Behavioral alterations following blood-brain barrier disruption stimulated by focused ultrasound

Yang, Feng; Huang, Sheng; Cheng, Irene H.

doi:10.18632/oncotarget.8444

Cited by 15 publications

(11 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The forelimb grip strength test was carried out from PD8 to PD14 to assess neuromuscular function [ 19 ]. The duration of forelimb grip of a metal bar (diameter × length = 2 mm × 7.5 cm) was measured using a low-force testing system (Model-RX-5, Aikoh Engineering, Nagoya, Japan).…”

Section: Methodsmentioning

confidence: 99%

Periconceptional Folic Acid Supplementation Benefit to Development of Early Sensory-Motor Function through Increase DNA Methylation in Rat Offspring

Shou

et al. 2018

Nutrients

View full text Add to dashboard Cite

Periconceptional maternal folate levels may alter DNA methylation patterns and health outcomes in offspring. We hypothesized that maternal folic acid supplementation alters fetal neural development through DNA methylation in the fetal brain. Twenty-eight rats were randomly assigned to four groups: three groups of the female rats were fed folate-normal, folate-deficient or folate-supplemented diets from seven days before mating to delivery. In another group, folic acid supplementation diet short-period group was fed a folate-normal diet, except for 10 days (begin mating) when this group was fed a folate-supplemented diet. After delivery, the diets were changed to folate-normal diet for all four groups. The cliff avoidance and forelimb grip tests were used to assess sensory motor function of rat offspring. The results indicate that maternal folic acid supplementation improved the early development of sensory-motor function in offspring. Maternal folic acid supplementation increased the methylation potential, global DNA methylation (5-mC) and DNA methyltransferase expression and activity in the brains of the offspring. In conclusion, maternal folic acid supplementation increases DNA methylation pattern in offspring brain and improves the early development of sensory-motor function.

show abstract

Section: Methodsmentioning

confidence: 99%

Periconceptional Folic Acid Supplementation Benefit to Development of Early Sensory-Motor Function through Increase DNA Methylation in Rat Offspring

Shou

et al. 2018

Nutrients

View full text Add to dashboard Cite

show abstract

“…In addition, BBB permeability may also be increased by the activation of transcellular transport pathways . At the same time, FUS with microbubbles can induce neuromodulation of neuronal activity, decrease glucose uptake, trigger a sterile inflammatory response, and even produce behavioral alterations . These effects may occur in parallel to or as a consequence of the BBB opening.…”

Section: Bbb Opening To Halt Nigrostriatal Neurodegenerationmentioning

confidence: 99%

Focused ultrasound in Parkinson's disease: A twofold path toward disease modification

et al. 2019

View full text Add to dashboard Cite

A major unmet need in Parkinson's disease (PD) is to slow the inexorable progression of neurodegeneration. Clinical trials that evaluated promising pharmacological strategies have repeatedly failed. Nonetheless, the advent of focused ultrasound provides new opportunities toward the goal of developing a safe and effective disease‐modifying therapy for PD. Here we discuss the rationale, possible avenues, and challenges along this path, exploiting the potential of focused ultrasound for (1) performing focal thermal lesions to restore the basic basal ganglia abnormalities associated with dopamine depletion, and (2) transiently opening the blood–brain barrier for targeted delivery of therapeutic agents. First, the classic idea of excitotoxicity mediated by hyperactivity of the subthalamic nucleus suggests that focused ultrasound subthalamotomy may offer a clinically viable disease‐modifying therapy in very‐early PD. Second, the concept of retrograde nigrostriatal neurodegeneration, supported by our recent cortical pathogenic theory of PD, points toward the putamen as a principal site for focused ultrasound blood–brain barrier opening and targeted drug delivery. In principle, both therapeutic strategies—subthalamotomy and putaminal blood–brain barrier opening—could eventually be applied in the same patient. Clinical application is still a long road ahead; nevertheless, focused ultrasound may open a twofold path toward disease modification in PD. © 2019 International Parkinson and Movement Disorder Society

show abstract

“…A major challenge in the chronic use of ultrasound-mediated drug release in the brain has been that previous approaches either required or caused unavoidable BBB opening 10,21 . Recently it has been shown that BBB opening can induce sterile inflammation 18 under certain conditions, has strong effects on cell activity and behavior [21][22][23] , and is implicated in neurodegenerative diseases 19,20 . Therefore, for use in chronic treatments of many brain disorders, it is vital to achieve FUS-mediated drug release without compromising BBB as we demonstrated here.…”

Section: Discussionmentioning

confidence: 99%

“…Hence, while FUS-mediated BBB opening might be acceptable for one-time acute delivery of viral vectors or other macromolecules, it is currently unclear what risks repeated BBB opening may pose for long-term treatment of neurological and neuropsychiatric disorders. Furthermore, since BBB opening on its own modulates neuronal activity and behavior in rodents and primates [21][22][23] , it cannot be used in circuit investigations without confounding effects.…”

mentioning

confidence: 99%

Non-invasive molecularly-specific millimeter-resolution manipulation of brain circuits by ultrasound-mediated aggregation and uncaging of drug carriers

et al. 2020

View full text Add to dashboard Cite

Non-invasive, molecularly-specific, focal modulation of brain circuits with low off-target effects can lead to breakthroughs in treatments of brain disorders. We systemically inject engineered ultrasound-controllable drug carriers and subsequently apply a novel two-component Aggregation and Uncaging Focused Ultrasound Sequence (AU-FUS) at the desired targets inside the brain. The first sequence aggregates drug carriers with millimeter-precision by orders of magnitude. The second sequence uncages the carrier’s cargo locally to achieve high target specificity without compromising the blood-brain barrier (BBB). Upon release from the carriers, drugs locally cross the intact BBB. We show circuit-specific manipulation of sensory signaling in motor cortex in rats by locally concentrating and releasing a GABAA receptor agonist from ultrasound-controlled carriers. Our approach uses orders of magnitude (1300x) less drug than is otherwise required by systemic injection and requires very low ultrasound pressures (20-fold below FDA safety limits for diagnostic imaging). We show that the BBB remains intact using passive cavitation detection (PCD), MRI-contrast agents and, importantly, also by sensitive fluorescent dye extravasation and immunohistochemistry.

show abstract

Behavioral alterations following blood-brain barrier disruption stimulated by focused ultrasound

Cited by 15 publications

References 31 publications

Periconceptional Folic Acid Supplementation Benefit to Development of Early Sensory-Motor Function through Increase DNA Methylation in Rat Offspring

Periconceptional Folic Acid Supplementation Benefit to Development of Early Sensory-Motor Function through Increase DNA Methylation in Rat Offspring

Focused ultrasound in Parkinson's disease: A twofold path toward disease modification

Non-invasive molecularly-specific millimeter-resolution manipulation of brain circuits by ultrasound-mediated aggregation and uncaging of drug carriers

Contact Info

Product

Resources

About