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At least 667 records · Page 37Linked to original sources
PubMed2004

Selectivity of 18F-FLT and 18F-FDG for differentiating tumor from inflammation in a rodent model.

UNLABELLED: Increased glucose metabolism of inflammatory tissues is the main source of false-positive (18)F-FDG PET findings in oncology. It has been suggested that radiolabeled nucleosides might be more tumor specific. METHODS: To test this hypothesis, we compared the biodistribution of 3'-deoxy-3'-(18)F-fluorothymidine (FLT) and (18)F-FDG in Wistar rats that bore tumors (C6 rat glioma in the right shoulder) and also had sterile inflammation in the left calf muscle (induced by injection of 0.1 mL of turpentine). Twenty-four hours after turpentine injection, the rats received an intravenous bolus (30 MBq) of either (18)F-FLT (n = 5) or (18)F-FDG (n = 5). Pretreatment of the animals with thymidine phosphorylase (>1,000 U/kg, intravenously) before injection of (18)F-FLT proved to be necessary to reduce the serum levels of endogenous thymidine and achieve satisfactory tumor uptake of radioactivity. RESULTS: Tumor-to-muscle ratios of (18)F-FDG at 2 h after injection (13.2 +/- 3.0) were higher than those of (18)F-FLT (3.8 +/- 1.3). (18)F-FDG showed high physiologic uptake in brain and heart, whereas (18)F-FLT was avidly taken up by bone marrow. (18)F-FDG accumulated in the inflamed muscle, with 4.8 +/- 1.2 times higher uptake in the affected thigh than in the contralateral healthy thigh, in contrast to (18)F-FLT, for which this ratio was not significantly different from unity (1.3 +/- 0.4). CONCLUSION: In (18)F-FDG PET images, both tumor and inflammation were visible, but (18)F-FLT PET showed only the tumor. Thus, the hypothesis that (18)F-FLT has a higher tumor specificity was confirmed in our animal model.

Animals↗
PubMed1997

Effective reduction of infarct volume by gap junction blockade in a rodent model of stroke.

Several lines of evidence indicate that the extent of ischemic injury is not defined immediately following arterial occlusion; rather that infarction expands over time. Episodes of spreading depression have been linked to this secondary increase in infarct volume. Tissue bordering the infarct fails to repolarize following spreading depression and is incorporated into the infarction. The result is that ischemic infarcts expand stepwise following each episode of spreading depression. Another line of evidence has demonstrated that gap junction blockers effectively inhibit spreading depression. These observations suggest that the efflux of potentially harmful cytosolic messengers from ischemic cells into surrounding nonischemic cells might cause amplification of injury in focal stroke. It is therefore conceivable that minimizing gap junction permeability might reduce final infarct volume. To test this hypothesis, the authors pretreated rats with the gap junction blocker, octanol, before occluding the middle cerebral artery and compared the sizes of the ischemic lesions to those in rats that received vehicle dimethyl sulfoxide prior to arterial occlusion. Histopathological analysis was performed 24 hours later. The 12 octanol-treated animals showed a significantly decreased mean infarction volume (80 +/- 16 mm3) compared with the nine control rats (148 +/- 9 mm3). In a separate set of experiments, the frequency of experimentally induced waves of spreading depression was evaluated following octanol treatment. Octanol pretreatment resulted in complete inhibition in two of nine animals, transient inhibition in five of nine, and no inhibition in two of nine. The results indicate that gap junction inhibitors, when not limited by toxicity, have significant therapeutic potential in the treatment of acute stroke.

Journal Article↗
PubMed2003

Study of the effects of electroacupuncture in a rodent model of cerebral ischaemia.

The effects of electroacupuncture (EA) has been studied in a model of global cerebral ischaemia performed in gerbils through the bilateral carotid artery occlusion (BCAO). Animals, under isofluorane anaesthesia, underwent 5 min of BCAO and were killed after 7 days. The effects of EA were evaluated both on functional (with electrophysiological recordings of synaptic potentials in hippocampal slices) and morphological parameters (by counting the number of survived neurons in CA1 area of the hippocampus). The results demonstrated that the treatment of animals with EA (5 min before, during and 20 min after BCAO and 30 min per day in the following 5 days) did not modify either the ischaemia-induced reduction of synaptic potentials amplitude, either ischaemia-induced neuronal loss in the hippocampus. We conclude that, at least in this animal model of cerebral ischaemia, EA does not exert a neuroprotective effect.

Animals↗
PubMed2004

Changes in metabotropic glutamate receptor 4 expression and the effects of L-2-amino-4-phosphonobutyrate in a rodent model of diffuse brain injury.

