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The immunology of stroke: from mechanisms to translation

Immunity and inflammation are key elements of the pathobiology of stroke, a devastating illness second only to cardiac ischemia as a cause of death worldwide. The immune system participates in the brain damage produced by ischemia, and the damaged brain, in turn, exerts an immunosuppressive effect that promotes fatal infections that threaten the survival of people after stroke. Inflammatory signaling is involved in all stages of the ischemic cascade, from the early damaging events triggered by arterial occlusion to the late regenerative processes underlying post-ischemic tissue repair. Recent developments have revealed that stroke engages both innate and adaptive immunity. But adaptive immunity triggered by newly exposed brain antigens does not have an impact on the acute phase of the damage. Nevertheless, modulation of adaptive immunity exerts a remarkable protective effect on the ischemic brain and offers the prospect of new stroke therapies. As immunomodulation is not devoid of deleterious side effects, a better understanding of the reciprocal interaction between the immune system and the ischemic brain is essential to harness the full therapeutic potential of the immunology of stroke.

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Figure 1: Early vascular, perivascular and parenchymal events triggered by ischemia and reperfusion.

Katie Vicari

Figure 2: Cell death and activation of pattern recognition receptors set the stage adaptive immunity.
Figure 3: Deleterious and beneficial roles of T cells in stroke.

Katie Vicari

Figure 4: Resolution of inflammation and tissue repair.

Katie Vicari

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Acknowledgements

Supported by the US National Institutes of Health grants R37-NS34179 and NS35806. We apologize that the scope of the topic prevented citation of many important studies.

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Correspondence to Costantino Iadecola.

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Iadecola, C., Anrather, J. The immunology of stroke: from mechanisms to translation. Nat Med 17, 796–808 (2011). https://doi.org/10.1038/nm.2399

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