scholarly journals Sailuotong Capsule Prevents the Cerebral Ischaemia-Induced Neuroinflammation and Impairment of Recognition Memory through Inhibition of LCN2 Expression

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Yehao Zhang ◽  
Jianxun Liu ◽  
Mingjiang Yao ◽  
WenTing Song ◽  
Yongqiu Zheng ◽  
...  
Keyword(s):  
Vascular Dementia ◽  
Cerebral Ischaemia ◽  
Glucose Deprivation ◽  
Lipocalin 2 ◽  
Sprague Dawley ◽  
Male Adult ◽  
Induced Expression ◽  
Memory Recovery ◽  
Ischaemic Brain

Background. Astrogliosis can result in astrocytes with hypertrophic morphology after injury, indicated by extended processes and swollen cell bodies. Lipocalin-2 (LCN2), a secreted glycoprotein belonging to the lipocalin superfamily, has been reported to play a detrimental role in ischaemic brains and neurodegenerative diseases. Sailuotong (SLT) capsule is a standardized three-herb preparation composed of ginseng, ginkgo, and saffron for the treatment of vascular dementia. Although recent clinical trials have demonstrated the beneficial effect of SLT on vascular dementia, its potential cellular mechanism has not been fully explored. Methods. Male adult Sprague-Dawley (SD) rats were subjected to microsphere-embolized cerebral ischaemia. Immunostaining and Western blotting were performed to assess astrocytic reaction. Human astrocytes exposed to oxygen-glucose deprivation (OGD) were used to elucidate the effects of SLT-induced inflammation and astrocytic reaction. Results. A memory recovery effect was found to be associated with the cerebral ischaemia-induced expression of inflammatory proteins and the suppression of LCN2 expression in the brain. Additionally, SLT reduced the astrocytic reaction, LCN2 expression, and the phosphorylation of STAT3 and JAK2. For in vitro experiments, OGD-induced expression of inflammation and LCN2 was also decreased in human astrocyte by the SLT treatment. Moreover, LCN2 overexpression significantly enhanced the above effects. SLT downregulated these effects that were enhanced by LCN2 overexpression. Conclusions. SLT mediates neuroinflammation, thereby protecting against ischaemic brain injury by inhibiting astrogliosis and suppressing neuroinflammation via the LCN2-JAK2/STAT3 pathway, providing a new idea for the treatment strategy of ischaemic stroke.

scholarly journals Expression of Urotensin II During Focal Cerebral Ischemic in Diabetic Rats

2014 ◽  
Vol 41 (4) ◽  
pp. 498-503 ◽  
Author(s):  
Lin Tian ◽  
Yunqian Li ◽  
Wei Hua ◽  
Ying Jia ◽  
Min Zhou ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Cerebral Ischaemia ◽  
Artery Occlusion ◽  
Diabetic Rats ◽  
Focal Cerebral Ischaemia ◽  
Urotensin Ii ◽  
Sprague Dawley ◽  
Protein Levels ◽  
Ischaemic Brain ◽  
Cerebral Ischemic

Background:The objective of this study was to explore the expression of urotensin II (UII), its receptor (GPR14), and vascular endothelial growth factor (VEGF), as well as their associations in the ischaemic brains of rats with focal cerebral ischaemia, under normal and diabetic conditions.Methods:Diabetes mellitus (DM) was induced by injection of streptozotocin (STZ) into Sprague—Dawley rats. Focal cerebral ischaemia was induced by middle cerebral artery occlusion (MCAO) four weeks after DM onset by STZ. Rats (n=80) were divided into four groups: normal control, DM, MCAO, and DM/MCAO. Immunohistochemistry and reverse-transcriptase-polymerase chain reaction (RT-PCR) were used to detect the expression of UII, GPR14 and VEGF in the diabetic and ischaemic brain.Results:Expression of UII and GPR14 was increased at mRNA and protein levels in the DM and MCAO group compared with controls. In the DM/MCAO group, expression of UII and GPR14 was increased significantly in the ischaemic brain, and was accompanied by a significantly increased VEGF expression.Conclusion:Diabetes mellitus was seen to aggravate brain lesions after ischaemia, and UII may have an important role.

