scholarly journals Spinal NMDA receptor activation constrains inactivity-induced phrenic motor facilitation in Charles River Sprague-Dawley rats

2014 ◽  
Vol 117 (7) ◽  
pp. 682-693 ◽  
Author(s):  
K. A. Streeter ◽  
T. L. Baker-Herman
Keyword(s):  
Motor Neurons ◽  
Neural Activity ◽  
Receptor Activation ◽  
Motor Nucleus ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Tnf Α ◽  
Burst Amplitude ◽  
Nmdar Activation ◽  
Factor Α

Reduced spinal synaptic inputs to phrenic motor neurons elicit a unique form of spinal plasticity known as inactivity-induced phrenic motor facilitation (iPMF). iPMF requires tumor necrosis factor-α (TNF-α) and atypical protein kinase C (aPKC) activity within spinal segments containing the phrenic motor nucleus to stabilize early, transient increases in phrenic burst amplitude into long-lasting iPMF. Here we tested the hypothesis that spinal N-methyl-d-aspartate receptor (NMDAR) activation constrains long-lasting iPMF in some rat substrains. Phrenic motor output was recorded in anesthetized, ventilated Harlan (HSD) and Charles River (CRSD) Sprague-Dawley rats exposed to a 30-min central neural apnea. HSD rats expressed a robust, long-lasting (>60 min) increase in phrenic burst amplitude (i.e., long-lasting iPMF) when respiratory neural activity was restored. By contrast, CRSD rats expressed an attenuated, transient (∼15 min) iPMF. Spinal NMDAR inhibition with DL-2-amino-5-phosphonopentanoic acid (APV) before neural apnea or shortly (4 min) prior to the resumption of respiratory neural activity revealed long-lasting iPMF in CRSD rats that was phenotypically similar to that in HSD rats. By contrast, APV did not alter iPMF expression in HSD rats. Spinal TNF-α or aPKC inhibition impaired long-lasting iPMF enabled by NMDAR inhibition in CRSD rats, suggesting that similar mechanisms give rise to long-lasting iPMF in CRSD rats with NMDAR inhibition as those giving rise to long-lasting iPMF in HSD rats. These results suggest that NMDAR activation can impose constraints on TNF-α-induced aPKC activation after neural apnea, impairing stabilization of transient iPMF into long-lasting iPMF. These data may have important implications for understanding differential responses to reduced respiratory neural activity in a heterogeneous human population.

The time course of inflammatory cytokine secretion in a rat model of postoperative pain does not coincide with the onset of mechanical hyperalgesia

2007 ◽  
Vol 85 (6) ◽  
pp. 613-620 ◽  
Author(s):  
Lisa C. Loram ◽  
Andreas C. Themistocleous ◽  
Linda G. Fick ◽  
Peter R. Kamerman
Keyword(s):  
Postoperative Pain ◽  
Inflammatory Cytokine ◽  
Time Course ◽  
Mechanical Stimulus ◽  
Sprague Dawley ◽  
Tissue Samples ◽  
Sprague Dawley Rats ◽  
Tnf Α ◽  
Primary Hyperalgesia ◽  
Factor Α

We characterized the time course of inflammatory cytokine release at the site of injury and in plasma after surgery on the rat tail. Anesthetized Sprague–Dawley rats had a 20 mm long incision made through the skin and fascia of their tails. Control rats were anesthetized, but no incision was made. Blood and tissue samples were taken 2 h and 1, 2, 4, and 8 days after surgery and analysed by ELISA for interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and cytokine-induced neutrophil chemoattractant-1 (CINC-1). In another group of rats, daily behavioral measurements were made of the rats’ responses to a blunt noxious mechanical stimulus (4 Newtons) applied to their tails. Primary hyperalgesia developed within 2 h of surgery and lasted for 6 days. The tissue concentrations of IL-1β, IL-6, and CINC-1 increased within 24 h of surgery, and TNF-α concentration increased within 48 h of surgery. Thereafter, cytokine concentrations remained elevated for 4 (IL-1β and IL-6) to 8 days (CINC-1, TNF-α) after surgery. Control animals did not develop hyperalgesia and no changes in cytokines concentrations were detected. Thus, in our model of postoperative pain, secretion of inflammatory cytokines IL-1β, IL-6, TNF-α, and CINC-1 was not essential for the initiation of postoperative hyperalgesia.

scholarly journals TNF-α-Mediated RIPK1 Pathway Participates in the Development of Trigeminal Neuropathic Pain in Rats

