title: Risperidone enhances the vulnerability to stroke in hypertensive rats.
abstract: BACKGROUND
  Stroke is the second most common cause of death and a major cause of disability worldwide. Risperidone is an atypical antipsychotic drug that may increase the risk of stroke. The present work examined whether risperidone enhances the vulnerability to stroke in hypertensive rats and the potential mechanisms underlying such action.
  
  
  METHODS
  Experiment 1: Wistar-Kyoto (WKY) rats, spontaneously hypertensive rats (SHRs) and stroke-prone SHRs (SHR-SPs) were treated with risperidone (0.8 and 2.4 mg/kg/d) or vehicle for 30 consecutive days. Tissue damage in response to middle cerebral artery occlusion (MCAO) was measured microscopically. The activity of superoxide dismutase, glutathione peroxidase, the levels of malondialdehyde were also determined. Experiment 2: Survival data were recorded in SHR-SPs that received daily risperidone perpetually. Experiment 3: Effect of risperidone on interleukin-6 and tumor necrosis factor-α was examined in quiescent or LPS-activated cortical microglias from WKY rats. Experiment 4: Potential damage of risperidone exposure to neurons was examined in primary neuronal culture obtained from WKY rats, SHRs, and SHR-SPs.
  
  
  RESULTS
  Risperidone increased infarct areas upon MCAO in SHR-SPs and SHRs, but not in WKY rats. Survival time in SHR-SPs was shortened by risperidone. Apoptosis was augmented by risperidone through enhanced Bax. Risperidone also increased endothelial injury.
  
  
  CONCLUSIONS
  Risperidone enhances the vulnerability to stroke in hypertensive rats through increasing neuronal apoptosis and endothelial injury.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, China.
authors.forename: Shu-Wei
authors.initials: SW
authors.lastname: Song
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.forename: Bei-Lin
authors.initials: BL
authors.lastname: Su
authors.forename: Chong
authors.initials: C
authors.lastname: Liu
authors.forename: Chu
authors.initials: C
authors.lastname: Yang
authors.forename: Theophile
authors.initials: T
authors.lastname: Godfraind
authors.forename: Ding-Feng
authors.initials: DF
authors.lastname: Su
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D006973:Hypertension / Q000150:complications / Q000473:pathology*; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018967:Risperidone / Q000633:toxicity*; D020521:Stroke / Q000139:chemically induced* / Q000209:etiology / Q000473:pathology*
chemical_list: D018967:Risperidone