title: The neuroprotective effect of agmatine after 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 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.
authors: Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors: Huisong
authors: H
authors: Cui
authors: Jae Hoon
authors: JH
authors: Lee
authors: Ji Young
authors: JY
authors: Kim
authors: Bon-Nyeo
authors: BN
authors: Koo
authors: Jong Eun
authors: JE
authors: Lee
mesh_terms: D000376:Agmatine / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001786:Blood Glucose / Q000502:physiology; D015153:Blotting, Western; D001835:Body Weight / Q000502:physiology; D001929:Brain Edema / Q000188:drug therapy / Q000473:pathology; D002560:Cerebrovascular Circulation; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control; D002546:Ischemic Attack, Transient / Q000188:drug therapy*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D045442:Rotarod Performance Test
chemical_list: D001786:Blood Glucose; D018696:Neuroprotective Agents; D009569:Nitric Oxide; D000376:Agmatine; D019001:Nitric Oxide Synthase