title: A cerebroprotective dose of intravenous citrate/sorbitol-stabilized dehydroascorbic acid is correlated with increased cerebral ascorbic acid and inhibited lipid peroxidation after murine reperfused stroke.
abstract: OBJECTIVE
  Oxidative damage has been implicated in the pathogenesis of cerebral ischemia. We previously demonstrated that exogenously supplied dehydroascorbic acid (DHA), an oxidized, blood-brain barrier transportable form of the antioxidant ascorbic acid (AA), improves outcome after experimental stroke.
  
  
  METHODS
  To investigate the neuroprotective effect of DHA therapy, we measured cerebral AA levels using a novel assay, quantified markers of lipid peroxidation, and evaluated infarct volume after reperfused stroke in a murine model. All experiments were performed using a new citrate/sorbitol-stabilized DHA formulation to improve the stability of the compound.
  
  
  RESULTS
  Intraparenchymal AA levels declined after cerebral ischemia/reperfusion and were repleted in a dose-dependent fashion by postischemic administration of intravenous DHA (P < 0.01). Repletion of these levels was associated with reductions in cerebral malondialdehyde levels (P < 0.05), which were also elevated after reperfused stroke. DHA repletion of interstitial AA levels and reduction in cerebral lipid peroxidation was associated with dose-dependent reductions in infarct volume (P < 0.05).
  
  
  CONCLUSIONS
  Together, these results indicate that an intravenous cerebroprotective dose of citrate/sorbitol-stabilized DHA is correlated with increased brain ascorbate levels and a suppression of excessive oxidative metabolism.
authors.affiliation: Department of Neurological Surgery, College of Physicians & Surgeons, Columbia University, New York, New York 10032, USA. wjm32@columbia.edu
authors.forename: William J
authors.initials: WJ
authors.lastname: Mack
authors.forename: J
authors.initials: J
authors.lastname: Mocco
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Ducruet
authors.forename: Ilya
authors.initials: I
authors.lastname: Laufer
authors.forename: Ryan G
authors.initials: RG
authors.lastname: King
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Weijia
authors.initials: W
authors.lastname: Guo
authors.forename: David J
authors.initials: DJ
authors.lastname: Pinsky
authors.forename: E Sander
authors.initials: ES
authors.lastname: Connolly
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D001205:Ascorbic Acid / Q000378:metabolism*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002544:Cerebral Infarction / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D019343:Citric Acid / Q000737:chemistry / Q000494:pharmacology; D003683:Dehydroascorbic Acid / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D005079:Excipients / Q000737:chemistry / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D007275:Injections, Intravenous; D015227:Lipid Peroxidation / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D013012:Sorbitol / Q000737:chemistry / Q000494:pharmacology; D016896:Treatment Outcome; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D000975:Antioxidants; D005079:Excipients; D018696:Neuroprotective Agents; D019343:Citric Acid; D013012:Sorbitol; D001205:Ascorbic Acid; D003683:Dehydroascorbic Acid