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01.12.2007 | Original Paper

Soluble Neuroprotective Antioxidant Uric Acid Analogs Ameliorate Ischemic Brain Injury in Mice

verfasst von: Frank Haberman, Sung-Chun Tang, Thiruma V. Arumugam, Dong-Hoon Hyun, Qian-Sheng Yu, Roy G. Cutler, Zhihong Guo, Harold W. Holloway, Nigel H. Greig, Mark P. Mattson

Erschienen in: NeuroMolecular Medicine | Ausgabe 4/2007

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Abstract

Uric acid is a major antioxidant in the blood of humans that can protect cultured neurons against oxidative and metabolic insults. However, uric acid has a very low solubility which compromises its potential clinical use for neurodegenerative disorders. Here we describe the synthesis, characterization and preclinical development of neuroprotective methyl- and sulfur-containing analogs of uric acid with increased solubility. In vitro and cell culture screening identified 1,7-dimethyluric acid (mUA2) and 6,8-dithiouric acid (sUA2) as two analogs with high antioxidant and neuroprotective activities. When administered intravenously in mice, uric acid analogs mUA2 and sUA2 lessened damage to the brain and improved functional outcome in an ischemia-reperfusion mouse model of stroke. Analogs sUA2 and mUA2 were also effective in reducing damage to the cerebral cortex when administered up to 4 h after stroke onset in a permanent middle cerebral artery occlusion mouse model. These findings suggest a therapeutic potential for soluble analogs of uric acid in the treatment of stroke and related neurodegenerative conditions.

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Titel: Soluble Neuroprotective Antioxidant Uric Acid Analogs Ameliorate Ischemic Brain Injury in Mice
verfasst von: Frank Haberman
Sung-Chun Tang
Thiruma V. Arumugam
Dong-Hoon Hyun
Qian-Sheng Yu
Roy G. Cutler
Zhihong Guo
Harold W. Holloway
Nigel H. Greig
Mark P. Mattson
Publikationsdatum: 01.12.2007
Verlag: Humana Press Inc
Erschienen in: NeuroMolecular Medicine / Ausgabe 4/2007
Print ISSN: 1535-1084
Elektronische ISSN: 1559-1174
DOI: https://doi.org/10.1007/s12017-007-8010-1

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