Abstract
What is the origin of the complex vascular changes that exist in the CNS lesions of Multiple Sclerosis (MS)? From the beginning of the study of the pathological changes in MS in the 19th century, lesions were seen to be associated with veins. On a microscopic level, there have been numerous pathological changes to these vessels including altered structure and permeability, fibrinolysis, iron-related alterations and collagen deposition. Vascular changes in inflammatory conditions outside the CNS are well documented and we hypothesize that angiogenesis (the generation of new blood vessels from existing) is an integral process of lesion development and spread in MS. We demonstrated similar vascular abnormalities in MS and in the animal model, EAE. We measured the increase in angiogenesis-related genes in EAE and review herein the effectiveness of chemical inhibitors of angiogenesis (SU5416, thalidomide and several derivatives). We postulate that interference with angiogenesis provides a suitable non-immunological target for investigation in MS.
Keywords: thalidomide, Multiple sclerosis, neuroinflammation, EAE, angiogenesis, SU5416, CNS, blood-brain barrier (BBB)
Central Nervous System Agents in Medicinal Chemistry
Title:Targeting Vascular Changes in Lesions in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis
Volume: 12 Issue: 1
Author(s): Stephen J. Karlik, Wendi A. Roscoe, Cindy Patinote, Christiane Contino-Pepin
Affiliation:
Keywords: thalidomide, Multiple sclerosis, neuroinflammation, EAE, angiogenesis, SU5416, CNS, blood-brain barrier (BBB)
Abstract: What is the origin of the complex vascular changes that exist in the CNS lesions of Multiple Sclerosis (MS)? From the beginning of the study of the pathological changes in MS in the 19th century, lesions were seen to be associated with veins. On a microscopic level, there have been numerous pathological changes to these vessels including altered structure and permeability, fibrinolysis, iron-related alterations and collagen deposition. Vascular changes in inflammatory conditions outside the CNS are well documented and we hypothesize that angiogenesis (the generation of new blood vessels from existing) is an integral process of lesion development and spread in MS. We demonstrated similar vascular abnormalities in MS and in the animal model, EAE. We measured the increase in angiogenesis-related genes in EAE and review herein the effectiveness of chemical inhibitors of angiogenesis (SU5416, thalidomide and several derivatives). We postulate that interference with angiogenesis provides a suitable non-immunological target for investigation in MS.
Export Options
About this article
Cite this article as:
Stephen J. Karlik, Wendi A. Roscoe, Cindy Patinote, Christiane Contino-Pepin , Targeting Vascular Changes in Lesions in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis, Central Nervous System Agents in Medicinal Chemistry 2012; 12 (1) . https://dx.doi.org/10.2174/187152412800229125
DOI https://dx.doi.org/10.2174/187152412800229125 |
Print ISSN 1871-5249 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6166 |
- 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
-
Polyphenols Beyond Barriers: A Glimpse into the Brain
Current Neuropharmacology Association of Viruses in the Development of Cardiovascular Diseases
Current Pharmaceutical Design Inflammatory Signaling Networks as Targets for Pharmacological Intervention of Chronic Diseases
Current Signal Transduction Therapy Intravenous Immunoglobulin Preparations and Autoimmune Disorders: Mechanisms of Action
Current Pharmaceutical Biotechnology Internal Ribosome Entry Site Elements in Eukaryotic Genomes
Current Genomics Immunomodulatory Properties of Antibiotics
Current Molecular Pharmacology The Skeletal Muscle Environment and Its Role in Immunity and Tolerance to AAV Vector-Mediated Gene Transfer
Current Gene Therapy Neuroinflammation, Microglia and Mast Cells in the Pathophysiology of Neurocognitive Disorders: A Review
CNS & Neurological Disorders - Drug Targets From the Molecular Mechanism to Pre-clinical Results: Anti-epileptic Effects of Fingolimod
Current Neuropharmacology Putative Immune Regulatory Role of Statins
Current Immunology Reviews (Discontinued) Chemokines and Chemokine Receptors: Potential Therapeutic Targets in Multiple Sclerosis
Current Drug Targets - Inflammation & Allergy Therapeutic Impact of Sphingosine 1-phosphate Receptor Signaling in Multiple Sclerosis
Mini-Reviews in Medicinal Chemistry Correlating Low-Similarity Peptide Sequences and Allergenic Epitopes
Current Pharmaceutical Design Microbiome Regulation of Autoimmune, Gut and Liver Associated Diseases
Inflammation & Allergy - Drug Targets (Discontinued) CCR1 Chemokine Receptor Antagonist
Current Pharmaceutical Design The Identification and Optimization of Orally Efficacious, Small Molecule VLA-4 Antagonists
Current Topics in Medicinal Chemistry Neurotuberculosis: An Overview
Central Nervous System Agents in Medicinal Chemistry Pharmacological Targeting of IDO-Mediated Tolerance for Treating Autoimmune Disease
Current Drug Metabolism Early Diagnosis of Multiple Sclerosis Based on Optical and Electrochemical Biosensors: Comprehensive Perspective
Current Analytical Chemistry The Impact of Fc Receptors on the Development of Autoimmune Diseases
Current Pharmaceutical Design