Cerebral ischaemia is the third leading cause of death in the western world and present there remains no effective treatment for this pathological condition. Activation of cannabinoid (CB) receptors has been show to protect the rat brain against ischaemic insult. In addition cannabinoid receptor agonists have been shown to influence the production of the pro-inflammatory cytokine interleukin-1 (IL-1), inhibition of which has also been demonstrated to reduce the amount of neuronal damage following an ischaemic insult.
The aims of this project are to characterise the effects of cannabinoid agonists on neuronal cell death caused by permanent middle cerebral artery occlusion in the rat and to determine the receptors involved by using antagonists specific to either CB1 or CB2 receptors. The project will also investigate the time window of efficacy of these compounds, and determine the role of IL-1 in the cannabinoid-mediated effect by investigating the influence of the cannabinoid ligands on expression of IL-1/IL-1 receptor antagonist following an experimental ischaemic episode. The results of this project will provide a greater light into the mechanisms behind the neuroprotective effects of cannabinoids and clarify theu relationship to IL-1. Furthermore they will provide a foundation on which to build a drug discovery strategy for the identification of new pharmacological treatments of stroke.