Anales RANF

P.38 CONTROL OF THE BLOOD-BRAIN BARRIER INTEGRITY DURING SEIZURES VIA THE ATP-GATED P2X7 RECEPTOR L. de Diego García 1 , J Smith 1,2 and T Engel 1 1 . Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland; 2 . FutureNeuro Center, Dublin, Ireland. Epilepsy is a chronic neurological disease affecting more than 60 million people worldwide. Despite more than 25 anti-epileptic drugs available, 30% of patients are pharmacoresistant. The blood-brain barrier (BBB) is a specialized regulator that separates the bloodstream from the brain parenchyma. A functional BBB is crucial in maintaining brain homeostasis and preventing the entry of aberrant compounds and immune cells into the Central Nervous System (CNS). However, during epilepsy the permeability of the BBB may increase, resulting in blood-borne molecules and cells entering the CNS. Leakage of the BBB is one of the earliest characteristic disturbances following status epilepticus (SE) and may play an important role in the development of epilepsy. The purinergic P2X7 receptor (P2X7R) has been associated with numerous damaging mechanisms related to epileptogenesis, such as inflammation and inducing leakage of the BBB. However, we do not know whether seizure induced changes of the BBB are dependent on P2X7R signalling and whether this process can be targeted. P2X7R’s impact on the BBBs integrity during seizures was studied using the intra- amygdala kainic acid model in a newly developed P2X7R overexpressing mouse model. Brains were removed at different time-points post-SE and were analysed by immunohistological techniques. Then, we evaluated changes in Podocalyxin (PODXL) that plays crucial roles in the proper functioning of the BBB as well as in disease progression. We identified an overall increase in the expression of P2X7R at 4 and 8hours post-SE. Moreover, in these overexpressed P2X7R cells there was an enrichment in PODXL expression. Finally, our study demonstrates that following SE there is an increase of P2X7R in blood vessels suggesting P2X7R impacting on BBB permeability. This result indicates that P2X7R signalling may underlie pathological changes in BBB permeability and has an impact in the epileptogenesis process. Consequently, drugs targeting BBB function and P2X7R may represent novel treatment strategies in epilepsy.