title: Optimal dosages of fluoxetine in the treatment of hypoxic brain injury induced by 3-nitropropionic acid: implications for the adjunctive treatment of patients after acute ischemic stroke.
abstract: OBJECTIVE
  The serotonin selective reuptake inhibitor fluoxetine (Flx) has tried to treat patients suffered acute ischemic stroke because of its possible neuroprotective actions. However, besides the neuroprotective effect, Flx at high concentration also induces some actions in contradiction to neuroprotection in the brain. The purpose of this study was to investigate whether Flx presents neuroprotective effect against 3-nitropropionic acid (3-NP)-induced hypoxic brain injury, and what is the most suitable dosage of Flx.
  
  
  METHODS
  Mouse model was established by subacute systemic administration of 3-NP. Rotarod and pole tests were used to evaluate motor deficit. The oxidative stress and oxidative DNA damage were assessed respectively by measuring malondialdehyde and 8-hydroxydeoxyguanosine content in brain homogenates.
  
  
  RESULTS
  According to measurements in the rotarod test, 7 days pretreatment plus 5 days treatment of Flx at low (2.5 mg/kg/day) and, to a lesser degree, medium (5 mg/kg/day) doses exerted a rapid and strong protection against the neurotoxicity induced by 3-NP, whereas Flx at high dose (10mg/kg/day) showed a much late and light effect. Similarly, in the pole test, Flx at 2.5 mg/kg/day had the strongest protective effects. Again, only Flx administration at 2.5 mg/kg/day canceled out the enhancement of malondialdehyde and 8-hydroxydeoxyguanosine in striatum following 3-NP neurotoxication.
  
  
  CONCLUSIONS
  Flx attenuated the motor deficits induced by 3-NP in a dose-dependent manner. In contrary to the high dose, Flx at the lower doses had a more remarkable effect against 3-NP insult, similar to acute ischemic stroke.
authors.affiliation: Department of Physiology, Tongji University School of Medicine, Shanghai, China. binggen.zhu@tongji.edu.cn
authors.forename: Bing-Gen
authors.initials: BG
authors.lastname: Zhu
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.forename: Zhi-Qi
authors.initials: ZQ
authors.lastname: Sun
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.forename: Cheng-Hao
authors.initials: CH
authors.lastname: Zhou
authors.forename: Rong-Shen
authors.initials: RS
authors.lastname: Zhu
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D005473:Fluoxetine / Q000008:administration & dosage*; D002534:Hypoxia, Brain / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051379:Mice; D009574:Nitro Compounds / Q000633:toxicity*; D011422:Propionates / Q000633:toxicity*; D011897:Random Allocation; D020521:Stroke / Q000188:drug therapy* / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D009574:Nitro Compounds; D011422:Propionates; D005473:Fluoxetine; C015392:3-nitropropionic acid