Activation of the Phagocyte NADPH Oxidase/NOX2 and Myeloperoxidase in the Mouse Brain During Pilocarpine-induced Temporal Lobe Epilepsy and Inhibition by Ketamine

Overview

Journal Inflammopharmacology

Specialty Pharmacology

Date 2019 Nov 1

PMID 31667656

Citations 8

Authors

Fatma Tannich

Asma Tlili

Coralie Pintard

Amina Chniguir

Bruno Eto

Pham My-Chan Dang

Ouajdi Souilem

Jamel El-Benna

Affiliations

Soon will be listed here.

Abstract

Excessive reactive oxygen species (ROS) production can induce tissue injury involved in a variety of neurodegenerative disorders such as neurodegeneration observed in pilocarpine-induced temporal lobe epilepsy. Ketamine, a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist has beneficial effects in pilocarpine-induced temporal lobe epilepsy, when administered within minutes of seizure to avoid the harmful neurological lesions induced by pilocarpine. However, the enzymes involved in ROS productions and the effect of ketamine on this process remain less documented. Here we show that during pilocarpine-induced epilepsy in mice, the expression of the phagocyte NADPH oxidase NOX2 subunits (NOX2/gp91, p22, and p47) and the expression of myeloperoxidase (MPO) were dramatically increased in mice brain treated with pilocarpine. Interestingly, treatment of mice with ketamine before or after pilocarpine administration decreased this process, mainly when injected before pilocarpine. Finally, our results showed that pilocarpine induced p47 phosphorylation and HO production in mice brain and ketamine was able to inhibit these processes. Our results show that pilocarpine induced NOX2 activation to produce ROS in mice brain and that administration of ketamine before or after the induction of temporal lobe epilepsy by pilocarpine inhibited this activation in mice brain. These results suggest a key role of the phagocyte NADPH oxidase NOX2 and MPO in epilepsy and identify a novel effect of ketamine.

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