scholarly journals Blood-brain barrier opening for facilitating drug delivery in neurological and neurodegenerative diseases in non-human primates

2018 ◽  
Author(s):  
Elisa E. Konofagou
Keyword(s):  
Neurodegenerative Diseases ◽  
Blood Brain Barrier ◽  
Focused Ultrasound ◽  
Neurological Diseases ◽  
Brain Barrier ◽  
Blood Brain ◽  
Therapeutic Molecules ◽  
After Cancer ◽  
Large Animals

After cancer and heart disease, neurodegenerative diseases, such as Alzheimer's, Parkinson's, multiple sclerosis (MS), amythrophic lateral sclerosis (ALS), and neurological diseases take more lives each year than any other illness. Although great progress has been made in recent years toward understanding of central nervous system (CNS) diseases, few effective treatments and no cures are currently available. This is mainly because the blood-brain barrier (BBB) limits the delivery of the vast majority of systemically-administered drugs available to treat those diseases. The underlying hypothesis of this study is that delivery of therapeutic molecules is safe and effective through the blood-brain barrier (BBB) using Focused Ultrasound (FUS) in large animals in vivo. Our preliminary results have shown that the FUS technique can induce BBB opening entirely noninvasively, selectively and be monitored with MRI at sub-millimeter resolution in vivo. The specific aims are therefore to: 1) build a MRcompatible system for FUS targeting and monitoring in the MRI system; 2) test and demonstrate delivery of neurotrophic factors to the hippocampus and putamen of monkeys; 3) test and demonstrate delivery of inhibitors to the visual cortex of monkeys; and 4) assess the safety of the FUS method in monkeys.

Engineered models for studying blood-brain-barrier-associated brain physiology and pathology

Organoid ◽  
2021 ◽  
Vol 1 ◽  
pp. e10
Author(s):  
Hong Nam Kim
Keyword(s):  
Neurodegenerative Diseases ◽  
Blood Brain Barrier ◽  
Three Dimensional ◽  
Brain Barrier ◽  
Sufficient Information ◽  
Transport Barrier ◽  
Brain Physiology ◽  
Blood Brain ◽  
The Brain

The blood-brain barrier (BBB) is a transport barrier that suppresses the translocation of potentially harmful substances to the brain tissue. Although the BBB is known to be associated with many kinds of neuropathology, such as neuroinflammation and neurodegenerative diseases, the conventionally used animal and Transwell models cannot provide sufficient information due to genetic and functional heterogeneity in comparison with humans and limited monitoring capabilities. Recently, human cell-based three-dimensional BBB models have been developed, and these models provide in vivo-like BBB structures and functions. In this review, we provide an overview of the recent advances in BBB models with a particular focus on the simulation of BBB-associated brain physiology and neuropathology. To this end, important factors for recapitulating the in vivo characteristics of the BBB are described. Furthermore, approaches to recapitulate the BBB physiology using engineering methods are summarized. The applications of BBB models in the study of neuropathology, such as inflammation and neurodegenerative diseases, are also presented.

scholarly journals Targeting Effects on the Volume of the Focused Ultrasound-Induced Blood–Brain Barrier Opening in Nonhuman Primates In Vivo

2017 ◽  
Vol 64 (5) ◽  
pp. 798-810 ◽  
Author(s):  
Maria Eleni Marilena Karakatsani ◽  
Gesthimani Mania Samiotaki ◽  
Matthew E. Downs ◽  
Vincent P. Ferrera ◽  
Elisa E. Konofagou
Keyword(s):  
Blood Brain Barrier ◽  
Nonhuman Primates ◽  
Focused Ultrasound ◽  
Brain Barrier ◽  
Blood Brain ◽  
Barrier Opening ◽  
Blood Brain Barrier Opening

scholarly journals Blood–Brain Barrier and Neurodegenerative Diseases—Modeling with iPSC-Derived Brain Cells

2021 ◽  
Vol 22 (14) ◽  
pp. 7710
Author(s):  
Ying-Chieh Wu ◽  
Tuuli-Maria Sonninen ◽  
Sanni Peltonen ◽  
Jari Koistinaho ◽  
Šárka Lehtonen
Keyword(s):  
Stem Cell ◽  
Neurodegenerative Diseases ◽  
Blood Brain Barrier ◽  
Current Knowledge ◽  
Neurological Diseases ◽  
Induced Pluripotent Stem Cell ◽  
Brain Barrier ◽  
Blood Brain ◽  
Induced Pluripotent ◽  
The Brain

The blood–brain barrier (BBB) regulates the delivery of oxygen and important nutrients to the brain through active and passive transport and prevents neurotoxins from entering the brain. It also has a clearance function and removes carbon dioxide and toxic metabolites from the central nervous system (CNS). Several drugs are unable to cross the BBB and enter the CNS, adding complexity to drug screens targeting brain disorders. A well-functioning BBB is essential for maintaining healthy brain tissue, and a malfunction of the BBB, linked to its permeability, results in toxins and immune cells entering the CNS. This impairment is associated with a variety of neurological diseases, including Alzheimer’s disease and Parkinson’s disease. Here, we summarize current knowledge about the BBB in neurodegenerative diseases. Furthermore, we focus on recent progress of using human-induced pluripotent stem cell (iPSC)-derived models to study the BBB. We review the potential of novel stem cell-based platforms in modeling the BBB and address advances and key challenges of using stem cell technology in modeling the human BBB. Finally, we highlight future directions in this area.

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