Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “rat model”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9Linked to original sources
PubMed1996

Preliminary physiologically based pharmacokinetic model for cocaine in the rat: model development and scale-up to humans.

A physiologically based multicompartmental model has been developed to describe the concentration-time course of cocaine in plasma and tissues in the rat. The compartments included in the model were brain, heart, gut, liver, muscle, fat, venous blood, arterial blood, and a mass-balance compartment. Drug delivery to the tissues was assumed to be flow limited. The model incorporated a nonsaturable binding site for cocaine in the liver. Elimination occurred via both blood and hepatic elimination. The model was validated using independently derived data. The model was scaled to humans and accurately predicted the cocaine levels following intranasal and inhalation administration. However, a poor fit was observed following intravenous administration. Future models incorporating non-constant blood flow and pharmacodynamics need to be developed.

Animals↗
PubMed2005

Heat shock protein 72 protects retinal ganglion cells in rat model of acute glaucoma.

PURPOSE: To investigate whether the induction of heat shock protein (HSP)72 by heat stress (HS) or zinc (Zn2+ ) administration can increase survival of retinal ganglion cells (RGC)in rat model of acute experimental glaucoma. METHODS: Acute glaucoma model was made by intracameral irrigation with BSS at 10(2) mmHg for two hours in right eyes of male Wistar rats. Glaucoma model rats were treated with HS once a week (six rats) or intraperitoneal injection of zinc sulfate (24.6 mg/kg) every two weeks (six rats), and were referred to as HS group and zinc group, respectively. Untreated model rats served as damage group (six rats). In control groups, quercetin (400 mg/kg) was intraperitoneally injected to inhibit the induction of heat shock proteins 6 hours before HS or zinc administration, and were referred to as HS+que group (six rats) and zinc+que group (six rats), respectively. Subsequent to 16 days of IOP elevation, the rats were sacrificed. Eyes were quickly enucleated, and the retinas were dissected. RGC were labeled with Nissl staining and counted under microscope. RESULTS: The average RGC density in normal Wistar rats was (2504+/-181) cells/mm(2). In damage group, it decreased to (2015+/-1111) cells/mm(2). The RGC densities at 1, 2, and 3 mm from the center of the optic nerve head were (2716+/-215), (2496+/-168), and (2317+/-171) cells/mm(2), respectively, for normal rats and (2211+/-133), (1969+/-154), and (1872+/-68) cells/mm(2), respectively, for damage group. The latter was significantly lower at all locations compared with the former (P=0.027 for each, Mann-Whitney test). The average RGC densities were (2207+/-200) cells/mm(2) for HS group, (2272+/-155) cells/mm(2) for zinc group, (1964+/-188) cells/mm(2) for HS+que group, (2051+/-214) cells/mm(2 )for zinc+que group and (2015+/-111) cells/mm(2) for damage group. There were significant differences in density of labeled RGCs among the five groups (P=0.040, Kruskal-Wallis test). Both HS and zinc group had higher RGC densities than damage group (P =0.036 between HS and damage group, P=0.019 between zinc and damage group, Mann-Whitney test). There was no significant difference in RGC density between control groups and damage group(P=-0.260 between HS+que and damage group, P-0.748 between zinc+que and damage group, Mann-Whitney test). CONCLUSIONS: The results demonstrated that the induction of HSP72 in RGCs by HS or zinc administration plays an important role in the survival of RGCs in rat model of acute glaucoma. A novel therapeutic approach to glaucoma through an enhanced induction of endogenous HSP72 could be possible.

Animals↗
PubMed1989

The effect of circulating antigen on radioimmunodetection and monoclonal antibody localisation: studies in a normal rat model.

