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Neuroprotective Effect of Triptolide in Colony-Stimulating Factor 1 Receptor Inhibitor Treated Mice Model of Cerebral Ischemia
31 Pages Posted: 22 Sep 2019
More...Abstract
Background: Microglia activation is essential for regulating neuronal apoptosis, promoting neurogenesis and functional recovery in stroke. Ki20227, a specific inhibitor of colony-stimulating factor 1 receptor (CSF1R), regulates the morphology and density of microglia and neuronal synaptic plasticity. Triptolide (TP) has neuroprotective in stroke via regulation of autophagy and oxidative stress. However, regarding Ki20227 treated mice, the neuroprotective mechanism of TP has not been elucidated.
Methods: We built a stroke model after administering Ki20227 for 7 days in C57BL/6 mice. Behavioral tests, Golgi staining, immunofluorescence and western blot were assessed to evaluate the neuroprotective effects of TP.
Finding: TP improved the neurobehavioral function score of mice treated with Ki20227. The expression of the synaptic protein expressions, PSD95 and SYN, and the density of dendritic spines were increased in Ki20227 treated stroke mice with TP administration. Also, there was an upregulation of BDNF and Akt protein expressions whereas LC3II/I and Atg5 protein expressions were downregulated in Ki20227 treated stroke mice with TP administration.
Interpretation: Taking our results into consideration, TP can improve cerebral ischemia by inhibiting autophagy and activate the BDNF-Akt signaling pathway to increase the density of dendritic spine and synaptic proteins, which in turn enhances neurobehavioral function.
Funding Statement: This study was supported by the National Natural Science Foundation of China to Marong Fang (grant numbers 81671138 and 81871063).
Declaration of Interests: The authors have declared no conflict of interest.
Ethics Approval Statement: All Institutional and National Guidelines for the care and use of animals were followed. Animal treatment was approved by the Ethics Committee for Use of Experimental Animals in Zhejiang University.
Keywords: Stroke, triptolide, synaptic plasticity, colony-stimulating factor 1 receptor inhibitor, Ki20227
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