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Sample records for rat kindling model

  1. Anticonvulsant and proconvulsant effects of tramadol, its enantiomers and its M1 metabolite in the rat kindling model of epilepsy

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    Potschka, Heidrun; Friderichs, Elmar; Löscher, Wolfgang

    2000-01-01

    The centrally acting analgesic tramadol has recently been reported to cause seizures at re-commended dosages in patients, whereas animal experiments had indicated that seizures only occur in high, toxic doses. Tramadol has a dual mechanism of action that includes weak agonistic effects at the mu-opioid receptor as well as inhibition of monoamine (serotonin, norepinephrine) re-uptake. Its major (M1) metabolite mono-O-desmethyltramadol, which is rapidly formed in vivo, has a markedly higher affinity for mu receptors and may thus contribute to the effects of the parent compound. Furthermore, the pharmacological effects of tramadol appear to be related to the different, but complementary and interactive pharmacologies of its enantiomers. In the present study, we evaluated (±)-tramadol, its enantiomers, and its M1 metabolite ((+)-enantiomer) in the amygdala kindling model of epilepsy in rats. Adverse effects determined in kindled rats were compared to those in nonkindled rats. At doses within the analgesic range, (±)-tramadol and its enantiomers induced anticonvulsant effects in kindled rats. However, at only slightly higher doses seizures occurred. With (±)-tramadol, generalized seizures were observed at 30 mg kg−1 in most kindled but not in nonkindled rats. The (−)-enantiomer induced myoclonic seizures at 30 mg kg−1 in most kindled but not in nonkindled rats, although myoclonic seizure activity was observed in some nonkindled rats at 10 or 20 mg kg−1. Seizures were also observed after the (+)-enantiomer and the (+)-enantiomer of the M1 metabolite, but experiments with higher doses of these compounds were limited by marked respiratory depression. The data demonstrate that kindling enhances the susceptibility of rats to convulsant adverse effects of tramadol and its enantiomers, indicating that a preexisting lowered seizure threshold increases the risk of tramadol-induced seizures. PMID:10991912

  2. Quantitative assessments of extracellular EEG to classify specific features of main phases of seizure acquisition based on kindling model in Rat.

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    Jalilifar, Mostafa; Yadollahpour, Ali; Moazedi, Ahmad Ali; Ghotbeddin, Zohreh

    2017-08-24

    Quantitative assessments of extracellular EEG to identify specific features of three main phases of seizure acquisition based on kindling model in Rat. Male rats were divided into 2 groups including kindled (n=10) and sham (n=7) and respectively underwent an amygdala rapid kindling and placebo kindling. EEG signals in stages 1-2 (initial seizure stages (ISSs)), 3 (localized seizure stage (LSS)), and 4-5 generalized seizure stages (GSSs) were divided into 5 bands: delta (0-4Hz), theta (4-8Hz), alpha (8-12Hz), beta (12-28Hz), and gamma (28-40Hz). Spectral power of the sub bands and the ratios of theta/alpha and delta/beta were compared in the three phases and between the sham and kindling groups. Beta power significantly increased during kindling acquisition, though it was significantly lower than sham. Delta oscillation in ISSs was higher than LSS and GSSs, but the difference was significant only with LSS. Moreover, delta power was higher in all stages of kindling than sham. Gamma power in all stages of kindling was significantly lower than sham. Alpha power was significantly reduced in ISSs, compared with sham, but gradually increased during epileptogenesis. Theta/alpha and delta/beta increased in all stages, compared with sham (pISSs (pISSs and LSS (PISSs significantly decreased, but gradually increased along with kindling progression. Furthermore, delta power significantly increased during kindling process. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Decreased Expression of Sox-1 in Cerebellum of Rat with Generalized Seizures Induced by Kindling Model.

