Type

Journal Article

Authors

David C Henshall
Geraldine B Boylan
Anindya Bhattacharya
Ronán M Conroy
Cristina R Reschke
Sean Quinlan
Tobias Engel
Eva M Jimenez-Mateos
Natalia Rodriguez-Alvarez

Subjects

Biochemistry

Topics
human receptor surface hypoxia brain caspase 1 neonatal seizures mice

Effects of P2X7 receptor antagonists on hypoxia-induced neonatal seizures in mice. (2016)

Abstract Neonatal seizures are a common consequence of hypoxic/ischemic encephalopathy (HIE). Phenobarbital remains the frontline treatment for neonatal seizures but is often ineffective. The P2X7 receptor (P2X7R) is a cell surface-expressed ionotropic receptor activated by high amounts of ATP which may be released during seizures or as a consequence of tissue injury. Here, we explored the role of the P2X7R in a mouse model of neonatal seizures induced by hypoxia. Exposure of postnatal day 7 (P7) mouse pups to global hypoxia (5% O2 for 15 min) produced electrographically-defined seizures with behavioural correlates that persisted after restitution of normoxia. Expression of the P2X7R showed age-dependent increases in the hippocampus and neocortex of developing mice and was present in human neonatal brain. P2X7R transcript and protein levels were increased 24 h after neonatal hypoxia-induced seizures in mouse pups. EEG recordings in pups determined that injection of the P2X7R antagonist A-438079 (25 mg/kg(-1), intraperitoneal) reduced electrographic seizure number, EEG power and spiking during hypoxia. A-438079 did not reduce post-hypoxia seizures. Caspase-1 processing and molecular markers of inflammation and microglia were reduced in A438079-treated mice. Electrographic seizure-suppressive effects were also observed with a second P2X7R antagonist, JNJ-47965567, in the same model. The present study shows hypoxia-induced seizures alter expression of purinergic and neuroinflammatory signalling components and suggest potential applications but also limitations of the P2X7R as a target for the treatment of HIE and other causes of neonatal seizures.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

David C Henshall, Geraldine B Boylan, Anindya Bhattacharya, Ronán M Conroy, Cristina R Reschke, Sean Quinlan, Tobias Engel, Eva M Jimenez-Mateos, Natalia Rodriguez-Alvarez

Experts in our system

1
David C Henshall
Royal College of Surgeons in Ireland
Total Publications: 127
 
2
Geraldine B Boylan
University College Cork
Total Publications: 141
 
3
Anindya Bhattacharya
Royal College of Surgeons in Ireland
Total Publications: 4
 
4
Ronán Conroy
Royal College of Surgeons in Ireland
Total Publications: 150
 
5
Cristina R Reschke
Royal College of Surgeons in Ireland
Total Publications: 8
 
6
Sean Quinlan
Royal College of Surgeons in Ireland
Total Publications: 6
 
7
Tobias Engel
Royal College of Surgeons in Ireland
Total Publications: 66
 
8
Eva M Jimenez-Mateos
Royal College of Surgeons in Ireland
Total Publications: 55
 
9
Natalia Rodriguez-Alvarez
Royal College of Surgeons in Ireland