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

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.

The Role of Copper Overload in Modulating Neuropsychiatric Symptoms

“…The brain cells receive copper from the BBB and through the BCB, with choroid plexus cells playing a key role in regulating copper entry into the CSF and endothelial cells of intraparenchymal capillaries regulating copper entry into the brain parenchyma [ 27 ]. In recent years, the neurovascular unit (NVU) has been introduced in the literature as a collective term including all cell types participating in the integrity of the BBB: brain microvascular endothelial cells (BMECs), pericytes, astrocytes, neurons, microglia, and oligodendrocytes [ 28 ]. The highest rate of copper ions’ transport into the brain parenchyma, compared to the CSF, clearly indicates that the BBB is the principal site through which copper enters the CNS [ 29 ].…”

Presenilin: A Multi-Functional Molecule in the Pathogenesis of Alzheimer’s Disease and Other Neurodegenerative Diseases

“…The blood-brain barrier (BBB) is essential for maintaining the brain's microenvironment. Recent studies have revealed that presenilin is involved in BBB integrity through interactions with a reduced barrier function, reduced drug efflux pump activity, and dimin-ished glucose metabolism [47,48] Dysfunction of the BBB can lead to increased neuroinflammation and infiltration of peripheral immune cells, exacerbating AD pathology [49].…”

Emerging Perspectives on Prime Editor Delivery to the Brain

“…Research has also shown that aging, cerebrovascular accident (CVA), carcinogenetic neoplasms, infections, injuries, ischemic events, neuroinflammation, neurodegenerative diseases (i.e., AD), and hydrocephalus may compromise these protective barrier structures, permeability, and functionality and potentially increase the BBB's permeability [93][94][95].…”

“…Research has also shown that aging, cerebrovascular accident (CVA), carcinogenetic neoplasms, infections, injuries, ischemic events, neuroinflammation, neurodegenerative diseases (i.e., AD), and hydrocephalus may compromise these protective barrier structures, permeability, and functionality and potentially increase the BBB’s permeability [ 93 , 94 , 95 ]. Moreover, in vitro studies on SARS-COVID-19 SARS-CoV-2 pathogens have indicated that the pathogens’ S1 and S2 spike proteins trigger a pro-inflammatory reaction in brain endothelial cells, potentially leading to alterations in BBB functionality [ 96 , 97 , 98 , 99 , 100 ].…”