Presentation Abstract

Program#/Poster#: 249.14/I8
Presentation Title: Molecular hydrogen protects against central nervous system white matter ischemic injury
Location: Hall F-J
Presentation time: Sunday, Oct 14, 2012, 2:00 PM - 3:00 PM
1Lab. Pathophysiol, Grad Sch. Pharm, Kyushu Univ., Fukuoka, Japan; 2Dept. of Neurol., Univ. of Washington Sch. of Med., Seattle, WA; 3Dept. of Oral Anat. and Cell Biol., Grad. Sch. of Dent. Sciences, Kyushu University,, Fukuoka, Japan; 4Corporate Engin. Division, Appliances Company,, Panasonic Corp., Kusatsu, Japan; 5Div. of Neurofunctional Genomics, Med. Inst. of Bioregulation, Kyushu Univ., Fukuoka, Japan
Abstract: Background: Molecular hydrogen selectively reduces hydroxyl radicals, the most cytotoxic of reactive oxygen species (ROS). Hydrogen (H2) in drinking water reduced dopaminergic neuronal loss by buffering ROS both in substantia nigra and in striatum in MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-treated mice (Fujita et al., 2009). The central nervous system (CNS) white matter (WM) ischemia is an important clinical problem and may produce injury, in part, by ROS-induced mitochondrial dysfunction. Using the mouse optic nerve (MON) WM model, we tested whether hydrogen in drinking water reduced functional WM ischemic injury, and if it reduced cellular lipid peroxidation and mitochondrial dysfunction including mitochondrial and nuclear DNA oxidation. Functional integrity of MON was determined by quantitatively monitoring the area of MON compound action potential (CAP) before, during and after a standardized 60 min period of oxygen and glucose deprivation (OGD), the ischemia equivalent ex vivo.
Results: A 60 min period of OGD caused prompt loss of the CAP followed by an average 20% recovery. After mice received H2-containing drinking water for 7-10 days, the CAP area did not disappear during ischemia and recovered to a significantly great extent during reperfusion with oxygen and glucose. Immunostaining of axonal neurofilament by SMI-31 labeling also showed significant protection by previous drinking of H2-water. Accumulation of nuclear 8-oxoguanine, a marker of oxidative DNA damage, was observed mainly in oligodendrocytes after OGD. The level of 8-oxoguanine after OGD were significantly reduced in optic nerves from H2-water drinking mice. The ‘protection’ induced by 7-10 days of H2 drinking lasted several days.
Conclusions: Our results show that several days of H2 exposure reduced the extent of CNS WM irreversible injury associated with OGD. The importance of these observations is that ischemic protection of myelinated CNS WM took several days to develop, lasted several days and provided partial protection in a novel manner from what has been previously described. These observations raise intriguing therapeutic options.
Fujita et al. Hydrogen in drinking water reduces dopaminergic neuronal loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease. PLoS One. Sep 30;4(9):e7247 (2009)
Acknowledgement: We greatly thank Dr. Selba Baltan for her experimental support.
Disclosures:  M. Noda: None. K. Fujita: None. M.A. Hamner: None. M. Yamafuji: None. M.A. Kido: None. Y. Tanaka: None. Y. Nakabeppu: None. B.R. Ransom: None.
Keyword(s): WHITE MATTER
Support: Grant-in-Aid from Japan Society for Promotion of Science MN22590084
[Authors]. [Abstract Title]. Program No. XXX.XX. 2012 Neuroscience Meeting Planner. New Orleans, LA: Society for Neuroscience, 2012. Online.

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