scholarly journals Stress Induces the Danger-Associated Molecular Pattern HMGB-1 in the Hippocampus of Male Sprague Dawley Rats: A Priming Stimulus of Microglia and the NLRP3 Inflammasome

2015 ◽  
Vol 35 (1) ◽  
pp. 316-324 ◽  
Author(s):  
M. D. Weber ◽  
M. G. Frank ◽  
K. J. Tracey ◽  
L. R. Watkins ◽  
S. F. Maier
Keyword(s):  
Nlrp3 Inflammasome ◽  
Sprague Dawley ◽  
Priming Stimulus ◽  
Molecular Pattern ◽  
Sprague Dawley Rats

scholarly journals eNAMPT neutralization reduces preclinical ARDS severity via rectified NFkB and Akt/mTORC2 signaling

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Tadeo Bermudez ◽  
Saad Sammani ◽  
Jin H. Song ◽  
Vivian Reyes Hernon ◽  
Carrie L. Kempf ◽  
...  
Keyword(s):  
Lung Injury ◽  
Signaling Pathway ◽  
Unmet Need ◽  
Serum Lactate ◽  
Sprague Dawley ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Molecular Pattern ◽  
Sprague Dawley Rats ◽  
Pathway Activation ◽  
Nfkb Pathway

AbstractDespite encouraging preclinical data, therapies to reduce ARDS mortality remains a globally unmet need, including during the COVID-19 pandemic. We previously identified extracellular nicotinamide phosphoribosyltransferase (eNAMPT) as a novel damage-associated molecular pattern protein (DAMP) via TLR4 ligation which regulates inflammatory cascade activation. eNAMPT is tightly linked to human ARDS by biomarker and genotyping studies in ARDS subjects. We now hypothesize that an eNAMPT-neutralizing mAb will significantly reduce the severity of ARDS lung inflammatory lung injury in diverse preclinical rat and porcine models. Sprague Dawley rats received eNAMPT mAb intravenously following exposure to intratracheal lipopolysaccharide (LPS) or to a traumatic blast (125 kPa) but prior to initiation of ventilator-induced lung injury (VILI) (4 h). Yucatan minipigs received intravenous eNAMPT mAb 2 h after initiation of septic shock and VILI (12 h). Each rat/porcine ARDS/VILI model was strongly associated with evidence of severe inflammatory lung injury with NFkB pathway activation and marked dysregulation of the Akt/mTORC2 signaling pathway. eNAMPT neutralization dramatically reduced inflammatory indices and the severity of lung injury in each rat/porcine ARDS/VILI model (~ 50% reduction) including reduction in serum lactate, and plasma levels of eNAMPT, IL-6, TNFα and Ang-2. The eNAMPT mAb further rectified NFkB pathway activation and preserved the Akt/mTORC2 signaling pathway. These results strongly support targeting the eNAMPT/TLR4 inflammatory pathway as a potential ARDS strategy to reduce inflammatory lung injury and ARDS mortality.

scholarly journals EXPRESS: Endothelial-derived eNAMPT drives EndMT and preclinical PH: Rescue by an eNAMPT-neutralizing mAb

2021 ◽  
pp. 204589402110597
Author(s):  
Mohamed Ahmed ◽  
Nahla Zaghloul ◽  
Prisca Zimmerman ◽  
Nancy G. Casanova ◽  
Xiaoguang Sun ◽  
...  
Keyword(s):  
Vascular Remodeling ◽  
Unmet Need ◽  
Sprague Dawley ◽  
Mesenchymal Transition ◽  
Molecular Pattern ◽  
Sprague Dawley Rats ◽  
Sequencing Studies ◽  
Pulmonary Arterial ◽  
Nicotinamide Phosphoribosyl Transferase

