Agmatine reduces infarct area in a mouse model of transient focal cerebral ischemia and protects cultured neurons from ischemia-like injury

J. H. Kim, M. A. Yenari, R. G. Giffard, S. W. Cho, K. A. Park, J. E. Lee

Research output: Contribution to journalArticlepeer-review

110 Citations (Scopus)

Abstract

Agmatine is a primary amine formed by the decarboxylation of L-arginine synthesized in mammalian brain. In this study, we investigated the neuroprotective effect of agmatine on ischemic and ischemia-like insults. Primary cortical neuronal cultures were subjected to oxygen-glucose deprivation (OGD), a model of ischemia-like injury, and treated with agmatine before or at the start of OGD, or upon reperfusion. Neuronal death was reduced when agmatine was present during OGD, and this protection was associated with a reduction of nitric oxide (NO) and neuronal nitric oxide synthase (nNOS), but not inducible NOS (iNOS). Protection by agmatine was also studied at the in vivo level using a model of middle cerebral artery occlusion (MCAO) in mice. Mice were subjected to 2 h MCAO. Agmatine was administered either 30 min before ischemia, at the start of MCAO, at the start of reperfusion, or 2 or 5 h into reperfusion. Agmatine markedly reduced infarct area in all treatment groups except when treatment was delayed 5 h. The number of nNOS immunopositive cells was correlated with neuroprotection. Interestingly, immunoreactivity for iNOS was reduced only when agmatine was administered before and at the onset of MCAO. Our study suggests that agmatine may be a novel therapeutic strategy to reduce cerebral ischemic injury, and may act by inhibiting the detrimental effects of nNOS.

Original languageEnglish
Pages (from-to)122-130
Number of pages9
JournalExperimental Neurology
Volume189
Issue number1
DOIs
Publication statusPublished - 2004 Sep

Bibliographical note

Funding Information:
This study was supported by a grant of the Korea Health 21 R and D Project, Ministry of Health and Welfare, Republic of Korea. (02-PJ1-PG10-21304-0007, JEL) and NIH NINDS grant NS 40516(MAY). The authors wish to thank Dr. Guo Hua Sun for expert technical assistance and Beth Hoyte and Dave Schaal for assistance preparing the manuscript.

All Science Journal Classification (ASJC) codes

  • Neurology
  • Developmental Neuroscience

Fingerprint

Dive into the research topics of 'Agmatine reduces infarct area in a mouse model of transient focal cerebral ischemia and protects cultured neurons from ischemia-like injury'. Together they form a unique fingerprint.

Cite this