P2X7 receptor antagonism reduces the severity of spontaneous seizures in a chronic model of temporal lobe epilepsy

Neuropharmacology
Halima AmhaoulStefanie Dedeurwaerdere

Abstract

The available pharmacotherapy for patients with epilepsy primarily address the symptoms and are ineffective in about 40% of patients. Brain inflammation gained support as potential target for developing new therapies, especially the P2X7 receptor (P2X7R), involved in processing of IL-1β, might be an interesting candidate. This study was designed to investigate the effect of a novel P2X7R antagonist on the severity and on the number of chronic spontaneous recurrent seizures (SRS), which was unexplored until now. After one-week of vehicle treatment (20% HP-β-cyclodextrin), JNJ-42253432 was administered subcutaneously for another week under continuous video-electroencephalography monitoring (n = 17) in Sprague Dawley rats 3 months after kainic acid-induced status epilepticus. The proportion of different seizure classes, as well as the number of SRS/day were calculated for the vehicle and treatment period. In addition, post-mortem microglial activation and astrogliosis were assessed. A significant decrease of the proportion of type 4-5 SRS (p < 0.05), while an increase of type 1-3 was demonstrated (p < 0.05) from the vehicle to the treatment period. There was no effect of the P2X7R antagonist on the number of SRS/day or the glial m...Continue Reading

References

Mar 1, 1972·Electroencephalography and Clinical Neurophysiology·R J Racine
Dec 1, 1980·Journal of Neuroscience Methods·G PaxinosP C Emson
Feb 5, 2000·The New England Journal of Medicine·P Kwan, M J Brodie
Apr 8, 2000·Neuroimmunomodulation·S HuC C Chao
Oct 4, 2000·The Journal of Biological Chemistry·M SolleC A Gabel
Jun 18, 2002·Journal of Neurochemistry·Beáta SperlághE Sylvester Vizi
Dec 29, 2004·Annals of Neurology·Celine DubéTallie Z Baram
Mar 25, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·David StellwagenRobert C Malenka
Jul 25, 2006·Neurobiology of Disease·T RavizzaE Aronica
Jan 24, 2007·FEBS Letters·Silviu LocoveiGerhard Dahl
Dec 20, 2007·Epilepsia·Maura PugliattiPatrik Sobocki
Jun 3, 2008·Seminars in Nuclear Medicine·Karolien GoffinWim Van Paesschen
Jun 13, 2008·Nature Protocols·Thomas D Schmittgen, Kenneth J Livak
Sep 12, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Elena AvignoneEtienne Audinat
Nov 21, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Bin JiTetsuya Suhara
Feb 21, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Philip A WilliamsF Edward Dudek
Jul 2, 2010·British Journal of Pharmacology·J SchlichtigerH Potschka
Dec 8, 2010·Nature Reviews. Neurology·Annamaria VezzaniTallie Z Baram
Dec 15, 2010·CNS & Neurological Disorders Drug Targets·Stephen D Skaper
Dec 15, 2010·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Julius BenickyJuan M Saavedra
Aug 17, 2011·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Hea Kyung ChoiTae-Cheon Kang
Dec 27, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Tobias EngelMiguel Diaz-Hernandez
Jan 5, 2012·Frontiers in Neuroendocrinology·Michael A GalicQuentin J Pittman
Sep 12, 2012·Nature Reviews. Neurology·Samuel Wiebe, Nathalie Jette
Nov 10, 2012·EJNMMI Research·Stefanie DedeurwaerdereMarie-Claude Grégoire
May 10, 2013·Epilepsia·Donald F Weaver, Bernd Pohlmann-Eden
Apr 23, 2014·CNS Neuroscience & Therapeutics·Guillaume MesuretDavid C Henshall
Jun 15, 2014·Pharmacological Reviews·Rachael BartlettRonald Sluyter
Oct 2, 2014·The Journal of Pharmacology and Experimental Therapeutics·Brian LordAnindya Bhattacharya
Apr 7, 2015·Epilepsy & Behavior : E&B·David C Henshall, Tobias Engel

❮ Previous
Next ❯

Citations

Jun 10, 2016·PloS One·Wolfgang FischerTobias Engel
Jul 3, 2019·Nature Reviews. Neurology·Annamaria VezzaniTeresa Ravizza
Jun 16, 2016·Journal of Neuroscience Research·François Rassendren, Etienne Audinat
Jun 6, 2017·Journal of Neuroscience Research·Andrew S Lapato, Seema K Tiwari-Woodruff
Feb 18, 2017·Frontiers in Neuroscience·Edward BeamerTobias Engel
Jul 18, 2019·Frontiers in Neurology·Dominik KobylarekWojciech Kozubski
Jun 12, 2020·Epilepsia Open·Pablo M Casillas-EspinosaTerence J O'Brien
Sep 29, 2020·Frontiers in Molecular Neuroscience·Giorgia ConteTobias Engel
May 14, 2020·Epilepsia·Robb WesselinghMastura Monif
Dec 17, 2020·Frontiers in Neurology·Quirijn P VerhoogErwin A van Vliet
Aug 24, 2020·Fitoterapia·Paulo Anastácio Furtado PachecoRobson Xavier Faria
Apr 24, 2021·Frontiers in Cellular Neuroscience·Paul R Territo, Hamideh Zarrinmayeh
Jun 19, 2021·Progress in Neurobiology·Edward BeamerTobias Engel
Jun 14, 2021·European Journal of Nuclear Medicine and Molecular Imaging·Viviane Bouilleret, Stefanie Dedeurwaerdere
Jul 27, 2021·Journal of Inflammation Research·Tobias EngelMariana Alves

❮ Previous
Next ❯

Related Concepts

Related Feeds

Amygdala: Sensory Processes

Amygdalae, nuclei clusters located in the temporal lobe of the brain, play a role in memory, emotional responses, and decision-making. Here is the latest research on sensory processes in the amygdala.

Anti-inflammatory Treatments

A drug or substance that reduces inflammation (redness, swelling, and pain) in the body. Anti-inflammatory agents block certain substances in the body that cause inflammation and swelling. Discover the latest research on anti-inflammatory treatments here

Amygdala and Midbrain Dopamine

The midbrain dopamine system is widely studied for its involvement in emotional and motivational behavior. Some of these neurons receive information from the amygdala and project throughout the cortex. When the circuit and transmission of dopamine is disrupted symptoms may present. Here is the latest research on the amygdala and midbrain dopamine.

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.