VEGF-induced neuroprotection, neurogenesis, and angiogenesis after focal cerebral ischemia

Yunjuan Sun, Kunlin Jin, Lin Xie, Jocelyn Childs, Xiao Ou Mao, Anna Logvinova, David A. Greenberg

Research output: Contribution to journalArticle

947 Scopus citations

Abstract

Vascular endothelial growth factor (VEGF) is an angiogenic protein with therapeutic potential in ischemic disorders, including stroke. VEGF confers neuroprotection and promotes neurogenesis and cerebral angiogenesis, but the manner in which these effects may interact in the ischemic brain is poorly understood. We produced focal cerebral ischemia by middle cerebral artery occlusion for 90 minutes in the adult rat brain and measured infarct size, neurological function, BrdU labeling of neuroproliferative zones, and vWF-immunoreactive vascular profiles, without and with intracerebroventricular administration of VEGF on days 1-3 of reperfusion. VEGF reduced infarct size, improved neurological performance, enhanced the delayed survival of newborn neurons in the dentate gyrus and subventricular zone, and stimulated angiogenesis in the striatal ischemic penumbra, but not the dentate gyrus. We conclude that in the ischemic brain VEGF exerts an acute neuroprotective effect, as well as longer latency effects on survival of new neurons and on angiogenesis, and that these effects appear to operate independently. VEGF may, therefore, improve histological and functional outcome from stroke through multiple mechanisms.

Original languageEnglish
Pages (from-to)1843-1851
Number of pages9
JournalJournal of Clinical Investigation
Volume111
Issue number12
DOIs
StatePublished - Jun 2003

Fingerprint Dive into the research topics of 'VEGF-induced neuroprotection, neurogenesis, and angiogenesis after focal cerebral ischemia'. Together they form a unique fingerprint.

  • Cite this