A patient-derived amyotrophic lateral sclerosis blood-brain barrier cell model reveals focused ultrasound-mediated anti-TDP-43 antibody delivery DOI Open Access
Joanna M. Wasielewska, Mauricio Castro Cabral-da-Silva, Martina Pecoraro

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 27, 2024

Abstract Background Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disorder with minimally effective treatment options. An important hurdle in ALS drug development the non-invasive therapeutic access to motor cortex currently limited by presence of blood-brain barrier (BBB). Focused ultrasound and microbubble (FUS +MB ) an emerging technology that was successfully used patients temporarily open cortical BBB. However, FUS -mediated delivery across patients’ BBB has not yet been reported. Similarly, effects on human cells remain unexplored. Methods Here we established first -compatible, fully-human patient-cell-derived model based induced brain endothelial-like (iBECs) study anti-TDP-43 antibody bioeffects vitro . Results Generated iBECs recapitulated disease-specific hallmarks pathology, including changes integrity, permeability TDP-43 proteinopathy. Our results also identified differences between sporadic familial ( C9orf72 expansion carrying) reflecting patient heterogeneity associated disease subgroups. Studies these models revealed successful iBEC monolayer opening lack adverse cellular This accompanied molecular expression tight adherens junction markers, transporter inflammatory mediators, generating transient specific responses. Additionally, demonstrated increase (2.7-fold) (1.9-fold) providing proof-of-concept evidence can be enhance large molecule therapeutics model. Conclusions Together, our describes characterisation responses provides platform for screening

Язык: Английский

Exploiting sound for emerging applications of extracellular vesicles DOI
Zhuhao Wu, Hongwei Cai,

Chunhui Tian

и другие.

Nano Research, Год журнала: 2023, Номер 17(2), С. 462 - 475

Опубликована: Июль 1, 2023

Язык: Английский

Процитировано

13
A patient-derived amyotrophic lateral sclerosis blood-brain barrier model for focused ultrasound-mediated anti-TDP-43 antibody delivery DOI Creative Commons
Joanna M. Wasielewska,

Juliana C.S. Chaves,

Mauricio Castro Cabral-da-Silva

и другие.

Fluids and Barriers of the CNS, Год журнала: 2024, Номер 21(1)

Опубликована: Авг. 13, 2024

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disorder with minimally effective treatment options. An important hurdle in ALS drug development the non-invasive therapeutic access to motor cortex currently limited by presence of blood-brain barrier (BBB). Focused ultrasound and microbubble (FUS

Язык: Английский

Процитировано

4
Neurological glycogen storage diseases and emerging therapeutics DOI Creative Commons
Matthieu Colpaert, Pankaj K. Singh,

Katherine J. Donohue

и другие.

Neurotherapeutics, Год журнала: 2024, Номер unknown, С. e00446 - e00446

Опубликована: Сен. 1, 2024

Язык: Английский

Процитировано

4
Design and Structure of a Non-Coaxial Multi-Focal Composite Fresnel Acoustic Lens for Synergistic Ultrasound Stimulation of Multiple Brain Regions DOI Creative Commons

Ruijun Wu,

F. Shi, Juan Tao

и другие.

Sensors, Год журнала: 2025, Номер 25(11), С. 3299 - 3299

Опубликована: Май 24, 2025

Transcranial focused ultrasound (TcFUS) neuromodulation is hindered by skull-induced acoustic limitations. To enable synergistic multi-region brain stimulation, we designed non-coaxial multi-focal composite Fresnel lenses, including an overlapping lens (OFL) and alternating-segmented (ASFL). These lenses convert planar into multiple foci. Based on theory, fields were analyzed via simulations experiments, validating the generation of four foci (10/30 mm focal lengths) from a 1 MHz wave using both OFL ASFL. The influence parameters pressure distribution was investigated, morphology quantified linear least-squares method. Significant differences in intensity between ASFL provide crucial guidance for optimizing multi-target TcFUS strategies.

Язык: Английский

Процитировано

0
Role of P2 × 7 receptor during focused ultrasound induced blood brain barrier modulation DOI Creative Commons
Junwon Park, Young Cheol Na, Jihyeon Lee

и другие.

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 6, 2025

Although low-intensity focused ultrasound (LiFUS) with microbubbles is used to temporally open the blood-brain barrier (BBB), underlying mechanism not fully understood. This study aimed analyze BBB-related alterations in brain microenvironment after LiFUS, a focus on involvement of purinergic P2 × 7 receptor. Sprague-Dawley rats were sonicated LiFUS at 0.3 MPa energy. The impact receptor and inflammatory-related proteins, including NLRP3 interleukin-1β, was analyzed through western blotting. BBB-associated tight junction zonula occludens-1 (ZO-1) occludin, also analyzed. BBB permeability assessed by quantifying amount Evans blue dye penetration using spectrophotometry. Furthermore, safety sonication procedure verified via terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay hematoxylin eosin staining. Substantial increases its downstream signaling confirmed sonicating for 1 h (p < 0.05). Conversely, lowest expression observed 0.001). Both responses normalized back original state over time. No evidence damage during procedure. antagonist-injected group showed reduced compared that FUS, indicating mitigated BBB. Herein, we elucidate which affects BBB, Our findings demonstrate extent opening varies upon regulation provides valuable insights into mechanisms modulation thereby laying foundation expanding applications.

