| First Author | Vaibhav K | Year | 2018 |
| Journal | J Exp Med | Volume | 215 |
| Issue | 10 | Pages | 2636-2654 |
| PubMed ID | 30190288 | Mgi Jnum | J:360006 |
| Mgi Id | MGI:6203490 | Doi | 10.1084/jem.20171905 |
| Citation | Vaibhav K, et al. (2018) Remote ischemic post-conditioning promotes hematoma resolution via AMPK-dependent immune regulation. J Exp Med 215(10):2636-2654 |
| abstractText | 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, AMPKalpha1, 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. |
