Abstract P212: Kidney Injury Caused By Preeclamptic Pregnancy Improves Postpartum In A Transgenic Rat Model

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Sarah M Kedziora ◽  
Kristin Kraeker ◽  
Lajos Markó ◽  
Dominik N Mueller ◽  
Ralf Dechend ◽  
...  
Keyword(s):  
Blood Pressure ◽  
High Blood Pressure ◽  
Rat Model ◽  
Cardiac Remodeling ◽  
Kidney Injury ◽  
Male Rats ◽  
Transgenic Rat ◽  
Arterial Blood ◽  
Pregnancy And Postpartum ◽  
Transgenic Rat Model

Preeclamptic pregnancies involve mild renal injuries. However, there has been evidence that women with a history of preeclampsia (PE) have an increased risk to develop kidney disease in association to high blood pressure later in life. This study aims to characterize renal injury during pregnancy and postpartum in an established transgenic rat model for PE. Female Sprague-Dawley rats transgenic for the human angiotensinogen gene develop a PE phenotype in pregnancy, including cardiac remodeling, when mated with male rats harboring the human renin gene. Postpartum, blood pressure restores but cardiac remodeling persists. We hypothesize that PE during pregnancy mediates kidney injuries but does not fully restore after ending of the high blood pressure (postpartum). The renal alterations were analyzed by histological staining, gene expression and urine analysis. PE rats have elevated mean arterial blood pressure during pregnancy (PE d19 148.4 ± 20.7 mmHg) compared to normotensive values in control animals (WT d19 105.3 ± 4.6 mmHg). During PE increased expression of kidney injury marker 1 ( Kim-1/18S : PE d21 4.14 ± 3.26; WT d21 0.08 ± 0.02), neutrophil gelatinase associated lipocalin 2 ( Ngal/18S : PE d21 1.64 ± 0.83; WT d21 0.59 ± 0.28) and connective-tissue growth factor ( Ctgf/18S: PE d21 1.51 ± 0.46; WT d21 0.92 ± 0.32) were detected. Kidneys of PE rats showed mild glomerular (PAS-positive glomerular area PE d21 86.2 ± 4.4%; WT d21 79.1 ± 3.2%) and tubular changes during PE pregnancy resulting in albuminuria (albumin/creatinine ratio PE d19 2193.8 ± 1878.2; WT d19 290.4 ± 252.0). However, 4 weeks after pregnancy (approx. 2 years in humans) most of the PE related renal damages were absent including albuminuria and elevated expression of biomarkers ( Kim-1/18S : PE d50 0.09 ± 0.05; WT d50 0.23 ± 0.13; Ctgf/18S : PE d50 0.78 ± 0.25; WT d50 0.8 ± 0.25; Ngal/18S : PE d50 0.37 ± 0.17; WT 50 0.47 ± 0.11). Only mild enlargement of glomerular tuft area (PE d50 7523.8 ± 418.7 μm 2 ; WT d50 7058.4 ± 198.8 μm 2 ) was detected. Overall, the glomerular and tubular injuries are present during pregnancy in this transgenic PE rat. Most restore postpartum, speculating long-term kidney failure observed in humans is associated to hypertension and additional cardiovascular events.

scholarly journals Kidney Injury Caused by Preeclamptic Pregnancy Recovers Postpartum in a Transgenic Rat Model

2021 ◽  
Vol 22 (7) ◽  
pp. 3762
Author(s):  
Sarah M. Kedziora ◽  
Kristin Kräker ◽  
Lajos Markó ◽  
Julia Binder ◽  
Meryam Sugulle ◽  
...  
Keyword(s):  
Rat Model ◽  
Renal Damage ◽  
Kidney Injury ◽  
Tissue Growth ◽  
Female Rats ◽  
Male Rats ◽  
Renal Diseases ◽  
Transgenic Rat ◽  
Increased Risk ◽  
Before And After

Preeclampsia (PE) is characterized by the onset of hypertension (≥140/90 mmHg) and presence of proteinuria (>300 mg/L/24 h urine) or other maternal organ dysfunctions. During human PE, renal injuries have been observed. Some studies suggest that women with PE diagnosis have an increased risk to develop renal diseases later in life. However, in human studies PE as a single cause of this development cannot be investigated. Here, we aimed to investigate the effect of PE on postpartum renal damage in an established transgenic PE rat model. Female rats harboring the human-angiotensinogen gene develop a preeclamptic phenotype after mating with male rats harboring the human-renin gene, but are normotensive before and after pregnancy. During pregnancy PE rats developed mild tubular and glomerular changes assessed by histologic analysis, increased gene expression of renal damage markers such as kidney injury marker 1 and connective-tissue growth factor, and albuminuria compared to female wild-type rats (WT). However, four weeks postpartum, most PE-related renal pathologies were absent, including albuminuria and elevated biomarker expression. Only mild enlargement of the glomerular tuft could be detected. Overall, the glomerular and tubular function were affected during pregnancy in the transgenic PE rat. However, almost all these pathologies observed during PE recovered postpartum.