2022 ◽  
Vol 23 (1) ◽  
pp. 506
Author(s):  
Jo Young Son ◽  
Jin Sook Ju ◽  
Yu Mi Kim ◽  
Dong Kuk Ahn
Keyword(s):  
Neuropathic Pain ◽  
Nerve Injury ◽  
Mechanical Allodynia ◽  
Inflammatory Responses ◽  
Inferior Alveolar Nerve ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Tnf Α ◽  
Factor Α ◽  
Inferior Alveolar Nerve Injury

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) participates in the regulation of cellular stress and inflammatory responses, but its function in neuropathic pain remains poorly understood. This study evaluated the role of RIPK1 in neuropathic pain following inferior alveolar nerve injury. We developed a model using malpositioned dental implants in male Sprague Dawley rats. This model resulted in significant mechanical allodynia and upregulated RIPK1 expression in the trigeminal subnucleus caudalis (TSC). The intracisternal administration of Necrosatin-1 (Nec-1), an RIPK1 inhibitor, blocked the mechanical allodynia produced by inferior alveolar nerve injury The intracisternal administration of recombinant rat tumor necrosis factor-α (rrTNF-α) protein in naive rats produced mechanical allodynia and upregulated RIPK1 expression in the TSC. Moreover, an intracisternal pretreatment with Nec-1 inhibited the mechanical allodynia produced by rrTNF-α protein. Nerve injury caused elevated TNF-α concentration in the TSC and a TNF-α block had anti-allodynic effects, thereby attenuating RIPK1 expression in the TSC. Finally, double immunofluorescence analyses revealed the colocalization of TNF receptor and RIPK1 with astrocytes. Hence, we have identified that astroglial RIPK1, activated by the TNF-α pathway, is a central driver of neuropathic pain and that the TNF-α-mediated RIPK1 pathway is a potential therapeutic target for reducing neuropathic pain following nerve injury.

Attenuated febrile response to lipopolysaccharide in rats with biliary obstruction

2000 ◽  
Vol 279 (1) ◽  
pp. G172-G177 ◽  
Author(s):  
L. K. McCullough ◽  
Y. Takahashi ◽  
T. Le ◽  
Q. J. Pittman ◽  
M. G. Swain
Keyword(s):  
Serum Levels ◽  
Sham Operation ◽  
Sprague Dawley ◽  
Febrile Response ◽  
Perioperative Morbidity ◽  
Sprague Dawley Rats ◽  
Tnf Α ◽  
Factor Α ◽  
Generation Male ◽  
Necrosis Factor

Patients with biliary tract obstruction have unexplained, inordinately high rates of perioperative morbidity and mortality, whereas cholestatic animals display abnormal hypothalamic responses to pyrogenic stimuli. We asked if obstructive cholestasis was associated with abnormal fever generation. Male Sprague-Dawley rats (250 g) underwent laparotomy for implantation of thermistors and either bile duct resection (BDR) or sham operation. After recovery, temperatures were recorded by telemetry and conscious, unrestrained rats in each group were injected intraperitoneally with either interleukin-1β (IL-1β;1 μg/kg) or Escherichia colilipopolysaccharide (LPS; 50 μg/kg). Baseline temperatures in both groups were similar. Febrile responses after IL-1β injection in BDR and sham groups were not significantly different. However, in response to LPS injection, BDR rats showed an initial hypothermia with a subsequently attenuated febrile response. Administration of anti-tumor necrosis factor-α (TNF-α) antibody 2 h before LPS injection blocked the LPS-induced hypothermia seen in BDR animals. However, serum levels of TNF-α were not significantly different between sham and BDR animals after LPS injection at any time point measured (0, 1.5, and 3 h).

scholarly journals Anti-Inflammation Effect of Small Molecule Oligopeptides Prepared from Panax ginseng C. A. Meyer in Rats

Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 858 ◽  
Author(s):  
Meihong Xu ◽  
Qihe Chen ◽  
Rui Fan ◽  
Junbo Wang ◽  
Yong Li
Keyword(s):  
Platelet Activating Factor ◽  
Sprague Dawley ◽  
Edema Formation ◽  
Leukotriene D4 ◽  
Sprague Dawley Rats ◽  
Tnf Α ◽  
G 12 ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Acute And Chronic Inflammation