scholarly journals Ginkgolide B Alleviates Learning and Memory Impairment in Rats With Vascular Dementia by Reducing Neuroinflammation via Regulating NF-κB Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Lijuan Huang ◽  
Yijie Shi ◽  
Liang Zhao
Keyword(s):  
Vascular Dementia ◽  
Learning And Memory ◽  
Memory Impairment ◽  
Cognitive Learning ◽  
Glucose Deprivation ◽  
Potential Effect ◽  
Learning Ability ◽  
Inflammatory Factors ◽  
Sprague Dawley ◽  
Nissl Staining

Ginkgobalide B (GB) as the main active ingredient of traditional Chinese medicine Ginkgo biloba extract is reported to reduce neuroinflammation, protect neurons and promote cognitive learning ability. To explore that GB can reduce neuroinflammation through regulating nuclear factor-kappaB (NF-κB) signaling pathway and overcome cognitive dysfunction in rats with vascular dementia (VD), we aim at investigating the potential effect of GB on enhancing cognitive function in rats with VD. It was found that GB improved survival of oxygen-glucose deprivation (OGD) treated SH-SY5Y cells by attenuating inflammatory response via Toll-like Receptor 4 (TLR4)/NF-κB pathway. When rats were treated with bilateral common carotid artery occlusion (BCCAO) for 24 h, saline and GB were administered in Sprague-Dawley (SD) rats via a single intraperitoneal injection for consecutive 14 days. The behavioral changes of VD like rats treated with GB were observed through open field test, Morris water maze (MWM) and Y-maze electric maze. Nissl staining and immunofluorescence were used to observe changes of neurons in the hippocampus of rats. Western blot analysis was performed by detecting NF-κB pathway related inflammatory factors. The results found that GB can significantly improve the learning and memory ability of VD rats by reducing TLR4/NF-κB mediated neuroinflammation. In conclusion, GB seemed to be a potential drug for amelioration of learning and memory impairment in rats with VD.

Hydroxysafflor Yellow A Reprograms TLR9 Signalling Pathway in Ischaemic Cortex after Cerebral Ischaemia and Reperfusion

2018 ◽  
Vol 17 (5) ◽  
pp. 370-382 ◽  
Author(s):  
Zhe Gong ◽  
Jingrui Pan ◽  
Xiangpen Li ◽  
Hongxuan Wang ◽  
Lei He ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Cerebral Ischaemia ◽  
Glucose Deprivation ◽  
Signalling Pathway ◽  
Neurological Deficits ◽  
Sprague Dawley ◽  
Hydroxysafflor Yellow A ◽  
Ischaemia And Reperfusion ◽  
Anti Inflammatory ◽  
Acute Cerebral Ischaemia

Background and Objective: Hydroxysafflor yellow A (HSYA) was reported to suppress inflammation in ischaemic microglia. However, the mechanism through which HSYA inhibits inflammation caused by cerebral ischaemia and reperfusion injury remains unknown. Here, we have mimicked acute cerebral ischaemia and reperfusion injury by subjecting male Sprague-Dawley rats to transient middle cerebral artery occlusion for 90 minutes and have demonstrated that toll-like receptor 9 (TLR9) was upregulated from day 3 after reperfusion, accompanied by the persistent activation of the pro-inflammatory nuclear factor-κB (NF-κB) pathway from 6 hours to day 7. HSYA was injected intraperitoneally at a dose of 6 mg/kg per day, which activated TLR9 in microglia of ischaemic cortex at 6 hours after reperfusion and then obviously suppressed the NF-κB pathway from day 1 to day 7. Meanwhile, HSYA also activated the anti-inflammatory pathway through interferon regulatory factor 3 from day 1 to day 3. The anti-inflammatory effect of HSYA was partially reversed by TLR9-siRNA interference in primary microglia, which was stimulated by oxygen-glucose deprivation and reoxygenation treatment. The regulation of TLR9-mediated inflammation by HSYA was consistent with the recovery of neurological deficits in rats. Conclusion: Therefore, our findings support that HSYA exerts anti-inflammatory effects by reprogramming the TLR9 signalling pathway during treatment of acute cerebral ischaemia and reperfusion injury.

