Blood-brain Barrier Research Articles

Generation of Advanced Blood-Brain Barrier Spheroids Using Human-Induced Pluripotent Stem Cell-Derived Brain Capillary Endothelial-Like Cells.

Extensively studied blood-brain barrier (BBB) in-vitro models are established on 2D cell culture inserts. However, they do not accurately represent 3D in-vivo microenvironments due to lack of direct neurovascular unit cellular contacts. Here, the establishment and characterization of a self-assembled 3D BBB spheroid model using human-induced pluripotent stem cell (hiPSC)-derived brain capillary endothelial-like cells (iBCECs) in combination with primary human astrocytes (ACs) and pericytes (PCs) are reported. This investigation compares 3D spheroids with 2D mono-cultured iBCECs derived from two different hiPSC lines and two differentiation strategies. It is observed that spheroid properties vary depending on the differentiation strategy or type of hiPSC line applied for model generation. However, spheroids demonstrate in-vivo like tight junction ultrastructure and, in comparison to 2D models, higher transcript expression of BBB specific genes. Furthermore, they possess characteristic barrier integrity, barrier functionality, and protein expression. It is inferred that hiPSC-derived BBB spheroids hold a strong potential as a reliable future BBB in-vitro test system.

Computational Modeling of Pharmaceuticals with an Emphasis on Crossing the Blood–Brain Barrier

The discovery and development of new pharmaceutical drugs is a costly, time-consuming, and highly manual process, with significant challenges in ensuring drug bioavailability at target sites. Computational techniques are highly employed in drug design, particularly to predict the pharmacokinetic properties of molecules. One major kinetic challenge in central nervous system drug development is the permeation through the blood–brain barrier (BBB). Several different computational techniques are used to evaluate both BBB permeability and target delivery. Methods such as quantitative structure–activity relationships, machine learning models, molecular dynamics simulations, end-point free energy calculations, or transporter models have pros and cons for drug development, all contributing to a better understanding of a specific characteristic. Additionally, the design (assisted or not by computers) of prodrug and nanoparticle-based drug delivery systems can enhance BBB permeability by leveraging enzymatic activation and transporter-mediated uptake. Neuroactive peptide computational development is also a relevant field in drug design, since biopharmaceuticals are on the edge of drug discovery. By integrating these computational and formulation-based strategies, researchers can enhance the rational design of BBB-permeable drugs while minimizing off-target effects. This review is valuable for understanding BBB selectivity principles and the latest in silico and nanotechnological approaches for improving CNS drug delivery.

A covalent peptide-based lysosome-targeting protein degradation platform for cancer immunotherapy

The lysosome-targeting chimera (LYTAC) strategy provided a very powerful tool for the degradation of membrane proteins. However, the synthesis of LYTACs, antibody-small molecule conjugates, is challenging. The ability of antibody-based LYTACs to penetrate solid tumor is limited as well, especially to cross the blood-brain barrier (BBB). Here, we propose a covalent chimeric peptide-based targeted degradation platform (Pep-TACs) by introducing a long flexible aryl sulfonyl fluoride group, which allows proximity-enabled cross-linking upon binding with the protein of interest. The Pep-TACs platform facilitates the degradation of target proteins through the mechanism of recycling transferrin receptor (TFRC)-mediated lysosomal targeted endocytosis. Biological experiments demonstrate that covalent Pep-TACs can significantly degrade the expression of PD-L1 on tumor cells, dendritic cells and macrophages, especially under acidic conditions, and markedly enhance the function of T cells and tumor phagocytosis by macrophages. Furthermore, both in anti-PD-1-responsive and -resistant tumor models, the Pep-TACs exert significant anti-tumor immune response. It is noteworthy that Pep-TACs can cross the BBB and prolong the survival of mice with in situ brain tumor. As a proof-of-concept, this study introduces a modular TFRC-based covalent peptide degradation platform for the degradation of membrane protein, and especially for the immunotherapy of brain tumors.

