title: VEGF protects rat cortical neurons from mechanical trauma injury induced apoptosis via the MEK/ERK pathway.
abstract: Traumatic brain injury (TBI) is a serious insult that frequently leads to neurological dysfunction or death. Vascular endothelial growth factor (VEGF) is a major regulator of angiogenesis and vascular permeability. Recently, VEGF has been identified as a neurotrophic factor and has been implicated in the pathogenic mechanisms of TBI. However, the possible mechanisms of VEGF in primary or secondary injuries after TBI are largely unknown. The present study attempted to determine whether VEGF has a protective effect on primary cortical neurons against mechanical trauma injury, which is an in vitro insult mimicking traumatic brain injury. We found that pretreatment of primary cortical neurons in culture with VEGF decreased neuronal death in a concentration-dependent manner, and VEGF counteracted the mechanical trauma mediated apoptotic death of cultured cortical neurons. VEGF up-regulates the activity of ERK (extracellular signal-regulated kinase) in cultured cortical neurons and U0126 (a mitogen activated protein kinase kinase (MEK) inhibitor) suppressed VEGF induced activity of ERK. Furthermore, incubation of cells with U0126 attenuated the ability of VEGF to protect neurons against mechanical trauma-induced apoptosis. Therefore, the present study supports the notion that MEK/ERK pathway is involved in VEGF mediated neuroprotection against mechanical trauma injury.
authors.affiliation: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Yihui
authors.initials: Y
authors.lastname: Ma
authors.forename: Wenbo
authors.initials: W
authors.lastname: Liu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Chao
authors.forename: Yan
authors.initials: Y
authors.lastname: Qu
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: Zhou
authors.initials: Z
authors.lastname: Fei
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001930:Brain Injuries / Q000473:pathology / Q000503:physiopathology; D002478:Cells, Cultured; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases