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PubMed1994

Ventral root avulsion: an experimental model of death of adult motor neurons.

The present study proposes a reproducible model of experimental degeneration of adult motor neurons in the rat. Avulsion of ventral roots in the adult lumbar cord transects motor axons at the root exit and leads to retrograde cell death of 80% of motor neurons 2 weeks later; this result follows a series of retrograde changes, including chromatolysis, loss of transmitter phenotype, and accumulation of phosphorylated neurofilaments in perikarya. Glial cells recruited at the site of retrograde injury express both microglia-specific epitopes (as exemplified by OX-42 immunoreactivity) and macrophage-specific markers (e.g., ED-1 immunoreactivity). Macrophage-specific markers become particularly intense 7 days postaxotomy and provide additional evidence of active phagocytosis of injured neurons. Ventral root avulsion is a very useful model for assessing mechanisms of motor neuron death and testing the ability of trophic factors and other agents to preserve the phenotype and promote the survival of adult motor neurons in vivo.

Animals↗

PubMed1975

Disseminated candidiasis. i. an experimental model in the guinea pig.

A model of experimental disseminated candidiasis was developed in the guinea pig; Candida albicans was injected intraperitoneally or intravenously. The kidney was the most severely affected organ, with maximal colony counts of 26,208 plus or minus 9,152 colony-forming units/g of tissue five days after a sublethal inocluation (one-sixth of the 50% lethal dose) of viable organisms. The heart was the next most severely affected organ, and other organs were affected little. Histologic studies confirmed the data from colony counts and showed a progression of inflammation similar to that seen in human disease. A leukocytosis predominantly of mononuclear cells, and to a lesser degree of granulocytes, occurred and was maximal four days after inoculation. This model will provide the framework for a series of future studies of the various factors important in natural host defense against infection with Candida, as well as the effects of various immunosuppressive agents, particularly corticosteroids, on the development and expression of immunity and protection against infection.

Adrenal Glands↗

PubMedDate not supplied

[Experimental models of acute pancreatitis. Critical review].

Experimental models of acute pancreatitis have been developed for more than a century. Although not closely comparable to human disease, they have contributed to our understanding of the physiopathology and cell biology of the disease. The methods used for the induction are subjected to critical examination. In the relevant literature findings, the advantages of each group are underscored, and reference is made to their defects with regard to reproducibility and reliability, with a view to extending the results obtained to human pathology. A proper understanding and standardization of these models may enable us to choose the most suitable model for studying a given aspect of the disease or for evaluating new treatment protocols. The data collected has made it possible to select standardization criteria for a comparative experimental study in the laboratory.

Acute Disease↗

PubMed1989

Comparison of intimal platelet accumulation in cerebral arteries in two experimental models of subarachnoid hemorrhage.

Intimal accumulation of indium-111-labeled platelets in the middle cerebral arteries was examined in two different models of experimental subarachnoid hemorrhage (SAH) in the cat. SAH was produced in 7 subjects by a transorbital rupture of the right middle cerebral artery (RMCA) and in 10 subjects by the transorbital cisternal injection of 2 ml of autologous arterial blood around the RMCA. Animals in both experimental groups were sacrificed at 2, 4, 24, and 48 hours after SAH. The radioactivity (in counts per minute) of the RMCA segment was divided by that of the left middle cerebral artery (LMCA) to produce a radioactivity ratio (RMCA/LMCA). This radioactivity ratio was determined for each animal and was scored as positive if it was 1.25 or greater, and as negative if it was less than 1.25. The scores derived from the radioactivity ratios in both experimental SAH groups were mostly positive (86 and 70%, respectively) and were significantly different (P less than 0.05) from those of intact controls (n = 7) or sham-operated controls (n = 5; n = 4). There was, however, no significant difference (P = 0.35) between the scores of the two experimental groups in the first 48 hours after SAH. The results indicate that subarachnoid blood placed upon the adventitial surface of intact cerebral arteries activates platelet aggregation to a degree comparable to that which occurs after mechanical vessel rupture in the acute stages of SAH. We suggest that the noxious agents responsible for arterial injury and subsequent intimal platelet aggregation after SAH exert their influence primarily from the abluminal surface of the cerebral artery.

