scholarly journals Lipid Transport and Metabolism at the Blood-Brain Interface: Implications in Health and Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Fabien Pifferi ◽  
Benoit Laurent ◽  
Mélanie Plourde
Keyword(s):  
Fatty Acids ◽  
Neurodegenerative Diseases ◽  
Current Knowledge ◽  
Lipid Transport ◽  
Omega 3 ◽  
Blood Brain ◽  
Brain Interface ◽  
The Central Nervous System ◽  
Health And Disease ◽  
The Brain

Many prospective studies have shown that a diet enriched in omega-3 polyunsaturated fatty acids (n-3 PUFAs) can improve cognitive function during normal aging and prevent the development of neurocognitive diseases. However, researchers have not elucidated how n-3 PUFAs are transferred from the blood to the brain or how they relate to cognitive scores. Transport into and out of the central nervous system depends on two main sets of barriers: the blood-brain barrier (BBB) between peripheral blood and brain tissue and the blood-cerebrospinal fluid (CSF) barrier (BCSFB) between the blood and the CSF. In this review, the current knowledge of how lipids cross these barriers to reach the CNS is presented and discussed. Implications of these processes in health and disease, particularly during aging and neurodegenerative diseases, are also addressed. An assessment provided here is that the current knowledge of how lipids cross these barriers in humans is limited, which hence potentially restrains our capacity to intervene in and prevent neurodegenerative diseases.

scholarly journals The blood–brain barrier in health and disease: Important unanswered questions

2020 ◽  
Vol 217 (4) ◽  
Author(s):  
Caterina P. Profaci ◽  
Roeben N. Munji ◽  
Robert S. Pulido ◽  
Richard Daneman
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Blood Brain Barrier ◽  
Current Knowledge ◽  
Brain Barrier ◽  
Barrier Dysfunction ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Health And Disease ◽  
Neurological Conditions

The blood vessels vascularizing the central nervous system exhibit a series of distinct properties that tightly control the movement of ions, molecules, and cells between the blood and the parenchyma. This “blood–brain barrier” is initiated during angiogenesis via signals from the surrounding neural environment, and its integrity remains vital for homeostasis and neural protection throughout life. Blood–brain barrier dysfunction contributes to pathology in a range of neurological conditions including multiple sclerosis, stroke, and epilepsy, and has also been implicated in neurodegenerative diseases such as Alzheimer’s disease. This review will discuss current knowledge and key unanswered questions regarding the blood–brain barrier in health and disease.

scholarly journals Omega – 3 fatty acids in schizophrenia – part I: importance in the pathophysiology of schizophrenia

2016 ◽  
Vol 17 (3) ◽  
pp. 198-213
Author(s):  
Joanna Róg ◽  
Hanna Karakuła-Juchnowicz
Keyword(s):  
Fatty Acids ◽  
Nervous System ◽  
Essential Fatty Acids ◽  
Dry Weight ◽  
Omega 3 ◽  
Metabolic Complications ◽  
The Central Nervous System ◽  
David Horrobin ◽  
The Brain

AbstractDespite the increasing offer of antipsychotic drugs, the effectiveness of pharmacotherapy in schizophrenia is still unsatisfactory. Drug resistance, lack of complete remission and the increasing risk of metabolic complications are the reasons why the new forms of therapy in schizophrenia among which unsaturated essential fatty acids omega 3 (EFAs ω-3) affecting the proper functioning of nervous system, are mentioned, are being looked for.Fatty acids represent 50-60% of the dry weight of the brain and diet is one of the factors that influence the value of each of the fat fractions in the neuron membranes. Patients with schizophrenia tend to have irregular nutritional status concerning essential fatty acids ω-3, which might result from metabolic disorders or irregular consumption of fatty acids.Apart from being a review of the literature on this subject, this very paper characterizes essential fatty acids ω-3, their metabolism, the most important sources in the diet and the opinions of experts in the field about the recommended intake. It pays attention to the role of essential fatty acids in both the structure and functioning of the central nervous system is, as well as their role in the pathophysiology of schizophrenia, with particular emphasis on the membrane concept by David Horrobin. The assessment of the errors in consumption and metabolism of essential fatty acids are described as well.The evidence was found both in epidemiological and modeling studies. It supports the participation of EFAs in etiopathogenesis and pathophysiology of schizophrenia. Further research is needed, both observational and interventional, as to the role of essential fatty acids ω-3 in the functioning of the CNS as well as the development and course of schizophrenia.

