Immune responses to stroke: mechanisms, modulation, and therapeutic potential
Costantino Iadecola, … , Marion S. Buckwalter, Josef Anrather
Costantino Iadecola, … , Marion S. Buckwalter, Josef Anrather
Published May 11, 2020
Citation Information: J Clin Invest. 2020;130(6):2777-2788. https://doi.org/10.1172/JCI135530.
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Immune responses to stroke: mechanisms, modulation, and therapeutic potential

Abstract

Stroke is the second leading cause of death worldwide and a leading cause of disability. Most strokes are caused by occlusion of a major cerebral artery, and substantial advances have been made in elucidating how ischemia damages the brain. In particular, increasing evidence points to a double-edged role of the immune system in stroke pathophysiology. In the acute phase, innate immune cells invade brain and meninges and contribute to ischemic damage, but may also be protective. At the same time, danger signals released into the circulation by damaged brain cells lead to activation of systemic immunity, followed by profound immunodepression that promotes life-threatening infections. In the chronic phase, antigen presentation initiates an adaptive immune response targeted to the brain, which may underlie neuropsychiatric sequelae, a considerable cause of poststroke morbidity. Here, we briefly review these pathogenic processes and assess the potential therapeutic value of targeting immunity in human stroke.

Authors

Costantino Iadecola, Marion S. Buckwalter, Josef Anrather

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Figure 3

Timing and success of selected immunomodulatory therapies for stroke.

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Timing and success of selected immunomodulatory therapies for stroke. Hu...
Human studies were selected as those that were later stage and utilized immunomodulatory drugs or antibodies. For each agent, the human studies are listed in chronological order, with the length of the bars indicating the treatment period from the time the participant was last seen normal. Below the human trials are animal studies with that agent where the first dose was delivered after stroke, and either infarct size or neurological outcome was tested. If both were positive, the animal studies are marked with a circle, and if both were negative, they are marked with an x. In cases where only neurological outcome or only stroke size was tested, or where one was positive and the other negative, the study is not marked with a symbol. Comorbidities in animal studies were aging, diabetes, hypertension, and hypercholesterolemia. Additional details and references are in Supplemental Table 1. *This study had a positive effect in males but not females. **Drug dose timing listed only as mean ± SD, which is graphed here.