HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Nitric oxide synthase activity and inhibition after neonatal hypoxia ischemia in the mouse brain.

Abstract
Despite the emergence of therapies for hypoxic-ischemic injury to the mature nervous system, there have been no proven efficacious therapies for the developing nervous system. Recent studies have shown that pharmacological blockade of neuronal nitric oxide synthase (nNOS) activity can ameliorate damage after ischemia in the mature rodent. We have previously shown that elimination of nNOS neurons, either by targeted disruption of the gene or by pharmacological depletion with intraparenchymal quisqualate, can decrease injury after hypoxia-ischemia. Using a simpler pharmacological approach, we studied the efficacy of a systemically administered NOS inhibitor, 7-nitroindazole, a relatively selective inhibitor of nNOS activity. Using multiple doses and concentrations administered after the insult, we found that there was only a trend for protection with higher doses of the drug. A significant decrease in NOS activity was seen at 18 h and 5 days in the cortex, and at 2 h and 18 h in the hippocampus after the hypoxia-ischemia. nNOS expression decreased and remained depressed for at least 18 h after the insult. When nNOS expression was normalized to MAP2 expression, a decrease was seen at 18 h in the cortex and at 2 and 18 h in the hippocampus. These data suggest that further inhibition of NOS activity at early timepoints may not provide substantial benefit. At 5 days after the insult, however, NOS activity and normalized nNOS expression returned to baseline or higher in the hippocampus, the region showing the most damage. These data suggest that delayed administration of nNOS inhibitor after hypoxic-ischemic injury might be beneficial.
AuthorsK Muramatsu, R A Sheldon, S M Black, M Täuber, D M Ferriero
JournalBrain research. Developmental brain research (Brain Res Dev Brain Res) Vol. 123 Issue 2 Pg. 119-27 (Oct 28 2000) ISSN: 0165-3806 [Print] Netherlands
PMID11042340 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Enzyme Inhibitors
  • Indazoles
  • Microtubule-Associated Proteins
  • Neuroprotective Agents
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type I
  • Nos1 protein, mouse
  • 7-nitroindazole
Topics
  • Animals
  • Animals, Newborn (physiology)
  • Blotting, Western
  • Brain (enzymology, growth & development, pathology)
  • Brain Ischemia (enzymology, pathology)
  • Enzyme Inhibitors (pharmacology)
  • Female
  • Hypoxia, Brain (enzymology, pathology)
  • Indazoles (pharmacology)
  • Male
  • Mice
  • Microtubule-Associated Proteins (biosynthesis, metabolism)
  • Neuroprotective Agents (pharmacology)
  • Nitric Oxide Synthase (antagonists & inhibitors, metabolism)
  • Nitric Oxide Synthase Type I

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: