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The neuroprotective effect of agmatine after focal cerebral ischemia in diabetic rats

 Cui, Huisong  ;  Lee, Jae Hoon  ;  Kim, Ji Young  ;  Koo, Bon-Nyeo  ;  Lee, Jong Eun 
 Journal of Neurosurgical Anesthesiology, Vol.24(1) : 39-50, 2012 
Journal Title
 Journal of Neurosurgical Anesthesiology 
Issue Date
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 present study was to investigate the neuroprotective effect of agmatine (AGM) on cerebral ischemic damage in diabetic rats. METHODS: Normoglycemic (n=30) and streptozocine-induced diabetic rats (n=82) were subjected to 30 minutes of suture-occlusion of the middle cerebral artery (MCAO) with 24 or 72 hours of reperfusion. Thirty-nine diabetic rats were treated with AGM (100 mg/kg, intraperitoneal) immediately after 30 minutes of MCAO. To evaluate the motor function, a modified neurological examination and rota-rod exercise were performed. The brain infarct volume and edema volume were assessed. Caspase-3 activity and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining were used to evaluate cellular apoptosis. Western blot and immunohistochemical analysis were performed to determine the expression of neuronal nitric oxide synthase (NOS) and inducible NOS in ischemic brain tissues. RESULTS: AGM posttreatment improved the neurobehavioral activity of diabetic MCAO rats at 24 and 72 hours after reperfusion. The infarct size and edema volume were reduced in AGM-treated diabetic rats compared with those in diabetic rats without AGM posttreatment (P<0.01). Immunohistochemical analysis showed that AGM treatment significantly decreased the number of caspase-3-positive and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling-positive cells in diabetic MCAO rats at 24 and 72 hours after reperfusion (P<0.01). Western blotting and immunohistochemistry results indicated that AGM treatment significantly decreased neuronal NOS and inducible NOS expression in diabetic rats at 24 and 72 hours after reperfusion (all P<0.05). CONCLUSIONS: AGM posttreatment reduced cerebral infarct size and neurological deficit expression in diabetic rats subjected to MCAO. The reduced infarct size was associated with a decrease in apoptosis and NOS expression.
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1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
Yonsei Authors
구본녀(Koo, Bon-Nyeo) ORCID logo https://orcid.org/0000-0002-3189-1673
김지영(Kim, Ji Young) ORCID logo https://orcid.org/0000-0001-5822-0338
이재훈(Lee, Jae Hoon) ORCID logo https://orcid.org/0000-0001-6679-2782
이종은(Lee, Jong Eun) ORCID logo https://orcid.org/0000-0001-6203-7413
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