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Role of vascular endothelial growth factor in neuronal DNA damage and repair in rat brain following a transient cerebral ischemia
Author(s) -
Yang ZengJin,
Bao WeiLi,
Qiu MeiHong,
Zhang LingMei,
Lu ShiDuo,
Huang YaLin,
Sun FengYan
Publication year - 2002
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.10380
Subject(s) - penumbra , vascular endothelial growth factor , in situ hybridization , ischemia , biology , pathology , neuroprotection , brain ischemia , messenger rna , medicine , cancer research , pharmacology , vegf receptors , biochemistry , gene
The antisense knockdown technique and confocal laser scanning microscopic analysis were used to elucidate vascular endothelial growth factor (VEGF) induction and its effect on DNA damage and repair in rat brain following a transient middle cerebral artery occlusion. Immunohistochemical study and in situ hybridization showed that the expression of VEGF and its mRNA was enhanced in the ischemic core and penumbra of ischemic brain. Western blot analysis further illustrated that VEGF induction was time‐dependently changed in these areas. Double‐staining analysis indicated that VEGF‐positive staining existed in the neuron, but not in the glia, and it colocalized with excision repair cross‐complementing group 6 (ERCC6) mRNA, a DNA repair factor. VEGF antisense oligodeoxynucleotide infusion reduced VEGF induction and resulted in an enlargement of infarct volume of the brain caused by ischemia. Moreover, it also increased the number of DNA damaged cells and lessened the induction of ERCC6 mRNA in ischemic brains. These results suggest that the induction of endogenous VEGF in ischemic neurons plays a neuroprotective role probably associated with the expression of ERCC6 mRNA. © 2002 Wiley‐Liss, Inc.