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At least 109 records · Page 6Linked to original sources
PubMed1996

Transplantation of human fetal striatum into a rodent model of Huntington's disease ameliorates locomotor deficits.

Previous studies have demonstrated that syngeneic transplants of striatal tissue can ameliorate locomotor deficits in rodent models of Huntington's disease (HD). In the present study, we have examined whether human to rat xenografts of fetal striatal tissue can exert a similar recovery of function. Rodents with unilateral striatal lesions were transplanted with human striatal cells from a donor 14 weeks post-conception, and subsequently displayed a progressive decrease in rotational asymmetry in comparison to sham (saline) transplanted animals. Histological analysis revealed acetylcholinesterase (AChE)-positive fibers and NADPH-diaphorase (NADPH-d)-positive neurons within transplanted tissue. These results suggest that human fetal striatum at a gestational age of 14 weeks may potentially be useful as a source of donor tissue for transplantation in the treatment of HD.

Acetylcholinesterase↗
PubMedDate not supplied

Neonatal cocaine exposure, activity, and responsivity to cocaine in a rodent model.

This study examined the effects of neonatal cocaine exposure on running wheel activity and subsequent responsivity to cocaine using a rodent model. Subjects were artificially reared from postnatal (PND) days 4-10 via an intragastric cannula. The four treatment groups included two cocaine doses (20 mg/kg/day and 40 mg/kg/day), an artificially reared control and a normally reared suckled control. Subjects were tested at either PND 21 through PND 24 (Experiment 1) or PND 60 through PND 70 (Experiment 2) for 2 consecutive days. Testing consisted of a 30-min habituation period followed by injection of either saline (Day 1) or cocaine (Day 2) and an additional 60-min test session. Neonatal treatment had little effect on baseline activity or activity following saline injection at either age. All subjects showed an activation with cocaine injections, however, the activation was more pronounced in juveniles. Again, neonatal treatment did not interact with response to cocaine. These findings suggest that neonatal cocaine exposure does not alter activity or long-term responsivity to 20 mg/kg cocaine as measured in the running wheel apparatus.

Aging↗
PubMed1998

Effects of N-[2-(1-azabicyclo[3,3,0]octan-5-yl)ethyl]2-nitroaniline fumarate (SK-946), a novel cognition activator, on learning and memory in rodent models.

We examined the effects of N-[2-(1-azabicyclo[3,3,0]octan-5-yl)ethyl]2-nitroaniline fumarate (SK-946) on cognition in various rodent models. SK-946 slightly suppressed spontaneous motor activity, but had no effect on scopolamine-induced motor facilitation. SK-946 ameliorated scopolamine-, pirenzepine-, cycloheximide- and electric shock-induced passive avoidance deficits in rodents when administered before acquiring the training. In an active avoidance test, SK-946 accelerated avoidance acquisition in the later half of training without a marked increase in lever-pressing. In more reliable models of cognitive disorders, i.e. an AF64A intracerebroventricular infusion model using the step-through passive avoidance test, an aged rat model using the step-down passive avoidance test and methylazoxymethanol (MAM)-induced microencephalic rat model using the Morris water maze test, SK-946 ameliorated impaired learning and memory. These results suggest an ability of SK-946 to enhance cognitive functions.

Aging↗
PubMed2006

Relevance of rodent models of intravenous MDMA self-administration to human MDMA consumption patterns.

RATIONALE: Despite decades of research specifying harmful effects produced by 3,4-methylenedioxymethamphetamine (MDMA; a principal component of 'ecstasy' pills), young people (and adults) continue to use it. In an attempt to model human MDMA consumption patterns, preclinical investigators have sought to establish reliable patterns of intravenous MDMA self-administration in rodents. OBJECTIVE: The objective of this report is to offer a critical review of published data (including our own novel findings) that reveal MDMA self-administration in rodents. RESULTS: The data indicate that MDMA serves as a reinforcer in rodents, though the responses are not similar to those previously reported for psychostimulants (i.e., cocaine). Important differences between rodent models and human use patterns include frequency of dosing and dosage exposure, routes of administration, tolerance that develops to MDMA after repeated exposure, polydrug use in humans but not by rodents, limits on the repertoire of behaviors that can be exhibited by rodents undergoing IV self-administration procedures, and the question of neurotoxicity as it relates to models of self-administration. CONCLUSIONS: While MDMA is not as potent a reinforcer as other drugs of abuse, the fact remains that young people and adults continue to use the drug, and therefore, additional research is needed to determine why drugs with low reinforcing effects continue to be abused.