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    Rubio-Osornio, Carmen; Eguiluz-Meléndez, Aldo; Trejo-Solís, Cristina; Custodio, Veronica; Rubio-Osornio, Moises; Rosiles-Abonce, Artemio; Martínez-Lazcano, Juan C; González, Edith; Paz, Carlos

    2016-01-01

    The single feature of all malformations in cortical development is the clinical association with epilepsy. It has been proven that Sox-1 expression is essential during neurodevelopment and it is reported that Sox-1 knockout mice present spontaneous generalized seizures. Particularly in cerebellum, Sox-1 plays a key role in the Bergmann´s glia (BG) function, which allows the correct function of the Purkinje cells (PC). The targets of PC are the dentate and interpositus nuclei, which form the main cerebellar efferents involved in the physiopathology of epilepsy. Here we present the Sox-1 expression in cerebellum of rats during electric amygdala-kindling. We obtained seizures and once they had 3, 15 and 45 electric stimuli, the animals were sacrificed; the cerebellum was processed for inmunohistochemistry and Western blot analysis was performed to determine Sox-1 expression. Liquid chromatography was performed to examine gammaaminobutyric acid (GABA) and glutamate concentration. According to the literature, a progressive increase was observed in the electrographic and behavioral parameters. We found that Sox-1 expression in 15 and 45-stimuli groups had a statistically significant decrease as compared with controls, while the 3-stimuli group was similar to the control group. The concentration of glutamate was increased in rats with 45 stimuli. We can conclude that Sox-1 expression decreases as the number of seizures increases, and this is probably due to an altered glutamate regulation by a dysfunctional BG. In this way, we can suggest this mechanism as a one possible explanation of how the cerebellum participates in the pathophysiology of epilepsy.

  4. Persistence of Acquired Epileptogenesis in Amygdaloid-Kindled Rats: Relationship between the Initial Kindling Stages and Seizure Development in Rekindling

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    TAKEO, Shigeki; Yoshioka, Shin-ichi; Maeda, Kazuhisa; Takasu, Junji; Ueda, Toshiyuki; Kawahara, Ryuzo

    2000-01-01

    In order to gain insight into mechanisms underlying the persistence of the partial kindling effect, we suspended amygdaloid kindling at different seizure stages in rats, and investigated the effects on subsequent rekindling after a rest period of 2 months. Ten-week-old rats, implanted with bipolar electrodes, were separated by various initial kindling stages into 5 groups of rats, partially kindled to stages 1 (n = 7) and 2 (n = 10), fully kindled to stages 4 (n = 11) and 5 (n = 11), and cont...

  5. Analysis of Seizure EEG in Kindled Epileptic Rats

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    A. K. Sen

    2007-01-01

    Full Text Available Using wavelet analysis we have detected the presence of chirps in seizure EEG signals recorded from kindled epileptic rats. Seizures were induced by electrical stimulation of the amygdala and the EEG signals recorded from the amygdala were analyzed using a continuous wavelet transform. A time–frequency representation of the wavelet power spectrum revealed that during seizure the EEG signal is characterized by a chirp-like waveform whose frequency changes with time from the onset of seizure to its completion. Similar chirp-like time–frequency profiles have been observed in newborn and adult patients undergoing epileptic seizures. The global wavelet spectrum depicting the variation of power with frequency showed two dominant frequencies with the largest amounts of power during seizure. Our results indicate that a kindling paradigm in rats can be used as an animal model of human temporal lobe epilepsy to detect seizures by identifying chirp-like time–frequency variations in the EEG signal.

  6. Inhibitory Effect of High Dose of the Flavonoid Quercetin on Amygdala Electrical Kindling in Rats

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    Tourandokht Baluchnejadmojarad

    2010-05-01

    Full Text Available A B S T R A C T Introduction: Epilepsy is a chronic neurological disorder in which patients experience spontaneous recurrent seizures. Although the most commonly recommended therapy is drug treatment, some patients do not achieve adequate control of their seizures on existing drugs. New medications with novel mechanisms of action are needed to help those patients whose seizures are resistant to currently-available drugs. Therefore, the anti-convulsant effect of a high dose of quercetin was evaluated in amygdala kindling model in male rats. Methods: Rats were divided into sham-operated group, quercetintreated SH, kindled, and quercetin-treated kindled rats. Quercetin was administered i.p. one day before amygdale kindling for 3 weeks (40 mg/kg/day. The parameters seizure stage, AD duration, the latency to the onset of stage 4, and the duration of stage 5 were analyzed. Results: The results showed that quercetin pretreatment causes a lower seizure intensity in treated kindled rats (p<0.05-0.01, a lower after-discharge duration (p<0.05-0.01, and a higher latency to stage IV (p<0.05 as compared to untreated kindled ones. Discussion: To conclude, chronic administration of quercetin inhibits amygdala electrical kindling and more studies are warranted to clarify its underlying mechanisms.

