CD98hc is a target for brain delivery of biotherapeutics.

Brain exposure of systemically administered biotherapeutics is highly restricted by the blood-brain barrier (BBB). Here, we report the engineering and characterization of a BBB transport vehicle targeting the CD98 heavy chain (CD98hc or SLC3A2) of heterodimeric amino acid transporters (TV). The pharmacokinetic and biodistribution properties of a CD98hc antibody transport vehicle (ATV) are assessed in humanized CD98hc knock-in mice and cynomolgus monkeys.

Expression of ABCB1, ABCC1 and 3 and ABCG2 in glioblastoma and their relevance in relation to clinical survival surrogates.

Purpose: Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumors in adults. Patients invariably relapse during or after first-line therapy and the median overall survival is 14.6 months.

Neuronal Activity Regulates Blood-Brain Barrier Efflux Transport through Endothelial Circadian Genes.

The blood vessels in the central nervous system (CNS) have a series of unique properties, termed the blood-brain barrier (BBB), which stringently regulate the entry of molecules into the brain, thus maintaining proper brain homeostasis. We sought to understand whether neuronal activity could regulate BBB properties. Using both chemogenetics and a volitional behavior paradigm, we identified a core set of brain endothelial genes whose expression is regulated by neuronal activity.

Multidimensional Proteome Profiling of Blood-Brain Barrier Perturbation by Group B .

Group B (GBS) remains the leading cause of neonatal meningitis, a disease associated with high rates of adverse neurological sequelae. The relationship between GBS and brain tissues remains poorly characterized, partly because past studies had focused on microbial rather than host processes. Additionally, the field has not capitalized on systems-level technologies to probe the host-pathogen relationship.

The amazing brain drain.

In this issue of JEM, Antila et al. (https://doi.org/10.

Formation and maintenance of the BBB.

The central nervous system (CNS) is vascularized by a dense capillary network that is critical to deliver oxygen and nutrients, and remove carbon dioxide and waste products, from the neural tissue. These blood vessels contain a series of properties, termed the blood-brain barrier (BBB), which distinguishes them from vasculature in other tissues, enabling CNS vessels to stringently regulate the transfer of ions, molecules and cells between the blood and the tissue. This barrier is critical to maintain brain homeostasis which allows for proper neuronal function and also to protect the tissue from injury and disease and many neurological diseases are associated with BBB dysfunction, including traumatic brain injuries, Alzheimer's disease, stroke, epilepsy, and multiple sclerosis.

Optimization of the reference region method for dual pharmacokinetic modeling using Gd-DTPA/MRI and (18) F-FDG/PET.

Purpose: The combination of MRI and positron emission tomography (PET) offers new possibilities for the development of novel methodologies. In pharmacokinetic image analysis, the blood concentration of the imaging compound as a function of time, [i.e.

Impact of drug size on brain tumor and brain parenchyma delivery after a blood-brain barrier disruption.

Drug delivery to the brain is influenced by the blood-brain barrier (BBB) and blood-tumor barrier (BTB) to an extent that is still debated in neuro-oncology. In this paper, we studied the delivery across the BTB and the BBB of compounds with different molecular sizes in normal and glioma-bearing rats. Studies were performed at baseline as well as after an osmotic BBB disruption (BBBD) using dynamic contrast-enhanced magnetic resonance imaging and two T₁ contrast agents (CAs), Magnevist (743 Da) and Gadomer (17,000 Da).

Conversion of arterial input functions for dual pharmacokinetic modeling using Gd-DTPA/MRI and 18F-FDG/PET.

Reaching the full potential of magnetic resonance imaging (MRI)-positron emission tomography (PET) dual modality systems requires new methodologies in quantitative image analyses. In this study, methods are proposed to convert an arterial input function (AIF) derived from gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) in MRI, into a (18)F-fluorodeoxyglucose ((18)F-FDG) AIF in PET, and vice versa. The AIFs from both modalities were obtained from manual blood sampling in a F98-Fisher glioblastoma rat model.

A new method of quantitatively assessing the opening of the blood-brain barrier in murine animal models.

The blood-brain barrier (BBB) restricts the delivery of drugs into the brain. Different strategies have been developed to circumvent this obstacle. One such approach, the osmotic BBB disruption (BBBD), has been under pre-clinical study since the 70's.

Blood-brain barrier disruption in the treatment of brain tumors.

Standard chemotherapy administered systemically has a limited efficacy in the treatment of brain tumors. One of the major obstacles in the treatment of brain neoplasias is the impediment to delivery across the intact blood-brain barrier (BBB). Many innovative approaches have been developed to circumvent this obstacle.

Real-time monitoring of gadolinium diethylenetriamine penta-acetic acid during osmotic blood-brain barrier disruption using magnetic resonance imaging in normal wistar rats.

Objective: Treatment of malignant gliomas is hampered by several factors, one of which is the blood-brain barrier (BBB). Thus, innovative strategies to cross the BBB have been developed, such as the BBB disruption procedure. Although it has been studied extensively, details regarding the physiology of the procedure remain obscure.

Recent advances in blood-brain barrier disruption as a CNS delivery strategy.

The blood-brain barrier (BBB) is a complex functional barrier composed of endothelial cells, pericytes, astrocytic endfeets and neuronal cells. This highly organized complex express a selective permeability for molecules that bear, amongst other parameters, adequate molecular weight and sufficient liposolubility. Unfortunately, very few therapeutic agents currently available do cross the BBB and enters the CNS.