scholarly journals 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

Antioxidants ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 168
Author(s):  
Jin Ah Ryuk ◽  
Byoung Seob Ko ◽  
Na Rang Moon ◽  
Sunmin Park

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.

Foods ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2697
Author(s):  
Ting Zhang ◽  
Myeong-Seon Ryu ◽  
Xuangao Wu ◽  
Hee-Jong Yang ◽  
Su Ji Jeong ◽  
...  

Short-term fermented soybeans (chungkookjang) with specific Bacillus (B.) spp. have anti-obesity, antidiabetic, and anti-stroke functions. We examined the hypothesis that the long-term consumption of B. amyloliquefaciens SCGB 1 fermented (CKJ1) and B. subtilis SCDB 291 (CKJ291) chungkookjang can alleviate clinical symptoms and hyperglycemia after ischemic stroke by promoting the gut microbiota–brain axis. We examined this hypothesis in Mongolian male gerbils with stroke symptoms induced by carotid artery occlusion. The artery-occluded gerbils were divided into five groups: no supplementation (Control, Normal-control), 4% cooked soybeans (CSB), CKJ1, or CKJ291 in a high-fat diet for 3 weeks. The carotid arteries of gerbils in the Control, CSB, CKJ1, and CKJ291 groups were occluded for 8 min and they then continued on their assigned diets for an additional 3 weeks. Normal-control gerbils had no artery occlusion. The diets in all groups contained an identical macronutrient composition using starch, casein, soybean oil, and dietary fiber. The CSB, CKJ1, and CKJ291 groups exhibited less neuronal cell death than the Control group, while the CKJ1 group produced the most significant reduction among all groups, as much as 85% of the Normal-control group. CKJ1 and CKJ291 increased the blood flow and removal of blood clots, as determined by Doppler, more than the Control. They also showed more improvement in neurological disorders from ischemic stroke. Their improvement showed a similar tendency as neuronal cell death. CKJ1 treatment improved memory impairment, measured with Y maze and passive avoidance tests, similar to the Normal-control. The gerbils in the Control group had post-stroke hyperglycemia due to decreased insulin sensitivity and β-cell function and mass; the CKJ291, CSB, and CKJ1 treatments protected against glucose disturbance after artery occlusion and were similar to the Normal-control. CKJ1 and CKJ291 also reduced serum tumor necrosis factor-α concentrations and hippocampal interleukin-1β expression levels, compared to the Control. CKJ1 and CKJ291 increased the contents of Lactobacillus, Bacillus, and Akkermansia in the cecum feces, similar to the Normal-control. Picrust2 analysis showed that CKJ1 and CKJ291 increased the propionate and butyrate metabolism and the starch and glucose metabolism but reduced the lipopolysaccharide biosynthesis and fatty acid metabolism compared to the Control. In conclusion, daily CKJ1 and CKJ291 intake prevented neuronal cell death and memory dysfunction from the artery occlusion by increasing blood flow and β-cell survival and reducing post-stroke-hyperglycemia through modulating the gut microbiome composition and metabolites to influence the host metabolism, especially inflammation and insulin resistance, protecting against neuronal cell death and brain dysfunction. CKJ1 had better effects than CKJ291.


2020 ◽  
Author(s):  
qingxiu zhang ◽  
Lei He ◽  
Mo Chen ◽  
Hui Yang ◽  
Xiaowei Cao ◽  
...  