  7. Anticonvulsive and antiepileptogenic effects of levetiracetam in the audiogenic kindling model

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    Vinogradova, L.V.; Rijn, C.M. van

    2008-01-01

    Purpose: To study anticonvulsive and antiepileptogenic effects of singe levetiracetam (LEV) administration in the model of audiogenic kindling. Methods: Rats of Krushinsky-Molodkina (KM) strain genetically susceptible to severe audiogenic seizures received one intraperitoneal injection of saline,

  8. Effect of meclofenoxate on pentylenetetrazol kindling in albino rats.

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    Lazarova, M; Georgiev, V; Markovska, V; Genkova, M; Petkov, V D

    1987-01-01

    The effects of a single and 5-day treatment of male albino rats with meclofenoxate in a dose of 100 mg/kg on the clonic-tonic convulsions during the kindling phenomenon, induced by multiple injection of a subconvulsive dose (40 mg/kg) pentylenetetrazol (PTZ) were tested. Its effects on convulsions, induced by a single convulsive dose of 100 mg/kg, were investigated for the sake of comparison. Meclofenoxate, introduced in a single dose of 100 mg/kg, lowered the intensity of the convulsions in PTZ-kindled rats. Meclofenoxate treatment for 5 days had an even more pronounced inhibitory effect on PTZ kindling. As regards the convulsions induced by a single injection of a convulsive PTZ dose, meclofenoxate only tends to decrease the percentage of rats with tonic convulsion and the lethality. On the basis of the results of earlier studies, the role of the serotoninergic neurotransmitter system for the observed inhibitory effect of meclofenoxate on PTZ kindling in albino rats is discussed.

  9. [Stimulation of gastric mucosa afferents by phenylephrine potentiates anticonvulsive and eliminates sedative action of sodium valproate in the pentylenetetrazol kindling model in rats].

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    Serdiuk, S E; Gmiro, V E; Veselkina, O S

    2014-01-01

    Sodium valproate after chronic intragastric administration in the high dose of 100-200 mg/kg eliminates generalized clonic-tonic pentylenetetrazol seizures in 100 % of rats, but only in 33-57 % of rats it prevents local clonic kindling seizures. Strong sedation is induced by the specified doses of sodium valproate. The combined oral chronic administration of phenylephrine in threshold, noneffective alone dose of 0.2 mg/kg and sodium valproate in high doses of 100 mg/kg and 200 mg/kg potentiates anticonvulsive action of sodium valproate, because prevents both clonic-tonic kindling. seizures in 100 % of rats and clonic kindling seizures in 86-100 % of rats, and also it increases in 1.7-1.9 times anticonvulsive activity of valproate. The specified combinations of sodium valproate with phenylephrine do not produce the sedative side effect. The basis of the mechanism of potentiation of anticonvulsive action and elimination of sedative action of sodium valproate in high doses is the stimulation of gastric mucosa afferents by phenylephrine.

