Autoimmunity in acute ischemic stroke and the role of blood--brain barrier: the dark side or the light one?

Abstract

This article presents a synopsis of the current data on the mechanisms of blood--brain barrier (BBB) alteration and autoimmune response in acute ischemic stroke. Most researchers confirm the relationship between the severity of immunobiochemical changes and clinical outcome of acute ischemic stroke. Ischemic stroke is accompanied by aseptic inflammation, which alters the brain tissue and exposes the co-stimulatory molecules of the immune system and the neuronal antigens. To date, BBB is not considered the border between the immune system and central nervous system, and the local immune subsystems are found within and behind the BBB. BBB disruption contributes to the leakage of brain autoantigens and induction of secondary autoimmune response to neuronal antigens and long-term inflammation. Glymphatic system function is altered and jeopardized both in hemorrhagic and ischemic stroke types. The receptors of innate immunity (toll-like receptor-2 and toll-like receptor-4) are also involved in acute ischemia--reperfusion injury. Immune response is related to the key processes of blood clotting and fibrinolysis. At the same time, the stroke-induced immune activation may promote reparation phenomena in the brain. Subsequent research on the reduction of the acute ischemic brain injury through the target regulation of the immune response is promising.

Keywords

stroke / blood–brain barrier / autoimmunity / innate immunity / inflammation / cell death

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Acknowledgements

This work was partially supported by the grant of the Government of the Russian Federation for the state support of scientific research carried out under the supervision of leading scientists, agreement 14.W03.31.0009, on the basis of SPbU project 15.34.3.2017.

Compliance with ethics guidelines

Nikolay V. Tsygan, Alexandr P. Trashkov, Igor V. Litvinenko, Viktoriya A. Yakovleva, Alexandr V. Ryabtsev, Andrey G. Vasiliev, and Leonid P. Churilov declare no financial conflicts of interests. This manuscript is a review article and does not involve a research protocol requiring approval by a relevant institutional review board or ethics committee.

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