Animals↗

PubMed1985

Sequential behaviour of extracellular matrix glycoproteins in an experimental model of hepatic fibrosis.

The behaviour of extracellular matrix glycoproteins (fibronectin, laminin, basement membrane heparan-sulphate proteoglycan, type III, IV and V collagens) has been investigated in a sequential model of experimental hepatic fibrosis, using an immunofluorescence technique. The presence of some basement membrane macromolecules (such as type IV and V collagens, laminin and basement membrane heparan-sulphate proteoglycan) is detectable only in the early stages of septa formation, while type III collagen and fibronectin persist in late septa. These data suggest that hepatic fibroplasia proceeds through different steps in which stromal glycoproteins are preferentially engaged, as happens during organogenesis.

Animals↗

PubMed1989

[An experimental model of pulmonary aspergillosis].

The model of experimental chronic pulmonary aspergillosis has been obtained in mice and guinea pigs by the intrapulmonary infection of the animals with the suspension of Aspergillus mycelium and spores in complete Freund's adjuvant. Such method of infection has made it possible to produce chronic local mycotic process. Morphologically, focal inflammatory changes of the lung tissue with the subsequent formation of a multitude of small abscesses in these areas have been observed as characteristic manifestations of aspergillosis.

Animals↗

PubMed1998

Effects of chronic combined treatment with captopril and pravastatin on the progression of insulin resistance and cardiovascular alterations in an experimental model of obesity in dogs.

Obesity is a metabolic disorder in which multiple clinical and biochemical alterations coexist. However, the progression of these alterations in relation to weight gain has not been investigated in detail. Therefore, we studied the evolution of insulin resistance and associated risk factors in a model of experimental obesity in dogs. We also studied whether chronic exposure to these pathogenic factors could induce cardiac and vascular alterations. Twenty male age- and body weight-matched beagle dogs were divided into four groups (n = 5), according to diet and pharmacologic therapy received, and followed for 2 years. Control animals were maintained with a regular diet, while the 15 remaining animals were fed a high-fat diet. The Obese group of dogs received no therapy, whereas the Capto group received 25 mg/12 h captopril, and the Prava+Capto was treated with 10 mg/24 h pravastatin plus the same dose of captopril throughout the study. Periodical determinations of clinical and biochemical parameters were made, and the degree of insulin resistance was also estimated. After the 2-year follow-up, the dogs were killed and vascular thickening in the aorta and the coronary arteries was evaluated. In addition, cardiac hypertrophy was estimated by heart weight and free-wall left ventricular width. Chronic pravastatin plus captopril treatment, together with decreasing weight gain rate, ameliorated the progression of insulin resistance and associated risk factors (hyperinsulinemia, hypercholesterolemia) related to this severe model. In addition, this combined therapy showed cardioprotective action, as cardiac and vascular hypertrophy observed in the Obese group was prevented. These positive results seems to emerge from the synergistic effects of both drugs, as captopril as monotherapy induced only a slight benefit on these parameters.

Animals↗

PubMed1995

The scid mouse as an experimental model for the evaluation of anti-Pneumocystis carinii therapy.