scholarly journals RNA sequencing reveals induction of specific renal inflammatory pathways in a rat model of malignant hypertension

2021 ◽  
Author(s):  
Carlos Menendez-Castro ◽  
Nada Cordasic ◽  
Fabian B. Fahlbusch ◽  
Arif B. Ekici ◽  
Philipp Kirchner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Blood Pressure ◽  
Rna Sequencing ◽  
High Blood Pressure ◽  
Rat Model ◽  
Kidney Injury ◽  
Malignant Hypertension ◽  
Kidney Cortex ◽  
List Type ◽  
Complement Deposition

Abstract In malignant hypertension, far more severe kidney injury occurs than in the “benign” form of the disease. The role of high blood pressure and the renin–angiotensin–aldosterone system is well recognized, but the pathogenesis of the renal injury of malignant hypertension (MH) remains incompletely understood. Using the rat model of two-kidney, one-clip renovascular hypertension in which some but not all animals develop MH, we performed a transcriptomic analysis of gene expression by RNA sequencing to identify transcriptional changes in the kidney cortex specific for MH. Differential gene expression was assessed in three groups: MH, non-malignant hypertension (NMH), and normotensive, sham-operated controls. To distinguish MH from NMH, we considered two factors: weight loss and typical renovascular lesions. Mean blood pressure measured intraarterially was elevated in MH (220 ± 6.5 mmHg) as well as in NMH (192 ± 6.4 mmHg), compared to controls (119 ± 1.7 mmHg, p < 0.05). Eight hundred eighty-six genes were exclusively regulated in MH only. Principal component analysis revealed a separated clustering of the three groups. The data pointed to an upregulation of many inflammatory mechanisms in MH including pathways which previously attracted relatively little attention in the setting of hypertensive kidney injury: Transcripts from all three complement activation pathways were upregulated in MH compared to NMH but not in NMH compared with controls; immunohistochemistry confirmed complement deposition in MH exclusively. The expression of chemokines attracting neutrophil granulocytes (CXCL6) and infiltration of myeloperoxidase-positive cells were increased only in MH rats. The data suggest that these pathways, especially complement deposition, may contribute to kidney injury under MH. Key messages The most severe hypertension-induced kidney injury occurs in malignant hypertension. In a rat model of malignant hypertension, we assessed transcriptional responses in the kidney exposed to high blood pressure. A broad stimulation of inflammatory mechanisms was observed, but a few specific pathways were activated only in the malignant form of the disease, notably activation of the complement cascades. Complement inhibitors may alleviate the thrombotic microangiopathy of malignant hypertension even in the absence of primary complement abnormalities.

Riluzole Exhibits No Therapeutic Efficacy on a Transgenic Rat model of Amyotrophic Lateral Sclerosis

2020 ◽  
Vol 17 (3) ◽  
pp. 275-285 ◽  
Author(s):  
Si Chen ◽  
Qiao Liao ◽  
Ke Lu ◽  
Jinxia Zhou ◽  
Cao Huang ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neurons ◽  
Rat Model ◽  
Microglial Activation ◽  
Transgenic Rat ◽  
Intragastric Administration ◽  
Behavioral Deficits ◽  
Als Patients ◽  
Lateral Sclerosis ◽  
Transgenic Rat Model

Background: Amyotrophic lateral sclerosis (ALS) is a neurological disorder clinically characterized by motor system dysfunction, with intraneuronal accumulation of the TAR DNAbinding protein 43 (TDP-43) being a pathological hallmark. Riluzole is a primarily prescribed medicine for ALS patients, while its therapeutical efficacy appears limited. TDP-43 transgenic mice are existing animal models for mechanistic/translational research into ALS. Methods: We developed a transgenic rat model of ALS expressing a mutant human TDP-43 transgene (TDP-43M337V) and evaluated the therapeutic effect of Riluzole on this model. Relative to control, rats with TDP-43M337V expression promoted by the neurofilament heavy subunit (NEF) gene or specifically in motor neurons promoted by the choline acetyltransferase (ChAT) gene showed progressive worsening of mobility and grip strength, along with loss of motor neurons, microglial activation, and intraneuronal accumulation of TDP-43 and ubiquitin aggregations in the spinal cord. Results: Compared to vehicle control, intragastric administration of Riluzole (30 mg/kg/d) did not mitigate the behavioral deficits nor alter the neuropathologies in the transgenics. Conclusion: These findings indicate that transgenic rats recapitulate the basic neurological and neuropathological characteristics of human ALS, while Riluzole treatment can not halt the development of the behavioral and histopathological phenotypes in this new transgenic rodent model of ALS.

