Abstract
Stroke is one of the most devastating diseases worldwide. The Chinese herbal preparation SaiLuoTong (SLT) capsule showed outstanding therapeutic effects on stroke and its sequelae. The aim of this study was to further elucidate its therapeutic mechanism. We duplicated a permanent cerebral ischemia model in rats by MCAO and used SLT (33 and 16.5 mg/kg) to intervene. The results showed SLT dose dependently decreased infarction volumes, relieved neuron degeneration and loss, and ameliorated neurological functions, and the dose of 33 mg/kg had statistical significance (compared with the model group, p < 0.05); SLT of 33 mg/kg also significantly inhibited the elevation in brain water content and the loss in claudin-1 and occludin expressions; additionally, it significantly increased nucleus translocation of Nrf2, elevated the expression of HO-1, and raised the activity of SOD and content of GSH (compared with the model group, p < 0.05 or 0.01). These results testified SLT’s anti-brain ischemia effect and hint this effect may be related to the protection of brain microvascular endothelial cells (BMECs) that is dependent on the Nrf2 pathway. To further testify, we cultured hCMEC/D3 cells, duplicated OGD/R model to simulate ischemia, and used SLT (3.125, 6.25, and 12.5 mg/L) to treat. SLT dose dependently and significantly inhibited the drop in cell viabilities, and activated the Nrf2 pathway by facilitating Nrf2 nucleus translocation, and increasing HO-1 expression, SOD activity, and GSH content (compared with the model group, p < 0.05 or 0.01); last, the anti-OGD/R effects of SLT, including raising cell viabilities, inhibiting the elevation in dextran permeability, and preserving expressions of claudin-1 and occludin, were all abolished by Nrf2 siRNA interference. The in vitro experiment undoubtedly confirmed the direct protective effect of SLT on BMECs and the obligatory role of the Nrf2 pathway in it. Collectively, data of this study suggest that SLT’s therapeutic effect on brain ischemia is related to its Nrf2-dependent BMECs protection.
Highlights
Stroke is one of the leading causes of disability and death worldwide, which produces immense health and economic burdens
In the sham group, no neuron damage, neuron loss, or other notable morphological abnormalities were shown in the brain microscopy; necrosis of large areas was observed in the model group, in which severe neuron loss, neuron cell degeneration including cytoplasm acidophilic degeneration, and nuclear pyknosis were shown; tissue edema and neuron hydropic degeneration were shown in the regions peripheral to necrosis, and these lesions were notably attenuated in SLT-treated groups, especially in the SLT-H group (Figure 1C)
Neurological deficit scores were significantly elevated in the model group in comparison to the sham group (p < 0.01), indicating a severe injury in neurological function was induced by brain ischemia
Summary
Stroke is one of the leading causes of disability and death worldwide, which produces immense health and economic burdens. Most of strokes are the ischemic type, which occupies 80% of the total cases. It is usually triggered by obstructions of one or more cerebral arteries, which lead to a critical reduction of regional cerebral blood flow, causing a waterfall-like cascade, and resulting in massive neuron deaths (Donnan et al, 2008). In this damage cascade, the ruin of the brain–blood barrier (BBB) plays a pivotal role. The endothelium of cerebral microvascular is unique compared to that in other tissues, as they have continuous intercellular tight junctions (TJs) and efflux transporters, and the endothelium and their TJs form a barrier-like structure, which can greatly limit both the paracellular and transcellular diffusion of vascular inclusions, and constitute the BBB (Bazzoni et al, 2004; Abbott et al, 2006)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
