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

Huisong Cui, Jae Hoon Lee, Ji Young Kim, Bon Nyeo Koo, Jong Eun Lee

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16 Citations (Scopus)

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 sutureocclusion 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 transferasemediated 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 witha decrease in apoptosis and NOS expression.

Original languageEnglish
Pages (from-to)39-50
Number of pages12
JournalJournal of Neurosurgical Anesthesiology
Volume24
Issue number1
DOIs
Publication statusPublished - 2012 Jan

All Science Journal Classification (ASJC) codes

  • Surgery
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

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