Metabolism, Seizures, and Blood Flow in Brain Following Organophosphate Exposure: Mechanisms of Action and Possible Therapeutic Agents
Abstract
Organophosphate (OP) compounds comprise a major class of chemicals used as insecticides, primarily by agricultural workers and in chemical warfare. These compounds are highly toxic, and an accidental overdose can result in confusion, loss of reflexes, seizure, coma, and ultimately, death (1). The development of effective prophylactic or therapeutic intervention methods requires the thorough understanding of the mechanism(s) of action and the sequential events leading to the pathophysiological state. Because OP compounds are potent cholinesterace inhibitors most previous work has focused on their actions at the neuromuscular junctions. In recent years, evidence has been growing to suggest that OP toxicity is not exclusively the result of inhibition of acetylcholinesterase, but also of a number of pathophysiological alterations occurring in the central nervous system. In this report, we present studies using the isolated canine brain perfused at constant pressure to allow cerebral blood circulation to vary freely in response to changes in vascular resistance. These studies are the conclusion of a research project designed to examine the effects of OP exposure on brain metabolism and blood flow with the goals of understanding the underlying mechanisms of OP intoxication and suggesting means of therapy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 31, 1991
- Accession Number
- ADA238401
Entities
People
- Lester R Drewes
Organizations
- University of Minnesota Duluth