Rapamycin preconditioning attenuates transient focal cerebral ischemia/reperfusion injury in mice

Int J Neurosci. 2012 Dec;122(12):748-56. doi: 10.3109/00207454.2012.721827. Epub 2012 Oct 4.

Abstract

Rapamycin, an mTOR inhibitor and immunosuppressive agent in clinic, has protective effects on traumatic brain injury and neurodegenerative diseases. But, its effects on transient focal ischemia/reperfusion disease are not very clear. In this study, we examined the effects of rapamycin preconditioning on mice treated with middle cerebral artery occlusion/reperfusion operation (MCAO/R). We found that the rapamycin preconditioning by intrahippocampal injection 20 hr before MCAO/R significantly improved the survival rate and longevity of mice. It also decreased the neurological deficit score, infracted areas and brain edema. In addition, rapamycin preconditioning decreased the production of NF-κB, TNF-α, and Bax, but not Bcl-2, an antiapoptotic protein in the ischemic area. From these results, we may conclude that rapamycin preconditioning attenuate transient focal cerebral ischemia/reperfusion injury and inhibits apoptosis induced by MCAO/R in mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Brain Edema / etiology
  • Brain Edema / prevention & control
  • Brain Infarction / etiology
  • Brain Infarction / prevention & control
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation / drug effects
  • Hippocampus / drug effects
  • Hippocampus / physiology
  • Infarction, Middle Cerebral Artery / blood
  • Infarction, Middle Cerebral Artery / mortality
  • Infarction, Middle Cerebral Artery / prevention & control*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • NF-kappa B / blood
  • Nervous System Diseases / etiology
  • Nervous System Diseases / prevention & control
  • Neurologic Examination
  • Reperfusion Injury / complications
  • Reperfusion Injury / mortality
  • Reperfusion Injury / prevention & control*
  • Sirolimus / therapeutic use*
  • Survival Rate
  • Tumor Necrosis Factor-alpha / blood
  • bcl-2-Associated X Protein / blood

Substances

  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • bcl-2-Associated X Protein
  • Sirolimus