Blood-brain Barrier Function Research Articles

Modular cone-and-plate device for mechanofluidic assays in Transwell inserts

In this work, we present a cost effective and open-source modular cone-and-plate (MoCAP) device that incorporates shear stress in the popular Transwell® insert system. This system acts as a lid that incorporates flow into 24-well Transwell® inserts while preserving the ability to conduct molecular profiling assays. Moreover, the MoCAP device can be rapidly reconfigured to test multiple shear stress profiles within a single device. To demonstrate the utility of the MoCAP, we conducted select assays on several different brain microvascular endothelial cell (BMEC) lines that comprise models of the blood-brain barrier (BBB), since shear stress can play an important role in BBB function. Our results characterize how shear stress modulates passive barrier function and GLUT1 expression across the different BMEC lines. Overall, we anticipate this low cost mechanofluidic device will be useful to the mechanobiology community.

Diabetes Mellitus Impairs Blood-Brain Barrier Integrality and Microglial Reactivity.

Diabetes mellitus (DM), a chronic metabolic disorder that adversely affects the blood-brain barrier (BBB) and microglial function in the central nervous system (CNS), contributing to neuronal damage and neurodegenerative diseases. However, the underlying molecular mechanisms linking diabetes to BBB dysfunction and microglial dysregulation remain poorly understood. Here, we assessed the impacts of diabetes on BBB and microglial reactivity and investigated its mechanisms. We found diabetes severely disrupted the BBB integrity and microglial response to vascular injury. We also revealed a potential relationship between BBB disruption and impaired microglial function, whereby increasing BBB permeability led to a downregulation of microglial P2RY12 expression, thereby impairing microglial protection against cerebrovascular injury. Understanding these mechanisms may contribute to the developing of therapeutic strategies for diabetes-related neurological complications.

Nutrition: A non-negligible factor in the pathogenesis and treatment of Alzheimer's disease.

Alzheimer's disease (AD) is a degenerative disease characterized by progressive cognitive dysfunction. The strong link between nutrition and the occurrence and progression of AD pathology has been well documented. Poor nutritional status accelerates AD progress by potentially aggravating amyloid beta (Aβ) and tau deposition, exacerbating oxidative stress response, modulating the microbiota-gut-brain axis, and disrupting blood-brain barrier function. The advanced stage of AD tends to lead to malnutrition due to cognitive impairments, sensory dysfunctions, brain atrophy, and behavioral and psychological symptoms of dementia (BPSD). This, in turn, produces a vicious cycle between malnutrition and AD. This review discusses how nutritional factors and AD deteriorate each other from the early stage of AD to the terminal stages of AD, focusing on the potential of different levels of nutritional factors, ranging from micronutrients to diet patterns. This review provides novel insights into reducing the risk of AD, delaying its progression, and improving prognosis. HIGHLIGHTS: Two-fifths of Alzheimer's disease (AD) cases worldwide have been attributed to potentially modifiable risk factors. Up to ≈26% of community-dwelling patients with AD are malnourished, compared to 7%∼76% of institutionalized patients. Undernutrition effects the onset, progression, and prognosis of AD through multiple mechanisms. Various levels of nutritional supports were confirmed to be protective factors for AD via specific mechanisms.

Effects of blood-brain barrier opening using ultrasound on tauopathies: A systematic review.

This systematic review, conducted through searches using Pubmed, Embase, Web of Science and Cochrane Central databases, extracted results of 15 studies reporting effects of blood-brain barrier opening using ultrasound on tau proteins. This review of the literature indicates that blood-brain barrier opening using ultrasound can decrease the extent of the tau pathology or potentialize the effect of a therapeutic drug. However, selected studies report paradoxically that blood-brain barrier opening can increase tau pathology burden and induce brain damage. Apparent discrepancies between reports could originate from the variability in protocols or analytical methods that may impact the effects of blood-brain barrier opening with ultrasound on tauopathies, glial populations, tissue integrity and functional outcomes. This calls for a better standardization effort combined with improved methodologies allowing between-studies comparisons, and for further understanding of the effects of blood-brain barrier opening on tau pathology as an essential prerequisite before translation to clinic.

Cadmium-induced iron dysregulation contributes to functional impairment in brain endothelial cells via the ferroptosis pathway.