The Fetal Effect of Maternal Caffeine Consumption During Pregnancy—A Review

Caffeine is commonly used to excess by the general public, and most pregnant women drink caffeine on a daily basis, which can become a habit. Maternal caffeine intake during pregnancy is associated with severe gestational outcomes. Due to its lipophilic nature, caffeine can cross the blood–brain barrier, placental barrier, and even amniotic fluid. It can be found in substantive amounts in breast milk and semen. There has been a reported drop in neonatal anthropometric measurements with increased caffeine consumption in some cohort studies. This narrative review using literature titles and abstracts from the electronic databases of PubMed, Embase, and Scopus investigates the data linking maternal caffeine use to unfavorable pregnancy outcomes. It also evaluates the validity of the recommendations made by health professionals on caffeine consumption by mothers from the available literature. The results of our comprehensive literature search of case–control studies, cohort studies, randomized control trials, and meta-analyses, imply that caffeine use during pregnancy is linked to miscarriage, stillbirth, low birth weight, and babies that are small for gestational age. It was also found that there may be effects on the neurodevelopment of the child and links to obesity and acute leukemia. These effects can even be seen at doses well below the daily advised limit of 200 mg. The genetic variations in caffeine metabolism and epigenetic changes may play a role in the differential response to caffeine doses. It is crucial that women obtain solid, evidence-based guidance regarding the possible risks associated with caffeine.

Effects of Montelukast on Neuroinflammation in Parkinson's Disease: An Open Label Safety and Tolerability Trial with CSF Markers and [11C]PBR28 PET.

Dysregulated leukotriene signaling is proposed to be involved in pathogenesis of Parkinson's disease (PD). The objective was to examine the safety and tolerability of montelukast, a cysteinyl-leukotriene receptor1 and GPR17 antagonist, in patients with PD. Secondary outcomes were target engagement, effects on PD signs/symptoms, and central neuroinflammation. Fifteen PD patients were recruited to a 12-week open-label trial of 20 mg bi-daily montelukast treatment. Patients underwent ratings with the Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS), the Montreal Cognitive Assessment (MoCA), Beck's Depression Inventory (BDI), Parkinson's Disease Questionnaire-39 (PDQ-39), [11C]PBR28-PET, and lumbar punctures before and during montelukast treatment. All patients completed the study. Three patients reported loose stool. No serious adverse events related to treatment were reported. MDS-UPDRS-Total scores improved by 6.9 points. Very low levels of montelukast were detected in all cerebrospinal fluid (CSF) samples and resulted in a reduction in inflammation/metabolism markers. [11C]PBR28 binding was lowered in high, but not mixed, affinity binders after montelukast. Montelukast crosses the blood-brain barrier at very low levels and is well tolerated and safe in PD patients. Preliminary effects on neuroinflammation and clinical scores motivate a future randomized controlled trial (RCT) in PD. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Microbubble dynamics in brain microvessels.

Focused ultrasound stimulation of microbubbles is being tested in clinical trials for its ability to deliver drugs across the blood-brain barrier (BBB). This technique has the potential to treat neurological diseases by preferentially delivering drugs to targeted regions. Yet despite its potential, the physical mechanisms by which microbubbles alter the BBB permeability remain unclear, as direct observations of microbubbles oscillating in brain microvessels have never been previously recorded. The purpose of this study was to reveal how microbubbles respond to ultrasound when within the microvessels of living brain tissue. Microbubbles in acute brain slices acquired from juvenile rats perfused with a concentrated solution of SonoVue® and dye were exposed to ultrasound pulses typically used in BBB disruption (center frequency: 1 MHz, peak-negative pressure: 0.2-1 MPa, pulse length: up to 10 ms) and observed using high-speed microscopy at up to 10 million frames per second. We observed that microbubbles can exert mechanical stresses on a wide region of tissue beyond their initial location and immediate surroundings. A single microbubble can apply mechanical stress to parenchymal tissues several micrometers away from the vessel. Microbubbles can travel at high velocities within the microvessels, extending their influence across tens of micrometers during a single pulse. With longer pulses and higher pressures, microbubbles could penetrate the vessel wall and move through the parenchyma. The probability of extravasation scales approximately with mechanical index, being rare at low pressures, but much more common at a mechanical index ≥ 0.6. These results present the first direct observations of ultrasound-driven microbubbles within brain tissue, and illustrate a range of microbubble behaviors that have the potential to lead to safe drug delivery or tissue damage.