The usefulness of scid mice bearing endogenous Pneumocystis carinii infection as a model for experimental chemotherapy was examined using standard compounds known to be effective against P. carinii. Trimethoprim/sulphamethoxazole was able to reduce pulmonary P. carinii cysts in a dose-dependent manner within the dose range studied (10/50 to 100/500 TMP/SMX mg/kg/d, bd, po, 5 days per week for 30 treatments). However, alterations in associated symptoms of infection (reduced body weight, increased lung weight, increased blood leucocytes and erythrocytes), was apparently not linearly dose-dependent. Blood and lung lavage fluid levels of sulphamethoxazole one hour post administration of trimethoprim/sulphamethoxazole was dose-dependent, but not linear with dose, and was apparently correlated to cyst reduction; trimethoprim was below the limit of detection at this time. Treatment of mice with 100/500 mg/kg/day trimethoprim/sulphamethoxazole required 2 weeks (bd for 10 days of treatment) before changes in indices of infection became significant. Pentamidine (20 mg/kg, sc, three times per week for 3 weeks) was nearly as effective as high-dose trimethoprim/sulphamethoxazole in reducing cysts, whereas lower doses were ineffective. Despite being unable to reduce pulmonary P. carinii infection, even low doses of pentamidine (6 or 2 mg/kg, sc, three times per week for 3 weeks) were able to reduce lung weights and blood leucocyte levels. This model of pulmonary P. carinii infections is amenable to chemotherapeutic intervention in an apparently dose-dependent fashion, and can be used to evaluate the capacity of compounds to eradicate P. carinii and resolve signs of infection.

Animals↗

PubMed1976

Biphasic effects of imipramine in experimental models of epilepsy.

In a variety of laboratory models of experimental epilepsy, imipramine exerts a biphasic action on the CNS as manifested by antiepileptic properties at low doses and convulsant effects at higher doses. In mice, imipramine (17.5-25 mg/kg, i.p.) blocks maximal electroshock seizures while exerting little or no effect on pentylenetetrazol-induced seizures. In cats, imipramine (2.5-15 mg/kg, i.v.) reduces penicillin and estrogen-induced epileptiform discharge, shortens afterdischarge duration and elevates afterdischarge threshold. Higher doses in mice induce neurotoxicity, including clonic seizures. In cats, doses above 20 mg/kg intensify chemically and electrically induced seizures and induce spontaneous epileptiform episodes. Such a biphasic action of imipramine may limit the drug's clinical utility as an antiepileptic agent and may provide an interesting tool for studies of catecholamines and brain excitability.

Animals↗

PubMed1989

The effects of heparin and cortisone on an experimental model of pannus.

The effects of heparin and cortisone were investigated in a model of experimental pannus-mediated cartilage degradation. Rat femoral head cartilages were implanted bilaterally (sc.) into female mice either non-wrapped or wrapped in cotton. Animals were treated with tap water (p.o.), heparin 1000 Units (p.o.), cortisone 2 mg/kg (s.c) and heparin-cortisone combined. After 14 days, the implants were removed and analysed for exudate volume, granulation-tissue dry weight and cartilage glycosamino-glycan (GAG) content. In the heparin-treated animals there was a significant (p less than 0.001) increase in the granulation-tissue dry weight, whilst combined treatment significantly (p less than 0.001) reduced both exudate volume and cartilage degradation. It is possible that the effects on angiogenesis may indicate novel treatment for the growth of pannus and cartilage breakdown.

Animals↗

PubMed1999

MR imaging of intrarenal macrophage infiltration in an experimental model of nephrotic syndrome.

The objective of this study was to use MR imaging to detect macrophage infiltration of the kidney after injection of ultrasmall superparamagnetic iron oxide (USPIO) particles in a rat model of experimental nephropathy. Ninety micromol of USPIO were injected intravenously in 10 rats with nephropathy secondary to intravenous injection of 5 mg of puromycin aminonucleoside (PAN), and in 10 control rats. The signal intensity was measured in each kidney compartment before and 24 h after injection of the contrast agent. FLASH sequences were performed on a spectrometer operating at 4.7 T. MR findings were compared with histological data. Twenty-four hours after injection of USPIO, a significant decrease (P < 0.0001) was observed in signal intensity in each kidney compartment in the PAN group. There was no variation in the control group. In the diseased kidneys, histological data revealed the presence of macrophages with iron oxide particles within their cytoplasm and lysosomes. Using USPIO, MR imaging can evidence infiltration of the rat kidney by macrophages.

Animals↗

PubMed2005

Effects of cocaine in an experimental model of traumatic brain injury.

