Ziprasidone Attenuates Brain Injury After Focal Cerebral Ischemia Induced by Middle Cerebral Artery Occlusion in Rats

Prog Neuropsychopharmacol Biol Psychiatry. 2012 Oct 1;39(1):69-74. doi: 10.1016/j.pnpbp.2012.05.010. Epub 2012 May 21.

Abstract

Ziprasidone is an atypical antipsychotic drug used for the treatment of schizophrenia. Recent studies have reported that atypical antipsychotics have neuroprotective effects against brain injury. In the present study, the effect of ziprasidone on ischemic brain injury was investigated. Focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in rats. All the animals experienced ischemia for 1h and then underwent reperfusion. The infarct size induced by MCAO was significantly reduced in the animals that received acute treatment with 5mg/kg ziprasidone and subchronic treatment with 2.5mg/kg ziprasidone for 7 days compared with that in the vehicle-treated animals. The acute treatment with ziprasidone significantly improved neurological functions, as measured by the modified neurological severity score, in a dose-dependent manner. The subchronic treatment produced more rapid recovery from functional deficits than the vehicle treatment. The immunohistochemical investigation revealed that the subchronic treatment prevented severe loss of neuronal marker intensity and attenuated the increased in microglial marker intensity in the infarcted cortical area. These results suggest that ziprasidone has neuroprotective effects in a rat model of ischemic stroke and provide new insight for its clinical applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Nuclear / metabolism*
  • Antipsychotic Agents / pharmacology
  • Antipsychotic Agents / therapeutic use
  • Biomarkers / metabolism
  • Brain Injuries / drug therapy*
  • Brain Injuries / metabolism
  • Brain Injuries / pathology
  • Brain Injuries / physiopathology
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / metabolism
  • Brain Ischemia / pathology
  • Brain Ischemia / physiopathology
  • Calcium-Binding Proteins / metabolism*
  • Cerebral Infarction / drug therapy
  • Cerebral Infarction / prevention & control
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Male
  • Microfilament Proteins / metabolism*
  • Microglia / metabolism
  • Nerve Tissue Proteins / metabolism*
  • Neurons / metabolism
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • Piperazines / pharmacology*
  • Piperazines / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function / drug effects*
  • Recovery of Function / physiology
  • Severity of Illness Index
  • Thiazoles / pharmacology*
  • Thiazoles / therapeutic use

Substances

  • Aif1 protein, rat
  • Antigens, Nuclear
  • Antipsychotic Agents
  • Biomarkers
  • Calcium-Binding Proteins
  • Microfilament Proteins
  • Nerve Tissue Proteins
  • Neuroprotective Agents
  • Piperazines
  • Rbfox3 protein, rat
  • Thiazoles
  • ziprasidone