Abstract
Mature brain-derived neurotrophic factor (mBDNF) has neuroprotection in cerebral ischemia. Conversely, the precursor of brain-derived neurotrophic factor (proBDNF) has the opposite function to its mature form, inducing apoptosis. However, whether the neuroprotection of Panax notoginsenoside Rb1 (PNS-Rb1) on ischemic stroke is due to, at least partially, its modulation of suppressing proBDNF/P75NTR/sortilin or upregulation of mBDNF is not clear. To test this hypothesis, rats induced by photothrombotic stroke were treated with PNS-Rb1 100 mg/kg or nimodipine 1 mg/kg twice a day until 3, 7, and 14 days. Our data indicate that PNS-Rb1 significantly reduced cerebral infarction rate, proBDNF/P75NTR/sortilin, and plasminogen activator inhibitor-1 (PAI-1) protein levels, and improved sensorimotor dysfunctions induced by ischemic stroke, upregulation of BDNF/TrkB levels, and its processing enzymes (tissue plasminogen activator, tPA) in a time-dependent manner. Taken together, our findings indicate that the improvement of sensorimotor dysfunctions by PNS-Rb1 following ischemic stroke is made, at least partially, by activating the BDNF/TrkB and inhibiting proBDNF/sortilin/P75NTR.
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Author Contribution Statements
Study design: HY Luo and J Sun. Study conduct: CY Yang and JY Yang. Data collection: YX Xiong. Data analysis: H Su, S Hu, and XF Zhuang. Data interpretation: JQ Ma. Drafting manuscript: CY Yang and HY Luo. Revising manuscript content: XF Zhou. All authors have read and approved the final submitted manuscript.
Funding
This work was supported by the National Natural Science Foundation of China (81760064), Yunnan Applied Basic Research Project(2019FA040), Joint Special Fund Project of Yunnan Provincial Science and Technology Department-Kunming Medical University (2017FE467-025, 160, 163, 2017FE468-135, U012017515, and 2018FE001(-162)), Scientific Research Fund of Yunnan Provincial Education Department (2015Y180), and Innovative Experimental Program for Undergraduates in Kunming Medical University.
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All experimental procedures involving animals were approved by the Animal Ethics Committee of Kunming Medical University and conducted between 7 a.m. and 7 p.m. in accordance with the guidelines of the National Health and Medical Research Council of China. Rats were acclimatized for a week before any procedures were initiated.
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Yang, CY., Yang, JY., Xiong, YX. et al. Panax notoginsenoside Rb1 Restores the Neurotrophic Imbalance Following Photothrombotic Stroke in Rats. Neurotox Res 36, 441–451 (2019). https://doi.org/10.1007/s12640-019-00058-2
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DOI: https://doi.org/10.1007/s12640-019-00058-2