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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

See all articles by Xiaoxue Du

Xiaoxue Du

Zhejiang University - Institute of Neuroscience

Xiaoning Tan

Zhejiang University - Institute of Neuroscience

Benson O. A. Botchway

Zhejiang University - Institute of Neuroscience

Nashwa Amin

Zhejiang University - Institute of Neuroscience

Zhiying Hu

Hangzhou Red Cross Hospital

Marong Fang

Zhejiang University - Institute of Neuroscience

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

Suggested Citation

Du, Xiaoxue and Tan, Xiaoning and Botchway, Benson O. A. and Amin, Nashwa and Hu, Zhiying and Fang, Marong, Neuroprotective Effect of Triptolide in Colony-Stimulating Factor 1 Receptor Inhibitor Treated Mice Model of Cerebral Ischemia (September 20, 2019). Available at SSRN: https://ssrn.com/abstract=3454687 or http://dx.doi.org/10.2139/ssrn.3454687

Xiaoxue Du

Zhejiang University - Institute of Neuroscience

Hangzhou, 310058
China

Xiaoning Tan

Zhejiang University - Institute of Neuroscience

Hangzhou, 310058
China

Benson O. A. Botchway

Zhejiang University - Institute of Neuroscience

Hangzhou, 310058
China

Nashwa Amin

Zhejiang University - Institute of Neuroscience

Hangzhou, 310058
China

Zhiying Hu

Hangzhou Red Cross Hospital ( email )

Hangzho
China

Marong Fang (Contact Author)

Zhejiang University - Institute of Neuroscience ( email )

Hangzhou, 310058
China

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