctional stability and barrier resilience. BECLIN-1 (BECN1), a central regulator of both pathways, coordinates localized membrane dynamics through its interaction with the class III phosphatidylinositol 3-kinase (PtdIns3K) PIK3C3/VPS34. Recent advances reveal that BECN1's dual role in autophagy and endocytic trafficking is crucial for maintaining barriers in diverse tissues, including the gut, skin, and blood-brain barrier. Conversely, BECN1 dysfunction can compromise junctional integrity, driving inflammatory and degenerative diseases. This review summarizes the emerging evidence linking BECN1 to membrane trafficking, stress adaptation, and immune regulation across barrier tissues, highlighting its potential as a therapeutic target for barrier-associated diseases.
    Keywords:  Adherens junction; BECLIN-1/BECN1; autophagy; endocytic trafficking; endothelium; epidermis; epithelium; intestinal epithelium; tight junction; tissue barrier
    DOI:  https://doi.org/10.1080/27694127.2025.2566129
  9. Neurology. 2025 Nov 11. 105(9): e214220
    Alzheimer Disease, Vascular Disease, and Blood-Brain Barrier Permeability Biomarkers in Middle-Aged Adults.
    Natalie C Edwards, Patrick Lao, Mohamad J Alshikho, Jessica Mazen, Benjamin Huber, Christiane Hale, Joncarlos Berroa, Natalie Morel, Alicia Pacheco, Sara Walker, Mathieu Herman, Jose Gutierrez, Donna M Wilcock, Sabrina Simoes, Jennifer J Manly, Adam M Brickman.
       BACKGROUND AND OBJECTIVES: Cerebrovascular disease (CVD) influences Alzheimer disease (AD) risk and progression, but the link between vascular disease and AD pathophysiology remains unclear, particularly in midlife when the impact of CVD on AD risk may be strongest. This study examined the relationship of recently validated vascular cognitive impairment (VCI) plasma biomarker concentrations that reflect aspects of blood-brain barrier dysfunction with MRI markers of CVD and AD plasma biomarker concentrations.
    METHODS: The study included middle-aged participants from the Offspring Study of Racial and Ethnic Disparities in AD who had MRI and plasma biomarker data available. Biomarker concentrations of vascular endothelial growth factor (VEGF) family members (VEGF-D, placental growth factor [PlGF], and basic fibroblast growth factor [bFGF]) were measured using the Meso Scale Discovery platform. β-Amyloid (Aβ42, Aβ40), phosphorylated tau 181 (p-tau181), astrocytosis (glial fibrillary acidic protein [GFAP]), and neurodegeneration (neurofilament light chain [NfL]) biomarkers were measured with Simoa immunoassays. White matter hyperintensity (WMH) volumes were derived from T2-weighted MRI scans. Bivariate relationships of WMH, Aβ42/Aβ40 ratio, p-tau181, GFAP, and NfL with VEGF biomarkers were tested, and path analyses examined potential causal pathways linking each VEGF biomarker concentration to WMH and GFAP, as well as their downstream associations with tau pathology and neurodegeneration.
    RESULTS: We analyzed data from 488 participants (mean [SD] age = 54.3 [10.5]; 66.8% women). Higher PlGF levels were associated with older age (R [CI] = 0.25 [0.17-0.33]); greater WMH volume (R [CI] = 0.2 [0.11-0.29]); and higher levels of GFAP (R [CI] = 0.11 [0.02-0.2]), p-tau181 (R [CI] = 0.12 [0.03-0.21]), and NfL (R [CI] = 0.19 [0.1-0.27]). Higher VEGF-D was associated with increased GFAP (R [CI] = 0.11 [0.02-0.19]) and NfL (R [CI] = 0.16 [0.07-0.25]) levels. bFGF concentration was associated with a lower Aβ42/40 ratio (R [CI] = -0.1 [-0.19 to -0.02]) and higher p-tau181 levels (R [CI] = 0.13 [0.04-0.21]). The best fitting path model showed that PlGF had an indirect effect on GFAP levels mediated by WMH. GFAP subsequently had a direct positive effect on p-tau181, which in turn had a positive effect on NfL levels. VEGF-D and bFGF levels also had a positive direct effect on NfL.
    DISCUSSION: The findings suggest that permeability of the blood-brain barrier is linked to AD pathophysiology, contributes to cerebrovascular lesions observed on MRI, and is associated with neuroinflammation in middle age.
    DOI:  https://doi.org/10.1212/WNL.0000000000214220
This page is being maintained by Thomas Krichel. It was last updated on 2025‒10‒20 at 10:26.