High-dose acetaminophen does not acutely compromise blood-brain barrier permeability in mice.

Acetaminophen is widely recognized for its safety as a pain reliever and fever reducer at recommended doses. However, in addition to the well-known hepatotoxic and nephrotoxic effects at overdoses recent animal studies in rats have raised the possibility that acetaminophen at a high dose of 500 mg/kg may lead to acute impairment of the blood-brain barrier (BBB). Because species differences in hepatic and renal toxicity of acetaminophen are present, we assessed here the effect of moderate and severe overdoses of acetaminophen (300 mg/kg and 600 mg/kg, respectively) after intraperitoneal administration in mice on BBB permeability.

Discovery of pan-EphB tyrosine kinase inhibitor for metabolic syndrome sparing EphB3 signaling in mice.

The global prevalence of metabolic syndrome had created one of the most pressing public health dilemmas and significant financial burden to the healthcare system. Despite the surge of glucagon-like peptide-1 agonists, recent studies showed that 40 % of body weight loss is due to lean mass loss, raising the concern about induction of musculoskeletal arthritis. Therefore, there is an urgent need to develop novel therapeutic strategies to tackle the progression of metabolic disorders with minimal adverse effects.

Assessing blood-brain barrier (BBB) integrity in an Alzheimer's disease mouse model: is the BBB globally or locally disrupted?

Alzheimer's disease (AD), marked by amyloid-beta (Aβ) plaques and tau tangles, involves cerebral amyloid angiopathy (CAA), which may compromise blood-brain barrier (BBB) integrity. However, the extent and nature of BBB disruption in AD remain unclear. This study assessed BBB permeability in Tg2576 AD mice by evaluating unidirectional paracellular transport from blood to brain following intravenous injection of the stable isotope-labeled marker [¹³C₁₂]sucrose.

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.

Evaluation of systemic and brain pharmacokinetic parameters for repurposing metformin using intravenous bolus administration.

Metformin's potential in treating ischemic stroke and neurodegenerative conditions is of growing interest. Yet, the absence of established systemic and brain pharmacokinetic (PK) parameters at relevant preclinical doses presents a significant knowledge gap. This study highlights these PK parameters and the importance of using pharmacologically relevant preclinical doses to study pharmacodynamics in stroke and related neurodegenerative diseases.

The Acute Impact of Propofol on Blood-Brain Barrier Integrity in Mice.

Purpose: We investigated whether short term infusion of propofol, a highly lipophilic agonist at GABA receptors, which is in widespread clinical use as anesthetic and sedative, affects passive blood-brain barrier (BBB) permeability in vivo.

Methods: Mice were anesthetized with an intraperitoneal injection of ketamine/xylazine followed by a continuous IV infusion of propofol in lipid emulsion through a tail vein catheter. Control groups received ketamine/xylazine anesthesia and an infusion of Intralipid, or ketamine/xylazine anesthesia only.

Higher Brain Uptake of Gentamicin and Ceftazidime under Isoflurane Anesthesia Compared to Ketamine/Xylazine.

We have recently shown that the volatile anesthetics isoflurane and sevoflurane acutely enhance the brain uptake of the hydrophilic markers sucrose and mannitol about two-fold from an awake condition, while the combined injection of the anesthetic agents ketamine and xylazine has no effect. The present study investigated two small-molecule hydrophilic drugs with potential neurotoxicity, the antibiotic agents ceftazidime and gentamicin. Transport studies using an in vitro blood-brain barrier (BBB) model, a monolayer of induced pluripotent stem cell-derived human brain microvascular endothelial cells seeded on Transwells, and LC-MS/MS analysis demonstrated the low permeability of both drugs in the range of sucrose, with permeability coefficients of 6.

Systemic and Brain Pharmacokinetics of Milnacipran in Mice: Comparison of Intraperitoneal and Intravenous Administration.

