New experimental models of the blood-brain barrier for CNS drug discovery

Kaisar, Mohammad A.; Sajja, Ravi K.; Prasad, Shikha; Abhyankar, Vinay V.; Liles, Taylor; Cucullo, Luca

doi:10.1080/17460441.2017.1253676

Cited by 104 publications

(115 citation statements)

References 140 publications

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“…Still, the BBB has been identified as the main target for brain drug delivery, as drug delivery into the CNS requires transport across the BBB. Many in vitro BBB models, including 2D, 3D, and BBB-on-a-chip models, have been developed to characterize drug permeability [196,197], intercellular signaling, which mediates neuroinflammation [198], and mechanisms of brain tumor development and brain infections [199,200]. For example, one study conducted by Eugenin et al examined the role of human immunodeficiency virus (HIV)-infected astrocytes in BBB disruption using a 2D Transwell model [201].…”

Section: Bbb-on-a-chipmentioning

confidence: 99%

In vitro and ex vivo systems at the forefront of infection modeling and drug discovery

Shi

Wang

et al. 2019

Biomaterials

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A B S T R A C TBacterial infections and antibiotic resistant bacteria have become a growing problem over the past decade. As a result, the Centers for Disease Control predict more deaths resulting from microorganisms than all cancers combined by 2050. Currently, many traditional models used to study bacterial infections fail to precisely replicate the in vivo bacterial environment. These models often fail to incorporate fluid flow, bio-mechanical cues, intercellular interactions, host-bacteria interactions, and even the simple inclusion of relevant physiological proteins in culture media. As a result of these inadequate models, there is often a poor correlation between in vitro and in vivo assays, limiting therapeutic potential. Thus, the urgency to establish in vitro and ex vivo systems to investigate the mechanisms underlying bacterial infections and to discover new-age therapeutics against bacterial infections is dire. In this review, we present an update of current in vitro and ex vivo models that are comprehensively changing the landscape of traditional microbiology assays. Further, we provide a comparative analysis of previous research on various established organ-disease models. Lastly, we provide insight on future techniques that may more accurately test new formulations to meet the growing demand of antibiotic resistant bacterial infections. Lack of adequate model systemsCommonly, a variety of inconsistent, in vitro and in vivo models have been progressively utilized for antibiotic/drug development and pathophysiological studies. These systems range from simple in vitro models using microtiter plate assays and flow cells to more complex in https://doi.

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Section: Bbb-on-a-chipmentioning

confidence: 99%

In vitro and ex vivo systems at the forefront of infection modeling and drug discovery

Shi

Wang

et al. 2019

Biomaterials

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“…3D printing may also be of use in the advancement of drug delivery mechanisms via production of advanced blood brain barrier modelling for in vitro platforms, enhancing the current understanding of the cerebrovascular mechanisms for central nervous system (CNS) drug delivery (73). …”

Section: Research Directions In 3d Printingmentioning

confidence: 99%

Logistics of Three-dimensional Printing

et al. 2018

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The Association of University Radiologists Radiology Research Alliance Task Force on three-dimensional (3D) printing presents a review of the logistic considerations for establishing a clinical service using this new technology, specifically focused on implications for radiology. Specific topics include printer selection for 3D printing, software selection, creating a 3D model for printing, providing a 3D printing service, research directions, and opportunities for radiologists to be involved in 3D printing. A thorough understanding of the technology and its capabilities is necessary as the field of 3D printing continues to grow. Radiologists are in the unique position to guide this emerging technology and its use in the clinical arena.

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“…One shortcoming of cromolyn, though, is that it does not cross the blood-brain barrier and requires central administration to produce its behavioral effects (Nautiyal et al, 2008). However, recent advances in blood-brain barrier assays (Kaisar et al, 2016) and delivery methods (i.e., molecular Trojan horses; Pardridge, 2007) may circumvent this problem in the near future. Taken together, our results show that mast cell activity differs in rats that are vulnerable or resilient to addiction-like behaviors and suggest that inhibiting mast cells may be a viable strategy for addiction treatment.…”

Section: Discussionmentioning

confidence: 99%

Thalamic mast cell activity is associated with sign-tracking behavior in rats

Fitzpatrick

Morrow

2017

Brain, Behavior, and Immunity

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Mast cells are resident immune cells in the thalamus that can degranulate and release hundreds of signaling molecules (i.e., monoamines, growth factors, and cytokines) both basally and in response to environmental stimuli. Interestingly, mast cell numbers in the brain show immense individual variation in both rodents and humans. We used a Pavlovian conditioned approach (PCA) procedure to examine whether mast cells are associated with individual variation in the attribution of incentive-motivational value to reward-related cues. During the PCA procedure, a lever response-independently predicts the delivery of a food pellet into a magazine, and over training sessions three conditioned responses (CRs) develop: sign-tracking (lever-directed CRs), goal-tracking (magazine-directed CRs), and an intermediate response (both CRs). In Experiment 1, we measured thalamic mast cell number/activation using toluidine blue and demonstrated that sign-trackers have increased degranulated (activated) but not granulated (inactive) mast cells. In Experiment 2, we infused the mast cell inhibitor, cromolyn (200 µg/rat; i.c.v.), immediately before five daily PCA training sessions and demonstrated that mast cell inhibition selectively impairs the acquisition of sign-tracking behavior. Taken together, these results demonstrate that thalamic mast cells contribute to the attribution of incentive-motivational value to reward-related cues and suggest that mast cell inhibition may be a novel target for addiction treatment.

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New experimental models of the blood-brain barrier for CNS drug discovery

Cited by 104 publications

References 140 publications

In vitro and ex vivo systems at the forefront of infection modeling and drug discovery

In vitro and ex vivo systems at the forefront of infection modeling and drug discovery

Logistics of Three-dimensional Printing

Thalamic mast cell activity is associated with sign-tracking behavior in rats

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