A Comparative Study of Common Anesthetics Propofol, Sevoflurane, Isoflurane and Ketamine on Lipid Membrane Fluidity

The membrane fluidity increases induced by popular anesthetic agents (propofol, isoflurane, sevoflurane, and ketamine/xylazine) were measured at the clinical and supra-clinical concentrations in red blood cell (RBC) membrane as well as four model membranes. Membrane fluidity changes were monitored using the excimer/monomer (E/M) ratio of dipyrene-PC and fluorescence anisotropies of DPH-PC and TMA-DPH. Propofol, sevoflurane and isoflurane increased membrane fluidity instantaneously. The largest increase occurs in membranes made of saturated lipids. RBCs were labeled with TMA-DPH, and the increase in membrane fluidity at clinical concentrations of isoflurane and sevoflurane was more than that induced by ten times the legal limit of alcohol in human blood. However, membrane fluidity was essentially unchanged by ketamine/xylazine up to 210 µM. These results strongly correlate with our recent in vivo experiments and reveal a clear connection between increasing membrane fluidity in model membranes, increasing the blood–brain barrier (BBB) permeability in mice, and inducing effective anesthesia in animals. Interestingly, at the most commonly used clinical concentrations, the membrane fluidity increases induced by propofol, sevoflurane, and isoflurane were very similar, despite the fact that different categories of anesthetics were used and their chemical concentrations were different by 100 times. This indicates that at clinical concentrations of these anesthetics, a similar level of membrane disruption at the BBB is achieved. Thus, our results strongly support the lipid hypothesis of the mechanism of general anesthetics.

Roles, Functions, and Pathological Implications of Exosomes in the Central Nervous System

Exosomes are a subset of extracellular vesicles (EVs) secreted by nearly all cell types and have emerged as a novel mechanism for intercellular communication within the central nervous system (CNS). These vesicles facilitate the transport of proteins, nucleic acids, lipids, and metabolites between neurons and glial cells, playing a pivotal role in CNS development and the maintenance of homeostasis. Current evidence indicates that exosomes from CNS cells may function as either inhibitors or enhancers in the onset and progression of neurological disorders. Furthermore, exosomes have been found to transport disease-related molecules across the blood–brain barrier, enabling their detection in peripheral blood. This distinctive property positions exosomes as promising diagnostic biomarkers for neurological conditions. Additionally, a growing body of research suggests that exosomes derived from mesenchymal stem cells exhibit reparative effects in the context of neurological disorders. This review provides a concise overview of the functions of exosomes in both physiological and pathological states, with particular emphasis on their emerging roles as potential diagnostic biomarkers and therapeutic agents in the treatment of neurological diseases.

In Vivo Time-Resolved Single-Cell RNA-Seq Reveals Chemotherapy-Induced Transcriptional Dynamics in Tumor Infiltrating Lymphocytes.

Single-cell RNA sequencing (scRNA-seq) using metabolic RNA labeling enables detailed analysis of dynamic gene expression within single cells. However, most studies are limited to in vitro settings, restricting the exploration of in vivo transcriptomic dynamics. To address this, we developed scDyna-seq, a time-resolved scRNA-seq method for in vivo applications using 4-thiouridine (4sU) labeling. scDyna-seq efficiently captures nascent RNA, allowing for precise tracking of gene expression in both in vitro and in vivo contexts, including crossing the blood-brain and blood-fetal barriers. It is also compatible with other single-cell multiomics approaches. In a mouse bladder cancer model, scDyna-seq revealed that cisplatin (cis-diaminodichloroplatinum, CDDP) induced significant dynamic changes in tumor-infiltrating lymphocytes, particularly in genes related to costimulation, effector functions, and exhaustion, which were not detected by conventional methods. When coupled with scTCR-seq, scDyna-seq showed increased TCR clonal expansion linked to CDDP-induced immunogenic death and neoantigen production. In conclusion, scDyna-seq offers safe, precise in vivo RNA labeling as well as single-cell analysis, expanding our understanding of cellular dynamics and facilitating research in health and disease.