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.

scholarly journals The Aryl Hydrocarbon Receptor: A Mediator and Potential Therapeutic Target for Ocular and Non-Ocular Neurodegenerative Diseases

2020 ◽  
Vol 21 (18) ◽  
pp. 6777
Author(s):  
Mayur Choudhary ◽  
Goldis Malek
Keyword(s):  
Neurodegenerative Diseases ◽  
Aryl Hydrocarbon Receptor ◽  
Current Knowledge ◽  
Transcriptional Response ◽  
Cellular Processes ◽  
Aryl Hydrocarbon ◽  
Metabolic Products ◽  
The Central Nervous System ◽  
Health And Disease

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor, which senses environmental, dietary or metabolic signals to mount a transcriptional response, vital in health and disease. As environmental stimuli and metabolic products have been shown to impact the central nervous system (CNS), a burgeoning area of research has been on the role of the AHR in ocular and non-ocular neurodegenerative diseases. Herein, we summarize our current knowledge, of AHR-controlled cellular processes and their impact on regulating pathobiology of select ocular and neurodegenerative diseases. We catalogue animal models generated to study the role of the AHR in tissue homeostasis and disease pathogenesis. Finally, we discuss the potential of targeting the AHR pathway as a therapeutic strategy, in the context of the maladies of the eye and brain.

scholarly journals THE ROLE OF OXIDATIVE STRESS IN THE ETIOPATHOGENESIS OF DEPRESSION

2019 ◽  
Vol 17 (1) ◽  
pp. 81-93 ◽  
Author(s):  
D. Komsiiska ◽  
Y. Petkov
Keyword(s):  
Oxidative Stress ◽  
Fatty Acids ◽  
Central Nervous System ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Cytotoxic Effects ◽  
Negative Effect ◽  
The Central Nervous System ◽  
The Brain

In recent years, the role of oxidative stress in the etiopathogenesis of depression has been increasingly discussed. The mechanisms by which stress has a negative effect on the brain are not yet fully understood. Free radicals cause rapid damage to certain cellular macromolecules that may be involved in cytotoxic effects in the central nervous system. The effectiveness of new types of supplementation therapy with antioxidants - vitamins A, E, C, Omega-3 fatty acids, Coenzyme Q10 and Zn are being studied.

scholarly journals Monitoring and Modulating Inflammation-Associated Alterations in Synaptic Plasticity: Role of Brain Stimulation and the Blood–Brain Interface

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 359
Author(s):  
Maximilian Lenz ◽  
Amelie Eichler ◽  
Andreas Vlachos
Keyword(s):  
Synaptic Plasticity ◽  
Brain Stimulation ◽  
Vascular Function ◽  
Neuropsychiatric Symptoms ◽  
Systemic Infection ◽  
Brain Functions ◽  
Blood Brain ◽  
Brain Interface ◽  
The Central Nervous System

Inflammation of the central nervous system can be triggered by endogenous and exogenous stimuli such as local or systemic infection, trauma, and stroke. In addition to neurodegeneration and cell death, alterations in physiological brain functions are often associated with neuroinflammation. Robust experimental evidence has demonstrated that inflammatory cytokines affect the ability of neurons to express plasticity. It has been well-established that inflammation-associated alterations in synaptic plasticity contribute to the development of neuropsychiatric symptoms. Nevertheless, diagnostic approaches and interventional strategies to restore inflammatory deficits in synaptic plasticity are limited. Here, we review recent findings on inflammation-associated alterations in synaptic plasticity and the potential role of the blood–brain interface, i.e., the blood–brain barrier, in modulating synaptic plasticity. Based on recent findings indicating that brain stimulation promotes plasticity and modulates vascular function, we argue that clinically employed non-invasive brain stimulation techniques, such as transcranial magnetic stimulation, could be used for monitoring and modulating inflammation-induced alterations in synaptic plasticity.

scholarly journals Can Natural Products Exert Neuroprotection without Crossing the Blood–Brain Barrier?

2021 ◽  
Vol 22 (7) ◽  
pp. 3356
Author(s):  
Manon Leclerc ◽  
Stéphanie Dudonné ◽  
Frédéric Calon
Keyword(s):  
Natural Products ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Brain Diseases ◽  
Omega 3 ◽  
Indirect Pathway ◽  
Brain Functions ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Peripheral Metabolism

The scope of evidence on the neuroprotective impact of natural products has been greatly extended in recent years. However, a key question that remains to be answered is whether natural products act directly on targets located in the central nervous system (CNS), or whether they act indirectly through other mechanisms in the periphery. While molecules utilized for brain diseases are typically bestowed with a capacity to cross the blood–brain barrier, it has been recently uncovered that peripheral metabolism impacts brain functions, including cognition. The gut–microbiota–brain axis is receiving increasing attention as another indirect pathway for orally administered compounds to act on the CNS. In this review, we will briefly explore these possibilities focusing on two classes of natural products: omega-3 polyunsaturated fatty acids (n-3 PUFAs) from marine sources and polyphenols from plants. The former will be used as an example of a natural product with relatively high brain bioavailability but with tightly regulated transport and metabolism, and the latter as an example of natural compounds with low brain bioavailability, yet with a growing amount of preclinical and clinical evidence of efficacy. In conclusion, it is proposed that bioavailability data should be sought early in the development of natural products to help identifying relevant mechanisms and potential impact on prevalent CNS disorders, such as Alzheimer’s disease.