1,8-cineole ameliorates ischaemic brain damage via TRPC6/CREB pathways in rats

2021 ◽  
Author(s):  
Chen Meng ◽  
Wenjing Zeng ◽  
Jing Lv ◽  
Yu Wang ◽  
Meiling Gao ◽  
...  
Keyword(s):  
Brain Damage ◽  
Transient Receptor Potential ◽  
Infarct Volume ◽  
Glucose Deprivation ◽  
Neurological Dysfunction ◽  
Male Rats ◽  
Neuroprotective Effects ◽  
Ischaemic Brain

Abstract Objectives A previous in vitro study reported that the monoterpene oxide 1,8-cineole (cineole) attenuates neuronal caused by oxygen–glucose deprivation/reoxygenation in culture. However, to date, there is no in vivo evidence showing neuroprotective effects of cineole against stroke. This study aimed to investigate whether cineole attenuates cerebral ischaemic damage in rats. Methods A rat model of middle cerebral artery occlusion (MCAO) followed by 24 h reperfusion was applied. Male rats were treated with oral cineole (100 mg/kg) for 7 consecutive days, then subjected to MCAO surgery. Infarct volume, neurologic deficits, apoptosis and expression levels of all-spectrin breakdown products of 145 kDa (SBDP145), transient receptor potential canonical (subtype) 6 (TRPC6) and phosphorylated CREB (p-CREB) were measured in ischaemic brain tissues. Key findings Cineole treatment significantly reduced infarct volume, neurological dysfunction, neuronal apoptosis, SBDP145 formation and TRPC6 degradation and enhanced p-CREB expression in MCAO rats compared with vehicle treatment. These neuroprotective effects were markedly suppressed by pharmacological inhibition of MEK or CaMKIV signalling. Conclusions Our study provides in vivo evidence demonstrating that cineole pretreatment attenuates ischaemic stroke-induced brain damage, mainly through blocking calpain-induced TRPC6 degradation and activating CREB via MEK/CREB and CaMKIV/CREB signalling pathways.

Regulation of intracellular xanthine oxidase by endothelial-derived nitric oxide

1996 ◽  
Vol 271 (5) ◽  
pp. L869-L874 ◽  
Author(s):  
C. G. Cote ◽  
F. S. Yu ◽  
J. J. Zulueta ◽  
R. J. Vosatka ◽  
P. M. Hassoun
Keyword(s):  
Nitric Oxide ◽  
Xanthine Oxidase ◽  
Fold Increase ◽  
Sprague Dawley ◽  
Male Adult ◽  
Dose Dependent Decrease ◽  
Arginine Supplementation ◽  
Hypoxia Reoxygenation

We have previously shown that nitric oxide (NO) donors, such as nitrosoglutathione, inhibit endothelial cell (EC) xanthine dehydrogenase (XD)/xanthine oxidase (XO) activity. The purpose of this study was to assess whether endothelial-derived NO plays any role in the regulation of intracellular XD/XO. We exposed rat pulmonary microvascular EC to L-arginine (precursor of NO) or inhibitors of nitric oxide synthase (NOS), i.e., NG-nitro-L-arginine methyl esther (L-NAME) and NG-nitro-L-arginine, in conditions of normoxia, hypoxia, and hypoxia followed by reoxygenation. Hypoxia alone caused a 1.9- and a 6.6-fold increase in XO and a 5-fold increase in XO + XD activities after 24 and 48 h of exposure, respectively. The combination of hypoxia and L-NAME (300 microM) treatment amounted at 48 h to a 10- and 7.5-fold increase in XO and XO + XD activities, respectively, compared with normoxic untreated cells. L-NAME also prevented the decline in XD/XO activity that occurred in untreated EC after hypoxia-reoxygenation. On the other hand, treatment with L-arginine caused a dose-dependent decrease in XD/XO activity in hypoxic EC compared with cells provided with L-arginine-free medium. In separate experiments, we assessed the role of L-arginine supplementation on the in vivo regulation of lung XD/XO by exposing male adult Sprague-Dawley rats for a period of 5 days to a hypoxic hypobaric atmosphere (0.5 atm). Exposure to hypoxia produced a significant increase in lung tissue XO activity and an increase in the ratio of XO to XD. L-Arginine supplementation in the drinking water prevented the increase in lung XO and the XO-to-XD ratio in hypoxic rats and caused a significant decrease in XO and XD in rats exposed to normoxia. In conclusion, this study suggests that endogenous NO has a significant role in the regulation of XD/XO both in vitro and in vivo. By inhibiting XD/XO activity, NO may have a modulating effect in conditions of hypoxia and hypoxia-reoxygenation, where this enzyme is thought to be important.

