The Anti-inflammatory Effects of Agmatine on Transient Focal Cerebral Ischemia in Diabetic Rats

Abstract

BACKGROUND: In the previous study, we observed agmatine (AGM) posttreatment immediately after 30 minutes of suture occlusion of the middle cerebral artery (MCAO) reduced the infarct size and neurological deficit in diabetic rats. The aim of the present study was to investigate the anti-inflammatory effect of AGM to reduce cerebral ischemic damage in diabetic rats.

MATERIALS AND METHODS: Normoglycemic (n=20) and streptozotocin-induced diabetic rats (n=40) were subjected to 30 minutes of MCAO followed by reperfusion. Twenty diabetic rats were treated with AGM (100 mg/kg, intraperitoneal) immediately after 30 minutes of MCAO. Modified neurological examinations and rotarod exercises were performed to evaluate motor function. Western blot and immunohistochemical analysis were performed to determine the expression of inflammatory cytokines in ischemic brain tissue. Real-time polymerase chain reaction was performed to measure the mRNA expression of high-mobility group box 1, receptor for advanced glycation end products (RAGE), Toll-like receptor (TLR)2, and TLR4 RESULTS AND CONCLUSIONS:: AGM posttreatment improved the neurobehavioral activity and motor function of diabetic MCAO rats at 24 and 72 hours after reperfusion. Immunohistochemical analysis showed that AGM treatment significantly decreased the expression of inflammatory cytokines in diabetic MCAO rats at 24 and 72 hours after reperfusion (P<0.01). Western blotting and real-time polymerase chain reaction results indicated that AGM treatment significantly decreased the expression of high-mobility group box 1, RAGE, TLR2, and TLR4 in diabetic rats at 24 hours after reperfusion (P<0.05). This neuroprotective effect of AGM after MCAO was associated with modulation of the postischemic neuronal inflammation cascade.