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  • Review Article
  • Published:

Remote ischaemic conditioning—a new paradigm of self-protection in the brain

Nature Reviews Neurology volume 11, pages 698–710 (2015)Cite this article

Subjects

Key Points

  • Remote ischaemic conditioning remotely triggers self-protective pathways in the brain and can be easily administered by repetitive inflation and deflation of a blood pressure cuff on the limb

  • The exact mechanisms of signal transmission and remote organ protection are unknown, but both circulating mediators and neural mechanisms have central roles

  • Results of a trial of RIC in acute ischaemic stroke suggest that it is of benefit when administered during ischaemia

  • Acute RIC should be tested during the transfer of patients to comprehensive stroke centres, for use with mechanical thrombectomy, and in patients who have had a cardiac arrest

  • Two small clinical trials showed that chronic daily RIC at home for >6 months reduced the risk of stroke and transient ischaemic attacks in patients with symptomatic intracranial atherosclerosis

  • Chronic daily RIC is a promising therapy for chronic neurological conditions, such as white matter disease and vascular cognitive impairment

Abstract

Remote ischaemic conditioning (RIC) triggers endogenous protective pathways in distant organs such as the kidney, heart and brain, and represents an exciting new paradigm in neuroprotection. RIC involves repetitive inflation and deflation of a blood pressure cuff on the limb, and is safe and feasible. The exact mechanism of signal transmission from the periphery to the brain is not known, but both humoral factors and an intact nervous system seem to have critical roles. Early-phase clinical trials have already been conducted to test RIC in the prehospital setting in acute ischaemic stroke, and in subarachnoid haemorrhage for the prevention of delayed cerebral ischaemia. Furthermore, two small randomized clinical trials in patients with symptomatic intracranial atherosclerosis have shown that RIC can reduce recurrence of stroke and have neuroprotective activity. RIC represents a highly practical and translatable therapy for acute, subacute, and chronic neurological diseases with an ischaemic or inflammatory basis. In this Review, we consider the principles and mechanisms of RIC, evidence from preclinical models and clinical trials that RIC is beneficial in neurological disease, and how the procedure might be used in the future in disorders such as vascular cognitive impairment and traumatic brain injury.

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Figure 1: Protocols of remote ischaemic conditioning in the acute and chronic settings.
Figure 2: Ischaemic preconditioning in the heart by various methods reduces the size of an infarct.
Figure 3: Possible mechanisms by which the signal initiated by remote limb preconditioning is transmitted to the brain to bring about protection against ischaemia.
Figure 4: Trial profile of the prehospital acute stroke trial.108,109

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Authors and Affiliations

  1. Department of Neurology, Medical College of Georgia, Georgia Regents University, 1120 15th Street, Augusta, 30912, GA, USA

    David C. Hess

  2. Department of Medical Laboratory, Imaging, and Radiologic Sciences, College of Allied Health Sciences, Georgia Regents University, 1120 15th Street, Augusta, 30912, GA, USA

    Md Nasrul Hoda

  3. Department of Neurology, Aarhus University Hospital, Norrebrogade 44, Aarhus C, DK-8000, Denmark

    Rolf A. Blauenfeldt, Grethe Andersen & Kristina D. Hougaard

  4. Department of Neurosurgery, Wayne State University, 4160 John R. Street, Suite 930, Detroit, 48201, MI, USA

    Yuchuan Ding

  5. Xuanwu Hospital, Beijing Capital University, 45 Changchun Street, Xuanwu District, 100053, Beijing, China

    Xunming Ji

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  3. Grethe Andersen
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Contributions

All authors researched data for the article, made substantial contributions to discussion of the content, and reviewed and/or edited the manuscript before submission. D.C.H., R.A.B., G.A., K.D.H., Y.D. and X.J. wrote the article.

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Correspondence to David C. Hess.

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Competing interests

X.J. has a patent on a remote conditioning device. All other authors declare no competing interests.

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Hess, D., Blauenfeldt, R., Andersen, G. et al. Remote ischaemic conditioning—a new paradigm of self-protection in the brain. Nat Rev Neurol 11, 698–710 (2015). https://doi.org/10.1038/nrneurol.2015.223

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