Novel neuroprotective tetramethylpyrazine analog T-006 promotes neurogenesis and neurological restoration in a rat model of stroke

Neuroreport. 2019 Jun 12;30(9):658-663. doi: 10.1097/WNR.0000000000001256.

Abstract

Neuronal death is among the deleterious pathological changes that occur after cerebral ischemia and can lead to transient or permanent neurological deficits. The tetramethylpyrazine analog T-006 has been shown to be a multifunctional neuroprotective agent; however, its neuroprotective effect and mechanism of action have not been studied in ischemic stroke model rats. This study investigated the neuroprotective effects of T-006 in rat stroke model using a battery of behavioral and molecular biological tests. Results indicated that T-006 treatment significantly improved neurological function and behavior. Double immunofluorescence staining showed that T-006 visibly improved the number of NeuN/BrdU, Nestin/BrdU, and DCX/BrdU cells and induced neuronal regeneration. Western blot analyses indicated that T-006 upregulated neurogenesis-related protein expression of postsynaptic density protein 95, brain-derived neurotrophic factor, synaptophysin, and myelin basic protein. Collectively, these data suggest that T-006 stimulated neurogenesis in rats with middle cerebral artery occlusion and restored neurological functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Doublecortin Protein
  • Hydrazones / pharmacology*
  • Male
  • Nerve Regeneration / drug effects
  • Neurogenesis / drug effects*
  • Neuroprotective Agents / pharmacology*
  • Pyrazines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function / drug effects*
  • Stroke / pathology*

Substances

  • Dcx protein, rat
  • Doublecortin Protein
  • Hydrazones
  • Neuroprotective Agents
  • Pyrazines
  • T-006 compound