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).

CONCLUSION:

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: William J Mack, J Mocco, Andrew F Ducruet, Ilya Laufer, Ryan G King, Yuan Zhang, Weijia Guo, David J Pinsky, E Sander Connolly Jr
• Journal: Neurosurgery (Neurosurgery) Vol. 59 Issue 2 Pg. 383-8; discussion 383-8 (Aug 2006) ISSN: 1524-4040 [Electronic] United States
• PMID: 16883179 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Excipients
• Neuroprotective Agents
• Citric Acid
• Sorbitol
• Ascorbic Acid
• Dehydroascorbic Acid

Topics

• Animals
• Antioxidants (pharmacology, therapeutic use)
• Ascorbic Acid (metabolism)
• Brain Ischemia (drug therapy, metabolism, physiopathology)
• Cerebral Cortex (drug effects, metabolism, physiopathology)
• Cerebral Infarction (drug therapy, physiopathology, prevention & control)
• Citric Acid (chemistry, pharmacology)
• Dehydroascorbic Acid (chemistry, pharmacology, therapeutic use)
• Disease Models, Animal
• Excipients (chemistry, pharmacology)
• Infarction, Middle Cerebral Artery (drug therapy, metabolism, physiopathology)
• Injections, Intravenous
• Lipid Peroxidation (drug effects, physiology)
• Mice
• Mice, Inbred C57BL
• Nerve Degeneration (drug therapy, physiopathology, prevention & control)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Oxidative Stress (drug effects, physiology)
• Reperfusion Injury (drug therapy, metabolism, physiopathology)
• Sorbitol (chemistry, pharmacology)
• Treatment Outcome
• Up-Regulation (drug effects, physiology)