Abstract P089: Assessment Of Sensorimotor Function To Establish A Clinically Relevant Animal Model Of Intracerebral Hemorrhage (ICH) Using The Hypertensive Transgenic Rat (mRen2)27

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Nicholas J Contillo ◽  
Anthony Anzalone ◽  
Nathan McMullen ◽  
Keyan Peterson ◽  
Christine Tschoe ◽  
...  

Uncontrolled hypertension is the leading cause of spontaneous ICH and elevated SBP is a strong predictor of poor outcomes in ICH patients. An animal model of the chronically hypertensive, metabolically dysfunctional and pro-inflammatory state of the ICH patient population is needed to advance clinically-relevant ICH research. Transgenic (mRen2)27 rats overexpress the murine Ren2 gene and develop hypertension and metabolic syndrome by 12-14 weeks of age. Indices of diastolic and systolic cardiac function are in decline in (mRen2)27 males by 30 weeks of age, but are preserved in females at this age. To establish whether (mRen2)27 rats exhibit sensorimotor dysfunction as compared with control Sprague Dawley (SD) rats, male and female (mRen2)27 rats underwent corner turn (CT), vibrissae evoked forelimb placing (VEF), cage wire hang (CWH), and open-field (OF) testing for five consecutive weeks starting at 20-weeks of age (n=16; female=8; each strain). Despite the significant between-strain difference in SBP [189 ± 3 mmHg in (mRen2)27 and 119 ± 3 mmHg in SD; p<0.001], there were no significant between-strain differences in sensorimotor testing at weeks 20, 22, 23, and 24 (Table 1). At week 21, a significant between-strain difference was identified isolated to the VEF test (p<0.01). As sensorimotor testing is critical to assess the effect of experimentally-induced ICH in rodent models, the lack of strain differences supports the viability of (mRen2)27 rats as a clinically relevant model for the comparison of ICH superimposition in the two strains at this age without consistent baseline sensorimotor deficits. (Cardiovascular Sci. and Hypertension & Vasc. Res. Ctrs; Neurosurgery)

2002 ◽  
Vol 93 (3) ◽  
pp. 974-983 ◽  
Author(s):  
Matthew R. Hodges ◽  
Hubert V. Forster ◽  
Paula E. Papanek ◽  
Melinda R. Dwinell ◽  
Genevieve E. Hogan

Our purpose in this study was to identify different ventilatory phenotypes among four different strains of rats. We examined 114 rats from three in-house, inbred strains and one outbred strain: Brown Norway (BN; n = 26), Dahl salt-sensitive ( n = 24), Fawn-hooded Hypertensive (FHH: n = 27), and outbred Sprague-Dawley rats (SD; n = 37). We measured eupneic (room air) breathing and the ventilatory responses to hypoxia (12% O2-88% N2), hypercapnia (7% CO2), and two levels of submaximal exercise. Primary strain differences were between BN and the other strains. BN rats had a relatively attenuated ventilatory response to CO2 ( P < 0.001), an accentuated ventilatory response to exercise ( P < 0.05), and an accentuated ventilatory roll-off during hypoxia ( P < 0.05). Ventilation during hypoxia was lower than other strains, but hyperventilation during hypoxia was equal to the other strains ( P > 0.05), indicating that the metabolic rate during hypoxia decreased more in BN rats than in other strains. Another strain difference was in the frequency and timing components of augmented breaths, where FHH rats frequently differed from the other strains, and the BN rats had the longest expiratory time of the augmented breaths (probably secondary to the blunted CO2 sensitivity). These strain differences not only provide insight into physiological mechanisms but also indicate traits (such as CO2 sensitivity) that are genetically regulated. Finally, the data establish a foundation for physiological genomic studies aimed at elucidating the genetics of these ventilatory control mechanisms.


