Type

Journal Article

Authors

David C Henshall
Miguel Diaz-Hernandez
M Teresa Miras-Portugal
Alba Jimenez-Pacheco
Amaya Sanz-Rodriguez
Ellen V Hessel
Tobias Engel
Guillaume Mesuret

Subjects

Pharmacology

Topics
3 5 2 3 dichlorophenyl 1h tetrazol 1 yl methylpyridine bumetanide purinergic p2x receptor antagonists excitatory amino acid agonists rats sprague dawley chemically induced metabolism injuries toxicity female hippocampus therapeutic use drug effects kainic acid dose response relationship drug luotonin b drug therapy tetrazoles disease progression diagnostic use sodium potassium chloride symporter inhibitors male cell death pathology status epilepticus pyridines amygdala physiology pharmacology quinazolines animals animals newborn rats disease models animal

P2X7 receptor inhibition interrupts the progression of seizures in immature rats and reduces hippocampal damage. (2014)

Abstract Early-life seizures, particularly when prolonged, may be harmful to the brain. Current pharmacotherapy is often ineffective; therefore, novel neuro- and/or glio-transmitter systems should be explored for targeting. The P2X7 receptor is a cation-permeable channel with trophic and excitability effects on neurons and glia which is activated by high amounts of ATP that may be released in the setting of injury after severe seizures. Here, we tested the effects of A-438079, a potent and selective P2X7 receptor antagonist in a lesional model of early-life status epilepticus. Seizures were induced by intra-amygdala kainic acid in 10-day-old rat pups. Electrographic seizure severity, changes to P2X7 receptor expression, inflammatory responses and histological effects were evaluated. Seizures induced by intra-amygdala kainic acid increased levels of P2X7 receptor protein and interleukin-1β and caused significant cell death within the ipsilateral hippocampus. A-438079 rapidly reached the brain following systemic injection in P10 rats. Intraperitoneal injection of A-438079 (5 and 15 mg/kg) 60 min after triggering seizures reduced seizure severity and neuronal death within the hippocampus. A-438079 had superior neuroprotective effects compared with an equally seizure-suppressive dose of phenobarbital (25 mg/kg). These results suggest P2X7 receptor antagonists may be suitable as frontline or adjunctive treatments of pediatric status epilepticus or other early-life seizures, particularly when associated with brain damage.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

David C Henshall, Miguel Diaz-Hernandez, M Teresa Miras-Portugal, Alba Jimenez-Pacheco, Amaya Sanz-Rodriguez, Ellen V Hessel, Tobias Engel, Guillaume Mesuret

Experts in our system

1
David C Henshall
Royal College of Surgeons in Ireland
Total Publications: 127
 
2
Miguel Diaz-Hernandez
Royal College of Surgeons in Ireland
Total Publications: 13
 
3
M Teresa Miras-Portugal
Royal College of Surgeons in Ireland
Total Publications: 12
 
4
Alba Jimenez-Pacheco
Royal College of Surgeons in Ireland
Total Publications: 10
 
5
Amaya Sanz-Rodriguez
Royal College of Surgeons in Ireland
Total Publications: 18
 
6
Tobias Engel
Royal College of Surgeons in Ireland
Total Publications: 66