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During cerebral ischemia-reperfusion conditions, the excessive reactive oxygen species in the ischemic penumbra region, resulting in neuronal oxidative stress, constitute the main pathological mechanism behind ischemia-reperfusion damage. Swiftly reinstating blood perfusion in the ischemic penumbra zone and suppressing neuronal oxidative injury are key to effective treatment. Presently, antioxidants in clinical use suffer from low bioavailability, a singular mechanism of action, and substantial side effects, severely restricting their therapeutic impact and widespread clinical usage. Recently, nanomedicines, owing to their controllable size and shape and surface modifiability, have demonstrated good application potential in biomedicine, potentially breaking through the bottleneck in developing neuroprotective drugs for ischemic strokes. This manuscript intends to clarify the mechanisms of cerebral ischemia-reperfusion injury and provides a comprehensive review of the design and synthesis of antioxidant nanomedicines, their action mechanisms and applications in reversing neuronal oxidative damage, thus presenting novel approaches for ischemic stroke prevention and treatment., Competing Interests: Declaration of competing interest All authors of this research group have no conflicts of interest related to the publication of this article to declare., (Copyright © 2024. Published by Elsevier B.V.)

Caveolae-associated signaling toward mitochondria contributes to the cardioprotective mechanisms against ischemia-reperfusion (I/R) injury induced by ischemic postconditioning. In this work, we evaluated the role that the actin-cytoskeleton network exerts on caveolae-mitochondria communication during postconditioning. Isolated rat hearts subjected to I/R and to postconditioning were treated with latrunculin A, a cytoskeleton disruptor. Cardiac function was compared between these hearts and those exposed only to I/R and to the cardioprotective maneuver. Caveolae and mitochondria structures were determined by electron microscopy and maintenance of the actin-cytoskeleton was evaluated by phalloidin staining. Caveolin-3 and other putative caveolae-conforming proteins were detected by immunoblot analysis. Co-expression of caveolin-3 and actin was evaluated both in lipid raft fractions and in heart tissue from the different groups. Mitochondrial function was assessed by respirometry and correlated with cholesterol levels. Treatment with latrunculin A abolishes the cardioprotective postconditioning effect, inducing morphological and structural changes in cardiac tissue, reducing F-actin staining and diminishing caveolae formation. Latrunculin A administration to post-conditioned hearts decreases the interaction between caveolae-forming proteins, the co-localization of caveolin with actin and inhibits oxygen consumption rates in both subsarcolemmal and interfibrillar mitochondria. We conclude that actin-cytoskeleton drives caveolae signaling to mitochondria during postconditioning, supporting their functional integrity and contributing to cardiac adaption against reperfusion injury.

Purpose: Endovascular thrombectomy is highly effective in patients with proximal large artery occlusion but the relevance of reperfusion injury after recanalization is a matter of debate. The aim of this study was to investigate potential residual metabolic distress and microstructural tissue damage or edema after reperfusion using quantitative oxygen-sensitive T2' and T2-mapping in patients successfully treated by thrombectomy., Methods: Included in this study were 11 patients (mean age 70 ± 11.4 years) with acute ischemic stroke due to internal carotid artery and/or middle cerebral artery occlusion. Quantitative T2 and T2' (1/T2' = 1/T2* - 1/T2) were determined within the ischemic core and hypoperfused but salvaged tissue with delayed time-to-peak (TTP) in patients before and after successful thrombectomy and compared to a control region within the unaffected hemisphere., Results: Decreased T2' values within hypoperfused tissue before thrombectomy showed a normalization after recanalization (p < 0.01). In formerly hypoperfused but salvaged tissue, T2 values increased significantly after thrombectomy (p < 0.05) but did not differ from reference values in the control region. In salvaged tissue, increases of quantitative T2' and T2 to follow-up were more pronounced in areas with severe TTP delay., Conclusion: After successful recanalization, T2' re-increased back to normal in formerly hypoperfused areas as a sign of prompt normalization of oxygen metabolism. Furthermore, quantitative T2 in the formerly hypoperfused tissue did not differ from reference values in unaffected tissue. These results indicate complete restitution of salvaged tissue after reperfusion and support the overall safety of endovascular thrombectomy with respect to microstructural tissue integrity.

Background: Laparoscopic partial nephrectomy, which minimizes renal function loss due to its nephron sparing nature, has become a standard technique among many experienced centers worldwide for surgical treatment of localized kidney tumors. Although partial nephrectomy will remain the gold standard, we need to improve perioperative management and surgical method to prevent postoperative acute kidney injury. Aims: To demonstrate the frequency of the development of postoperative acute kidney injury following laparoscopic partial nephrectomy in patients with healthy contralateral kidney and determine the early predictive effects of serum neutrophil gelatinaseassociated lipocalin on ischemia-reperfusion injury and its association with warm ischemia time. Study Design: Cross-sectional study. Methods: Eighty patients were included. We analyzed tumor size, operating time, duration of anesthesia, and warm ischemia time. Serum samples were obtained for measurement of serum creatinine, estimated glomerular filtration rate, and neutrophil gelatinaseassociated lipocalin level preoperatively, at the postoperative 2nd hour, and on postoperative days 1 and 2. We used receiver operating characteristic curve for determining the cut-off point of neutrophil gelatinase-associated lipocalin to detect postoperative acute kidney injury. Correlation analysis was performed using Spearman's test. Results: Twenty-seven patients developed acute kidney injury on postoperative day 2, and the neutrophil gelatinase-associated lipocalin level increased significantly at the postoperative 2nd hour in the acute kidney injury group (p=0.048). For a cut-off of 129.375 ng/ mL neutrophil gelatinase-associated lipocalin, the test showed 70.0% sensitivity and 68.3% specificity for the detection of acute kidney injury at the postoperative 2nd hour. For a cut-off of 184.300 ng/mL neutrophil gelatinase-associated lipocalin, the test exhibited 73.3% sensitivity and 63.3% specificity for the detection of acute kidney injury on postoperative day 1. A significant correlation was found between warm ischemia time and neutrophil gelatinase-associated lipocalin level at the postoperative 2nd hour (r=0.398, p=0.003). The creatinine values were significantly higher and the estimated glomerular filtration rates were significantly lower on postoperative days 1 and 2 in the acute kidney injury group compared with those in the non-acute kidney injury group (p<0.001) Conclusion: The neutrophil gelatinase-associated lipocalin may be used as an alternative biomarker to serum creatinine in differentiation of ischemic damage in patients undergoing laparoscopic partial nephrectomy. [ABSTRACT FROM AUTHOR]