The effect of circulating antigen (human kappa light chains (LC] on radioimmunoscintigraphy was examined in a normal rat model. Rats were implanted subcutaneously with kappa (test) and lambda (control) LC coupled to sepharose beads (500 micrograms LC/ml swollen gel). When 131I-labelled monoclonal antibody, K-1-21 was injected, clear images of specific antibody localisation to the kappa implant were seen 6 days later. The kappa implant: blood ratio (K:B) was 7.69 +/- 0.45, which represented an implant uptake of 2.52 +/- 0.20 percent injected dose per gram (%ID/g). When 131I-K-1-21 was preincubated with 125I-kappa LC at ratios of up to 1:10 antibody: antigen, (w/w) before injection; or if antigen was given daily by bolus injection or continuously infused via an osmotic pump, very clear specific images of antibody localisation to the kappa implant were still obtained. There was, however, a decline in the absolute uptake of label by the kappa implant. The greatest change was observed following continuous antigen infusion, when kappa implant uptake fell to 1.26 +/- 0.1 %ID/g. Nevertheless, the K:B ratio was still maintained at 6.8 +/- 0.2, due to increased clearance of antibody from the blood. Thus, in this case, where antigen and antibody might be expected to form small, soluble immune complexes, there was no major deleterious effect on radioimmunoscintigraphy.

Animals↗
PubMed1994

Metoclopramide inhibits development of esophageal varices in rat model.

We examined the preventive effect of metoclopramide on the development of esophageal varices in a rat model. Thirty rats were divided into three groups: metoclopramide (7.5 mg/kg twice a day, intraperitoneally), control group I (saline 2 ml/kg twice a day, intraperitoneally), and control group II (incised lower esophageal sphincter and metoclopramide 7.5 mg/kg twice a day, intraperitoneally). On the 14th postoperative day, lower esophageal sphincter pressure in the metoclopramide group (8.6 +/- 1.4 cm H2O) increased more than in the control groups (5.4 +/- 0.5, 5.0 +/- 0.5 cm H2O, P < 0.01). Development of small collateral vessels from the spleen to the retroperitoneum was evident only in the metoclopramide group, as seen on the portography (P < 0.01). Histologically, the variceal area of the horizontal cross section of the esophagus in the metoclopramide group (0.62 +/- 0.26 mm2) was significantly smaller than in the controls (2.67 +/- 0.95, 2.78 +/- 0.82 mm2), determined using an image processor-analyzer for photographing histological specimens (P < 0.01). We also investigated the effect of metoclopramide on smooth muscle cells in the rat portal vein, using isometric-tension recording. Metoclopramide relaxed the smooth muscle precontracted with norepinephrine, in a concentration-dependent manner. Thus, metoclopramide inhibits the development of esophageal varices in this rat model due to both an increase in resistance of the lower esophagus and to development of small collaterals.

Animals↗
PubMed2005

[The role of cyclic AMP in repair of hemisection of spinal cord in rats models].

OBJECTIVE: To study the role of cAMP in repair of hemisection of spinal cord in rats models. METHODS: Rats models of spinal cord hemisection were made and cAMP were injected once in the motor cortex or continuously input in the lesion area or in the subarachnoid cistern for 3 d. NFs, GFAP, CSTs and spinal axons in the lesion areas were observed by immunohistochemistry and hind limb movements were evaluated in BBB scales. RESULTS: Many regenerated axons were presented in the lesion areas in cAMP groups though no continuous long regenerated axons traversed the lesion area when cAMP was input in the motor cortex or in the local lesion area. In control group, no regenerated axon were presented in the lesion areas. When cAMP was input in the subarachnoid cistern, only few-labelled CST axon survived and presented in the lesion area comparing no labelled CST axon presented in the lesion area. More NFs and less GFAP were distributed and extended in the lesion area in the cAMP groups. All the rats restored to normally walk 4-5 weeks after operations and no significance existed between cAMP groups and control groups comparing the BBB scales of hind limb movements. CONCLUSION: cAMP injected in the brain cortex or continuously input in the lesion area can induce the axonal regeneration.

Administration, Topical↗
PubMed2000

[Effect of sijunzi decoction on gastric emptying rate in rat model of spleen deficiency syndrome].