scholarly journals Polyunsaturated Fatty Acids: Impact on Health and Disease Status

2021 ◽  
Vol 2 (2) ◽  
pp. 12
Author(s):  
Samina Akbar ◽  
Muhammad Zeeshan Bhatti ◽  
Rida Fatima Saeed ◽  
Asma Saleem Qazi
Keyword(s):  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Disease Status ◽  
Epidemiological Studies ◽  
Lipid Lowering ◽  
Therapeutic Effects ◽  
Omega 3 ◽  
Beneficial Effects ◽  
Omega 6 ◽  
Health And Disease

Over the last decades, the polyunsaturated fatty acids (PUFAs) have been largely explored not only for their nutritional value but also for the numerous biological functions and therapeutic effects. The serum and erythrocyte levels of PUFAs depend on the genetic control of metabolism as well as the dietary intake and are considered to reflect the health and disease status of an individual. Two families of PUFAs, omega-3 (n-3) and omega-6 (n-6), have gained much attention because of their involvement in the production of bioactive lipid mediators and therefore, a balanced omega-6/omega-3 ratio is crucial in maintaining the overall health of an individual. Omega-3 PUFAs, notably eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) have been shown to exert beneficial effects, possibly due to their lipid-lowering, anti-inflammatory, anti-hypertensive and cardioprotective effects, whereas omega-6 fatty acids such as arachidonic acid (ARA, 20:4n-6) exhibit the opposite properties. Even though, numerous epidemiological studies and clinical interventions have clearly established the effectiveness of omega-3 PUFAs in various pathological conditions including dyslipidemia, obesity, diabetes, cancer, cardiovascular and neurodegenerative diseases, some controversies do exist about the beneficial effects of omega-3 PUFAs and need to be clarified. Larger clinical trials with extended follow-up periods are required along with a careful dose selection, in order to confirm the clinical significance and efficacy of omega-3 PUFAs as therapeutic agents.

scholarly journals New Insights on the Effects of Dietary Omega-3 Fatty Acids on Impaired Skin Healing in Diabetes and Chronic Venous Leg Ulcers

Foods ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2306
Author(s):  
Simona Serini ◽  
Gabriella Calviello
Keyword(s):  
Fatty Acids ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Healing Process ◽  
Vascular Diseases ◽  
Lower Limbs ◽  
Bioactive Metabolites ◽  
Omega 3 ◽  
Patients With Diabetes ◽  
Skin Healing

Long-chain Omega-3 polyunsaturated fatty acids (Omega-3 PUFAs) are widely recognized as powerful negative regulators of acute inflammation. However, the precise role exerted by these dietary compounds during the healing process is still largely unknown, and there is increasing interest in understanding their specific effects on the implicated cells/molecular factors. Particular attention is being focused also on their potential clinical application in chronic pathologies characterized by delayed and impaired healing, such as diabetes and vascular diseases in lower limbs. On these bases, we firstly summarized the current knowledge on wound healing (WH) in skin, both in normal conditions and in the setting of these two pathologies, with particular attention to the cellular and molecular mechanisms involved. Then, we critically reviewed the outcomes of recent research papers investigating the activity exerted by Omega-3 PUFAs and their bioactive metabolites in the regulation of WH in patients with diabetes or venous insufficiency and showing chronic recalcitrant ulcers. We especially focused on recent studies investigating the mechanisms through which these compounds may act. Considerations on the optimal dietary doses are also reported, and, finally, possible future perspectives in this area are suggested.

scholarly journals The Gut Ecosystem: A Critical Player in Stroke

2020 ◽  
Author(s):  
Rosa Delgado Jiménez ◽  
Corinne Benakis
Keyword(s):  
Current Knowledge ◽  
Critical Factor ◽  
Intestinal Microbiome ◽  
Brain Disorders ◽  
Therapeutic Approaches ◽  
Health And Disease ◽  
Brain Stroke ◽  
The Brain ◽  
Improve Patient

AbstractThe intestinal microbiome is emerging as a critical factor in health and disease. The microbes, although spatially restricted to the gut, are communicating and modulating the function of distant organs such as the brain. Stroke and other neurological disorders are associated with a disrupted microbiota. In turn, stroke-induced dysbiosis has a major impact on the disease outcome by modulating the immune response. In this review, we present current knowledge on the role of the gut microbiome in stroke, one of the most devastating brain disorders worldwide with very limited therapeutic options, and we discuss novel insights into the gut-immune-brain axis after an ischemic insult. Understanding the nature of the gut bacteria-brain crosstalk may lead to microbiome-based therapeutic approaches that can improve patient recovery.

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