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

Lopes Pinheiro, Melissa A; Kooij, Gijs; Mizee, Mark R; Kamermans, Alwin; Enzmann, Gaby; Lyck, Ruth; Schwaninger, Markus; Engelhardt, Britta; de Vries, Helga E (2016). Immune cell trafficking across the barriers of the central nervous system in multiple sclerosis and stroke. Biochimica et biophysica acta - molecular basis of disease, 1862(3), pp. 461-471. Elsevier 10.1016/j.bbadis.2015.10.018

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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 treatment in acute stroke, modulates the pathogenesis of MS. Endogenous tPA is released from endothelium and astroglia and acts on the BBB, microglia and other neuroinflammatory cells. Thus, the vascular perspective of stroke research provides important input into the mechanisms on how endothelial cells and the BBB regulate inflammation in MS, particularly the invasion of immune cells into the CNS. In the current review we will first discuss pathogenesis of both diseases and current treatment regimens and will provide a detailed overview on pathways of immune cell migration across the barriers of the CNS and the role of activated astrocytes in this process. This article is part of a Special Issue entitled: Neuro inflammation: A common denominator for stroke, multiple sclerosis and Alzheimer's disease, guest edited by Helga de Vries and Markus Swaninger.

Item Type:

Journal Article (Review Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Enzmann, Gaby; Lyck, Ruth and Engelhardt, Britta

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0925-4439

Publisher:

Elsevier

Language:

English

Submitter:

Ursula Zingg-Zünd

Date Deposited:

14 Mar 2016 15:24

Last Modified:

29 May 2017 17:28

Publisher DOI:

10.1016/j.bbadis.2015.10.018

PubMed ID:

26527183

Uncontrolled Keywords:

Astrocyte; Blood–brain barrier; Immune cell trafficking; Multiple sclerosis; Stroke

BORIS DOI:

10.7892/boris.77179

URI:

https://boris.unibe.ch/id/eprint/77179

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