Immune cell trafficking across the barriers of the central nervous system in multiple sclerosis and stroke

• Published in: Biochimica et biophysica acta 2016-03, Vol.1862 (3), p.461-471
• Main Authors: Lopes Pinheiro, Melissa A., Kooij, Gijs, Mizee, Mark R., Kamermans, Alwin, Enzmann, Gaby, Lyck, Ruth, Schwaninger, Markus, Engelhardt, Britta, de Vries, Helga E.
• Format: Article
• Language: English
• Subjects: Animals; Astrocyte; Astrocytes - immunology; Astrocytes - pathology; Blood-Brain Barrier - immunology; Blood-Brain Barrier - pathology; Blood–brain barrier; Brain - immunology; Brain - pathology; Central Nervous System - immunology; Central Nervous System - pathology; Humans; Immune cell trafficking; Immunity, Cellular; Inflammation - immunology; Inflammation - pathology; Multiple sclerosis; Multiple Sclerosis - immunology; Multiple Sclerosis - pathology; Stroke; Stroke - immunology; Stroke - pathology
• ISSN: 0925-4439; 0006-3002; 1879-260X
• DOI: 10.1016/j.bbadis.2015.10.018

Each year about 650,000 Europeans die from stroke and a similar number lives with the sequelae of multiple sclerosis (MS). Stroke and MS differ in their etiology. Although cause and likewise clinical presentation set the two diseases apart, they share common downstream mechanisms that lead to damage and recovery. Demyelination and axonal injury are characteristics of MS but are also observed in stroke. Conversely, hallmarks of stroke, such as vascular impairment and neurodegeneration, are found in MS. However, the most conspicuous common feature is the marked neuroinflammatory response, marked by glia cell activation and immune cell influx. In MS and stroke the blood–brain barrier is disrupted allowing bone marrow-derived macrophages to invade the brain in support of the resident microglia. In addition, there is a massive invasion of auto-reactive T-cells into the brain of patients with MS. Though less pronounced a similar phenomenon is also found in ischemic lesions. Not surprisingly, the two diseases also resemble each other at the level of gene expression and the biosynthesis of other proinflammatory mediators. While MS has traditionally been considered to be an autoimmune neuroinflammatory disorder, the role of inflammation for cerebral ischemia has only been recognized later. In the case of MS the long track record as neuroinflammatory disease has paid off with respect to treatment options. There are now about a dozen of approved drugs for the treatment of MS that specifically target neuroinflammation by modulating the immune system. Interestingly, experimental work demonstrated that drugs that are in routine use to mitigate neuroinflammation in MS may also work in stroke models. Examples include Fingolimod, glatiramer acetate, and antibodies blocking the leukocyte integrin VLA-4. Moreover, therapeutic strategies that were discovered in experimental autoimmune encephalomyelitis (EAE), the animal model of MS, turned out to be also effective in experimental stroke models. This suggests that previous achievements in MS research may be relevant for stroke. Interestingly, the converse is equally true. Concepts on the neurovascular unit that were developed in a stroke context turned out to be applicable to neuroinflammatory research in MS. Examples include work on the important role of the vascular basement membrane and the BBB for the invasion of immune cells into the brain. Furthermore, tissue plasminogen activator (tPA), the only established drug treatme