Role of miR-323b-5p in Inflammation, Oxidative Stress and Apoptosis During Cerebral Ischemia/Reperfusion Injury

2019 ◽  
Vol 9 (6) ◽  
pp. 829-838
Author(s):  
Chuan Liu ◽  
Juan Du ◽  
Zhaohui Wang ◽  
Fanhua Meng
Keyword(s):  
Cerebral Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Luciferase Assay ◽  
Ros Generation ◽  
Wild Type ◽  
Induced Expression ◽  
Cerebral Ischemia Reperfusion

Objective: The aims of this study is to investigate the potential effects of miR-323b-5p in an in vitro cerebral ischemia-reperfusion (I/R) model via targeting BCL2L11. Materials and methods: PC-12 cells exposed to oxygen-glucose deprivation/reperfusion condition (OGD/R) were classified into control, OGD/R model, miR-323b-5p inhibitor, inhibitor NC, sh-BCL2L11, shRNA NC, miR-323b5p inhibitor + shRNA NC, miR-323b-5p inhibitor + sh-BCL2L11, as well as the wild type cells. Cell apoptosis was observed by flow cytometry. The targeting relationship between miR-323b-5p and BCL2L11 was verified by luciferase assay. ELISA, qRT-PCR, and Western blot were performed to evaluate expressions of related molecules. Results: Compared with wild type, OGD/R significantly induced expression level of miR-323b-5p. In addition, downregulation of miR-323b-5p suppressed the OGD/R induced expression of pro-inflammation factors such as TNFα, IL-1β, IL-6 and monocyte chemotactic protein-1 (MCP-1), OGD/R induced reactive oxygen species (ROS) generation and lactate dehydrogenase (LDH) release. Increased ROS often leads to increased levels of malondialdehyde (MDA) and decreased anti-oxidants super oxide dismutase (SOD), and these OGD/R induced results were reversed by downregulation of miR-323b-5p. Decreased miR-323b-5p also inhibited the OGD/R induced apoptosis. Moreover, miR-323b-5p mediated apoptosis was mediated by directly targeting BCL2L11. Conclusions: miR-323b-5p may regulate cerebral I/R injury by targeting BCL2L11 and is a potential therapeutic and diagnostic biomarker for cerebral I/R injury.

scholarly journals Effects of Cerebral Ischemia on Neuronal Hemoglobin

2008 ◽  
Vol 29 (3) ◽  
pp. 596-605 ◽  
Author(s):  
Yangdong He ◽  
Ya Hua ◽  
Wenquan Liu ◽  
Haitao Hu ◽  
Richard F Keep ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Ischemic Preconditioning ◽  
Glucose Deprivation ◽  
Artery Occlusion ◽  
Sprague Dawley ◽  
Cerebral Neurons

This study examined whether neuronal hemoglobin (Hb) is present in rats. It then examined whether cerebral ischemia or ischemic preconditioning (IPC) affects neuronal Hb levels in vivo and in vitro. In vivo, male Sprague-Dawley rats were subjected to either 15 mins of transient middle cerebral artery occlusion (MCAO) with 24 h of reperfusion, an IPC stimulus, or 24 h of permanent MCAO (pMCAO), or IPC followed 3 days later by 24 h of pMCAO. In vitro, primary cultured neurons were exposed to 2 h of oxygen—glucose deprivation (OGD) with 22 h of reoxygenation. Results showed that Hb is widely expressed in rat cerebral neurons but not astrocytes. Hemoglobin expression was significantly upregulated in the ipsilateral caudate and the cortical core of the middle cerebral artery territory after IPC. Hemoglobin levels also increased more in the penumbral cortex and the contralateral hemisphere 24 h after pMCAO, but expressions in the ipsilateral caudate and the cortical core area were decreased. Ischemic preconditioning modified pMCAO-induced brain Hb changes. Neuronal Hb levels in vitro were increased by 2 h of OGD and 22 h of reoxygenation. These results indicate that Hb is synthesized in neurons and can be upregulated by ischemia.

scholarly journals Cerebroprotective effect of xantohumol sensu experimental stroke model: study design and preliminary results

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Aigul Saitgareyeva ◽  
Leyla Akhmadeyeva
Keyword(s):  
Ischemic Stroke ◽  
Cortical Neurons ◽  
Glucose Deprivation ◽  
Experimental Stroke ◽  
Control Group ◽  
Stroke Model ◽  
Sprague Dawley ◽  
Preliminary Results

