Brain Barriers and Multiple Sclerosis: Novel Treatment Approaches from a Brain Barriers Perspective
Multiple sclerosis (MS) is considered a prototypic organ specific autoimmune disease targeting the central nervous system (CNS). Blood–brain barrier (BBB) breakdown and enhanced immune cell infiltration into the CNS parenchyma are early hallmarks of CNS l
- PDF / 663,072 Bytes
- 35 Pages / 439.37 x 666.142 pts Page_size
- 45 Downloads / 212 Views
Contents 1 Introduction 2 The Brain Barriers (Fig. 1) 2.1 The Endothelial Blood-Brain Barrier (BBB) 2.2 Glia Limitans 2.3 Choroid Plexus and Blood-Cerebrospinal Fluid Barrier (BCSFB) 2.4 Additional Brain Barriers 3 Cell Trafficking Across Brain Barriers 3.1 Immune Cell Trafficking Across the BBB 3.2 Immune Cell Trafficking Across the Glia Limitans 3.3 Immune Cell Trafficking via the Choroid Plexus 3.4 Immune Cell Trafficking Across Additional Barriers 4 Mechanisms of Brain Barriers Impairment in MS 4.1 BBB 4.2 The Glia Limitans 4.3 Blood–Cerebrospinal Fluid Barrier (BCSFB) of the Choroid Plexus 4.4 Arachnoid Barrier 5 Therapeutic Strategies Targeting Brain Barriers 5.1 Current MS Therapies Directly Targeting Brain Barriers 5.2 Current MS Therapies Indirectly Targeting the Brain Barriers 6 Future Directions for Direct or Indirect Therapeutic Targeting of the Brain Barriers for Treating MS 6.1 Direct Targeting Approaches 6.2 Indirect Targeting Approaches 7 Conclusions and Outlook Glossary References
H. Nishihara (*) · B. Engelhardt (*) Theodor Kocher Institute, University of Bern, Bern, Switzerland e-mail: [email protected]; [email protected] # Springer Nature Switzerland AG 2020 Handbook of Experimental Pharmacology, https://doi.org/10.1007/164_2020_407
H. Nishihara and B. Engelhardt
Abstract
Multiple sclerosis (MS) is considered a prototypic organ specific autoimmune disease targeting the central nervous system (CNS). Blood–brain barrier (BBB) breakdown and enhanced immune cell infiltration into the CNS parenchyma are early hallmarks of CNS lesion formation. Therapeutic targeting of immune cell trafficking across the BBB has proven a successful therapy for the treatment of MS, but comes with side effects and is no longer effective once patients have entered the progressive phase of the disease. Beyond the endothelial BBB, epithelial and glial brain barriers establish compartments in the CNS that differ in their accessibility to the immune system. There is increasing evidence that brain barrier abnormalities persist during the progressive stages of MS. Here, we summarize the role of endothelial, epithelial, and glial brain barriers in maintaining CNS immune privilege and our current knowledge on how impairment of these barriers contributes to MS pathogenesis. We discuss how therapeutic stabilization of brain barriers integrity may improve the safety of current therapeutic regimes for treating MS. This may also allow for the development of entirely novel therapeutic approaches aiming to restore brain barriers integrity and thus CNS homeostasis, which may be specifically beneficial for the treatment of progressive MS. Keywords
Adhesion molecules · Arachnoid barrier · Blood–brain barrier · Blood– cerebrospinal fluid barrier · Glia limitans · Immune cell trafficking · Multiple sclerosis · Permeability · Tight junctions
1
Introduction
Multiple sclerosis (MS) is considered an autoimmune disorder affecting the central nervous system (CNS) of young adults. If untreated in its early stages, MS leads to irreversib
Data Loading...
