Structure, Function, and Regulation of the Blood-Brain Barrier Tight Junction in Central Nervous System Disorders

Frontiers in Physiology, Journal Year: 2020, Volume and Issue: 11

Published: Aug. 6, 2020

The blood-brain barrier (BBB) allows the brain to selectively import nutrients and energy critical neuronal function while simultaneously excluding neurotoxic substances from peripheral circulation. In contrast highly permeable vasculature present in most organs that reside outside of central nervous system (CNS), BBB exhibits a high transendothelial electrical resistance along with low rate transcytosis greatly restricted paracellular permeability. property permeability is controlled by tight junction protein complexes seal route between apposing microvascular endothelial cells. Although are principal contributors physical properties, they not static nature. Rather, dynamic structures where expression and/or localization individual constituent proteins can be modified response pathophysiological stressors. These stressors induce modifications involve de novo synthesis new or discrete trafficking mechanisms. Such responsiveness junctions diseases indicates these for maintenance CNS homeostasis. fulfillment this vital role, also major obstacle therapeutic drug delivery brain. There an opportunity overcome substantial optimize neuropharmacology via acquisition detailed understanding structure, function, regulation. review, we discuss physiological characteristics how properties regulate therapeutics treatment neurological diseases. Specifically, will modulation regulation both context disease states setting pharmacotherapy. particular, highlight potentially manipulated at molecular level increase levels transport

Language: Английский

---

Pathophysiology of Blood–Brain Barrier Permeability Throughout the Different Stages of Ischemic Stroke and Its Implication on Hemorrhagic Transformation and Recovery

Frontiers in Neurology, Journal Year: 2020, Volume and Issue: 11

Published: Dec. 9, 2020

The blood-brain barrier (BBB) is a dynamic interface responsible for maintaining the central nervous system homeostasis. Its unique characteristics allow protecting brain from unwanted compounds, but its impairment involved in vast number of pathological conditions. Disruption BBB and increase permeability are key development several neurological diseases have been extensively studied stroke. Ischemic stroke most prevalent type characterized by myriad events triggered an arterial occlusion that can eventually lead to fatal outcomes such as hemorrhagic transformation (HT). seems follow multiphasic pattern throughout different stages associated with distinct biological substrates. In hyperacute stage, sudden hypoxia damages BBB, leading cytotoxic edema increased permeability; acute neuroinflammatory response aggravates injury, higher consequent risk HT be motivated reperfusion therapy; subacute stage (1-3 weeks), repair mechanisms take place, especially neoangiogenesis. Immature vessels show leaky this has improved clinical recovery. chronic (>6 restoration factors leads start decreasing permeability. Nonetheless, will persist some degree weeks after injury. Understanding behind dysregulation pathophysiology could potentially help guide care decisions new therapeutic targets; however, effective translation into practice still lacking. review, we address physiological through ischemic their role

Language: Английский

---

Alzheimer’s Disease and Vascular Aging

Journal of the American College of Cardiology, Journal Year: 2020, Volume and Issue: 75(8), P. 942 - 951

Published: Feb. 24, 2020

Alzheimer's disease, the leading cause of dementia in elderly, is a neurodegenerative condition characterized by accumulation amyloid plaques and neurofibrillary tangles brain. However, age-related vascular changes accompany or even precede development pathology, raising possibility that they may have pathogenic role. This review provides an appraisal alterations cerebral systemic vasculature, heart, hemostasis occur disease their relationships to cognitive impairment. Although molecular pathogenesis these remains be defined, amyloid-β likely contributor brain as heart. Collectively, evidence suggests pathology dementia, including inextricably linked onset progression. Consequently, contribution factors should considered preventive, diagnostic, therapeutic approaches address one major health challenges our time.

Language: Английский

---

What is a cell type and how to define it?

Cell, Journal Year: 2022, Volume and Issue: 185(15), P. 2739 - 2755

Published: July 1, 2022

Language: Английский

---

Preventing dementia by preventing stroke: The Berlin Manifesto

Alzheimer s & Dementia, Journal Year: 2019, Volume and Issue: 15(7), P. 961 - 984

Published: July 1, 2019

Abstract The incidence of stroke and dementia are diverging across the world, rising for those in low‐ middle‐income countries falling high‐income countries. This suggests that whatever factors cause these trends potentially modifiable. At population level, neurological disorders as a group account largest proportion disability‐adjusted life years globally (10%). Among disorders, (42%) (10%) dominate. Stroke confer risks each other share some same, largely modifiable, risk protective factors. In principle, 90% strokes 35% dementias have been estimated to be preventable. Because doubles chance developing is more common than dementia, third could prevented by preventing stroke. Developments at pathological, pathophysiological, clinical level also point new directions. Growing understanding brain pathophysiology has unveiled reciprocal interaction cerebrovascular disease neurodegeneration identifying therapeutic targets include protection endothelium, blood‐brain barrier, components neurovascular unit. addition, targeting amyloid angiopathy aspects inflammation genetic manipulation hold testable promise. meantime, accumulating evidence whole populations experiencing improved education, lower vascular factor profiles (e.g., reduced prevalence smoking) disease, including stroke, better cognitive function rates. individual levels, trials demonstrated anticoagulation atrial fibrillation can reduce 48% systolic blood pressure 140 mmHg may brain. Based on considerations, World Organization issued proclamation, endorsed all major international organizations focused global cardiovascular health, calling joint prevention dementia. article summarizes translation into action.

Language: Английский

---