The Effects of Hydrazines of Neuronal Excitability

Abstract

Hydrazines (HZ) are toxic compounds which have numerous industrial applications including their use as missile propellants in advanced aircraft such as the F-16 and space vehicles. The extremely high toxicity of HZs and the recurrent accidental exposure due to routine storage, use, and disposal of these compounds have created a significant health hazard among aerospace and defense industry personnel. HZ exposure can result in lethal complications involving repeated seizures and eventual respiratory collapse. Acute HZ exposure produces repeated tonic-clonic seizures in animals and man due to the strong convulsant properties of these compounds. In order to develop effective therapies for HZ toxicity, It is important to determine the mechanisms by which HZs produce their neuronal excitatory effects. Initial studies in our laboratory of the electrophysiological effects of HZs have shown that HZ exposure induces spontaneous and evoked epileptiform activity in mammalian hippocampus, recorded in vitro. In cultured hippocampal neurons, we have found that HZs decrease the postburst afterhyperpolarization, a primary postsynaptic mechanism utilized by many types of neurons to terminate bursts, and maintain a check on hyperexcitability. As expected, this AHP reduction by HZs increases the rate of sustained repetitive firing in these neurons, and may be one mechanism contributing to HZ convulsant actions., The overall objective of this study is to describe and pharmacologically characterize HZ-induced epileptiform actions in hippocampus, and to examine the effects of HZs on ion conductances in mammalian hippocampal neurons, in order to provide insight into the mechanisms of HZ toxicity which may underlie the excitatory and epileptogenic properties of these compounds.

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Document Details

Document Type
Technical Report
Publication Date
Jan 10, 1992
Accession Number
ADA247142

Entities

People

  • Robert J. Delorenzo

Organizations

  • Virginia Commonwealth University School of Medicine

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Amino Acids
  • Amplitude
  • Anticonvulsants
  • Biological Sciences
  • Brain
  • Central Nervous System
  • Central Nervous System Stimulants
  • Inventions
  • Kinetics
  • Medical Personnel
  • Nervous System
  • Neurology
  • Pharmacology
  • Research Facilities
  • Seizures
  • Spinal Cord
  • Universities

Readers

  • Neuroscience
  • Systems Analysis and Design
  • Toxicology/Environmental Toxicology

Technology Areas

  • Space