OBJECTIVE: To examine the changes in the expression of mGluR4 after diffuse brain injury (DBI) and to determine the role of its specific agonist L-2-amino-4-phosphonobutyrate (L-AP4) in vivo. METHODS: A total of 161 male SD rats were randomized into the following groups. Group A included normal control, sham-operated control and DBI group. DBI was produced according to Marmarou's diffuse head injury model. mRNA expression of mGluR4 was detected by hybridization in situ. Group B included DBI alone, DBI treated with normal saline and DBI treated with L-AP4. All DBI rats were trained in a series of performance tests, following which they were subjected to DBI. At 1 and 12 hours, animals were injected intraventricularly with L-AP4 (100 mmol/L, 10 microl) or normal saline. Motor and cognitive performances were tested at 1, 3, 7, 14 days after injury and the damaged neurons were also detected. RESULTS: There was no significant difference between normal control group and sham-operated group in the expression of mGluR4 (P>0.05). The animals exposed to DBI showed significantly increased expression of mRNA of mGluR4 compared with the sham-operated animals 1 h after injury (P<0.05). At 6 hours, the evolution of neuronal expression of mGluR4 in the trauma alone group was relatively static. Compared with saline-treated control animals, rats treated with L-AP4 showed an effective result of decreased number of damaged neurons and better motor and cognitive performances. CONCLUSIONS: Increased expression of mGluR4 is important in the pathophysiological process of DBI and its specific agonist L-AP4 can provide remarkable neuroprotection against DBI not only at the histopathological level but also in the motor and cognitive performance.

Aminobutyrates↗
PubMed2005

Rodent models of rheumatoid arthritis.

The study of rheumatoid arthritis is greatly facilitated by animal models that enable investigation of a complex system involving inflammation, immunological tolerance, and autoimmunity. Although the models cover several species and pathogenetic mechanisms and can be classified as induced or spontaneous, all converge on arthritis. However, because each model features a different mechanism driving disease expression, the merits of each should be evaluated carefully in making the appropriate choice for the scientific question to be addressed. In addition, because the incidence and kinetics of disease vary by model, careful thought should be given to protocol design to minimize animal use.

Animals↗
PubMed2005

A rodent model for artificial gravity: VOR adaptation and Fos expression.

Vestibulo-ocular reflex (VOR) adaptation and brainstem Fos expression as a result of short radius cross-coupling stimuli were investigated to find neural correlates of the inherent Coriolis force asymmetry from an artificial gravity (AG) environment. Head-fixed gerbils (Meriones unguiculatus, N=79) were exposed, in the dark, to 60--90 minutes of cross-coupled rotations, combinations of pitch (or roll) and yaw rotation, while binocular horizontal, vertical, and torsional eye position were determined using infrared video-oculography. Centripetal acceleration in combination with angular cross-coupling was also studied. Simultaneous sinusoidal rotations in two planes (yaw with roll or pitch) provided a net symmetrical stimulus for the right and left labyrinths. In contrast, a constant velocity yaw rotation during sinusoidal roll or pitch provided the asymmetric stimulus model for AG. We found orthogonally oriented half-cycle VOR gain changes. The results depended on the direction of horizontal rotation during asymmetrical cross-coupling, and other aspects of the stimulus, including the phase relationship between the two rotational inputs, the symmetry of the stimulus, and training. Fos expression also revealed laterality differences in the prepositus and inferior olivary C subnucleus. In contrast the inferior olivary beta and ventrolateral outgrowth were labeled bilaterally. Additional cross-coupling dependent labeling was found in the flocculus, hippocampus, and several cortical regions, including the perirhinal and temporal association cortices. Analyses showed significant differences across the brain regions for several factors (symmetry, rotation velocity and direction, the presence of centripetal acceleration or a visual surround, and training). Finally, animals compensating from a unilateral surgical labyrinthectomy who received multiple cross-coupling training sessions had improved half-cycle VOR gain in the ipsilateral eye with head rotation toward the intact side. We hypothesize that cross-coupling vestibular training can benefit aspects of motor recovery or performance.

Adaptation, Physiological↗
PubMed2006

Clinical laboratory, virologic, and pathologic changes in hamsters experimentally infected with Pirital virus (Arenaviridae): a rodent model of Lassa fever.

The clinical laboratory, virologic, and pathologic changes occurring in hamsters after infection with Pirital virus (Arenaviridae) are described. Pirital virus infection in the hamsters was characterized by high titered viremia, leukocytosis, coagulopathy, pulmonary hemorrhage and edema, hepatocellular and splenic necrosis, and marked elevation of serum transaminase levels. All of the animals died within 9 days. The clinical and histopathological findings in the Pirital virus-infected hamsters were very similar to those reported in severe human cases of Lassa fever, suggesting that this new animal model could serve as a low-cost and relatively safe alternative for studying the pathogenesis and therapy of Lassa fever.