Rationale: Pharmacologic interventions to halt/reverse the vascular remodeling and right ventricular (RV) dysfunction in pulmonary arterial hypertension (PAH) remains an unmet need. We previously demonstrated extracellular nicotinamide phosphoribosyl-transferase (eNAMPT) as a DAMP (damage-associated molecular pattern protein) contributing to PAH pathobiology via TLR4 ligation. We examined the role of endothe-lial cell (EC)-specific eNAMPT in experimental PH and an eNAMPT-neutralizing mAb as a therapeutic strategy to reverse established PH. Methods: Hemodynam-ic/echocardiographic measurements and tissue analyses were performed in Sprague Dawley rats exposed to 10% hypoxia/Sugen (3 weeks) followed by return to normoxia and weekly intraperitoneal delivery of the eNAMPT mAb (1 mg/kg). WT C57BL/6J mice and conditional EC-cNAMPTec-/- mice were exposed to 10% hypoxia (3 weeks). Bio-chemical and RNA sequencing studies were performed on rat PH lung tissues and human PAH PBMCs. Results: Hypoxia/Sugen-exposed rats exhibited multiple indices of severe PH (RVSP, Fulton index), including severe vascular remodeling, compared to control rats. PH severity indices and plasma levels of eNAMPT, IL-6, and TNF-a were all significantly attenuated by eNAMPT mAb neutralization. Compared to hypoxia-exposed WT mice, cNAMPTec-/- KO mice exhibited significantly reduced PH severity and evidence of EC to mesenchymal transition (EndMT). Finally, biochemical and RNAseq analyses revealed eNAMPT mAb-mediated rectification of dysregulated inflammatory signaling pathways (TLR/NF-κB, MAP kinase, Akt/mTOR) and EndMT in rat PH lung tissues and human PAH PBMCs. Conclusions: These studies underscore EC-derived eNAMPT as a key contributor to PAH pathobiology and support the eNAMPT/TLR4 inflammatory pathway as a highly druggable therapeutic target to reduce PH severity and reverse PAH.

Ultrastructural Investigation of Spontaneous Pituitary Adenomas in Aging Sprague-Dawley Rats

1982 ◽  
Vol 40 ◽  
pp. 216-217
Author(s):  
D. J. McComb ◽  
J. Beri ◽  
F. Zak ◽  
K. Kovacs
Keyword(s):  
Microscopic Study ◽  
Pituitary Adenomas ◽  
Wistar Rats ◽  
Microscopic Level ◽  
Sprague Dawley ◽  
Prolactin Cells ◽  
Light Microscopic Level ◽  
Ultrastructural Investigation ◽  
Sprague Dawley Rats ◽  
Long Evans

Investigation of the spontaneous pituitary adenomas in rat have been limited mainly to light microscopic study. Furth et al. (1973) described them as chromophobic, secreting prolactin. Kovacs et al. (1977) in an ul trastructural investigation of adenomas of old female Long-Evans rats, found that they were composed of prolactin cells. Berkvens et al. (1980) using immunocytochemistry at the light microscopic level, demonstrated that some spontaneous tumors of old Wistar rats could contain GH, TSH or ACTH as well as PRL.

Early Development of Drug-Induced Hepatic Necrosis

1971 ◽  
Vol 29 ◽  
pp. 576-577
Author(s):  
F. G. Zaki ◽  
E. Detzi ◽  
C. H. Keysser
Keyword(s):  
Early Development ◽  
Hepatic Necrosis ◽  
Screening Tests ◽  
Dense Matrix ◽  
Sprague Dawley ◽  
Electron Microscopic ◽  
Drug Induced ◽  
Hepatocellular Damage ◽  
Sprague Dawley Rats ◽  
Microscopic Studies

This study represents the first in a series of investigations carried out to elucidate the mechanism(s) of early hepatocellular damage induced by drugs and other related compounds. During screening tests of CNS-active compounds in rats, it has been found that daily oral administration of one of these compounds at a dose level of 40 mg. per kg. of body weight induced diffuse massive hepatic necrosis within 7 weeks in Charles River Sprague Dawley rats of both sexes. Partial hepatectomy enhanced the development of this peculiar type of necrosis (3 weeks instead of 7) while treatment with phenobarbital prior to the administration of the drug delayed the appearance of necrosis but did not reduce its severity.Electron microscopic studies revealed that early development of this liver injury (2 days after the administration of the drug) appeared in the form of small dark osmiophilic vesicles located around the bile canaliculi of all hepatocytes (Fig. 1). These structures differed from the regular microbodies or the pericanalicular multivesicular bodies. They first appeared regularly rounded with electron dense matrix bound with a single membrane. After one week on the drug, these vesicles appeared vacuolated and resembled autophagosomes which soon developed whorls of concentric lamellae or cisterns characteristic of lysosomes (Fig. 2). These lysosomes were found, later on, scattered all over the hepatocytes.