Abstract Background: Postsynaptic density 93 (PSD-93) mediates glutamate excitotoxicity induced by ischemic brain injury, which then induces microglial inflammatory response. However, the underlying mechanisms of how PSD-93 mediates the crosstalk between neurons and microglia in the postsynaptic dense region remain elusive. CX3 chemokine ligand 1 (CX3CL1) is a chemokine specifically expressed in neurons while its receptor CX3CR1 is highly expressed in microglia. In this study, we aimed to investigate the role of PSD-93 and CX3CL1 interaction in the crosstalk between neuron and microglia in acute ischemic stroke.Methods: Male C57BL/6 mice were used to establish middle cerebral artery occlusion model and co-immunoprecipitation and immunoblotting were used to detect the binding of PSD-93 and CX3CL1 at different time points following cerebral ischemic/reperfusion (I/R). ELISA was used to detect soluble CX3CL1. Yeast two-hybrid and co-immunoprecipitation were used to identify special amino acid sequences responsible for the interaction between PSD-93 and CX3CL1. Finally, a fusion small peptide Tat-CX3CL1 was designed to inhibit PSD-93 and CX3CL1 interaction.Results: The binding of PSD-93 and CX3CL1 peaked at 6 h after I/R. The binding sites were located in the 420-535 amino acid sequence of PSD-93 and 357-395 amino acid sequence of CX3CL1. Tat-CX3CL1 (357-395aa) could inhibit the interaction of PSD-93 and CX3CL1 and inhibited the pro-inflammatory cytokine IL-1β and TNF-α expression and provided neuroprotection following reperfusion.Conclusions: PSD-93 binds CX3CL1 to activate microglia and initiate neuroinflammation. Specific blockade of PSD-93-CX3CL1 interaction reduces I/R induced neuronal cell death, and provides a new therapeutic target for ischemic stroke.


2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Joen-Rong Sheu ◽  
Zhih-Cherng Chen ◽  
Thanasekaran Jayakumar ◽  
Duen-Suey Chou ◽  
Ting-Lin Yen ◽  
...  

Abstract Thrombosis and stroke are major causes of disability and death worldwide. However, the regular antithrombotic drugs may have unsatisfactory results and side effects. Platonin, a cyanine photosensitizing dye, has been used to treat trauma, ulcers and some acute inflammation. Here, we explored the neuroprotective effects of platonin against middle cerebral artery occlusion (MCAO)-induced ischemic stroke in mice. Platonin(200 μg/kg) substantially reduced cerebral infarct volume, brain edema, neuronal cell death and neurological deficit scores, and improved the MCAO-reduced locomotor activity and rotarod performance. Platonin(5–10 μM) potently inhibited platelet aggregation and c-Jun NH2-terminal kinase (JNK) phosphorylation in collagen-activated platelets. The antiaggregation effect did not affect bleeding time but increased occlusion time in platonin(100 and 200 μg/kg)-treated mice. Platonin(2–10 μM) was potent in diminishing collagen- and Fenton reaction-induced ∙OH formation. Platonin(5–10 μM) also suppressed the expression of nitric oxide, inducible nitric oxide synthase, cyclooxygenase-2, interleukin-1β, and JNK phosphorylation in lipopolysaccharide-stimulated macrophages. MCAO-induced expression of 3-nitrotyrosine and Iba1 was apparently attenuated in platonin(200 μg/kg)-treated mice. In conclusion, platonin exhibited remarkable neuroprotective properties against MCAO-induced ischemia in a mouse model through its antiaggregation, antiinflammatory and antiradical properties. The observed therapeutic efficacy of platonin may consider being a novel medcine against ischemic stroke.


Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Koichi Arimura ◽  
Tetsuro Ago ◽  
Masahiro Kamouchi ◽  
Hiroshi Sugimori ◽  
Junya Kuroda ◽  
...  

Brain pericytes are a constituent of the neurovascular unit and play various important roles in brain functions, such as regulation of capillary blood flow, maintenance of blood-brain barrier and angiogenesis. Previous reports have elucidated that PDGF-B prevents neuronal cell death during ischemic insults in adult rodent models; however, the detailed mechanisms by which PDGF-B signaling protects neurons from ischemic damage are not fully understood. In the present study, we investigated whether brain pericytes play neuroprotective roles in brain ischemia, using a permanent middle cerebral artery occlusion stroke model (MCAO) and cultured human brain pericytes. Immunohistochemistry revealed that the expression of PDGF receptorβ(PDGFRβ) was induced predominantly in pericytes in peri-infarct areas. PDGF-B induced marked phosphorylation of Akt in cultured pericytes. Consistently, Akt was markedly phosphorylated in the PDGFRβ-expressing pericytes in peri-infarct areas. PDGF-B upregulated the expression of neurotrophins, such as neuronal growth factor (NGF) and neurotrophin-3 (NT-3), through Akt activation in the cultured pericytes. We subjected PDGFRβheterozygous knockout (PDGFRβ+/-) mice to MCAO. Infarct volume, as assessed by MAP2 immunostaining, was significantly greater in PDGFRβ+/- than wild-type mice ( 48% increase at day 7, p < 0.01 , n=5). The number of TUNEL positive apoptotic cells was significantly greater in PDGFRβ+/- mice (54 % increase at day 4, p < 0.001 , n=6). Production of NGF and NT-3 at mRNA and protein levels in infarct areas was significantly decreased in PDGFRβ+/- mice (NGF: 28% decrease, p<0.05, NT-3: 22% decrease, p<0.05). Since it has been established that neurotrophin receptors are induced in peri-infarct areas, the decreases in neurotrophin production may increase apoptotic neuronal cell death in the PDGFRβ+/- mice. In conclusion, brain pericytes may have a direct neuroprotective role through secreting neurotrophins via PDGFRβ-Akt signaling, thereby decreasing infarct volume in ischemic stroke.


Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Dan-Victor V Giurgiutiu ◽  
Albert J Yoo ◽  
Kaitlin Fitzpatrick ◽  
Zeshan Chaudhry ◽  
Lee H Schwamm ◽  
...  

Background: Selecting patients most likely to benefit (MLTB) from intra-arterial therapy (IAT) is essential to assure favorable outcomes after intervention for acute ischemic stroke (AIS). Leukoaraiosis (LA) has been linked to infarct growth, risk of hemorrhage after IV rt-PA, and poor post-stroke outcomes. We investigated whether LA severity is associated with AIS outcomes after IAT. Methods: We analyzed consecutive AIS subjects from our institutional GWTG-Stroke database enrolled between 01/01/2007-06/30/2009, who met our pre-specified criteria for MLTB: CTA and MRI within 6 hours from last known well, NIHSS score ≥8, baseline DWI volume (DWIv) ≤ 100 cc, and proximal artery occlusion and were treated with IAT. LA volume (LAv) was assessed on FLAIR using validated, semi-automated protocols. We analyzed CTA to assess collateral grade; post-IAT angiogram for recanalization status (TICI score ≥2B); and the 24-hour CT for symptomatic ICH (sICH). Logistic regression was used to determine independent predictors of good functional outcome (mRS≤ 2) and mortality at 90 days post-stroke. Results: There were 48 AIS subjects in this analysis (mean age 69.2, SD±13.8; 55% male; median LAv 4cc, IQR 2.2-8.8cc; median NIHSS 15, IQR 13-19; median DWIv 15.4cc, IQR 9.2-20.3cc). Of these, 34 (72%) received IV rt-PA; 3 (6%) had sICH; 21 (44.7%) recanalized; and 23 (50%) had collateral grade ≥3. At 90 days, 15/48 (36.6%) were deceased and 15/48 had mRS≤ 2. In univariate analysis, recanalization (OR 6.2, 95%CI 1.5-25.5), NIHSS (OR 0.8 per point, 95%CI 0.64-0.95), age (OR 0.95 per yr, 95%CI 0.89-0.99) were associated with good outcome, whereas age (OR 1.1, 95%CI 1.01-1.14) and HTN (OR 5.6, 95%CI 1.04-29.8) were associated with mortality. In multivariable analysis including age, NIHSS, recanalization, collateral grade, and LAv, only recanalization independently predicted good functional outcome (OR 21.3, 95%CI 2.3-199.9) and reduced mortality (OR 0.15, 95%CI 0.02-1.12) after IAT. Conclusions: LA severity is not associated with poor outcome in patients selected MLTB for IAT. Among AIS patients considered likely to benefit from IAT, only recanalization independently predicted good functional outcome and decreased mortality.


