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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.
Neurosurgery. 2006 Aug; 59(2):383-8; discussion 383-8.N

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.

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Authors+Show Affiliations

Mack WJ
Department of Neurological Surgery, College of Physicians & Surgeons, Columbia University, New York, New York 10032, USA. wjm32@columbia.edu
Mocco J
No affiliation info available
Ducruet AF
No affiliation info available
Laufer I
No affiliation info available
King RG
No affiliation info available
Zhang Y
No affiliation info available
Guo W
No affiliation info available
Pinsky DJ
No affiliation info available
Connolly ES
No affiliation info available

MeSH

AnimalsAntioxidantsAscorbic AcidBrain IschemiaCerebral CortexCerebral InfarctionCitric AcidDehydroascorbic AcidDisease Models, AnimalExcipientsInfarction, Middle Cerebral ArteryInjections, IntravenousLipid PeroxidationMiceMice, Inbred C57BLNerve DegenerationNeuroprotective AgentsOxidative StressReperfusion InjurySorbitolTreatment OutcomeUp-Regulation

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16883179

Citation

Mack, William J., et al. "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." Neurosurgery, vol. 59, no. 2, 2006, pp. 383-8; discussion 383-8.
Mack WJ, Mocco J, Ducruet AF, et al. 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. Neurosurgery. 2006;59(2):383-8; discussion 383-8.
Mack, W. J., Mocco, J., Ducruet, A. F., Laufer, I., King, R. G., Zhang, Y., Guo, W., Pinsky, D. J., & Connolly, E. S. (2006). 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. Neurosurgery, 59(2), 383-8; discussion 383-8.
Mack WJ, et al. 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. Neurosurgery. 2006;59(2):383-8; discussion 383-8. PubMed PMID: 16883179.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Mack,William J, AU - Mocco,J, AU - Ducruet,Andrew F, AU - Laufer,Ilya, AU - King,Ryan G, AU - Zhang,Yuan, AU - Guo,Weijia, AU - Pinsky,David J, AU - Connolly,E Sander,Jr PY - 2006/8/3/pubmed PY - 2006/9/22/medline PY - 2006/8/3/entrez SP - 383-8; discussion 383-8 JF - Neurosurgery JO - Neurosurgery VL - 59 IS - 2 N2 - 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. SN - 1524-4040 UR - https://www.unboundmedicine.com/medline/citation/16883179/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_ L2 - https://academic.oup.com/neurosurgery/article-lookup/doi/10.1227/01.NEU.0000223496.96945.A7 DB - PRIME DP - Unbound Medicine ER -