دورية أكاديمية
أعرض في EDS

Molecules of various pharmacologically-relevant sizes can cross the ultrasound-induced blood-brain barrier opening in vivo.

التفاصيل البيبلوغرافية
العنوان: Molecules of various pharmacologically-relevant sizes can cross the ultrasound-induced blood-brain barrier opening in vivo.
المؤلفون: Choi JJ; Department of Biomedical Engineering, Columbia University, New York, NY, USA., Wang S, Tung YS, Morrison B 3rd, Konofagou EE
المصدر: Ultrasound in medicine & biology [Ultrasound Med Biol] 2010 Jan; Vol. 36 (1), pp. 58-67.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: Pergamon Press Country of Publication: England NLM ID: 0410553 Publication Model: Print Cited Medium: Internet ISSN: 1879-291X (Electronic) Linking ISSN: 03015629 NLM ISO Abbreviation: Ultrasound Med Biol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Oxford, New York, Pergamon Press.
مواضيع طبية MeSH: Blood-Brain Barrier/*metabolism , Dextrans/*administration & dosage , Drug Delivery Systems/*methods , Ultrasonic Therapy/*methods, Animals ; Capillary Permeability ; Dextrans/chemistry ; Fluorescence ; Hippocampus/anatomy & histology ; Hippocampus/blood supply ; Hippocampus/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Microbubbles ; Microscopy, Fluorescence ; Molecular Weight ; Ultrasonic Therapy/instrumentation
مستخلص: Focused ultrasound (FUS) is hereby shown to noninvasively and selectively deliver compounds at pharmacologically relevant molecular weights through the opened blood-brain barrier (BBB). A complete examination on the size of the FUS-induced BBB opening, the spatial distribution of the delivered agents and its dependence on the agent's molecular weight were imaged and quantified using fluorescence microscopy. BBB opening in mice (n=13) was achieved in vivo after systemic administration of microbubbles and subsequent application of pulsed FUS (frequency: 1.525MHz, peak-rarefactional pressure in situ: 570 kPa) to the left murine hippocampus through the intact skin and skull. BBB-impermeant, fluorescent-tagged dextrans at three distinct molecular weights spanning over several orders of magnitude were systemically administered and acted as model therapeutic compounds. First, dextrans of 3 and 70 kDa were delivered trans-BBB while 2000 kDa dextran was not. Second, compared with 70 kDa dextran, a higher concentration of 3 kDa dextran was delivered through the opened BBB. Third, the 3 and 70 kDa dextrans were both diffusely distributed throughout the targeted brain region. However, high concentrations of 70 kDa dextran appeared more punctated throughout the targeted region. In conclusion, FUS combined with microbubbles opened the BBB sufficiently to allow passage of compounds of at least 70 kDa, but not greater than 2000 kDa into the brain parenchyma. This noninvasive and localized BBB opening technique could, thus, provide a unique means for the delivery of compounds of several magnitudes of kDa that include agents with shown therapeutic promise in vitro but whose in vivo translation has been hampered by their associated BBB impermeability. (E-mail: ek2191@columbia.edu).
References: Proc Natl Acad Sci U S A. 2006 Aug 1;103(31):11719-23. (PMID: 16868082)
Exp Neurol. 1976 Sep;52(3):447-58. (PMID: 954917)
Ultrason Imaging. 2008 Jul;30(3):189-200. (PMID: 19149463)
Physiol Rev. 2008 Oct;88(4):1277-340. (PMID: 18923183)
Int J Cancer. 2007 Aug 15;121(4):901-7. (PMID: 17437269)
Pharm Res. 2007 Sep;24(9):1733-44. (PMID: 17554607)
Exp Neurol. 1978 Feb;58(3):549-61. (PMID: 620709)
Radiology. 2001 Sep;220(3):640-6. (PMID: 11526261)
Phys Med Biol. 2007 Sep 21;52(18):5509-30. (PMID: 17804879)
PLoS One. 2008 May 14;3(5):e2175. (PMID: 18478109)
Ultrasound Med Biol. 2007 Jan;33(1):95-104. (PMID: 17189051)
Eur J Neurosci. 2007 Jan;25(1):231-8. (PMID: 17241284)
NeuroRx. 2005 Jan;2(1):3-14. (PMID: 15717053)
Cancer Chemother Pharmacol. 1990;25(5):320-5. (PMID: 2306791)
Ultrasound Med Biol. 2008 Jul;34(7):1093-104. (PMID: 18378064)
Proc Natl Acad Sci U S A. 2006 Apr 4;103(14):5567-72. (PMID: 16567637)
J Comp Neurol. 1994 Feb 22;340(4):566-76. (PMID: 8006217)
Exp Neurol. 1975 Dec;49(3):671-90. (PMID: 1204702)
معلومات مُعتمدة: R01 EB009041 United States EB NIBIB NIH HHS; R01 EB009041-01 United States EB NIBIB NIH HHS; R21 EY018505 United States EY NEI NIH HHS; R21 EY018505-02 United States EY NEI NIH HHS
المشرفين على المادة: 0 (Dextrans)
تواريخ الأحداث: Date Created: 20091111 Date Completed: 20100302 Latest Revision: 20220309
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC2997717
DOI: 10.1016/j.ultrasmedbio.2009.08.006
PMID: 19900750
قاعدة البيانات: MEDLINE
الوصف
تدمد:1879-291X
DOI:10.1016/j.ultrasmedbio.2009.08.006