International Journal of Molecular Sciences

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Special Issue Editor

Dr. Monique F. Stins

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Guest Editor

1. Associate Professor, Biomedical Research Institute of Southern California, Oceanside, CA, USA
2. Associate Professor, Adj. Department Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
3. Associate Professor, Adj. Department Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA
Interests: blood–brain barrier, neuro-infectious diseases, e.g., cerebral malaria, Plasmodium, neurologic sequelae, heterogeneity of cerebral vasculature, differential pathology, white matter versus gray matter; neuronal dysfunction

Special Issue Information

Dear Colleagues,

The blood–brain barrier is situated at the interface of the central nervous system (CNS) and the periphery and protects the brain from undue influences, thus guaranteeing optimal neuronal functioning. However, many peripheral microbial diseases, including COVID19, bacteria, their toxic components, and organ activation, such as intestinal or kidney inflammation, influence the blood–brain barrier (BBB). This can result in the inflammation of the BBB endothelium with an increased release of chemokines and cytokines, an elevated presence of cell adhesion molecules, and alterations of the integrity of the BBB, leading to an influx of plasma components and/or immune cells into the brain.

Changes in the functionality of the BBB have been associated with various neurological conditions, such as epilepsy, amyotrophic lateral sclerosis, multiple sclerosis, neuro-infections, such as HIV infection, Lyme disease, cerebral malaria and COVID-19. Blunt force trauma induced by sports or accidents, stroke, tumors, sickle cell disorders and age-related neurological conditions such as Parkinson’s disease and Alzheimer’s disease also have components of BBB endothelial dysfunction. More recently, psychiatric disorders have also been associated with an altered BBB function.

Although the role of the BBB endothelium in these various disorders and conditions is receiving more and more attention, many gaps in our knowledge exist.

Neuroprotective treatments for these various neurological conditions are very limited. There is a great demand for novel neuroprotective approaches, and for strategies that improve drug delivery to the CNS. In addition, to better understand regional differences in the various neuropathologies, improved knowledge of BBB heterogeneity is needed. A better understanding of BBB heterogeneity may also aid in the improvement of pharmacological therapies and the more targeted delivery of neuroprotective drugs to the affected brain regions.

We welcome submissions to this Special Issue of IJMS that address the basic and clinical neuropathological disease processes and highlight their underlying biomolecular science.

Dr. Monique F. Stins
Guest Editor

Manuscript Submission Information

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Keywords

blood–brain barrier
neuro-infectious diseases
cerebral malaria
Plasmodium
cerebral vasculature
vascular heterogeneity
white matter
gray matter

Published Papers (2 papers)

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Research

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24 pages, 2627 KiB

Open AccessArticle

Anti-Inflammatory Action of Resveratrol in the Central Nervous System in Relation to Glucose Concentration—An In Vitro Study on a Blood–Brain Barrier Model

by Justyna Komorowska, Mateusz Wątroba, Małgorzata Bednarzak, Anna D. Grabowska and Dariusz Szukiewicz

Int. J. Mol. Sci. 2024, 25(6), 3110; https://doi.org/10.3390/ijms25063110 - 7 Mar 2024

Viewed by 863

Abstract

Unbalanced blood glucose levels may cause inflammation within the central nervous system (CNS). This effect can be reversed by the action of a natural neuroprotective compound, resveratrol (RSV). The study aimed to investigate the anti-inflammatory effect of RSV on astrocyte cytokine profiles within an in vitro model of the blood–brain barrier (BBB) under varying glucose concentrations (2.2, 5.0, and 25.0 mmol/L), corresponding to hypo-, normo-, and hyperglycemia. The model included co-cultures of astrocytes (brain compartment, BC) and endothelial cells (microvascular compartment, MC), separated by 0.4 µm wide pores. Subsequent exposure to 0.2 μM LPS in the brain compartment (BC) and 50 μM RSV in the microvascular compartment (MC) of each well was carried out. Cytokine levels (IL-1 α, IL-1 β, IL-2, IL-4, IL-6, IL-8) in the BC were assessed using a Multi-Analyte ELISArray Kit before and after the addition of LPS and RSV. Statistical analysis was performed to determine significance levels. The results demonstrated that RSV reduced the concentration of all studied cytokines in the BC, regardless of glucose levels, with the most substantial decrease observed under normoglycemic conditions. Additionally, the concentration of RSV in the BC was highest under normoglycemic conditions compared to hypo- and hyperglycemia. These findings confirm that administration of RSV in the MC exerts anti-inflammatory effects within the BC, particularly under normoglycemia-simulating conditions. Further in vivo studies, including animal and human research, are warranted to elucidate the bioavailability of RSV within the central nervous system (CNS). Full article

(This article belongs to the Special Issue Activation of the Blood–Brain Barrier and Neurological Dysfunction)

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Review

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40 pages, 4629 KiB

Open AccessReview

Blood–Brain Barrier Breakdown in Neuroinflammation: Current In Vitro Models

by Sarah Brandl and Markus Reindl

Int. J. Mol. Sci. 2023, 24(16), 12699; https://doi.org/10.3390/ijms241612699 - 11 Aug 2023

Cited by 3 | Viewed by 3789

Abstract

The blood–brain barrier, which is formed by tightly interconnected microvascular endothelial cells, separates the brain from the peripheral circulation. Together with other central nervous system-resident cell types, including pericytes and astrocytes, the blood–brain barrier forms the neurovascular unit. Upon neuroinflammation, this barrier becomes leaky, allowing molecules and cells to enter the brain and to potentially harm the tissue of the central nervous system. Despite the significance of animal models in research, they may not always adequately reflect human pathophysiology. Therefore, human models are needed. This review will provide an overview of the blood–brain barrier in terms of both health and disease. It will describe all key elements of the in vitro models and will explore how different compositions can be utilized to effectively model a variety of neuroinflammatory conditions. Furthermore, it will explore the existing types of models that are used in basic research to study the respective pathologies thus far. Full article

(This article belongs to the Special Issue Activation of the Blood–Brain Barrier and Neurological Dysfunction)

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