Abstract
Background: Ischemic stroke is a common disease with poor prognosis, which has become one of the leading causes of morbidity and mortality worldwide. Astragaloside IV (AS-IV) is the main bioactive ingredient of Astragali Radix (which has been used for ischemic stroke for thousands of years) and has been found to have multiple bioactivities in the nervous system. In the present study, we aimed to explore the neuroprotective effects of AS-IV in rats with cerebral ischemia/reperfusion (CIR) injury targeting the Sirt1/Mapt pathway. Methods: Sprague–Dawley rats (male, 250–280 g) were randomly divided into the Sham group, middle cerebral artery occlusion/reperfusion (MCAO/R) group, AS-IV group, MCAO/R + EX527 (SIRT1-specific inhibitor) group, and AS-IV + EX527 group. Each group was further assigned into several subgroups according to ischemic time (6 h, 1 d, 3 d, and 7 days). The CIR injury was induced in MCAO/R group, AS-IV group, MCAO/R + EX527 group, and AS-IV + EX527 group by MCAO surgery in accordance with the modified Zea Longa criteria. Modified Neurological Severity Scores (mNSS) were used to evaluate the neurological deficits; TTC (2,3,5-triphenyltetrazolium chloride) staining was used to detect cerebral infarction area; Western Blot was used to assess the protein levels of SIRT1, acetylated MAPT (ac-MAPT), phosphorylated MAPT (p-MAPT), and total MAPT (t-MAPT); Real-time Quantitative Polymerase Chain Reaction (qRT-PCR) was used in the detection of Sirt1 and Mapt transcriptions. Results: Compared with the MCAO/R group, AS-IV can significantly improve the neurological dysfunction (p < 0.05), reduce the infarction area (p < 0.05), raise the expression of SIRT1 (p < 0.05), and alleviate the abnormal hyperacetylation and hyperphosphorylation of MAPT (p < 0.05). While compared with the AS-IV group, AS-IV + EX527 group showed higher mNSS scores (p < 0.05), more severe cerebral infarction (p < 0.05), lower SIRT1 expression (p < 0.01), and higher ac-MAPT and p-MAPT levels (p < 0.05). Conclusion: AS-IV can improve the neurological deficit after CIR injury in rats and reduce the cerebral infarction area, which exerts neuroprotective effects probably through the Sirt1/Mapt pathway.
Highlights
Ischemic stroke has become one of the leading causes of death and acquired disability world widely (James et al, 2018)
After a week of adaptation to the experimenter, SD rats were randomly divided into 5 groups: Sham group, middle cerebral artery occlusion/reperfusion (MCAO/R) group, Astragaloside IV (AS-IV) group, MCAO/R + EX527 group, and AS-IV + EX527 group
The neurological deficiency score (NDS) was evaluated at 6 h, 1 d, 3 d, and 7 days after cerebral ischemia/reperfusion (CIR) according to modified neurological severity score (mNSS) criteria
Summary
Ischemic stroke has become one of the leading causes of death and acquired disability world widely (James et al, 2018). Early intervention after symptom onset is important to improve the prognosis of ischemic stroke. Intravenous thrombolysis and mechanical thrombectomy are effective therapies according to the 2018 guideline from the American Heart Association/ American Stroke Association (AHA/ASA) (Khatri et al, 2018; Powers et al, 2019). Mechanical thrombectomy should be performed within 24 h, requiring trained vascular surgeons and specialized stroke centers, which limits its universality (Moussaddy et al, 2018). It is urgent to explore novel treatment options of ischemic stroke. Ischemic stroke is a common disease with poor prognosis, which has become one of the leading causes of morbidity and mortality worldwide. We aimed to explore the neuroprotective effects of AS-IV in rats with cerebral ischemia/reperfusion (CIR) injury targeting the Sirt1/Mapt pathway
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