Description
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 nerveoutputs 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.
Period | 01 Feb 2010 → 31 Aug 2020 |
---|---|
Examinee | Martin Combs |
Examination held at | |
Degree of Recognition | National |
Keywords
- lolitrem B
- perennial ryegrass
- toxicosis
- bromide
- sheep
- therapeutic
Related content
-
Impacts
-
Granted patent: AU2014353885A1 Prevention and treatment of toxicoses.
Impact: Economic Impact
-
PATENT - Prevention and treatment of toxicosis. Publication date 13/03/2018
Impact: Other Impact
-
Research Outputs
-
Development of a model for investigation of perennial ryegrass toxicosis in sheep
Research output: Contribution to journal › Article › peer-review
-
A single exposure to the tremorgenic mycotoxin lolitrem B inhibits voluntary motor activity and spatial orientation but not spatial learning or memory in mice
Research output: Contribution to journal › Article › peer-review
-
Potassium bromide mitigates clinical signs of intoxication caused by the indole diterpenoid toxin lolitrem B
Research output: Other contribution to conference › Poster › peer-review
-
Pharmacokinetics of bromide in adult sheep following oral and intravenous administration
Research output: Contribution to journal › Article › peer-review
-
Tremorgenic effects and functional metabolomics analysis of lolitrem B and its biosynthetic intermediates
Research output: Contribution to journal › Article › peer-review
-
Perennial ryegrass toxicosis: effects of the indole diterpenoid mycotoxins on movement and metabolism in a mouse model
Research output: Other contribution to conference › Poster › peer-review
-
Reducing induction stress in the Australian feedlot sector
Research output: Book/Report › Commissioned report (public)
-
Effects of the indole diterpenoid mycotoxin lolitrem B and its pathway intermediates on movement and metabolic status in a mouse model of perennial ryegrass toxicosis
Research output: Other contribution to conference › Poster › peer-review
-
New insights into the clinicopathological mechanisms and presentation of perennial ryegrass toxicosis in Australia
Research output: Other contribution to conference › Abstract › peer-review
-
A functional metabolomics analysis of lolitrem B and its biosynthetic intermediates in the murine brain
Research output: Other contribution to conference › Abstract
-
Treatment of clinical signs of perennial rye grass toxicosis in sheep
Research output: Book/Report › Commissioned report (public)
-
Treatment of Perennial Ryegrass Staggers with Potassium Bromide
Research output: Other contribution to conference › Poster › peer-review
-
Press/Media
-
New treatment hope for ryegrass staggers
Press/Media: Press / Media