Animals↗
PubMed1995

Diagnostic tunica vaginoscopy in a rodent model of testicular torsion.

OBJECTIVES: To evaluate the effectiveness of percutaneous endoscopy of the tunica vaginalis for identifying testicular torsion in a rodent model. METHODS: One testis was randomly selected in 10 Wistar rats weighing 500 to 600 g. Following 2 hours of 720 degree torsion, bilateral percutaneous endoscopy of the tunica vaginalis was performed by a blinded investigator utilizing a 70 degree cystoscope lens through a single midline 3 to 4 mm scrotal cutdown incision. RESULTS: Using this technique, the blinded investigator was able to identify the torsed testis rapidly in every case, which was distinguished by its cyanotic color and by the size and color of the testicular surface vessels. CONCLUSIONS: Tunica vaginoscopy is a simple, accurate, rapidly performed, minimally invasive, diagnostic technique in this experimental model of testicular torsion.

Animals↗
PubMed2006

Retinal gene profiling in a hereditary rodent model of elevated intraocular pressure.

PURPOSE: To characterize the changes in retinal gene expression induced by elevated intraocular pressure (IOP) in a hereditary rodent model. METHODS: A rat model derived from the RCS-rdy- strain develops IOP elevation spontaneously without experimental manipulation. Retinal gene expression after IOP elevation was compared with age-matched RCS-rdy- retinas having normal IOP levels The MWG Rat 10k array, which comprises 9715 rat genes spotted onto one array was used. Quantitative real-time PCR (qRT-PCR) was used to verify the expression of heat shock protein-27 (Hsp-27), SA hypertension-associated gene, c-myc, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), vascular endothelial growth factor (VEGF), myocilin, interleukin-7 (IL-7), mitogen activated protein kinase 13 (MAPK-13) and crystallin beta-A1 (Cryba1). The cellular distribution of c-myc, glial fibrillary acidic protein (GFAP), VEGF, and SA was assessed using immunohistochemistry. RESULTS: Elevated IOP of 37.7+/-5.0 mmHg shifted the retina's program of gene expression, with 75 genes being upregulated (equal to or higher than 3.0 fold) and 45 genes being downregulated (equal to or lower than 0.3 fold). These genes mediate various cellular processes such as cell adhesion, cell structure, hypertension, immunity, protein sythesis, proteolysis, transcription, and signaling. The regulation pattern of SA, VEGF, c-myc, IL-7, and MAPK-13, which are uniquely regulated in our model were confirmed by qRT-PCR experiments. The regulation of Hsp-27, TIMP-1, myocilin, and Cryba1, which have previously been associated with elevated IOP were also confirmed with qRT-PCR. The protein products of c-myc, SA, and GFAP were localized to astrocytes and Müller cells. Neurons in the ganglion cell layer and inner nuclear layer were VEGF-immunopositive. CONCLUSIONS: This study identified some of the genes that are differentially regulated, probably in response to long-term IOP exposure, in this animal model. The expression pattern of many genes is common to experimental models of elevated IOP and other retinal disorders such as diabetic retinopathy. However many genes are uniquely expressed in the retina of our model. This suggests that the mode of IOP elevation be it experimental or spontaneous could be relevant in determining which genes are regulated. Müller glia acquire a reactive phenotype as indicated by the upregulation of GFAP, c-myc, SA, and other Müller cell markers, emphasizing their relevance in pressure related- and other types of retinal injury. These data provide further evidence that IOP-mediated retinal injury is multifactorial and depends upon the interaction of different neuronal, glial, extracellular matrix, and vasogenic components.

Animals↗
PubMed2005

Effect of TGF-beta2 and anti-TGF-beta2 antibody in a new in vivo rodent model of posterior capsule opacification.

