Over-expressed EGR1 may exaggerate ischemic injury after experimental stroke by decreasing BDNF expression

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.

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.

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.