Protection against Neurological Symptoms by Consuming Corn Silk Water Extract in Artery-Occluded Gerbils with Reducing Oxidative Stress, Inflammation, and Post-Stroke Hyperglycemia through the Gut-Brain Axis

Corn silk (Stigma maydis), rich in flavonoids, is traditionally used to treat edema, depression, and hyperglycemia and may alleviate ischemic stroke symptoms in Chinese medicine. This study examined whether corn silk water extract (CSW) could alleviate ischemic stroke symptoms and post-stroke hyperglycemia in Mongolian gerbils with transient cerebral ischemia and reperfusion (I/R). After being given 0.05% (I/R-LCSW) and 0.2% (I/R-HCSW), 0.02% aspirin (I/R-aspirin), and cellulose (I/R-control) in their 40 energy% fat diets for three weeks, the gerbils underwent an artery occlusion for eight minutes and reperfusion. They took the assigned diet for an additional three weeks. Sham-operated gerbils without artery occlusion had the same diet as Sham-control. CSW intake reduced neuronal cell death in gerbils with I/R and dose-dependently improved the neurological symptoms, including drooped eyes, crouched posture, flexor reflex, and walking patterns. CSW intake also alleviated the short-term memory and spontaneous alteration and grip strength compared to the I/R-control group. The protection against ischemic stroke symptoms was associated with the reduced tumor necrosis factor-α, interleukin-1β, superoxide, and lipid peroxide levels, promoting superoxide dismutase activity in the hippocampus in the CSW groups, compared to the I/R-control. The blood flow measured by Doppler was improved with CSW compared to the I/R-control. Furthermore, CSW intake prevented the post-stroke hyperglycemia related to decreasing pancreatic β-cell mass as much as the Sham-control, and it was related to protection against β-cell apoptosis, restoring the β-cell mass similar to the Sham-control. CSW intake elevated the relative abundance of Lactobacillus, Bifidobacterium, Allobaculum, and Akkermansia compared to the I/R-control. Picrust2 analysis showed that CSW increased the propionate and butyrate metabolism and the starch and glucose metabolism but reduced lipopolysaccharide biosynthesis compared to the I/R-control. In conclusion, CSW intake protects against neuronal cell death and post-hyperglycemia by reducing oxidative stress and inflammation and increasing blood flow and the β-cell mass. The alleviation was associated with promoting the gut-brain axis by changing the gut microbiome community.

Evolution of Hypodensity on Non-Contrast CT in Correlation with Collaterals in Anterior Circulation Stroke with Successful Endovascular Reperfusion

Introduction: The aim of the study was to assess the impact of collaterals on the evolution of hypodensity on non-contrast CT (NCCT) in anterior circulation stroke with reperfusion by mechanical thrombectomy (MT). Methods: We retrospectively included stroke patients with middle cerebral artery occlusion who were reperfused by MT in early and late time window. Artificial intelligence (AI)-based software was used to calculate of hypodensity volumes at baseline NCCT (V1) and at follow-up NCCT 24 h after MT (V2), along with the difference between the two volumes (V2-V1) and the follow-up (V2)/baseline (V1) volume ratio (V2/V1). The same software was used to classify collateral status by using a 4-point scale where the score of zero indicated no collaterals and the score of three represented contrast filling of all collaterals. The volumetric values were correlated with the collateral scores. Results: Collateral scores had significant negative correlation with V1 (p = 0.035), V2, V2− V1 and V2/V1 (p < 0.001). In cases with collateral score = 3, V2 was significantly smaller or absent compared to V1; in those with collateral score 2, V2 was slightly larger than V1, and in those with scores 1 and 0 V2 was significantly larger than V1. These relationships were observed in both early and late time windows. Conclusions: The collateral status determined the evolution of the baseline hypodensity on NCCT in patients with anterior circulation stroke who had MT reperfusion. Damage can be stable or reversible in patients with good collaterals while in those with poor collaterals tissues that initially appear normal will frequently appear as necrotic after 24 h. With good collaterals, it is stable or can be reversible while with poor collaterals, normal looking tissue frequently appears as necrotic in follow-up exam. Hence, acute hypodensity represents different states of the ischemic brain parenchyma.

