Sevoflurane Post-conditioning Enhanced Hippocampal Neuron Resistance to Global Cerebral Ischemia Induced by Cardiac Arrest in Rats through PI3K/Akt Survival Pathway

Abstract

The purpose of this current study was to evaluate whether improvement of mitochondrial dysfunction was involved in the therapeutic effect of sevoflurane post-conditioning in global cerebral ischemia after cardiac arrest (CA) via the PI3K/Akt pathway. In the first experiment, animals were randomly divided into three groups: a sham group, a CA group, a CA+sevoflurane post-conditioning group (CA+SE). Sevoflurane post-conditioning was achieved by administration of 2.5% sevoflurane for 30 min after resuscitation. Sevoflurane post-conditioning has a significant neuroprotective effect by increasing survival rates and reducing neuronal apoptosis. Additionally, the gene and protein expression of PGC-1α, NRF-1, and TFAM, the master regulators of mitochondrial biogenesis, were up-regulated in the CA+SE group, when compared to the CA group. Similarly, in contrast to the CA group, mitochondria-specific antioxidant enzymes, including heat-shock protein 60 (HSP60), peroxiredoxin 3 (Prx3), and thioredoxin 2 (Trx2) were also increased in the CA+SE group. Finally, administration of sevoflurane ameliorated mitochondrial reactive oxygen species (ROS) formation and maintained mitochondrial integrity. In the second experiment, we investigated the relationship between the PI3K/Akt pathway and mitochondrial biogenesis and mitochondria-specific antioxidant enzymes in sevoflurane-induced neuroprotection. The selective PI3K inhibitor wortmannin not only eliminated the beneficial biochemical processes of sevoflurane by reducing the level of mitochondrial biogenesis-related proteins and aggravating mitochondrial integrity, but also reversed the elevation of mitochondria-specific antioxidant enzymes induced by sevoflurane. Therefore, our data suggested that sevoflurane post-conditioning provides neuroprotection via improving mitochondrial biogenesis and integrity, as well as increasing mitochondria-specific antioxidant enzymes by a mechanism involving the PI3K/Akt pathway.

Retracted: Effects of microRNA‐206 and its target gene IGF‐1 on sevoflurane‐induced activation of hippocampal astrocytes in aged rats through the PI3K/AKT/CREB signaling pathway

“…The activation of glial cells, such as astrocytes, by synaptic activity is accompanied by feedback modulation of synaptic efficacy and short‐term plasticity (Serrano, Haddjeri, Lacaille, & Robitaille, ). As a novel volatile anesthetic with minimal pungency, sevoflurane is characterized by low solubility and less toxicity, and is widely used in anesthetic practice and may delay the activation of astrocytes (Karwacki et al, , Wang, Ye, Huang, Wang, & Wang, ). Sevoflurane is capable of reducing necrosis, apoptosis, and ischemic neuronal damage by means of protecting cerebral autoregulation and increasing cerebral blood flow (Li, Cao, Wang, Fang, & Tan, ).…”

Impact of age on cardiovascular function, inflammation, and oxidative stress in experimental asphyxial cardiac arrest

“…However, despite the relatively higher isoflurane concentration in the aged animals, the MAP was higher in these animals at baseline indicating that they were not hemodynamically challenged by the anesthesia itself. Experimental CA studies have shown that volatile anesthetics possess cardioprotective properties, whereas the effect on the post‐CA brain is less unequivocal, with studies showing both neuroprotective and neurodamaging effects . Thus, the use of isoflurane could have weakened the difference in cardiac function measures between the two groups.…”

ALDH 2 conferred neuroprotection on cerebral ischemic injury by alleviating mitochondria-related apoptosis through JNK/caspase-3 signing pathway

“…The mitochondrial fraction of the harvested brain tissues and cells was obtained according to the previous method [32].…”

“…The experimental cycle threshold (CT) value was regularized to β-actin, which was quantified on the same plate. The fold differences in gene expression were calculated with the 2-ΔΔCt method [32].…”