Cholinergic Neurotoxicity: Mechanisms and Prevention
Abstract
Systematic treatment of adult rats with a high dose of pilocarpine (pilo) or with a low dose of lithium (li) followed by a low dose of pilo causes a cholinotoxic syndrome consisting of persistent seizures and a disseminated pattern of seizure-related brain damage. Our preliminary observations suggested that this type of brain damage resembles that seen in rats following persistent seizures induced by other convulsants such as kainic acid, which, in turn, resembles excitotoxic type of damage that the excitatory transmitter glutamate is known to cause. To further assess the similarities between the pilo or li-pilo cholinotoxic syndromes and other seizure-related brain damage syndromes, we studied the progression of electrophysiological (surface and depth recordings), metabolic (2-deoxyglucose autoradiography) and neuropathological (light and electron microscopic) changes in various regions of rat brain during the acute period in which seizure activity and brain damage occur. We measured enzyme markers for the gamma aminobutyric acid and cholinergic transmitter systems in various brain regions and studied 3H-glutamate receptor binding by autoradiography at chronic time points after rats had sustained seizure-related brain damage from li-pilo treatment. The results obtained so far are consistent with the hypothesis that the neuropathological changes seen in the cholintoxic syndrome could be mediated by an excitotoxic mechanism, i.e., by excessive activation of the glutamate transmitter system.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 30, 1986
- Accession Number
- ADA210308
Entities
People
- John W. Olney
- Madelon T. Price
Organizations
- University of Washington