Neuroprotective capabilities of TSA against cerebral ischemia/reperfusion injury via PI3K/Akt signaling pathway in rats

Int J Neurosci. 2015 Feb;125(2):140-6. doi: 10.3109/00207454.2014.912217. Epub 2014 May 27.

Abstract

Background: Hundreds of previous studies demonstrated the cytoprotective effect of trichostatin-A (TSA), a kind of histone deacetylases inhibitors (HDACIs), against cerebral ischemia/reperfusion insult. Meanwhile, phosphatidylinositol-3 kinase/Akt (PI3K/Akt) is a well-known, important signaling pathway that mediates neuroprotection. However, it should be remains unclear whether the neuroprotective capabilities of TSA against cerebral ischemia/reperfusion is mediated by activation of the PI3K/Akt signaling pathway.

Methods: Five groups rats (n = 12 each), with middle cerebral artery occlusion (MCAO) except sham group, were used to investigate the neuroprotective effect of certain concentration (0.05 mg/kg) of TSA, and whether the neuroprotective effect of TSA is associated with activation of the PI3K/Akt signaling pathway through using of wortmannin (0.25 mg/kg).

Results: TSA significantly increased the expression of p-Akt protein, reduced infarct volume, and attenuated neurological deficit in rats with transient MCAO, wortmannin weakened such effect of TSA dramatically.

Conclusions: TSA could significantly decrease the neurological deficit scores and reduce the cerebral infarct volume during cerebral ischemia/reperfusion injury, which was achieved partly by activation of the PI3K/Akt signaling pathway via upgrading of p-Akt protein.

Keywords: Akt; PI3K/Akt signal pathway; TSA; cerebral ischemia/reperfusion injury; p-Akt.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Androstadienes / pharmacology
  • Animals
  • Brain Injuries / etiology
  • Brain Injuries / prevention & control
  • Brain Ischemia / complications
  • Brain Ischemia / drug therapy*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Hydroxamic Acids / therapeutic use*
  • Male
  • Nervous System Diseases / etiology
  • Nervous System Diseases / prevention & control
  • Neuroprotective Agents / therapeutic use*
  • Oncogene Protein v-akt / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / complications
  • Reperfusion Injury / prevention & control*
  • Signal Transduction / drug effects*
  • Wortmannin

Substances

  • Androstadienes
  • Enzyme Inhibitors
  • Hydroxamic Acids
  • Neuroprotective Agents
  • trichostatin A
  • Phosphatidylinositol 3-Kinases
  • Oncogene Protein v-akt
  • Wortmannin