Abstract
Stroke is the second-leading cause of death worldwide, and tissue plasminogen activator (TPA) is the only drug used for a limited group of stroke patients in the acute phase. Buyang Huanwu Decoction (BHD), a traditional Chinese medicine prescription, has long been used for improving neurological functional recovery in stroke. In this study, we characterized the therapeutic effect of TPA and BHD in a cerebral ischemia/reperfusion (CIR) injury mouse model using multiplex proteomics approach. After the iTRAQ-based proteomics analysis, 1310 proteins were identified from the mouse brain with <1% false discovery rate. Among them, 877 quantitative proteins, 10.26% (90/877), 1.71% (15/877), and 2.62% (23/877) of the proteins was significantly changed in the CIR, BHD treatment, and TPA treatment, respectively. Functional categorization analysis showed that BHD treatment preserved the integrity of the blood–brain barrier (BBB) (Alb, Fga, and Trf), suppressed excitotoxicity (Grm5, Gnai, and Gdi), and enhanced energy metabolism (Bdh), thereby revealing its multiple effects on ischemic stroke mice. Moreover, the neurogenesis marker doublecortin was upregulated, and the activity of glycogen synthase kinase 3 (GSK-3) and Tau was inhibited, which represented the neuroprotective effects. However, TPA treatment deteriorated BBB breakdown. This study highlights the potential of BHD in clinical applications for ischemic stroke.
Highlights
Stroke is a devastating neurological disease and the second-leading cause of death worldwide, with stroke cases being ischemic
After Buyang Huanwu Decoction (BHD) (1.0 g/kg, p.o., twice daily) or tissue plasminogen activator (TPA) (10 mg/kg, i.v., by tail vein at day one) treatment led to an improved the locomotor activity and behavior response in a novel open field were used to analyze neurological deficits in the cerebral ischemia/reperfusion (CIR) mice
The typical neurological deficit pattern was still observed in the TPA-treated group, it was distinctly improved in the BHD-treated group
Summary
Stroke is a devastating neurological disease and the second-leading cause of death worldwide, with stroke cases being ischemic. Excessive glutamate release stimulates neurons and induces neuronal death via oxidative stress, the overproduction of reactive oxygen species (ROS), and the massive inflammation generated by recruited leukocytes and activated microglial cells [2]. This acute inflammation can result in the activation of an inflammatory transcription factor (i.e., nuclear factor κB), which disrupts the blood–brain barrier (BBB) [3]. Increased GSK-3 activity contributes to the generation of a neuroinflammatory environment and impairs adult neurogenesis [9, 10] These results support the idea that the inhibition of GSK-3 is a potential target in the treatment of ischemic stroke. Any effective treatments for stroke are yet to be developed
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