In Vitro Blood–Brain Barrier-Integrated Neurological Disorder Models Using a Microfluidic Device

Abstract

The blood–brain barrier (BBB) plays critical role in the human physiological system such as protection of the central nervous system (CNS) from external materials in the blood vessel, including toxicants and drugs for several neurological disorders, a critical type of human disease. Therefore, suitable in vitro BBB models with fluidic flow to mimic the shear stress and supply of nutrients have been developed. Neurological disorder has also been investigated for developing realistic models that allow advance fundamental and translational research and effective therapeutic strategy design. Here, we discuss introduction of the blood–brain barrier in neurological disorder models by leveraging a recently developed microfluidic system and human organ-on-a-chip system. Such models could provide an effective drug screening platform and facilitate personalized therapy of several neurological diseases.

Recent Developments in Microfluidic Technologies for Central Nervous System Targeted Studies

“…Appropriate endpoints for readouts also need to be established [122]. Progresses in each of these areas will allow the creation of more high-end, sophisticated, but still, nonetheless, practical platforms, that can facilitate the early diagnosis of various NDs and the development of effective therapeutic agents [6].…”

“…The BBB is a highly complex dynamic interface between the bloodstream and the brain, effectively protecting the CNS from potentially harmful external elements and maintaining cerebral homeostasis [6,7]. BBB disruption, linked with increased permeability, impairment of influx/efflux mechanisms and infiltration of toxins and immune cells in the CNS, is a common factor to many NDs [7].…”

“…BBB disruption, linked with increased permeability, impairment of influx/efflux mechanisms and infiltration of toxins and immune cells in the CNS, is a common factor to many NDs [7]. The establishment of in vitro biomimetic platforms that can precisely replicate the functional/structural properties of the BBB and enable the monitoring of changes to its integrity, could therefore enhance the understanding of NDs, as well as accelerate the research and development of innovative therapies [6,7]. Ideally, to faithfully recapitulate the human brain endothelium, in vitro BBB models should possess some of its essential features, including interactions between different types of cells (e.g., vascular endothelial cells, astrocytes and pericytes), a 3D vessel-like structure of the endothelial cells, the presence of a basement membrane and flow-induced sheer stress [6,7].…”

Modeling Alpha-Synuclein Pathology in a Human Brain-Chip to Assess Blood-Brain Barrier Disruption in Parkinson’s Disease

“…Organs-on-Chips enable the recreation of a more physiological mircroenvironement, including coculture of cells on tissue-specific extracellular matrices (ECM), the application of flow to enable a dynamic microenvironment and in vivo-relevant mechanical forces such as fluidic sheer stress. There have been several approaches to model the Blood-Brain Barrier (BBB) in a chip, with models that have been designed to reconstitute the cerebrovascular interface, however they often have not included combinations of key cell types, such as region-specific neurons, astrocytes, and microglia, to more fully reconstruct the complex physiology of neurovascular unit milieu [30][31][32][33][34] .…”

Resveratrol targeting tau proteins, amyloid‐beta aggregations, and their adverse effects: An updated review

“…The estimates demonstrate the enhanced incidence rate of NDs and annually, a high number of individuals are diagnosed with NDs. It seems that this trend is going to be ascending in the following years, demanding new strategies in treatment, management and prevention of NDs (Choi, Santhosh, & Choi, 2020). A number of symptoms are associated with NDs including seizures, pain, loss of consciousness, low coordination, paralysis, and muscle weakness.…”