Animals↗
PubMedDate not supplied

Application of surface roughness analysis on micro-computed tomographic images of bone erosion: examples using a rodent model of rheumatoid arthritis.

Quantifying the bone erosion in preclinical models of rheumatoid arthritis is valuable for the evaluation of drug treatments. This study introduces a three-dimensional method for bone surface roughness measurement from micro-computed tomographic data obtained from rats subjected to collagen-induced arthritis (CIA), in which the degree of bone erosion is related to the severity and the duration of the disease. In two studies of rat CIA, the surface roughness of the talus bone following 21 days of disease increased 559% and 486% from the control group. At 41 days following disease induction, the roughness of the bone surface increased 857% above baseline. The roughness of the control samples was similar from each study (less than 4% different), demonstrating the robustness of the algorithm. Treatment with methotrexate at 0.1 mg/kg daily demonstrated significant protection from bone erosion, whereas the 0.05 mg/kg daily dose was not efficacious (98% versus 22% inhibition of roughness-measured bone erosion). The main advantage of such an algorithm is demonstrated in the preclinical drug study of rat CIA with methotrexate treatment, indicating the immediate utility of this approach in drug development studies.

Algorithms↗
PubMedDate not supplied

A rodent model for studying four well defined toxic endpoints during bupivacaine infusion.

An animal model with four well defined endpoints for studying the cardiotoxicity and neurotoxicity of bupivacaine is described. Five male Wistar rats (264-324 g) were anesthetized, tracheostomized and ventilated, and ECG and EEG leads were placed. Femoral arteries and veins were then cannulated. Twenty minutes before bupivacaine infusion, 0.1 mg/kg pancuronium was given intravenously, and anesthesia was adjusted to halothane 0.5%, 30% O2 and 70% N2O. Bupivacaine infusion was then begun at 2 mg/kg/minute. Bupivacaine doses producing the following endpoints were then determined: (1) first ventricular arrhythmia (ARR), (2) seizures (SZ), (3) isoelectric EEG (ISO EEG), and (4) asystole (ASYS). The doses of bupivacaine (in mg/kg +/- SD) precipitating AAR, SZ, ISO EEG and ASYS were 4.22 +/- 1.87, 7.08 +/- 1.55, 11.05 +/- 5.15 and 20.4 +/- 6.49 mg/kg, respectively. These endpoints were present and readily determined in all animals. The doses of bupivacaine producing ARR and SZ were not significantly different (p greater than 0.05). The doses producing SZ, ISO EEG and ASYS were significantly different from each other (p greater than 0.05, ANOVA and the Duncan test). These results indicate that it is possible to study, in the anesthetized and paralyzed rat that is intensely monitored, many of the variables associated with local anesthetic toxicity currently of clinical interest. The use of a constant local anesthetic infusion allows ready observation of the progression of toxic signs.

Animals↗
PubMed1991

Poloxamer 407 as an intraperitoneal barrier material for the prevention of postsurgical adhesion formation and reformation in rodent models for reproductive surgery.

Comtemporary adhesion-prevention regimens for infertility surgery emphasize the use of barrier materials to effect physical separation of injured surfaces before reperitonealization. Poloxamer 407 is a biocompatible polymer that displays reverse thermal gelation characteristics; that is, the material exists as a liquid at room temperature and as a solid at body temperature. These properties make it an ideal material for use in laparoscopic surgery. The antiadhesion properties of poloxamer 407 were evaluated in two models. In the first experiment, Golden hamsters were subjected to a standardized adhesion-producing lesion in the left uterine horn. Poloxamer solutions in concentrations ranging from 15-35% were applied to the injured horn. Location, thickness, and extent of adhesion formation were assessed 14 days later. Significant reduction in post-traumatic adhesion formation was observed following treatment with the 30-35% solutions. The second experiment was designed as a paradigm of the typical situation encountered in infertility surgery: prevention of adhesion reformation after lysis of established adhesions. New Zealand White rabbits were subjected to three laparotomies at 14-day intervals for placement of the adhesion-producing lesion, evaluation (prescore) and surgical lysis of induced adhesions, and subsequent evaluation of adhesion reformation (post-score). The effect of applying poloxamer 407 after adhesiotomy was compared with controls (no treatment). Adhesion reformation (post-score) was markedly reduced by poloxamer-407 treatment. Further trials of this material in the clinical setting are indicated.

Animals↗
PubMed1988

Protective, restorative, and therapeutic properties of recombinant human IL-1 in rodent models.