Author(s):  
Stephanie M. Himmler ◽  
Jena M. Lewis ◽  
Sergio M. Pellis

During play fighting, rats attack and defend the nape, which if contacted is nuzzled with the snout. While all strains of rats can use all defensive tactics to protect the nape, there are strain-typical preferences for using particular tactics This study tests two hypotheses for this strain difference: (1) that each strain has strain-specific thresholds for each tactic, or (2) that each strain attacks differently which leads to strain differences in which defense tactics are used. Juvenile Long-Evans and Sprague-Dawley males were tested with both unfamiliar (experiment 1) and familiar (experiment 2) same-strain and different-strain partners. Experiment two was conducted to determine if familiarity with a different strain might allow rats to modify their strain-typical pattern of play. If hypothesis (1) were true, they would maintain strain-typical defense patterns irrespective of partner strain, whereas for (2) it would vary with partner strain. Hypothesis (1) was supported in the first experiment; all the rats maintained their strain-typical patterns regardless of the partner’s strain. However, the second experiment supported neither hypothesis, as each animal displayed strain-divergent behavior when playing with partners of a different strain as well as with partners of the same strain. Given that in the second experiment subjects were reared in mixed-strain groups, it is possible that, during the early juvenile period, animals are susceptible to discordant social experiences


Author(s):  
D. J. McComb ◽  
J. Beri ◽  
F. Zak ◽  
K. Kovacs

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.


Pancreas ◽  
2006 ◽  
Vol 33 (4) ◽  
pp. 506-507 ◽  
Author(s):  
A. Vonlaufen ◽  
Z. Xu ◽  
B. Daniel ◽  
S. Joshi ◽  
R. K. Kumar ◽  
...  

2018 ◽  
Vol 27 (3) ◽  
pp. 137-44
Author(s):  
Siti Farida ◽  
Desak G.B. Krisnamurti ◽  
Ninik Mudjihartini ◽  
Erni H. Purwaningsih ◽  
Imelda M. Sianipar ◽  
...  

Background: Approximately 80–85% of strokes are ischemic and lead to alterations in neuronal cell morphology and cell death. There is a lack of studies on the effect of the combination of Acalypha indica L. (AI) and Centella asiatica L. (CA) in terms of its neurotherapy property. This study was conducted to investigate the neurotherapeutic effect of the combination of AI–CA extracts in improving rat’s hippocampal neuron injury post-hypoxia.Methods: A total of 36 Sprague-Dawley rats were categorized into six groups and placed in a hypoxia chamber for 7 consecutive days. Then, they were moved to normoxia cages and treated for 7 consecutive days as follows: control group without treatment as a negative control; treatment groups were administered citicoline 50 mg/kgBW as a positive control; three different dose combinations of AI150–CA150, AI200–CA150, and AI250–CA150 mg/kgBW, respectively. Histological analyses were performed to assess the improvement in nerve cell damage in the hippocampus.Results: Treatment with citicoline significantly decreased the damage of nerve cells (30.8%); the combination of the AI–CA extracts of AI150–CA150, AI200–CA150, and AI250–CA150 also significantly decreased the damage of nerve cells (36%, 36.4%, and 30.4%, respectively) compared to the control rats (15.4%).Conclusion: The combination of AI–CA extracts decreased the neuronal damage in the hypoxia-induced hippocampal injury animal model. The improvement effect of the combination of AI–CA extracts was not significantly different to citicoline.


1986 ◽  
Vol 251 (4) ◽  
pp. F655-F661 ◽  
Author(s):  
M. A. Rudd ◽  
R. S. Grippo ◽  
W. J. Arendshorst