The present study was designed to investigate the anti-inflammatory effects of ginseng oligopeptides (GOPs). For the anti-inflammatory activity, dextran-induced paw edema and granuloma models were used in Sprague-Dawley rats (180–200 g, 12 weeks old, n = 10). Rats were treated orally with GOPs (0, 62.5, 125, 250 and 500 mg/kg) for prophylaxis. In the granuloma model, the levels of NO, Tumor necrosis factor-α (TNF-α), interleukin IL-β, and interleukin IL-10 in serum were evaluated. In addition, in the edema model, the level of TNF-α, prostaglandin E2 (PGE2), Leukotriene D4 (LTD4), and the platelet activating factor (RAF) in paw tissue were detected. PCR assessed the effect of GOPs on the expression of MAPK and NF-κB. The results showed that oral administration of GOPs inhibited inflammation caused by cotton pellet and dextran. GOPs significantly inhibited the edema formation via MAPK and NF-κB. These findings suggested that GOPs have a beneficial effect on acute and chronic inflammation, and the mechanism possibly mediated by inhibiting gene expression involved in inflammation and downregulating inflammatory mediators.

scholarly journals The anti-apoptotic, antioxidant and anti-inflammatory effects of curcumin on acrylamide-induced neurotoxicity in rats

2020 ◽  
Author(s):  
Jie Guo ◽  
Xiaolu Cao ◽  
Xianmin Hu ◽  
Shulan Li ◽  
Jun Wang
Keyword(s):  
Oxidative Stress ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Tunel Staining ◽  
Apoptotic Cells ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Necrosis Factor

Abstract Background: Acrylamide (ACR) formed during heating of tobacco and carbohydrate-rich food as well as widely applied in industries has been known as a well-established neurotoxic pollutant. Although the precise mechanism is unclear, enhanced apoptosis, oxidative stress and inflammation have been demonstrated to contribute to the ACR-induced neurotoxicity. In this study, we assessed the possible anti-apoptotic, antioxidant and anti-inflammatory effects of curcumin, the most active component in a popular spice known as turmeric, on the neurotoxicity caused by ACR in rats.Methods: Curcumin at the dose of 50 and 100 mg/kg was orally given to ACR- intoxicated Sprague-Dawley rats exposed by ACR at 40mg/kg for 4 weeks. All rats were subjected to behavioral analysis. The HE staining and terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL) staining were used to detect histopathological changes and apoptotic cells, respectively. The mRNA and protein expressions of apoptosis-related molecule telomerase reverse transcriptase (TERT) were detected using real-time PCR and immunohistochemistry, respectively. The contents of malondialdehyde (MDA) and glutathione (GSH) as well as the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured as the indicators for evaluating the level of oxidative stress in brain. The levels of pro-inflammatory cytokinestumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the cerebral homogenates were detected using ELISA assay.Results: ACR-induced weigh loss, deficits in motor function as well as pathological alterations in brains were significantly improved in rats administrated with 50 and 100 mg/kg curcumin. TUNEL-positive apoptotic cells in curcumin-treated ACR intoxicated brains were less than those in the ACR model group. Curcumin administration especially at the dose of 100 mg/kg upregulated the TERT mRNA expression and enhanced the number of TERT-positive cells in ACR-intoxicated cortex tissues. Moreover, curcumin treatment reduced the concentrations of TNF-α, IL-1β and MDA, while increased the GSH contents as well as the SOD and GSH-Px activities in the cerebral homogenates, in comparison to ACR control group.Conclusions: These data suggested the anti-apoptotic, antioxidant and anti-inflammatory effects of curcumin on ACR-induced neurotoxicity in rats. Maintaining TERT-related anti-apoptotic function might be one mechanism underlying the protective effect of curcumin on ACR-intoxicated brains.

Abstract 400: A Nonpeptide Angiotensin (Ang) II Type 2 Receptor (AT2R) Agonist Improves Diabetic Nephropathy via Inhibition of Renal Inflammation

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Luis Matavelli ◽  
Helmy M Siragy
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Inflammatory Factors ◽  
Sprague Dawley ◽  
Renal Inflammation ◽  
Sprague Dawley Rats ◽  
Tnf Α ◽  
Compound 21 ◽  
Factor Α

