Effects of nitric oxide synthase inhibition on the cerebral circulation and brain damage during kainic acid-induced seizures in newborn rabbits.
The nitric oxide (NO) synthase inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME), was used to investigate the effect of endogenous NO on the cerebral circulation and brain damage during kainic acid (KA)-induced seizures in newborn rabbits. The cerebral blood flow (CBF), by laser doppler flowmetry, cerebral oxygenation (concentrations of oxy-(HbO2), deoxy-(HbR) and total hemoglobin (tHb) in brain tissue), by near-infrared spectroscopy (NIRS), mean arterial blood pressure (MABP), electroencephalography (EEG), and hippocampal neuronal damage were evaluated. Pretreatment with L-NAME caused significant decreases in CBF, HbO2, and tHb, and a significant increase in HbR during KA-induced seizures, compared with pretreatment with saline (P < 0.05), without a significant difference in MABP. Our study also demonstrated that pretreatment with L-NAME reduced the seizure activity and neuronal cell death in the hippocampus elicited by the systemic administration of KA in the neonatal brain. These results suggest that NO is of major importance in the neurodestructive process in spite of its roles in maintaining both the CBF and cerebral oxygenation during KA-induced seizures in the neonatal brain.
Department of Pediatrics, Tokyo Medical University, Japan. yukito-t@tokyo-med.ac.jp
Y
Y
Takei
S
S
Takashima
J
J
Ohyu
T
T
Takami
T
T
Miyajima
A
A
Hoshika
D000818:Animals; D000831:Animals, Newborn; D001784:Blood Gas Analysis; D002540:Cerebral Cortex / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004569:Electroencephalography / Q000187:drug effects; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D007608:Kainic Acid; D017078:Laser-Doppler Flowmetry; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009474:Neurons / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010100:Oxygen / Q000378:metabolism; D011817:Rabbits; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology*; D019265:Spectroscopy, Near-Infrared
D006454:Hemoglobins; D019001:Nitric Oxide Synthase; D010100:Oxygen; D007608:Kainic Acid; D019331:NG-Nitroarginine Methyl Ester