  10. A new rapid kindling variant for induction of cortical epileptogenesis in freely moving rats

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    Juan Carlos Morales

    2014-07-01

    Full Text Available Kindling, one of the most used models of experimental epilepsy is based on daily electrical stimulation in several brain structures. Unlike the classic or slow kindling protocols (SK, the rapid kindling types (RK described until now require continuous stimulation at suprathreshold intensities applied directly to the same brain structure used for subsequent electrophysiological and inmunohistochemical studies, usually the hippocampus. However, the cellular changes observed in these rapid protocols, such as astrogliosis and neuronal loss, could be due to experimental manipulation more than to epileptogenesis-related alterations. Here, we developed a new RK protocol in order to generate an improved model of temporal lobe epilepsy (TLE which allows gradual progression of the epilepsy as well as obtaining an epileptic hippocampus, thus avoiding direct surgical manipulation and electric stimulation over this structure. This new protocol consists of basolateral amygdala (BLA stimulation with 10 trains of biphasic pulses (10s;50Hz per day with 20 minutes-intervals, during 3 consecutive days, using a subconvulsive and subthreshold intensity, which guarantees tissue integrity. The progression of epileptic activity was evaluated in freely moving rats through EEG recordings from cortex and amygdala, accompanied with synchronized video recordings. Moreover, we assessed the effectiveness of RK protocol and the establishment of epilepsy by evaluating cellular alterations of hippocampal slices from kindled rats. RK protocol induced convulsive states similar to SK protocols but in 3 days, with persistently lowered threshold to seizure induction and epileptogenic-dependent cellular changes in amygdala projection areas. We concluded that this novel RK protocol introduces a new variant of the chronic epileptogenesis models in freely moving rats, which is faster, highly reproducible and causes minimum cell damage with respect to that observed in other experimental

  11. Effect of eslicarbazepine acetate in the corneal kindling progression and the amygdala kindling model of temporal lobe epilepsy.

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    Potschka, Heidrun; Soerensen, Jonna; Pekcec, Anton; Loureiro, Ana; Soares-da-Silva, Patrício

    2014-02-01

    The present study was aimed at determining the effect of eslicarbazepine acetate (ESL), eslicarbazepine and (R)-licarbazepine administration in the mouse corneal kindling and amygdala kindling models. NMRI mice were kindled by bilateral corneal stimulation twice daily. In amygdala kindling, mice were stimulated once daily via an implanted depth electrode until 10 generalized seizures were elicited. Maximal electroshocks (MES) were administered via corneal electrodes. The average number of stimulations to reach a fully kindled generalized seizure was markedly increased by ESL. Administration of eslicarbazepine also inhibited the acquisition of kindling, whereas administration of R-licarbazepine did not affect the number of stimulations necessary to induce a specific seizure stage, and did not exert any relevant effect on mean seizure severity during kindling progression. ESL dose-dependently increased the focal seizure threshold and reduced seizure severity in amygdala kindling. Whereas eslicarbazepine treatment increased the afterdischarge threshold in a significant manner, (R)-licarbazepine treatment failed to exert a significant effect on thresholds in fully kindled mice. Administration of ESL and of eslicarbazepine significantly protected mice against MES-induced seizures, whereas that of (R)-licarbazepine failed to provide protection. These data provide evidence of the anticonvulsant effect of ESL and its active metabolite eslicarbazepine on partial-onset seizures in corneal and amygdala kindling models. Based on an effect of the parent compound and the active metabolite eslicarbazepine, ESL treatment may not merely suppress seizure activity but may also provide a disease-modifying or antiepileptogenic effect. Future studies will be necessary to further evaluate a putative preventive effect, in particular when considering that re-stimulation following wash-out did not indicate a persistent effect. The findings reported here raise doubts on the contribution of

  12. Dataset of quantitative spectral EEG of different stages of kindling acquisition in rats

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    Mostafa Jalilifar

    2018-02-01

    Full Text Available The data represented here are in relation with the manuscript "Quantitative assessments of extracellular EEG to classify specific features of main phases of seizure acquisition based on kindling model in Rat" (Jalilifar et al., 2017 [1] which quantitatively classified different main stages of the kindling process based on their electrophysiological characteristics using EEG signal processing. The data in the graphical form reported the contribution of different sub bands of EEG in different stages of kindling- induced epileptogenesis. Only EEG signals related to stages 1–2 (initial seizure stages (ISSs, 3 (localized seizure stage (LSS, and 4–5 (generalized seizure stages (GSSs were transferred into frequency function by Fast Fourier Transform (FFT and their power spectrum and power of each sub bands including delta (1–4 Hz, Theta (4–8 Hz, alpha (8–12 Hz, beta (12–28 Hz, gamma (28–40 Hz were calculated with MATLAB 2013b. Accordingly, all results were obtained quantitatively which can contribute to reduce the errors in the behavioral assessments.

