Korean J Anat.  2009 Sep;42(3):149-160.

Agmatine Attenuates Nitric Oxide Synthesis and Protects ER-structure from Global Cerebral Ischemia in Rats

• Mun CH
• Kim JH
• Park KA
• Lee WT
• Baik JH
• Lee JE

Abstract

In ischemic strokes, apoptosis is caused by excitotoxicity, ionic imbalance, oxidative/nitrosative stress, and apoptotic-like pathways. Nitric oxide (NO), a free radical, is elevated after ischemic insult. NO, which is generated primarily by neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS), promotes neuronal damage following ischemia. Evidence obtained in recent years has demonstrated that endoplasmic reticulum (ER)-mediated cell death plays an important role in cerebral ischemia. Agmatine is an endogenous substance synthesized from L-arginine by arginine decarboxylase (ADC) and is present in mammalian brain. We had previously reported that agmatine contributes to neuroprotection against ischemic injury. In continuation of our earlier work, we intended to investigate whether agmatine protects brain from transient global ischemia, and also tried to determine the neuroprotective mechanism of agmatine. Twenty minutes of transient global ischemia was induced by 4 vessel occlusion (4-VO). Agmatine (100 mg/kg, IP) was administered simultaneously with reperfusion. Samplings of brain were done at 6, 24, 48, and 72 h after reperfusion to determine the effect of agmatine on ischemic injured hippocampus. ER-damage was also investigated using electron microscope. Results showed that agmatine treatment prevented delayed neuronal cell death in hippocampal CA1 neurons after global cerebral ischemia. It also blocked NOS expression in the rat brain. Agmatine induced the increased expression of glucose-regulated protein 78 (Grp78). These results suggest that agmatine inhibits the production of NO by decreasing the expression of nNOS and iNOS on global forebrain ischemia and the neuroprotective effect of agmatine were concerned with the ER stress-mediated condition.

Keyword

Agmatine; Global ischemia; Nitric oxide synthase; Neuronal cell death; ER stress

MeSH Terms

Agmatine
Animals
Apoptosis
Arginine
Brain
Brain Ischemia
Carboxy-Lyases
Cell Death
Electrons
Endoplasmic Reticulum
Glycosaminoglycans
Hippocampus
Ischemia
Neurons
Neuroprotective Agents
Nitric Oxide
Nitric Oxide Synthase
Nitric Oxide Synthase Type I
Nitric Oxide Synthase Type II
Prosencephalon
Rats
Reperfusion
Stroke
Agmatine
Arginine
Carboxy-Lyases
Glycosaminoglycans
Neuroprotective Agents
Nitric Oxide
Nitric Oxide Synthase
Nitric Oxide Synthase Type I
Nitric Oxide Synthase Type II