OBJECTIVE: To observe the effect of Sijunzi decoction (SJZ) on gastric emptying rate in rat model of Spleen Deficiency Syndrome (SDS) and to explore the mechanism of "Yiqi Jianpi" (replenishing Qi and invigorating Spleen) effect with gastroduodenal myoelectrical activity and brain-gut peptide concentration. METHODS: After intramuscular injection of reserpine for 14 days, the rat model of SDS was established. Rats were randomly divided into 5 groups, group A treated by SJZ, group B treated by Liuwei Dihuang decoction (LWDH), group C naturally recovered, group D SDS rat model, consecutively treated for 14 days, and compared with group E, the normal control. Using radioisotopic technique to monitor 30 min gastric liquid emptying rate, and using the implanted bipolar silver electrode to observe the antral and duodenal myoelectrical slow wave, and the plasma and hypothalamus levels of motilium (MOT), cholecystokinin (CCK) and somatostatin (SS) were measured by radioimmunoassay (RIA) 14 days later respectively. RESULTS: Compared with the normal control, gastric liquid emptying rate of rat SDS model was lowered (P < 0.01, P < 0.05); the hypothalamus and plasma levels of MOT and SS reduced, both hypothalamus and plasma had higher CCK levels (P < 0.01, P < 0.05); in comparing with the controls, the rhythm, amplitude and motility index of myogastric slow wave were lower also. After treated with SJZ, the aforesaid data were normalized with insignificant difference in comparing with the normal control (P < 0.01), but the rat SDS model treated by LWDH and in natural recovery had no significant improvement. CONCLUSION: SJZ can promote gastric liquid emptying rate of rat SDS model by improving the myogastric electrical movement as well as regulating the levels of MOT, CCK and SS.

Animals↗
PubMed1985

Effect of vitamin D metabolites on bone metabolism in a rat model of postmenopausal osteoporosis.

A rat model of postmenopausal osteoporosis was introduced, using ovariectomized rats on a low Ca diet. CT treatment of these animals for one month prevented the decrease in both mineral contents and physical properties of the femoral bone. Treatment of the animals with 1,25(OH)2D3 was effective in increasing bone mineral contents and maintaining positive mineral balance, but did not increase the physical tolerance of bones. In contrast, 24,25(OH)2D3 increased the breaking force of the femoral bone, with minimal effect on bone mineral contents and mineral balance. These results suggest that 1,25(OH)2D3 and 24,25(OH)2D3 act differently on the matrix phase and mineral phase of bones, but that they act together to maintain mineral balance and structural integrity of bones. The mechanism of how these vitamin D metabolites affect bone metabolism remain to be clarified.

24,25-Dihydroxyvitamin D 3↗
PubMed2003

Dopamine hypofunction possibly results from a defect in glutamate-stimulated release of dopamine in the nucleus accumbens shell of a rat model for attention deficit hyperactivity disorder--the spontaneously hypertensive rat.

RUSSELL, V.A. Dopamine hypofunction possibly results from a defect in glutamate-stimulated release of dopamine in the nucleus accumbens shell of a rat model for attention deficit hyperactivity disorder-the spontaneously hypertensive rat. NEUROSCI. BIOBEHAV. REV.27(2003). Disturbances in glutamate, dopamine and norepinephrine function in the brain of a genetic animal model for attention-deficit hyperactivity disorder (ADHD), the spontaneously hypertensive rat (SHR), and information obtained from patients with ADHD, suggest a defect in neuronal circuits that are required for reward-guided associative learning and memory formation. Evidence derived from (i). the neuropharmacology of drugs that are effective in treating ADHD symptoms, (ii). molecular genetic and neuroimaging studies of ADHD patients, as well as (iii). the behaviour and biochemistry of animal models, suggests dysfunction of dopamine neurons. SHR have decreased stimulation-evoked release of dopamine as well as disturbances in the regulation of norepinephrine release and impaired second messenger systems, cAMP and calcium. In addition, evidence supports a selective deficit in the nucleus accumbens shell of SHR which could contribute to impaired reinforcement of appropriate behaviour.

Animals↗
PubMed1987

Effect of antidepressant on behavior and central catecholamine of depression-model rats.

Effect of antidepressant on behavior and central catecholamine were investigated in depression-model rats produced by long-term forced running stress. Changes in the spontaneous running activity and the concentration and turnover of catecholamine were examined in non-stressed rats injected with saline and depression-model rats injected with saline, imipramine and MOD-20 (a candidate for a tetracyclic antidepressant). Running activity was significantly restored by injection of imipramine and MOD-20. In depression-model rats, the concentrations of central catecholamine increased in the cell bodies and nerve terminals of the ascending noradrenaline system, and turnover rates of the catecholamine decreased in the terminal region. The increased concentrations were returned to the non-stressed level after injection of the drugs. However, decreased turnover rates were not recovered after the injection. These results suggested that MOD-20 was a potent antidepressant and the therapeutic efficacy of antidepressants might be due to the restoration of catecholamine concentrations.

