The immune system and stroke: from current targets to future therapy

Abstract

Stroke is a major cause of morbidity and mortality worldwide. Despite the intensive search for new therapies, hundreds of agents targeting various pathophysiological mechanisms have failed clinical trials, and the thrombolytic agent tissue plasminogen activator is currently the only FDA-approved medication for the treatment of acute ischemic stroke. The immune system is involved in all stages of stroke, from the pathogenesis of risk factors to neurotoxicity, to tissue remodeling and repair. There is a bidirectional interaction between the brain and the immune system, with stroke-induced immunosuppression and subsequent infection a principal source of patient mortality. Newer work also points to a role for the gut microbiota in the immune response to stroke, while clinical sequelae such as dementia might now also be explained in immune terms. However, the exact roles of innate and adaptive components have not been fully elucidated, with studies reporting both detrimental and beneficial functions. Time is a key determinant in defining whether immunity and inflammation are neuroprotective or neurotoxic. The local inflammatory milieu also has a clear influence on many proposed treatments. This review examines the individual components of the immune response to stroke, highlighting the most promising future stroke immunotherapies.

Alteration of perivascular spaces in early cognitive decline

“…According to our results the APOE haplotype did not influence the PVS volume fraction and distribution in ASM and CSO-WM. Pathological changes in the structure and/or function of cerebral microvasculature has been shown to play a major role in dementia [21,81,82]. PVS, as direct biomarker of the cerebral glia-lymphatic pathway and indirect biomarker of cerebrovascular health, represent a "bridge" between two key mechanisms underlying neurodegeneration and may therefore be a novel indicator of early pathophysiological processes leading to cognitive impairment.…”

Immunological partners: the gut microbiome in homeostasis and disease

“…6 To complement these articles from Immunology, are six from Immunology & Cell Biology that investigate and discuss the involvement of immune factors (interferon inducible transmembrane genes) 7 or immune cells (MAIT cells) 8 in regulating the local gut environment to maintain epithelial homeostasis and immune-microbial balance. The benefit of a balanced and regulated microbiota is also discussed by Malone et al in the context of how the gut-brain axis influences stroke outcomes 9 and by McCoy et al 10 in how the microbiome shapes immune memory. These reviews highlight the potential of targeted microbiome interventions in the treatment of stroke or to maximize vaccine efficacy.…”

“…Taken together, this collection of articles and editorials from Immunology [1][2][3][4][5][6] and Immunology & Cell Biology [7][8][9][10][11][12][13] begin to dissect the complex partnership that has evolved, and continues to evolve, between microbes and humans. The consequences of an unhealthy relationship (i.e.…”

A joint spotlight on research into the microbial immunity: beyond mere correlations

“…Six articles from each journal are featured in this Virtual Issue. [1][2][3][4][5][6][7][8][9][10][11][12] We will highlight the ICB articles here. The companion articles in Immunology are described in our accompanying Editorial in Immunology.…”

“…13 The ICB articles cover a wide range of topics, from reviews describing mechanistic interactions with components of the immune system, 1,2 through original articles describing novel molecular interactions with the microbiota and their influence on inflammation 3 and vaccine responses, 4 to investigations of the relationships between the microbiota and diabetes in NOD mice, 5 and in patients with stroke. 6 Two of the ICB articles are reviews discussing interactions between the host, the microbiota and pathogenic microorganisms. 1,2 The influence of the microbiota on the development of both adaptive memory and innate "memory" is the focus of the review by McCoy et al, which is placed in the topical context of vaccine efficiency ( Figure 1①).…”