title: NADPH oxidase-2: linking glucose, acidosis, and excitotoxicity in stroke.
abstract: CONCLUSIONS
  Neuronal superoxide production contributes to cell death in both glutamate excitotoxicity and brain ischemia (stroke). NADPH oxidase-2 (NOX2) is the major source of neuronal superoxide production in these settings, and regulation of NOX2 activity can thereby influence outcome in stroke.
  
  
  BACKGROUND
  Reduced NOX2 activity can rescue cells from oxidative stress and cell death that otherwise occur in excitotoxicity and ischemia. NOX2 activity is regulated by several factors previously shown to affect outcome in stroke, including glucose availability, intracellular pH, protein kinase ζ/δ, casein kinase 2, phosphoinositide-3-kinase, Rac1/2, and phospholipase A2. The newly identified functions of these factors as regulators of NOX2 activity suggest alternative mechanisms for their effects on ischemic brain injury.
  
  
  RESULTS
  Key aspects of these regulatory influences remain unresolved, including the mechanisms by which rac1 and phospholipase activities are coupled to N-methyl-D-aspartate (NMDA) receptors, and whether superoxide production by NOX2 triggers subsequent superoxide production by mitochondria.
  
  
  CONCLUSIONS
  It will be important to establish whether interventions targeting the signaling pathways linking NMDA receptors to NOX2 in brain ischemia can provide a greater neuroprotective efficacy or a longer time window to treatment than provided by NMDA receptor blockade alone. It will likewise be important to determine whether dissociating superoxide production from the other signaling events initiated by NMDA receptors can mitigate the deleterious effects of NMDA receptor blockade.
authors.affiliation: 1 Department of Neurology, University of California San Francisco , San Francisco, California.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Brennan-Minnella
authors.forename: Seok Joon
authors.initials: SJ
authors.lastname: Won
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Swanson
mesh_terms: D000138:Acidosis / Q000201:enzymology* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D020521:Stroke / Q000201:enzymology* / Q000378:metabolism
chemical_list: D008562:Membrane Glycoproteins; D016194:Receptors, N-Methyl-D-Aspartate; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D005947:Glucose