Animals↗
PubMed2006

Apoptosis signaling pathway in a subtotal nephrectomy rat model.

To investigate the role and mechanisms of apoptosis and apoptosis signaling pathway in 5/6 nephrectomy rat model (SN(x)), the mRNA and protein levels of caspase-3, -8, -9 and apoptosis were detected by in situ end labeling (TUNEL), immunohistochemistry, RT-PCR, Western-blotting 1, 2, 4, 8, 12, 16, 26 and 40 weeks after 5/6 nephrectomy rat model was made respectively. The rats in the model group developed glomerular sclerosis and renal interstitial fibrosis. The number of the apoptototic cells in glomeruli, renal tubule and renal interstitium was remarkably higher in the model group than that in the control group (P < 0.05, P < 0.01). Changes of mRNA and protein level of caspase-3, -8, -9 had the same tendency and was up-regulated wavily in the rat model compared with the control group (P < 0.05). Peaks in model appeared on the 4th and the 40th week respectively. The growth amplitude of caspase-9 was remarkably higher than that of caspase-8. It is concluded that the development of 5/6 nephrectomy rat model was correlated with the apoptosis of glomeruli, renal tubule and renal interstitium. Both of death receptor and mitochondria signaling pathways are involved in the process and the latter might play a primary role.

Animals↗
PubMed1989

Effects of electrical stimulation on joint contracture in a rat model.

This study was intended to delineate whether electrical stimulation could significantly reduce the amount of joint contracture in a rat model. Rat knees were surgically immobilized in 150 degrees of flexion. Two groups of rats had sham electrodes, and two groups were electrically stimulated. All rats were killed 14 days after surgery. The degree of joint contracture was assessed by measuring the femorotibial angles with a 0.015-Nm extension moment applied. When the electrical current was applied in a transverse manner, there was a statistically significant reduction in the amount of posterior capsule (p less than 0.005) and anterior cruciate ligament (ACL) (p less than 0.05) contracture. When the electrical current was applied longitudinally, no significant difference in the amount of joint contracture was found. These findings support the hypothesis that electrical stimulation can inhibit joint contracture. These findings also suggest that the effect occurs when the electrical current is applied transversely as opposed to longitudinally.

Animals↗
PubMed2005

[Learning and memory amelioration of transplantation of the neural stem cells modified with human brain-derived neurotrophic factor gene on Alzheimer disease model rat].

OBJECTIVE: To investigate the memory amelioration of the Alzheimer disease (AD) model rat after being transplanted the single neural stem cells (NSC) and NSC modified with human brain-derived neurotrophic factor (hBDNF) gene. METHODS: Forty SD rats were divided evenly into 4 groups randomly. The AD model rats were made by cutting unilaterally the fibria-fornix of male rats. Ten to twelve days after surgery, the genetically modified and unmodified NSC were implanted into the lateral cerebral ventricle of group III and group IV respectively. Two weeks after transplantation, the amelioration of memory impairment of the rats was detected by Morris water maze. RESULTS: The average escaping latency of the group III and group IV (41.84 +/- 21.76 s, 25.23 +/- 17.06 s respectively) was shorter than that of the group II (70.91 +/- 23.67 s) (P<0.01). The percentage of swimming distance in the platform quadrant in group III (36.9%) and in group IV (42.0%) was higher than that in the group II (26.0%) (P<0.01). More marginal and random strategies were used in group II. The percentage of swimming distance in the platform quadrant in group IV was also greater than that in group III (P<0.05). There were no significant differences in the average escaping latency, the percentage of swimming distance in the platform quadrant and the probe strategy between group IV and group I (P>0.05). More lineal and oriented strategies were used in group IV. CONCLUSION: The behavioral amelioration of AD model rat was obtained by transplanting single NSC and hBDNF-gene-modified NSC. The effect of the NSC group modified with hBDNF gene is better than that of the group III.

Alzheimer Disease↗
PubMedDate not supplied

2001 Harry M. Vars Research Award. Enteral nutrients alter enterocyte function within an in vitro model similar to an acute in vivo rat model during hypoxia.

