Abstract
Ischemic stroke is a common disease with high morbidity and mortality. Remote ischemic preconditioning (RIPC) can stimulate endogenous protection mechanisms by inducing ischemic tolerance to reduce subsequent damage caused by severe or fatal ischemia to non-ischemic organs. This study was designed to assess the therapeutic properties of RIPC in ischemic stroke and to elucidate their underlying mechanisms. Neurobehavioral function was evaluated with the modified neurological severity score (mNSS) test and gait analysis. PET/CT was used to detect the ischemic volume and level of glucose metabolism. The protein levels of cytochrome c oxidase-IV (COX-IV) and heat shock protein 60 (HSP60) were tested by Western blotting. TUNEL and immunofluorescence staining were used to analyze apoptosis and to observe the nuclear translocation and colocalization of apoptosis-inducing factor (AIF) and endonuclease G (EndoG) in apoptotic cells. Transmission electron microscopy (TEM) was used to detect mitochondrial-derived vesicle (MDV) production and to assess mitochondrial ultrastructure. The experimental results showed that RIPC exerted significant neuroprotective effects, as indicated by improvements in neurological dysfunction, reductions in ischemic volume, increases in glucose metabolism, inhibition of apoptosis, decreased nuclear translocation of AIF and EndoG from mitochondria and improved MDV formation. In conclusion, RIPC alleviates ischemia/reperfusion injury after ischemic stroke by inhibiting apoptosis via the endogenous mitochondrial pathway.
Highlights
RIPC can effectively improve the symptoms of neurological deficits and reduce the volume of ischemic lesions after cerebral ischemia
We speculate that RIPC increases the resistance of cells to ischemic insults by promoting MDV formation to remove damaged segments of mitochondria, maintain mitochondrial structural and functional integrity, decrease mitochondrial degradation and decrease nuclear translocation of AIF and EndoG from mitochondria to inhibit the mitochondrial pathway
Further studies and an optimized experimental design taking the results of this study into consideration are required to better understand and verify the mechanisms
Summary
Healthy adult C57BL/6 mice weighing 23–26 g and aged 8–9 weeks were provided by the SPF. Laboratory Animal Center of Southwest Medical University. All of the animals were housed in the same animal care facility under standard temperature (23 ± 2 °C), lighting (12-h light/dark cycle) and relative humidity (65 ± 5%) conditions and with free access to food and water. The experimental protocol complied with the guidelines of the People’s Republic of China on experimental animals. The animal protocol was approved by the Animal Ethical Committee of the Animal Center of Southwest Medical University (Luzhou, Sichuan), and the experimental procedures were optimized to minimize the number of animal deaths and reduce the pain felt by the experimental animals. The mice were randomly divided into four groups: the sham operation (sham) group, the cerebral ischemia/reperfusion (I/R) group, the RIPC group, and the RIPC + I/R group
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
