Blood brain barrier

Saposhnikoviae Radix (SR) may enhance the pharmacodynamics of Huangqi Chifeng Tang (HQCFT) in the treatment of cerebral infarction according to our previous research, but the underlying mechanism is unknown. Herein, an in vivo pharmacokinetic assay in rats and in vitro MDCK-MDR1 cell assays were used to investigate the possible mechanism of SR, its main components, and its interactions with Astragali Radix (AR) and Paeoniae Radix (PR). An ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC‒MS/MS)-based analytical method for quantifying astragaloside IV (ASIV) and paeoniflorin (PAE) in microdialysis and transport samples was developed...

Tumor Treating Fields (TTFields) extend the survival of glioblastoma (GBM) patients by interfering with a broad range of tumor cellular processes. Among these, TTFields disrupt primary cilia stability on GBM cells. Here we asked if concomitant treatment of TTFields with other agents that interfere with GBM ciliogenesis further suppress GBM cell proliferation in vitro. Aurora kinase A (AURKA) promotes both cilia disassembly and GBM growth. Inhibitors of AURKA, such as Alisertib, inhibit cilia disassembly and increase ciliary frequency in various cell types...

Human heavy-chain ferritin is a naturally occurring protein with high stability and multifunctionality in biological systems. This study aims to utilize a prokaryotic expression system to produce recombinant human heavy-chain ferritin nanoparticles and investigate their targeting ability in brain tissue. The human heavy-chain ferritin gene was cloned into the prokaryotic expression vector pET28a and transformed into Escherichia coli BL21 (DE3) competent cells to explore optimal expression conditions. The recombinant protein was then purified to evaluate its immunoreactivity and characteristics...

Leptomeningeal metastasis (LM) is a devastating complication of advanced non-small cell lung cancer (NSCLC). Diagnosis and monitoring of LM can be challenging. Extracellular vesicles (EVs) microRNAs (miRNAs) have become a new noninvasive diagnostic biomarker. The purpose of this study was to examine the clinical value and role of EVs miRNAs in NSCLC-LM. According to next-generation sequencing (NGS), miRNAs with differential expression of EVs in serum of NSCLC patients with LM and non-LM were detected to find biological markers for the diagnosis of LM...

Cerebral microhemorrhages (CMHs, also known as cerebral microbleeds) are a critical but frequently underestimated aspect of cerebral small vessel disease (CSVD), bearing substantial clinical consequences. Detectable through sensitive neuroimaging techniques, CMHs reveal an extensive pathological landscape. They are prevalent in the aging population, with multiple CMHs often being observed in a given individual. CMHs are closely associated with accelerated cognitive decline and are increasingly recognized as key contributors to the pathogenesis of vascular cognitive impairment and dementia (VCID) and Alzheimer's disease (AD)...

Annexins, a group of Ca2+ -dependent phospholipid-binding proteins, exert diverse roles in neuronal development, normal central nervous system (CNS) functioning, neurological disorders, and CNS tumors. This paper reviews the roles of individual annexins (A1-A13) in these contexts. Annexins possess unique structural and functional features, such as Ca2+ -dependent binding to phospholipids, participating in membrane organization, and modulating cell signaling. They are implicated in various CNS processes, including endocytosis, exocytosis, and stabilization of plasma membranes...

Aim: This study aims to investigate the passive diffusion of protein kinase inhibitors through the blood-brain barrier (BBB) and to develop a model for their permeability prediction. Materials & methods: We used the parallel artificial membrane permeability assay to obtain logPe values of each of 34 compounds and calculated descriptors for these structures to perform quantitative structure-property relationship modeling, creating different regression models. Results: The logPe values have been calculated for all 34 compounds...

SARS-CoV-2-induced excessive inflammation in brain leads to damage of blood-brain barrier, hypoxic-ischemic injury, and neuron degeneration. The production of inflammatory cytokines by brain microvascular endothelial cells and microglia is reported to be critically associated with the brain pathology of COVID-19 patients. However, the cellular mechanisms for SARS-CoV-2-inducing activation of brain cells and the subsequent neuroinflammation remain to be fully delineated. Our research, along with others', has recently demonstrated that SARS-CoV-2-induced accumulation and activation of mast cells (MCs) in mouse lung could further induce inflammatory cytokines and consequent lung damages...

[This corrects the article DOI: 10.3389/fnmol.2022.895429.].

During neuroinflammation, the proinflammatory cytokine interleukin-1β (IL-1β) impacts blood-brain barrier (BBB) function by disrupting brain endothelial tight junctions, promoting vascular permeability, and increasing transmigration of immune cells. Here, we examined the effects of Il-1β on the in vivo initiation of BBB development. We generated doxycycline-inducible transgenic zebrafish to secrete Il-1β in the CNS. To validate the utility of our model, we showed Il-1β dose-dependent mortality, recruitment of neutrophils, and expansion of microglia...

N-methyl-D-aspartate (NMDA) receptors, i.e., inotropic glutamate receptors, are important in synaptic plasticity, brain growth, memory, and learning. The activation of NMDA is done by neurotransmitter glutamate and co-agonist (glycine or D-serine) binding. However, the over-activation of NMDA elevates the intracellular calcium influx, which causes various neurological diseases and disorders. Therefore, to prevent excitotoxicity and neuronal death, inhibition of NMDA must be done using its antagonist. This review delineates the structure of subunits of NMDA and the conformational changes induced after the binding of agonists (glycine and D-serine) and antagonists (ifenprodil, etc...

