Document Detail


Neuroprotective mechanisms of curcumin against cerebral ischemia-induced neuronal apoptosis and behavioral deficits.
MedLine Citation:
PMID:  16075466     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Increased oxidative stress has been regarded as an important underlying cause for neuronal damage induced by cerebral ischemia/reperfusion (I/R) injury. In recent years, there has been increasing interest in investigating polyphenols from botanical source for possible neuroprotective effects against neurodegenerative diseases. In this study, we investigated the mechanisms underlying the neuroprotective effects of curcumin, a potent polyphenol antioxidant enriched in tumeric. Global cerebral ischemia was induced in Mongolian gerbils by transient occlusion of the common carotid arteries. Histochemical analysis indicated extensive neuronal death together with increased reactive astrocytes and microglial cells in the hippocampal CA1 area at 4 days after I/R. These ischemic changes were preceded by a rapid increase in lipid peroxidation and followed by decrease in mitochondrial membrane potential, increased cytochrome c release, and subsequently caspase-3 activation and apoptosis. Administration of curcumin by i.p. injections (30 mg/kg body wt) or by supplementation to the AIN76 diet (2.0 g/kg diet) for 2 months significantly attenuated ischemia-induced neuronal death as well as glial activation. Curcumin administration also decreased lipid peroxidation, mitochondrial dysfunction, and the apoptotic indices. The biochemical changes resulting from curcumin also correlated well with its ability to ameliorate the changes in locomotor activity induced by I/R. Bioavailability study indicated a rapid increase in curcumin in plasma and brain within 1 hr after treatment. Together, these findings attribute the neuroprotective effect of curcumin against I/R-induced neuronal damage to its antioxidant capacity in reducing oxidative stress and the signaling cascade leading to apoptotic cell death.
Authors:
Qun Wang; Albert Y Sun; Agnes Simonyi; Michael D Jensen; Phullara B Shelat; George E Rottinghaus; Ruth S MacDonald; Dennis K Miller; Dennis E Lubahn; Gary A Weisman; Grace Y Sun
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of neuroscience research     Volume:  82     ISSN:  0360-4012     ISO Abbreviation:  J. Neurosci. Res.     Publication Date:  2005 Oct 
Date Detail:
Created Date:  2005-10-03     Completed Date:  2006-02-07     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7600111     Medline TA:  J Neurosci Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  138-48     Citation Subset:  IM    
Copyright Information:
(c) 2005 Wiley-Liss, Inc.
Affiliation:
Department of Biochemistry, University of Missouri, Columbia, Missouri 65212, USA.
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Animals
Antigens, CD13 / drug effects
Apoptosis / drug effects*
Astrocytes / metabolism,  pathology
Behavior, Animal
Behavioral Symptoms / etiology,  prevention & control*
Brain / drug effects,  growth & development,  pathology
Brain Ischemia / complications*,  pathology
Caspase 3
Caspases / metabolism
Cell Count / methods
Curcumin / therapeutic use*
Cytochromes c / metabolism
Disease Models, Animal
Gerbillinae
Glial Fibrillary Acidic Protein / metabolism
Histocytochemistry / methods
Immunohistochemistry / methods
In Situ Nick-End Labeling / methods
Indoles / diagnostic use
Lectins / metabolism
Lipid Peroxidation / drug effects
Liver / drug effects,  metabolism
Male
Microglia / metabolism,  pathology
Mitochondria / drug effects
Motor Activity / drug effects
Neurons / metabolism,  pathology
Neuroprotective Agents / therapeutic use*
Time Factors
Grant Support
ID/Acronym/Agency:
1 P01 AG18357/AG/NIA NIH HHS; 5P01 ES10535/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Glial Fibrillary Acidic Protein; 0/Indoles; 0/Lectins; 0/Neuroprotective Agents; 458-37-7/Curcumin; 47165-04-8/DAPI; 9007-43-6/Cytochromes c; EC 3.4.11.2/Antigens, CD13; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

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