Abstract
Background Astrogliosis can result in astrocytes with hypertrophic morphology after injury, indicated by extended processes and swollen cell bodies. Lipocalin-2 (LCN2), a secreted glycoprotein belonging to the lipocalin superfamily, has been reported to play a detrimental role in ischaemic brains and neurodegenerative diseases. Sailuotong (SLT) capsule is a standardized three-herb preparation composed of ginseng, ginkgo, and saffron for the treatment of vascular dementia. Although recent clinical trials have demonstrated the beneficial effect of SLT on vascular dementia, its potential cellular mechanism has not been fully explored. Methods Male adult Sprague-Dawley (SD) rats were subjected to microsphere-embolized cerebral ischaemia. Immunostaining and Western blotting were performed to assess astrocytic reaction. Human astrocytes exposed to oxygen-glucose deprivation (OGD) were used to elucidate the effects of SLT-induced inflammation and astrocytic reaction. Results A memory recovery effect was found to be associated with the cerebral ischaemia-induced expression of inflammatory proteins and the suppression of LCN2 expression in the brain. Additionally, SLT reduced the astrocytic reaction, LCN2 expression, and the phosphorylation of STAT3 and JAK2. For in vitro experiments, OGD-induced expression of inflammation and LCN2 was also decreased in human astrocyte by the SLT treatment. Moreover, LCN2 overexpression significantly enhanced the above effects. SLT downregulated these effects that were enhanced by LCN2 overexpression. Conclusions SLT mediates neuroinflammation, thereby protecting against ischaemic brain injury by inhibiting astrogliosis and suppressing neuroinflammation via the LCN2-JAK2/STAT3 pathway, providing a new idea for the treatment strategy of ischaemic stroke.
Highlights
The incidence of stroke around the world has reached epidemic levels
These injuries are caused by a decrease in blood circulation, followed by the activation of intravascular leukocytes and the concomitant release of inflammatory cytokines from the ischaemic brain parenchyma and endothelium, all of which have the potential to increase the damage to central nervous system (CNS) tissues [3]
We investigated two questions: does SLT treatment alleviate reactive astrocytes and, mediate neuroinflammation, and if so, does the benefit of SLT treatment involve the inhibition of Janus kinase-2 (JAK2) signal transducer and activator of transcription-3(STAT3-) mediated LCN2 expression?
Summary
The incidence of stroke around the world has reached epidemic levels. In the past two decades, there have been marked increases in strokes, the number of living stroke victims, the population-level loss of life (called disability-adjusted life years or DALYs), and the number of deaths related to strokes [1]. Inflammation is a serious aspect of the disease development of ischaemic stroke and other types of ischaemic brain injury. These injuries are caused by a decrease in blood circulation, followed by the activation of intravascular leukocytes and the concomitant release of inflammatory cytokines from the ischaemic brain parenchyma and endothelium, all of which have the potential to increase the damage to central nervous system (CNS) tissues [3]. A memory recovery effect was found to be associated with the cerebral ischaemia-induced expression of inflammatory proteins and the suppression of LCN2 expression in the brain. OGD-induced expression of inflammation and LCN2 was decreased in human astrocyte by the SLT treatment. SLT mediates neuroinflammation, thereby protecting against ischaemic brain injury by inhibiting astrogliosis and suppressing neuroinflammation via the LCN2-JAK2/STAT3 pathway, providing a new idea for the treatment strategy of ischaemic stroke
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.
