Nitric Oxide and CNS O2 Toxicity Biochemical Modeling and Risk Prediction
Abstract
The objective of this project was to elucidate the biological mechanisms and specific pathways that implicate the gaseous signaling molecule nitric oxide (NO) as a critical factor in producing the convulsions of central nervous system (CNS) oxygen (O2) toxicity, and to obtain data that could be the basis for mathematical risk predictions of O2 convulsions. For the past 3 years, data obtained in this project have supported the hypothesis that NO contributes to CNS O2 toxicity through several mechanisms: (1) by increasing the availability of NO in the brain, which in turn eliminates cerebral vasoconstriction, leading to hyperemia and the delivery of a toxic dose of oxygen; (2) by stimulating NO production and O2 generation, both of which are implicated in the formation of ONOO, a potent neurotoxic agent; and (3) by altering the excitatory/inhibitory balance in vulnerable brain regions during the early stage of extreme hyperoxia, prior to the appearance of O2 seizures. In rats protected with the inhibitor of NO production (L-NAME), no significant changes were observed in the excitotoxic index. A bibliography of 9 papers and 5 abstracts is included.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2004
- Accession Number
- ADA425587
Entities
People
- B. W. Allen
- Claude A. Piantadosi
- I. T. Demchenko