Analysis of the endocannabinoid system and potential effects of anti-seizure medications in chemical and genetic models of epilepsy

Epilepsy is understood as a condition of variable origins which produces excessive neuronal firing, seizures and associated co-morbidities in the patient. Current treatments for seizures can produce undesirable side effects and have a relatively high rate of failure. Therefore, it is necessary to examine new drugs, including the recently legalized cannabis, and its impacts on epileptic behaviours. Such analyses can be accomplished using the D. rerio (zebrafish) model organism which has been previously used to examine seizure-like behaviours and associated drug treatments in the past. Phytocannabinoids, specific therapeutic compounds originating from cannabis known to reduce seizing in conditions such as Dravet Syndrome, are examined using a chemically-induced model, alongside a CRISPR mutant line targeting kcnq3, which is linked to childhood epilepsy disorders. As well, an examination of novel anti-epileptic drugs Alogabat and Darigabat was performed using behavioural tracking techniques. Investigations of specific receptor interactions in the brain�s endocannabinoid system, which is linked to neuroprotection, are performed using D. rerio specimens, alongside investigation of changes in concentration of endocannabinoid molecules before and after drug treatment and seizure induction using a novel UHPLC-MS/MS method. Finally, a brief investigation of the ability of multi-electrode array technologies to identify neurological activity before and after anti-epileptic drug application to the subject was performed. Overall, this investigation seeks to portray multiple approaches to epilepsy examinations using the D. rerio model organism, while also identifying additional treatments for this condition.