Activation of the phagocyte NADPH oxidase/NOX2 and myeloperoxidase in the mouse brain during pilocarpine-induced temporal lobe epilepsy and inhibition by ketamine

Fatma Tannich (1, 2, 3) , Asma Tlili (1) , Coralie Pintard (1) , Amina Chniguir (1) , Bruno Eto (4) , Pham My-Chan Dang (1) , Ouajdi Souilem (2) , Jamel El-Benna (1)

1 CRI (UMR_S_1149 / ERL_8252 / U1149) - Centre de recherche sur l'Inflammation
2 UMA - Université de la Manouba [Tunisie]
3 UTM - Université de Tunis El Manar
4 Université de Lille

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 phox , p22 phox , and p47 phox) 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 phox phosphorylation and H 2 O 2 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.

Mots clés: Epilepsy; Phagocytes; Neutrophils; NOX2; p47phox; Ketamine; ROS; Myeloperoxidase; Neuro-Inflammation

Domaines: Neurobiologie; Immunologie

Fatma Tannich, Asma Tlili, Coralie Pintard, Amina Chniguir, Bruno Eto, et al.. Activation of the phagocyte NADPH oxidase/NOX2 and myeloperoxidase in the mouse brain during pilocarpine-induced temporal lobe epilepsy and inhibition by ketamine. Inflammopharmacology, 2020, 28 (2), pp.487-497. ⟨10.1007/s10787-019-00655-9⟩. ⟨hal-03026124⟩