scholarly journals Nuclear Factor-Kappa B Activity Regulates Brain Expression of P-Glycoprotein in the Kainic Acid-Induced Seizure Rats

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Nian Yu ◽  
Qing Di ◽  
Hao Liu ◽  
Yong Hu ◽  
Ying Jiang ◽  
...  
Keyword(s):  
Kainic Acid ◽  
Saline Control ◽  
Control Group ◽  
Pyrrolidine Dithiocarbamate ◽  
Seizure Susceptibility ◽  
Seizure Onset ◽  
Over Expression ◽  
P Glycoprotein ◽  
Brain Expression ◽  
Pre Treatment

This study was aimed to investigate the effect of NF-κB activity on the seizure susceptibility, brain damage, and P-gp expression in kainic acid- (KA-) induced seizure rats. Male SD rats were divided into saline control group (NS group), KA induced epilepsy group (EP group), and epilepsy group intervened with NF-κB inhibitor-pyrrolidine dithiocarbamate salt (PDTC group) or with dexamethasone (DEX group). No seizures were observed in the rats of NS group. Compared with NS group, increased P-gp expression and NF-κB activation in the rat brain of the EP group were observed after KA micro-injection. Both PDTC and DEX pre-treatment significantly increased the latency to grade III or V seizure onset compared to EP group but failed to show neuron-protective effect as the number of survival neurons didn't significantly differ from that in EP group. Furthermore, PDTC pre-treatment significantly decreased P-gp expression along with NF-κB activation in the hippocampus CA3 area and amygdala complex of rats compared with the EP group, implying that NF-κB activation involved in the seizure susceptibility and seizure induced brain P-gp over-expression. Additionally, DEX pre-treatment only decreased P-gp expression level without inhibition of NF-κB activation, suggesting NF-κB independent pathway may also participate in regulating seizure induced P-gp over-expression.

scholarly journals The Prophylactic Use of Bovine Colostrum in a Murine Model of TNBS-Induced Colitis

Animals ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 492 ◽  
Author(s):  
Laura Menchetti ◽  
Giulio Curone ◽  
Iulia Elena Filipescu ◽  
Olimpia Barbato ◽  
Leonardo Leonardi ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Clinical Signs ◽  
Interleukin 10 ◽  
Bovine Colostrum ◽  
Saline Control ◽  
Control Group ◽  
Microbial Composition ◽  
Expression Levels ◽  
Pre Treatment ◽  
Prophylactic Use

This study investigated the effects of a short-term administration of bovine colostrum (BC) in a TNBS model of induced colitis. Colitis was induced by TNBS treatment after seven days of BC (BC group, n = 12) or saline (control group, n = 12) administration in mice. Clinical signs, histopathological characteristics, expression levels of Toll-like receptor 4 (TLR4), pro- and anti-inflammatory cytokines, and microbial composition were assessed. BC was well tolerated and did not induce any histological damage or clinical symptoms. After TNBS treatment, the BC group showed a reduction in body weight (BW) loss compared to Control (p < 0.05). Moreover, expression levels of TLR4 (p < 0.01), Interleukin-1β (IL-1β; p < 0.001), Interleukin-8 (IL-8; p < 0.001), and Interleukin-10 (IL-10; p < 0.001) were lower in mice administered with BC. Finally, Escherichia coli were higher (p < 0.05), while Enterococci (p < 0.001), Lactobacillus spp. (p < 0.001), and Bifidobacterium spp. (p < 0.05) were lower in Control than BC group. This study confirms that pre-treatment with BC modulates the expression of genes and the count of microbes involved in the etiopathogenesis of colitis.

scholarly journals Effects of intravenous infusion of E.coli lipopolysaccharide in early pregnant cows

Reproduction ◽  
2018 ◽  
Author(s):  
Kathrin Herzog ◽  
Letizia Debertolis ◽  
John P Kastelic ◽  
Marion Schmicke ◽  
Susanne E Ulbrich ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Blood Flow ◽  
Saline Control ◽  
Control Group ◽  
Saline Control Group ◽  
Blood Samples ◽  
Luteal Tissue ◽  
Embryonic Loss ◽  
Pre Treatment ◽  
Embryonic Viability