P3-328: Dissection of physiological and pathological phosphorylation in Axon transgenic rat model of neurofibrillary pathology

2006 ◽  
Vol 2 ◽  
pp. S471-S471
Author(s):  
Miroslava Pevalova ◽  
Jozef Hanes ◽  
Norbert Zilka ◽  
Ludmila Cuninkova ◽  
Martin Cente ◽  
...  
Keyword(s):  
Rat Model ◽  
Transgenic Rat ◽  
Neurofibrillary Pathology ◽  
Transgenic Rat Model

Abstract 119: Influence of Anesthetics on the Hemodynamic Response in a Rat Model of Hemorrhagic Shock

Circulation ◽  
2019 ◽  
Vol 140 (Suppl_2) ◽  
Author(s):  
Claudius Balzer ◽  
Franz J Baudenbacher ◽  
Susan S Eagle ◽  
Michele M Salzman ◽  
William J Cleveland ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Hemorrhagic Shock ◽  
Rat Model ◽  
Cardiovascular Response ◽  
Femoral Vein ◽  
Blood Pressure Measurement ◽  
Experimental Models ◽  
Sprague Dawley ◽  
Compensatory Mechanisms ◽  
Arterial Blood

Introduction: Experimental models of hemorrhagic shock (HS) in rats are important to test new treatments that may improve outcomes in humans, and general anesthesia is required during these experiments. The volatile anesthetic Isoflurane is known for its beneficial effects in rat HS models. Focusing on cardiovascular compensatory mechanisms, we wanted to evaluate Isoflurane versus the injectable anesthetic Pentobarbital in our rat model of mild HS (class 2). We hypothesize that Isoflurane during development of HS improves hemodynamics compared to Pentobarbital. Methods: Twelve Sprague-Dawley rats were initially anesthetized with an intraperitoneal (IP) injection of Pentobarbital (45 mg/kg) and intubated (1 L/min, FiO 2 0.25); heart rate (HR) was monitored by subcutaneous ECG needles. Femoral artery and vein were cannulated for continuous blood pressure measurement and delivery of fluids, respectively. In one group (n=7), anesthesia was continued with repeated IP injections of Pentobarbital (dose mg/kg), the other group (n=5) received continuous Isoflurane (1%). After 30 min of stabilization and administration of Heparin (100 IU/kg), HS was induced by removal of 1 ml of blood over 1 min via the femoral vein, repeated every 3 min until a volume of 5 ml of blood was removed. Mean arterial blood pressure (MAP) and HR were recorded and analyzed in LabChart. Results: During baseline, rats showed no significant differences in HR and MAP between both groups. After 5 ml of hemorrhage, both groups showed significant changes compared to baseline, with significantly higher MAP and HR in rats given only Pentobarbital. Conclusions: In our rat model of HS, Isoflurane dampens the physiologic response to compensate for mild hemorrhage. The cardiovascular response of rats in the Isoflurane group was a decrease of HR and MAP to every ml of hemorrhage, while rats given only Pentobarbital were able to maintain their MAP by raising their HR until decompensation.

scholarly journals Transplants of Adult Mesenchymal and Neural Stem Cells Provide Neuroprotection and Behavioral Sparing in a Transgenic Rat Model of Huntington's Disease

Stem Cells ◽  
2014 ◽  
Vol 32 (2) ◽  
pp. 500-509 ◽  
Author(s):  
Julien Rossignol ◽  
Kyle Fink ◽  
Kendra Davis ◽  
Steven Clerc ◽  
Andrew Crane ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Rat Model ◽  
Transgenic Rat ◽  
Transgenic Rat Model

An EGP-2/Ep-CAM-expressing transgenic rat model to evaluate antibody-mediated immunotherapy

1999 ◽  
Vol 48 (6) ◽  
pp. 303-311 ◽  
Author(s):  
Pamela M. J. McLaughlin ◽  
Bart-Jan Kroesen ◽  
Wim H. A. Dokter ◽  
Henk van der Molen ◽  
Martijn de Groot ◽  
...  
Keyword(s):  
Rat Model ◽  
Transgenic Rat ◽  
Transgenic Rat Model
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