The role of PI3K-mediated AMPA receptor changes in post-conditioning of propofol in brain protection

Abstract

Background We aimed to study the role of amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR) glutamate receptor 2 (GluR2) subunit trafficking, and activity changes in short-term neuroprotection provided by propofol post-conditioning. We also aimed to determine the role of phosphoinositide-3-kinase (PI3K) in the regulation of these processes. Methods Rats underwent 1 h of focal cerebral ischemia followed by 23 h of reperfusion were randomly divided into 6 groups (n = 36 per group): sham- operation (S), ischemia–reperfusion (IR), propofol (P group, propofol 20 mg/kg/h at the onset of reperfusion for 2 h after 60 min of occlusion), and LY294002 (PI3K non-selective antagonist) + sham (L + S, LY294002 of 1.5 mg/kg was infused 30 min before sham operation), LY294002+ ischemia–reperfusion (L + IR, LY294002 of 1.5 mg/kg was infused 30 min before middle cerebral artery occlusion), LY294002 + IR + propofol (L + P, LY294002 of 1.5 mg/kg was infused 30 min before middle cerebral artery occlusion and propofol 20 mg/kg/h at the onset of reperfusion for 2 h after 60 min of occlusion). Results Compared with group IR, rats in group P had significant lower neurologic defect scores and infarct volume. Additionally, consistent with enhanced expression of PI3K-AMPAR GluR2 subunit complex substances in ipsilateral hippocampus, GluR2 subunits showed increased levels in both the plasma and postsynaptic membranes of neurons, while pGluR2 expression was reduced in group P. Furthermore, LY294002, the PI3K non-selective antagonist, blocked those effects. Conclusion These observations demonstrated that propofol post-conditioning revealed acute neuroprotective role against transient MCAO in rats. The short-term neuroprotective effect was contributed by enhanced GluR2 subunits trafficking to membrane and postsynaptic membranes of neurons, as well as down-regulated the expression of pGluR2 in damaged hippocampus. Finally, the above-mentioned protective mechanism might be contributed by increased combination of PI3K to AMPAR GluR2 subunit, thus maintained the expression and activation of AMPAR GluR2 in the ipsilateral hippocampus.

Propofol Protects against Cerebral Ischemia/Reperfusion Injury by Down-Regulating Long Noncoding RNA SNHG14

“…As an anesthetic, PPF has the same neuroprotective properties as other general anesthetics. PPF post-conditioning alleviates transient MCAO in rats by exerting the acute neuroprotective effects . PPF promotes PTEN degradation, which contributes to reducing hippocampal neuronal loss and memory deficit in CI/R injury rats .…”

“…PPF post-conditioning alleviates transient MCAO in rats by exerting the acute neuroprotective effects. 22 PPF promotes PTEN degradation, which contributes to reducing hippocampal neuronal loss and memory deficit in CI/R injury rats. 23 Our study also confirmed the neuroprotective effect of PPF in CI/R injury through the SNHG14/ miR-30b-5p/Atg5/Beclin 1 axis.…”

Edaravone alleviated propofol‐induced neural injury in developing rats by BDNF/TrkB pathway

“…23 In addition, the activation of PI3K/AKT/CREB signalling pathway is positively associated with the neuroprotective function that can cause neonatal hypoxia ischaemia. 7,19,31 Furthermore, CREB is a protein that controls gene transcription and affects the regulation of downstream caspase 3 gene transcription and protein translation. Besides, its active form is a key factor in memory formation and the normal development of neurons (Figure 6G).…”

“…The mature BDNF binds to TrkB so as to activate the downstream signalling pathways responsible for regulating gene expression encoding proteins involved in neural cell survival, axon and dendrite growth, as well as synapsis plasticity 23 . In addition, the activation of PI3K/AKT/CREB signalling pathway is positively associated with the neuroprotective function that can cause neonatal hypoxia ischaemia 7,19,31 . Furthermore, CREB is a protein that controls gene transcription and affects the regulation of downstream caspase 3 gene transcription and protein translation.…”

Contralateral C7 nerve transfer in the treatment of central hemiplegia after stroke under general anesthesia: A case report

“…Anesthesia management includes the choice of anesthetic and the management of intraoperative circulation. Many anesthetics have protective effects on the brain, 8 , 9 , 10 but there are few reports about the effects of anesthetics on patients with a history of stroke. The operation requires electrophysiology to find the C7 nerve accurately.…”