PURPOSE: This study evaluated the effect of transforming growth factor (TGF)-beta2 and anti-TGF-beta2 antibody in a rodent model of posterior capsule opacification (PCO). METHODS: An extracapsular lens extraction (ECLE) was performed in 72 Sprague-Dawley rats. At the end of the procedure, 10 microL TGF-beta2 (TGF-beta2-treated group), fetal calf serum (FCS)/phosphate-buffered saline (PBS; FCS/PBS-treated control group), a human monoclonal TGF-beta2 antibody (anti-TGF-beta2-treated group), or a null control IgG4 antibody (null antibody-treated control group) was injected into the capsule. Animals were killed 3 and 14 days postoperatively. Eyes were evaluated clinically prior to euthanatization, then enucleated and processed for light microscopy and immunohistochemistry afterward. PCO was evaluated clinically and histopathologically. Student's t-test and chi(2) were used to assess differences between groups. RESULTS: There were no statistically significant clinical or histopathological differences in degree of PCO between the TGF-beta2- and FCS/PBS-treated groups at 3 and 14 days after ECLE. Nor were there differences between the anti-TGF-beta2- and the null antibody-treated groups, with the exception of the histopathology score for capsule wrinkling 3 days after ECLE (P = 0.02). alpha-Smooth-muscle actin staining was observed in the lens capsular bag only in areas where there was close contact with the iris. CONCLUSIONS: No sustained effect of TGF-beta2 or anti-TGF-beta2 antibody on PCO was found in rodents at the dose and timing administered in this study. Iris cells may play a role in the process of epithelial mesenchymal transition linked to PCO.

Actins↗
PubMed1998

Endothelin-1-like immunoreactivity in a new rodent model of spontaneous hypertension.

The purpose of this study was to determine plasma and tissue endothelin-1 (ET-1)-like immunoreactivity in a new rodent model of spontaneous hypertension. Plasma and tissues were procured from pentobarbital-anesthetized 16- to 18-week-old male hamsters with spontaneous hypertension and genetically/age-matched normotensive hamsters. We found that ET-1-like immunoreactivity in the plasma was similar in both groups. However, renal and cardiac ET-1-like immunoreactivity was 11- and 1.7-fold higher in spontaneously hypertensive hamsters relative to normotensive hamsters, respectively (P < .05). ET-1-like immunoreactivity was slightly, but significantly, lower in the lung and spleen of spontaneously hypertensive hamsters relative to normotensive hamsters (P < .05). ET-1-like immunoreactivity in the liver and brain was similar in both groups. We conclude that ET-1-like immunoreactivity is significantly higher in two target organs for hypertension, kidney and heart, but not in plasma or brain of adult male hamsters with spontaneous hypertension, relative to genetically/age-matched normotensive hamsters. We suggest that renal and cardiac ET-1 could play a role in the natural history of spontaneous hypertension in hamsters.

Animals↗
PubMed2003

Aspartic proteases from Plasmodium chabaudi: a rodent model for human malaria.

Intraerythrocytic malaria parasites degrade haemoglobin to provide nutrients for their own growth and maturation. Plasmodium aspartic proteases known as plasmepsins play an important role on haemoglobin degradation and are being studied as drug targets for chemotherapy of malaria. The rodent model for human malaria, Plasmodium chabaudi, is an experimentally good model for therapy drug design. The gene encoding an aspartic protease precursor (proplasmepsin) from the rodent malaria parasite P. chabaudi was cloned and sequenced. A theoretical 3D structure model was constructed by comparative homology and used for superimposition with other known models. Analysis of the P. chabaudi and Plasmodium yoelli genomes revealed in both the presence of at least seven plasmepsins and each one has sequence similarity to its plasmepsin counterpart of the human malaria Plasmodium falciparum. The predicted proteins were confirmed as plasmepsins by detection on Blocks Database of three characteristic blocks of the eukaryotic and viral aspartic protease family. Analysis of the proline-rich loop amino acid sequence of these plasmepsins suggests that they constitute characteristic motifs of each plasmepsin group suggesting that these sequence variations are related with different substrate specificities.

Amino Acid Sequence↗
PubMed2006

The temporal expression of osteopontin (SPP-1) in the rodent model of alcoholic steatohepatitis: a potential biomarker.

Previous studies from our laboratory have shown that osteopontin (OPN) mediates neutrophil infiltration into the liver in a rodent model of alcoholic steatohepatitis (ASH). The objective of this study was to investigate the temporal and spatial pattern of hepatic OPN mRNA and protein expression during the progression of alcoholic liver disease. OPN mRNA and protein expression were evaluated using real time PCR, in situ hybridization, Western blot and immunohistochemistry respectively. ASH was induced in male Sprague-Dawley rats by feeding EtOH-containing Lieber-DeCarli diet for 6 weeks, followed by a single injection of lipopolysaccharide (LPS, 10 mg/kg, ip). Rats were sacrificed 2-, 12-and 24-hour post LPS injection. A progressive induction of OPN mRNA was observed that preceded hepatic neutrophil infiltration and the increase in OPN mRNA correlated with increases in OPN protein expression. OPN mRNA was localized primarily to the biliary epithelium. The data indicates that OPN is transcribed and translated within the biliary epithelium. These findings suggest a potential role of OPN as an early biomarker in predicting inflammatory liver diseases such as ASH.

Alanine Transaminase↗
PubMedDate not supplied

The squirrel as a rodent model of the human visual system.

Over the last 50 years, studies of receptive fields in the early mammalian visual system have identified many classes of response properties in brain areas such as retina, lateral geniculate nucleus (LGN), and primary visual cortex (V1). Recently, there has been significant interest in understanding the cellular and network mechanisms that underlie these visual responses and their functional architecture. Small mammals like rodents offer many advantages for such studies, because they are appropriate for a wide variety of experimental techniques. However, the traditional rodent models, mice and rats, do not rely heavily on vision and have small visual brain areas. Squirrels are highly visual rodents that may be excellent model preparations for understanding mechanisms of function and disease in the human visual system. They use vision for navigating in their environment, predator avoidance, and foraging for food. Visual brain areas such as LGN, V1, superior colliculus, and pulvinar are particularly large and well elaborated in the squirrel, and the squirrel has several extrastriate cortical areas lateral to V1. Unlike many mammals, most squirrel species are diurnal with cone-dominated retinas, similar to the primate fovea, and have excellent dichromatic color vision that is mediated by green and blue cones. Owing to their larger size, squirrels are physiologically more robust than mice and rats under anesthesia, and some hibernating species are particularly tolerant of hypoxia that occurs during procedures such as brain slicing. Finally, many basic anatomical and physiological properties in the early visual system of squirrel have now been described, permitting investigations of cellular mechanisms. In this article, we review four decades of anatomical, behavioral, and physiological studies in squirrel and make comparisons with other species.

Animals↗
PubMed2006

Establishment of a rodent model of HIV-associated sensory neuropathy.

Human immunodeficiency virus (HIV)-associated sensory neuropathy (SN) is the most common neurological complication of HIV infection in the current highly active antiretroviral therapy era. The painful sensory neuropathy is associated with the use of dideoxynucleoside antiretrovirals, and its development limits the choice of antiretroviral drugs in affected patients. There are presently no effective therapies for HIV-SN, and moreover there has been no robust animal model of HIV-SN in which candidate therapeutic agents can be tested. In this paper, we show that we have established a rodent model of HIV-SN by oral administration of a dideoxynucleoside drug, didanosine, to transgenic mice expressing the HIV coat protein gp120 under a GFAP promoter. The neuropathy in these rodents is characterized by distal degeneration of unmyelinated sensory axons, similar to the "dying back" pattern of C-fiber loss seen in patients with HIV-SN. This model will be useful in examining mechanisms of distal axonal degeneration and testing potential neuroprotective compounds that may prevent development of the sensory neuropathy.

Animals↗
PubMed1990

Evaluation of Bay R 3783 in rodent models of superficial and systemic candidiasis, meningeal cryptococcosis, and pulmonary aspergillosis.

The triazole Bay R 3783 was compared with fluconazole, itraconazole, ketoconazole, and amphotericin B in rodent models of superficial and systemic candidiasis, meningocerebral cryptococcosis, and pulmonary aspergillosis. Overall, Bay R 3783 was comparable or slightly superior to fluconazole and markedly superior to itraconazole and ketoconazole in both survival and short-term organ load experiments in models of candidiasis and cryptococcosis but was less effective than amphotericin B. Of the antifungal agents tested, only Bay R 3783 and itraconazole showed any efficacy in the model of pulmonary aspergillosis.

