title: Hippocampal neurogenesis after traumatic brain injury is mediated by vascular endothelial growth factor receptor-2 and the Raf/MEK/ERK cascade.
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.
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
authors.forename: Kwok-Tung
authors.initials: KT
authors.lastname: Lu
authors.forename: Chien-Lun
authors.initials: CL
authors.lastname: Sun
authors.forename: Peter Y Y
authors.initials: PY
authors.lastname: Wo
authors.forename: Hao-Han
authors.initials: HH
authors.lastname: Yen
authors.forename: Tsao-Hao
authors.initials: TH
authors.lastname: Tang
authors.forename: Ming-Chong
authors.initials: MC
authors.lastname: Ng
authors.forename: Min-Lang
authors.initials: ML
authors.lastname: Huang
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Yang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D001930:Brain Injuries / Q000378:metabolism*; D002934:Cinnamates / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D008297:Male; D018613:Microscopy, Confocal; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D018709:Statistics, Nonparametric; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*; D048490:raf Kinases / Q000378:metabolism*
chemical_list: D002934:Cinnamates; C483044:SU 1498; D040301:Vascular Endothelial Growth Factor Receptor-2; D048490:raf Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D020930:MAP Kinase Kinase Kinases