The Influence of Cerebral Arterial Circle on Prominent Hypointense Vessel Signs in Patients With Internal Carotid Artery Occlusion

Background and PurposePrevious studies on the presence of asymmetrical prominent cortical and medullary vessel signs (APCV/APMV) and collateral circulation in patients with internal carotid artery occlusion internal carotid artery occlusion (ICAO) are rare, and the conclusions are inconsistent. Our study aimed to investigate the relationship between the presence of APCV/APMV and collateral circulation in patients with ICAO.MethodsPatients with acute ischemic stroke with ICAO were recruited in this study. All 74 patients were divided into two groups depending on the presence of APCV and APMV. The status of the cerebral arterial circle (CAC) was graded as poor or good. The poor CAC was defined as MCA was invisible. Severe stroke was defined as cerebral watershed infarction (CWI) or territorial infarction (TI). Clinical and radiological markers were compared between these two groups. Logistic regression was used to investigate the association between the APCV/APMV and clinical and radiological markers.ResultsA total of 74 patients with ICAO were enrolled. Forty-three patients (58.1%) presented with an APCV and APMV was found in 35 (47.2%) patients. Compared with patients with non-APCV, patients with APCV had a more severe stroke (P = 0.038) and had a significantly higher incidence of poor CAC (P = 0.022) than those with APCV. Patients with APMV had a more severe stroke (P = 0.001). Logistic regression showed that poor CAC was independently associated with APCV and severe stroke were independently associated with APMV.ConclusionsOur study demonstrates that poor CAC was independently associated with the presence of the APCV in patients with ICAO. Severe stroke was independently associated with the APMV.

Post-stroke treatment with argon preserved neurons and attenuated microglia/macrophage activation long-termly in a rat model of transient middle cerebral artery occlusion (tMCAO)

In a previous study from our group, argon has shown to significantly attenuate brain injury, reduce brain inflammation and enhance M2 microglia/macrophage polarization until 7 days after ischemic stroke. However, the long-term effects of argon have not been reported thus far. In the present study, we analyzed the underlying neuroprotective effects and potential mechanisms of argon, up to 30 days after ischemic stroke. Argon administration with a 3 h delay after stroke onset and 1 h after reperfusion demonstrated long-term neuroprotective effect by preserving the neurons at the ischemic boundary zone 30 days after stroke. Furthermore, the excessive microglia/macrophage activation in rat brain was reduced by argon treatment 30 days after ischemic insult. However, long-lasting neurological improvement was not detectable. More sensorimotor functional measures, age- and disease-related models, as well as further histological and molecular biological analyses will be needed to extend the understanding of argon’s neuroprotective effects and mechanism of action after ischemic stroke.

Factor VII activating protease (FSAP) inhibits the outcome of ischemic stroke in mouse models.

Factor VII activating protease (FSAP) is a circulating serine protease, and individuals with the Marburg I (MI) single nucleotide polymorphism (SNP), which results in an inactive enzyme, have an increased risk of stroke. The outcome of ischemic stroke is more marked in FSAP-deficient mice compared to their wild-type (WT) counterparts. Plasma FSAP levels are raised in patients as well as mice after stroke. In vitro, FSAP promotes fibrinolysis by cleavage of fibrinogen, activates protease-activated receptors and decreases the cellular cytotoxicity of histones. Since these are desirable properties in stroke treatment, we tested the effect of recombinant serine protease domain of FSAP (FSAP-SPD) on ischemic stroke in mice. A combination of tissue plasminogen activator (tPA) and FSAP-SPD enhanced clot lysis, improved microvascular perfusion and neurological outcome and reduced infarct volumes in a mouse model of thromboembolic stroke. In the tail bleeding model FSAP-SPD treatment provoked a faster clotting time indicating that it has a pro-coagulant effect that is described before. FSAP-SPD improved stroke outcome and diminished the negative effects of co-treatment with tPA in the transient middle cerebral artery occlusion model. The inactive MI-isoform of FSAP did not have any effects in either model. In mice with FSAP deficiency there were minor differences in the outcomes of stroke but the treatment with FSAP-SPD was equally effective. Thus, FSAP represents a promising novel therapeutic strategy in the treatment of ischemic stroke that requires further evaluation.

Betaine Ameliorates Brain Damage in a Rat Model of Ischemia/Reperfusion Injury

Brain ischemia and reperfusion (I/R) injury may lead to a poor prognosis for ischemic stroke, which could be alleviated by anti-oxidants with diminished oxidative stress. Betaine is a natural nutrient found in beetroot and seafood to improve cognitive performance in the elderly. The present study investigated whether betaine could protect the brain from I/R injury. Results showed that betaine treatment could reduce H2O2-induced cell death in the PC12 cell line. Pretreatment with betaine reduced the brain infarct volume and neuronal apoptosis in a rat I/R injury model induced by two-hour middle cerebral artery occlusion (MCAO). Biochemical analyses indicated that betaine treatment decreased pro-inflammatory cytokine production and reduced oxidative stress after I/R injury. Betaine increased the expression of anti-oxidative enzymes, such as glutathione peroxidase 4 (Gpx4) and superoxide dismutase 1 (Sod1), and anti-oxidative non-enzymatic genes, such as 3-mercaptopyruvate sulfurtransferase (Mpst), methionine sulfoxide reductases b1 (Msrb1), and Msrb2. These data suggest that betaine exerts a neuroprotective effect in I/R injury through enzymatic and non-enzymatic anti-oxidative systems and anti-inflammatory mechanisms.