Abstract
The blood-brain barrier (BBB) is a critical regulator of brain homeostasis. Additionally, the BBB is the most significant obstacle to effective CNS drug delivery. It possesses specific charcteristics (i.e., tight junction protein complexes, influx and efflux transporters) that control permeation of circulating solutes including therapeutic agents. In order to form this “barrier,” brain microvascular endothelial cells require support of adjacent astrocytes and microglia. This intricate relationship also occurs between endothelial cells and other cell types and structures of the CNS (i.e., pericytes, neurons, extracellular matrix), which implies existence of a “neurovascular unit.” Ischemic stroke can disrupt the neurovascular unit at both the structural and functional level, which leads to an increase in leak across the BBB. Recent studies have identified several pathophysiological mechanisms (i.e., oxidative stress, activation of cytokinemediated intracellular signaling systems) that mediate changes in the neurovascular unit during ischemic stroke. This review summarizes current knowledge in this area and emphasizes pathways (i.e., oxidative stress, cytokine-mediated intracellular signaling, glial-expressed receptors/targets) that can be manipulated pharmacologically for i) preservation of BBB and glial integrity during ischemic stroke and ii) control of drug permeation and/or transport across the BBB. Targeting these pathways present a novel opportunity for optimization of CNS delivery of therapeutics in the setting of ischemic stroke.
Keywords: Astrocyte, blood-brain barrier, drug delivery, endothelial cell, ischemic stroke, tight junction, transporters, brain homeostasis, CNS, neurovascular unit.
Current Pharmaceutical Design
Title:Blood-Brain Barrier Integrity and Glial Support: Mechanisms that can be Targeted for Novel Therapeutic Approaches in Stroke
Volume: 18 Issue: 25
Author(s): Patrick T. Ronaldson and Thomas P. Davis
Affiliation:
Keywords: Astrocyte, blood-brain barrier, drug delivery, endothelial cell, ischemic stroke, tight junction, transporters, brain homeostasis, CNS, neurovascular unit.
Abstract: The blood-brain barrier (BBB) is a critical regulator of brain homeostasis. Additionally, the BBB is the most significant obstacle to effective CNS drug delivery. It possesses specific charcteristics (i.e., tight junction protein complexes, influx and efflux transporters) that control permeation of circulating solutes including therapeutic agents. In order to form this “barrier,” brain microvascular endothelial cells require support of adjacent astrocytes and microglia. This intricate relationship also occurs between endothelial cells and other cell types and structures of the CNS (i.e., pericytes, neurons, extracellular matrix), which implies existence of a “neurovascular unit.” Ischemic stroke can disrupt the neurovascular unit at both the structural and functional level, which leads to an increase in leak across the BBB. Recent studies have identified several pathophysiological mechanisms (i.e., oxidative stress, activation of cytokinemediated intracellular signaling systems) that mediate changes in the neurovascular unit during ischemic stroke. This review summarizes current knowledge in this area and emphasizes pathways (i.e., oxidative stress, cytokine-mediated intracellular signaling, glial-expressed receptors/targets) that can be manipulated pharmacologically for i) preservation of BBB and glial integrity during ischemic stroke and ii) control of drug permeation and/or transport across the BBB. Targeting these pathways present a novel opportunity for optimization of CNS delivery of therapeutics in the setting of ischemic stroke.
Export Options
About this article
Cite this article as:
T. Ronaldson Patrick and P. Davis Thomas, Blood-Brain Barrier Integrity and Glial Support: Mechanisms that can be Targeted for Novel Therapeutic Approaches in Stroke, Current Pharmaceutical Design 2012; 18 (25) . https://dx.doi.org/10.2174/138161212802002625
DOI https://dx.doi.org/10.2174/138161212802002625 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
The Developmental Origins of Osteoporosis
Current Genomics An Evolving Role of Piperazine Moieties in Drug Design and Discovery
Mini-Reviews in Medicinal Chemistry Moderate Hyperhomocysteinemia and Immune Activation
Current Pharmaceutical Biotechnology Interleukin-1 and Occlusive Arterial Diseases
Cardiovascular & Hematological Agents in Medicinal Chemistry Nutrition Status and Weight Management in Chinese Women
Current Women`s Health Reviews Nanotechnology and Alzheimer's Disease: What has been Done and What to Do'
Current Medicinal Chemistry Overview
Mini-Reviews in Medicinal Chemistry Red Wine, Arterial Stiffness and Central Hemodynamics
Current Pharmaceutical Design Adiponectin as a Target in Obesity-related Inflammatory State
Endocrine, Metabolic & Immune Disorders - Drug Targets Enzymes To Die For: Exploiting Nucleotide Metabolizing Enzymes for Cancer Gene Therapy
Current Gene Therapy Overexpression of a Modified Amaranth Protein in Escherichia coli with Minimal Media and Lactose as Inducer
Recent Patents on Biotechnology Role of Oxidative Stress in Polycystic Ovary Syndrome
Current Women`s Health Reviews Review on Bosentan, A Dual Endothelin Receptor Antagonist for the Treatment of Pulmonary Arterial Hypertension
Recent Patents on Cardiovascular Drug Discovery Recombinant Activated Factor VII as a General Haemostatic Agent:Evidence-Based Efficacy and Safety
Current Drug Safety A Recent Update on the Effects of Omega-3 Fatty Acids in Alzheimer’s Disease
Current Clinical Pharmacology Nonfasting Hyperlipidemia and Cardiovascular Disease
Current Drug Targets Effect of Rosuvastatin on Non-alcoholic Steatohepatitis in Patients with Metabolic Syndrome and Hypercholesterolaemia: A Preliminary Report
Current Vascular Pharmacology Are Sex Differences in Outcomes of Patients with ACS from Observational Registries Similar to the Findings from Randomized Clinical Trials?
Current Pharmaceutical Design Docosahexaenoic Acid and Membrane Lipid Domains
Current Organic Chemistry Recent Advances in the Methodology and Application for the Metabolism of Phytochemical Compounds-An Update Covering the Period of 2009-2014
Current Drug Metabolism