The Impact of Serial Remote Ischemic Conditioning on Dynamic Cerebral Autoregulation and Brain Injury Related Biomarkers

Abstract

ObjectiveRecent studies have demonstrated the positive roles of remote ischemic conditioning (RIC) in patients with cerebrovascular diseases; however, the mechanisms remain unclear. This study aimed to explore the effect of serial RIC on dynamic cerebral autoregulation (dCA) and serum biomarkers associated with brain injury, both of which are related to the prognosis of cerebrovascular disease.MethodsThis was a self-controlled interventional study in healthy adults. The RIC was conducted twice a day for 7 consecutive days (d1–d7) and comprised 4 × 5-min single arm cuff inflation/deflation cycles at 200 mmHg. All participants underwent assessments of dCA ten times, including baseline, d1, d2, d4, d7, d8, d10, d14, d21, and d35 of the study. Blood samples were collected four times (baseline, d1, d7, and d8) immediately after dCA measurements. The transfer function parameters [phase difference (PD) and gain] were used to quantify dCA. Four serum biomarkers associated with brain injury, ubiquitin C-terminal hydrolase-L1, neuron-specific enolase, glial fibrillary acidic protein, and S100β were tested.ResultsTwenty-two healthy adult volunteers (mean age 25.73 ± 1.78 years, 3 men [13.6%], all Asian) were enrolled in this study. Bilateral PD values were significantly higher since four times of RIC were completed (d2) compared with PD values at baseline (left: 53.31 ± 10.53 vs. 45.87 ± 13.02 degree, p = 0.015; right: 54.90 ± 10.46 vs. 45.96 ± 10.77 degree, p = 0.005). After completing 7 days of RIC, the significant increase in dCA was sustained for at least 28 days (d35, left: 53.11 ± 14.51 degree, P = 0.038; right: 56.95 ± 14.57 degree, p < 0.001). No difference was found in terms of different serum biomarkers related to brain injury before and after RIC.ConclusionThe elevation in dCA was detected immediately after four repeated times of RIC, and 7-day consecutive RIC induced a sustained increase in dCA for at least 28 days and did not affect blood biomarkers of brain injury in healthy adults. These results will help us to formulate detailed strategies for the safe and effective application of RIC in patients with cerebrovascular disease.

Baseline systolic blood pressure, hypertension history, and efficacy of remote ischemic conditioning

“…As discussed above, this phenomenon may be attributed to the beneficial effect of RIC on cerebral autoregulation, collateral circulation, and cerebral reservoir. 24,30,32 In this study, we further found that previous hypertension history might be associated with poor efficacy of RIC. We speculate that this may be related to pathological vascular remodeling induced by hypertension.…”

“…As discussed above, this phenomenon may be attributed to the beneficial effect of RIC on cerebral autoregulation, collateral circulation, and cerebral reservoir. 24 , 30 , 32 …”

“… 23 In this context, we hypothesize that hypertension and SBP may affect efficacy of RIC in ischemic stroke, given their effect of RIC on cerebral autoregulation. 24 The issue is of importance but is never investigated. In this post hoc secondary analysis, we aimed to investigate this issue based on RICAMIS data.…”

Neuroadaptive Biochemical Mechanisms of Remote Ischemic Conditioning

“…There are studies suggesting that RIC applications improve microcirculation in various organs under normal and pathological conditions [57][58][59]. Although it is technically difficult to assess the effect of RIC on brain microcirculation, there is evidence that multiple RIC applications improve cerebral blood flow [60] and enhance dynamic cerebral autoregulation in healthy individuals [61], which requires further study of its effects on brain vasculature and endothelial remodeling. Nevertheless, it is already evident that RIC in pre-and postconditioning modes is protective against brain cerebrovascular cognitive dysfunction [62].…”

Safety and efficacy of remote ischemic conditioning combined with endovascular thrombectomy for acute ischemic stroke due to large vessel occlusion of anterior circulation: A multicenter, randomized, parallel-controlled clinical trial (SERIC-EVT): Study protocol

“…7 Previous studies have reported that RIC stimulates endogenous protective mechanisms and has a protective role particularly in brain tissue. [8][9][10] In an experimental ischemia-reperfusion model, RIC has been shown to reduce cerebral ischemia-reperfusion injury, inflammatory substances, brain edema, and neuronal apoptosis. 11,12 Thus, RIC might be beneficial for patients who have undergone EVT treatment because cerebral recanalization after ischemia is similar to ischemia-reperfusion models.…”