BACKGROUND: Early enteral nutrition in patients following traumatic injury is an important intervention. However, after shock-resuscitation, intestinal hypoperfusion persists despite adequate systemic resuscitation. Our previous in vivo rat studies indicate that hypoperfusion impairs mucosal function in the small intestine. Therefore, the current study sought to improve previous in vitro models by the following means: (1) We used Caco-2 monolayers stably transfected with the brush-border sodium-glucose co-transporter (SGLT-1); and (2) we created an environment that mimicked the physiologic enterocyte environment. We hypothesized that hypoxic alterations of epithelial function in an in vitro model are comparable to those of an in vivo rat model. METHODS: After 21 days, monolayers were randomized to receive 24 hours of incubation in a normoxic or hypoxic environment. Cells were further randomized to receive 1 of 4 nutrient treatments: mannitol (an osmotic control), glucose (uses SGLT-1 and is metabolized), 3-O-methylglucose (3-O-mg; uses SGLT-1 and is not metabolized), or fructose (does not use SGLT-1 but can be metabolized). RESULTS: Transepithelial resistance (p = .007) and short-circuit current (p = .05) were lower in hypoxic groups. When compared with normoxic groups, hypoxic groups had significantly impaired glucose (p < .001) but not glutamine transport, irrespective of nutrient treatment. Additionally, adenosine triphosphate/adenosine diphosphate ratio was reduced (p = .01) and lactate concentration was increased (p < .001) during hypoxia. CONCLUSIONS: In summary, results from this in vitro study using Caco-2BBe cells stably transfected with SGLT-1 correspond to results obtained in the in vivo rat model. Therefore, this is an appropriate in vitro model in which to study cellular alterations caused by the hypoxic small intestine, with the goal of ensuring safe early enteral nutrition following traumatic injury.

3-O-Methylglucose↗
PubMed1999

An adenosine kinase inhibitor attenuates tactile allodynia in a rat model of diabetic neuropathic pain.

The present study was conducted to characterize the development of tactile allodynia in the streptozotocin-induced rat model of diabetes, and to evaluate the antinociceptive effects of systemically administered morphine and the adenosine kinase inhibitor, 5'-deoxy-5-iodotubercidin (5'd-5IT) in this model. Rats were injected with 75 mg/kg streptozotocin (i.p.), and blood glucose levels were determined 3-4 weeks later. Diabetic (blood glucose levels > or = 250 mg/dl) and vehicle-injected rats were examined weekly for the development of tactile allodynia by measuring the threshold for hind paw withdrawal using von Frey hairs. Withdrawal thresholds were reduced to 6.8+/-0.6 g (mean+/-S.E.M.) in approximately one-third of streptozotocin-treated rats 7 weeks after streptozotocin treatment as compared to control thresholds (13.2+/-0.1 g), and this allodynia persisted for at least an additional 7 weeks. In additional experiments, morphine sulfate (5-21 micromol/kg, i.p.) produced dose-dependent antinociceptive effects on tactile allodynia for up to 2 h post-dosing. The adenosine kinase inhibitor, 5'd-5IT (2.5 and 5 micromol/kg, i.p.) also dose-dependently attenuated tactile allodynia. Pretreatment with the opioid receptor antagonist, naloxone (27 micromol/kg, i.p.) or the non-selective adenosine receptor antagonist, theophylline (111 micromol/kg, i.p.) significantly diminished the anti-allodynic effects of morphine and 5'd-5IT, respectively. The present study demonstrates that the potent and selective adenosine kinase inhibitor, 5'd-5IT, is equally effective as morphine in blocking tactile allodynia in this model.

Adenosine Kinase↗
PubMed1999

Focal epileptogenesis in a rat model of polymicrogyria.

