Abstract
Reperfusion is the only existing strategy for patients with acute ischemic stroke, however it causes further brain damage itself. A feasible therapy targeting reperfusion injury is remote ischemic conditioning (RIC). This was a two-centre, randomized, blinded international study, using translational imaging endpoints, aimed to examine the neuroprotective effects of RIC in ischemic stroke model. 80 male rats underwent 90-min middle cerebral artery occlusion. RIC consisted of 4 × 5 min cycles of left hind limb ischemia. The primary endpoint was infarct size measured on T2-weighted MRI at 24 h, expressed as percentage of the area-at-risk. Secondary endpoints were: hemispheric space-modifying edema, infarct growth between per-occlusion and 24 h MRI, neurofunctional outcome measured by neuroscores. 47 rats were included in the analysis after applying pre-defined inclusion criteria. RIC significantly reduced infarct size (median, interquartile range: 19% [8%; 32%] vs control: 40% [17%; 59%], p = 0.028). This effect was still significant after adjustment for apparent diffusion coefficient lesion size in multivariate analysis. RIC also improved neuroscores (6 [3; 8] vs control: 9 [7; 11], p = 0.032). Other secondary endpoints were not statistically different between groups. We conclude that RIC in the setting of acute ischemic stroke in rats is safe, reduces infarct size and improves functional recovery.
Highlights
Reperfusion is the only existing strategy for patients with acute ischemic stroke, it causes further brain damage itself
Despite a successful recanalization achieved in more than 70% of cases, functional independence was obtained only in nearly 45% of patients treated with mechanical thrombectomy (MT) + /− intravenous tissue recombinant plasminogen activator[5]
47 animals were analyzed after applying all the exclusion criteria (n = in the control group and n = in the remote ischemic conditioning (RIC) group)
Summary
Reperfusion is the only existing strategy for patients with acute ischemic stroke, it causes further brain damage itself. A feasible therapy targeting reperfusion injury is remote ischemic conditioning (RIC) This was a two-centre, randomized, blinded international study, using translational imaging endpoints, aimed to examine the neuroprotective effects of RIC in ischemic stroke model. Despite a successful recanalization achieved in more than 70% of cases, functional independence (modified Rankin score mRs 0–2 at 3 months after ischemic stroke) was obtained only in nearly 45% of patients treated with MT + /− intravenous tissue recombinant plasminogen activator[5] This reveals the need to develop new adjunctive neuroprotective strategies alongside reperfusion therapy. To date, the two completed trials[17,18,19] did not show a benefit in such patients This may question the results of the numerous singlecentre animal studies that demonstrated an infarct-limiting effect of RIC in acute stroke models (reviewed in20,21). International collaboration has been identified as a factor providing high levels of complementarity in pre-clinical stroke s tudies[25]
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