Neuronal expression of the NADPH oxidase NOX4, and its regulation in mouse experimental brain ischemia

• Published in: Neuroscience Vol. 132; no. 2; pp. 233 - 238
• Main Authors: Vallet, P., Charnay, Y., Steger, K., Ogier-Denis, E., Kovari, E., Herrmann, F., Michel, J.-P., Szanto, I.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 2005; Elsevier
• Subjects: Animals; Biological and medical sciences; Blotting, Northern - methods; Blotting, Western - methods; brain ischemia; Brain Ischemia - enzymology; Disease Models, Animal; Functional Laterality - physiology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Enzymologic - physiology; Immunohistochemistry - methods; In Situ Hybridization - methods; Infarction, Middle Cerebral Artery - enzymology; Kidney - enzymology; MCAO; Medical sciences; Mice; Mice, Inbred C57BL; NADPH oxidase; NADPH Oxidase 4; NADPH Oxidases - genetics; NADPH Oxidases - metabolism; neoangiogenesis; Neurology; Neurons - enzymology; NOX4; reactive oxygen species; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - metabolism; Time Factors; Vascular diseases and vascular malformations of the nervous system; Vertebrates: nervous system and sense organs; MCAO; brain ischemia; NADPH oxidase; neoangiogenesis; NOX; reactive oxygen species; ROS; NOX4; NADPH; Oxygen; Enzyme; Rodentia; Central nervous system; Oxidase; Cardiovascular disease; Encephalon; Vertebrata; Mammalia; Ischemia; Mouse; Animal; Oxidoreductases
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2004.12.038

Ischemia-induced neuronal damage has been linked to elevated production of reactive oxygen species (ROS) both in animal models and in humans. NADPH oxidase enzymes (NOX-es) are a major enzymatic source of ROS, but their role in brain ischemia has not yet been investigated. The present study was carried out to examine the expression of NOX4, one of the new NADPH oxidase isoforms in a mouse model of focal permanent brain ischemia. We demonstrate that NOX4 is expressed in neurons using in situ hybridization and immunohistochemistry. Ischemia, induced by middle cerebral artery occlusion resulted in a dramatic increase in cortical NOX4 expression. Elevated NOX4 mRNA levels were detectable as early as 24 h after the onset of ischemia and persisted throughout the 30 days of follow-up period, reaching a maximum between days 7 and 15. The early onset suggests neuronal reaction, while the peak period corresponds to the time of neoangiogenesis occurring mainly in the peri-infarct region. The occurrence of NOX4 in the new capillaries was confirmed by immunohistochemical staining. In summary, our paper reports the presence of the ROS producing NADPH oxidase NOX4 in neurons and demonstrates an upregulation of its expression under ischemic conditions. Moreover, a role for NOX4 in ischemia/hypoxia-induced angiogenesis is suggested by its prominent expression in newly formed capillaries.