We explored the hypothesis that direct AT2R stimulation improves albuminuria in diabetes by reducing renal inflammation and improving oxidative stress. Sham and DM Sprague-Dawley rats were treated for 4 weeks with vehicle (V) or AT2R agonist Compound 21 (C21; 0.3 mg/kg/d). C21 was infused systemically by osmotic minipump. Diabetes was induced by streptozotocin (65 mg/kg IP). At the end of study, we monitored BP, 24h urine collection for measurements of urinary albumin to creatinine ratio (UACR), and renal interstitial fluid (RIF) levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), nitric oxide (NO), cGMP, and 8-isoprostane (ISO). Data are shown as mean±SE. There were no significant differences in BP between different treatments. UACR (μg/mg), compared to Control+V (14±2), increased significantly in DM+V (60±3, p<0.001) and did not change in Control+C21 (16±2). Compared to DM+V, UACR decreased significantly by 20% in DM+C21 (50±3, P<0.04). RIF TNF-α and IL-6 (pg/min), compared to Control+V (0.040±0.001 and 0.613±0.012, respectively), increased in DM+V (0.046±0.001 and 0.652±0.005, P<0.01) and did not change in Control+C21 (0.041±0.001 and 0.622±0.008). Compared to DM+V, RIF TNF-α and IL-6 decreased in DM+C21 (0.041±0.001 and 0.616±0.007, P<0.01). RIF NO (μmol/min) and cGMP (fmol/min), compared to Control+V (7.0±0.3 and 3.8±0.4), decreased in DM+V (4.3±0.5 and 1.7±0.2, P<0.001) and did not change in Control+C21 (6.6±0.3 and 3.7±0.5). RIF NO and cGMP increased in DM+C21 (6.2±0.8 and 2.7±0.4, P<0.04) compared to DM+V. RIF ISO (pmol/min), compared to Control+V (0.135±0.005), increased in DM+V (0.158±0.007, P<0.02) and did not change in Control+C21 (0.134±0.010). Compared to DM+V, RIF ISO significantly decreased in DM+C21 (0.135±0.006, P<0.03). We concluded that direct AT2R stimulation by the nonpeptide agonist C21 improves diabetic nephropathy through the reduction of renal inflammatory factors and improvement of oxidative stress.

Mineralocorticoid Receptor Activation by Aldosterone or Corticosterone Induces Hypertension, Myocardial Infarction and Proteinuria

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 723-723
Author(s):  
Qing-Feng Tao ◽  
Diego Martinez vasquez ◽  
Ricardo Rocha ◽  
Gordon H Williams ◽  
Gail K Adler
Keyword(s):  
Myocardial Infarction ◽  
Drinking Water ◽  
Mineralocorticoid Receptor ◽  
Critical Role ◽  
Weight Ratio ◽  
Myocardial Necrosis ◽  
Receptor Activation ◽  
Control Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

P165 Aldosterone through its interaction with the mineralocorticoid receptor (MR) plays a critical role in the development of hypertension and cardiovascular injury (CVI). Normally, MR is protected by 11β-hydroxysteroid dehydrogenase (11β-HSD) which inactivates glucocorticoids preventing their binding to MR. We hypothesis that if activation of MR by either aldosterone or glucocorticoids induces hypertension and CVI, then the inhibition of 11β-HSD with glycyrrhizin (GA), a natural inhibitor of 11β-HSD, should induce damage similar to that observed with aldosterone. Sprague-Dawley rats were uninephrectomized, and treated for 4 weeks with 1% NaCl (in drinking water) for the control group, 1% NaCl + aldosterone infusion (0.75 μg/h), or 1% NaCl + GA (3.5 g/l in drinking water). After 4 weeks, aldosterone and GA caused significant increases in blood pressure compared to control rats ([mean ± SEM] 211± 9, 205 ± 12, 120 ± 9 mmHg, respectively, p<0.001). Both aldosterone- and GA-treated rats had a significant increase in proteinuria (152.2 ± 8.7 and 107.7 ± 19.5 mg/d, respectively) versus controls (51.2 ± 9.5 mg/d). There was a significant increase (p<0.001) in heart to body weight ratio in the rats treated with aldosterone or GA compared with control (3.92 ± 0.10, 3.98 ± 0.88, and 3.24 ± 0.92 mg/g, respectively). Hearts of GA and aldosterone treated rats showed similar histological changes consisting of biventricular myocardial necrosis and fibrinoid necrosis of small coronary arteries and arterioles. These data suggests that in rodents activation of MR by either aldosterone or corticosterone leads to severe hypertension, vascular injury, proteinuria and myocardial infarction. Thus, 11β-HSD plays an important role in protecting the organism from injury.

