Neuroprotective effects of the salidroside derivative SHPL-49 via the BDNF/TrkB/Gap43 pathway in rats with cerebral ischemia - 27/04/24
Abstract |
Ischemic stroke is a common intravascular disease and one of the leading causes of death and disability. The salidroside derivative SHPL-49, which we previously synthesized, significantly attenuates cerebral ischemic injury in a rat model of permanent middle cerebral artery occlusion. To explore the neuroprotective mechanism of SHPL-49, the effects of SHPL-49 on the expression levels of neurotrophic factors in neurons and microglia and the polarization of microglia were investigated in the present study. SHPL-49 activated the brain-derived neurotrophic factor (BDNF) pathway, decreased the number of degenerated neurons, and accelerated neurogenesis in rats with cerebral ischemia. In addition, SHPL-49 promoted the polarization of microglia toward the M2 phenotype to alleviate neuroinflammation. In BV2 cells, SHPL-49 upregulated CD206 mRNA and protein levels and inhibited CD86 mRNA and protein levels. SHPL-49 also increased neurotrophic factor secretion in BV2 cells, which indirectly promoted the survival of primary neurons after oxygen-glucose deprivation (OGD). Proteomics analysis revealed that SHPL-49 promoted growth-associated protein 43 (Gap43) expression. SHPL-49 enhanced synaptic plasticity and increased Gap43 protein levels via activation of the BDNF pathway in the OGD primary neuron model. These results indicate that SHPL-49 prevents cerebral ischemic injury by activating neurotrophic factor pathways and altering microglial polarization. Thus, SHPL-49 is a potential neuroprotective agent.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
We have a graphical abstract as shown in Fig. 10. (Line 2, Page 32)
We have a graphical abstract as shown in Fig. 10. (Line 2, Page 32)Le texte complet de cet article est disponible en PDF.
Highlights |
• | This study aims to investigate-neuroprotective mechanism of SHPL-49 in pMCAO rats. |
• | SHPL-49 exerts neuroprotective roles through BDNF/TrkB/Gap43 pathway. |
• | SHPL-49can be used as a potential neuroprotective agent in clinical trials. |
Keywords : Salidroside derivative, BDNF, Microglia, Polarization, Neuroprotection
Plan
Vol 174
Article 116460- mai 2024 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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