Korean J Anesthesiol.  2003 Sep;45(3):393-401. 10.4097/kjae.2003.45.3.393.

Effect of Inducible Nitric Oxide Synthase Inhibitor on Apoptosis in Hypoxic-Ischemic Injury of the Neonatal Rat Brain: 1H Magnetic Resonance Spectroscopy Study

• Hwang HS
• Bang JY
• Park PH

• KMID: 2239929
• DOI: http://doi.org/10.4097/kjae.2003.45.3.393

Abstract

BACKGROUND: Inducible nitric oxide synthase (iNOS) is expressed during the late stage of ischemia and may play an important role in the delayed progression of ischemic brain injury. This study was conducted to investigate the effect of N-(3-[aminomethyl] benzyl] acetamidine (1,400 W), a selective inhibitor of iNOS on hypoxic ischemic injury in a neonatal rat model.
METHODS
Seven-day old Sprague-Dawley rats were used. The right common carotid artery was ligated under halothane anesthesia. Three 3 hours after recovery, animals were exposed to 8% oxygen in 92% nitrogen. The treatment group (n = 14) received 7 intraperitoneal injection of 20 mg/kg of 1,400 W. The first dose was given 18 hours after the injury and interval between injections was 8 hours. The control group (n = 13) did not receive 1,400 W. The degree of ischemic damage and apoptosis were evaluated 3 days after injury by 1H magnetic resonance spectroscopy (MRS) and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end-labeling (TUNEL) staining. The authors obtained Lipid/N-acetyl aspartate (Lip/NAA) and lipid/ creatine (Lip/Cr) ratios as apoptotic markers via 1H MRS, and counted the apoptotic cell number by TUNEL staining in the right hemisphere. Data were analyzed using the unpaired t-test.
RESULTS
There were no significant differences in the Lip/NAA or Lip/Cr ratios of the 2 groups, and no significant differences were found in terms of the number of TUNEL positive cells between 2 groups, either.
CONCLUSIONS
The iNOS inhibitor investigated did not show protective effects against delayed neuronal damage and apoptosis after the hypoxic-ischemic injury in newborn rats, at least during the 3 days following injury. Our results suggest that NO has different roles in cerebral hypoxia-ischemia according to the stage of neonatal cerebral development.

Keyword

apoptosis; 1H-magnetic resonance spectroscopy; hypoxic-ischemic cerebral injury; N-(3-[aminomethyl] benzyl) acetamidine (1,400 W)

MeSH Terms

Anesthesia
Animals
Apoptosis*
Aspartic Acid
Brain Injuries
Brain*
Carotid Artery, Common
Cell Count
Creatine
Halothane
Humans
Hypoxia-Ischemia, Brain
In Situ Nick-End Labeling
Infant, Newborn
Injections, Intraperitoneal
Ischemia
Magnetic Resonance Spectroscopy*
Models, Animal
Neurons
Nitric Oxide Synthase Type II*
Nitrogen
Oxygen
Rats*
Rats, Sprague-Dawley
Aspartic Acid
Creatine
Halothane
Nitric Oxide Synthase Type II
Nitrogen
Oxygen