Human rIL-1 alpha and -1 beta are shown to increase significantly the CFU-culture activity in the spleen as well as at other sites after i.v. or i.p. administration. IL-1 can also significantly increase survival and can "rescue" a number of animals if administered either before or after lethal doses of cyclophosphamide or gamma-irradiation. The protective and reconstitutive activities of the rIL-1 are shown to correlate with increased CFU-culture frequency and total number, as well as increased cellularity in the bone marrow and peripheral blood, suggesting that this is one of their mechanisms of action. The sequence and timing of administration of human rIL-1 is critical for the protection or rescue of animals receiving DNA-damaging agents; maximal activity is achieved when IL-1 is given 20 h before insult or 48 h after alkylating agent administration. Minimal therapeutic activity is observed with IL-1 as a single agent for the treatment of metastatic disease compared with other biologic response modifiers including IFN-gamma.

Animals↗
PubMed1988

Rodent model of chemoradiotherapy-induced white matter necrosis.

This report describes a laboratory model that permits study of the radiochemotherapy interactions in the CNS. Rats are stereotaxically implanted with a cerebroventricular cannula attached to an osmotic minipump, which slowly infuses a chemotherapeutic agent into CSF for up to 14 days. The cervical cord is irradiated, and forelimb paralysis develops 4-6 months later at an effective dose for paresis in 50% of the animals; the doses with radiotherapy alone are 2,125 cGy for a single fraction and 2,950 cGy for split fractions. Investigations with the model indicate that mature CNS tissue is not sensitized to either single-fraction or split-dose irradiation with either simultaneous or post-radiation exposure to high concentrations of methotrexate.

Animals↗
PubMedDate not supplied

Exploratory studies of a rodent model for inhalant abuse.

For simulation of inhalant abuse exposure conditions, male and female rats were exposed to high concentrations (10,000-30,000 ppm) toluene vapor until unconscious (8-12 min periods). Sex differences were observed in the mean times to onset of sleep during exposure; linear regression lines of min to sleep onset as a function of toluene/kg body wt had slopes of -0.7492 for males and -0.4515 for females. Animals were removed from the exposure chamber to clean air and both spontaneous horizontal locomotor activity (2/3 animals) and ppm toluene in exhaled air (1/3 animals) were monitored for the first hr post-exposure. Animals regained consciousness within the first 6-7 min and consistently displayed a characteristic pattern of locomotor activity: activity increased initially to 2-3 times baseline level (1 hr preceding exposure) and remained elevated for approximately 10 min; activity then decreased to baseline range for a time before a period of inactivity and/or sleep by 60 min post-exposure. Immediately after regaining consciousness the concentration of toluene exhaled decreased rapidly for the first 10 min, somewhat less rapidly for the next 10-20 min and levelled off at 100-200 ppm for the following 30-40 min. The occurrence and duration of hyperactivity coincided with the period of rapid elimination of unchanged toluene through the lungs.

Animals↗
PubMed1985

Autotransplantation of adrenal cortical tissue: a rodent model.

Autotransplantation of human adrenal tissue has been attempted often, but results have been difficult to evaluate and success has been infrequent. Factors that may affect success include: volume of transplanted tissue, recipient site, inclusion of cortical capsule with the autograft, systemic or local growth factors, and the timing of evaluation. We have evaluated a model of autotransplantation in rats that will permit examination of these factors. Male Sprague-Dawley rats were assigned to (1) bilateral adrenalectomy (ADX), (2) bilateral adrenalectomy with immediate autotransplantation to a flank muscle pocket of one third of a single adrenal gland with its capsule attached (TX), or (3) sham operation. Animals were provided with 0.9% saline solution ad lib. At 2, 4, 6, and 12 weeks after surgery animals were stressed by brief exposure to ether and 15 minutes later had blood collected for determination of corticosterone concentration (C). ADX animals consistently weighed less than either TX or sham-operated animals; weights of sham-operated and TX animals were similar. Sham-operated animals uniformly had C levels higher than ADX or TX animals. At 2 and 4 weeks after surgery, C was similar in ADX and TX; but at 6 and 12 weeks, TX animals had higher values than had ADX animals. With this model, graft function can be demonstrated at 2 weeks by comparing body weight and at 6 weeks by comparing postether levels of C in TX animals to ADX animals. ADX animals can be maintained without steroid replacement on a regular diet with 0.9% saline solution ad lib. This model will permit examination of technical and physiologic influences on transplant success with both fresh and cryopreserved tissue and may lend itself to radionuclide or nuclear magnetic resonance assessment of graft function.

Adrenal Cortex↗