Effect of PUN282987 on global cerebral ischemia-reperfusion injury in aged rats

Abstract

Objective To evaluate the effect of PUN282987 on global cerebral ischemia-reperfusion (I/R) injury in aged rats. Methods One hundred and twenty pathogen-free healthy male Sprague-Dawley rats, aged 18-22 months, weighing 450-600 g, were divided into 3 groups (n=40 each) using a random number table: sham operation group (group S), global cerebral I/R group (group I/R) and α7 nicotinic acetylcholine receptor (α7nAChR) agonist PNU282987 group (group PUN). The animals were anesthetized with intraperitoneal 10% chloral hydrate 0.4 ml/100g, and global cerebral I/R was produced by 4-vessel occlusion technique in I/R and PUN groups.PUN282987 2.4 mg/kg was injected intraperitoneally before ischemia in group PUN.At 1, 5, 12 and 24 h of reperfusion, 10 rats were randomly selected in each group and then sacrificed, and the brains were removed for detection of the neuronal apoptosis and for determination of the expression of α7nAChR, choline acetyltransferase (ChAT), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the hippocampal CA1 region.Apoptosis rate was calculated. Results Compared with group S, the apoptosis rate was significantly increased, and the expression of α7nAChR, ChAT, TNF-α and IL-1β was up-regulated at each time point in I/R and PUN groups (P<0.05). Compared with group I/R, the apoptosis rate was significantly decreased, the expression of α7nAChR and ChAT was up-regulated, and the expression of TNF-α and IL-1β was down-regulated at each time point in group PUN (P<0.05). Conclusion PUN282987 can reduce global cerebral I/R injury in aged rats. Key words: Reperfusion injury; Brain; Cholinergic agonists; Aged