Abstract
Cerebral ischemia is one of the major causes of disability worldwide. In cerebral ischemic stroke, occlusion of a major cerebral artery by an embolus or local thrombosis can result in transient or permanent reduction of cerebral blood flow to a portion of the brain, resulting in deprivation of glucose and oxygen. Since the brain relies on a continuous supply of nutrients and ions via mostly carrier mediated processes across the blood-brain barrier (BBB), any irregularity in these transport mechanisms dramatically affects neuronal function and outcome after acute and chronic stroke. Despite numerous encouraging breakthroughs in preclinical stroke studies that evaluate monotherapies and a prevailing neurocentric approach that has yielded disappointing clinical translation, preclinical stroke studies investigating additional therapeutic targets might be used more effectively in combination with thrombolysis. In this context, this current review discusses the current understanding of dysfunctionional BBB nutrient and ion transport mechanisms involved in stroke pathophsyiology as novel therapeutic approaches. Recognition of the important role of the neurovascular unit in pathophysiology of stroke will provide new opportunities to treat ischemic brain injury, and maintenance of nutrient and ionic homeostasis should facilitate brain repair after stroke.
Keywords: Blood brain barrier, neurovascular unit, stroke, edema, glucose, SGLT, NKCC, NHE, NCX, Phlorizin, insulin.
Current Pharmaceutical Design
Title:The Role of Blood-Brain Barrier Transporters in Pathophysiology and Pharmacotherapy of Stroke
Volume: 20 Issue: 10
Author(s): Kaushik Shah and Thomas Abbruscato
Affiliation:
Keywords: Blood brain barrier, neurovascular unit, stroke, edema, glucose, SGLT, NKCC, NHE, NCX, Phlorizin, insulin.
Abstract: Cerebral ischemia is one of the major causes of disability worldwide. In cerebral ischemic stroke, occlusion of a major cerebral artery by an embolus or local thrombosis can result in transient or permanent reduction of cerebral blood flow to a portion of the brain, resulting in deprivation of glucose and oxygen. Since the brain relies on a continuous supply of nutrients and ions via mostly carrier mediated processes across the blood-brain barrier (BBB), any irregularity in these transport mechanisms dramatically affects neuronal function and outcome after acute and chronic stroke. Despite numerous encouraging breakthroughs in preclinical stroke studies that evaluate monotherapies and a prevailing neurocentric approach that has yielded disappointing clinical translation, preclinical stroke studies investigating additional therapeutic targets might be used more effectively in combination with thrombolysis. In this context, this current review discusses the current understanding of dysfunctionional BBB nutrient and ion transport mechanisms involved in stroke pathophsyiology as novel therapeutic approaches. Recognition of the important role of the neurovascular unit in pathophysiology of stroke will provide new opportunities to treat ischemic brain injury, and maintenance of nutrient and ionic homeostasis should facilitate brain repair after stroke.
Export Options
About this article
Cite this article as:
Shah Kaushik and Abbruscato Thomas, The Role of Blood-Brain Barrier Transporters in Pathophysiology and Pharmacotherapy of Stroke, Current Pharmaceutical Design 2014; 20 (10) . https://dx.doi.org/10.2174/13816128113199990465
DOI https://dx.doi.org/10.2174/13816128113199990465 |
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
?Revolutionizing Cancer Treatment: Nano-Therapeutics Targeting Tumor Microenvironment?
This thematic issue explores the forefront of cancer treatment, centering on the groundbreaking potential of nano-therapeutics meticulously designed to target the tumor microenvironment. At its core, the issue aims to unravel the latest advancements in nanotechnology, showcasing innovative materials, formulations, and delivery systems that hold promise for redefining cancer therapeutics. ...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
- 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
-
Nanotechnological Strategies for the Treatment of Neglected Diseases
Current Pharmaceutical Design Cranial Ultrasound - Optimizing Utility in the NICU
Current Pediatric Reviews Autophagy as a Potential Therapeutic Target in Breast Cancer Treatment
Current Cancer Drug Targets Selective Neuronal Nitric Oxide Synthase Inhibitors
Current Topics in Medicinal Chemistry Carbon Monoxide - Toxicity of Low-Dose Application
Current Pharmaceutical Biotechnology Imaging in Inflammatory Bowel Disease Mucosal Healing in Ulcerative Colitis: Relevance for Clinical Outcomes
Current Drug Targets Inhibitors of the Microsomal Prostaglandin E2 Synthase-1 as Alternative to Non Steroidal Anti-Inflammatory Drugs (NSAIDs) – A Critical Review
Current Medicinal Chemistry Applications of Arterial Spin Labelling in Mild Cognitive Impairment, Alzheimers Disease and Other Forms of Dementia
Current Medical Imaging All Cognitive Systems but Speed and Visuospatial Functions Reduce the Effect of CSF Pathology on Other Systems
Current Alzheimer Research Antiinflammatory Activity of Melatonin in Central Nervous System
Current Neuropharmacology Progress of In Vivo Electroporation in the Rodent Brain
Current Gene Therapy Adult Neurogenesis and Parkinsons Disease
CNS & Neurological Disorders - Drug Targets Mitochondrial Permeability Transition Pore as a Suitable Targ e t for Neuroprotective Agents Against Alzheimer’s Disease
CNS & Neurological Disorders - Drug Targets Longitudinal Functional MRI of Motor and Cognitive Recovery Following Stroke: A Review
Current Medical Imaging Bone Marrow Derived Cells for Brain Repair: Recent Findings and Current Controversies
Current Molecular Medicine Pharmacological Interventions and Rehabilitation Approach for Enhancing Brain Self-repair and Stroke Recovery
Current Neuropharmacology Mevalonate Cascade and Neurodevelopmental and Neurodegenerative Diseases: Future Targets for Therapeutic Application
Current Molecular Pharmacology Rho-ROCK Inhibitors for the Treatment of CNS Injury
Recent Patents on CNS Drug Discovery (Discontinued) Biosynthesis and Biological Activities of In Vitro Derived Solasodine Glycoalkaloids from <i>Solanum laciniatum</i>
The Natural Products Journal Brain Drug Delivery System: An Overview
Current Drug Therapy