The objective was to characterize effects of Escherichia coli LPS (given iv) on corpus luteum (CL) and embryonic viability in early pregnant cattle. Eight non-lactating German Holstein cows were given 0.5 µg/kg LPS on 35 ± 3 d (mean ± SEM) of pregnancy, whereas seven heifers, 41 ± 6 d pregnant, were given 10 ml saline (Control group). Transrectal B-mode examinations of the CL were done at -1, 3, 6, 12, 24, 48, 72, and 96 h relative to treatment. Blood samples were collected at -1, 0.5, 1, 2, 3, 4, 6, 9, 12, 24, 48, 72, and 96 h. At 12 and 48 h, the CL was biopsied. None of the cows still in the experiment 10 d after LPS (n=7) had embryonic loss. In LPS-treated cows, luteal area decreased (from 4.1 to 3.1 cm2; P≤0.05) within 6 h and until 48 h. Luteal blood flow decreased by 39% (P≤0.05) within the first 6 h after LPS, but returned to pre-treatment values by 48 h. Plasma P4 decreased by 62% (P≤0.05), reached a nadir (2.7±0.6 ng/mL) at 12 h after LPS and was not restored to pre-treatment (P≤0.05). In luteal tissue, mRNAs for StAR and for FGF1 were lower (P≤0.05) in LPS- than in saline-treated cattle at 12 h, with no difference between groups at 48 h. Levels of mRNAs for Casp3 and FGF2 were not different between groups (P>0.05) at 12 or 48 h after treatment. In conclusion, LPS transiently suppressed CL function, but did not induce embryonic mortality.

scholarly journals Exploring with [18F]UCB-H the in vivo Variations in SV2A Expression through the Kainic Acid Rat Model of Temporal Lobe Epilepsy

2020 ◽  
Vol 22 (5) ◽  
pp. 1197-1207 ◽  
Author(s):  
Maria Elisa Serrano ◽  
Mohamed Ali Bahri ◽  
Guillaume Becker ◽  
Alain Seret ◽  
Charlotte Germonpré ◽  
...  
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Kainic Acid ◽  
Temporal Lobe ◽  
Rat Model ◽  
Chronic Phase ◽  
Male Rats ◽  
Saline Control ◽  
Control Group ◽  
Significant Group

Abstract Purpose The main purpose of this study was to understand how the positron emission tomography (PET) measure of the synaptic vesicle 2A (SV2A) protein varies in vivo during the development of temporal lobe epilepsy (TLE) in the kainic acid rat model. Procedures Twenty Sprague Dawley male rats were administered with multiple systemic doses of saline (control group, n = 5) or kainic acid (5 mg/kg/injection, epileptic group, n = 15). Both groups were scanned at the four phases of TLE (early, latent, transition, and chronic phase) with the [18F]UCB-H PET radiotracer and T2-structural magnetic resonance imaging. At the end of the scans (3 months post-status epilepticus), rats were monitored for 7 days with electroencephalography for the detection of spontaneous electrographic seizures. Finally, the immunofluorescence staining for SV2A expression was performed. Results Control rats presented a significant increase in [18F]UCB-H binding at the last two scans, compared with the first ones (p < 0.001). This increase existed but was lower in epileptic animals, producing significant group differences in all the phases of the disease (p < 0.028). Furthermore, the quantification of the SV2A expression in vivo with the [18F]UCB-H radiotracer or ex vivo with immunofluorescence led to equivalent results, with a positive correlation between both. Conclusions Even if further studies in humans are required, the ability to detect a progressive decrease in SV2A expression during the development of temporal lobe epilepsy supports the use of [18F]UCB-H as a useful tool to differentiate, in vivo, between healthy and epileptic animals along with the development of the epileptic disease.

scholarly journals Pre-treatment with dexamethasone attenuates experimental ventilator-induced lung injury

2016 ◽  
Vol 42 (3) ◽  
pp. 166-173 ◽  
Author(s):  
Fernando Fonseca dos Reis ◽  
Maycon de Moura Reboredo ◽  
Leda Marília Fonseca Lucinda ◽  
Aydra Mendes Almeida Bianchi ◽  
Maria Aparecida Esteves Rabelo ◽  
...  
Keyword(s):  
Lung Injury ◽  
Wistar Rats ◽  
Sham Group ◽  
Saline Control ◽  
Control Group ◽  
Ventilator Induced Lung Injury ◽  
Arterial Blood ◽  
Cell Counts ◽  
Dexamethasone Group ◽  
Pre Treatment