Cadmium (Cd2+) is a heavy metal that is a major hazardous environmental contaminant, ubiquitously present in the environment. Cd2+ exposure has been closely associated with an increased prevalence and severity of neurological and cardiovascular diseases (CVD). The blood-brain barrier (BBB) plays a crucial role in protecting the brain from external environmental factors. Mitochondria play an important role in maintaining the barrier function of brain endothelial cells by regulating energy metabolism and redox homeostasis. In this study, we aimed to assess the cytotoxic effects of Cd2+ on the integrity and function of brain endothelial cells. After 24h of exposure, Cd2+ reduced cell survival, tight junction protein expression, and trans-endothelial electrical resistance (TEER) in bEnd.3 cells suggest a potential BBB integrity disruption by Cd2+ exposure. To clarify the underlying mechanism, we further investigated the role of mitochondria in iron overload-mediated cell death following Cd2+ exposure. Cd2+ induced a substantial reduction in mitochondrial basal respiration and ATP production in brain endothelial cells, suggesting mitochondrial dysfunction. In addition, Cd2+ exposure led to impaired autophagy, elevated iron levels, and increased lipid peroxidation, indicating the initiation of ferroptosis, a form of cell death triggered by iron. In summary, our research suggests that Cd2+ exposure can disrupt BBB function by causing mitochondrial dysfunction and disrupting iron homeostasis.

Inhibition of diacylglycerol lipase α induced blood-brain barrier breach in female Sprague-Dawley rats.

The endocannabinoid system's significance in maintaining blood-brain barrier (BBB) integrity under physiological and pathological conditions is suggested by several reports, but the underlying molecular mechanisms are not well understood. In this paper, we investigated the effects of depletion of 2-arachidonoylglycerol (2-AG), one of the main endocannabinoids in the central nervous system, on BBB integrity using pharmacological tools. Female Sprague-Dawley rats were injected with the diacylglycerol lipase α (DAGLα) inhibitor LEI-106 (40mg/kg, i.p.), followed by assessment of BBB integrity via in situ brain perfusion. Liquid chromatography-mass spectrometry, western immunoblotting, light transmittance experiments and pressure myography were also used to further examine the results of DAGLα blockade on the BBB and vascular reactivity. We found that DAGLα inhibition caused BBB opening in cortical brain areas, manifesting as increased sucrose transport measured by in situ brain perfusion. This was accompanied by reduced levels of 2-AG and decreased detection of the tight junction protein zonula occludens-1 (ZO-1). The protein level in cortical areas of neuronal PAS domain protein 4 (NPAS4), encoded by an activity-dependent immediate early gene, was increased without the presence of cortical spreading depression after LEI-106 administration. We also observed a significant increase in pressure-induced constriction within the parenchymal microcirculation after inhibition of DAGLα, possibly altering shear stress in the microcirculation. These results support the role of endogenous 2-AG in maintaining normal tight junction function. This improved understanding of the molecular mechanisms of endocannabinoid system function at the neurovascular unit can help to unlock the therapeutic potentials of cannabinoids in central nervous system disorders associated with BBB dysfunction. KEY POINTS: The administration of the diacylglycerol lipase α (DAGLα) inhibitor LEI-106 (40mg/kg, i.p.) induced blood-brain barrier (BBB) opening of cortical brain areas in female Sprague-Dawley rats. This BBB disruption was accompanied by reduced levels of 2-arachidonoylglycerol (2-AG) and decreased detection of the tight junction protein zonula occludens-1 (ZO-1). The protein level in cortical areas of neuronal PAS domain protein 4 (NPAS4), encoded by an activity-dependent immediate early gene, was increased without the presence of cortical spreading depression after LEI-106 administration. A significant increase in pressure-induced constriction within the parenchymal microcirculation was also observed after inhibition of DAGLα, possibly altering shear stress. These results support the role of endogenous 2-AG in maintaining normal tight junction function.

Multimodal imaging of murine cerebrovascular dynamics induced by transcranial pulse stimulation.

