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P.35 THE CONTRIBUTION OF THE P2X7R TO DRUG REFRACTORY STATUS EPILEPTICUS J. Morgan 1 , E. Beamer 1 , M. Alves 1 , A. Nicke 2 , T.Engel 1 1 Royal College of Surgeons in Ireland, Dublin, Ireland; 2 Ludwig-Maximilians- Universität München, Munich, Germany. 1. Introduction 60 million people worldwide suffer from epilepsy and there are currently approximately 25 marketed anti-epileptic drugs (AED). With almost 30% of epilepsy patients becoming refractory to these drugs, it is paramount to focus on targeting specific therapeutic areas of the brain to fully impact on disease progression. P2X7R has been shown to play a pivotal role in inflammation but the question still remains as to its specific behavior and how it can affect sensitivity to anti-convulsant treatment. It has been shown previously that P2X7R antagonism reduces seizure duration, seizure- induced neuronal death and was also neuroprotective. Here, we are attempting to understand its influence on anti-convulsant drugs and whether P2X7R antagonism is a potential therapeutic strategy to treat drug-refratory epilepsy. 2. Methods We are using a novel, transgenic P2X7R overexpressing mouse to determine the effects of the receptor on the efficacy of anti-convulsants and its cell-specific expression. Green fluorescent protein (GFP) is bound on the promoter region of the P2X7 protein so that it is observable using fluorescent microscopy where the receptor is expressed. Investigation of the effects of P2X7 overexpression is carried out using a combination of EEG analysis, immunohistochemistry, western blotting as well as qPCR to determine the differences/patterns of seizure activity, protein and mRNA expression, cell death and response in epileptic mice. 3. Statistical Analysis GraphPad Prism is used to carry out statistical analysis, where group comparisons of will be analysed using unpaired t-tests and ANOVA analysis as appropriate. 4. Results and Conclusion Firstly, we showed P2X7 activation occurs during inflammation, and observed increased P2X7 at 72hrs. We then carried out intra-amygdala kainic acid (KA) injections to induce epilepsy. Following KA administration, we found no effect of P2X7 overexpression on the severity of electrographic seizures. Despite no difference in seizure severity, however, overexpression of P2X7 led to a marked resistance to lorazepam, midazolam and carbamazepine with ongoing increased power in the EEG, compared to controls. We concluded that P2X7 may contribute to drug resistance during SE and epilepsy, thus, P2X7 antagonists may be a good as an adjunctive treatment for epilepsy.