The objective of our study was to evaluate the cerebroprotective effect of xanthohumol (ХN) on experimental models of acute ischemic stroke in vivo and in vitro. Materials and methods. We used middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation (OGD) as in vivo and in vitro models. Our study subjects were Sprague-Dawley rats, which were randomly assigned to three groups: the control group and two MCAO groups with and without XN. The primary culture of cortical neurons was obtained from newborn rats. We employed the Bederson test and the corner test to evaluate neurological disorders. Results. The preliminary results indicated a possible cerebroprotective effect of XN in an ischemic stroke model. Conclusion. Preventive administration of XN before cerebral ischemia in an experiment can effectively reduce the volume of cerebral infarction and improve neurologic deficit 24 hours after MCAO.

scholarly journals Knockdown lncRNA NEAT1 regulates the activation of microglia and reduces AKT signaling and neuronal apoptosis after cerebral ischemic reperfusion

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Xunran Ni ◽  
Qian Su ◽  
Wenbo Xia ◽  
Yanli Zhang ◽  
Kejuan Jia ◽  
...  
Keyword(s):  
Cerebral Ischaemia ◽  
Molecular Mechanisms ◽  
Glucose Deprivation ◽  
Therapeutic Interventions ◽  
Stat3 Pathway ◽  
Neuronal Viability ◽  
Microglial Polarization ◽  
Beneficial Effects ◽  
Lncrna Neat1

AbstractAcute cerebral ischaemia may lead to serious consequences, including brain injury caused by uncontrolled reperfusion, which occurs when circulation is re-established. The long non-coding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) plays an important role in the immune system. However, the potential roles and underlying molecular mechanisms of NEAT1 in cerebral ischaemia/reperfusion (I/R) injury remain unclear. The aim of the present study was to investigate the function of the lncRNA NEAT1 in cerebral I/R injury and its potential beneficial effects on neurons. In our study, oxygen–glucose deprivation (OGD)/reoxygenation (OGD/R) was induced in vitro to mimic cerebral I/R injury. Cholecystokinin-octopeptide (CCK-8) was used to measure cell viability, and flow cytometry was used to measure cell apoptosis. Real-time quantitative PCR (qRT-PCR) was used to measure the expression of phenotypic markers of classically activated (M1) and alternatively activated (M2) microglia, and western blotting was performed to detect the levels of proteins related to the AKT/STAT3 pathway. The expression of the lncRNA NEAT1 was significantly upregulated in patients with ischaemic stroke, and knockdown of the lncRNA NEAT1 alleviated OGD/R-induced apoptosis and increased neuronal viability. Furthermore, the lncRNA NEAT1 may inhibit microglial polarization towards the M1 phenotype to reduce the damage caused by OGD/R and reduce the activity of the AKT/STAT3 pathway. In conclusion, the lncRNA NEAT1 may be a potential target for new therapeutic interventions for cerebral I/R.

Preparation of cultured astrocytes for x-ray microanalysis

1989 ◽  
Vol 47 ◽  
pp. 988-989
Author(s):  
N.K.R. Smith ◽  
K.E. Hunter ◽  
P. Mobley ◽  
L.P. Felpel
Keyword(s):  
Cultured Cells ◽  
Elemental Content ◽  
Elemental Distribution ◽  
Sprague Dawley ◽  
X Ray ◽  
Cultured Astrocytes ◽  
Freeze Dried ◽  
Ultimate Objective

Electron probe energy dispersive x-ray microanalysis (XRMA) offers a powerful tool for the determination of intracellular elemental content of biological tissue. However, preparation of the tissue specimen , particularly excitable central nervous system (CNS) tissue , for XRMA is rather difficult, as dissection of a sample from the intact organism frequently results in artefacts in elemental distribution. To circumvent the problems inherent in the in vivo preparation, we turned to an in vitro preparation of astrocytes grown in tissue culture. However, preparations of in vitro samples offer a new and unique set of problems. Generally, cultured cells, growing in monolayer, must be harvested by either mechanical or enzymatic procedures, resulting in variable degrees of damage to the cells and compromised intracel1ular elemental distribution. The ultimate objective is to process and analyze unperturbed cells. With the objective of sparing others from some of the same efforts, we are reporting the considerable difficulties we have encountered in attempting to prepare astrocytes for XRMA.Tissue cultures of astrocytes from newborn C57 mice or Sprague Dawley rats were prepared and cultured by standard techniques, usually in T25 flasks, except as noted differently on Cytodex beads or on gelatin. After different preparative procedures, all samples were frozen on brass pins in liquid propane, stored in liquid nitrogen, cryosectioned (0.1 μm), freeze dried, and microanalyzed as previously reported.

Sign in / Sign up

Export Citation Format

Share Document