Transcranial pulse stimulation (TPS) is increasingly being investigated as a promising potential treatment for Alzheimer's disease (AD). Although the safety and preliminary clinical efficacy of TPS short pulses have been supported by neuropsychological scores in treated AD patients, its fundamental mechanisms are uncharted. Herein, we used a multi-modal preclinical imaging platform combining real-time volumetric optoacoustic tomography, contrast-enhanced magnetic resonance imaging, and ex vivo immunofluorescence to comprehensively analyze structural and hemodynamic effects induced by TPS. Cohorts of healthy and AD transgenic mice were imaged during and after TPS exposure at various per-pulse energy levels. TPS enhanced the microvascular network, whereas the blood-brain barrier remained intact following the procedure. Notably, higher pulse energies were necessary to induce hemodynamic changes in AD mice, arguably due to their impacted vessels. These findings shed light on cerebrovascular dynamics induced by TPS treatment, and hence are expected to assist improving safety and therapeutic outcomes. ·Transcranial pulse stimulation (TPS) facilitates transcranial wave propagation using short pulses to avoid tissue heating. ·Preclinical multi-modal imaging combines real-time volumetric optoacoustic (OA) tomography, contrast-enhanced magnetic resonance imaging (CE-MRI), and ex vivo immunofluorescence to comprehensively analyze structural and hemodynamic effects induced by TPS. ·Blood volume enhancement in microvascular networks was reproducibly observed with real-time OA imaging during TPS stimulation. ·CE-MRI and gross pathology further confirmed that the brain architecture was maintained intact without blood-brain barrier (BBB) opening after TPS exposure, thus validating the safety of the procedure. ·Higher pulse energies were necessary to induce hemodynamic changes in AD compared to wild-type animals, arguably due to their pathological vessels.

Repetitive and extensive focused ultrasound-mediated bilateral frontal blood-brain barrier opening for Alzheimer's disease.

Focused ultrasound (FUS)-mediated blood-brain barrier (BBB) opening is safe and potentially beneficial in patients with Alzheimer's disease (AD) for the removal of amyloid-beta (Aβ) plaques. However, the optimal BBB opening intervals and number of treatment sessions for clinical improvement remain undefined. Therefore, the aim of this study was to evaluate the safety and benefits of repeated and more extensive BBB opening alone. In this open-label prospective study, 6 patients with AD were enrolled from June 2022 to July 2023. FUS-mediated BBB opening was performed three times at 2-month intervals targeting the bilateral frontal lobes. 18F-florbetaben positron emission tomography (FBB-PET) was performed before the first procedure and after the third procedure. Patients were administered neuropsychological and neuropsychiatric evaluations. All 6 participants completed the study without any acute treatment-related adverse events. An extensive area of BBB opening (mean 43.1 cm3), more than twice as large as the opening volume (mean 20 cm3) in the authors' previous study, was confirmed by contrast-enhanced MRI. FBB-PET scans demonstrated a 14.9-Centiloid average decrease in Aβ plaques in 4 of the 6 participants (67%), but the Aβ plaques increased in 2 participants after BBB opening, compared with baseline. No significant changes were observed in the Korean version of the Mini-Mental State Examination in either group. Caregiver-Administered Neuropsychiatric Inventory scores improved in 5 of 6 participants (83%), indicating an improvement in neuropsychiatric symptoms. This study confirmed the safety and efficacy of more frequent and extensive bilateral frontal BBB opening over multiple sessions in patients with AD. Furthermore, this is the first clinical trial to demonstrate improvement in neuropsychiatric symptoms through BBB opening alone, without concurrent administration of antibody medications.

The Crucial Role of the Blood-Brain Barrier in Neurodegenerative Diseases: Mechanisms of Disruption and Therapeutic Implications.

The blood-brain barrier (BBB) is a crucial structure that maintains brain homeostasis by regulating the entry of molecules and cells from the bloodstream into the central nervous system (CNS). Neurodegenerative diseases such as Alzheimer's and Parkinson's disease, as well as ischemic stroke, compromise the integrity of the BBB. This leads to increased permeability and the infiltration of harmful substances, thereby accelerating neurodegeneration. In this review, we explore the mechanisms underlying BBB disruption, including oxidative stress, neuroinflammation, vascular dysfunction, and the loss of tight junction integrity, in patients with neurodegenerative diseases. We discuss how BBB breakdown contributes to neuroinflammation, neurotoxicity, and the abnormal accumulation of pathological proteins, all of which exacerbate neuronal damage and facilitate disease progression. Furthermore, we discuss potential therapeutic strategies aimed at preserving or restoring BBB function, such as anti-inflammatory treatments, antioxidant therapies, and approaches to enhance tight junction integrity. Given the central role of the BBB in neurodegeneration, maintaining its integrity represents a promising therapeutic approach to slow or prevent the progression of neurodegenerative diseases.

Single Exposure to Low-Intensity Focused Ultrasound Causes Biphasic Opening of the Blood-Brain Barrier Through Secondary Mechanisms.

