Table 1.
Experimental and Clinical Studies Available at Present of Remote Ischemic Conditioning in Ischemic Stroke
| Type | Study | Stroke Model | RIC Organ | RIC Timing | RIC Protocol | Main Pathway Investigated | Improve CBF |
|---|---|---|---|---|---|---|---|
| Experimental studies | Chen et al (2018)4 | 2 h of middle cerebral artery occlusion followed by 24 h of reperfusion, male Sprague Dawley rats | Femoral arteries | Remote ischemic postconditioning | 3 cycles of 15 min ischemia and 15 min reperfusion, once at the beginning of middle cerebral artery reperfusion | The mTOR/p70S6K signal pathway | Not mentioned |
| Cheng et al (2018)5 | Transient middle cerebral artery occlusion, adult male C57BL/6 mice | Bilateral femoral arteries | Remote ischemic postconditioning | 3 cycles of 10 min ischemia and 10 min reperfusion, once immediately after reperfusion | Astrocytic plasticity | Not mentioned | |
| Kitagawa et al (2018)6 | 45 min of left middle cerebral artery occlusion, adult C57BL/6 mice | Upper thigh | Remote ischemic preconditioning, remote ischemic preconditioning and remote ischemic postconditioning | 4 cycles of 5 min ischemia and 5 min reperfusion, 24 h or 5 min before, during, or 5 min after middle cerebral artery occlusion | Collateral circulation | Yes | |
| Ren et al (2018)2 | 90 min of middle cerebral artery occlusion, adult male Sprague Dawley rats | Hind limb | Remote ischemic preconditioning and remote ischemic postconditioning | 3 cycles of 10 min ischemia and 10 min reperfusion, once immediately after MCAO surgery and once at 1 day after reperfusion, then repeated every day thereafter up to endpoint of study (7 or 14 days) | Notch signal pathway | Yes | |
| Gao et al (2017)7 | Transient middle cerebral artery occlusion, male Sprague Dawley rats | Bilateral femoral artery | Remote ischemic postconditioning | 3 cycles of 10 min ischemia and 10 min reperfusion, after 0, 10 or 30 min of brain reperfusion (R-0, R-10 and R-30 groups, respectively) | BID-mediated mitochondrial apoptotic pathway | Not mentioned | |
| Huang et al (2017)8 | Middle cerebral artery occlusion, male Sprague Dawley rats | Bilateral hind limbs | Remote ischemic postconditioning | 3 cycles of 10 min ischemia and 10 min reperfusion, once | No specific pathway mentioned | Not mentioned | |
| Khaksari et al (2017)9 | Bilateral carotid artery occlusion for 20 min followed by reperfusion for 72 h, adult male BALB/C mice | Left renal artery | Remote ischemic preconditioning | 3 cycles of 5 min ischemia and 5 min reperfusion, 24 h before global cerebral ischemia | Erythropoietin | Not mentioned | |
| Ma et al (2017)10 | Middle cerebral artery occlusion, male Sprague Dawley rats | Bilateral femoral artery | Remote ischemic preconditioning | 3 cycles of 15 min ischemia and 15 min reperfusion, once at 60 min after middle cerebral artery occlusion | Prevention of collateral collapse | Yes | |
| Ramagiri et al (2017)11 | Bilateral common carotid occlusion, male Wistar rats | Bilateral femoral artery | Remote ischemic postconditioning | 3 cycles of 10 min ischemia and 10 min reperfusion, once after cerebral ischemia | Heme oxygenase-1/BDNF pathway | Not mentioned | |
| Xu et al (2017)12 | 30 min of bilateral common carotid arteries occlusion combined with permanent occlusion of the left distal middle cerebral artery, adult male Sprague Dawley rats | Left femoral artery | Remote ischemic postconditioning | 3 cycles of 15 min ischemia and 15 min reperfusion, once at 1.5 h before distal middle cerebral artery occlusion | Extrinsic apoptotic pathway and TRAIL-receptors expression | Not mentioned | |
| Zhang et al (2017)13 | Middle cerebral artery occlusion, male Sprague Dawley rats | Bilateral femoral artery | Remote ischemic postconditioning | 3 cycles of 10 min ischemia and 10 min reperfusion, once at the beginning of the reperfusion | AKT pathway | Not mentioned | |
| Chen et al (2016)14 | Middle cerebral artery occlusion, male Sprague Dawley rats | Left femoral artery | Remote ischemic postconditioning | 3 cycles of 5 min ischemia and 5 min reperfusion, once at 0, 1 or 3 h after reperfusion | MyD88-TRAF6-P38 MAP-kinase pathway of neutrophils | Not mentioned | |
