NADPH oxidases as potential pharmacological targets against increased seizure susceptibility after systemic inflammation

Journal of Neuroinflammation
Wan-Yu HuangHung-Ming Wu

Abstract

Systemic inflammation associated with sepsis can induce neuronal hyperexcitability, leading to enhanced seizure predisposition and occurrence. Brain microglia are rapidly activated in response to systemic inflammation and, in this activated state, release multiple cytokines and signaling factors that amplify the inflammatory response and increase neuronal excitability. NADPH oxidase (NOX) enzymes promote microglial activation through the generation of reactive oxygen species (ROS), such as superoxide anion. We hypothesized that NOX isoforms, particularly NOX2, are potential targets for prevention of sepsis-associated seizures. To reduce NADPH oxidase 2-derived ROS production, mice with deficits of NOX regulatory subunit/NOX2 organizer p47phox (p47phox-/-) or NOX2 major subunit gp91phox (gp91phox-/-) were used or the NOX2-selective inhibitor diphenyleneiodonium (DPI) was used to treat wild-type (WT) mice. Systemic inflammation was induced by intraperitoneal injection of lipopolysaccharide (LPS). Seizure susceptibility was compared among mouse groups in response to intraperitoneal injection of pentylenetetrazole (PTZ). Brain tissues were assayed for proinflammatory gene and protein expression, and immunofluorescence staining was ...Continue Reading

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Citations

Dec 15, 2019·Molecular Nutrition & Food Research·Rebeca AlvariñoLuis M Botana
Mar 15, 2019·International Journal of Molecular Sciences·Candace N RecenoKeith C DeRuisseau
Jan 26, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Geir BjørklundSalvatore Chirumbolo
Aug 3, 2021·Oxidative Medicine and Cellular Longevity·Yuhei NishimuraHiroaki Aoyama

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Methods Mentioned

BETA
Protein Assay
PCR
fluorescence microscopy

Software Mentioned

StatLIAs
GraphPad Prism

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