Clinical and pathological characterisation of perennial ryegrass toxicosis and investigation of bromide as a therapeutic intervention

Research output: ThesisDoctoral Thesis

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Abstract

This thesis evaluates the therapeutic efficacy of potassium bromide within murine and ovine models of Perennial Ryegrass Toxicosis (PRGT). PRGT is a clinical syndrome of herbivores in southern regions of Australia and New Zealand grazing pasture with a high proportion of perennial ryegrass. Peak times of disease are typically late spring and late summer/ early autumn. To date no clinically applicable therapy has been available to treat clinical cases of PRGT or to prevent the disease.
PRGT, is a complex toxicity with multiple alkaloids involved and disease ranging from subclinical productivity losses to a severe neurological syndrome with ataxia, tremor, recumbency and occasionally death. Lolitrem B, the primary toxin responsible for neurological signs with PRGT, is thought to block calcium activated potassium channels (BK Channels). In the brain this will have a number of effects; generally it will make neurons unstable or hyperactive. In the cerebellum however the effect is to reduce nerve outputs to other parts of the brain. As the cerebellum is involved in regulating movement the effect of intoxication is for movement to become less regulated and more exaggerated (cerebellar ataxia).
This thesis considered the use of bromide, an accepted therapy for epilepsy in animals and humans, as a treatment for PRGT. Although the mechanism of action has not been fully explained, it is generally accepted that bromide enters brain cells through chloride channels and thereby exerts an inhibitory effect on nerve firing. Bromide could be considered likely to have a non-specific action against the neuronal instability created by BK channel blockade.
Trials in this thesis demonstrate that bromide is effective at reducing tremor and ataxia. Because of its limited side effects, high oral bioavailability, high safety margin and low cost, bromide is a good potential on-farm therapy for PRGT.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • Charles Sturt University
Supervisors/Advisors
  • Quinn, Jane, Principal Supervisor
  • Raidal, Shane, Co-Supervisor
  • Edwards, Scott, Co-Supervisor
  • Hamlin, Adam, Co-Supervisor
Place of PublicationAustralia
Publisher
Publication statusPublished - 01 Sep 2020

Grant Number

  • B.AHE.0233
  • B.STU.0242

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