scholarly journals Altered Blood-Brain Barrier and Blood-Spinal Cord Barrier Dynamics in Amyotrophic Lateral Sclerosis: Impact on Medication Efficacy and Safety

2021 ◽  
Author(s):  
Yijun Pan ◽  
Joseph Nicolazzo
Keyword(s):  
Spinal Cord ◽  
Amyotrophic Lateral Sclerosis ◽  
Neurodegenerative Diseases ◽  
Blood Brain Barrier ◽  
Large Body ◽  
Brain Barrier ◽  
Blood Brain ◽  
Blood Spinal Cord Barrier ◽  
The Brain ◽  
Lateral Sclerosis

The access of drugs into the central nervous system (CNS) is regulated by the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB). A large body of evidence supports perturbation of these barriers in neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. Modifications to the BBB and BSCB are also reported in amyotrophic lateral sclerosis (ALS), albeit these modifications have received less attention relative to those in other neurodegenerative diseases. Such alterations to the BBB and BSCB have the potential to impact on CNS exposure of drugs in ALS, modulating the effectiveness of drugs intended to reach the brain and the toxicity of drugs that are not intended to reach the brain. Given the clinical importance of these phenomena, this review will summarise reported modifications to the BBB and BSCB in ALS, discuss their impact on CNS drug exposure and suggest further research directions so as to optimise medicine use in people with ALS.

scholarly journals Blood–Brain Barrier Driven Pharmacoresistance in Amyotrophic Lateral Sclerosis and Challenges for Effective Drug Therapies

2017 ◽  
Vol 19 (6) ◽  
pp. 1600-1614 ◽  
Author(s):  
Loqman A. Mohamed ◽  
Shashirekha Markandaiah ◽  
Silvia Bonanno ◽  
Piera Pasinelli ◽  
Davide Trotti
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Blood Brain Barrier ◽  
Effective Drug ◽  
Brain Barrier ◽  
Blood Brain ◽  
Lateral Sclerosis

scholarly journals First-in-human trial of blood–brain barrier opening in amyotrophic lateral sclerosis using MR-guided focused ultrasound

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Agessandro Abrahao ◽  
Ying Meng ◽  
Maheleth Llinas ◽  
Yuexi Huang ◽  
Clement Hamani ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Cortex ◽  
Blood Brain Barrier ◽  
Focused Ultrasound ◽  
Primary Motor Cortex ◽  
Brain Barrier ◽  
Human Trial ◽  
Blood Brain ◽  
Lateral Sclerosis ◽  
Bbb Opening

Abstract MR-guided focused ultrasound (MRgFUS) is an emerging technology that can accurately and transiently permeabilize the blood-brain barrier (BBB) for targeted drug delivery to the central nervous system. We conducted a single-arm, first-in-human trial to investigate the safety and feasibility of MRgFUS-induced BBB opening in eloquent primary motor cortex in four volunteers with amyotrophic lateral sclerosis (ALS). Here, we show successful BBB opening using MRgFUS as demonstrated by gadolinium leakage at the target site immediately after sonication in all subjects, which normalized 24 hours later. The procedure was well-tolerated with no serious clinical, radiologic or electroencephalographic adverse events. This study demonstrates that non-invasive BBB permeabilization over the motor cortex using MRgFUS is safe, feasible, and reversible in ALS subjects. In future, MRgFUS can be coupled with promising therapeutics providing a targeted delivery platform in ALS.

scholarly journals Blood–Brain Barrier Disruption Is Not Associated With Disease Aggressiveness in Amyotrophic Lateral Sclerosis

2021 ◽  
Vol 15 ◽  
Author(s):  
Tino Prell ◽  
Benjamin Vlad ◽  
Nayana Gaur ◽  
Beatrice Stubendorff ◽  
Julian Grosskreutz
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Blood Brain Barrier ◽  
Rating Scale ◽  
Cross Sectional Study ◽  
Brain Barrier ◽  
Cross Sectional ◽  
Blood Brain Barrier Disruption ◽  
Progression Model ◽  
Blood Brain ◽  
Lateral Sclerosis

