The anti-inflammatory effects of agmatine on transient focal cerebral ischemia in diabetic rats

Abstract

Background: Diabetes mellitus is a metabolic disorder associated with structural and functional alterations of various organ systems, including the central nervous system. The aim of the present study was to investigate the neuroprotective effect of agmatine (AGM) on cerebral ischemic damage in diabetic rats.Method: Normoglycemic (n = 30) and streptozotocin-induced diabetic rats (n = 82) were subjected to 30 minutes of suture occlusion of the middle cerebral artery (MCAO) followed by reperfusion. Thirty-nine diabetic rats were treated with AGM (100 mg∙kg-1, intraperitoneal) immediately after 30 minutes of MCAO. Modified neurological examination and rotarod exercise were performed to evaluate motor function. Brain infarct volume was assessed by triphenyl tetraxolium chloride staining and microPET imaging. Western blot and immunohistochemical analysis were performed to determine the expression of inflammatory cytokines in ischemic brain tissue. Real-time PCR (RT-PCR) was performed to measure the mRNA expression of high-mobility group box 1 (HMGB1), Receptor for Advanced Glycation Endproducts (RAGE), Toll-like Receptor (TLR)2, and TLR4.Result: AGM post-treatment improved the neurobehavioral activity and motor function of diabetic MCAO rats at 24 and 72 hours after reperfusion. The infarct size was reduced in AGM-treated diabetic rats compared with diabetic rats without AGM post-treatment (p < 0.01). 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 RT-PCR results indicated that AGM treatment significantly decreased the expression of HMGB1, RAGE, TLR2, and TLR4 in diabetic rats at 24 and 72 hours after reperfusion (p < 0.05).Conclusion: Immediate AGM treatment after 30 minutes of MCAO reduced the infarct size and neurological deficit in diabetic rats at 24 and 72 hours after reperfusion. This effect of AGM was associated with modulation of the post-ischemic neuronal inflammation cascade.