A non-invasive transport system for GDNF across the blood–brain barrier

Neuroreport ◽  
1997 ◽  
Vol 8 (9) ◽  
pp. 2293-2298 ◽  
Author(s):  
David S. Albeck ◽  
Barry J. Hoffer ◽  
David Quissell ◽  
Linda A. Sanders ◽  
Gary Zerbe ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Transport System ◽  
Brain Barrier ◽  
Non Invasive ◽  
Blood Brain

scholarly journals Safety evaluation of a clinical focused ultrasound system for neuronavigation guided blood-brain barrier opening in non-human primates

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Antonios N. Pouliopoulos ◽  
Nancy Kwon ◽  
Greg Jensen ◽  
Anna Meaney ◽  
Yusuke Niimi ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Safety Profile ◽  
Focused Ultrasound ◽  
Multiple Case Study ◽  
Brain Barrier ◽  
Non Invasive ◽  
Blood Brain ◽  
Multiple Case ◽  
Bbb Opening

AbstractAn emerging approach with potential in improving the treatment of neurodegenerative diseases and brain tumors is the use of focused ultrasound (FUS) to bypass the blood–brain barrier (BBB) in a non-invasive and localized manner. A large body of pre-clinical work has paved the way for the gradual clinical implementation of FUS-induced BBB opening. Even though the safety profile of FUS treatments in rodents has been extensively studied, the histological and behavioral effects of clinically relevant BBB opening in large animals are relatively understudied. Here, we examine the histological and behavioral safety profile following localized BBB opening in non-human primates (NHPs), using a neuronavigation-guided clinical system prototype. We show that FUS treatment triggers a short-lived immune response within the targeted region without exacerbating the touch accuracy or reaction time in visual-motor cognitive tasks. Our experiments were designed using a multiple-case-study approach, in order to maximize the acquired data and support translation of the FUS system into human studies. Four NHPs underwent a single session of FUS-mediated BBB opening in the prefrontal cortex. Two NHPs were treated bilaterally at different pressures, sacrificed on day 2 and 18 post-FUS, respectively, and their brains were histologically processed. In separate experiments, two NHPs that were earlier trained in a behavioral task were exposed to FUS unilaterally, and their performance was tracked for at least 3 weeks after BBB opening. An increased microglia density around blood vessels was detected on day 2, but was resolved by day 18. We also detected signs of enhanced immature neuron presence within areas that underwent BBB opening, compared to regions with an intact BBB, confirming previous rodent studies. Logistic regression analysis showed that the NHP cognitive performance did not deteriorate following BBB opening. These preliminary results demonstrate that neuronavigation-guided FUS with a single-element transducer is a non-invasive method capable of reversibly opening the BBB, without substantial histological or behavioral impact in an animal model closely resembling humans. Future work should confirm the observations of this multiple-case-study work across animals, species and tasks.

scholarly journals BOT-01 BLOOD-BRAIN BARRIER OPENING USING 220-KHZ TRANSCRANIAL MRI-GUIDED FOCUSED ULTRASOUND AND MICROBUBBLES IN MOUSE AND RAT

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii12-ii12
Author(s):  
Michiharu Yoshida ◽  
Kazuo Maruyama ◽  
Yasutaka Kato ◽  
Rachmilevitch Itay ◽  
Syuji Suzuki ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Blood Brain Barrier ◽  
Focused Ultrasound ◽  
Brain Barrier ◽  
Maximum Temperature ◽  
Non Invasive ◽  
Therapeutic Drugs ◽  
Blood Brain ◽  
Mri Guided ◽  
Bbb Opening

Abstract OBJECTIVE In neuro-oncology, it is believed that one major obstacle to effective chemotherapy is the high vascularity and heterogenous permeability of brain tumors. Focused ultrasound (FUS) exposure with the microbubbles has been shown to transiently open the blood-brain barrier (BBB) without depositing thermal energy, and thus may enhance the delivery of various therapeutic drugs into brain tumors. The aim of this study was to evaluate the BBB opening using 220-kHz transcranial MRI-guided FUS (TcMRgFUS) device and microbubbles in mouse and rat. METHODS The experiments were performed with the 220-kHz ExAblate Neuro TcMRgFUS system (InSightec) and novel lipid bubbles (LB, Teikyo Univ.). Normal mouse and rat brains were irradiated with TcMRgFUS (output power, 5W; duration of irradiation, 30 s; duty cycle 100%) following intravenous injection of 6x107 LB per mouse and rat, respectively. On irradiation, target temperature rise & cavitation signal were monitored by MR thermometry and cavitation receiver, respectively. Immediately after irradiation, BBB opening and complications were detected based on T1, T2, T2*, and Gadolinium (Gd) enhanced T1-weighted images. RESULTS The maximum temperature of brain tissue was under 42 C. There were no risky-cavitation signals causing hemorrhage. The FUS-LB exposure induced successful BBB opening effect in both mouse and rat, confirmed by Gd enhancement in the target region, lateral ventricles, and sulcus. In addition, there were no complications such as edema, coagulation, and hemorrhage. CONCLUSIONS Although there remain many conditions to be optimized, BBB opening using a 220-kHz TcMRgFUS device and LB can offer a non-invasive and feasible drug delivery for brain malignancies.