Exploring the Expanded Role of Astrocytes in Primate Brain Evolution via Changes in Gene Expression.

Astrocytes are a subtype of glial cells, which are non-neuronal cells that do not produce electrical impulses. Rather, astrocytes are involved in various functions vital to a functioning brain including nutrient supply to neuronal cells, blood brain barrier maintenance, regulation of synaptic transmission, and repair following CNS injury. While in the past astrocytes were mostly examined in rodents, it is now clear that there is a large amount of astrocyte heterogeneity and increased complexity in mammals and primates (Oberheim et al. 2009; Falcone et al. 2019; Falcone et al. 2021; Falcone and Martinez-Cerdeno 2023). Astrocytes have expanded in the human lineage (density, soma volume, and ratio of astrocytes to total glial cells). The human prefrontal cortex also possesses an overall increased glia:neuron ratio relative to other primates, coinciding with allometric expectations based on overall brain size. What are the underlying changes in astrocytes in primate evolution? For this review, we will focus on gene expression evolution and gene regulation in astrocytes as a read out of the phenotypic changes seen in cellular morphology. This is an exciting time to understand this cell type in a more dynamic and complex way with new technologies such as induced pluripotent stem cells (iPSCs) and single-cell RNA sequencing (scRNA-Seq). Furthermore, understanding the evolution of astrocytes across primates will help to explain their role in neurological disease, as alterations in astrocyte function are implicated in many neurodegenerative states such as Alzheimer's disease and Parkinson's Disease.

Identifying natural inhibitors against FUS protein in dementia through machine learning, molecular docking, and dynamics simulation

Dementia, a complex and debilitating spectrum of neurodegenerative diseases, presents a profound challenge in the quest for effective treatments. The FUS protein is well at the center of this problem, as it is frequently dysregulated in the various disorders. We chose a route of computational work that involves targeting natural inhibitors of the FUS protein, offering a novel treatment strategy. We first reviewed the FUS protein's framework; early forecasting models using the AlphaFold2 and SwissModel algorithms indicated a loop-rich protein—a structure component correlating with flexibility. However, these models showed limitations, as reflected by inadequate ERRAT and Verify3D scores. Seeking enhanced accuracy, we turned to the I-TASSER suite, which delivered a refined structural model affirmed by robust validation metrics. With a reliable model in hand, our study utilized machine learning techniques, particularly the Random Forest algorithm, to navigate through a vast dataset of phytochemicals. This led to the identification of nimbinin, dehydroxymethylflazine, and several other compounds as potential FUS inhibitors. Notably, dehydroxymethylflazine and cleroindicin C identified during molecular docking analyses—facilitated by AutoDock Vina—for their high binding affinities and stability in interaction with the FUS protein, as corroborated by extensive molecular dynamics simulations. Originating from medicinal plants, these compounds are not only structurally compatible with the target protein but also adhere to pharmacokinetic profiles suitable for drug development, including optimal molecular weight and LogP values conducive to blood-brain barrier penetration. This computational exploration paves the way for subsequent experimental validation and highlights the potential of these natural compounds as innovative agents in the treatment of dementia.

