title: Neuroprotective mechanisms of curcumin against cerebral ischemia-induced neuronal apoptosis and behavioral deficits.
abstract: 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.affiliation: Department of Biochemistry, University of Missouri, Columbia, Missouri 65212, USA.
authors.forename: Qun
authors.initials: Q
authors.lastname: Wang
authors.forename: Albert Y
authors.initials: AY
authors.lastname: Sun
authors.forename: Agnes
authors.initials: A
authors.lastname: Simonyi
authors.forename: Michael D
authors.initials: MD
authors.lastname: Jensen
authors.forename: Phullara B
authors.initials: PB
authors.lastname: Shelat
authors.forename: George E
authors.initials: GE
authors.lastname: Rottinghaus
authors.forename: Ruth S
authors.initials: RS
authors.lastname: MacDonald
authors.forename: Dennis K
authors.initials: DK
authors.lastname: Miller
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Lubahn
authors.forename: Gary A
authors.initials: GA
authors.lastname: Weisman
authors.forename: Grace Y
authors.initials: GY
authors.lastname: Sun
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001522:Behavior, Animal; D001526:Behavioral Symptoms / Q000209:etiology / Q000517:prevention & control*; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications* / Q000473:pathology; D018826:CD13 Antigens / Q000187:drug effects; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D003474:Curcumin / Q000627:therapeutic use*; D045304:Cytochromes c / Q000378:metabolism; D004195:Disease Models, Animal; D005849:Gerbillinae; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006651:Histocytochemistry / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D007211:Indoles; D037102:Lectins / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D005904:Glial Fibrillary Acidic Protein; D007211:Indoles; D037102:Lectins; D018696:Neuroprotective Agents; C007293:DAPI; D045304:Cytochromes c; D018826:CD13 Antigens; D053148:Caspase 3; D020169:Caspases; D003474:Curcumin