BACKGROUND: Cocaine intoxication is found in a significant subset of emergency department (ED) patients presenting with traumatic brain injury (TBI). OBJECTIVES: To investigate the effects of acute cocaine intoxication on physiologic and metabolic parameters in a model of experimental TBI. METHODS: Under inhalational anesthesia, swine were instrumented and subjected to fluid percussion TBI of 3 atm. Two groups were studied: TBI and cocaine (n = 7) and TBI only (n = 7). Two sequential doses of cocaine hydrochloride were administered intravenously to the animals receiving cocaine: 4 mg/kg 10 minutes prior to injury and 2 mg/kg 1 minute prior to injury. Control animals received normal saline. Cardiorespiratory and cerebral physiologic data were monitored for 180 minutes following injury. Cerebral blood flow (CBF) was measured using dye-labeled microspheres. Serum cocaine levels were measured by gas chromatography/mass spectrometry. RESULTS: Mean (+/- SD) cocaine levels at the time of injury were 1,771 (+/- 403) ng/mL. All animals survived the 180-minute observation period. There was a trend toward higher intracranial pressure (ICP) in the control (15.4 +/- 8.2) vs. cocaine-treated (11.1 +/- 5.8) animals, although this did not reach statistical significance (p = 0.18). Cerebral venous lactate (CVL) levels also trended higher in the control (1.14 +/- 0.22) vs. cocaine-treated (0.91 +/- 0.19) groups (p = 0.06). Cerebral perfusion pressures (CPPs), however, did not differ between groups. The CBF values decreased significantly from baseline in both groups but were not different between groups. CONCLUSIONS: Cocaine-intoxicated animals subjected to TBI showed no significant difference in primary outcome measures of CPP or CBF, although a nonsignificant trend toward lower ICP was noted. Overall, acute cocaine intoxication did not adversely affect the physiologic parameters examined in this TBI model.

Animals↗

PubMedDate not supplied

Morphological recovery in the reattached retina of the toad Bufo marinus: a new experimental model of retinal detachment.

BACKGROUND: The retinal pigment epithelium (RPE) of the toad (Bufo marinus) has been used in many studies as a model for understanding its role and interaction with the neural retina. The toad's retina has been used to establish a new in vitro model of experimental retinal detachment (RD) and replacement . It has been shown that the electrophysiological measures of retinal function recovered following complete RD. The toad was chosen because its RPE is similar to the mammalian RPE . In this report, light microscopy was used to characterize the morphologic changes that occur in the RPE and neural retina following RD/replacement and to correlate these findings with recovery of electrophysiologic function. METHODS: Retinas from Bufo marinus were studied in vitro. The neural retina completely detached from the RPE and then replaced. At various times after replacement, neural retina-RPE tissues were processed for light microscopy. RESULTS: At 30 min after replacement, the subretinal space was greatly expanded, and the apical processes that normally ensheath the rod outer segments were short and no longer contacted the rod outer segments. The RPE was swollen, contained many vacuoles and the apical surface was rounded. By 2 h after replacement, the subretinal space was significantly resorbed and contained many shredded rod outer segments; RPE cells were still swollen, although less. During the next 5-10 h, the number of phagosomes in the RPE cytoplasm increased and the number of shredded rod outer segments in the subretinal space decreased. RPE cells regained their normal size and interdigitation of apical processes and rod outer segments were observed. CONCLUSIONS: These results demonstrate the re-establishment of morphological interactions between the RPE and neural retina within hours following RD/replacement. Morphological recovery coincides with recovery of electrophysiologic parameters. This is a good model to investigate the retinal pigment epithelium (RPE) and neural retina mechanisms involved in retinal adhesion and recovery from retinal detachment.

Animals↗

PubMed2006

[Mutation window for the "pneumococcus-fluoroquinolone" couple. Contribution of experimental models].

