Remote ischemic conditioning: the brain's endogenous defense against stroke

Several systemic pathways have been described for RIC: 1) blood-borne factor release, 2) neuronal pathway activation, 3) systemic modification of immune cells, and 4) activation of hypoxia inducible genes (Tapuria et al., 2008; Le Page and Prunier, 2015; Anttila et al., 2016) [Figure 1]A. While the literature centers around cardioprotective pathways, consistencies between organs systems are apparent. Conditioning increases reactive oxygen species scavenging astrocytes that also support the blood brain barrier, stimulates pre-ischemic microvessel formation and post-ischemic vessel dilation, and reduces leukocyte adhesion via intercellular adhesion molecule 1 downregulation (Wang et al., 2015). [...]each of the conditioning stimuli would have provided neuroprotection for 1 week maximum via the delayed conditioning response rooted in de novo protein translation. In their retrospective study, where peripheral arterial disease was used as a mechanism for hypoperfusion, they illustrated improved clinical outcomes (lower admission National Institute of Health Stroke Scale and 3-month modified ranking scale), smaller infarct volumes, and lower mortality rates in peripheral arterial disease afflicted patients.