Academic Journal

Protocol to Induce the Temporary Opening of the Blood–Brain Barrier with Short-Time Focused Ultrasound in Rats

التفاصيل البيبلوغرافية
العنوان: Protocol to Induce the Temporary Opening of the Blood–Brain Barrier with Short-Time Focused Ultrasound in Rats
المؤلفون: Jorge A. Rodríguez, Mario I. Gutiérrez, Arturo Vera, Daniel A. Hernández, Juan M. Gutiérrez, Daniel Martínez-Fong, Lorenzo Leija
المصدر: Pharmaceutics, Vol 15, Iss 12, p 2733 (2023)
بيانات النشر: MDPI AG, 2023.
سنة النشر: 2023
المجموعة: LCC:Pharmacy and materia medica
مصطلحات موضوعية: Blood–Brain Barrier, craniotomy, focused ultrasound, reversible opening, Pharmacy and materia medica, RS1-441
الوصف: Brain neurodegenerative diseases are central nervous system (CNS) affections typically common in older adults. A new therapeutic approach for them consists of providing specific drugs to the CNS through blood circulation; however, the Blood–Brain Barrier (BBB) prevents almost 100% of neurotherapeutics from reaching the brain. There are indications that Focused Ultrasound (FUS), temporarily placed in the BBB, can achieve a controlled increase in temperature at its focus, allowing temporary, localized, and reversible opening of this barrier, which facilitates the temporary delivery of specific drugs. This work presents a FUS-based protocol for the local, temporary, and reversible opening of the BBB in Wistar rats. The proposed protocol specifies certain power, treatment times, and duty cycle to controllably increase the temperature at the region of interest, i.e., the substantia nigra. Numerical simulations using commercial software based on the finite element method were carried out to determine the optimal size of the craniotomies for nearly full-acoustic transmission. Experiments in rats were performed with the parameters used during computational simulations to determine the adequate opening of the BBB. For this, craniotomies of different sizes were made at coordinates of the substantia nigra, and FUS was applied from the exterior. The opening of the BBB was evaluated using Evans Blue (EB) as an indicator of the crossing of the dye from the blood vessels to brain tissue. Numerical simulations demonstrated a major distance reached by the ultrasound focus with a bigger diameter. Experimental results show the local, temporary, and reversible opening of the BBB through a 10 mm diameter craniotomy, which effectively allowed placing the ultrasound focus over the substantia nigra, unlike a 6 mm diameter craniotomy in which there is a deviation of the focus through that window. Moreover, from these results, it was also determined that the disruption of the BBB was reversible, with an opening duration of 6 h after FUS application. The experimental work developed in this study resulted in a minimally invasive method for the temporary opening of the BBB.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1999-4923
Relation: https://www.mdpi.com/1999-4923/15/12/2733; https://doaj.org/toc/1999-4923
DOI: 10.3390/pharmaceutics15122733
URL الوصول: https://doaj.org/article/97c4cbc79b8b4e97a065af96cc71a184
رقم الانضمام: edsdoj.97c4cbc79b8b4e97a065af96cc71a184
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:19994923
DOI:10.3390/pharmaceutics15122733