Effect of propofol post-conditioning on expression of GluR1-containing AMPA receptors during cerebral ischemia-reperfusion injury in rats

Abstract

Objective To evaluate the effect of propofol post-conditioning on the expression of GluR1-containing AMPA receptors during cerebral ischemia-reperfusion (I/R) injury in rats. Methods Sixty-four healthy male Sprague-Dawley rats, aged 7-8 weeks, weighing 250-280 g, were randomly divided into 3 groups (n = 18 each) using a random number table: sham operation group (group S), I/R group and propofol group (group P). Focal cerebral ischemia was induced by occlusion of the middle cerebral artery for 1 h followed by reperfusion in I/R and P groups. Propofol was infused at 20 mg·kg-1·h-1 for 2 h starting from the onset of reperfusion in group P, and the equal volume of normal saline was given in S and I/R groups. Fear conditioning test was performed on 7, 14 and 28 days after operation. The time spent freezing induced by context and condition was recorded, and the percentage was calculated. The modified neurological deficit score (NDS) was measured at 24 h of infusion. The cerebral infarct size was measured by TTC. The hippocampal samples were isolated for determination of the expression of protein kinase A (PKA), A-kinase anchoring protein 150(AKAP150) and AMPA receptor GluR1 subunit and phosphorylation of GluR1 at serine 845(Ser845) site (pGluR1 Ser845). Results Compared with group S, the NDS and cerebral infarct size were significantly increased, the expression of PKA and pGluR1 Ser845 was down-regulated, and the percentage of time spent freezing induced by context and condition was decreased on 7 and 14 days after operation in I/R and P groups. Compared with group I/R, the NDS and cerebral infarct size were significantly decreased, the expression of PKA and pGluR1 Ser845 was up-regulated, and the percentage of time spent freezing induced by context and condition was increased on 7 and 14 days after operation in group P. Conclusion The mechanism by which propofol postconditioning reduces cerebral I/R injury is related to phosphorylation of AMPA receptor GluR1 subunit in rats. Key words: Propofol; Brain; Reperfusion injury; Receptors, AMPA