title: Neuroprotection via maintenance or increase of antioxidants and neurotrophic factors in ischemic gerbil hippocampus treated with tanshinone I.
abstract: BACKGROUND
  Danshen (Radix Salvia miltiorrhizae) has been used as a traditional medicine in Asia for treatment of various microcirculatory disturbance related diseases. Tanshinones are mainly hydrophobic active components, which have been isolated from Danshen and show various biological functions. In this study, we observed the neuroprotective effect of tanshinone I (TsI) against ischemic damage in the gerbil hippocampal CA1 region (CA1) after transient cerebral ischemia and examined its neuroprotective mechanism.
  
  
  METHODS
  The gerbils were divided into vehicle-treated-sham-group, vehicle-treated-ischemia-group, TsI-treated-sham-group, and TsI-treated-ischemia-group. TsI was administrated intraperitoneally three times (once a day for three days) before ischemia-reperfusion. The neuroprotective effect of TsI was examined using H&E staining, neuronal nuclei (NeuN) immunohistochemistry and Fluoro-Jade B staining. To investigate the neuroprotective mechanism of TsI after ischemia-reperfusion, immunohistochemical (IHC) and Western blotting analyses for Cu, Zn-superoxide dismutase (SOD1), Mn-superoxide dismutase (SOD2), brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-I (IGF-I) were performed.
  
  
  RESULTS
  Treatment with TsI protected pyramidal neurons from ischemia-induced neuronal death in the CA1 after ischemia-reperfusion. In addition, treatment with TsI maintained the levels of SOD1 and SOD2 as determined by IHC and Western blotting in the CA1 after ischemia-reperfusion compared with the vehicle-ischemia-group. In addition, treatment with TsI increased the levels of BDNF and IGF-I determined by IHC and Western blotting in the TsI-treated-sham-group compared with the vehicle-treated-sham-group, and their levels were maintained in the stratum pyramidale of the ischemic CA1 in the TsI-treated-ischemia-group.
  
  
  CONCLUSIONS
  Treatment with TsI protects pyramidal neurons of the CA1 from ischemic damage induced by transient cerebral ischemia via the maintenance of antioxidants and the increase of neurotrophic factors.
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea.
authors.forename: Joon Ha
authors.initials: JH
authors.lastname: Park
authors.affiliation: Division of Analytical Bio-Imaging, Chuncheon Center, Korea Basic Science Institute, Chuncheon 200-701, South Korea.
authors.forename: Ok Kyu
authors.initials: OK
authors.lastname: Park
authors.affiliation: Department of Integrative Traditional & Western Medicine, Medical College, Yangzhou University, Yangzhou, Jiangsu 225001, China.
authors.forename: Bingchun
authors.initials: B
authors.lastname: Yan
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea.
authors.forename: Ji Hyeon
authors.initials: JH
authors.lastname: Ahn
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea.
authors.forename: In Hye
authors.initials: IH
authors.lastname: Kim
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea.
authors.forename: Jae-Chul
authors.initials: JC
authors.lastname: Lee
authors.affiliation: Division of Analytical Bio-Imaging, Chuncheon Center, Korea Basic Science Institute, Chuncheon 200-701, South Korea.
authors.forename: Seung-Hae
authors.initials: SH
authors.lastname: Kwon
authors.affiliation: Department of Oral Anatomy, College of Dentistry, Gangneung-Wonju National University, Gangneung 210-702, South Korea.
authors.forename: Ki-Yeon
authors.initials: KY
authors.lastname: Yoo
authors.affiliation: Department of Pharmacy, College of Pharmacy, Dankook University, Cheonan 330-714, South Korea.
authors.forename: Choong Hyun
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul 151-742, South Korea.
authors.forename: In Koo
authors.initials: IK
authors.lastname: Hwang
authors.affiliation: Department of Anatomy, College of Veterinary Medicine, Kangwon National University, Chuncheon 200-701, South Korea.
authors.forename: Jung Hoon
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea. Email: mhwon@kangwon.ac.kr.
authors.forename: Moo-Ho
authors.initials: MH
authors.lastname: Won
authors.affiliation: Division of Food Science and Biotechnology, College of Agriculture and Life Sciences, Kangwon National University, Chuncheon 200-701, South Korea. Email: jongdai@cc.kangwon.ac.kr.
authors.forename: Jong-Dai
authors.initials: JD
authors.lastname: Kim
mesh_terms: D045784:Abietanes / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D015153:Blotting, Western; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D005849:Gerbillinae; D006624:Hippocampus / Q000378:metabolism*; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D009414:Nerve Growth Factors / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2
chemical_list: D045784:Abietanes; D000975:Antioxidants; D019208:Brain-Derived Neurotrophic Factor; D007334:Insulin-Like Growth Factor I; D009414:Nerve Growth Factors; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2; C021751:tanshinone