Aspirin upregulates the expression of neuregulin 1 and survivin after focal cerebral ischemia/reperfusion in rats

Abstract

Neuregulin 1 (NGR1) and survivin have been shown to be neuroprotective. However, the link between their expression and aspirin in the treatment of cerebral ischemia remains unclear. Here, we investigated the effect of aspirin on NGR1 and survivin expression after focal cerebral ischemia/reperfusion in rats. Sprague Dawley rats were randomly divided into an aspirin treatment group (n=40) and a control group (n=40). Each group was further divided into five subgroups according to the time after reperfusion. A middle cerebral artery model was established by an occlusion suture. At 24 h, 3, 5 and 7 days after reperfusion, the Bederson neurological deficit scores were 1.47±0.11, 1.22±0.08, 0.85±0.15 and 0.59±0.12 in the treatment group, and 1.87±0.18, 1.45±0.14, 1.05±0.08 and 0.75±0.15 in the control group, respectively, indicating a significant difference at each time point (P<0.05). In the infarct center, the number of NGR1- and survivin-positive cells reached the maximum at 6 h and decreased gradually to a minimum at 7 days, while in the peri-infarct area, the number was few at 6 h, peaked at 3 days and then was reduced gradually with significant differences between the two time points (P<0.05). There were more NGR1- and survivin-positive cells in the treatment group compared to the control group (P<0.05). In conclusion, the neuroprotective effect of aspirin is at least partly mediated by the upregulation of NGR1 and survivin expression after ischemia.

Figure 1.

Intracerebral NGR1 expression at different sites after CI/RP in rats. Brown staining represents positive NGR1 expression. (A) Infarct center in the treatment group (6 h). (B) Infarct center in the control group (6 h). (C) Infarct center in the treatment group (24 h). (D) Infarct center in the control group (24 h). (E) Infarct center in the treatment group (3 days). (F) Infarct center in the control group (3 days). (G) Peri-infarct area (cortical pyramidal layer) in the treatment group (3 days). (H) Peri-infarct area (cortical pyramidal layer) in the control group (3 days). (I) Peri-infarct area (cortical pyramidal layer) in the treatment group (5 days). (J) Peri-infarct area (cortical pyramidal layer) in the control group (5 days). Magnification, x400.

Figure 2.

Survivin expression in different infarct areas in CI/RP rats. Brown staining represents positive survivin expression. (A) Infarct center in the treatment group (6 h). (B) Infarct center in the control group (6 h). (C) Infarct center in the treatment group (3 days). (D) Infarct center in the control group (3 days). Survivin expression was also detected in small vascular endothelial cells (indicated by arrow). (E) Peri-infarct area (cortical pyramidal layer) in the treatment group (3 days). (F) Peri-infarct area (cortical pyramidal layer) in the control group (3 days). (G) Peri-infarct area (cortical pyramidal layer) in the treatment group (5 days). (H) Peri-infarct area (cortical pyramidal layer) in the control group (5 days). Magnification, x400.