Fluid Flow and Mass Transport in Brain Tissue

Despite its small size, the brain consumes 25% of the body’s energy, generating its own weight in potentially toxic proteins and biological debris each year. The brain is also the only organ lacking lymph vessels to assist in removal of interstitial waste. Over the past 50 years, a picture has been developing of the brain’s unique waste removal system. Experimental observations show cerebrospinal fluid, which surrounds the brain, enters the brain along discrete pathways, crosses a barrier into the spaces between brain cells, and flushes the tissue, carrying wastes to routes exiting the brain. Dysfunction of this cerebral waste clearance system has been demonstrated in Alzheimer’s disease, traumatic brain injury, diabetes, and stroke. The activity of the system is observed to increase during sleep. In addition to waste clearance, this circuit of flow may also deliver nutrients and neurotransmitters. Here, we review the relevant literature with a focus on transport processes, especially the potential role of diffusion and advective flows.

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Neurotoxic and Neuroprotective Role of Exosomes in Parkinson’s Disease

Current Pharmaceutical Design ◽

10.2174/1381612825666191113103537 ◽

2020 ◽

Vol 25 (42) ◽

pp. 4510-4522 ◽

Cited By ~ 5

Author(s):

Biancamaria Longoni ◽

Irene Fasciani ◽

Shivakumar Kolachalam ◽

Ilaria Pietrantoni ◽

Francesco Marampon ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Potential Role ◽

Current Knowledge ◽

Biological Fluids ◽

Cell Communication ◽

Target Cells ◽

Cellular Debris ◽

The Brain

: Exosomes are extracellular vesicles produced by eukaryotic cells that are also found in most biological fluids and tissues. While they were initially thought to act as compartments for removal of cellular debris, they are now recognized as important tools for cell-to-cell communication and for the transfer of pathogens between the cells. They have attracted particular interest in neurodegenerative diseases for their potential role in transferring prion-like proteins between neurons, and in Parkinson’s disease (PD), they have been shown to spread oligomers of α-synuclein in the brain accelerating the progression of this pathology. A potential neuroprotective role of exosomes has also been equally proposed in PD as they could limit the toxicity of α-synuclein by clearing them out of the cells. Exosomes have also attracted considerable attention for use as drug vehicles. Being nonimmunogenic in nature, they provide an unprecedented opportunity to enhance the delivery of incorporated drugs to target cells. In this review, we discuss current knowledge about the potential neurotoxic and neuroprotective role of exosomes and their potential application as drug delivery systems in PD.

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Acid ceramidase, a double-edged sword in cancer aggression: A minireview

Current Cancer Drug Targets ◽

10.2174/1568009620666201223154621 ◽

2020 ◽

Vol 20 ◽

Author(s):

Helen Shiphrah Vethakanraj ◽

Niveditha Chandrasekaran ◽

Ashok Kumar Sekar

Keyword(s):

Cell Fate ◽

Cancer Progression ◽

Potential Role ◽

Tumour Progression ◽

Acid Ceramidase ◽

The Core ◽

The Past ◽

Sphingosine 1 Phosphate ◽

Key Enzyme

: Acid ceramidase (AC), the key enzyme of the ceramide metabolic pathway hydrolyzes pro-apoptotic ceramide to sphingosine, which by the action of sphingosine-1-kinase is metabolized to mitogenic sphingosine-1-phosphate. The intracellular level of AC determines ceramide/sphingosine-1-phosphate rheostat which in turn decides the cell fate. The upregulated AC expression during cancerous condition acts as a “double-edged sword” by converting pro-apoptotic ceramide to anti-apoptotic sphingosine-1-phosphate, wherein on one end, the level of ceramide is decreased and on the other end, the level of sphingosine-1-phosphate is increased, thus altogether aggravating the cancer progression. In addition, cancer cells with upregulated AC expression exhibited increased cell proliferation, metastasis, chemoresistance, radioresistance and numerous strategies were developed in the past to effectively target the enzyme. Gene silencing and pharmacological inhibition of AC sensitized the resistant cells to chemo/radiotherapy thereby promoting cell death. The core objective of this review is to explore AC mediated tumour progression and the potential role of AC inhibitors in various cancer cell lines/models.

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Chemo- and Optogenetic Strategies for the Elucidation of Pain Pathways

The Oxford Handbook of the Neurobiology of Pain ◽

10.1093/oxfordhb/9780190860509.013.33 ◽

2019 ◽

pp. 816-832 ◽

Cited By ~ 1

Author(s):

Sascha R. A. Alles ◽

Anne-Marie Malfait ◽

Richard J. Miller

Keyword(s):

Chronic Pain ◽

Pain Response ◽

Conscious Perception ◽

Novel Therapies ◽

The Past ◽

Nociceptive Pathways ◽

Pain Pathways ◽

Technical Advances ◽

The Brain

Pain is not a simple phenomenon and, beyond its conscious perception, involves circuitry that allows the brain to provide an affective context for nociception, which can influence mood and memory. In the past decade, neurobiological techniques have been developed that allow investigators to elucidate the importance of particular groups of neurons in different aspects of the pain response, something that may have important translational implications for the development of novel therapies. Chemo- and optogenetics represent two of the most important technical advances of recent times for gaining understanding of physiological circuitry underlying complex behaviors. The use of these techniques for teasing out the role of neurons and glia in nociceptive pathways is a rapidly growing area of research. The major findings of studies focused on understanding circuitry involved in different aspects of nociception and pain are highlighted in this article. In addition, attention is drawn to the possibility of modification of chemo- and optogenetic techniques for use as potential therapies for treatment of chronic pain disorders in human patients.

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The Microbiota–Gut–Brain Axis and Alzheimer Disease. From Dysbiosis to Neurodegeneration: Focus on the Central Nervous System Glial Cells

Journal of Clinical Medicine ◽

10.3390/jcm10112358 ◽

2021 ◽

Vol 10 (11) ◽

pp. 2358

Author(s):

Maria Grazia Giovannini ◽

Daniele Lana ◽

Chiara Traini ◽

Maria Giuliana Vannucchi

Keyword(s):

Alzheimer Disease ◽

Glial Cells ◽

Cell Types ◽

The Past ◽

The Central Nervous System ◽

Diseased State ◽

The Brain ◽

Alzheimer Disease Pathogenesis ◽

Brain Homeostasis

The microbiota–gut system can be thought of as a single unit that interacts with the brain via the “two-way” microbiota–gut–brain axis. Through this axis, a constant interplay mediated by the several products originating from the microbiota guarantees the physiological development and shaping of the gut and the brain. In the present review will be described the modalities through which the microbiota and gut control each other, and the main microbiota products conditioning both local and brain homeostasis. Much evidence has accumulated over the past decade in favor of a significant association between dysbiosis, neuroinflammation and neurodegeneration. Presently, the pathogenetic mechanisms triggered by molecules produced by the altered microbiota, also responsible for the onset and evolution of Alzheimer disease, will be described. Our attention will be focused on the role of astrocytes and microglia. Numerous studies have progressively demonstrated how these glial cells are important to ensure an adequate environment for neuronal activity in healthy conditions. Furthermore, it is becoming evident how both cell types can mediate the onset of neuroinflammation and lead to neurodegeneration when subjected to pathological stimuli. Based on this information, the role of the major microbiota products in shifting the activation profiles of astrocytes and microglia from a healthy to a diseased state will be discussed, focusing on Alzheimer disease pathogenesis.

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Anti-phospholipid syndrome and COVID-19 thrombosis: connecting the dots

Rheumatology Advances in Practice ◽

10.1093/rap/rkaa081 ◽

2021 ◽

Vol 5 (1) ◽

Author(s):

Moon Ley Tung ◽

Bryce Tan ◽

Robin Cherian ◽

Bharatendu Chandra

Keyword(s):

