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  • Review Article
  • Published:

Immune interventions in stroke

Nature Reviews Neurology volume 11, pages 524–535 (2015)Cite this article

Subjects

Key Points

  • Recognition that immune mechanisms contribute to stroke and an increasing ability to manipulate the immune system have prompted suggestions that immunomodulation could be a feasible therapy for acute stroke

  • Immune interventions—including nonspecific anti-inflammatory drugs and approaches that target immune cells, inflammatory mediators and adhesion molecules—have been tested in patients with acute ischaemic stroke, with mixed outcomes

  • Proof-of-concept studies have demonstrated that fingolimod can attenuate brain inflammation and improve neurological outcomes in patients with acute stroke; a large international trial of natalizumab is nearly complete

  • Trials have shown that drugs that target multiple elements of the immune system, and that act quickly, could be viable candidates

  • Future success of immunomodulation as a therapy for stroke depends on further elucidation of immune interactions during stroke, and on the ability to limit immune-mediated tissue damage and promote tissue repair

Abstract

Approaches for the effective management of acute stroke are sparse, and many measures for brain protection fail. However, our ability to modulate the immune system and modify the progression of multiple sclerosis is increasing. As a result, immune interventions are currently being explored as therapeutic interventions in acute stroke. In this Review, we compare the immunological features of acute stroke with those of multiple sclerosis, identify unique immunological features of stroke, and consider the evidence for immune interventions. In patients with acute stroke, microglial activation and cell death products trigger an inflammatory cascade that damages vessels and the parenchyma within minutes to hours of the ischaemia or haemorrhage. Immune interventions that restrict brain inflammation, vascular permeability and tissue oedema must be administered rapidly to reduce acute immune-mediated destruction and to avoid subsequent immunosuppression. Preliminary results suggest that the use of drugs that modify disease in multiple sclerosis might accomplish these goals in ischaemic and haemorrhagic stroke. Further elucidation of the immune mechanisms involved in stroke is likely to lead to successful immune interventions.

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Figure 1: The effects of cross-talk between lymphocytes and ischaemic neurons on the time window for immune intervention.
Figure 2: The effects of fingolimod in patients with AIS and ICH.

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Acknowledgements

The authors would like to thank members of their laboratories and clinical teams for their passionate work in immunology and stroke. They would also like to thank C. Iadecola (Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, NY, USA), D. Huang (Neurology and Neuroscience Associates, Unity Health Network, Akron, OH, USA), T. Vollmer (Department of Neurology, University of Colorado School of Medicine, Aurora, CO, USA) and A. La Cava (Department of Medicine, University of California at Los Angeles, CA, USA) for fruitful discussions and advice, and P. Minick and K. Wood (Department of Neurology, Barrow Neurological Institute, Phoenix, AZ, USA) for editorial assistance. The authors' research programmes are supported in part by the National Basic Research Program of China (2013CB966900), National Natural Science Foundation of China (81230,028), National Key Clinical Speciality Construction Project of China, NIH (R01AI083294, R01NS34179 and R01NS081179), the American Heart Association (14GRNT18970031) and the Foundation Leducq. This paper is dedicated to our families.

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  1. Departments of Neurology and Immunology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China

    Ying Fu, Qiang Liu & Fu-Dong Shi

  2. Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, 525 East 68th Street, PO Box 117, New York, 10065, NY, USA

    Josef Anrather

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Y.F. and F.-D.S. researched data for the article, and Y.F., Q.L., J.A. and F.-D.S. wrote the article. F.-D.S. made a substantial contribution to the discussion of content, and all authors reviewed and/or edited the manuscript before submission.

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Correspondence to Fu-Dong Shi.

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The authors declare no competing financial interests.

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Fu, Y., Liu, Q., Anrather, J. et al. Immune interventions in stroke. Nat Rev Neurol 11, 524–535 (2015). https://doi.org/10.1038/nrneurol.2015.144

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