Type

Journal Article

Authors

Miguel Diaz-Hernandez
David C Henshall
M Teresa Miras-Portugal
Paula Garcia-Huerta
Amaya Sanz-Rodriguez
Guillaume Mesuret
Katsuhiro Tanaka
Rosa Gomez-Villafuertes
Tobias Engel

Subjects

Pharmacology

Topics
therapeutic use glutamic acid microglia metabolism adenosine triphosphate anticonvulsants hippocampus cytology seizures drug effects mice knockout prevention control drug therapy physiopathology purinergic p2x receptor antagonists purinergic p2x receptor agonists genetics interleukin 1beta neurons pathology status epilepticus male pharmacology mice inbred c57bl neuroprotective agents kainic acid lorazepam excitatory amino acid agonists receptors purinergic p2x7 animals cells cultured chemically induced mice

Seizure suppression and neuroprotection by targeting the purinergic P2X7 receptor during status epilepticus in mice. (2011)

Abstract Prolonged seizures [status epilepticus (SE)] constitute a neurological emergency that can permanently damage the brain. SE results from a failure of the normal mechanisms to terminate seizures; in particular, γ-amino butyric acid-mediated inhibition, and benzodiazepine anticonvulsants are often incompletely effective. ATP acts as a fast neurotransmitter via ionotropic ligand-gated P2X receptors. Here we report that SE induced by intra-amygdala kainic acid in mice selectively increased hippocampal levels of P2X7 receptors relative to other P2X receptors. Using transgenic P2X7 reporter mice expressing enhanced green fluorescent protein, we identify dentate granule neurons as the major cell population transcribing the P2X7 receptor after SE. Pretreatment of mice with an intracerebroventricular microinjection of 1.75 nmol A438079, a P2X7 receptor antagonist, reduced seizure duration by 58% and reduced seizure-induced neuronal death by 61%. Injection of brilliant blue G (1 pmol), another selective antagonist, reduced seizure duration by 48% and was also neuroprotective. A438079 was seizure-suppressive when injected shortly after induction of SE, and coinjection of A438079 with lorazepam 60 min after triggering SE, when electrographic seizure-responsiveness to lorazepam had decreased, also terminated SE. Our results suggest that P2X7 receptor antagonists may be a promising class of drug for seizure abrogation and neuroprotection in SE.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Miguel Diaz-Hernandez, David C Henshall, M Teresa Miras-Portugal, Paula Garcia-Huerta, Amaya Sanz-Rodriguez, Guillaume Mesuret, Katsuhiro Tanaka, Rosa Gomez-Villafuertes, Tobias Engel

Experts in our system

1
Miguel Diaz-Hernandez
Royal College of Surgeons in Ireland
Total Publications: 13
 
2
David C Henshall
Royal College of Surgeons in Ireland
Total Publications: 127
 
3
M Teresa Miras-Portugal
Royal College of Surgeons in Ireland
Total Publications: 12
 
4
Amaya Sanz-Rodriguez
Royal College of Surgeons in Ireland
Total Publications: 18
 
5
Tobias Engel
Royal College of Surgeons in Ireland
Total Publications: 66