Anatomy and physiology of the blood–brain barrier

Serlin, Yonatan; Shelef, Ilan; Knyazer, Boris; Friedman, Alon

doi:10.1016/j.semcdb.2015.01.002

Cited by 300 publications

(188 citation statements)

References 64 publications

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“…Systemic MNP administration is typically avoided for MHT of GBM due to the presence of the BBB. In the healthy brain, the BBB preserves normal brain function by maintaining a homeostatic neuronal environment [67]. This highly selective barrier prevents exposure of brain tissue to many possibly harmful compounds.…”

Section: Magnetic Hyperthermia Therapymentioning

confidence: 99%

Magnetic hyperthermia therapy for the treatment of glioblastoma: a review of the therapy’s history, efficacy and application in humans

Mahmoudi

Bouras

Bozec

et al. 2018

International Journal of Hyperthermia

280

195

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Hyperthermia therapy (HT) is the exposure of a region of the body to elevated temperatures to achieve a therapeutic effect. HT anticancer properties and its potential as a cancer treatment have been studied for decades. Techniques used to achieve a localised hyperthermic effect include radiofrequency, ultrasound, microwave, laser and magnetic nanoparticles (MNPs). The use of MNPs for therapeutic hyperthermia generation is known as magnetic hyperthermia therapy (MHT) and was first attempted as a cancer therapy in 1957. However, despite more recent advancements, MHT has still not become part of the standard of care for cancer treatment. Certain challenges, such as accurate thermometry within the tumour mass and precise tumour heating, preclude its widespread application as a treatment modality for cancer. MHT is especially attractive for the treatment of glioblastoma (GBM), the most common and aggressive primary brain cancer in adults, which has no cure. In this review, the application of MHT as a therapeutic modality for GBM will be discussed. Its therapeutic efficacy, technical details, and major experimental and clinical findings will be reviewed and analysed. Finally, current limitations, areas of improvement, and future directions will be discussed in depth.

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Section: Magnetic Hyperthermia Therapymentioning

confidence: 99%

Magnetic hyperthermia therapy for the treatment of glioblastoma: a review of the therapy’s history, efficacy and application in humans

Mahmoudi

Bouras

Bozec

et al. 2018

International Journal of Hyperthermia

280

195

View full text Add to dashboard Cite

show abstract

“…In addition, the BBB serves as the conduit to supply the brain with the essential nutrients it needs, while facilitating the excretion of waste products through efflux [2]. The hallmark of the BBB is the presence of endothelial cells that are tightly connected by tight junction protein complexes, which are composed of claudins, occludins, and junction adhesion molecules [3]. In addition to endothelia, the BBB has a thick basal membrane with pericytes and astrocytic foot processes in close proximity [4, 5].…”

Section: Introductionmentioning

confidence: 99%

Permeability across a novel microfluidic blood-tumor barrier model

Terrell-Hall

Ammer

Griffith

et al. 2017

Fluids Barriers CNS

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BackgroundThe lack of translatable in vitro blood-tumor barrier (BTB) models creates challenges in the development of drugs to treat tumors of the CNS and our understanding of how the vascular changes at the BBB in the presence of a tumor.MethodsIn this study, we characterize a novel microfluidic model of the BTB (and BBB model as a reference) that incorporates flow and induces shear stress on endothelial cells. Cell lines utilized include human umbilical vein endothelial cells co-cultured with CTX-TNA2 rat astrocytes (BBB) or Met-1 metastatic murine breast cancer cells (BTB). Cells were capable of communicating across microfluidic compartments via a porous interface. We characterized the device by comparing permeability of three passive permeability markers and one marker subject to efflux.ResultsThe permeability of Sulforhodamine 101 was significantly (p < 0.05) higher in the BTB model (13.1 ± 1.3 × 10−3, n = 4) than the BBB model (2.5 ± 0.3 × 10−3, n = 6). Similar permeability increases were observed in the BTB model for molecules ranging from 600 Da to 60 kDa. The function of P-gp was intact in both models and consistent with recent published in vivo data. Specifically, the rate of permeability of Rhodamine 123 across the BBB model (0.6 ± 0.1 × 10−3, n = 4), increased 14-fold in the presence of the P-gp inhibitor verapamil (14.7 ± 7.5 × 10−3, n = 3) and eightfold with the addition of Cyclosporine A (8.8 ± 1.8 × 10−3, n = 3). Similar values were noted in the BTB model.ConclusionsThe dynamic microfluidic in vitro BTB model is a novel commercially available model that incorporates shear stress, and has permeability and efflux properties that are similar to in vivo data.

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“…The blood-brain barrier actively regulates influx of nutrients and oxygen and efflux of waste products between CNS tissue and peripheral blood while providing protection to neuronal cells from toxins and pathogens that circulate throughout the body [12]. The insulating nature of this vascular membrane is the result of endothelial cells forming continuous intracellular tight junctions with one another, supported by astrocytes and pericytes that provide additional mechanical and trophic support to the blood-brain interface [13].…”

Section: Current Understanding Of Tissue Response To Injurymentioning

confidence: 99%

The role of oligodendrocytes and their progenitors on neural interface technology: A novel perspective on tissue regeneration and repair

2018

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Oligodendrocytes and their precursors are critical glial facilitators of neurophysiology, which is responsible for cognition and behavior. Devices that are used to interface with the brain allow for a more in-depth analysis of how neurons and these glia synergistically modulate brain activity. As projected by the BRAIN Initiative, technologies that acquire a high resolution and robust sampling of neural signals can provide a greater insight in both the healthy and diseased brain and support novel discoveries previously unobtainable with the current state of the art. However, a complex series of inflammatory events triggered during device insertion impede the potential applications of implanted biosensors. Characterizing the biological mechanisms responsible for the degradation of intracortical device performance will guide novel biomaterial and tissue regenerative approaches to rehabilitate the brain following injury. Glial subtypes which assist with neuronal survival and exchange of electrical signals, mainly oligodendrocytes, their precursors, and the insulating myelin membranes they produce, are sensitive to inflammation commonly induced from insults to the brain. This review explores essential physiological roles facilitated by oligodendroglia and their precursors and provides insight into their pathology following neurodegenerative injury and disease. From this knowledge, inferences can be made about the impact of device implantation on these supportive glia in order to engineer effective strategies that can attenuate their responses, enhance the efficacy of neural interfacing technology, and provide a greater understanding of the challenges that impede wound healing and tissue regeneration during pathology.

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Anatomy and physiology of the blood–brain barrier

Cited by 300 publications

References 64 publications

Magnetic hyperthermia therapy for the treatment of glioblastoma: a review of the therapy’s history, efficacy and application in humans

Magnetic hyperthermia therapy for the treatment of glioblastoma: a review of the therapy’s history, efficacy and application in humans

Permeability across a novel microfluidic blood-tumor barrier model

The role of oligodendrocytes and their progenitors on neural interface technology: A novel perspective on tissue regeneration and repair

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