title: Over-expressed EGR1 may exaggerate ischemic injury after experimental stroke by decreasing BDNF expression.
abstract: OBJECTIVE
  This study aimed to clarify whether ischemia-induced early growth response 1 (EGR1) influenced the outcomes of experimental stroke by regulating brain-derived neurotrophic factor (BDNF) expression.
  
  
  RESULTS
  To mimic ischemia, mice were subjected to middle cerebral artery occlusion, and neurons challenged with oxygen-glucose deprivation. The expression of EGR1 was increased immediately and reached the peak 24h after reperfusion. To increase and to decrease EGR1 expressions, two types of recombinant lentiviruses were constructed. EGR1 over-expression induced by recombinant lentiviruses expanded infarct volumes and increased the numbers of terminal deoxynucleoitidyl transferase-mediated dUTP nick end labeling (TUNEL) and Fluoro-Jade C-positive cells; while decreased EGR1 expression induced by recombinant lentiviruses diminished infarct volumes and decreased the numbers of TUNEL- and Fluoro-Jade C-positive cells. Both in vitro and in vivo, increasing EGR1 expression with recombinant lentiviruses lead to decreased BDNF expressions; while silencing EGR1 expression with recombinant lentiviruses lead to increased BDNF expressions. Results from electrophoretic mobility shift assay indicated that EGR1 influenced the BDNF expression by binding to its promoter.
  
  
  CONCLUSIONS
  Ischemia-induced EGR1 expression may exaggerate brain injury by reducing BDNF expression. Inhibiting EGR1 may become a potential treatment for improving outcomes of ischemic stroke.
authors: Department of Neurology, Jinling Hospital, Southern Medical University, Nanjing, Jiangsu, China.
authors: L
authors: L
authors: Yang
authors: Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China.
authors: Y
authors: Y
authors: Jiang
authors: Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China.
authors: Z
authors: Z
authors: Wen
authors: Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China.
authors: X
authors: X
authors: Xu
authors: Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China.
authors: X
authors: X
authors: Xu
authors: Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China.
authors: J
authors: J
authors: Zhu
authors: Department of Neurology, Jinling Hospital, Southern Medical University, Nanjing, Jiangsu, China.
authors: X
authors: X
authors: Xie
authors: Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China.
authors: L
authors: L
authors: Xu
authors: Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China.
authors: Y
authors: Y
authors: Xie
authors: Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China.
authors: X
authors: X
authors: Liu
authors: Department of Neurology, Jinling Hospital, Southern Medical University, Nanjing, Jiangsu, China; Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China. Electronic address: gelinxu@gmail.com.
authors: G
authors: G
authors: Xu
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism*; D018014:Gene Transfer Techniques; D005947:Glucose / Q000172:deficiency; D006801:Humans; D020244:Infarction, Middle Cerebral Artery; D008297:Male; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D020521:Stroke / Q000378:metabolism* / Q000473:pathology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D005947:Glucose
keywords: BDNF; EGR1; infarct volume; ischemic stroke