Endothelial Dysfunction ◽

Severe Acute Respiratory Syndrome ◽

Potential Role ◽

Molecular Mimicry ◽

Thromboembolic Events ◽

The Past ◽

High Prevalence ◽

Connecting The Dots ◽

Anti Phospholipid Syndrome

Abstract As the coronavirus disease 2019 (COVID-19) pandemic, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading rapidly worldwide, it has emerged as a leading cause of mortality, resulting in >1 million deaths over the past 10 months. The pathophysiology of COVID-19 remains unclear, posing a great challenge to the medical management of patients. Recent studies have reported an unusually high prevalence of thromboembolic events in COVID-19 patients, although the mechanism remains elusive. Several studies have reported the presence of aPLs in COVID-19 patients. We have noticed similarities between COVID-19 and APS, which is an autoimmune prothrombotic disease that is often associated with an infective aetiology. Molecular mimicry and endothelial dysfunction could plausibly explain the mechanism of thrombogenesis in acquired APS. In this review, we discuss the clinicopathological similarities between COVID-19 and APS, and the potential role of therapeutic targets based on the anti-phospholipid model for COVID-19 disease.

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SARS-CoV-2 journey to the brain with a focus on potential role of docosahexaenoic acid bioactive lipid mediators

Biochimie ◽

10.1016/j.biochi.2021.02.012 ◽

2021 ◽

Vol 184 ◽

pp. 95-103

Author(s):

Mayssa Hachem

Keyword(s):

Docosahexaenoic Acid ◽

Potential Role ◽

Lipid Mediators ◽

The Brain

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Nitric oxide: a new role in intensive care

Critical Care and Resuscitation ◽

10.51893/2020.1.sr1 ◽

2020 ◽

Vol 22 (1) ◽

pp. 72-79

Author(s):

Alexandra Lee ◽

◽

Warwick Butt ◽

◽

...

Keyword(s):

Nitric Oxide ◽

Potential Role ◽

Nitric Oxide Donors ◽

Ischaemia Reperfusion Injury ◽

Surface Receptors ◽

The Past ◽

Ischaemia Reperfusion ◽

Human Experiments ◽

Endogenous Nitric Oxide

Inhaled nitric oxide has been used for 30 years to improve oxygenation and decrease pulmonary vascular resistance. In the past 15 years, there has been increased understanding of the role of endogenous nitric oxide on cell surface receptors, mitochondria, and intracellular processes involving calcium and superoxide radicals. This has led to several animal and human experiments revealing a potential role for administered nitric oxide or nitric oxide donors in patients with systemic inflammatory response syndrome or ischaemia–reperfusion injury, and in patients for whom exposure of blood to artificial surfaces has occurred.

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3-Phenylcoumarins as a Privileged Scaffold in Medicinal Chemistry: The Landmarks of the Past Decade

Molecules ◽

10.3390/molecules26216755 ◽

2021 ◽

Vol 26 (21) ◽

pp. 6755

Author(s):

Maria J. Matos ◽

Eugenio Uriarte ◽

Lourdes Santana

Keyword(s):

Medicinal Chemistry ◽

Review Paper ◽

Relevant Literature ◽

Natural Origin ◽

Drug Candidates ◽

Heterocyclic Molecules ◽

The Past ◽

New Drug ◽

Privileged Scaffold

3-Phenylcoumarins are a family of heterocyclic molecules that are widely used in both organic and medicinal chemistry. In this overview, research on this scaffold, since 2010, is included and discussed, focusing on aspects related to its natural origin, synthetic procedures and pharmacological applications. This review paper is based on the most relevant literature related to the role of 3-phenylcoumarins in the design of new drug candidates. The references presented in this review have been collected from multiple electronic databases, including SciFinder, Pubmed and Mendeley.

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Fifty years ago: ‘The scope of occupational medicine in a university health service’

Why I Became an Occupational Physician and Other Occupational Health Stories ◽

10.1093/med/9780198862543.003.0161 ◽

2020 ◽

pp. 202-203

Author(s):

Anthony Ryle

Keyword(s):

Health Service ◽

Physical Health ◽

Occupational Medicine ◽

Potential Role ◽

Health And Safety ◽

Academic Achievements ◽

The Past ◽

Selection Of

This series provides a selection of articles from the past. In Fifty years ago: The scope of occupational medicine in a university health service Anthony Ryle briefly explores the potential role of a University Health Service in relation to students’ academic achievements and failures, rather than their physical health and safety.

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