The blood-brain barrier: Physiology and strategies for drug delivery

Advanced Drug Delivery Reviews, Journal Year: 2019, Volume and Issue: 165-166, P. 1 - 14

Published: Nov. 29, 2019

Language: Английский

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A Phase‐by‐Phase Review of Migraine Pathophysiology

Headache The Journal of Head and Face Pain, Journal Year: 2018, Volume and Issue: 58(S1), P. 4 - 16

Published: April 26, 2018

Migraine is a common, disabling neurological disorder characterized by multiple phases: premonitory, aura, headache, postdrome, and interictal. Our understanding of the pathophysiology each phase migraine has evolved over recent years. The premonitory begins as early 3 days before headache phase, involves complex interplay between various cortical subcortical brain regions, including hypothalamus brainstem nuclei that modulate nociceptive signaling. activation trigeminovascular system, pathway well characterized. In one‐third patients, an aura may occur during some attacks likely correlates with spreading depression‐like event; slowly propagating wave neuronal glial cell depolarization hyperpolarization. Improved characterization pathophysiological processes involved at stage attack will aid identification new therapeutic targets for prevention. This review provides update on prevailing concepts pathophysiology.

Language: Английский

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Targeting and Crossing the Blood-Brain Barrier with Extracellular Vesicles

Cells, Journal Year: 2020, Volume and Issue: 9(4), P. 851 - 851

Published: April 1, 2020

The blood–brain barrier (BBB) is one of the most complex and selective barriers in human organism. Its role to protect brain preserve homeostasis central nervous system (CNS). elements this physical physiological are endothelial cells that form a monolayer tightly joined covering capillaries. However, as regulate nutrient delivery waste product elimination, they very sensitive signals sent by surrounding their environment. Indeed, neuro-vascular unit (NVU) corresponds assembly extracellular matrix, pericytes, astrocytes, oligodendrocytes, microglia neurons have ability influence BBB physiology. Extracellular vesicles (EVs) play terms communication between cells. NVU no exception, each cell can produce EVs could help short or long distances. Studies shown able cross from bloodstream well blood CNS. Furthermore, peripheral interact with leading changes barrier’s properties. This review focuses on current knowledge potential applications regarding associated BBB.

Language: Английский

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Pericytes and Neurovascular Function in the Healthy and Diseased Brain

Frontiers in Cellular Neuroscience, Journal Year: 2019, Volume and Issue: 13

Published: June 28, 2019

Pericytes are multi-functional cells embedded within the walls of capillaries throughout body, including brain. were first identified in 1870s, but little attention was paid to them during following century. More recently, numerous vascular functions pericytes have been regulation cerebral blood flow, maintenance blood-brain barrier, and control development angiogenesis. can also facilitate neuroinflammatory processes possess stem cell-like properties. form part neurovascular unit, a collection that interactions between neurons vasculature meet energy demands Pericyte structure, expression profile, function brain differ depending on their location along bed. Until it has difficult accurately define sub-types pericytes, or specifically target with pharmaceutical agents, emerging techniques both vitro vivo will improve investigation allow for identification possible roles diseases. dysfunction is increasingly recognized as contributor progression diseases such stroke neurodegenerative Alzheimer's disease. The therapeutic potential repair vessels promote angiogenesis due ability behave like recently brought light. Here, we review history pericyte research, present used study brain, current research advancements characterize therapeutically future.

Language: Английский

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Chronic cerebral hypoperfusion: a key mechanism leading to vascular cognitive impairment and dementia. Closing the translational gap between rodent models and human vascular cognitive impairment and dementia

Clinical Science, Journal Year: 2017, Volume and Issue: 131(19), P. 2451 - 2468

Published: Sept. 28, 2017

Increasing evidence suggests that vascular risk factors contribute to neurodegeneration, cognitive impairment and dementia. While there is considerable overlap between features of dementia (VCID) Alzheimer’s disease (AD), it appears cerebral hypoperfusion the common underlying pathophysiological mechanism which a major contributor decline degenerative processes leading Sustained suggested be cause white matter attenuation, key feature both AD associated with small vessel (SVD). White changes increase for stroke, disability. A gap has been lack mechanistic insights into evolution progress VCID. However, this closing recent refinement rodent models replicate chronic hypoperfusion. In review, we discuss relevance advantages these in elucidating pathogenesis VCID explore interplay deposition amyloid β (Aβ) protein, as relates AD. We use examples our investigations illustrate utility model preclinical testing candidate drugs lifestyle factors. propose such necessary tackling urgently needed translational from clinical treatments.

