Silencing VEGF-B Diminishes the Neuroprotective Effect of Candesartan Treatment After Experimental Focal Cerebral Ischemia

Tauheed Ishrat, Sahar Soliman, Wael Eldahshan, Bindu Pillai, Adviye Ergul, Susan C. Fagan

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

The pro-survival effect of VEGF-B has been documented in different in vivo and in vitro models. We have previously shown an enhanced VEGF-B expression in response to candesartan treatment after focal cerebral ischemia. In this study, we aimed to silence VEGF-B expression to assess its contribution to candesartan’s benefit on stroke outcome. Silencing VEGF-B expression was achieved by bilateral intracerebroventricular injections of lentiviral particles containing short hairpin RNA (shRNA) against VEGF-B. Two weeks after lentiviral injections, rats were subjected to either 90 min or 3 h of middle cerebral artery occlusion (MCAO) and randomized to intravenous candesartan (1 mg/kg) or saline at reperfusion. Animals were sacrificed at 24 or 72 h and brains were collected and analyzed for hemoglobin (Hb) excess and infarct size, respectively. Functional outcome at 24, 48 and 72 h was assessed blindly. Candesartan treatment improved neurobehavioral and motor function, and decreased infarct size and Hb. While silencing VEGF-B expression diminished candesartan’s neuroprotective effect, candesartan-mediated vascular protection was maintained even in the absence of VEGF-B suggesting that this growth factor is not the mediator of candesartan’s vascular protective effects. However, VEGF-B is a mediator of neuroprotection achieved by candesartan and represents a potential drug target to improve stroke outcome. Further studies are needed to elucidate the underlying molecular mechanisms of VEGF-B in neuroprotection and recovery after ischemic stroke.

Original languageEnglish (US)
Pages (from-to)1869-1878
Number of pages10
JournalNeurochemical Research
Volume43
Issue number10
DOIs
StatePublished - Oct 1 2018

Keywords

  • Angiotensin II type-1 receptor blocker (ARB)
  • Candesartan
  • Neuroprotection
  • Stroke
  • Vascular endothelial growth factor-B (VEGF-B)

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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