Abstract
Ischaemic tolerance induced by remote ischaemic conditioning (RIC) has been extensively demonstrated in several preclinical models of cerebral ischaemia. However, animals with common stroke-related comorbidities do not benefit from the recent advances of RIC. Therefore, we investigated two alternative approaches for obese animals with stroke: (1) the efficacy of an additional round of the standard RIC protocol, and (2) the paracrine potential of the blood cell-derived secretome derived from RIC-induced healthy young rats. We found that a second round of remote ischaemic postconditioning (RIPostC) stimulus reduced neurodegeneration and exerted antioxidant effects but failed to decrease the infarct volume and alter glutamate homeostasis. However, when obese rats were administered the secretome from healthy, young RIC-stimulated rats, they exhibited improved neurological post-stroke outcomes. Intravenous administration of the tolerant secretome activated several endogenous mechanisms, including a reduction in the infarct volume and neurodegeneration in the penumbra. Furthermore, the blood cell-derived secretome accelerated brain-to-blood glutamate efflux in obese rats, and demonstrated antioxidant properties that may have contributed to the induction of tolerance in obese rats with stroke. These findings indicate that the blood cell-derived secretome has unique abilities and represents a new potential treatment for individuals with obesity and ischaemic stroke.