Venlafaxine treatment after endothelin-1-induced cortical stroke modulates growth factor expression and reduces tissue damage in rats

Rodrigo Zepeda, Valentina Contreras, Claudia Pissani, Katherine Stack, Macarena Vargas, Gareth I. Owen, Oscar M. Lazo, Francisca C. Bronfman

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Neuromodulators, such as antidepressants, may contribute to neuroprotection by modulating growth factor expression to exert anti-inflammatory effects and to support neuronal plasticity after stroke. Our objective was to study whether early treatment with venlafaxine, a serotonin-norepinephrine reuptake inhibitor, modulates growth factor expression and positively contributes to reducing the volume of infarcted brain tissue resulting in increased functional recovery. We studied the expression of BDNF, FGF2 and TGF-β1 by examining their mRNA and protein levels and cellular distribution using quantitative confocal microscopy at 5 days after venlafaxine treatment in control and infarcted brains. Venlafaxine treatment did not change the expression of these growth factors in sham rats. In infarcted rats, BDNF mRNA and protein levels were reduced, while the mRNA and protein levels of FGF2 and TGF-β1 were increased. Venlafaxine treatment potentiated all of the changes that were induced by cortical stroke alone. In particular, increased levels of FGF2 and TGF-β1 were observed in astrocytes at 5 days after stroke induction, and these increases were correlated with decreased astrogliosis (measured by GFAP) and increased synaptophysin immunostaining at twenty-one days after stroke in venlafaxine-treated rats. Finally, we show that venlafaxine reduced infarct volume after stroke resulting in increased functional recovery, which was measured using ladder rung motor tests, at 21 days after stroke. Our results indicate that the early oral administration of venlafaxine positively contributes to neuroprotection during the acute and late events that follow stroke.

Original languageEnglish
Pages (from-to)131-145
Number of pages15
JournalNeuropharmacology
Volume107
DOIs
Publication statusPublished - Aug 2016
Externally publishedYes

Keywords

  • Antidepressant
  • BDNF
  • FGF2
  • Neuroprotection
  • Sensorimotor recovery
  • Stroke
  • TGF-β1
  • Venlafaxine

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

Fingerprint

Dive into the research topics of 'Venlafaxine treatment after endothelin-1-induced cortical stroke modulates growth factor expression and reduces tissue damage in rats'. Together they form a unique fingerprint.

Cite this