Remote ischemic post-conditioning promotes hematoma resolution via AMPK-dependent immune regulation

Kumar Vaibhav, Molly Braun, Mohammad Badruzzaman Khan, Sumbul Fatima, Nancy Saad, Adarsh Shankar, Zenab T. Khan, Ruth B.S. Harris, Qiuhua Yang, Yuqing Huo, Ali S. Arbab, Shailendra Giri, Cargill H. Alleyne, John R. Vender, David C. Hess, Babak Baban, Md Nasrul Hoda, Krishnan M. Dhandapani

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Spontaneous intracerebral hemorrhage (ICH) produces the highest acute mortality and worst outcomes of all stroke subtypes. Hematoma volume is an independent determinant of ICH patient outcomes, making clot resolution a primary goal of clinical management. Herein, remote-limb ischemic post-conditioning (RIC), the repetitive inflation-deflation of a blood pressure cuff on a limb, accelerated hematoma resolution and improved neurological outcomes after ICH in mice. Parabiosis studies revealed RIC accelerated clot resolution via a humoral-mediated mechanism. Whereas RIC increased anti-inflammatory macrophage activation, myeloid cell depletion eliminated the beneficial effects of RIC after ICH. Myeloid-specific inactivation of the metabolic regulator, AMPKα1, attenuated RIC-induced anti-inflammatory macrophage polarization and delayed hematoma resolution, providing a molecular link between RIC and immune activation. Finally, chimera studies implicated myeloid CD36 expression in RIC-mediated neurological recovery after ICH. Thus, RIC, a clinically well-tolerated therapy, noninvasively modulates innate immune responses to improve ICH outcomes. Moreover, immunometabolic changes may provide pharmacodynamic blood biomarkers to clinically monitor the therapeutic efficacy of RIC.

Original languageEnglish (US)
Pages (from-to)2636-2654
Number of pages19
JournalThe Journal of experimental medicine
Volume215
Issue number10
DOIs
StatePublished - Oct 1 2018

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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