Low-level resistance to fluoroquinolones (in vitro susceptible but with topoisomerase mutation, parC) is currently rare among pneumococci in France. However, this resistance is more frequently observed in previously exposed patients and therapeutic failure has been reported. These issues were investigated by using a humanized model of experimental pneumonia induced by pneumococci exhibiting this low-level resistance profile. The results are as follows: 1) when the pneumonia is due to a wild type pneumococcus, humanized ciprofloxacin treatment is not effective because of resistant mutants with parC mutation; moreover, levoflaxin treatment is less bactericidal than gatiflo- or moxifloxacin (-4 vs -6 log CFU/g); 2) when an efflux strain is used, levo-treatment is not efficient but there are no mutants, a gatiflo-treatment is combined when mutants appear and moxiflo-treatment is effective; 3) when the pneumonia is induced with susceptible parC strains, treatment with either levo, or gati, or moxifloxacin is completely ineffective because resistant mutants appear (acquisition of another gyrA mutation). Measure of the mutation prevention concentration (MPC) allows anticipating these results since the mutation window can be determined. These results stress the necessity to identify patients with such pneumococcal strains in order to avoid therapeutic failure and the emergence of fluoroquinolone resistant mutants.

Animals↗

PubMed2000

Magnetization transfer and multicomponent T2 relaxation measurements with histopathologic correlation in an experimental model of MS.

Magnetization transfer and multicomponent T2 imaging techniques were implemented to study guinea pig in vivo. A chronic-progressive model of experimental allergic encephalomyelitis (EAE) was produced, and the inflammatory component of the disease was manipulated using antibodies against integrin. The magnetization transfer ratio (MTR) and T2 relaxation properties were measured in normal-appearing white matter (NAWM) with histological comparisons. Significant reductions in both the mean MTR and the myelin water percentage were measured in NAWM of EAE guinea pig brain. However, the MTR and myelin water percentage appear to measure different aspects of pathology in NAWM in EAE. Reductions in the MTR were prevented or reversed with suppression of inflammation. However, modulation of inflammatory activity was not reflected in the measurement of the myelin water percentage. Since the amount of myelin is not expected to vary with inflammatory-related changes, these observations support our hypothesis that the MTR is sensitive to physiological changes to myelin induced by inflammation, while the short T2 component is a more specific indicator of myelin content in tissue. Pathologic features other than demyelination may be important in the determination of the MTR.

Animals↗

PubMedDate not supplied

Acute effects of transluminal angioplasty in three experimental models of atherosclerosis.

Transluminal angioplasty has shown promise as a nonoperative treatment of atherosclerotic obstruction. Despite its increasing clinical use and potential importance, little is known of its mechanism and acute effects. To evaluate transluminal angioplasty, three rabbit models of experimental atherosclerosis were developed: Group 1 (n = 20) = high cholesterol diet plus balloon de-endothelialization; Group 2A (n = 12) = high cholesterol diet plus an indwelling catheter; Group 2B (n = 10) = normal diet plus an indwelling catheter. After 6 weeks or 8 weeks, distinct angiographic and pathological lesions in the iliac artery were evident in all groups. Group 1 showed predominant foam cell lesions, while Group 2 showed eccentric mixed fibrous and foam cell or only fibrous lesions. Significant angiographic stenosis was present in 78% of the animals. Angioplasty of the highest grade iliac stenosis resulted in at least a 20% reduction in luminal diameter narrowing in 26 of 37 animals (70%). Histopathological examination 1 day following angioplasty in 17 animals showed two patterns. In Group 1 animals, neointimal fracture and dissection were evident, while in Group 2 animals thinning and stretching of the nonatherosclerotic portion of the vessel walls could be demonstrated. This study demonstrates that the New Zealand rabbit can be used to produce a spectrum of morphologically distinct atherosclerotic lesions that lend themselves to the study of transluminal angioplasty. The immediate consequences of angioplasty, which appear to depend upon the underlying histopathology and widening of the narrowed lumen, are frequently concurrent with intimal fracture, dissection, or thinning of the nonatherosclerotic portion of the vessel wall.

Angioplasty, Balloon↗

PubMed2007

Mammalian target of rapamycin is activated in human gastric cancer and serves as a target for therapy in an experimental model.