Ultrastructural investigation of spontaneous pituitary gonadotroph cell adenomas in aging Sprague-Dawley rats

1983 ◽  
Vol 41 ◽  
pp. 702-703
Author(s):  
D. J. McComb ◽  
J. Beri ◽  
F. Zak ◽  
K. Kovacs
Keyword(s):  
Electron Microscopy ◽  
Animal Model ◽  
Epoxy Resin ◽  
Immunoelectron Microscopy ◽  
Tumor Type ◽  
Gonadal Function ◽  
Sprague Dawley ◽  
Male And Female ◽  
Reticulin Fibers ◽  
Sprague Dawley Rats

Gonadotroph cell adenomas of the pituitary are infrequent in human patients and are not invariably associated with altered gonadal function. To date, no animal model of this tumor type exists. Herein, we describe spontaneous gonadotroph cell adenomas in old male and female Sprague-Dawley rats by histology, immunocytology and electron microscopy.The material consisted of the pituitaries of 27 male and 38 female Sprague Dawley rats, all 26 months of age or older, removed at routine autopsy. Sections of formal in-fixed, paraffin-embedded tissue were stained with hematoxylin-phloxine-saffron (HPS), the PAS method and the Gordon-Sweet technique for the demonstration of reticulin fibers. For immunostaining, sections were exposed to anti-rat β-LH, anti-ratβ-TSH, anti-rat PRL, anti-rat GH and anti-rat ACTH 1-39. For electron microscopy, tissue was fixed in 2.5% glutaraldehyde, postfixed in 1% OsO4 and embedded in epoxy-resin. Tissue fixed in 10% formalin, embedded in epoxy resin without osmification, was used for immunoelectron microscopy.

Freeze-etch studies of epiphyseal growth plate cartilage reveal matrix vesicles associated with calcification

1978 ◽  
Vol 36 (2) ◽  
pp. 670-671
Author(s):  
Russell N. A. Cecil ◽  
H. Clarke Anderson
Keyword(s):  
Chromic Acid ◽  
Light And Electron Microscopy ◽  
Matrix Vesicles ◽  
Matrix Vesicle ◽  
Glycerol Solution ◽  
Sprague Dawley ◽  
Epiphyseal Growth Plate ◽  
Growth Plates ◽  
Sprague Dawley Rats ◽  
Tibial Epiphyseal

Unfixed proximal tibial epiphyseal growth plates were studied by freeze-etch to confirm the presence of extracellular calcifying matrix vesicles and to determine the substructure of matrix vesicle membranes as compared to plasma and other membranes of intact chondrocytes. Growth plates from 6-10 week old Sprague-Dawley rats were cut into 1x3 mm blocks whose long dimension was oriented either perpendicular or parallel to the long axis of the tibia. Some blocks were fixed at pH 7. 0 in 0. 2M cacodylate - buffered 2. 5% glutaraldehyde for 1 hour at 4ÅC. The blocks were immersed in 30% glycerol solution at 4ÅC for 1 hour, frozen in liquid nitrogen, and then fractured, etched for 2 minutes, and coated with platinum, carbon and 0. 2% Formvar solution. The replicas were cleaned with chromic acid, floated onto Formvar coated grids, and examined with a Phillips EM 300 electron microscope.Fixed and unfixed specimens appeared similar in ultrastructure. Chondrocytes, matrix, and matrix vesicles were identified. In specimens fractured parallel to the long axis of the tibia, the reserve, proliferative, hypertrophic, and calcifying zones could be discerned as described by light and electron microscopy.

Sarcolemmal permeability changes during early myocardial anoxia

1978 ◽  
Vol 36 (2) ◽  
pp. 642-643
Author(s):  
M. Ashraf ◽  
L. Landa ◽  
L. Nimmo ◽  
C. M. Bloor
Keyword(s):  
Cell Membrane ◽  
Membrane Permeability ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Cell Membrane Permeability ◽  
Enzyme Release ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Sarcolemmal Permeability ◽  
Membrane Changes

Following coronary artery occlusion, the myocardial cells lose intracellular enzymes that appear in the serum 3 hrs later. By this time the cells in the ischemic zone have already undergone irreversible changes, and the cell membrane permeability is variably altered in the ischemic cells. At certain stages or intervals the cell membrane changes, allowing release of cytoplasmic enzymes. To correlate the changes in cell membrane permeability with the enzyme release, we used colloidal lanthanum (La+++) as a histological permeability marker in the isolated perfused hearts. The hearts removed from sprague-Dawley rats were perfused with standard Krebs-Henseleit medium gassed with 95% O2 + 5% CO2. The hypoxic medium contained mannitol instead of dextrose and was bubbled with 95% N2 + 5% CO2. The final osmolarity of the medium was 295 M osmol, pH 7. 4.