ABSTRACT Objective: To evaluate the effects that administering dexamethasone before the induction of ventilator-induced lung injury (VILI) has on the temporal evolution of that injury. Methods: Wistar rats were allocated to one of three groups: pre-VILI administration of dexamethasone (dexamethasone group); pre-VILI administration of saline (control group); or ventilation only (sham group). The VILI was induced by ventilation at a high tidal volume. Animals in the dexamethasone and control groups were euthanized at 0, 4, 24, and 168 h after VILI induction. We analyzed arterial blood gases, lung edema, cell counts (total and differential) in the BAL fluid, and lung histology. Results: At 0, 4, and 24 h after VILI induction, acute lung injury (ALI) scores were higher in the control group than in the sham group (p < 0.05). Administration of dexamethasone prior to VILI induction decreased the severity of the lung injury. At 4 h and 24 h after induction, the ALI score in the dexamethasone group was not significantly different from that observed for the sham group and was lower than that observed for the control group (p < 0.05). Neutrophil counts in BAL fluid were increased in the control and dexamethasone groups, peaking at 4 h after VILI induction (p < 0.05). However, the neutrophil counts were lower in the dexamethasone group than in the control group at 4 h and 24 h after induction (p < 0.05). Pre-treatment with dexamethasone also prevented the post-induction oxygenation impairment seen in the control group. Conclusions: Administration of dexamethasone prior to VILI induction attenuates the effects of the injury in Wistar rats. The molecular mechanisms of such injury and the possible clinical role of corticosteroids in VILI have yet to be elucidated.

scholarly journals Glycinin-induced porcine IPEC-J2 cell damage via the NF-κB/MAPK signaling pathway

2020 ◽  
Author(s):  
Chenglu Peng ◽  
Zhifeng Sun ◽  
Lei Wang ◽  
Yingshuang Shu ◽  
Mengchu He ◽  
...  
Keyword(s):  
Cell Damage ◽  
Intestinal Barrier ◽  
Mapk Signaling ◽  
Control Group ◽  
Epithelial Cell Line ◽  
Pyrrolidine Dithiocarbamate ◽  
Nitric Oxide Synthase Inhibitor ◽  
P38 Inhibitor ◽  
Pre Treatment ◽  
Synthase Inhibitor

Abstract Background: Glycinin, a protein found in soybean, is a human and animal allergen. It been previously shown to damage the intestinal barrier. However, its mechanisms of action remain unclear. Therefore, in this study, the intestinal porcine epithelial cell line IPEC-J2 was used to study the effect of glycinin concentration on the intestinal epithelium and identify the related signaling pathways. Results: IPEC-J2 cells were divided into seven treatment groups and a control group; the cells were treated for 24 h with 1, 5, or 10 mg/mL glycinin or with 5 mg/mL glycinin after 30 min of pre-treatment with 1 μmol/L nuclear factor-kappa B (NF-κB) inhibitor (pyrrolidine dithiocarbamate), inducible nitric oxide synthase inhibitor (N-ω-nitro-l-arginine methyl ester), Jun N-terminal kinase (JNK) inhibitor (SP600125), or p38 inhibitor (SB202190). A series of molecular and biochemical experiments revealed that the levels of NF-κB, p38, and JNK, as well as their downstream proteins, increased after the treatment compared with those in the control group.

scholarly journals The Role of P-Glycoprotein in Transport of Danshensu across the Blood-Brain Barrier

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Peng-Fei Yu ◽  
Wen-Yan Wang ◽  
Gaowa Eerdun ◽  
Tian Wang ◽  
Lei-Ming Zhang ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Salvia Miltiorrhiza ◽  
Water Soluble ◽  
Brain Barrier ◽  
Saline Control ◽  
Control Group ◽  
P Glycoprotein ◽  
Blood Brain ◽  
The Brain