The mammalian target of rapamycin (mTOR) has become an interesting target for cancer therapy through its influence on oncogenic signals, which involve phosphatidylinositol-3-kinase and hypoxia-inducible factor-1alpha (HIF-1alpha). Since mTOR is an upstream regulator of HIF-1alpha, a key mediator of gastric cancer growth and angiogenesis, we investigated mTOR activation in human gastric adenocarcinoma specimens and determined whether rapamycin could inhibit gastric cancer growth in mice. Expression of phospho-mTOR was assessed by immunohistochemical analyses of human tissues. For in vitro studies, human gastric cancer cell lines were used to determine S6K1, 4E-BP-1 and HIF-1alpha activation and cancer cell motility upon rapamycin treatment. Effects of rapamycin on tumor growth and angiogenesis in vivo were assessed in both a subcutaneous tumor model and in an experimental model with orthotopically grown tumors. Mice received either rapamycin (0.5 mg/kg/day or 1.5 mg/kg/day) or diluent per intra-peritoneal injections. In addition, antiangiogenic effects were monitored in vivo using a dorsal-skin-fold chamber model. Immunohistochemical analyses showed strong expression of phospho-mTOR in 60% of intestinal- and 64% of diffuse-type human gastric adenocarcinomas. In vitro, rapamycin-treatment effectively blocked S6K1, 4E-BP-1 and HIF-1alpha activation, and significantly impaired tumor cell migration. In vivo, rapamycin-treatment led to significant inhibition of subcutaneous tumor growth, decreased CD31-positive vessel area and reduced tumor cell proliferation. Similar significant results were obtained in an orthotopic model of gastric cancer. In the dorsal-skin-fold chamber model, rapamycin-treatment significantly inhibited tumor vascularization in vivo. In conclusion, mTOR is frequently activated in human gastric cancer and represents a promising new molecular target for therapy.

Adenocarcinoma↗

PubMed1994

Inhibition of preretinal proliferation by free radical scavengers in an experimental model of tractional retinal detachment.

An original model of experimental proliferative vitreoretinopathy consisting of an intravitreal injection of 10(7) human platelets and 1 IU of hyaluronidase was developed in pigmented rabbits. One group of 11 eyes served as non-treated controls. Two other groups of 11 eyes each received Ginkgo Biloba extracts which are known free radical scavengers (EGb761, Ipsen, France), given orally in two doses, 50 mg kg-1 day-1 and 100 mg kg-1 day-1 respectively, from the day after the platelet injection to the end of the first month. The fourth group (11 eyes) was intravenously injected with a unique dose of 15000 U kg-1 of superoxide dismutase the day after platelet injection. All animals were ophthalmoscopically examined in a masked fashion twice a week for 1 month and killed at the end of the experiment for histological analysis. Vitreoretinal proliferation was graded according to a six-stage classification. The non-treated eyes showed a high rate of retinal detachment (11/11 eyes), with a mean final score of 3.91 +/- 0.94. Histologic examinations consistently showed retinal retraction by fibrocellular preretinal membranes spreading to both surfaces of the retina as well as preretinal neovascularization. Many cells positively reacted with anti-cytokeratin or anti-vimentin monoclonal antibodies. All three groups of treated eyes showed significantly lower scores of vitreoretinal proliferation at almost each time point of examination. At the end of the study, five retinal detachments were found in the EGb761 group at 50 mg kg-1 day-1 (mean final score 2.45 +/- 1.37), only one in the group receiving 100 mg kg-1 day-1 (mean score 1.64 +/- 1.03), and one in the SOD treated eyes. The lowest mean score found at day 28 was observed in the group receiving SOD (1.36 +/- 1.43), although this group presented during the first 3 weeks with an intense vitreous and sometimes anterior chamber inflammation. Statistical comparison between treatments did not show significant differences at most time points of the study. These results demonstrate that antioxidants may efficiently prevent preretinal proliferation, in clinicopathological entities where free radicals had not yet been shown to play a direct pathogenetic role. They are also among the first attempts for inhibiting preretinal proliferations with non-cytotoxic agents and using a non-ocular route.

Animals↗