title: Pre- and post-treatments with escitalopram protect against experimental ischemic neuronal damage via regulation of BDNF expression and oxidative stress.
abstract: Selective serotonin re-uptake inhibitors (SSRI) have been widely used in treatment of major depression because of their efficacy, safety, and tolerability. Escitalopram, an SSRI, is known to decrease oxidative stress in chronic stress animal models. In the present study, we examined the neuroprotective effects of pre- and post-treatments with 20 mg/kg and 30 mg/kg escitalopram in the gerbil hippocampal CA1 region (CA1) after transient cerebral ischemia. Pre-treatment with escitalopram protected against ischemia-induced neuronal death in the CA1 after ischemia/reperfusion (I/R). Post-treatment with 30 mg/kg, not 20 mg/kg, escitalopram had a neuroprotective effect against ischemic damage. In addition, 20 mg/kg pre- and 30 mg/kg post-treatments with escitalopram increased brain-derived neurotrophic factor (BDNF) protein levels in the ischemic CA1 compared to vehicle-treated ischemia animals. In addition, 20 mg/kg pre- and 30 mg/kg post-treatments with escitalopram reduced microglia activation and decreased 4-hydroxy-2-nonenal and Cu,Zn-superoxide dismutase immunoreactivity and their levels in the ischemic CA1 compared to vehicle-treated ischemia animals after transient cerebral ischemia. In conclusion, these results indicated that pre- and post-treatments with escitalopram can protect against ischemia-induced neuronal death in the CA1 induced by transient cerebral ischemic damage by increase of BDNF as well as decrease of microglia activation and oxidative stress.
authors: Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, South Korea.
authors: Choong Hyun
authors: CH
authors: Lee
authors: Joon Ha
authors: JH
authors: Park
authors: Ki-Yeon
authors: KY
authors: Yoo
authors: Jung Hoon
authors: JH
authors: Choi
authors: In Koo
authors: IK
authors: Hwang
authors: Pan Dong
authors: PD
authors: Ryu
authors: Do-Hoon
authors: DH
authors: Kim
authors: Young-Guen
authors: YG
authors: Kwon
authors: Young-Myeong
authors: YM
authors: Kim
authors: Moo-Ho
authors: MH
authors: Won
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D056547:CA1 Region, Hippocampal / Q000187:drug effects* / Q000378:metabolism; D015283:Citalopram / Q000008:administration & dosage / Q000627:therapeutic use*; D005849:Gerbillinae; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D015283:Citalopram; D017367:Selective Serotonin Reuptake Inhibitors; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1