Increased expression of the ATP‐gated P2X7 receptor reduces responsiveness to anti‐convulsants during status epilepticus in mice

2021 ◽  
Author(s):  
Edward Beamer ◽  
James Morgan ◽  
Mariana Alves ◽  
Aida Menéndez Méndez ◽  
Gareth Morris ◽  
...  
Keyword(s):  
Status Epilepticus ◽  
P2x7 Receptor

scholarly journals P2X7 Receptor-Dependent microRNA Expression Profile in the Brain Following Status Epilepticus in Mice

2020 ◽  
Vol 13 ◽  
Author(s):  
Giorgia Conte ◽  
Ngoc T. Nguyen ◽  
Mariana Alves ◽  
Laura de Diego-Garcia ◽  
Aidan Kenny ◽  
...  
Keyword(s):  
Status Epilepticus ◽  
Expression Profile ◽  
P2x7 Receptor ◽  
Microrna Expression ◽  
Microrna Expression Profile ◽  
The Brain

The effect of P2X7 receptor activation on nuclear factor-kappa B phosphorylation induced by status epilepticus in the rat hippocampus

Hippocampus ◽  
2013 ◽  
Vol 23 (6) ◽  
pp. 500-514 ◽  
Author(s):  
Ji-Eun Kim ◽  
Duk-Soo Kim ◽  
Hea Jin Ryu ◽  
Won Il Kim ◽  
Min-Ju Kim ◽  
...  
Keyword(s):  
Status Epilepticus ◽  
P2x7 Receptor ◽  
Nuclear Factor Kappa B ◽  
Receptor Activation ◽  
Rat Hippocampus ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa ◽  
P2x7 Receptor Activation

Seizure suppression and neuroprotection by targeting the purinergic P2X7 receptor during status epilepticus in mice

2011 ◽  
Vol 26 (4) ◽  
pp. 1616-1628 ◽  
Author(s):  
Tobias Engel ◽  
Rosa Gomez‐Villafuertes ◽  
Katsuhiro Tanaka ◽  
Guillaume Mesuret ◽  
Amaya Sanz‐Rodriguez ◽  
...  
Keyword(s):  
Status Epilepticus ◽  
P2x7 Receptor ◽  
Purinergic P2x7 Receptor ◽  
Seizure Suppression

scholarly journals Circulating P2X7 Receptor Signaling Components as Diagnostic Biomarkers for Temporal Lobe Epilepsy

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2444
Author(s):  
Giorgia Conte ◽  
Aida Menéndez-Méndez ◽  
Sebastian Bauer ◽  
Hany El-Naggar ◽  
Mariana Alves ◽  
...  
Keyword(s):  
Status Epilepticus ◽  
Blood Cell ◽  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Plasma Levels ◽  
P2x7 Receptor ◽  
Inflammatory Marker ◽  
Epileptic Seizures ◽  
Egfp Reporter ◽  
Signaling Components

Circulating molecules have potential as biomarkers to support the diagnosis of epilepsy and to assist with differential diagnosis, for example, in conditions resembling epilepsy, such as in psychogenic non-epileptic seizures (PNES). The P2X7 receptor (P2X7R) is an important regulator of inflammation and mounting evidence supports its activation in the brain during epilepsy. Whether the P2X7R or P2X7R-dependent signaling molecules can be used as biomarkers of epilepsy has not been reported. P2X7R levels were analyzed by quantitative ELISA using plasma samples from controls and patients with temporal lobe epilepsy (TLE) or PNES. Moreover, blood cell P2X7R expression and P2X7R-dependent cytokine signature was measured following status epilepticus in P2X7R-EGFP reporter, wildtype, and P2X7R-knockout mice. P2X7R plasma levels were higher in TLE patients when compared with controls and patients with PNES. Plasma levels of the broad inflammatory marker protein C-Reactive protein (CRP) were similar between the three groups. Using P2X7R-EGFP reporter mice, we identified monocytes as the main blood cell type expressing P2X7R after experimentally evoked seizures. Finally, cytokine array analysis in P2X7R-deficient mice identified KC/GRO as a potential P2X7R-dependent plasma biomarker following status epilepticus and during epilepsy. Our data suggest that P2X7R signaling components may be a promising subclass of circulating biomarkers to support the diagnosis of epilepsy.

scholarly journals Increased neocortical expression of the P2X7 receptor after status epilepticus and anticonvulsant effect of P2X7 receptor antagonist A-438079