  13. Dataset of quantitative spectral EEG of different stages of kindling acquisition in rats.

    Science.gov (United States)

    Jalilifar, Mostafa; Yadollahpour, Ali

    2018-02-01

    The data represented here are in relation with the manuscript "Quantitative assessments of extracellular EEG to classify specific features of main phases of seizure acquisition based on kindling model in Rat" (Jalilifar et al., 2017) [1] which quantitatively classified different main stages of the kindling process based on their electrophysiological characteristics using EEG signal processing. The data in the graphical form reported the contribution of different sub bands of EEG in different stages of kindling- induced epileptogenesis. Only EEG signals related to stages 1-2 (initial seizure stages (ISSs)), 3 (localized seizure stage (LSS)), and 4-5 (generalized seizure stages (GSSs) were transferred into frequency function by Fast Fourier Transform (FFT) and their power spectrum and power of each sub bands including delta (1-4 Hz), Theta (4-8 Hz), alpha (8-12 Hz), beta (12-28 Hz), gamma (28-40 Hz) were calculated with MATLAB 2013b. Accordingly, all results were obtained quantitatively which can contribute to reduce the errors in the behavioral assessments.

  14. The effect of hydroalcoholic extract of Pistacia vera on pentylenetetrazole-induced kindling in rat

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    F. Fatehi

    2017-04-01

    Full Text Available Background and objectives: Most antiepileptic drugs that are commonly being used in the clinic have a wide range of unwanted side effects; while some species of pistachioshave been used in the traditional medicine to treat epilepsy. The aim of the present study was to investigate the anticonvulsant effects of the hydroalcoholic extract of Pistacia vera L. in pentylenetetrazole (PTZ-induced chemical kindling. Methods: this study was carried out on 40 male Wistar rats. Chemical kindling was induced by intraperitoneal administration of PTZ (40 mg/kg on every alternate day (30 days. The hydroalcoholic extract of P. vera (50 and 100 mg/kg were administered orally every day (30 days. In days which animals received both PTZ and extract, PTZ was injected 30 min after extract administration. Convulsive behavior was observed for 30 min after PTZ injection and scored according to racine scale. Diazepam was used as the reference anticonvulsant drug. Results: Pretreatment with 50 and 100 mg/kg of P. vera extract decreased seizure scores, stage 4 latency and stage 5 duration compared to the control group. The anti-epileptic effects of P. vera extract were comparable to diazepam. Conclusion: The present findings demonstrated that the hydroalcoholic extract of P. vera may inhibit the development of seizure behavior following chronic PTZ-induced model of epilepsy in rats.

  15. The role of the substantia nigra pars reticulata in kindling resistance in rats with genetic absence epilepsy.

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    Akman, Ozlem; Gulcebi, Medine I; Carcak, Nihan; Ketenci Ozatman, Sema; Eryigit, Tugba; Moshé, Solomon L; Galanopoulou, Aristea S; Onat, Filiz Yilmaz

    2015-11-01

    Genetic Absence Epilepsy Rats from Strasbourg (GAERS) show a resistance to secondary generalization of focal limbic seizures evoked by kindling. The substantia nigra pars reticulata (SNR) is involved in the propagation and modulation of seizures in kindling. We first examined the role of the SNRanterior and SNRposterior subregions in the resistance to the development of kindling in GAERS. Subsequently, to determine whether kindling resistance relates to differential sensitivity of γ-aminobutyric acid γ-aminobutyric acid (GABA)ergic or dopaminergic SNR neurons to kindling, we studied the effects of kindling-inducing stimulations on parvalbumin (PRV; GABAergic neuron marker) or tyrosine hydroxylase (TH; dopaminergic neuron marker) immunoreactivity (ir), respectively, in GAERS and in nonepileptic control (NEC) Wistar rats that lack kindling resistance. Adult male GAERS were implanted with a stimulation electrode in the amygdala, and bilateral injection cannulas for lidocaine or saline injection (30 min before each kindling stimulation until the animals reached three stage 5 seizures or the 22 stimulations) into the SNRanterior or SNRposterior . In another experiment, PRV-ir in SNRanterior and SNRposterior and TH-ir in SNRposterior only were densitometrically compared in GAERS-SHAM, NEC-SHAM GAERS-STIM, and NEC-STIM animals (6 kindling stimulations). Bilateral SNRposterior infusions of lidocaine eliminated the kindling resistance and resulted in stage 5 generalized motor seizures in all kindled rats. Bilateral lidocaine infusions in the SNRanterior failed to alter the kindling resistance in GAERS. PRV-ir in the SNRposterior was unaltered in GAERS-STIM but increased in NEC-STIM group. Cellular TH-ir in the SNRposterior significantly increased by kindling stimulations in both NEC-STIM and GAERS-STIM groups. The kindling resistance in GAERS is mediated by the SNRposterior in a lidocaine-sensitive manner. The insensitivity to kindling stimulation of PRV-ir in