Biomimetic Chromatography/QSAR Investigations in Modeling Properties Influencing the Biological Efficacy of Phenoxyacetic Acid-Derived Congeners

A hybrid method—combining liquid biomimetic chromatography techniques (immobilized artificial membrane chromatography and biopartitioning micellar chromatography) and Quantitative Structure–Activity Relationships—was used to derive helpful models for predicting selected biological properties such as penetration through the plant cuticle, the skin and the blood–brain barrier, and binding to human serum albumin of phenoxyacetic acid-derived congeners regarded as potential herbicides. Reliable, high-concept models were developed indicating the lipophilicity, polarizability, and sum of hydrogen bond donors and acceptors as properties that determine the biological efficacy of the title compounds. These models were validated by leave-one-out cross-validation. Modeling the toxicity of phenoxyacetic acid-derived congeners to red blood cells allowed the identification of the most toxic substances as well as those molecular descriptors that determine their hemolytic properties.

Amyloid-β and heart failure in Alzheimer’s disease: the new vistas

Alzheimer’s disease (AD) is the most common cause of dementia and represents 75% of all dementia types. AD neuropathology is due to the progressive deposition of extracellular amyloid-beta (Aβ) peptide and intracellular hyperphosphorylated tau protein. The accumulated Aβ forms amyloid plaques, while the hyperphosphorylated tau protein forms neurofibrillary tangles (NFTs). Both amyloid plaques and NFTs are hallmarks of AD neuropathology. The fundamental mechanism involved in the pathogenesis of AD is still elusive, although Aβ is the more conceivable theory. Aβ-induced neurodegeneration and associated neuroinflammation, oxidative stress, endoplasmic reticulum stress (ER), and mitochondrial dysfunction contribute to the development of cognitive impairment and dementia. Of note, Aβ is not only originated from the brain but also produced peripherally and, via the blood–brain barrier (BBB), can accumulate in the brain and result in the development of AD. It has been shown that cardiometabolic conditions such as obesity, type 2 diabetes (T2D), and heart failure (HF) are regarded as possible risk factors for the development of AD and other types of dementia, such as vascular dementia. HF-induced chronic cerebral hypoperfusion, oxidative stress, and inflammation can induce the development and progression of AD. Interestingly, AD is regarded as a systemic disease that causes systemic inflammation and oxidative stress, which in turn affects peripheral organs, including the heart. Aβ through deranged BBB can be transported into the systemic circulation from the brain and accumulated in the heart, leading to the development of HF. These findings suggest a close relationship between AD and HF. However, the exact mechanism of AD-induced HF is not fully elucidated. Therefore, this review aims to discuss the link between AD and the risk of HF regarding the potential role of Aβ in the pathogenesis of HF.

Improvements in Exercise for Alzheimer's Disease: Highlighting FGF21-Induced Cerebrovascular Protection.

Alzheimer's disease (AD) is the most common neurodegenerative disease. Currently, it has shown a trend of earlier onset, with most patients experiencing a progressive decline in cognitive function following the disease's onset, which places a heavy burden on society and family. Since no drug cure for AD exists, exploring new ways for its treatment and prevention has become critical. Early vascular damage is an initial trigger for neuronal injury in AD, underscoring the importance of vascular health in the early stages of the disease. Patients with early AD experience abnormal blood-brain barrier transport of amyloid-β (Aβ) peptides, with excess Aβ being deposited in the cerebral vasculature. The toxic effects of Aβ lead to abnormalities in cerebrovascular structure and function. Fibroblast growth factor21 (FGF21) is an endocrine factor that positively regulates energy homeostasis and glucose-lipid metabolism. Notably, it is one of the effective targets for metabolic disease prevention and treatment. Recent studies have found that FGF21 has anti-aging and vasoprotective effects, with receptors for FGF21 present in the brain. Exercise stimulates the liver to produce large amounts of FGF21, which enters the blood-brain barrier with the blood to exert neurovascular protection. Therefore, we review the biological properties of FGF21, its role in the cerebrovascular structure and function in AD, and the mechanism of exercise-regulated FGF21 action on AD-related cerebrovascular changes, aiming to provide a new theoretical basis for using exercise to ameliorate degenerative neurological diseases.