The pathogenesis of the fatal neurodegenerative condition amyotrophic lateral sclerosis (ALS) remains to be fully understood. Blood–brain barrier damage (BBBD) has been implicated as an exacerbating factor in several neurodegenerative conditions, including ALS. Therefore, this cross-sectional study used the novel D50 progression model to assess the clinical relevance of BBBD within a cohort of individuals with either ALS (n = 160) or ALS mimicking conditions (n = 31). Routine laboratory parameters in cerebrospinal fluid (CSF) and blood were measured, and the ratio of CSF to serum albumin levels (Qalb) was used as a proxy measure of BBBD. In the univariate analyses, Qalb levels correlated weakly with disease aggressiveness (as indicated by individual D50 values) and physical function (as measured by ALS Functional Rating Scale). However, after adjustment for cofactors in the elastic net regularization, only having limb-onset disease was associated with BBBD. The results reported here emphasize the clinical heterogeneity of ALS and the need for additional longitudinal and multi-modal studies to fully clarify the extent and effect of BBBD in ALS.

scholarly journals Pathomechanisms of Blood-Brain Barrier Disruption in ALS

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Nicholas Kakaroubas ◽  
Samuel Brennan ◽  
Matthew Keon ◽  
Nitin K. Saksena
Keyword(s):  
Neurodegenerative Diseases ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain Barrier Disruption ◽  
Blood Brain ◽  
Neurological Processes ◽  
Brain Barrier Disruption ◽  
Pass Through ◽  
Blood Spinal Cord Barrier ◽  
Novel Therapeutic Strategies

The blood-brain barrier (BBB) and the blood-spinal cord barrier (BSCB) are responsible for controlling the microenvironment within neural tissues in humans. These barriers are fundamental to all neurological processes as they provide the extreme nutritional demands of neural tissue, remove wastes, and maintain immune privileged status. Being a semipermeable membrane, both the BBB and BSCB allow the diffusion of certain molecules, whilst restricting others. In amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases, these barriers become hyperpermeable, allowing a wider variety of molecules to pass through leading to more severe and more rapidly progressing disease. The intention of this review is to discuss evidence that BBB hyperpermeability is potentially a disease driving feature in ALS and other neurodegenerative diseases. The various biochemical, physiological, and genomic factors that can influence BBB permeability in ALS and other neurodegenerative diseases are also discussed, in addition to novel therapeutic strategies centred upon the BBB.

scholarly journals Stem Cell Therapy for Neurodegenerative Diseases: How Do Stem Cells Bypass the Blood-Brain Barrier and Home to the Brain?

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yvonne Cashinn Chia ◽  
Clarice Evey Anjum ◽  
Hui Rong Yee ◽  
Yenny Kenisi ◽  
Mike K. S. Chan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neurodegenerative Diseases ◽  
Blood Brain Barrier ◽  
Cellular Therapy ◽  
Immune Cell ◽  
Brain Barrier ◽  
Normal Brain ◽  
Brain Functions ◽  
Blood Brain ◽  
The Brain

Blood-brain barrier (BBB) is a term describing the highly selective barrier formed by the endothelial cells (ECs) of the central nervous system (CNS) homeostasis by restricting movement across the BBB. An intact BBB is critical for normal brain functions as it maintains brain homeostasis, modulates immune cell transport, and provides protection against pathogens and other foreign substances. However, it also prevents drugs from entering the CNS to treat neurodegenerative diseases. Stem cells, on the other hand, have been reported to bypass the BBB and successfully home to their target in the brain and initiate repair, making them a promising approach in cellular therapy, especially those related to neurodegenerative disease. This review article discusses the mechanism behind the successful homing of stem cells to the brain, their potential role as a drug delivery vehicle, and their applications in neurodegenerative diseases.

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.

Disruption of blood-brain barrier in amyotrophic lateral sclerosis: an update

2012 ◽  
Vol 6 (1) ◽  
pp. 64-70 ◽  
Author(s):  
L. V. Brylev ◽  
M. N. Zakharova ◽  
I. A. Zavalishin ◽  
N. V. Gulyaeva
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain ◽  
Lateral Sclerosis

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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