pd-151746 and Stroke

pd-151746 has been researched along with Stroke* in 1 studies

Other Studies

1 other study(ies) available for pd-151746 and Stroke

ArticleYear
Enriched housing promotes post-stroke neurogenesis through calpain 1-STAT3/HIF-1α/VEGF signaling.
    Brain research bulletin, 2018, Volume: 139

    Enriched environment (EE) has been shown to promote neurogenesis and functional recovery after ischemic stroke. However, the underlying molecular mechanisms are not fully understood. In this study, C57BL/6 mice underwent middle cerebral artery occlusion (60 min) followed by reperfusion, after which mice were housed in either standard environment (SE) or EE and allowed to survive for 3, 4, 6 or 10 weeks. Ipsilateral subventricular zone (SVZ) or striatum cells were dissociated from ischemic hemispheric brains of enriched mice at 14 days post-ischemia (dpi) and cultured in vitro. Our data showed that post-ischemic EE inhibited calpain 1 activity, and increased the expression of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in the ischemic hemisphere of enriched mice at 21 dpi. Calpain 1-specific inhibitor PD151746 further increased p-STAT3 expression and augmented the promoting effects of EE on post-stroke SVZ neural precursor cells (NPCs) proliferation and functional recovery. EE also increased the expression of hypoxia-inducible factor 1-alpha (HIF-1α) and vascular endothelial growth factor (VEGF) in the ischemic hemisphere at 21 dpi. Inhibition of the JAK/STAT3 pathway with AG490 decreased the expression of HIF-1α and VEGF. Furthermore, inhibition of HIF-1α with 2-methoxyestradiol robustly abolished EE-induced elevation of VEGF l expression. Furthermore, VEGF-A promoted the production and secretion of high mobility group box-1 protein (HMGB1) from reactive astrocytes in vitro. Culture supernatant from reactive astrocytes treated with VEGF-A promoted the proliferation and differentiation of NPCs. Glycyrrhizin reversed the promoting effects of EE on post-stroke neurorepair and functional recovery in vivo. Taken together, our data indicate that EE promotes post-stroke functional recovery through the inhibition of calpain 1 activity, and subsequent STAT3-HIF-1α-VEGF-mediated neurogenesis.

    Topics: Acrylates; Analysis of Variance; Animals; Astrocytes; Bromodeoxyuridine; Calpain; Cells, Cultured; Disease Models, Animal; Housing; Hypoxia-Inducible Factor 1, alpha Subunit; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; Neurogenesis; Psychomotor Performance; Recovery of Function; Signal Transduction; STAT3 Transcription Factor; Stroke; Swimming; Vascular Endothelial Growth Factor A

2018