title: Tanshinone IIA attenuates the cerebral ischemic injury-induced increase in levels of GFAP and of caspases-3 and -8.
abstract: Tanshinone IIA (TSA) is a lipid soluble agent derived from the root of Salvia miltiorrhiza (Danshen). This plant is a traditional Chinese herb, which has been used widely in China especially for enhancing circulation. However mechanisms underlying its efficacy remain poorly understood. The present study was designed to illuminate events that may underlie the apparently neuroprotective effects of TSA following ischemic insult. Adult Sprague-Dawley rats were subjected to transient focal cerebral ischemia by use of a middle cerebral artery occlusion model. They were then randomly divided into a sham-operated control group, and cerebral ischemia/reperfusion groups receiving a two-hour occlusion. Further subsets of groups received the same durations of occlusion or were sham-operated but then received daily i.p. injections of high or low doses of TSA, for seven or 15days. Hematoxylin and eosin staining revealed lesions in the entorhinal cortex of both rats subject to ischemia and to a lesser extent to those receiving TSA after surgery. Levels of glial fibrillary acidic protein (GFAP), caspase-3 and caspase-8, were quantified by both immunohistochemistry and Western blotting. TSA treatment after middle cerebral artery occlusion, markedly reduced infarct size, and reduced the expression of caspase-3 and caspase-8. These changes were considered protective and were generally proportional to the dose of TSA used. These results suggest that TSA may effect neuroprotection by way of reduction of the extent of cell inflammation and death within affected regions.
authors.affiliation: Department of Pathology, the Xiang-ya Hospital, Changsha 410008, China.
authors.forename: L
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Center for Occupational and Environmental Health, Department of Medicine, University of California, Irvine, CA 92697-1830, USA. Electronic address: scbondy@uci.edu.
authors.forename: S C
authors.initials: SC
authors.lastname: Bondy
authors.affiliation: Department of Clinical Microbiology and Immunology, Xiang-ya School of Medicine, Changsha 410013, China; Department of Neurology, the Third Xiang-ya Hospital, Changsha 410013, China.
authors.forename: L
authors.initials: L
authors.lastname: Jian
authors.affiliation: Department of Clinical Microbiology and Immunology, Xiang-ya School of Medicine, Changsha 410013, China; Department of Neurology, the Third Xiang-ya Hospital, Changsha 410013, China.
authors.forename: P
authors.initials: P
authors.lastname: Wen
authors.affiliation: Department of Clinical Microbiology and Immunology, Xiang-ya School of Medicine, Changsha 410013, China; Department of Neurology, the Third Xiang-ya Hospital, Changsha 410013, China.
authors.forename: F
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Clinical Microbiology and Immunology, Xiang-ya School of Medicine, Changsha 410013, China; Department of Neurology, the Third Xiang-ya Hospital, Changsha 410013, China.
authors.forename: H
authors.initials: H
authors.lastname: Luo
authors.affiliation: Department of Clinical Microbiology and Immunology, Xiang-ya School of Medicine, Changsha 410013, China; Department of Neurology, the Third Xiang-ya Hospital, Changsha 410013, China.
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.affiliation: Center of Experimental Medicine, the Xiang-ya Hospital, Changsha 410013, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism*; D053181:Caspase 8 / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D018728:Entorhinal Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism*; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley
chemical_list: D045784:Abietanes; D005904:Glial Fibrillary Acidic Protein; D018696:Neuroprotective Agents; C021751:tanshinone; C505410:Casp3 protein, rat; C505528:Casp8 protein, rat; D053148:Caspase 3; D053181:Caspase 8
keywords: Tanshinone IIA; caspase; cerebral ischemia; glial fibrillary acidic protein