Effect of zolpidem on functional recovery in a rat model of ischemic stroke

J Int Med Res. 2018 Jan;46(1):249-257. doi: 10.1177/0300060517723799. Epub 2017 Aug 23.

Abstract

Objective To evaluate the effects of zolpidem on functional recovery in a rat model of acute ischemic stroke. Methods Following ischemic stroke procedures, 42 rats (six in each group) were randomly assigned to receive zolpidem (0.1, 0.25, 0.5, 1.0, 2.0 or 4.0 mg/kg) or normal saline administer intraperitoneally once daily for two weeks. Motor behavioural index (MBI) scores, radial 8-arm maze (RAM) test times and brain MRI scans were obtained 24 hours (Day 1) and two weeks (Day 14) post-procedure. Immunohistochemistry was performed on Day 14. Results By comparison with the normal saline group, the 0.5 and 1.0 mg/kg zolpidem groups showed statistically significant improvements in MBI scores and increased numbers of brain-derived neurotrophic factor (BDNF) stained cells over the two week dosing period. By contrast, the 4.0 mg/kg zolpidem group had statistically significantly impaired MBI scores compared with the control group. No differences among groups were found in RAM times or infarction volumes. Conclusions This study in a rat model showed that 0.5-1.0 mg/kg of zolpidem had beneficial effects on behavioural recovery by enhancing neural plasticity without causing any memory impairment in acute ischemic stroke.

Keywords: Zolpidem; insomnia; ischemia; rat model of ischemic stroke; recovery; stroke.

MeSH terms

  • Animals
  • Brain Ischemia / diagnostic imaging
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / genetics
  • Brain Ischemia / physiopathology
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism
  • Disease Models, Animal
  • Drug Administration Schedule
  • GABA-A Receptor Agonists / pharmacology*
  • Gene Expression
  • Injections, Intraperitoneal
  • Magnetic Resonance Imaging
  • Male
  • Maze Learning / drug effects
  • Neuroimaging / methods
  • Neuronal Plasticity / drug effects
  • Neuroprotective Agents / pharmacology*
  • Psychomotor Performance / drug effects
  • Pyridines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function / drug effects*
  • Stroke / diagnostic imaging
  • Stroke / drug therapy*
  • Stroke / genetics
  • Stroke / physiopathology
  • Zolpidem

Substances

  • Brain-Derived Neurotrophic Factor
  • GABA-A Receptor Agonists
  • Neuroprotective Agents
  • Pyridines
  • Zolpidem