Evaluation of zonulin levels in patients with migraine

BackgroundZonulin regulates permeability in blood–brain and intestinal barriers. The pathophysiology of migraine is based on the effect of neurogenic inflammation. The aim of the current investigation was to examine the serum zonulin level in individuals suffering from migraine.MethodsThe sample comprised 40 individuals who had migraine and 40 controls. Disease duration, attack duration, attack frequency, Visual Analog Scale (VAS) scores, and comorbidities were available for the migraine group. Serum zonulin levels were evaluated by using the ELISA method.ResultsThere were no statistically significant differences between the two groups concerning age or gender (p > 0.05). The zonulin value of patients with migraine was higher when compared to the controls, indicating a significant difference (p = 0.037; p < 0.05). The zonulin level did not correlate with disease duration, attack duration, VAS score, or attack frequency (p > 0.05). The receiver operating characteristic curve analysis of zonulin revealed a cut-off value of 30.58 and above, at which it had 52.50% sensitivity, 77.5% specificity, 70% positive predictive value, and 62% a negative predictive value. The area under the curve was 63.6%, and the standard error value was 6.3%. The analysis also showed a statistically significant correlation between migraine diagnosis and a zonulin level of 30.58 (p = 0.006; p < 0.01).ConclusionsElevated zonulin levels in patients with migraine support the disruption of the intestinal barrier and neuroinflammation in these patients. The zonulin level may be a predictive biomarker of migraine. Multicenter, randomized trials are needed to evaluate treatments for intestinal permeability and zonulin levels in migraine patients.

A review on intrathecal administration of medications for leptomeningeal metastases in solid tumors

Leptomeningeal disease (LMD) is a particular mode of central metastasis in malignant tumors. It occurs when tumor cells infiltrate the subarachnoid space and cerebrospinal fluid (CSF), spreading throughout the central nervous system (CNS). LMD is a rare but devastating complication of malignant tumors. It can occur in various types of cancers, with lung and breast cancer being the most frequently associated. The treatment approach for LMD includes a combination of supportive care, surgery, chemotherapy, radiotherapy, targeted therapy, immunotherapy, and intrathecal (IT) therapy, among other modalities. Despite the challenges in determining the optimal treatment for LMD, IT therapy remains one of the primary therapeutic strategies. This therapy can directly circumvent the blood–brain barrier. Moreover, a low-dose medication can achieve a higher drug concentration in the CSF, resulting in better cytotoxic effects. Chemotherapy drugs such as methotrexate, cytarabine, and thiotepa have been widely studied as traditional IT therapies. In recent years, the advent of novel anti-tumor drugs has led to a growing number of agents being employed for IT administration in the treatment of malignant tumors with LMD. This article presents a comprehensive review of the current advancements in IT administration of chemotherapy, targeted, and immunotherapy drugs for the treatment of LMD in solid tumors. In addition, we also discuss the safety issues associated with IT therapy, summarize the advantages of IT administration of different types of anti-tumor drugs, and put forward some suggestions for reducing adverse reactions. It is hoped that future research will focus on exploring more potentially effective anti-tumor drugs for IT treatment, conducting in-depth pharmacokinetic studies, and developing long-acting and low-toxic IT administration regimens for the treatment of meningeal metastases.

The development of opioid vaccines as a novel strategy for the treatment of opioid use disorder and overdose prevention.

Opioid use disorder (OUD) affects over 40 million people worldwide, creating significant social and economic burdens. Medication for opioid use disorder (MOUD) is often considered the primary treatment approach for OUD. MOUD, including methadone, buprenorphine, and naltrexone, is effective for some, but its benefits may be limited by poor adherence to treatment recommendations. Immunopharmacotherapy offers an innovative approach by using vaccines to generate antibodies that neutralize opioids, blocking them from crossing the blood-brain barrier and reducing their psychoactive effects. To date, only 3 clinical trials for opioid vaccines have been published. While these studies demonstrated the potential of opioid vaccines for relapse prevention, there is currently no standardized protocol for evaluating their effectiveness. We have reviewed recent preclinical studies that demonstrated the efficacy of vaccines targeting opioids, including heroin, morphine, oxycodone, hydrocodone, and fentanyl. These studies showed that vaccines against opioids reduced drug reinforcement, decreased opioid-induced antinociception, and increased survival rates against lethal opioid doses. These studies also demonstrated the importance of vaccine formulation and the use of adjuvants in enhancing antibody production and specificity. Finally, we highlighted the strengths and concerns associated with the opioid vaccine treatment, including ethical considerations.

