The amount of BBB D relies on different ultrasound guidelines including Cyclopamine energy, dosage of ultrasound contrast agent, and how many sonications that are completed. 2 Many chemotherapy treatments are ineffective because drugs fail to attain therapeutic levels in the target brain tumor as a result of limited permeability of the BBB. 3 Previous works have reported that first line high dose chemotherapy provides a possible survival benefit in comparison with historical control patients receiving standard dose therapies. 4,5 Traditional high dose chemotherapy can improve treatment effectiveness, but its clinical application is often limited by systemic toxicity. Thus, it is important to find to provide adequate quantities of drugs to the prospective location, without increasing systemic dose.
We previously noted that the concentration of Evans blue in tumors and the tumefaction to normal brain ratio of EB in the brain are elevated after BBB N induction by pulsed FUS. More over, recurring pulsed FUS exposure further increases the efficiency of EB delivery Papillary thyroid cancer to the mind. 6?9 One study demonstrated that FUS publicity following EB injection gives almost a threefold increase in the amount of EB extravasated in sonicated hepatocellular carcinoma weighed against that from carcinoma sonicated prior to EB administration. When EB was used after sonication 10 Interestingly, the increased efficacy of FUS was missing. This result is consistent with a previous record of cardiac protein delivery. 11 Fluid microjets have the effect of the increased capillary permeability and temporary nanopores observed in cell membranes following FUS destruction of microbubbles.
12,13 These studies suggest that the drug administration procedure should be considered when implementing FUS therapy with therapeutic agents. Furthermore, FUS has been used to enhance local drug delivery and increase the antitumor effects in the treatment of brain tumors. 14?16 FK866 Within this study, we evaluated the delivery efficiency of EB administration before and after BBB D induced by FUS. In addition, we examined the results of various ultrasound parameters on the effectiveness of extravasation. Our intention was to optimize FUS mediated drug-delivery to the mind, to reduce tissue injury. Experimental animals Male Sprague?Dawley rats weighing from 280 to 350 g were utilized in this study.
All experiments were performed according to the approved practices of our institutional animal care and use committee. Mice were anesthetized with chloral hydrate by intraperitoneal injection, and body temperature was maintained at 37?C using a heating pad. The top of the skull was shaved and the scalp overlying the head was incised to facilitate use of the bregma being an anatomic landmark for targeting. The rat heads were installed on stereotaxic apparatus together with the nose bar positioned 3. 3 mm below the line.
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