Danshensu (3-(3, 4-dihydroxyphenyl) lactic acid), a water-soluble active component isolated from the root ofSalvia miltiorrhizaBunge, is widely used for the treatment of cerebrovascular diseases. The present study aims to investigate the role of P-glycoprotein in transport of Danshensu across the blood-brain barrier. Sprague-Dawley rats were pretreated with verapamil at a dose of 20 mg kg−1(verapamil group) or the same volume of normal saline (control group). Ninety minutes later, the animals were administrated with Danshensu (15 mg kg−1) by intravenous injection. At 15 min, 30 min, and 60 min after Danshensu administration, the levels of Danshensu in the blood and brain were detected by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). The results showed that Danshensu concentrations in the brain of the rats pretreated with verapamil were significantly increased. In addition, the brain-plasma ratios of the group pretreated with verapamil were much higher than that of the control group. There was no difference in Danshensu level in plasma between the verapamil group and control group. The findings indicated that Danshensu can pass the blood-brain barrier, and P-glycoprotein plays an important role in Danshensu transportation in brain.

scholarly journals MicroRNA-513b-5p targets COL1A1 and COL1A2 associated with the formation and rupture of intracranial aneurysm

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zheng Zheng ◽  
Yan Chen ◽  
Yinzhou Wang ◽  
Yongkun Li ◽  
Qiong Cheng
Keyword(s):  
Cell Death ◽  
Intracranial Aneurysm ◽  
Luciferase Reporter Assay ◽  
Luciferase Reporter ◽  
Control Group ◽  
Type I ◽  
Mrna Levels ◽  
Reporter Assay ◽  
Over Expression ◽  
Tnf Α

AbstractCollagen-type I alpha 1 chain (COL1A1) and COL1A2 are abnormally expressed in intracranial aneurysm (IA), but their mechanism of action remains unclear. This study was performed to investigate the mechanism of COL1A1 and COL1A2 affecting the occurrence and rupture of IA. Quantitative real-time polymerase chain reaction was used to measure the expression of hsa-miR-513b-5p, COL1A1, COL1A2, TNF-α, IL-6, MMP2, MMP3, MMP9 and TIMP4 in patients with ruptured IA (RA) (n = 100), patients with un-ruptured IA (UA) (n = 100), and controls (n = 100). Then, human vascular smooth muscle cells (HASMCs) were cultured, and dual luciferase reporter assay was performed to analyse the targeting relationship between miR-513b-5p and COL1A1 or COL1A2. The effects of the miR-513b-5p mimic and inhibitor on the proliferation, apoptosis, and death of HASMC and the RIP1-RIP3-MLKL and matrix metalloproteinase pathways were also explored. The effect of silencing and over-expression of COL1A1 and COL1A2 on the role of miR-513b-5p were also evaluated. Finally, the effects of TNF-α on miR-513b-5p targeting COL1A1 and COL1A2 were tested. Compared with those in the control group, the serum mRNA levels of miR-513b-5p, IL-6 and TIMP4 were significantly decreased in the RA and UA groups, but COL1A1, COL1A2, TNF-α, IL-1β, MMP2, MMP3 and MMP9 were significantly increased (p < 0.05). Compared with those in the UA group, the expression of COL1A1, COL1A2, TNF-α, IL-1β and MMP9 was significantly up-regulated in the RA group (p < 0.05). Results from the luciferase reporter assay showed that COL1A1 and COL1A were the direct targets of miR-513b-5p. Further studies demonstrated that miR-513b-5p targeted COL1A1/2 to regulate the RIP1-RIP3-MLKL and MMP pathways, thereby enhancing cell death and apoptosis. Over-expression of COL1A1 or COL1A2, rather than silencing COL1A1/2, could improve the inhibitory effect of miR-513b-5p on cell activity by regulating the RIP1-RIP3-MLKL and MMP pathways. Furthermore, over-expression of miR-513b-5p and/or silencing COL1A1/2 inhibited the TNF-α-induced cell proliferation and enhanced the TNF-α-induced cell death and apoptosis. The mechanism may be related to the inhibition of collagen I and TIMP4 expression and promotion of the expression of RIP1, p-RIP1, p-RIP3, p-MLKL, MMP2 and MMP9. MiR-513b-5p targeted the inhibition of COL1A1/2 expression and affected HASMC viability and extracellular mechanism remodelling by regulating the RIP1-RIP3-MLKL and MMP pathways. This process might be involved in the formation and rupture of IA.

scholarly journals PKA-RIIβ autophosphorylation modulates PKA activity and seizure phenotypes in mice