Clinical Trials of Focused Ultrasound for Brain Tumors

Background: It is unclear as to where we stand with respect to utilizing emerging focused ultrasound (FUS) technology in the setting of brain tumor treatment in pediatric patients, such as malignant diffuse intrinsic pontine glioma, and various adult counterparts. Correspondingly, the aim of this study was to present a contemporary summary of all pertinent clinical trials to date. Methods: The ClinicalTrials.gov database was reviewed in January 2025 for all possible clinical trials involving FUS in the management of brain tumors. These were then screened against selection criteria to identify pertinent clinical trials. Results: A total of 30 clinical trials were identified. The majority were focused on adult patients (24/30, 80%), with the most common tumor type being glioblastoma (GBM) (14/30, 47%). There were also trials focused on pediatric patients only (5/30, 17%), as well as diffuse intrinsic pontine glioma (DIPG) (5/30, 17%). The most prevalent primary outcome of interest was safety (26/30, 87%). The majority of trials were active, either recruiting currently (12/30, 40%), or active but not recruiting currently (3/30, 10%). North America (22/30, 73%) was the most common location for the primary coordinating institution, and the median number of institutions per trial was one. The median expected start year for all trials was 2021, and the completion year was 2024. To date, there have been no results (interim or final) formally reported, although preliminary reports in the literature indicate this to be a safe procedure. Anecdotal trends suggest later trials target the blood-brain barrier more, involve more pediatric patients, and are more based in the United States. Conclusion: There exists a number of early-stage clinical trials investigating FUS to treat a variety of brain tumors in pediatric patients, as well as adult patients, with a significant clinical potential to improve outcomes. To date, no official results have been published, however anecdotal evidence is promising, and a number of results are expected soon.

Correction to: Knockdown of NeuroD2 leads to seizure-like behavior, brain neuronal hyperactivity and a leaky blood-brain barrier in a Xenopus laevis tadpole model of DEE72

Correction to: Knockdown of <i>NeuroD2</i> leads to seizure-like behavior, brain neuronal hyperactivity and a leaky blood-brain barrier in a <i>Xenopus laevis</i> tadpole model of DEE72

Exploring Endothelial Cell Dysfunction's Impact on the Brain-Retina Microenvironment Connection: Molecular Mechanisms and Implications.

The intricate linking between the health of blood vessels and the functioning of neurons has attracted growing attention in the context of disorders that affect the neurological environment. Endothelial cells, forming the blood-brain barrier and blood-retinal barrier, play a fundamental role in maintaining the integrity of the brain-retina microenvironment connection. This review explores the molecular foundations of endothelial cell dysfunction and its implications for the brain-retina interaction. A comprehensive analysis of the complex factors contributing to endothelial dysfunction is presented, including oxidative stress, inflammation, reduced nitric oxide signaling, and disrupted vascular autoregulation. The significance of endothelial dysfunction extends to neurovascular coupling, synaptic plasticity, and trophic support. To our knowledge, there is currently no existing literature review addressing endothelial microvascular dysfunction and its interplay with the brain-retina microenvironment. The review also explains bidirectional communication between the brain and retina, highlighting how compromised endothelial function can disrupt this vital crosstalk and inhibit normal physiological processes. As neurodegenerative diseases frequently exhibit vascular involvement, a deeper comprehension of the interaction between endothelial cells and neural tissue holds promise for innovative therapeutic strategies. By targeting endothelial dysfunction, we may enhance our ability to preserve the intricate dynamics of the brain-retina microenvironment connection and ameliorate the progression of neurological disorders.