Transient P2X7 Receptor Antagonism Produces Lasting Reductions in Spontaneous Seizures and Gliosis in Experimental Temporal Lobe Epilepsy.
Alba Jimenez-PachecoMiguel Diaz-HernandezMarina Arribas-BlázquezAmaya Sanz-RodriguezLuis A Olivos-OréAntonio R ArtalejoMariana AlvesMichael LetavicM Teresa Miras-PortugalRonan M ConroyNorman DelantyMichael A FarrellDonncha F O'BrienAnindya BhattacharyaTobias EngelDavid C HenshallPublished in: The Journal of neuroscience : the official journal of the Society for Neuroscience (2017)
Temporal lobe epilepsy is the most common and drug-resistant form of epilepsy in adults. Neuroinflammation is implicated as a pathomechanism, but the upstream mechanisms driving gliosis and how important this is for seizures remain unclear. In our study, we show that the ATP-gated P2X7 receptor is upregulated in experimental epilepsy and resected hippocampus from epilepsy patients. Targeting the receptor with a new centrally available antagonist, JNJ-47965567, suppressed epileptic seizures well beyond the time of treatment and reduced underlying gliosis in the hippocampus. The findings suggest a potential disease-modifying treatment for epilepsy based on targeting the P2X7 receptor.
Keyphrases
- blood brain barrier
- temporal lobe epilepsy
- cerebral ischemia
- drug resistant
- end stage renal disease
- multidrug resistant
- prognostic factors
- chronic kidney disease
- traumatic brain injury
- peritoneal dialysis
- pseudomonas aeruginosa
- combination therapy
- lipopolysaccharide induced
- drug delivery
- subarachnoid hemorrhage
- smoking cessation