Molecular hydrogen protects against central nervous system white matter ischemic injury
Sunday, Oct 14, 2012, 2:00 PM - 3:00 PM
, K. FUJITA
, M. A. HAMNER
, M. YAMAFUJI
, M. A. KIDO
, Y. TANAKA
, Y. NAKABEPPU
, B. R. RANSOM
Lab. Pathophysiol, Grad Sch. Pharm, Kyushu Univ., Fukuoka, Japan;
Dept. of Neurol., Univ. of Washington Sch. of Med., Seattle, WA;
Dept. of Oral Anat. and Cell Biol., Grad. Sch. of Dent. Sciences, Kyushu University,, Fukuoka, Japan;
Corporate Engin. Division, Appliances Company,, Panasonic Corp., Kusatsu, Japan;
Div. of Neurofunctional Genomics, Med. Inst. of Bioregulation, Kyushu Univ., Fukuoka, Japan
Molecular hydrogen selectively reduces hydroxyl radicals, the most cytotoxic of reactive oxygen species (ROS). Hydrogen (H
) 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
A 60 min period of OGD caused prompt loss of the CAP followed by an average 20% recovery. After mice received H
-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 H
-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 H
-water drinking mice. The ‘protection’ induced by 7-10 days of H
drinking lasted several days.
Our results show that several days of H
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.
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.
2012 Copyright by the Society for Neuroscience all rights reserved. Permission to republish any abstract or part of any abstract in any form must be obtained in writing by SfN office prior to publication.
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