ABSTRACT
OBJECTIVE: To explore the effect and mechanism of schisandrin B (Sch B) in the treatment of cerebral ischemia in rats. METHODS: The cerebral ischemia models were induced by middle cerebral artery occlusion (MCAO) and reperfusion. Sprague-Dawley rats were divided into 6 groups using a random number table, including sham, MCAO, MCAO+Sch B (50 mg/kg), MCAO+Sch B (100 mg/kg), MCAO+Sch B (100 mg/kg)+LY294002, and MCAO+Sch B (100 mg/kg)+wortmannin groups. The effects of Sch B on pathological indicators, including neurological deficit scores, cerebral infarct volume, and brain edema, were subsequently studied. Tissue apoptosis was identified by terminal transferase-mediated dUTP nick end-labeling (TUNEL) staining. The protein expressions involved in apoptosis, inflammation response and oxidative stress were examined by immunofluorescent staining, biochemical analysis and Western blot analysis, respectively. The effect of Sch B on phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling was also explored. RESULTS: Sch B treatment decreased neurological deficit scores, cerebral water content, and infarct volume in MCAO rats (P<0.05 or P<0.01). Neuronal nuclei and TUNEL staining indicated that Sch B also reduced apoptosis in brain tissues, as well as the Bax/Bcl-2 ratio and caspase-3 expression (P<0.01). Sch B regulated the production of myeloperoxidase, malondialdehyde, nitric oxide and superoxide dismutase, as well as the release of cytokine interleukin (IL)-1 ß and IL-18, in MCAO rats (P<0.05 or P<0.01). Sch B promoted the phosphorylation of PI3K and AKT. Blocking the PI3K/AKT signaling pathway with LY294002 or wortmannin reduced the protective effect of Sch B against cerebral ischemia (P<0.05 or P<0.01). CONCLUSIONS: Sch B reduced apoptosis, inflammatory response, and oxidative stress of MCAO rats by modulating the PI3K/AKT pathway. Sch B had a potential for treating cerebral ischemia.
ABSTRACT
Cerebral edema (CDE) is a common complication in patients with acute ischemic stroke (AIS) and can reduce the benefit of endovascular therapy (EVT). To determine whether certain risk factors are associated with a poor prognosis mediated by CDE after EVT. The 759 patients with anterior circulation stroke treated by EVT at three comprehensive stroke centers in China from January 2014 to October 2020 were analyzed. Patients underwent follow-up for 3 months after inclusion. The primary endpoint was a measure of a poor prognosis (modified Rankin Scale score ≥ 3) at 3 months assessed in all patients receiving EVT. Least absolute shrinkage and selection operator and multivariate logistic regression were used to select variables for the prognostic nomogram. Based on these variables, the nomogram was established and validated. In addition, structural equation modeling was used to explore the pathways linking CDE and a poor prognosis. Seven predictors were identified, namely, diabetes, age, baseline Alberta Stroke Program Early CT score, modified Thrombolysis in Cerebral Infarction score, early angiogenic CDE, National Institutes of Health Stroke Scale score, and collateral circulation. The nomogram consisting of these variables showed the best performance, with a large area under the curve in both the internal validation set (0.850; sensitivity, 0.737; specificity, 0.887) and external validation set (0.875; sensitivity, 0.752; specificity, 0.878). In addition, CDE (total path coefficient = 0.24, P < 0.001) served as a significant moderator. A nomogram for predicting a poor prognosis after EVT in AIS patients was established and validated with CDE as a moderator.
