Products Cited in Publications Worldwide Targeting Nox2 Mitigates Seizure Susceptibility, Oxidative Stress, and Neuroinflammation in the Pentylenetetrazol Seizure Model

Targeting Nox2 Mitigates Seizure Susceptibility, Oxidative Stress, and Neuroinflammation in the Pentylenetetrazol Seizure Model

Singh, Prince Kumar; Maurya, Shweta; Saadi, Aseel; Shekh-Ahmad, Tawfeeq

DOI:

Abstract

Oxidative stress is a pivotal driver of epileptogenesis and seizure-induced neuronal pathology, with NADPH oxidase 2 (NOX2) serving as a major source of reactive oxygen species (ROS) in the brain. Despite its established role in seizure pathophysiology, the therapeutic implications of selective NOX2 inhibition in epilepsy remain insufficiently explored. Here, we evaluate the efficacy of , a potent NOX2 inhibitor, in attenuating epileptiform network activity, oxidative stress, neuroinflammation, and neuronal injury using an in vitro epileptiform model and a pentylenetetrazol (PTZ)-induced seizure rat model. significantly suppressed epileptiform activity in vitro, reducing synchronous Ca2+ oscillations and accumulation in mixed cortical neuroglial cultures. In PTZ-treated rats, markedly diminished seizure severity, duration, and cumulative seizure burden, independent of seizure onset latency. Molecular analyses revealed a significant downregulation of NOX2 mRNA in both the hippocampus and cortex, although protein|https://www.ambeed.com/protein.html levels remained unaltered. Additionally, mitigated oxidative , selectively preserved hippocampal neuronal integrity, and differentially modulated neuroinflammatory cytokines, including IL-6, IL-1β, and IL-10. These findings underscore NOX2 inhibition as a compelling neuroprotective strategy, highlighting the potential of to mitigate oxidative and inflammatory cascades in epilepsy. Targeting NOX2 may represent a promising avenue for precision therapeutics in oxidative stress-driven epilepsy.

Keywords

; NADPH Oxidase 2 ; Epileptiform activity ; Pentylenetetrazol ; Oxidative stress

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GSK2795039

A2519631415925-18-697%

GSK2795039

162.0/25mg

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