Background/Objective: The blood-brain barrier (BBB) is selectively permeable, but it also poses significant challenges for treating CNS diseases. Low-intensity focused ultrasound (LiFUS), paired with microbubbles is a promising, non-invasive technique for transiently opening the BBB, allowing enhanced drug delivery to the central nervous system (CNS). However, the downstream physiological effects following BBB opening, particularly secondary responses, are not well understood. This study aimed to characterize the time-dependent changes in BBB permeability, transporter function, and inflammatory responses in both sonicated and non-sonicated brain tissues following LiFUS treatment. Methods: We employed in situ brain perfusion to assess alterations in BBB integrity and transporter function, as well as multiplex cytokine analysis to quantify the inflammatory response. Results: Our findings show that LiFUS significantly increased vascular volume and glucose uptake, with reduced P-gp function in brain tissues six hours post treatment, indicating biphasic BBB disruption. Additionally, elevated levels of pro-inflammatory cytokines, including TNF-α and IL-6, were observed in both sonicated and non-sonicated regions. A comparative analysis between wild-type and immunodeficient mice revealed distinct patterns of cytokine release, with immunodeficient mice showing lower serum concentrations of IFN-γ and TNF-α, highlighting the potential impact of immune status on the inflammatory response to LiFUS. Conclusions: This study provides new insights into the biphasic nature of LiFUS-induced BBB disruption, emphasizing the importance of understanding the timing and extent of secondary physiological changes.

Endothelial-Ercc1 DNA repair deficiency provokes blood-brain barrier dysfunction

Aging of the brain vasculature plays a key role in the development of neurovascular and neurodegenerative diseases, thereby contributing to cognitive impairment. Among other factors, DNA damage strongly promotes cellular aging, however, the role of genomic instability in brain endothelial cells (EC) and its potential effect on brain homeostasis is still largely unclear. We here investigated how endothelial aging impacts blood-brain barrier (BBB) function by using excision repair cross complementation group 1 (ERCC1)-deficient human brain ECs and an EC-specific Ercc1 knock out (EC-KO) mouse model. In vitro, ERCC1-deficient brain ECs displayed increased senescence-associated secretory phenotype expression, reduced BBB integrity, and higher sprouting capacities due to an underlying dysregulation of the Dll4-Notch pathway. In line, EC-KO mice showed more P21+ cells, augmented expression of angiogenic markers, and a concomitant increase in the number of brain ECs and pericytes. Moreover, EC-KO mice displayed BBB leakage and enhanced cell adhesion molecule expression accompanied by peripheral immune cell infiltration into the brain. These findings were confined to the white matter, suggesting a regional susceptibility. Collectively, our results underline the role of endothelial aging as a driver of impaired BBB function, endothelial sprouting, and increased immune cell migration into the brain, thereby contributing to impaired brain homeostasis as observed during the aging process.

Coaxial bioprinting of a three-layer vascular structure exhibiting blood-brain barrier function for neuroprotective drug screening.

The in vitro blood-brain barrier (BBB) structures can offer advantages for studying cerebrovascular functions and developing neuroprotective drugs. However, currently developed BBB models are overly simplistic and inadequate for replicating the complex three-dimensional architecture of the in vivo BBB. In this study, a method is introduced for fabricating a three-layer vascular structure exhibiting BBB function using a coaxial extrusion bioprinting technique with a two-layer nozzle. Photocurable materials were incorporated into the inner layer of the coaxial nozzle, and photoinitiators from the outer layer diffused into the inner layer. As a result, only the materials in the inner layer at the interface between the inner and outer layers underwent crosslinking upon UV exposure. After removing the uncrosslinked materials, a two-layer vascular structure can be formed. Subsequently, a three-layer structure was established after seeding endothelial cells. The perfusion experiments demonstrated that the vascular structure facilitated the continuous flow of culture medium, thereby providing nutrients and oxygen to the surrounding neural tissue. The drug screening analysis indicated that this vascular structure could possess barrier function, allowing the passage of small molecular drugs while effectively blocking macromolecular drugs. Overall, these results suggest that the three-layer vascular structure exhibits excellent perfusion capacity and barrier function, making it a promising candidate for neuroprotective drug screening.

Innovative Approaches to Brain Cancer: The Use of Magnetic Resonance-guided Focused Ultrasound in Glioma Therapy.

