Determination of significant parameters in remote ischemic postconditioning for ischemic stroke in experimental models: A systematic review and meta‐analysis study

Abstract

Objectives:To systematically review studies using remote ischemia postconditioning (RIPostC) for ischemic stroke in experimental models and obtain factors that significantly influence treatment outcomes. Materials and Methods:Peer-reviewed studies were identified and selected based on the eligibility criteria, followed by extraction of data on potentially influential factors related to model preparation, postconditioning, and measure time based on outcome measures including infarct size, neurological scales, and cell tests with autophagy, apoptosis, normal-neuron, and damaged-neuron counting. Then, all data were preprocessed, grouped, and meta-analyzed with the indicator of the standardized mean difference. Results:Fifty-seven studies with 224 experiments (91 for infarct size, 92 for neurological scales, and 41 for cell-level tests) were included. There was little statistical difference between different model preparations, treated body parts, number of treatments, and sides. And treatment effect was generally a positive correlation with the duration of conditioning time to stroke onset with exceptions at some time points.Based on infarct size, the number of cycles per treatment, duration of occlusion, and release per cycle showed significant differences. Combined with the effect sizes by other measures, the occlusion/release duration of 8-10 min per cycle is better than 5 min, and three cycles per treatment were most frequently used with good effects.Effect also varied when measuring at different times, showing statistical differences in infarct size and most neurological scales. RIPostC is confirmed as an effective therapeutic intervention for ischemic stroke, while the RIPostC-mediated autophagy level being activated or inhibited remained conflicting. Conclusions: Conditioning time, number of cycles per treatment, duration of occlusion, and release per cycle were found to influence the treatment effects of RIPostC | 1493 LIU et aL.

Efficacy and safety of remote ischemic conditioning for acute ischemic stroke: A comprehensive meta‐analysis from randomized controlled trials

“…According to our studies, it is suggested that chronic RIC is a good option for patients who are not eligible for the narrow window for thrombolysis (within 4.5 h after symptom onset) and endovascular reconstruction (within 24 h after symptom onset based on two studies published online on Oct 13, 2022, in the New England Journal of Medicine, 5,8 ) and our result was consistent with most preclinical meta-analyses. 20,21,23,24 However, one study 23 performed within 48-72 h showed better effects compared with those performed in the hyperacute stage and 4-7 days. Given the limited evidence, the exact time window and the most effective neuroprotective RIC intervention period could not be fully determined.…”

“…Although there have been previous systematic reviews and meta‐analyses of RIC as a neuroprotective therapy, most of them focused on preclinical animal models 20–24 . However, translating treatment effects on stroke from animal ischemia models to clinical reality is often a great challenge due to nonphysiological experimental conditions in animals that do not reflect human conditions 25 .…”

“…[16][17][18][19] Although there have been previous systematic reviews and meta-analyses of RIC as a neuroprotective therapy, most of them focused on preclinical animal models. [20][21][22][23][24] However, translating treatment effects on stroke from animal ischemia models to clinical reality is often a great challenge due to nonphysiological experimental conditions in animals that do not reflect human conditions. 25 In addition, others made the summary of the completed RCTs on RIC in IS patients with a high percentage of participants lost to follow-up, a limited number of recruited subjects, and a lack of comprehensive analyses.…”

Impact of remote ischemic postconditioning on acute ischemic stroke in China: a systematic review and meta-analysis of randomized controlled trials

“…In exploring English-language databases, only four meta-analyses and systematic reviews relevant to this field have been identified, with two focusing on animal studies and the other on clinical trials. The reviews of animal studies [ 84 , 85 ], though encompassing a wide array of primary research and conducted across various species, provided a comprehensive and detailed assessment of the outcomes. These analyses present robust evidence supporting the preclinical efficacy of RIPostC.…”

Targeting cell death pathways in intestinal ischemia-reperfusion injury: a comprehensive review

“…Ischemic postconditioning (IPO) is a treatment method for I/R injury. The core of IPO is to mitigate reperfusion injury through short, alternating blood flow blockade and restoration during the reperfusion stage [ 105 ]. Research has shown that IPO can effectively protect intestinal I/R injury from ischemic postconditioning by inducing autophagy, activating Akt, inactivating GSK-3β, and activating Nrf2.…”