Elevated Serum Potassium Concentration Alleviates Cerebral Ischemia-Reperfusion Injury via Mitochondrial Preservation

Abstract

Background/Aims: The anti-apoptotic effect of an increase in the extracellular concentration of potassium ([K⁺]) has been confirmed in vitro. However, it is not yet known whether elevated serum [K⁺] exerts a cerebroprotective effect in vivo. In this study, we aimed to explore the effect of elevated serum [K⁺] in a rat model of middle cerebral artery occlusion and reperfusion (MCAO/R). Methods: Rats subjected to 90-min MCAO received 2.5% KCL, 1.25% KCL, or a normal saline solution at a dose of 3.2 mL/kg at the onset of reperfusion. Rats that were subjected to vascular exposure and ligation without MCAO were defined as the Sham group. Serum [K⁺] was determined using a blood gas analyzer at 1 min after medicine administration. At 24 h post-reperfusion, rat brains were harvested and processed for 2% 2,3,5-triphenyltetrazolium chloride staining, terminal deoxynucleotidyl transferase-mediated 2′-deoxyuridine 5′-triphosphate-biotin nick end labeling staining, detection of caspase-3 and cleaved-caspase-3 by western blotting, detection of reactive oxygen species (ROS) by dihydroethidium staining, and observation of mitochondrial structure by electron microscopy. In addition, malondialdehyde (MDA), adenosine triphosphate (ATP), total superoxide dismutase (T-SOD), cytochrome C oxidase (COX) activity, and mitochondrial permeability transition pore (MPTP) opening were measured using detection kits. Results: The results showed that elevated serum [K⁺] decreased cerebral injury and apoptosis, reduced ROS and MDA levels and MPTP opening, increased ATP levels and cytochrome C oxidase activity, and improved mitochondrial ultrastructural changes, although there was no significant difference in T-SOD activity. Conclusion: These findings suggested that elevated serum [K⁺] could alleviate cerebral ischemia-reperfusion injury and the mechanism may be associated with the preservation of mitochondrial function.

High‐potassium preconditioning enhances tolerance to focal cerebral ischemia‐reperfusion injury through anti‐apoptotic effects in male rats

“…In the present study, our results showed that increasing blood potassium concentrations with IV KCl solution before ischemia can markedly attenuate brain I/R injury as confirmed by decreases in infarct volumes and improvements in NDSs and neuronal morphology. Similar to our results, brain protective effects have also been observed when KCl solution was administered after ischemia in rats (Li et al, ). In addition, experiments with a cardiac arrest and cardiopulmonary resuscitation (CA/CPR) model revealed that high blood potassium levels may impact the tolerance of brain tissue to I/R injury.…”

“…In the present study, high‐potassium preconditioning increased SOD activity and reduced MDA levels compared to NS treatment, suggesting that high‐potassium preconditioning exerts antioxidant effects. In contrast, in a previous study by Li et al, elevated blood K + at the moment of reperfusion reduced ROS production but failed to improve antioxidant defenses (Li et al, ). This discrepancy may be due to differences between the two experimental protocols.…”

“…In an experiment on cultured human neutrophils, Kebir et al showed that high extracellular K + suppressed apoptosis by preventing mitochondrial dysfunction, protecting the mitochondrial transmembrane potential and attenuating cytochrome c release from mitochondria into the cytosol (El Kebir, Jozsef, Khreiss, & Filep, ). Furthermore, a previous experiment from our laboratory showed that elevated blood potassium at the onset of reperfusion can alleviate cerebral I/R injury by preserving mitochondrial function (Li et al, ). In the current study, preconditioning with high blood potassium elevated COX levels, improved SDH activity and increased the ATP content; these findings are consistent with the results of previous experiments and indicate that high serum potassium helps protect the brain both during ischemia and after reperfusion.…”

“…First, due to technical limitations, dynamic changes in blood K + concentrations and brain K + levels after NS/KCl administration were not continuously monitored in this study. Second, in this study, we examined the effects of high‐potassium preconditioning on neuronal apoptosis only in terms of mitochondrial energy metabolism; we did not analyses mitochondrial permeability, mitochondrial ROS levels or cytochrome c release, although a similar study (Li et al, ) has been conducted previously. Third, the doses of KCl were selected somewhat empirically.…”

“…Statistical analyses were performed using SPSS 20.0 statistical software (SPSS Inc., Cary, NC). The sample size in the present study was calculated based on our previous experiments and considering alpha = 0.05, power = 80% (Li et al, ). All data are presented as the mean ± standard deviation ( SD ) or as a percentage.…”