2007 ◽  
Vol 28 (1) ◽  
pp. 99-110 ◽  
Author(s):  
Willard J Costain ◽  
Ingrid Rasquinha ◽  
Jagdeep K Sandhu ◽  
Peter Rippstein ◽  
Bogdan Zurakowski ◽  
...  

Synaptic pathology is observed during hypoxic events in the central nervous system in the form of altered dendrite structure and conductance changes. These alterations are rapidly reversible, on the return of normoxia, but are thought to initiate subsequent neuronal cell death. To characterize the effects of hypoxia on regulators of synaptic stability, we examined the temporal expression of cell adhesion molecules (CAMs) in synaptosomes after transient middle cerebral artery occlusion (MCAO) in mice. We focused on events preceding the onset of ischemic neuronal cell death (< 48 h). Synaptosome preparations were enriched in synaptically localized proteins and were free of endoplasmic reticulum and nuclear contamination. Electron microscopy showed that the synaptosome preparation was enriched in spheres (≈650 nm in diameter) containing secretory vesicles and postsynaptic densities. Forebrain mRNA levels of synaptically located CAMs was unaffected at 3 h after MCAO. This is contrasted by the observation of consistent downregulation of synaptic CAMs at 20 h after MCAO. Examination of synaptosomal CAM protein content indicated that certain adhesion molecules were decreased as early as 3 h after MCAO. For comparison, synaptosomal Agrn protein levels were unaffected by cerebral ischemia. Furthermore, a marked increase in the levels of p-Ctnnb1 in ischemic synaptosomes was observed. p-Ctnnb1 was detected in hippocampal fiber tracts and in cornu ammonis 1 neuronal nuclei. These results indicate that ischemia induces a dysregulation of a subset of synaptic proteins that are important regulators of synaptic plasticity before the onset of ischemic neuronal cell death.


2016 ◽  
Vol Volume 12 ◽  
pp. 3083-3092 ◽  
Author(s):  
Shengtao Yao ◽  
Bo Tang ◽  
Gang Li ◽  
Ruiming Fan ◽  
Fang Cao

2009 ◽  
Vol 29 (5) ◽  
pp. 953-964 ◽  
Author(s):  
Rung-chi Li ◽  
Sofiyan Saleem ◽  
Gehua Zhen ◽  
Wangsen Cao ◽  
Hean Zhuang ◽  
...  

Hemoproteins undergo degradation during hypoxic/ischemic conditions, but the prooxidant free heme that is released cannot be recycled and must be degraded. The extracellular heme associates with its high-affinity binding protein, hemopexin (HPX). Hemopexin is shown here to be expressed by cortical neurons and it is present in mouse cerebellum, cortex, hippocampus, and striatum. Using the transient ischemia model (90-min middle cerebral artery occlusion followed by 96-h survival), we provide evidence that HPX is protective in the brain, as neurologic deficits and infarct volumes were significantly greater in HPX−/− than in wild-type mice. Addressing the potential protective HPX cellular pathway, we observed that exogenous free heme decreased cell survival in primary mouse cortical neuron cultures, whereas the heme bound to HPX was not toxic. Heme-HPX complexes induce HO1 and, consequently, protect primary neurons against the toxicity of both heme and prooxidant tert-butyl hydroperoxide; such protection was decreased in HO1−/− neuronal cultures. Taken together, these data show that HPX protects against heme-induced toxicity and oxidative stress and that HO1 is required. We propose that the heme-HPX system protects against stroke-related damage by maintaining a tight balance between free and bound heme. Thus, regulating extracellular free heme levels, such as with HPX, could be neuroprotective.


Sign in / Sign up

Export Citation Format

Share Document