Abstract
BackgroundWe 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.MethodsRats 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).ResultsCompared 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.ConclusionThese 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.
Highlights
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 showed that propofol (20 mg/kg/h) for 2 h postconditioning differentially regulated the co-expression of PI3K and GluR2 subunits, since a marked increase in the PI3K–GluR2 complex was observed in the ischemic hippocampus, which contributed to the trafficking of
As we showed in our current study, propofol post-conditioning might stabilize the GluR2 subunits expression on postsynaptic membrane rather than other membrane structure, which would depress the Ca2+-permeability of AMPARs with GluR2 subunits
Summary
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. For patients presenting with a high risk of cerebrovascular diseases, choosing an appropriately safe and effective anesthetic is a highly important challenge for anesthesiologists. Prophase work found propofol has protective effect on rat brain from ischemia–reperfusion injury by reducing the volume of cerebral infarction, and alleviating both nerve injury and neuronal apoptosis [3]. The phosphoinositide-3-kinase (PI3K)/protein kinase B (Akt) pathway plays an important role in the process of cerebral ischemia and brain protection. In the transient global cerebral ischemia model of the rat [4], the activation of the PI3K/Akt pathway may delay neuronal death in the hippocampal CA1 region [5]. Propofol post-conditioning enhanced expression of pAkt in 24 h after transient MCAO (middle cerebral artery occlusion) [3]
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