Neuroprotective Effect of VEGF-Mimetic Peptide QK in Experimental Brain Ischemia Induced in Rat by Middle Cerebral Artery Occlusion

Giuseppe Pignataro, Barbara Ziaco, Anna Tortiglione, Rosaria Gala, Ornella Cuomo, Antonio Vinciguerra, Dominga Lapi, Teresa Mastantuono, Serenella Anzilotti, Luca Domenico D'Andrea, Carlo Pedone, Gianfranco Di Renzo, Lucio Annunziato, Mauro Cataldi

Research output: Contribution to journalArticlepeer-review

Abstract

We investigated the effect of the VEGF-mimetic peptide, QK, on ischemic brain damage and on blood-brain barrier permeability in the rat. QK administered by the intracerebroventricular, intravenous, or intranasal route caused a 40% decrease in ischemic brain damage induced by permanent occlusion of the middle cerebral artery relative to that in controls. No increase in the volume of the ischemic hemisphere compared to that of the contralateral nonischemic hemisphere was observed in rats treated with QK, suggesting that this peptide did not cause brain edema. The effect of QK on vessel permeability was evaluated by intravital pial microvessel videoimaging, a technique that allows the pial vessels to be visualized through a surgically prepared open cranial window. The results showed that QK did not cause any leakage of intravenously injected fluorescein-dextran conjugates after intracarotid administration or topical application to the brain cortex. Collectively, these data suggest that QK may exert neuroprotective activity in the context of stroke without promoting any increase in vascular permeability. Because VEGF's neuroprotective activity may be overshadowed by the appearance of brain edema and microbleeds, QK could represent a significant step forward in stroke treatment.

Original languageEnglish
Pages (from-to)1517-1525
Number of pages9
JournalACS Chemical Neuroscience
Volume6
Issue number9
DOIs
Publication statusPublished - Jul 14 2015

Keywords

  • brain edema
  • Cerebral ischemia
  • neuroprotection
  • vascular endothelial growth factor
  • vascular permeability

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Physiology
  • Cognitive Neuroscience

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