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Jingliang Zhang ◽  
Chenyu Zhang ◽  
Xiaoling Chen ◽  
Bingwei Wang ◽  
Weining Ma ◽  
...  
Keyword(s):  
Therapeutic Target ◽  
Neurological Disorders ◽  
Neuronal Excitability ◽  
Granule Cells ◽  
Critical Role ◽  
Intrinsic Excitability ◽  
Seizure Susceptibility ◽  
Seizure Onset ◽  
Potential Therapeutic Target ◽  
Seizure Model

AbstractTemporal lobe epilepsy (TLE) is one of the most common and intractable neurological disorders in adults. Dysfunctional PKA signaling is causally linked to the TLE. However, the mechanism underlying PKA involves in epileptogenesis is still poorly understood. In the present study, we found the autophosphorylation level at serine 114 site (serine 112 site in mice) of PKA-RIIβ subunit was robustly decreased in the epileptic foci obtained from both surgical specimens of TLE patients and seizure model mice. The p-RIIβ level was negatively correlated with the activities of PKA. Notably, by using a P-site mutant that cannot be autophosphorylated and thus results in the released catalytic subunit to exert persistent phosphorylation, an increase in PKA activities through transduction with AAV-RIIβ-S112A in hippocampal DG granule cells decreased mIPSC frequency but not mEPSC, enhanced neuronal intrinsic excitability and seizure susceptibility. In contrast, a reduction of PKA activities by RIIβ knockout led to an increased mIPSC frequency, a reduction in neuronal excitability, and mice less prone to experimental seizure onset. Collectively, our data demonstrated that the autophosphorylation of RIIβ subunit plays a critical role in controlling neuronal and network excitabilities by regulating the activities of PKA, providing a potential therapeutic target for TLE.

scholarly journals Clinical outcomes of submassive pulmonary embolism thrombolysis—an Indian experience

2020 ◽  
Vol 72 (1) ◽  
Author(s):  
Nadeem U. Rehman ◽  
Mohd Iqbal Dar ◽  
Manish Bansal ◽  
R. R. Kasliwal
Keyword(s):  
Pulmonary Embolism ◽  
Pulmonary Artery ◽  
Systolic Dysfunction ◽  
Massive Pulmonary Embolism ◽  
Post Treatment ◽  
Control Group ◽  
Submassive Pulmonary Embolism ◽  
Venous Thromboembolic ◽  
Pre Treatment ◽  
And Control

Abstract Background Acute pulmonary thromboembolism is the most dangerous presentation of venous thromboembolic disease. The role of thrombolysis in massive pulmonary embolism has been studied extensively, but the same is not there for submassive pulmonary embolism. This study is aimed at evaluating the effects of thrombolysis in acute submassive pulmonary embolism. This was a prospective, case-control, observational study. Patients presenting with acute submassive pulmonary embolism were divided into thrombolysis group and control group depending on whether they received thrombolysis plus anticoagulation or anticoagulation only, respectively. Results A total of 86 patients were included in the study. Forty-two patients were in the thrombolysis group, and 44 patients were in the control group. The mean ± SD age in the control and thrombolysis groups was 63.3 ± 14.7 and 56.4 ± 13.8 years, respectively. The two groups were well matched in sex distribution and associated comorbidities like COPD, active surgery, major trauma, and immobilization. On echocardiography, dilated RA/RV in pre-treatment vs. post-treatment was seen in 20 (45.5%) vs. 20 (45.5%) in the control group and 26 (61.9%) vs. 11 (26.2%) in the thrombolysis group. Similarly, RV systolic dysfunction in pre-treatment vs. post-treatment was seen in 24 (54.5%) vs. 21 (47.7%) in the control group and 22 (52.4%) vs. 8 (19.0%) in the thrombolysis group. Pulmonary artery pressure in pre-treatment vs. post-treatment was 64.4 ± 15.0 vs. 45.9 ± 9.9 mmHg in the control group and 68.3 ± 17.4 vs. 31.4 ± 6.9 mmHg in the thrombolysis group. In control vs. thrombolysis group, there were 5 vs. 1 death, 6 vs. 1 hemodynamic decompensation, and 6 vs. 1 patient needing mechanical ventilation. Conclusion Thrombolysis in submassive pulmonary embolism is associated with better right ventricular functions, lower pulmonary artery pressures, and comparable mortality rates.

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