Activated Kupffer cells cause a hypermetabolic state after gentle in situ manipulation of liver in rats

2001 ◽  
Vol 280 (6) ◽  
pp. G1076-G1082 ◽  
Author(s):  
Peter Schemmer ◽  
Nobuyuki Enomoto ◽  
Blair U. Bradford ◽  
Hartwig Bunzendahl ◽  
James A. Raleigh ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Kupffer Cells ◽  
Cell Function ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Hypermetabolic State ◽  
Hypoxia Marker ◽  
Factor Α ◽  
Necrosis Factor

Harvesting trauma to the graft dramatically decreases survival after liver transplantation. Since activated Kupffer cells play a role in primary nonfunction, the purpose of this study was to test the hypothesis that organ manipulation activates Kupffer cells. To mimic what occurs with donor hepatectomy, livers from Sprague-Dawley rats underwent dissection with or without gentle organ manipulation in a standardized manner in situ. Perfused livers exhibited normal values for O2 uptake (105 ± 5 μmol · g−1 · h−1) measured polarigraphically; however, 2 h after organ manipulation, values increased significantly to 160 ± 8 μmol · g−1 · h−1 and binding of pimonidazole, a hypoxia marker, increased about threefold ( P < 0.05). Moreover, Kupffer cells from manipulated livers produced three- to fourfold more tumor necrosis factor-α and PGE2, whereas intracellular calcium concentration increased twofold after lipopolysaccharide compared with unmanipulated controls ( P < 0.05). Gadolinium chloride and glycine prevented both activation of Kupffer cells and effects of organ manipulation. Furthermore, indomethacin given 1 h before manipulation prevented the hypermetabolic state, hypoxia, depletion of glycogen, and release of PGE2 from Kupffer cells. These data indicate that gentle organ manipulation during surgery activates Kupffer cells, leading to metabolic changes dependent on PGE2 from Kupffer cells, which most likely impairs liver function. Thus modulation of Kupffer cell function before organ harvest could be beneficial in human liver transplantation and surgery.

scholarly journals THERAPEUTIC PROFILING OF NANO ENCAPSULATED DIOSGENIN VIA ATTENUATING HORMONAL STATUS, CELL PROLIFERATION, INFLAMMATORY RESPONSES, AND APOPTOSIS IN AN ANIMAL MODEL OF MAMMARY ONCOGENESIS

2021 ◽  
pp. 126-132
Author(s):  
MANOBHARATHI VENGAIMARAN ◽  
KALAIYARASI DHAMODHARAN ◽  
MIRUNALINI SANKARAN
Keyword(s):  
Cell Proliferation ◽  
Molecular Docking ◽  
Cyclin D1 ◽  
Inflammatory Responses ◽  
Chitosan Nanoparticles ◽  
Hormonal Status ◽  
Sprague Dawley ◽  
Therapeutic Impact ◽  
Sprague Dawley Rats ◽  
Tnf Α

Objective: The central motive of this study is to explore the therapeutic impact of Diosgenin encapsulated Chitosan nanoparticles (DG@CS-NP) on mammary carcinogenesis in female Sprague Dawley rats via modulating hormonal status, cell proliferation, inflammatory responses, and Apoptosis. Methods: 7,12-dimethylbenz(a)anthracene (DMBA) was administered subcutaneously near the mammary gland (25 mg/kg b. wt) to provoke mammary tumor in female Sprague Dawley rats. Following the progress of a tumor, DMBA-induced tumor-bearing rats were medicated orally with 5 mg/kg b. wt of DG@CS-NP. Consequently, the expression of ER, PR, PCNA, Cyclin D1, NF-κB, TNF-α, Bcl-2, Caspases-3, and p53 in experimental rats were revealed via architectural immunohistochemistry. Further, Diosgenin interactions with these proteins were evidently confirmed by molecular docking analysis. Results: As a result, we noticed diminished levels of ER, PR, PCNA, Cyclin D1, NF-κB, TNF-α, and Bcl-2 expressions in DG@CS-NP medicated rats as well as with elevated levels of Caspases-3 and p53 expressions. In DMBA rats, the expressions were vice versa. Additionally, molecular docking analyses support these outcomes by highlighting the strong interaction between Diosgenin and breast cancer targets. Conclusion: These reports prove that DG@CS-NP imposes its therapeutic impact by hormonal adjustments, downregulating proteins involved in inflammation and cellular proliferation, and thereby promotes apoptosis by impeding apoptotic inhibitors.

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