  16. Omega-3 polyunsaturated fatty acids in large doses attenuate seizures, cognitive impairment, and hippocampal oxidative DNA damage in young kindled rats.

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    Abdel-Wahab, Basel A; Al-Qahtani, Jobran M; El-Safty, Samy A

    2015-01-01

    Omega-3 (OM3) dietary polyunsaturated fatty acids have promising seizure-protective effects, as well as enhancing effects of cognitive development and memory-related learning. This study aimed to explore the effect of large doses of OM3 on cognitive impairment and hippocampal oxidative DNA damage produced by seizures in epileptic children using a PTZ-kindled young rat model. Cognitive functions, biomarkers of oxidative stress, and DNA damage were assessed in PTZ-kindled young rats (30 mg/kg, i.p. once every other day for 13 injections) pretreated with OM3 (200-500 mg/kg, p.o.). Pretreatment with OM3 at the tested doses significantly attenuated PTZ-induced seizures and decreased cognitive impairment in both passive avoidance and elevated plus maze tests in the PTZ-kindled rats. Moreover, OM3 significantly attenuated the increase in hippocampal malondialdehyde and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels, as well as the decrease in reduced glutathione (GSH) levels and GSH-peroxidase activity induced by PTZ kindling, in a dose-related manner. Relatively large dose levels of OM3 (200-500 mg/kg) effectively attenuated seizures and their associated cognitive deficits, and reduced oxidative stress and hippocampal DNA damage in PTZ-kindled young rats. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. [Seizure activity in the EEG of rats sensitive and resistant to pentylenetetrazol kindling].

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    Pavlova, T V; Fesenko, G N; Gekht, A B; Gulieva, N V; Koval'zon, V M

    2009-01-01

    Rats were subjected to pentylenetetrazol kindling and divided into 2 groups according to their ability to demonstrate convulsions: the "sensitive" and "tresistant" rats groups. Both groups demonstrated EEG afterdischarges; however, the number of the EEG seizures in "sensitive" rats was 60% higher, the latency by 45 sec longer, and the total duration during the first 45 min after injection 70% longer as compared to the "resistant" rats. The average duration of a single EEG seizure did not differ in these groups. The average EEG frequency power peak at 7.2 Hz was more pronounced in the "resistant" group. Thus, pentylenetetrazol kindling induces epileptiform activity in the rat EEG irrespective of the appearance of behavioral seizures; however, characteristics of this activity differ significantly between the "sensitive" and "resistant" rats.

  18. EFFECT OF DIFFERENT AGONISTIC EXPERIENCES ON BEHAVIORAL SEIZURES IN FULLY AMYGDALA KINDLED RATS

    NARCIS (Netherlands)

    BELDHUIS, HJA; KOOLHAAS, JM; BOHUS, B

    1992-01-01

    Fully amygdala kindled rats were exposed to two different inter-male agonistic experiences in order to study the interaction between epilepsy and acute social stress. Victory experience did not influence the severity of seizure behaviour, whereas a single acute defeat modified both ictal and

  19. Spinacia oleracea retards the development of Amygdala kindled epilepsy in rats

    OpenAIRE

    Sutapa Das and Debjani Guha*

    2011-01-01

    The protective role of Spinacia oleracea (SO) has been evaluated against the development of Amygdala kindled (AMK) experimental epileptogenesis. Thirty six Holtzman strain adult male albino rats (200-250 g) were equally divided into 1) control, 2) SO, 3) AMK, 4) SO+AMK, 5) DZ+AMK group. After discharge duration (ADD) were used as indices of kindled seizures. In AMK group, seizure stages reached upto stage 4–5 within the second week. EEG tracings showed that pretreatment with SO in AMK group d...