Light and electron microscopic investigation of adenohypophyses of germfree, food-restricted, and germfree-food restricted aging, male lobund-wistar rats

1988 ◽  
Vol 46 ◽  
pp. 352-353
Author(s):  
G. Ilse ◽  
K. Kovacs ◽  
N. Ryan ◽  
T. Sano ◽  
L. Stefaneanu ◽  
...  
Keyword(s):  
Wistar Rats ◽  
Microscopic Investigation ◽  
Electron Microscopic Investigation ◽  
Aging Male ◽  
Sprague Dawley ◽  
Electron Microscopic ◽  
Sprague Dawley Rats ◽  
Old Rats ◽  
Ad Libitum ◽  
Microscopic Findings

Germfree state and food restriction have been shown to increase life span and delay tumor occurrence in rats. We report here the histologic, immunocytochemical and electron microscopic findings of adenohypophyses of aging, male Lobund-Wistar rats raised at Lobund Laboratories. In our previous study, the morphologic changes in the adenohypophyses of old rats have been extensively investigated by histology, immunocytochemistry and electron microscopy. Lactotroph adenomas were frequent in Long-Evans and Sprague-Dawley rats, whereas gonadotroph adenomas were frequent in Sprague-Dawley and Wistar rats.Male Lobund-Wistar rats were divided into four groups: 1) conventional, which were raised under normal non-germfree environment and received food ad libitum; 2) germfree-food ad libitum; 3) conventional environment-food restricted and 4) germfree-food restricted. The adenohypophyses were removed from 6-month-, 18-month- and 30-month-old rats. For light microscopy, adenohypophyses were fixed in formalin and embedded in paraffin.

Permeability of the microcirculation in area postrema of rat

1988 ◽  
Vol 46 ◽  
pp. 348-349
Author(s):  
Shams M. Ghoneim ◽  
Frank M. Faraci ◽  
Gary L. Baumbach
Keyword(s):  
Brain Stem ◽  
Area Postrema ◽  
Upper Body ◽  
Sprague Dawley ◽  
Sodium Cacodylate ◽  
Acute Hypertension ◽  
Sprague Dawley Rats ◽  
Ultrastructural Characteristics ◽  
The Brain ◽  
Adjacent Brain

The area postrema is a circumventricular organ in the brain stem and is one of the regions in the brain that lacks a fully functional blood-brain barrier. Recently, we found that disruption of the microcirculation during acute hypertension is greater in area postrema than in the adjacent brain stem. In contrast, hyperosmolar disruption of the microcirculation is greater in brain stem. The objective of this study was to compare ultrastructural characteristics of the microcirculation in area postrema and adjacent brain stem.We studied 5 Sprague-Dawley rats. Horseradish peroxidase was injected intravenously and allowed to circulate for 1, 5 or 15 minutes. Following perfusion of the upper body with 2.25% glutaraldehyde in 0.1 M sodium cacodylate, the brain stem was removed, embedded in agar, and chopped into 50-70 μm sections with a TC-Sorvall tissue chopper. Sections of brain stem were incubated for 1 hour in a solution of 3,3' diaminobenzidine tetrahydrochloride (0.05%) in 0.05M Tris buffer with 1% H2O2.

A complex network of “snake-like tubules” revealed by the NADPase cytochemical reaction in the acinar cell of pancreas

1984 ◽  
Vol 42 ◽  
pp. 666-667
Author(s):  
A.R. Beaudoin ◽  
G. Grondin ◽  
A. Lord ◽  
M. Pelletier
Keyword(s):  
Acinar Cell ◽  
Lead Acetate ◽  
Ultrastructural Localization ◽  
Sodium Acetate Buffer ◽  
Zymogen Granules ◽  
Sprague Dawley ◽  
Dense Bodies ◽  
Sprague Dawley Rats ◽  
Cytochemical Reaction ◽  
Cellular Organelles

We have recently described the ultrastructural localization of NADPase activity in the exocrine pancreas of rat. The enzyme was found in the intermediate saccules of the Golgi apparatus, in dense bodies and lysosomes but was absent from zymogen granules. A very intense reaction was noticed in a peculiar structure which was termed “Snake-Like Tubule” (SLT). The purposes of the present study were firstly to delineate SLT distribution in the acinar cell and secondly to define any possible relationship or association with other cellular organelles.NADPase cytochemical reaction was performed on the pancreas of adult Sprague Dawley rats. Small lobules were excised and fixed for 50 min, at 4°C, in 2% glutaraldehyde buffered with 0.1M cacodylate at pH 7.2. Lobules were rinsed several times with the same buffer containing 570 sucrose and cut with a Mcllwayn tissue chopper. Sections were washed several times with buffer and incubated for 2 hr at 37°C in the following medium: 4mM NADPH; 40mM sodium acetate buffer, pH 5.0; 4mM lead acetate and 5% sucrose.

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