Probucol protects against brain damage caused by intra-neural pyroptosis in rats with vascular dementia through inhibition of the Syk/Ros pathway.

BACKGROUND: Neuronal injury in chronic cerebral hypoperfusion (CCH) is the main pathogenic factor of vascular dementia (VD). Clinically, there isn't a drug specifically for VD; instead, the majority of medications used to treat Alzheimer's disease (AD) are also used to treat VD. Based on the proven anti-inflammatory and antioxidant effects of Probucol, we hypothesized that it may have therapeutic effects on VD, but more research is required to determine its exact mechanism of action. METHODS: In vivo experiment: We used SD rats and most commonly used bilateral carotid artery occlusion (2-VO) in VD for modeling. After successful modeling, SD rats were given Probucol 3.5 mg/kg/day for 8 weeks to evaluate the therapeutic effect. In vitro experiment: BV-2 microglia of rats were cultured and divided into Control group and Probucol group. Each group was treated with hypoxia-hypoglycemia, hypoxia-hypoglycemia hydrogen peroxide and hypoxia-hypoglycemia hydrogen peroxide Syk inhibitor respectively. RESULTS: The results of immunofluorescence and Western blot showed that Probucol could significantly improve the cognitive impairment induced by CCH, and the neuronal damage was also attenuated. On the one hand, the underlying mechanism of Probucol was to reduce oxidative stress and cell apoptosis of hippocampal neurons by inhibiting the expression of phosphorylated spleen tyrosine kinase (P-Syk); On the other hand, it exerted a protective effect by reducing NLRP3-dependent cell pyroptosis and inhibiting neuroinflammation induced by microglia activation. CONCLUSION: Probucol could reduce oxidative stress and cell apoptosis by inhibiting the Syk/ROS signaling pathway, thereby improving CCH-induced cognitive impairment in vitro and in vivo.

Endovascular treatment vs drug therapy alone in patients with mild ischemic stroke and large infarct cores.

BACKGROUND: Treatment decision making is strictly associated with the outcomes in patients with ischemic stroke who show a large core infarct. Medical care alone may result in suboptimal treatment efficacy, and endovascular treatment may be accompanied by safety issues. Whether endovascular treatment is superior to medical care is not well investigated in the clinical studies. AIM: To investigate the efficacy of endovascular treatment and drug therapy alone in mild ischemic stroke patients with large infarct cores. METHODS: Fifty patients with mild ischemic stroke and 50 patients with acute ischemic stroke caused by anterior large vessel occlusion were selected at the First Affiliated Hospital of Hebei North University between January 2021 and December 2021. Patients were divided into an endovascular therapy group and a drug therapy group according to different treatment methods. In the endovascular therapy group, there were 28 patients with minor stroke and 22 patients with large infarct cores. The drug therapy group had 22 patients with minor stroke and 28 patients with large infarct cores. The National Institutes of Health Stroke Scale (NIHSS) scores were collected and compared between the two groups immediately after the operation and 24 h and 7 d after the operation. The modified Rankin scale (mRS) and/or activity of daily living were assessed at hospital discharge. RESULTS: There was no significant difference in NIHSS scores between the two groups before the operation (P > 0.05). NIHSS scores were lower in the endovascular therapy group than in the drug therapy group at 24 h and 7 d after the operation and at hospital discharge (all P < 0.05). The incidence of early neurologic deterioration was significantly lower in the endovascular therapy group than in the drug therapy group (P < 0.05). At hospital discharge, the mRS score was lower in the endovascular treatment group than in the drug therapy group, and the activity of daily living score was better in the endovascular treatment group than in the drug therapy group (all P < 0.05). During a follow-up of 3 mo, 17 patients (34.0%) had good prognosis (mRS ≤ 2), 33 patients (66.0%) had poor prognosis (mRS > 2), and 11 patients (22.0%) died. In the medical treatment group, 16 patients (mRS ≤ 2) had good prognosis (32.0%), 34 patients (mRS > 2) had poor prognosis (68.0%), and 14 patients (28.0%) died. There was no significant difference in prognosis and mortality between the two groups (P > 0.05). CONCLUSION: Endovascular therapy can improve NIHSS score and mRS score in patients with mild ischemic stroke and large infarct cores. It is suitable for clinical application.

Magnetic Resonance Images, Pathological Features of Thrombus, and Expression of NLRP Inflammasome in Patients with Acute Ischemic Stroke.

The aim of this study was to investigate imaging features of magnetic resonance imaging (MRI), pathological features of thrombus, and expression of nucleotide-binding oligomerization domain-like receptors protein 3 (NLRP3) inflammasome in acute ischemic stroke (AIS). Their relationship with the prognosis of patients was also explored. Sixty patients with AIS admitted to the hospital were selected as the observation group, and 20 healthy objects were in the control group. The shape of the thrombus was observed by MRI, pathological features of the thrombus were observed under hematoxylin-eosin (HE) staining, and the levels of NLRP3 inflammasome and inflammatory factors in serum were detected. The MRI-T2 weighted imaging (T2WI) signal ratio and plaque enhancement rate in the observation group were higher than those in the control group significantly (P < 0.05). In the observation group, the red/mixed thrombus in 6-12 h and 24 h were also much higher than that in 6 h (P < 0.05). The levels of NLRP3, interleukin-1ß (IL-1ß), interleukin-18 (IL-18), and tumor necrosis factor-α (TNF-α) in the observation group were higher than those in the control group in 6 h, 6-12 h, and 24 h (P < 0.05), and those reached the highest levels in 24 h. The ratio of fibrins/platelets in the cardiogenic thrombus reached (63.8 ± 15.6) %, which was significantly higher than that in the large-artery atherosclerotic thrombus (49.5 ± 14.2) %, P < 0.05. The ratio of red blood cells (RBCs) in the large atherosclerotic thrombus was (30.7 ± 14.3) %, considerably lower than (42.9 ± 15.2) %, P < 0.05. The prognosis of patients with the fibrin/platelet-rich thrombus was highly lower than that with the RBC-rich thrombus (P < 0.05). The levels with poor prognosis were higher than those with good prognosis (P < 0.05). MRI could be used to assist in the assessment of brain conditions in patients with AIS. NLRP3 inflammasome was involved in the inflammatory response of AIS and can be used for predicting the poor prognosis, having a certain clinical application value. In addition, different types of thrombi also laid a certain impact on prognosis.