Gliomas are a wide group of common brain tumors, with the most aggressive type being glioblastoma multiforme (GBM), with a 5-year survival rate of less than 5% and a median survival time of approximately 12-14 months. The standard treatment of GBM includes surgical excision, radiotherapy, and chemotherapy with temozolomide (TMZ). However, tumor recurrence and progression are common. Therefore, more effective treatment for GBM should be found. One of the main obstacles to the treatment of GBM and other gliomas is the blood-brain barrier (BBB), which impedes the penetration of antitumor chemotherapeutic agents into glioblastoma cells. Nowadays, one of the most promising novel methods for glioma treatment is Magnetic Resonance-guided Focused Ultrasound (MRgFUS). Low-intensity FUS causes the BBB to open transiently, which allows better drug delivery to the brain tissue. Under magnetic resonance guidance, ultrasound waves can be precisely directed to the tumor area to prevent side effects in healthy tissues. Through the open BBB, we can deliver targeted chemotherapeutics, anti-tumor agents, immunotherapy, and gene therapy directly to gliomas. Other strategies for MRgFUS include radiosensitization, sonodynamic therapy, histotripsy, and thermal ablation. FUS can also be used to monitor the treatment and progression of gliomas using blood-based liquid biopsy. All these methods are still under preclinical or clinical trials and are described in this review to summarize current knowledge and ongoing trials.

ROS Regulation in CNS Disorder Therapy: Unveiling the Dual Roles of Nanomedicine.

The treatment of brain diseases has always been the focus of attention. Due to the presence of the blood-brain barrier (BBB), most small molecule drugs are difficult to reach the brain, leading to undesirable therapeutic outcomes. Recently, nanomedicines that can cross the BBB and precisely target lesion sites have emerged as thrilling tools to enhance the early diagnosis and treat various intractable brain disorders. Extensive research has shown that reactive oxygen species (ROS) play a crucial role in the occurrence and progression of brain diseases, including brain tumors and neurodegenerative diseases (NDDs) such as Alzheimer's disease, Parkinson's disease, stroke, or traumatic brain injury, making ROS a potential therapeutic target. In this review, on the structure and function of BBB as well as the mechanisms are first elaborated through which nanomedicine traverses it. Then, recent studies on ROS production are summarizedthrough photodynamic therapy (PDT), chemodynamic therapy (CDT), and sonodynamic therapy (SDT) for treating brain tumors, and ROS depletion for treating NDDs. This provides valuable guidance for the future design of ROS-targeted nanomedicines for brain disease treatment. The ongoing challenges and future perspectives in developing nanomedicine-based ROS management for brain diseases are also discussed and outlined.

Key epigenetic and signaling factors in the formation and maintenance of the blood-brain barrier.

The blood-brain barrier (BBB) controls the movement of molecules into and out of the central nervous system (CNS). Since a functional BBB forms by mouse embryonic day E15.5, we reasoned that gene cohorts expressed in CNS endothelial cells (EC) at E13.5 contribute to BBB formation. In contrast, adult gene signatures reflect BBB maintenance mechanisms. Supporting this hypothesis, transcriptomic analysis revealed distinct cohorts of EC genes involved in BBB formation and maintenance. Here, we demonstrate that epigenetic regulator's histone deacetylase 2 (HDAC2) and polycomb repressive complex 2 (PRC2) control EC gene expression for BBB development and prevent Wnt/β-catenin (Wnt) target genes from being expressed in adult CNS ECs. Low Wnt activity during development modifies BBB genes epigenetically for the formation of functional BBB. As a Class-I HDAC inhibitor induces adult CNS ECs to regain Wnt activity and BBB genetic signatures that support BBB formation, our results inform strategies to promote BBB repair.

Engineering extracellular vesicles to transiently permeabilize the blood–brain barrier

BackgroundDrug delivery to the brain is challenging due to the restrict permeability of the blood brain barrier (BBB). Recent studies indicate that BBB permeability increases over time during physiological aging likely due to factors (including extracellular vesicles (EVs)) that exist in the bloodstream. Therefore, inspiration can be taken from aging to develop new strategies for the transient opening of the BBB for drug delivery to the brain.ResultsHere, we evaluated the impact of small EVs (sEVs) enriched with microRNAs (miRNAs) overexpressed during aging, with the capacity to interfere transiently with the BBB. Initially, we investigated whether the miRNAs were overexpressed in sEVs collected from plasma of aged individuals. Next, we evaluated the opening properties of the miRNA-enriched sEVs in a static or dynamic (under flow) human in vitro BBB model. Our results showed that miR-383-3p-enriched sEVs significantly increased BBB permeability in a reversible manner by decreasing the expression of claudin 5, an important tight junction protein of brain endothelial cells (BECs) of the BBB, mediated in part by the knockdown of activating transcription factor 4 (ATF4).ConclusionsOur findings suggest that engineered sEVs have potential as a strategy for the temporary BBB opening, making it easier for drugs to reach the brain when injected into the bloodstream.Graphical abstract

Single-cell transcriptomic analysis of glioblastoma reveals pericytes contributing to the blood-brain-tumor barrier and tumor progression.