Milnacipran is a dual serotonin and norepinephrine reuptake inhibitor, clinically used for the treatment of major depression or fibromyalgia. Currently, there are no studies reporting the pharmacokinetics (PK) of milnacipran after intraperitoneal (IP) injection, despite this being the primary administration route in numerous experimental studies using the drug. Therefore, the present study was designed to investigate the PK profile of IP-administered milnacipran in mice and compare it to the intravenous (IV) route.

Electrochemical and optical (bio)sensors for analysis of antibiotic residuals.

Antibiotic residuals in foods may lead to crucial health and safety issues in the human body. Rapid and in-time analysis of antibiotics using simple and sensitive techniques is in high demand. Among the most commonly applicable modalities, chromatography-based techniques like HPLC and LC-MS, along with immunological approaches, particularly ELISA have been exampled in the analysis of antibiotics.

Effects of Volatile Anesthetics versus Ketamine on Blood-Brain Barrier Permeability via Lipid-Mediated Alterations of Endothelial Cell Membranes.

The purpose of this study was to investigate the effects of the volatile anesthetic agents isoflurane and sevoflurane, at clinically relevant concentrations, on the fluidity of lipid membranes and permeability of the blood-brain barrier (BBB). We analyzed the in vitro effects of isoflurane or ketamine using erythrocyte ghosts (sodium fluorescein permeability), monolayers of brain microvascular endothelial cells ([C]sucrose and fluorescein permeability), or liposomes (fluorescence anisotropy). Additionally, we determined the effects of 30-minute exposure of mice to isoflurane on the brain tight junction proteins.

Advances in layered double hydroxide based labels for signal amplification in ultrasensitive electrochemical and optical affinity biosensors of glucose.

Since the development of enzyme electrodes, the research area of glucose biosensing has seen outstanding progress and improvement. Numerous sensing platforms have been developed based on different immobilization techniques and improved electron transfer between the enzyme and electrode. Interestingly, these platforms have consistently used innovative nanostructures and nanocomposites.

Advanced Microfluidic Vascularized Tissues as Platform for the Study of Human Diseases and Drug Development.

The vascular system plays a critical role in human physiology and diseases. It is a complex subject to study using in vitro models due to its dynamic and three-dimensional microenvironment. Microfluidic technology has recently become a popular technology in various biological fields for its advantages in mimicking complex microenvironments to an extent not achievable by more conventional platforms.

Recent trends in layered double hydroxides based electrochemical and optical (bio)sensors for screening of emerging pharmaceutical compounds.

The rapid expansion of the human population has given rise to new environmental and biomedical concerns, contributing to different advancements in the pharmaceutical industry. In the field of analytical chemistry over the last few years, layered double hydroxides (LDHs) have drawn significant attention, owing to their extraordinary properties. Furthermore, the novel advancement of LDH-based optical and electrochemical platforms to detect different pharmaceutical materials has acquired substantial attention because of their outstanding specificity, actual-time controlling, and user-friendliness.

A Semi-Physiological Three-Compartment Model Describes Brain Uptake Clearance and Efflux of Sucrose and Mannitol after IV Injection in Awake Mice.

Purpose: To evaluate a three-compartmental semi-physiological model for analysis of uptake clearance and efflux from brain tissue of the hydrophilic markers sucrose and mannitol, compared to non-compartmental techniques presuming unidirectional uptake.

Methods: Stable isotope-labeled [C]sucrose and [C]mannitol (10 mg/kg each) were injected as IV bolus into the tail vein of awake young adult mice. Blood and brain samples were taken after different time intervals up to 8 h.

A Quasi-Physiological Microfluidic Blood-Brain Barrier Model for Brain Permeability Studies.

Microfluidics-based organ-on-a-chip technology allows for developing a new class of in-vitro blood-brain barrier (BBB) models that recapitulate many hemodynamic and architectural features of the brain microvasculature not attainable with conventional two-dimensional platforms. Herein, we describe and validate a novel microfluidic BBB model that closely mimics the one in situ. Induced pluripotent stem cell (iPSC)-derived brain microvascular endothelial cells (BMECs) were juxtaposed with primary human pericytes and astrocytes in a co-culture to enable BBB-specific characteristics, such as low paracellular permeability, efflux activity, and osmotic responses.