Protective effect of aminoguanidine on hypoxic-ischemic brain damage and temporal profile of brain nitric oxide in neonatal rat

Pediatr Res. 2000 Jan;47(1):79-83. doi: 10.1203/00006450-200001000-00015.


Nitric oxide (NO) produced by inducible NO synthase contributes to ischemic brain damage. However, the role of inducible NO synthase-derived NO on neonatal hypoxic-ischemic encephalopathy has not been clarified. We demonstrate here that aminoguanidine, a relatively selective inhibitor of inducible NO synthase, ameliorated neonatal hypoxic-ischemic brain damage and that temporal profiles of NO correlated with the neuroprotective effect of aminoguanidine. Seven-day-old Wister rat pups were subjected to left carotid artery occlusion followed by 2.5 h of hypoxic exposure (8% oxygen). Infarct volumes (cortical and striatal) were assessed 72 h after the onset of hypoxia-ischemia by planimetric analysis of coronal brain slices stained with hematoxylin-eosin. Aminoguanidine (300 mg/kg i.p.), administered once before the onset of hypoxia-ischemia and then three times daily, significantly ameliorated infarct volume (89% reduction in the cerebral cortex and 90% in the striatum; p<0.001). NO metabolites were measured by means of chemiluminescence using an NO analyzer. In controls, there was a significant biphasic increase in NO metabolites in the ligated side at 1 h (during hypoxia) and at 72 h after the onset of hypoxia (p<0.05). Aminoguanidine did not suppress the first peak but significantly reduced the second one (p<0.05), and markedly reduced infarct size in a neonatal ischemic rat model. Suppression of NO production after reperfusion is a likely mechanism of this neuroprotection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Brain / drug effects*
  • Brain / metabolism
  • Brain Ischemia / etiology
  • Brain Ischemia / pathology
  • Brain Ischemia / prevention & control*
  • Guanidines / pharmacology
  • Guanidines / therapeutic use*
  • Hypoxia / complications*
  • Nitric Oxide / metabolism*
  • Rats


  • Guanidines
  • Nitric Oxide
  • pimagedine