Clearance experiments were conducted to determine the effect of acute unilateral renal denervation (DNX) on renal hemodynamics and salt and water excretion in anesthetized 6-wk-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto genetic control rats (WKY). Before DNX, SHR had higher mean arterial pressure (33%) and renal vascular resistance (RVR) (57%) and lower glomerular filtration rate (GFR) (10%); urine flow and sodium excretion were similar. Following DNX in SHR, sodium and water excretion increased by 138 and 62%, respectively (P less than 0.001); GFR and RVR were unchanged. In contrast, DNX in WKY did not affect urine flow (0%) or sodium excretion (-21%). These strain differences were observed in Okamoto-Aoki rats from two sources. Effective DNX was indicated by 95% reduction of norepinephrine content 3 days after DNX in both strains. Six-week-old Sprague-Dawley and Munich-Wistar rats, in contrast to WKY, responded to DNX with a natriuresis (+182%) and diuresis (+95%) (P less than 0.001). Renal function was unaffected by sham DNX in SHR. Our results indicate that efferent renal nerve activity has little tonic influence on the renal vasculature in these young rats. Augmented neurotransmitter release and/or tubular responsiveness may be involved in fluid and electrolyte retention and the pathogenesis of hypertension in SHR. Conversely, blunted renal neuroeffector responses may prevent WKY from developing hypertension.


2014 ◽  
Vol 22 (5) ◽  
pp. 453-459 ◽  
Author(s):  
Yang-Hee Jung ◽  
Sa-Ik Hong ◽  
Shi-Xun Ma ◽  
Ji-Young Hwang ◽  
Jun-Sup Kim ◽  
...  

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A1005-A1005
Author(s):  
Kathrin Sandra Tofil ◽  
Malek Mushref

Abstract Background: Pheochromocytomas and paragangliomas (PPGL) are rare neuro-endocrine tumors associated with a myriad of poor outcomes as a result of long-term exposure to catecholamines. Although paragangliomas are less commonly associated with increased catecholamine production than adrenal pheochromocytomas, there have been a few reports of catecholamine-induced cardiomyopathy in patients diagnosed with PPGL. We report a case of a PPGL associated with hypercoagulability and cardiomyopathy. Clinical Case: 42-year-old man with uncontrolled hypertension presented to the emergency department with abdominal pain. On CT imaging, he was found to have hepatic lesions, aortocaval lymph node concerning for metastatic disease, left renal infarct, and a left ventricular thrombus. Soon after his admission, he developed acute ataxia, gaze palsies and left hemiparalysis. CTA of the head showed a basilar artery thrombus [FJ1] which was treated with emergent thrombectomy. In addition patient had absent distal pulse of the right foot[FJ2], and found to have thrombus of the popliteal artery, which was treated with thrombectomy. Further workup with abdominal MRI showed retroperitoneal mass[FJ3] and multiple hepatic lesions concerning for metastatic extra-adrenal neuroendocrine tumor. Plasma normetanephrine was 4.5 nmol/L (ULN 0.89), plasma metanephrine 0.3 nmol/L (ULN 0.49) Chromogranin A was 387 ng/ml (ULN 160). Ga-68 DOTATE scan was consistent with an extra adrenal paraganglioma with less prominent radiotracer activity in hepatic lesion concerning for dedifferentiated metastatic disease. In addition, echocardiogram showed reduced LV ejection fraction of 24% with global hypokinesis, and confirmed the LV thrombus. Cardiac MRI showed infiltrative nonischemic cardiomyopathy and mild dilation of left ventricle, as well as patchy delayed enhancement in the basal and inferoseptal walls suggestive of myocarditis. Treatment included rivaroxaban[FJ4], lisinopril, doxazosin, furosemide, and carvedilol. Several months after discharge, his EF improved to 48%. Hepatic lesions concerning for dediffertiated tumor vs unrelated malignancy was biopsied[FJ5] and consistent with neuroendocrine tumor. Future plan for his PPGL include revaluation for resection of retroperitoneal mass or DOTA Lutathera therapy. Conclusions: This case highlights a young man who was incidentally found to have metastatic paraganglioma with catecholamine-induced cardiomyopathy. The patient was asymptomatic until he developed significant heart failure. Cardiomyopathy in this setting is thought to be secondary to uncontrolled hypertension, as well as sympathetic overdrive from overstimulation of norepinephrine. We present the case to highlight the management challenges in a patient with PPGL with significant cardiovascular compromise and limited therapeutic options.


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