Abstract
Ischemic stroke is still among the leading causes of mortality and morbidity worldwide. Despite intensive advancements in medical sciences, the clinical options to treat ischemic stroke are limited to thrombectomy and thrombolysis using tissue plasminogen activator within a narrow time window after stroke. Current state of the art knowledge reveals the critical role of local and systemic inflammation after stroke that can be triggered by interactions taking place at the brain and immune system interface. Here, we discuss different cellular and molecular mechanisms through which brain–immune interactions can take place. Moreover, we discuss the evidence how the brain influence immune system through the release of brain derived antigens, damage-associated molecular patterns (DAMPs), cytokines, chemokines, upregulated adhesion molecules, through infiltration, activation and polarization of immune cells in the CNS. Furthermore, the emerging concept of stemness-induced cellular immunity in the context of neurodevelopment and brain disease, focusing on ischemic implications, is discussed. Finally, we discuss current evidence on brain–immune system interaction through the autonomic nervous system after ischemic stroke. All of these mechanisms represent potential pharmacological targets and promising future research directions for clinically relevant discoveries.
Highlights
Cells 2021, 10, 2429 microtubule-associated protein 2 (MAP2), N-methyl-D-aspartic acid (NMDA) receptor subunit NR-2A, myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein [25] were found in tonsils and cervical lymph nodes of patients with stroke [26]
Elevated extracellular Adenosine Triphosphate (ATP) acts on purinergic receptors and activate immune cells leading to release of proinflammatory cytokines and activation of inflammasome in neurons and astrocytes [30]
Model of ischemic stroke, peroxiredoxin proteins such as Prx-1, Prx-2, Prx-5 and Prx-6 were found to be released from the injured brain cells and led to the increased expression of proinflammatory cytokines such as IL-23 from macrophages owing to the ligation of TLR-2 and TLR-4 [37]
Summary
Stroke is the third leading cause of death following heart diseases and cancer. Stroke affects around 15 million people yearly worldwide [1]. Stroke is the leading cause of long-term disability worldwide and poses a profound economic burden [1]. Despite years of intensive research, therapeutic options are still limited to recanalization strategies either by thrombectomy utilizing stent retrievers [4,5]. Thrombolysis with recombinant tissue plasminogen activator (rtPA) with a limited time window up to 4.5 h [6]. Both therapeutic options have their limitations and can lead to life threatening intracranial bleeding.
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