Cerebral infarction (CI), also known as ischemic stroke, is one of the most common cerebrovascular diseases, accounting for approximately 70% of all acute cerebrovascular diseases [1]. Acute cerebral infarction (ACI) eventually leads to neuronal apoptosis and ischemic necrosis of brain tissues, with a high risk of disability, death, and recurrence, which imposes a serious burden on society and families [2]. Notably, the pathophysiological process of ACI-caused brain injury involves multiple mechanisms such as inflammatory response [3], oxidative stress response [4], and neovascularization [5]. However, there is still a lack of clinically proven cerebral protection treatments, and searching for promising therapy for ACI is crucial for the well-being of ACI patients.

Remote ischemic preconditioning (RIPC) is a novel neuroprotective intervention whereby a sublethal, brief ischemic insult possesses the ability to result in a significant enhancement in the tolerance of brain tissues to subsequent prolonged, lethal ischemic attack [6]. It has the advantages of non-invasiveness and simplicity compared to ordinary ischemic preconditioning, which reduces cerebral infarct size and improves neurological function in ACI [7]. In addition, it is reported that RIPC attenuates free radical damage and inflammatory response in rats with cerebral ischemia-reperfusion [8].

microRNAs (miRNAs) are small non-coding RNAs that exert function in the physiopathological processes of multiple diseases [9]. Existing articles have revealed that various miRNAs, such as miR-409–3p [10], miR-133 [11], and miR-138–5p [12] are bound up with the development of ACI. RIPC can exert an effect on ACI-related diseases by regulating miRNA levels. As reported by Jiao et al., RIPC protects against cerebral ischemic injury in rats by up-regulating miR-204–5p [13]. RIPC treatment can inhibit the volume of cerebral infarction and nerve damage in middle cerebral artery occlusion model mice, and promote the expression of miR-153–5p [7]. Moroever, miR-582–5p has been found to be lowly expressed in hepatic ischemia-reperfusion injury [14], and miR-582–5p overexpression suppresses neuronal apoptosis in ischemic stroke by modulating PAR1 [15]. Additionally, miR-582–5p is down-regulated in myocardial infarction mice [16]. However, it remains unclear whether RIPC intervention has an impact on serum miR-582–5p levels in ACI patients.

High mobility group box-1 protein (HMGB1), a nuclear DNA binding protein and important injury-related molecular pattern, may promote activation of the inflammatory response by activating the related signals after rapid translocation to the cytoplasm or release from dead cells following brain ischemia [17], [18]. In the meantime, elevated serum HMGB1 levels in patients with ischemic stroke are associated with poor functional prognosis [19]. Moreover, Yang et al. have supported that miR-582–5p hinders neuroinflammation and oxidative stress via targeting HMGB1, thereby attenuating neonatal hypoxic-ischemic encephalopathy [20]. There are also research reports on the impact of RIPC on HMGB1 levels. For example, RIPC increases HMGB1 levels in plasma and urine of patients with acute kidney injury, which may be related to kidney protection [21]. RIPC and diazoxides protect against liver ischemia-reperfusion injury by inhibiting the TLR4/MyD88/NF-κB pathway induced by HMGB1 [22]. However, there is a dearth of reports in regard to the effects of RIPC intervention on serum levels of miR-582–5p/HMGB1 in ACI patients. Herein, we aimed to clarify the impacts of RIPC intervention in ACI patients.