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Abstract The inflammation and coagulopathy during coronavirus disease (COVID-19) impairs the efficiency of the current stroke treatments. Remote ischaemic conditioning (RIC) has shown potential in recent years to protect the brain and other organs against pathological conditions. This study aimed to evaluate the efficiency of RIC in brain infarct size using TTC staining and lung injury reduction by H&E staining during the hyper-inflammatory response in rats. The inflammation and coagulopathy were assessed by sedimentation rate, haematocrit, systemic oxidative stress and clotting time. Moreover, we observed changes in the cytokine profile. The results of the first part of the experiment showed that the inflammation and lung injury are fully developed after 24 h of intratracheal LPS administration. At this time, we induced focal brain ischaemia and examined the effect of RIC pre- and post-treatment. Our results showed that RIPre-C reduced the infarct size by about 23%, while RIPost-C by about 30%. The lung injury was also reduced following both treatments. Moreover, RIC modulated systemic inflammation. The level of chemokines CINC-1, LIX and RANTES decreased after 24 h of post-ischaemic reperfusion in treated animals compared to non-treated. The RIC-mediated decrease of inflammation was reflected in improved sedimentation rate and hematocrit, as well as reduced systemic oxidative stress. The results of this work showed neuroprotective and lung protective effects of RIC with a decrease in inflammation response. On the basis of our results, we assume that immunomodulation through the chemokines CINC-1, LIX, and RANTES play a role in RIC-mediated protection.

Background : Remote ischemic postconditioning (RIPostC) may protect the brain from ischemia/reperfusion (I/R) injury. The association between RIPostC and obesity has not yet been extensively studied. Methods : Twelve-week-old male Zucker diabetic fatty (ZDF; n=68) and Zucker diabetic lean (ZDL; n=51) rats were subjected to focal cerebral ischemia for 90 minutes, followed by 24 hours of reperfusion. RIPostC was performed with 5-minute I/R cycles using a tourniquet on the right hind limb. Results : The results showed a negative association between obesity and neurological impairment in ischemic animals. We observed a 70% greater infarct size in ZDF rats compared with their lean counterparts, as evaluated by 2,3,5-triphenyltetrazolium chloride staining. To measure the total fragmented DNA in peripheral lymphocytes, comet assay was performed. Obese rats exhibited higher levels of DNA damage (by approximately 135%) in peripheral blood lymphocytes even before the induction of stroke. RIPostC did not attenuate oxidative stress in the blood in obese rats subjected to ischemia. Focal cerebral ischemia increased core and penumbra tissue glutamate release in the brain and decreased it in the blood of ischemic ZDL rats, and these changes improved following RIPostC treatment. However, changes in blood and tissue glutamate content were not detected in ischemic ZDF rats or after RIPostC intervention. Conclusion : Our findings suggest that obese animals respond more severely to ischemia-reperfusion brain injury. However, obese animals did not achieve neuroprotective benefits of RIPostC treatment.

Background: Remote ischemic postconditioning (RIPostC) may protect the brain from ischemia/reperfusion (I/R) injury. The association between RIPostC and obesity has not yet been extensively studied., Methods: Twelve-week-old male Zucker diabetic fatty (ZDF; n=68) and Zucker diabetic lean (ZDL; n=51) rats were subjected to focal cerebral ischemia for 90 minutes, followed by 24 hours of reperfusion. RIPostC was performed with 5-minute I/R cycles using a tourniquet on the right hind limb., Results: The results showed a negative association between obesity and neurological impairment in ischemic animals. We observed a 70% greater infarct size in ZDF rats compared with their lean counterparts, as evaluated by 2,3,5-triphenyltetrazolium chloride staining. To measure the total fragmented DNA in peripheral lymphocytes, comet assay was performed. Obese rats exhibited higher levels of DNA damage (by approximately 135%) in peripheral blood lymphocytes even before the induction of stroke. RIPostC did not attenuate oxidative stress in the blood in obese rats subjected to ischemia. Focal cerebral ischemia increased core and penumbra tissue glutamate release in the brain and decreased it in the blood of ischemic ZDL rats, and these changes improved following RIPostC treatment. However, changes in blood and tissue glutamate content were not detected in ischemic ZDF rats or after RIPostC intervention., Conclusion: Our findings suggest that obese animals respond more severely to ischemia-reperfusion brain injury. However, obese animals did not achieve neuroprotective benefits of RIPostC treatment.

The successful implementation of remote ischaemic conditioning as a clinical neuroprotective strategy requires a thorough understanding of its basic principles, which can be modified for each patient. The mechanisms of glutamate homeostasis appear to be a key component. In the current study, we focused on the brain-to-blood glutamate shift mediated by glutamate transporters (excitatory amino acid transports [EAATs]) and the effect of remote ischaemic preconditioning (RIPC) as a mediator of ischaemic tolerance. We used model mimicking ischaemia-mediated excitotoxicity (intracerebroventricular administration of glutamate) to avoid the indirect effect of ischaemia-triggered mechanisms. We found quantitative changes in EAAT2 and EAAT3 and altered membrane trafficking of EAAT1 on the cells of the choroid plexus. These changes could underlie the beneficial effects of ischaemic tolerance. There was reduced oxidative stress and increased glutathione level after RIPC treatment. Moreover, we determined the stimulus-specific response on EAATs. While glutamate overdose stimulated EAAT2 and EAAT3 overexpression, RIPC induced membrane trafficking of EAAT1 and EAAT2 rather than a change in their expression. Taken together, mechanisms related to glutamate homeostasis, especially EAAT-mediated transport, represents a powerful tool of ischaemic tolerance and allow a certain amount of flexibility based on the stimulus used., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)