Язык: Английский

Процитировано

0
Potential Mechanism and Efficacy Evaluation of Transcranial Focused Ultrasound Therapy for Alzheimer's Disease DOI
Wei Qin,

Jiayi He,

Yi Zhou

и другие.

Journal of Neuroscience Methods, Год журнала: 2025, Номер unknown, С. 110428 - 110428

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
Overcoming the Blood-Brain Barrier: Focused Ultrasound in Glioblastoma Treatment DOI Open Access
Jonas Jurgaitis,

Karina Mickeviciute,

Valerija Jablonskienė

и другие.

Cureus, Год журнала: 2025, Номер unknown

Опубликована: Апрель 23, 2025

Despite recent advancements in neuro-oncology, glioblastoma remains one of the cancers with poorest prognosis. Tumor recurrence and progression are driven by tumor stem cells a high mutational burden. New potential treatment modalities actively being explored. One promising approach is focused ultrasound (FUS), which involves converging waves on specific region interest while avoiding damage to surrounding tissue. This mini-review highlights current understanding resistance positions FUS as therapeutic option. We discuss existing clinical research utilizing four key applications: (1) blood-brain barrier disruption, (2) histotripsy, (3) thermal ablation, (4) sonodynamic therapy.

Язык: Английский

Процитировано

0
Focused ultrasound heating in brain tissue/skull phantoms with 1 MHz single-element transducer DOI Creative Commons
Anastasia Antoniou, Nikolas Evripidou, Christakis Damianou

и другие.

Journal of Ultrasound, Год журнала: 2023, Номер 27(2), С. 263 - 274

Опубликована: Июль 30, 2023

Abstract Purpose The study aims to provide insights on the practicality of using single-element transducers for transcranial Focused Ultrasound (tFUS) thermal applications. Methods FUS sonications were performed through skull phantoms embedding agar-based tissue mimicking gels a 1 MHz spherically focused transducer. 3D printed with Acrylonitrile Butadiene Styrene (ABS) and Resin thermoplastics having exact bone geometry healthy volunteer. temperature field distribution during after heating was monitored in 3 T Magnetic Resonance Imaging (MRI) scanner MR thermometry. effect skull’s thickness intracranial investigated. Results A single sonication at focal acoustic intensities close 1580 W/cm 2 60 s free heated up agar phantom ablative temperatures reaching about 90 °C (baseline 37 °C). ABS strongly blocked ultrasonic waves, resulting zero increase within phantom. Considerable achieved skull, but it remained hyperthermia levels. Conversely, tFUS mm showed enhanced penetration heating, 70 °C. Conclusions demonstrated poorer performance terms compared owing its higher attenuation porosity. thin provided an efficient window delivering deep areas. results such studies could be particularly useful accelerating establishment wider range

Язык: Английский

Процитировано

8
Adding Value to Liquid Biopsy for Brain Tumors: The Role of Imaging DOI Open Access
Nastaran Khalili,

Hossein Shooli,

Nastaran Hosseini

и другие.

Cancers, Год журнала: 2023, Номер 15(21), С. 5198 - 5198

Опубликована: Окт. 29, 2023

Clinical management in neuro-oncology has changed to an integrative approach that incorporates molecular profiles alongside histopathology and imaging findings. While the World Health Organization (WHO) guideline recommends genotyping of informative alterations as a routine clinical practice for central nervous system (CNS) tumors, acquisition tumor tissue CNS is invasive not always possible. Liquid biopsy non-invasive provides opportunity capture complex heterogeneity whole through detection circulating biomarkers body fluids, such blood or cerebrospinal fluid (CSF). Despite all advantages, low abundance tumor-derived biomarkers, particularly well their short half-life limited application liquid practice. Thus, it crucial identify factors associated with presence these explore possible strategies can increase shedding tumoral components into biological fluids. In this review, we first describe applications including its roles early recurrence monitoring treatment response. We then discuss utilization identifying affect how image-guided interventions focused ultrasound help enhance blood–brain barrier (BBB) disruption.

Язык: Английский

Процитировано

7
Intracranial Gene Delivery Mediated by Albumin-Based Nanobubbles and Low-Frequency Ultrasound DOI Creative Commons

Takayuki Koga,

Hiroshi Kida,

Yutaro Yamasaki

и другие.

Nanomaterials, Год журнала: 2024, Номер 14(3), С. 285 - 285

Опубликована: Янв. 30, 2024

Research in the field of high-intensity focused ultrasound (HIFU) for intracranial gene therapy has greatly progressed over years. However, limitations conventional HIFU still remain. That is, genes are required to cross blood-brain barrier (BBB) order reach neurological disordered lesion. In this study, we introduce a novel direct delivery method, bypassing BBB using human serum albumin-based nanobubbles (NBs) injected through less invasive intrathecal route via lumbar puncture, followed by irradiation with low-frequency (LoFreqUS). Focusing on both plasmid DNA (pDNA) and messenger RNA (mRNA), our approach utilizes LoFreqUS deeper tissue acoustic penetration enhancing transfer efficiency. This drug method could be dubbed as “Spinal Back-Door Approach”, an alternative “front door” opening method. Experiments showed that NBs effectively responded LoFreqUS, significantly improving vitro U-87 MG cell lines. vivo experiments mice demonstrated increased expression pDNA; however, were unable obtain conclusive results mRNA. technique, combining offers promising, efficient, targeted, non-invasive solution central nervous system therapy, potentially transforming treatment landscape disorders.

Язык: Английский

Процитировано

2