A perspective on the potential role of remote ischemic conditioning in post-stroke depression: Mechanisms and future directions

Post-stroke depression (PSD) is one of the most common and debilitating neuropsychiatric complications following stroke, with a prevalence ranging from 10% to 40%. Despite its high incidence and profound impact on recovery and quality of life, current treatment options remain suboptimal. Although selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors are widely prescribed, their limited efficacy and potential safety concerns underscore the urgent need for more effective and targeted therapeutic strategies. Moreover, the underlying pathophysiological mechanisms of PSD are still not fully elucidated. Remote ischemic conditioning (RIC), a non-invasive neuroprotective intervention involving transient, repetitive ischemia-reperfusion cycles in distant limbs, has emerged as a promising therapeutic strategy. RIC activates endogenous protective pathways through neural, humoral, and immune mechanisms, potentially modulating key pathophysiological processes implicated in PSD, including neuroinflammation, impaired neuroplasticity and cerebrovascular dysfunction. This review synthesizes current evidence on the shared mechanisms between PSD and "classical" depression, highlights the neuroprotective effects of RIC, and proposes mechanistic hypotheses for RIC's potential role in mitigating PSD. Furthermore, we discuss the clinical and research implications, outlining future directions to optimize RIC as a viable strategy for improving neuropsychiatric outcomes in stroke survivors.