Administration, Oral↗
PubMed2000

Evaluation of the role of intercellular adhesion molecule 1 in a rodent model of chronic venous hypertension.

PURPOSE: To evaluate the role of intercellular adhesion molecule 1 (ICAM-1) in cutaneous leukocyte trapping in venous disease, we used our rodent model of venous hypertension (VH). MATERIALS AND METHODS: VH was created in adult rats by ligation of the inferior vena cava, bilateral common iliac veins, and bilateral common femoral veins. In the Phase I experimental (exptl) group, anti-ICAM-1 monoclonal antibody (1A29) was given intravenously prior to venous ligations. Acute venous pressures were measured in the exptl and control (ctrl) (ligation only) groups. Bilateral forelimb and hindlimb skin specimens were harvested for myeloperoxidase (MPO) assay. In Phase II, VH was created in a chronic group; in a sham-operated group, ties were placed around the same vessels without ligations. Two weeks later, venous pressures were measured and radiolabeled ((125)I and (131)I) monoclonal antibody (mAb) to ICAM-1 was injected and allowed to circulate for 5 min before the level of radiolabeled antibody within forelimb and hindlimb specimens was measured. RESULTS: In the acute study with 1A29, hindlimb pressures were significantly elevated in both the ctrl (n = 4) and exptl (n = 4) hindlimbs (15.4 +/- 0.239 and 13.8 +/- 1.89 mm Hg, respectively) compared with ctrl and exptl forelimbs (1.38 +/- 0.554 and 1.50 +/- 0.612 mm Hg, respectively). However, MPO activity was significantly elevated in the hindlimbs of the ctrl group compared with the hindlimbs of the exptl animals (19.8 +/- 1.54 U vs 6.71 +/- 2.46 U). In the chronic VH rats (n = 5) given radiolabeled anti-ICAM-1 mAb, the hindlimb pressures (10.1 +/- 4.52 mm Hg) were significantly elevated (P < 0.05) compared with forelimb pressures (1 +/- 0.447 mm Hg) and compared with the forelimb and hindlimb pressures in the sham-operated animals (n = 4) (1.63 +/- 0.813 and 4.25 +/- 2.13 mm Hg, respectively). However, there was not a significant difference in the quantity of ICAM-1-hindlimb versus forelimb or chronic VH versus sham. CONCLUSIONS: Anti-ICAM-1 mAb decreased MPO activity in hypertensive hindlimb skin, supporting the instrumental role of ICAM-1 in cutaneous leukocyte trapping. However, the constituent endothelial ICAM-1 is not elevated by VH.

Animals↗
PubMed2005

The impact of diabetes on cognition: what can be learned from rodent models?

Diabetes mellitus is associated with modest impairments in cognition, particularly in the elderly. In addition, the risk of dementia is increased. We review herein studies in rodent models that may help to identify the mechanisms that underlie these adverse effects of diabetes on the brain. Abnormalities in learning and memory, synaptic plasticity, and glutamatergic neurotransmission have now been identified in a number of these models. In general, observations in models characterized by chronic hyperglycaemia and hypoinsulinaemia (referred to as models of type 1 diabetes) are quite consistent, and these models are being increasingly used to study the pathogenesis and to develop new treatments. However, results from models characterized by insulin resistance, hyperinsulinaemia, and modest hyperglycaemia (referred to as models of type 2 diabetes) are much more variable. Moreover, the possible interaction between diabetes and aging has not been examined in sufficient detail. Because clinically relevant cognitive deficits mainly occur in elderly patients with type 2 diabetes, the challenge for researchers in this field will be to further develop adequate models.

Aging↗
PubMed1998

Rodent models of cardiopulmonary disease: their potential applicability in studies of air pollutant susceptibility.

