Document Detail


Combination effects of normobaric hyperoxia and edaravone on focal cerebral ischemia-induced neuronal damage in mice.
MedLine Citation:
PMID:  18577423     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We evaluated the potential neuroprotective effects of combination treatment with normobaric hyperoxia (NBO) and edaravone, a potent scavenger of hydroxyl radicals, on acute brain injuries after stroke. Mice subjected to 2-h filamental middle cerebral artery occlusion were treated with NBO (95% O2, during the ischemia) alone, with edaravone (1.5 mg/kg, intravenously after the ischemia) alone, with both of these treatments (combination), or with vehicle. The histological and neurological score were assessed at 22-h after reperfusion. Infarct volume was significantly reduced in the combination group [36.3+/-6.7 mm3 (n=10) vs. vehicle: 65.5+/-5.9 mm3 (n=14) P<0.05], but not in the two monotherapy-groups [NBO: 50.5+/-5.8 mm3 (n=14) and edaravone: 56.7+/-5.8 mm3 (n=10)]. The combination therapy reduced TUNEL-positive cells in the ischemic boundary zone both in cortex [6.0+/-1.4 x 10(2)/mm2 (n=5) vs. vehicle: 18.9+/-2.4 x 10(2)/mm2 (n=5), P<0.01] and subcortex [11.6+/-1.5 x 10(2)/mm2 (n=5) vs. vehicle: 22.5+/-2.1 x 10(2)/mm2 (n=5), P<0.01]. NBO and combination groups exhibited significantly reduced neurological deficit scores at 22-h after reperfusion (vs. vehicle, P<0.05). Combination therapy with NBO plus edaravone prevented the neuronal damage after focal cerebral ischemia and reperfusion in mice, compared with monotherapy of NBO or edaravone.
Authors:
Yuko Nonaka; Masamitsu Shimazawa; Shinichi Yoshimura; Toru Iwama; Hideaki Hara
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Publication Detail:
Type:  Journal Article     Date:  2008-06-18
Journal Detail:
Title:  Neuroscience letters     Volume:  441     ISSN:  0304-3940     ISO Abbreviation:  Neurosci. Lett.     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-07-15     Completed Date:  2008-11-05     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7600130     Medline TA:  Neurosci Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  224-8     Citation Subset:  IM    
Affiliation:
Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-8585, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antipyrine / analogs & derivatives*,  therapeutic use
Blood Pressure / drug effects
Cell Death / drug effects
Cerebral Infarction / etiology,  pathology*,  therapy*
Disease Models, Animal
Free Radical Scavengers / therapeutic use*
Hyperbaric Oxygenation / methods*
In Situ Nick-End Labeling / methods
Infarction, Middle Cerebral Artery / complications
Male
Mice
Neurologic Examination
Neurons / drug effects,  pathology*
Tetrazolium Salts / diagnostic use
Chemical
Reg. No./Substance:
0/Free Radical Scavengers; 0/Tetrazolium Salts; 60-80-0/Antipyrine; 89-25-8/phenylmethylpyrazolone; 902-00-1/triphenyltetrazolium

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