Hippocampal neurogenesis after traumatic brain injury is mediated by vascular endothelial growth factor receptor-2 and the Raf/MEK/ERK cascade

Kwok Tung Lu, Chien Lun Sun, Peter Y.Y. Wo, Hao Han Yen, Tsao Hao Tang, Ming Chong Ng, Min Lang Huang, Yi Ling Yang

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Adult neurogenesis occurs in the subgranular zone of the hippocampal dentate gyrus, and can be modulated by physiological and pathological events. We examined the effect of vascular endothelial growth factor (VEGF), and the correlation between VEGF and the Raf/MEK/ERK cascade in neurogenesis after traumatic brain injury (TBI). The expression of VEGF and the phosphorylation level of Raf/MEK/ERK were analyzed by Western blot, and TBI-induced neurogenesis was determined by immunofluorescence labeling and confocal microscopic detection. Hippocampal VEGF began to increase after 12 h, and reached a peak at day 7. Along with the upregulation of VEGF, neurogenesis in the hippocampus also increased. Administration of the VEGF antisense oligodeoxynucleotide, or the VEGF receptor-2 antagonist SU1498 (10 μg, ICV), attenuated the phosphorylation of the MAPK cascade proteins and caused a decrease in neurogenesis in the hippocampus. Similarly, administration of the ERK inhibitor PD98059 (500 ng, ICV) also exhibited a suppressive effect on neurogenesis. Our results indicate that VEGF plays an important role in neurogenesis after TBI, and that the process involves VEGF receptor-2 and the Raf/MEK/ERK cascade.

Original languageEnglish
Pages (from-to)441-450
Number of pages10
JournalJournal of Neurotrauma
Volume28
Issue number3
DOIs
Publication statusPublished - 2011 Mar 1

Keywords

  • hippocampus
  • mitogen-activated protein kinase
  • neurogenesis
  • rat
  • traumatic brain injury
  • vascular endothelial growth factor

ASJC Scopus subject areas

  • Clinical Neurology

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