Primary study for the therapeutic dose and time window of picroside II in treating cerebral ischemic injury in rats

Int J Mol Sci. 2012;13(3):2551-2562. doi: 10.3390/ijms13032551. Epub 2012 Feb 23.

Abstract

The aim of this study was to explore the optimal therapeutic dose and time window of picroside II for treating cerebral ischemic injury in rats according to the orthogonal test. The middle cerebral artery occlusion (MCAO) models were established by intraluminally inserting a thread into middle cerebral artery (MCA) from left external carotid artery (ECA). The successful rat models were randomly divided into 16 groups according to the orthogonal layout of [L(16)(4(5))] and treated by injecting picroside II intraperitoneally with different doses at various times. The neurological behavioral function was evaluated by Bederson's test and the cerebral infarction volume was measured by tetrazolium chloride (TTC) staining. The expressions of neuron specific enolase (NSE) and neuroglial mark-protein S-100 were determined by immunohistochemisty assay. The results indicated that the optimal compositions of the therapeutic dose and time window of picroside II in treating cerebral ischemic injury were ischemia 1.5 h with 20 mg/kg body weight according to Bederson's test, 1.0 h with 20 mg/kg body weight according to cerebral infarction volume, 1.5 h with 20 mg/kg body weight according to the expressions of NSE and S-100 respectively. Based on the principle of the minimization of medication dose and maximization of therapeutic time window, the optimal composition of the therapeutic dose and time window of picroside II in treating cerebral ischemic injury should be achieved by injecting picroside II intraperitoneally with 20 mg/kg body weight at ischemia 1.5 h.

Keywords: NSE; S-100; cerebral ischemia; picroside II; rats; therapeutic dose; time window.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / pathology*
  • Brain Ischemia / physiopathology
  • Cinnamates / administration & dosage*
  • Cinnamates / therapeutic use*
  • Dose-Response Relationship, Drug
  • Iridoid Glucosides / administration & dosage*
  • Iridoid Glucosides / therapeutic use*
  • Male
  • Phosphopyruvate Hydratase / metabolism
  • Rats, Wistar
  • S100 Proteins / metabolism
  • Time Factors

Substances

  • Cinnamates
  • Iridoid Glucosides
  • S100 Proteins
  • picroside II
  • Phosphopyruvate Hydratase