| Liu et al (2016)15 | 90 min occlusion of the right middle cerebral artery, male Sprague Dawley rats | Bilateral hind limb | Remote ischemic preconditioning | 4 cycles of 5 min reperfusion and 5 min ischemia, once at 1 h before middle cerebral artery occlusion | Significant alterations in peripheral immune responses | Not mentioned | |
| Wang et al (2016)16 | 120 min middle cerebral artery occlusion, adult male Sprague Dawley rats | The expression and location of HMGB1 | Remote ischemic preconditioning | 4 cycles of 5 min ischemia and 5 min reperfusion, once at 40 min prior to reperfusion | The expression and location of HMGB1 | Not mentioned | |
| Li et al (2015a)17 | Transient middle cerebral artery occlusion, male CD1 mice | Bilateral femoral artery | Remote ischemic postconditioning | 3 cycles of 5 min reperfusion and 5 min ischemia, once immediately after stroke onset | Nrf2 ARE (antioxidant response element) pathway | Not mentioned | |
| Li et al (2015b)18 | Transient middle cerebral artery occlusion, adult female Sprague Dawley rats | Bilateral femoral arteries | Remote ischemic postconditioning | 3 cycles of 10 min ischemia and 10 min reperfusion, once at the same time as reperfusion | AQP4 downregulation in astrocytes | Not mentioned | |
| Li et al (2015c)19 | Transient middle cerebral artery occlusion, male Sprague Dawley rats | Bilateral femoral arteries | Remote ischemic postconditioning | 3 cycles of 10 min ischemia and 10 min reperfusion, once at the same time as reperfusion | p38MAPK signal pathway | Not mentioned | |
| Qi et al (2015)20 | Middle cerebral artery occlusion, male Sprague Dawley rats | Bilateral femoral arteries | Remote ischemic preconditioning and remote ischemic postconditioning | 3 cycles of 10 min occlusion/10 min reperfusion, once at 30 min of ischemia or at the onset of reperfusion | AKT pathway | Not mentioned | |
| Xiao et al (2015)21 | Distal middle cerebral artery occlusion, adult male Sprague Dawley rats | Bilateral femoral arteries | Remote ischemic postconditioning | 3 cycles of 10 min ischemia and 10 min reperfusion, once at the same time as the bilateral common carotid arteries reperfusion | Peripheral nerves | Not mentioned | |
| Zong et al (2015)22 | Middle cerebral artery occlusion, male Sprague Dawley rats | Proximal hind limbs | Remote ischemic postconditioning | 3 cycles of 10 min ischemia and 10 min reperfusion, once at the beginning of reperfusion | HIF-1α | Not mentioned | |
| Chen et al (2014)23 | 2 h of middle cerebral artery occlusion, Sprague Dawley rats | Left femoral artery | Remote ischemic postconditioning | 3 cycles of 15 min reperfusion and 15 min ischemia, once at the same time as reperfusion | By reversing endothelial nitric oxide synthase uncoupling | Not mentioned | |
| Cheng et al (2014)24 | 90 min of middle cerebral artery occlusion, male Sprague Dawley rats | Right hind limb | Remote ischemic postconditioning | 3 cycles of 5 min reperfusion and 5 min ischemia, once at the beginning of reperfusion | Upregulating STAT3 and reducing apoptosis | Not mentioned | |
| Hoda et al (2014)25 | Embolic middle cerebral artery occlusion, C57BL/6J wild type ovariectomized mice | Limb | Remote ischemic preconditioning | 4 cycles of 10 min ischemia and 10 min reperfusion, once at 2 h poststroke | No specific pathway mentioned | Yes | |
| Hoda et al (2012)26 | Embolic middle cerebral artery occlusion, C57BL/6J wild-type male mice | Left limb | Remote ischemic preconditioning | 5 cycles of 5 min ischemia and 5 min reperfusion, once at 2 h after embolic middle cerebral artery occlusion | No specific pathway mentioned | Yes | |
| Hu et al (2012)27 | 2 h right middle cerebral artery occlusion, male Sprague Dawley rats | Right hind limb | Remote ischemic preconditioning | 3 cycles of 5 min ischemia and 5 min reperfusion, once at 1 h before brain ischemia | Depend on the activation of adenosine A1 receptors and by reduction in oxidative stress, inflammation and endogenous antioxidant preservation | Not mentioned | |
| Peng et al (2012)28 | 8 min of four-vessel occlusion in rats, adult male Sprague Dawley rats | Bilateral hind limbs | Remote ischemic postconditioning | 3 cycles of 15 min ischemia and 15 min reperfusion, once immediately after 8 min of four-vessel | PI3K/Akt pathway | Not mentioned | |