BACKGROUND: The blood-brain barrier serves as a critical interface between the bloodstream and brain tissue, mainly composed of pericytes, neurons, endothelial cells, and tightly connected basal membranes. It plays a pivotal role in safeguarding brain from harmful substances, thus protecting the integrity of the nervous system and preserving overall brain homeostasis. However, this remarkable selective transmission also poses a formidable challenge in the realm of central nervous system diseases treatment, hindering the delivery of large-molecule drugs into the brain...

Advancements in technology and technical expertise increasingly enable neurointerventionalists to deliver safer and more effective endovascular treatments to cancers of the brain, spine, head, and neck. In addition to established neuro-oncological interventions such as pre-surgical tumor embolization and percutaneous ablation, newer modalities focused on direct arterial infusion of chemotherapy, radioisotopes, and radiosensitizers continue to gain traction as complementary treatment options, while stem cell-mediated delivery of theranostic nanoparticles and oncolytic virus are being explored for even greater specificity in targeting cancers across the blood-brain barrier...

Intracerebral haemorrhage (ICH) presents significant challenges in clinical management because of the high morbidity and mortality, necessitating novel therapeutic approaches. This study aimed to assess the neuroprotective effects of loganin in a rat ICH model. Sprague-Dawley rats were used, subjected to a collagenase-induced ICH model, followed by loganin treatment at doses of 2.5, 5 and 10 mg/kg. Neurological functions were evaluated using the modified neurological severity score (mNSS) and a rotarod test...

OBJECTIVE: Low-density lipoprotein receptor-related protein-1 (LRP1) regulates energy homeostasis, blood-brain barrier integrity, and metabolic signaling in the brain. Deficiency of LRP1 in inhibitory gamma-aminobutyric acid (GABA)ergic neurons causes severe obesity in mice. However, the impact of LRP1 in inhibitory neurons on memory function and cognition in the context of obesity is poorly understood. METHODS: Mice lacking LRP1 in GABAergic neurons (Vgat-Cre; LRP1loxP/loxP ) underwent behavioral tests for locomotor activity and motor coordination, short/long-term and spatial memory, and fear learning/memory...

The role of microglia in triggering the blood-brain barrier (BBB) impairment and white matter damage after chronic cerebral hypoperfusion is unclear. Here we demonstrated that the vessel-adjacent microglia were specifically activated by the leakage of plasma low-density lipoprotein (LDL), which led to BBB breakdown and ischemic demyelination. Interestingly, we found that LDL stimulation enhanced microglial phagocytosis, causing excessive engulfment of myelin debris and resulting in an overwhelming lipid burden in microglia...

Previously, we demonstrated that linear peptide epoxyketones targeting the immunoproteasome (iP) could ameliorate cognitive deficits in mouse models of Alzheimer's disease (AD) independently of amyloid deposition. We also reported the first iP-targeting macrocyclic peptide epoxyketones, which exhibit improved metabolic stability compared with their linear counterparts. Here, we prepared additional macrocyclic peptide epoxyketones and compared them with existing macrocyclic iP inhibitors by assessing Caco2 cell-based permeability and microsomal stability, providing the four best macrocyclic iP inhibitors...

The blood-brain barrier (BBB) presents a formidable challenge in delivering therapeutic agents to the central nervous system. Ultrasound-mediated BBB disruption has emerged as a promising non-invasive technique to enhance drug delivery to the brain. This manuscript reviews fundamental principles of ultrasound-based techniques and their mechanisms of action in temporarily permeabilizing the BBB. Clinical trials employing ultrasound for BBB disruption are discussed, summarizing diverse applications ranging from the treatment of neurodegenerative diseases to targeted drug delivery for brain tumors...

The development of seizures in epilepsy syndromes associated with malformations of cortical development (MCDs) has traditionally been attributed to intrinsic cortical alterations resulting from abnormal network excitability. However, recent analyses at single-cell resolution of human brain samples from MCD patients have indicated the possible involvement of adaptive immunity in the pathogenesis of these disorders. By exploiting the MethylAzoxyMethanol (MAM)/pilocarpine (MP) rat model of drug-resistant epilepsy associated with MCD, we show here that the occurrence of status epilepticus and subsequent spontaneous recurrent seizures in the malformed, but not in the normal brain, are associated with the outbreak of a destructive autoimmune response with encephalitis-like features, involving components of both cell-mediated and humoral immune responses...

Although oligodendrocytes (OLs) synthesize laminin-γ1, the most widely used γ subunit, its functional significance in the CNS remains unknown. To answer this important question, we generated a conditional knockout mouse line with laminin-γ1 deficiency in OL lineage cells (γ1-OKO). γ1-OKO mice exhibit weakness/paralysis and die by post-natal day 33. Additionally, they develop blood-brain barrier (BBB) disruption in the cortex and striatum. Subsequent studies reveal decreased major facilitator superfamily domain containing 2a expression and increased endothelial caveolae vesicles, but unaltered tight junction protein expression and tight junction ultrastructure, indicating a transcellular, rather than a paracellular, mechanism of BBB breakdown...