The mechanisms by which increased mortality and morbidity occur in individuals with preexistent cardiopulmonary disease following acute episodes of air pollution are unknown. Studies involving air pollution effects on animal models of human cardiopulmonary diseases are both infrequent and difficult to interpret. Such models are, however, extensively used in studies of disease pathogenesis. Primarily they comprise those developed by genetic, pharmacologic, or surgical manipulations of the cardiopulmonary system. This review attempts a comprehensive description of rodent cardiopulmonary disease models in the context of their potential application to susceptibility studies of air pollutants regardless of whether the models have been previously used for such studies. The pulmonary disease models include bronchitis, emphysema, asthma/allergy, chronic obstructive pulmonary disease, interstitial fibrosis, and infection. The models of systemic hypertension and congestive heart failure include: those derived by genetics (spontaneously hypertensive, Dahl S. renin transgenic, and other rodent models); congestive heart failure models derived by surgical manipulations; viral myocarditis; and cardiomyopathy induced by adriamycin. The characteristic pathogenic features critical to understanding the susceptibility to inhaled toxicants are described. It is anticipated that this review will provide a ready reference for the selection of appropriate rodent models of cardiopulmonary diseases and identify not only their pathobiologic similarities and/or differences to humans but also their potential usefulness in susceptibility studies.

Air Pollutants↗
PubMed2004

Comparison of the predicted in vivo behaviour of the Sn(II)-APDDMP complex and the results as studied in a rodent model.

In a quest for more effective radiopharmaceuticals for pain palliation of metastatic bone cancer, this paper relates results obtained with ((117m)Sn labelled) Sn(II) complexed to the bone seeking bisphosphonate, N,N-dimethylenephosphonate-1-hydroxy-3-aminopropylidenediphosphonate (APDDMP). APDDMP is synthesised from the known bone cancer pain palliation agent 1-hydroxy-3-aminopropylidenediphosphonate (APD, Pamindronate). This work is performed to utilise the idea that the low bone marrow radio toxicity of (117m)Sn could afford a highly effective radiopharmaceutical in pain palliation but also in the curative treatment of bone metastasis. Complex-formation constants of APDDMP with the important blood plasma metal-ions, Ca(2+), Mg(2+), Zn(2+) as well as the added metal ion, Sn(2+) were measured by glass electrode potentiometry at 25 degrees C and I = 150 mM. Blood plasma models were constructed using the computer code ECCLES and the results compared with those gathered from tests on a rodent model. The ((117m)Sn-labelled) Sn(II)-APDDMP complex was found to have only some liver and bone uptake although a high trabecular to normal bone ratio was recorded. From the blood plasma model this was shown to be primarily due to the high affinity of APDDMP for Ca(II) causing some of the Sn(II)-APDDMP complex to dissociate. High kidney uptake and excretion as well as high bladder uptake was recorded which was shown to be due to the dissociation of the Sn(II)-APDDMP complex in blood plasma. Animal model observations could be explained by the blood plasma modelling.

Alkenes↗
PubMed2005

Rodent models of brain metastasis in melanoma.

Metastasis of melanoma to the central nervous system (CNS) remains one of the major barriers to successful treatment of this disease. Available treatment modalities are of limited clinical efficacy. This problem is compounded by the presence of the blood-brain barrier (BBB), an important consideration in the development of new therapeutic agents. Only in animal models can the dual properties of experimental tumours and the BBB be explored in one system. A variety of rodent models have been developed, utilizing both murine and human melanoma cell lines. These models have highlighted the complex biology of cerebral metastasis, involving apparent disease progression through the selection of subclones at each stage, eventually leading to disease in the brain. As demonstrated in a number of animal studies, different subpopulations of metastatic melanoma cells are likely to be responsible for parenchymal and leptomeningeal CNS disease. In addition, these animal systems have been used to demonstrate the potential efficacy of new chemotherapeutic drugs, radiation treatments and immunotherapeutic approaches for the treatment of melanoma brain metastasis. Key biological questions remain to be answered. In particular, the molecular and cellular mechanisms responsible for establishing cerebral melanoma must be clearly delineated. Several molecules, including vascular endothelial growth factor (VEGF) and integrins, appear to play important, but not definitive, roles. Other, as yet undefined, molecules appear to be critical. The identification of these factors in experimental models, with confirmatory studies in humans, will expand our understanding of cerebral melanoma and provide valuable new therapeutic targets for intervention in this difficult clinical problem.

Animals↗