Transport of alpha-keto analogues of amino acids across blood-brain barrier in rats

1982 ◽  
Vol 243 (4) ◽  
pp. E272-E277
Author(s):  
A. R. Conn ◽  
R. D. Steele
Keyword(s):  
Blood Brain Barrier ◽  
Transport System ◽  
Ketone Bodies ◽  
Brain Barrier ◽  
Sodium Pentobarbital ◽  
Keto Acid ◽  
Dual Isotope ◽  
Common System ◽  
Blood Brain ◽  
Keto Acids

The transport of 14C-labeled alpha-keto acids across the blood-brain barrier (BBB) was studied in rats anesthetized with sodium pentobarbital using a modification of a single-injection dual-isotope technique. alpha-Keto acids were found to cross the BBB via a saturable carrier-mediated transport system that may be specific based on lack of inhibition by glucose, isoleucine, and ketone bodies on the uptake of tracer levels of 14C-labeled alpha-keto acids. alpha-Ketobutyrate and alpha-keto-gamma-methiolbutyrate, both straight chain keto acids, and alpha-ketoisocaproate, a branched-chain keto acid, appeared to cross the barrier by a common carrier based on cross-inhibition studies. Aromatic keto acids had no effect on the uptake of tracer levels of these 14C-keto acids. The Km of transport of alpha-ketobutyrate, alpha-ketoisocaproate, and alpha-keto-gamma-methiolbutyrate, was 0.11, 0.60, and 0.33 mM, respectively. The corresponding Vmax was 15.7, 73.3, and 30.2 nmol . g-1 . min-1. Phenylpyruvate was found not to cross the BBB. Inhibition of brain uptake of alpha-keto acids by propionate and pyruvate, and not by DL-beta-hydroxybutyrate suggests that alpha-keto acids and monocarboxylic acids are transported either via a common system independent of ketone bodies or share an affinity with a monocarboxylic acid and an alpha-keto acid transport system.

scholarly journals Non-invasive ultrasonic modulation of visual evoked response by GABA delivery through the blood brain barrier

2020 ◽  
Vol 318 ◽  
pp. 223-231 ◽  
Author(s):  
Charlotte Constans ◽  
Harry Ahnine ◽  
Mathieu Santin ◽  
Stéphane Lehericy ◽  
Mickael Tanter ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Evoked Response ◽  
Brain Barrier ◽  
Visual Evoked Response ◽  
Non Invasive ◽  
Blood Brain ◽  
Visual Evoked

scholarly journals Non-invasive delivery of stealth, brain-penetrating nanoparticles across the blood − brain barrier using MRI-guided focused ultrasound

2014 ◽  
Vol 189 ◽  
pp. 123-132 ◽  
Author(s):  
Elizabeth Nance ◽  
Kelsie Timbie ◽  
G. Wilson Miller ◽  
Ji Song ◽  
Cameron Louttit ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Focused Ultrasound ◽  
Brain Barrier ◽  
Non Invasive ◽  
Blood Brain ◽  
Mri Guided

scholarly journals A Noninvasive Approach to Optogenetics Using Focused Ultrasound Blood Brain Barrier Disruption for the Delivery of Radioluminescent Particles

2020 ◽  
Author(s):  
Megan Rich ◽  
Eric Zhang ◽  
Ashley Dickey ◽  
Haley Jones ◽  
Kelli Cannon ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Focused Ultrasound ◽  
Brain Regions ◽  
Brain Barrier ◽  
Receptor Subtype ◽  
Spatiotemporal Resolution ◽  
Light Emitting ◽  
Non Invasive ◽  
Blood Brain ◽  
Essential Components

AbstractOptogenetics, the genetic incorporation of light-sensitive proteins such as Channelrhodopsin-2 (ChR2) into target mammalian neurons, has enabled activation, silencing, and receptor subtype specific neuromodulation with high spatiotemporal resolution. However, the essential components of the ontogenetic system require invasive procedures with very few non-invasive alternatives preventing its use as a translational tool. The implantation of light emitting fibers deep within brain structures is both technically demanding and causes tissue scarring in target brain regions. To overcome these limitations, while maintaining the highly-tuned components of optogenetics we have developed a novel noninvasive alternative. Our approach replaces fibers with light-emitting radioluminescent particles (RLPs) that can be activated non-invasively with X-ray exposure. Here, we report successful noninvasive delivery of RLPs to target brain regions using MRI-guided focused ultrasound (FUS) blood brain barrier opening. In addition, FUS BBBO can be used to deliver viral vectors for light sensitive channel expression. Combined, these components can provide a completely non-invasive optogenetic system.

Sign in / Sign up

Export Citation Format

Share Document