Language: Английский

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Neuroimmune Axes of the Blood–Brain Barriers and Blood–Brain Interfaces: Bases for Physiological Regulation, Disease States, and Pharmacological Interventions

Pharmacological Reviews, Journal Year: 2018, Volume and Issue: 70(2), P. 278 - 314

Published: March 1, 2018

Central nervous system (CNS) barriers predominantly mediate the immune-privileged status of brain, and are also important regulators neuroimmune communication. It is increasingly appreciated that communication between brain immune contributes to physiologic processes, adaptive responses, disease states. In this review, we discuss highly specialized features regulate in health disease. section I, concept privilege, provide working definitions barriers, outline historical work contributed understanding CNS barrier functions. II, unique anatomic, cellular, molecular characteristics vascular blood–brain (BBB), blood–cerebrospinal fluid barrier, tanycytic confer their functions as interfaces. III, consider BBB-mediated interactions categorized five axes: disruption, responses stimuli, uptake transport immunoactive substances, cell trafficking, secretions substances. IV, states, well pharmacological interventions for diseases. Throughout highlight many recent advances have modern interface

Language: Английский

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The blood–brain barrier in psychosis

The Lancet Psychiatry, Journal Year: 2017, Volume and Issue: 5(1), P. 79 - 92

Published: Aug. 3, 2017

Language: Английский

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Immune Cells in the BBB Disruption After Acute Ischemic Stroke: Targets for Immune Therapy?

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: June 23, 2021

Blood-Brain Barrier (BBB) disruption is an important pathophysiological process of acute ischemic stroke (AIS), resulting in devastating malignant brain edema and hemorrhagic transformation. The rapid activation immune cells plays a critical role BBB after stroke. Infiltrating blood-borne (neutrophils, monocytes, T lymphocytes) increase permeability, as they cause microvascular disorder secrete inflammation-associated molecules. In contrast, promote repair angiogenesis the latter phase profound immunological effects cerebral (microglia, astrocytes, pericytes) on have been underestimated Post-stroke microglia astrocytes can adopt both M1/A1 or M2/A2 phenotype, which influence integrity differently. However, whether pericytes acquire phenotype exert remains controversial. Thus, better understanding inflammatory mechanism underlying lead to identification more promising biological targets develop treatments that minimize onset life-threatening complications improve existing patients. early attempts inhibit infiltration circulating into by blocking adhesion molecules, were successful experimental failed clinical trials. Therefore, new immunoregulatory therapeutic strategies for are desperately warranted. Herein, we highlight crosstalk between them following Using robust theoretical background, discuss potential effective immunotherapeutic regulate permeability

Language: Английский

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Microvascular Dysfunction in Diabetes Mellitus and Cardiometabolic Disease

Endocrine Reviews, Journal Year: 2020, Volume and Issue: 42(1), P. 29 - 55

Published: Oct. 30, 2020

Abstract This review takes an inclusive approach to microvascular dysfunction in diabetes mellitus and cardiometabolic disease. In virtually every organ, dynamic interactions between the microvasculature resident tissue elements normally modulate vascular function a homeostatic fashion. regulation is disordered by mellitus, hypertension, obesity, dyslipidemia individually (or combined disease), with serving as early marker of change. particular, we suggest that familiar retinal, renal, neural complications are late-stage manifestations injury begins years earlier often abetted other disease (eg, dyslipidemia). We focus on evidence precedes anatomic these organs well heart, muscle, brain. on, and/or can each cause reversible accompanying dysfunction, which time may or not become irreversible anatomically identifiable basement membrane thickening, capillary rarefaction, pericyte loss, etc.). Consequences include vision renal insufficiency, neuropathy, but also heart failure, sarcopenia, cognitive impairment, escalating metabolic dysfunction. Our understanding normal rapidly evolving, aided innovative genetic imaging tools. leading, tissues like retina, testing novel preventive interventions at early, stages injury. Great hope lies possibility some develop into effective therapies.

Language: Английский

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Fatigue, Sleep, and Autoimmune and Related Disorders

Frontiers in Immunology, Journal Year: 2019, Volume and Issue: 10

Published: Aug. 6, 2019

Profound and debilitating fatigue is the most common complaint reported among individuals with autoimmune disease, such as systemic lupus erythematosus, multiple sclerosis, type 1 diabetes, celiac chronic syndrome, rheumatoid arthritis. Fatigue multi-faceted broadly defined, which makes understanding cause of its manifestations especially difficult in conditions diverse pathology including diseases. In general, defined by periods exhaustion that interfere normal activities. The severity duration episodes vary, but can difficulty for even simple tasks like climbing stairs or crossing room. exact mechanisms are not well understood, perhaps due to broad definition. Nevertheless, physiological processes known play a role include oxygen/nutrient supply, metabolism, mood, motivation, sleepiness—all affected inflammation. Additionally, an important contributing element central nervous system—a region impacted either directly indirectly numerous related disorders. This review describes how inflammation system contribute suggests potential involved likely exhibited

Language: Английский

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