NADPH oxidase in stroke and cerebrovascular disease

Abstract

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) was originally identified in immune cells as playing an important microbicidal role. In stroke and cerebrovascular disease, inflammation is increasingly being recognized as contributing negatively to neurological outcome, with NOX as an important source of superoxide. Several labs have now shown that blocking or deleting NOX in the experimental stroke models protects from brain ischemia. Recent work has implicated glucose as an important NOX substrate leading to reperfusion injury, and that NOX inhibition can improve the detrimental effects of hyperglycemia on stroke. NOX inhibition also appears to ameliorate complications of thrombolytic therapy by reducing blood–brain barrier disruption, edema formation, and hemorrhage. Further, NOX from circulating inflammatory cells seems to contribute more to ischemic injury more than NOX generated from endogenous brain residential cells. Several pharmacological inhibitors of NOX are now available. Thus, blocking NOX activation may prove to be a promising treatment for stroke as well as an adjunctive agent to prevent its secondary complications.

Keywords:

• Ischemia
• Inflammation
• Neuroprotection
• Superoxide
• NADPH oxidase

This work was supported by grants to MAY from: NIH NINDS (R01 NS40516, P50 NS014543), and a Veterans Affairs Merit Award, which were administered by the Northern California Institute for Research and Education, and with resources of the Veterans Affairs Medical Center, San Francisco, California.