| Qi et al (2012)29 | Transient middle cerebral artery occlusion, Sprague Dawley rats | Bilateral femoral artery | Remote ischemic postconditioning | 3 cycles of 10 min occlusion/10 min release, at 0, 10, or 30 min of reperfusion | AKT/GSK3β-dependent autophagy | Not mentioned | |
| Sun et al (2012)30 | 90 min of middle cerebral artery occlusion followed by 72 hrs of reperfusion, male Sprague Dawley rats | Bilateral femoral artery | Delayed remote limb ischemic postconditioning | 3 cycles of occlusion 15 seconds/5 mins/8 mins ischemia/15 seconds/5 mins/8 mins reperfusion, once at 3 or 6 h after reperfusion | Mitochondrial K(ATP) channels | Not mentioned | |
| Wei et al (2012)31 | Left distal middle cerebral artery occlusion, male Sprague Dawley rats | Left hind limb | Remote ischemic preconditioning | 3 cycles of 5 min ischemia and 5 min reperfusion, once immediately before stroke | No specific pathway mentioned | Not mentioned | |
| Yuan et al (2012)32 | Occlusion of the left common carotid arteries for 30 min combined with permanent occlusion of the left distal middle cerebral artery, male Wistar rats | Left thigh | Remote ischemic preconditioning | 3 cycles of 5 min ischemia and 5 min reperfusion, 3 times per day for 3 days | No specific pathway mentioned | Not mentioned | |
| Hahn et al (2011)33 | 120 min middle cerebral artery occlusion, and 24 h reperfusion, P60 rats | Left hind limb | Remote ischemic preconditioning and perconditioning | 4 cycles of 5 min ischemia and 5 min reperfusion, at 40 min prior to middle cerebral artery occlusion | No specific pathway mentioned | Not mentioned | |
| Ren et al (2009)34 | 30 min bilateral common carotid arteries occlusion combined with permanent occlusion of the left distal middle cerebral artery, male Sprague Dawley rats | Femoral artery occlusion in the left limb | Remote ischemic postconditioning | 3 cycles of 15 min ischemia and 15 min reperfusion, once at the beginning of reperfusion or 3 or 6 h after reperfusion | Protein synthesis inhibitor and nerve blocker eliminate the protective effect of rapid limb remote ischemic postconditioning | Not mentioned | |
| Ren et al (2008)35 | Permanent occlusion of the left distal middle cerebral artery combined with a 30 min occlusion of the bilateral common carotid arteries, male Sprague Dawley rats | Left femoral artery | Remote ischemic preconditioning | 2 or 3 cycles of 5- or 15-min occlusion followed with the same period of reperfusion, immediately or 12 h, 2 d before brain ischemia | No specific pathway mentioned | Not mentioned | |
| Clinical studies | (Che et al, 2019)36 | Acute ischemic stroke patients with intravenous recombinant tissue plasminogen activator thrombolysis | Bilateral upper limbs | Remote ischemic postconditioning | 5 cycles of alternating 5 mins inflation (200 mmHg) and 5 mins deflation, once on the first day after IVT, and twice a day for 6 consecutive days | No specific pathway mentioned | Not mentioned |
| Zhao et al (2018)37 | Patients with acute ischemic stroke having large‐vessel occlusion in the anterior circulation and scheduled for endovascular treatment (ET) within 6 hrs of ictus | Unilateral arm | Remote ischemic preconditioning and remote ischemic postconditioning | 4 cycles of alternating 5 mins inflation (200 mmHg) and 5 mins deflation, once pre-ET, once post-ET, and once daily for 7 consecutive days | No specific pathway mentioned | No | |
| (Li et al, 2018)38 | Nonthrombolysis patients with acute ischemic stroke within 72 hrs of ictus | The nonparetic arm | Remote ischemic postconditioning | 4 cycles of alternating 5 mins inflation (20 mmHg above systolic blood pressure) and 5 mins deflation, from the time of enrollment to Day 14 | No specific pathway mentioned | Not mentioned | |
| England et al (2017)39 | Patients with acute ischemic stroke of 24 h of ictus | The nonparetic arm | Remote ischemic preconditioning | 4 cycles of alternating 5 mins inflation (20 mmHg above systolic blood pressure) and 5 mins deflation, the control group received a sham procedure (cuff inflation to 30 mmHg), once within 24 h of ictus | No specific pathway mentioned | Not mentioned | |
| Hougaard et al (2014)40 | Patients with acute ischemic stroke | One arm | Remote ischemic preconditioning | 4 cycles of alternating 5 mins inflation (either 200 or 25 mmHg above systolic blood pressure) and 5 mins deflation, once before rt-PA treatment | No specific pathway mentioned | Not mentioned |