Cysteamine eliminates nitric oxide synthase activity but is not protective to the hypoxic-ischemic neonatal rat brain.
Blockade of nitric oxide synthase (NOS) activity in the developing nervous system may protect the brain from hypoxic-ischemic insult. We determined the efficacy in 7 day old rat pups of systemically administered cysteamine in reducing neuronal NOS and nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase reactivities and protection of the brain from an hypoxic-ischemic insult. Cysteamine reversibly reduced NOS immunoreactivity at 2 h after an intraperitoneal injection of 200 mg/kg. NADPH-diaphorase histochemical reactivity was reduced after 300 mg/kg but all animals had generalized seizures and succumbed to the hypoxia-ischemia. At lower doses, despite the blockade of NOS immunoreactivity, there was no difference in the number of injured animals compared to controls. These results demonstrate that NOS immunoreactivity does not represent all of NADPH-diaphorase reactivity and that blockade of this activity with cysteamine is not protective.
Spanggord
H
H
Department of Neurology, University of California San Francisco 94143-0114, USA.
Sheldon
R A
RA
Ferriero
D M
DM
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000098:blood supply* / Q000187:drug effects / Q000201:enzymology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000201:enzymology; D003543:Cysteamine / Q000494:pharmacology*; D000860:Hypoxia / Q000188:drug therapy / Q000201:enzymology; D009252:NADPH Dehydrogenase / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018696:Neuroprotective Agents; D011837:Radiation-Protective Agents; D003543:Cysteamine; D019001:Nitric Oxide Synthase; D009252:NADPH Dehydrogenase