Polymicrogyria, a developmental cortical malformation associated with epilepsy, can be modeled in rats with a transcortical freeze lesion on the day of birth (P0) or P1. We have used field potential recordings to characterize the incidence, propagation patterns, and distribution of epileptiform activity in slices from rats with experimental microgyri. Interictal-like epileptiform activity was evoked in slices from 85% of freeze-lesioned rats aged P12-P118. These data show age-specific properties of epileptogenesis, including: a delay in onset, a decrease in the incidence of epileptiform activity in rats >P40 that was specific to those lesioned on P0 as opposed to P1, and a shift in the likely site of initiation to areas further from the microgyrus in mature animals. Several observations suggest that the area adjacent to the microgyrus, which appears histologically normal in Nissl stains, contains the necessary epileptogenic neuronal circuits: 1) in 78% of slices, epileptiform activity could be evoked only from a focal zone adjacent to the microgyrus (paramicrogyral zone) and not within the microgyrus proper; 2) epileptiform activity consistently originated from a particular site within this paramicrogyral zone, independent of the location of the stimulating electrode, suggesting that the generator is outside of the microgyrus; 3) evoked epileptiform activities in the paramicrogyral cortex were unaltered after separation of this zone from the microgyrus with a transcortical cut; and 4) the short-latency graded field potential evoked in the paramicrogyral zone contained an additional negativity not seen in control slices. The epileptiform activity was blocked reversibly by N-methyl--aspartate receptor antagonists in slices from mature as well as immature freeze-lesioned rats. These results suggest that aberrant synaptic connectivity develops in rat cortex surrounding the microgyrus and produces a focal epileptogenic zone whose capacity to generate epileptiform activities does not depend on connections with the malformation itself. We hypothesize that afferents, originating from cortical and extracortical sites, lose their targets in the region of the malformation and make appropriate laminar contacts in the cortex adjacent to the malformation, creating an overabundance of excitatory input to this cortical zone. Increased excitatory feedback onto specific cortical elements may be one factor involved in epileptogenesis in this model of a cortical malformation.

Aging↗
PubMed2005

[Comparative study on effect of Tripterygium polyglycosides on mucous immune function of rat models of arthritis induced by collagen II and by adjuvant].

OBJECTIVE: To observe the effects of Tripterygium polyglycosides (TWP) on mucous immune function in rat models of arthritis induced respectively with collagen-II induced arthritis (CIA) & adjuvant arthritis (AA). METHODS: CIA and AA model rats were induced by immunization with collagen II emulsified with complete Freund's adjuvant and complete Freund's adjuvant respectively and treated with TWP. Rats' mucus, systemic immunological indexes (peripheral subsets of T cells), local inflammatory factors (IL-6, TNF-alpha, COX-2,and NF-kappaB, etc. ) were observed. RESULTS: In CIA model group, CD4+ in Peyer's Patch (PP), peripheral CD4+ and CD8+ positive T cells all raised, while in the AA model group, CD4+ lowered and CD8+ raised on PP, with both subsets increased. Effects of TWP on T lymphocyte subsets in PP and blood of the two models were different. High leveled IL-6, TNF-alpha, COX-2 and NF-kappaB expression could be seen in both model groups, and these inflammatory media could be inhibited by TWP. CONCLUSION: There exist similarities and differences between the two models in aspects of mucus immune response and effect of TWP on them.

Animals↗
PubMed2003

A rat model for the energetic regulation of gonadotropin secretion: role of the glucose-sensing mechanism in the brain.

Energy availability has been considered to regulate gonadal activity by modulating the release of gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) at various reproductive phases, such as lactation and puberty in domestic as well as wild animals. Experimental models with rats and sheep have demonstrated that fasting or glucoprivation suppresses pulsatile LH release. From those experiments, the information on energy deficiency is considered to be detected by specific central sensors and conveyed to the hypothalamus to regulate LH release as well as food intake. Noradrenergic neurons, originating in the medulla oblongata and projecting to the hypothalamic paraventricular nucleus (PVN), is reported to be one of the pathways mediating the response of LH release to energy deficiency. The other component is considered to be an energy-sensing mechanism in the brain. Glucose or other oxidizable fuels may function as a metabolic signal to regulate LH release. Previous studies suggest the presence of a glucose-sensing mechanism in the rat hindbrain. From our previous results in the rat, the ependymocytes lining the wall of the cerebroventricle could possibly serve as a glucose sensor to regulate GnRH/LH release. Greater understanding of the nature of the energy-sensing mechanism in the brain will contribute to the nutritional manipulation of reproductive performance in domestic animals in various conditions.

Animals↗