Epilepsia ◽  
2013 ◽  
Vol 54 (9) ◽  
pp. 1551-1561 ◽  
Author(s):  
Alba Jimenez-Pacheco ◽  
Guillaume Mesuret ◽  
Amaya Sanz-Rodriguez ◽  
Katsuhiro Tanaka ◽  
Claire Mooney ◽  
...  
Keyword(s):  
Status Epilepticus ◽  
Receptor Antagonist ◽  
P2x7 Receptor ◽  
Anticonvulsant Effect

Inhibition of P2X7 Receptor Ameliorates Nuclear Factor-Kappa B Mediated Neuroinflammation Induced by Status Epilepticus in Rat Hippocampus

2017 ◽  
Vol 63 (2) ◽  
pp. 173-184 ◽  
Author(s):  
Cheng Huang ◽  
Xiao-sa Chi ◽  
Rui Li ◽  
Xin Hu ◽  
Hai-xia Xu ◽  
...  
Keyword(s):  
Status Epilepticus ◽  
P2x7 Receptor ◽  
Nuclear Factor Kappa B ◽  
Rat Hippocampus ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa

P2X7 receptor differentially modulates astroglial apoptosis and clasmatodendrosis in the rat brain following status epilepticus

Hippocampus ◽  
2010 ◽  
Vol 21 (12) ◽  
pp. 1318-1333 ◽  
Author(s):  
Ji-Eun Kim ◽  
Hea Jin Ryu ◽  
Seong-Il Yeo ◽  
Tae-Cheon Kang
Keyword(s):  
Status Epilepticus ◽  
Rat Brain ◽  
P2x7 Receptor

scholarly journals The ATP-gated P2X7 receptor contributes to the development of drug-resistant status epilepticus in mice

2021 ◽  
Author(s):  
Edward Beamer ◽  
James Morgan ◽  
Mariana Alves ◽  
Aida Menendez Mendez ◽  
Gareth Morris ◽  
...  
Keyword(s):  
Status Epilepticus ◽  
P2x7 Receptor ◽  
Therapeutic Potential ◽  
Refractory Status Epilepticus ◽  
Knock Out ◽  
Mortality And Morbidity ◽  
Adult Mice ◽  
Refractory Status ◽  
Anti Inflammatory ◽  
Pre Treatment

Background and Purpose Refractory status epilepticus is a clinical emergency associated with high mortality and morbidity. Increasing evidence suggests neuroinflammatory pathways contribute to the development of drug-refractoriness during status epilepticus. The ATP-gated P2X7 receptor (P2X7R) has been described as potential link between inflammation and increased hyperexcitability. The aim of the present study was to determine the contribution of the P2X7R to drug-refractory status epilepticus and its therapeutic potential. Experimental Approach Status epilepticus was induced via a unilateral microinjection of kainic acid into the amygdala in adult mice. Severity of status epilepticus was compared in animals overexpressing or knock-out in the P2X7R, after inflammatory priming by the pre-injection of bacterial lipopolysaccharide (LPS) and in mice treated with P2X7R-targeting and anti-inflammatory drugs. Key Results P2X7R overexpressing mice were unresponsive to several anticonvulsants (lorazepam, midazolam, phenytoin and carbamazepine) during status epilepticus. P2X7R expression was increased in microglia during drug-refractory status epilepticus, P2X7R overexpression led to a pro-inflammatory phenotype in microglia during status epilepticus and the anti-inflammatory drug minocycline restored normal responsiveness to anticonvulsants in P2X7R overexpressing mice. Pre-treatment of wildtype mice with LPS increased P2X7R levels in the brain and promoted the development of pharmaco-resistant status epilepticus, which was overcome by either a genetic deletion of the P2X7R or the administration of the P2X7R antagonists AFC-5128 or ITH15004. Conclusion and Implications Our results demonstrate that P2X7R-induced pro-inflammatory effects contribute to resistance to pharmacotherapy during status epilepticus and suggest therapies targeting the P2X7R as novel adjunctive treatments for drug-refractory status epilepticus.

scholarly journals Characterization of the Expression of the ATP-Gated P2X7 Receptor Following Status Epilepticus and during Epilepsy Using a P2X7-EGFP Reporter Mouse

2020 ◽  
Vol 36 (11) ◽  
pp. 1242-1258 ◽  
Author(s):  
James Morgan ◽  
Mariana Alves ◽  
Giorgia Conte ◽  
Aida Menéndez-Méndez ◽  
Laura de Diego-Garcia ◽  
...  
Keyword(s):  
Status Epilepticus ◽  
P2x7 Receptor ◽  
Reporter Mouse ◽  
Egfp Reporter
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