The blood-brain barrier is often altered in glioblastoma (GBM) creating a blood-brain-tumor barrier (BBTB) composed of pericytes. The BBTB affects chemotherapy efficacy. However, the expression signatures of BBTB-associated pericytes remain unclear. We aimed to identify BBTB-associated pericytes in single-cell RNA sequencing data of GBM using pericyte markers, a normal brain pericyte expression signature, and functional enrichment. We identified parathyroid hormone receptor-1(PTH1R) as a potential marker of pericytes associated with BBTB function. These pericytes interact with other cells in GBM mainly through extracellular matrix-integrin signaling pathways. Compared with normal pericytes, pericytes in GBM exhibited upregulation of several ECM genes (including collagen IV and FN1), and high expression levels of these genes were associated with a poor prognosis. Cell line experiments showed that PTH1R knockdown in pericytes increased collagen IV and FN1 expression levels. In mice models, the expression levels of PTH1R, collagen IV, and FN1 were consistent with these trends. Evans Blue leakage and IgG detection in the brain tissue suggested a negative correlation between PTH1R expression levels and blood-brain barrier function. Further, a risk model based on differentially expressed genes in PTH1R+ pericytes had predictive value for GBM, as validated using independent and in-house cohorts.

Reversible Ca2+ signaling and enhanced paracellular transport in endothelial monolayer induced by acoustic bubbles and targeted microbeads

Ultrasound and microbubble mediated blood brain barrier opening is a non-invasive and effective technique for drug delivery to targeted brain region. However, the exact mechanisms are not fully resolved. The influences of Ca2+ signaling on sonoporation and endothelial tight junctional regulation affect the efficiency and biosafety of the technique. Therefore, an improved understanding of how ultrasound evokes Ca2+ signaling in the brain endothelial monolayer, and its correlation to endothelial permeability change is necessary. Here, we examined the effects of SonoVue microbubbles or integrin-targeted microbeads on ultrasound induced bioeffects in brain microvascular endothelial monolayer using an acoustically-coupled microscopy system, where focused ultrasound exposure and real-time recording of Ca2+ signaling and membrane perforation were performed. Microbubbles induced robust Ca2+ responses, often accompanied by cell poration, while ultrasound with microbeads elicited reversible Ca2+ response without membrane poration. At the conditions evoking reversible Ca2+ signaling, intracellular Ca2+ release and reactive oxygen species played key roles for microbubbles induced Ca2+ signaling while activation of mechanosensitive ion channels was essential for the case of microbeads. Trans-well diffusion analysis revealed significantly higher trans-endothelial transport of 70 kDa FITC-dextran for both integrin-targeted microbeads and microbubbles compared to the control group. Further immunofluorescence staining showed disruption of cell junctions with microbubble stimulation and reversible remodeling of many cell junctions by ultrasound with integrin-targeted microbeads. This investigation provides new insights for ultrasound induced Ca2+ signaling and its influence on endothelial permeability, which may help develop new strategies for safe and efficient drug/gene delivery in the vascular system.

Ultrasound blood-brain barrier opening: A new era of treatment for Alzheimer's disease?

Ultrasound blood-brain barrier opening: A new era of treatment for Alzheimer's disease?

Assessing Blood-Brain Barrier Function in the Context of Pain Management.

One essential component of the neurovascular system is known as the blood-brain barrier (BBB). This highly effective biological barrier plays a pivotal role in regulating the brain's internal microenvironment and carefully controlling the passage of various chemicals into and out of the brain. Notably, it serves as a safeguard for the brain, particularly when it comes to the selective transportation of drugs like opioids and non-steroidal anti-inflammatory medications (NSAIDs), which are commonly used in the management of chronic pain. It's important to note that during the development of chronic pain, the activation of microglia and astrocytes can potentially disrupt or damage the integrity of the BBB. In this comprehensive review, we aim to delve into the intricate interplay between the blood-brain barrier and the transportation of pain-relieving drugs, shedding light on the challenges and mechanisms involved in this process.