Mechanism of Low-Frequency Ultrasound in Opening Blood–Tumor Barrier by Tight Junction

Shang, Xiuli; Wang, Ping; Liu, Yunhui; Zhang, Zhen; Xue, Yixue

doi:10.1007/s12031-010-9451-9

Cited by 73 publications

(54 citation statements)

References 24 publications

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“…This could be due to bioeffects such as red blood cell lysis (13) or thrombus formation (14). Similar transient vascular damage has previously been reported for blood brain barrier vasculature resulting in erythrocyte extravasation (15)(16)(17). Acoustic research is currently in progress to use USMB for thrombolysis (18,19) however the results from this study indicate that USMB may also cause temporary thrombus formation.…”

Section: Discussionsupporting

confidence: 75%

Reversible and irreversible vascular bioeffects induced by ultrasound and microbubbles in chorioallantoic membrane model

Tarapacki¹,

Kuebler²,

Tabuchi³

et al. 2017

AIP Conference Proceedings

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Section: Discussionsupporting

confidence: 75%

Reversible and irreversible vascular bioeffects induced by ultrasound and microbubbles in chorioallantoic membrane model

Tarapacki¹,

Kuebler²,

Tabuchi³

et al. 2017

AIP Conference Proceedings

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“…63 Contrast enhanced MRI has shown that once the BBB is closed following FUS, the barrier remains impenetrable up to 4 weeks later. 24 Regardless of the precise mechanism of passage across the BBB, it has been repeatedly observed that enhanced permeability of the BBB by FUS and microbubbles leads to greater drug accumulation in the brain.…”

Section: ■ Cellular Mechanisms Of Fusmentioning

confidence: 99%

Noninvasive and Targeted Drug Delivery to the Brain Using Focused Ultrasound

Burgess

Hynynen

2013

ACS Chem. Neurosci.

117

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Brain diseases are notoriously difficult to treat due to the presence of the blood-brain barrier (BBB). Here, we review the development of focused ultrasound (FUS) as a noninvasive method for BBB disruption, aiding in drug delivery to the brain. FUS can be applied through the skull to a targeted region in the brain. When combined with microbubbles, FUS causes localized and reversible disruption of the BBB. The cellular mechanisms of BBB disruption are presented. Several therapeutic agents have been delivered to the brain resulting in significant improvements in pathology in models of glioblastoma and Alzheimer's disease. The requirements for clinical translation of FUS will be discussed. KEYWORDS:Focused ultrasound, blood-brain barrier, drug delivery B rain diseases, including psychiatric disorders, neurodegenerative diseases, and cancer, are among the most prevalent diseases worldwide. It has been estimated that 35% of all disease burden is attributable to brain disorders.1 Despite advancing research, which better understands the etiology and underlying mechanisms of disease, most of these diseases do not have effective treatments and essentially no cures exist.Designing therapeutic agents for the brain is very challenging. The brain is a well-protected organ, completely encased by the skull, making surgical access difficult and direct application of drugs impractical. However, perhaps the most limiting factor to successful treatment of brain disease is the blood-brain barrier (BBB) which prevents access of ∼98% of current pharmaceutical agents to the brain when delivered intravenously. ■ THE BLOOD-BRAIN BARRIER (BBB)The BBB is a specialized structure between the cerebral capillaries and the brain parenchyma that is relatively impermeable except for a selection of very small (<400 Da), lipophilic compounds. 3 The BBB is different from the barriers between the peripheral vasculature and other organs in the body due mainly to the presence of tight junctions between adjacent endothelial cells.3 Cell adhesion molecules, most notably claudins and occludins, connect the endothelial cells together to create the tight junctions. The intracellular domains of the proteins are anchored to the cytoskeleton and the extracellular domains form homodimers with proteins on adjacent endothelial cells. These independent tight junctional proteins work in concert to make the endothelial cellular layer impermeable to fluid thereby limiting paracellular transport mechanisms.

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“…Hence, how to open this barrier and improve the permeability of prostate is a difficult and hot point. Contrast agent, microbubble-mediated ultrasound can increase the gaps between capillary endothelial cells and biological membranes by cavitation, which helps drugs permeation from plasma overflow vessels, and through biological membranes to reach the treatment sites (Shang et al 2011). Previous study has showed that MB-mediated ultrasound irradiation can significantly improve the prostate permeability (Liu et al 2013).…”

Section: Introductionmentioning

confidence: 99%

“…Claudins are the major transmembrane components of TJs. Studies demonstrated that claudins played important roles in the regulation of the blood-tumor barrier by MB-mediated ultrasound irradiation (Shang et al 2011). In prostate, there are wide expressions of claudin-1, -3, -4, -5, -8, -7, -10 (Sakai et al 2007), but whether TJs and claudins are involved in the regulation of prostate permeability by MB-mediated ultrasound irradiation is unclear.…”

Section: Introductionmentioning

confidence: 99%

The Roles of Tight Junctions and Claudin-1 in the Microbubble-Mediated Ultrasound-Induced Enhancement of Drug Concentrations in Rat Prostate

et al. 2015

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Although microbubble-mediated ultrasound irradiation can enhance the prostate permeability, little is known about the mechanism. In our study, the healthy, adult male SD rats were divided into four groups: the BC, US, MB, and MMUS groups. A therapeutic ultrasound apparatus was used to treat the rats prostates in the presence of circulating MBs. Cefuroxime was injected to assess prostate permeability by HPLC. The structures of prostate tissues and TJs were observed by light and transmission electron microscopy. Western blot was used to assess claudin-1 expression. After treatment of microbubble-mediated ultrasound irradiation, the cefuroxime concentrations in the prostate were significantly increased. HE staining demonstrated that the gland epithelial cell layer became dropsical, thick, and disordered. In transmission electron microscopy, the TJs between adjacent capillary endothelial cells or gland epithelial cells were disjointed and partly interrupted. Furthermore, western blot showed the expression of claudin-1 was significantly decreased. However, these findings were not observed in the prostates exposed to microbubble or ultrasound alone, as well as the healthy control rats. In conclusion, microbubble-mediated ultrasound irradiation significantly enhanced the prostate permeability and improve the cefuroxime concentrations in prostate. The changes in TJs structure and the decreased claudin-1 expression may play important roles in this process.

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Mechanism of Low-Frequency Ultrasound in Opening Blood–Tumor Barrier by Tight Junction

Cited by 73 publications

References 24 publications

Reversible and irreversible vascular bioeffects induced by ultrasound and microbubbles in chorioallantoic membrane model

Reversible and irreversible vascular bioeffects induced by ultrasound and microbubbles in chorioallantoic membrane model

Noninvasive and Targeted Drug Delivery to the Brain Using Focused Ultrasound

The Roles of Tight Junctions and Claudin-1 in the Microbubble-Mediated Ultrasound-Induced Enhancement of Drug Concentrations in Rat Prostate

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