Anales RANF

P.37 THE P2X7 RECEPTOR’S CONTRIBUTION TO NEONATAL SEIZURES AND THE DEVELOPMENT OF CHRONIC EPILEPSY AND NEURO-COGNITIVE DEFICITS. Mr. J. Smith 1,2 , Dr. E.M. Jimenez-Mateos 3 , Prof. D. Henshall 1,2 , Dr. T. Engel 1,2 1 .Royal College of Surgeons in Ireland, Dublin, Ireland, 2. FutureNeuro Research Centre, Dublin, Ireland; 3. Trinity College Dublin, Dublin, Ireland. Neonatal seizures are a neurological emergency. Hypoxic-ischemic encephalopathy accounts for 60% of neonatal seizures and is associated with development of epilepsy and neuro-cognitive deficits in later life. Current treatments for neonatal seizures remain largely ineffective. The P2X7 receptor (P2X7R) is an ionotropic ATP-gated ion channel that is activated under pathological conditions, with a key role as a driver of inflammation. Antagonism of the P2X7R reduced the seizure burden in neonatal mice when exposed to global hypoxic conditions. The aim of this project is to further understand the mechanism of this action and the possible therapeutic use of P2X7R antagonism for neonatal seizures. Seizures are induced in P7 mouse pups by exposure to global hypoxia (5% oxygen) for 15mins. This study uses multiple transgenic mouse models that either globally overexpress or knockout the P2X7R. Acute electroencephalography and behavioural seizures will be recorded to investigate the P2X7R’s immediate role in neonatal seizures. At various times following seizure induction, markers of inflammation will be analysed by immunohistochemistry and ELISA methodology. Seizure related neuronal damage will be investigated with use of Silver Nissl staining. The overexpressing mouse model has P2X7R tagged with green fluorescent protein and will be used to locate where and what cell types P2X7R is upregulated following neonatal seizures. In a cohort of mice, a battery of behavioural assays and a seizure threshold test with kainic acid will be conducted 4 weeks post seizures after pharmacological antagonism of the P2X7R and in the transgenic models to investigate the P2X7R’s role in the development of neurocognitive deficits and later life epilepsy respectively.