  20. A mouse kindling model of perimenstrual catamenial epilepsy.

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    Reddy, Doodipala Samba; Gould, Jordan; Gangisetty, O

    2012-06-01

    Catamenial epilepsy is caused by fluctuations in progesterone-derived GABA(A) receptor-modulating anticonvulsant neurosteroids, such as allopregnanolone, that play a significant role in the pathophysiology of epilepsy. However, there is no specific mouse model of catamenial epilepsy. In this study, we developed and characterized a mouse model of catamenial epilepsy by using the neurosteroid-withdrawal paradigm. It is hypothesized that seizure susceptibility decreases when neurosteroid levels are high (midluteal phase) and increases during their withdrawal (perimenstrual periods) in close association with GABA(A) receptor plasticity. A chronic seizure condition was created by using the hippocampus kindling model in female mice. Elevated neurosteroid levels were induced by sequential gonadotropin treatment, and withdrawal was induced by the neurosteroid synthesis inhibitor finasteride. Elevated neurosteroid exposure reduced seizure expression in fully kindled mice. Fully kindled mice subjected to neurosteroid withdrawal showed increased generalized seizure frequency and intensity and enhanced seizure susceptibility. They also showed reduced benzodiazepine sensitivity and enhanced neurosteroid potency, similar to the clinical catamenial seizure phenotype. The increased susceptibility to seizures and alterations in antiseizure drug responses are associated with increased abundance of the α4 and δ subunits of GABA(A) receptors in the hippocampus. These findings demonstrate that endogenous neurosteroids protect against seizure susceptibility and their withdrawal, such as that which occurs during menstruation, leads to exacerbation of seizure activity. This is possibly caused by specific changes in GABA(A) receptor-subunit plasticity and function, therefore providing a novel mouse model of human perimenstrual catamenial epilepsy that can be used for the investigation of disease mechanisms and new therapeutic approaches.

  1. Gene expression in the neuropeptide Y system during ethanol withdrawal kindling in rats

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    Olling, Janne D; Ulrichsen, Jakob; Correll, Mette

    2010-01-01

    BACKGROUND: Multiple episodes of ethanol intoxication and withdrawal result in progressive, irreversible intensification of the withdrawal reaction, a process termed "ethanol withdrawal kindling." Previous studies show that a single episode of chronic ethanol intoxication and withdrawal causes...... of chronic ethanol intoxication by intragastric intubations followed by 5 days withdrawal. The study included 6 groups: 4 multiple withdrawal episode (MW) groups [peak withdrawal plus (MW+)/minus (MW-) seizures, 3-day (MW3d), and 1-month (MW1mth) withdrawal], a single withdrawal episode group (SW...... prominent changes in neuropeptide Y (NPY) and its receptors that have been implicated in regulating withdrawal hyperexcitability. This study for the first time examined the NPY system during ethanol withdrawal kindling. METHODS: Ethanol withdrawal kindling was studied in rats receiving 16 episodes of 2 days...

  2. The effect of Rosa damascena essential oil on the amygdala electrical kindling seizures in rat.

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    Ramezani, Roohollah; Moghimi, Ali; Rakhshandeh, Hassan; Ejtehadi, Hamid; Kheirabadi, Masoumeh

    2008-03-01

    We investigated the effect of Rosa damascena Mill, essential oil on the development of induced amygdala kindling seizures. Male Wistar rats were implanted with one tripolar and two monopolar electrodes in right basolateral amygdala and dura surface, respectively. The control group was injected solvent of essential oil and two experimental groups were injected 750 and 1000 mg kg(-1) of essential oil (ip), 30 min before a daily kindling stimulation. The number of stimulations required for the first appearance of seizure stages was significantly larger in two experimental groups than in control group. Mean after discharge duration was significantly different and essential oil reduced the increase of after discharge duration. Mean after discharge amplitude was also shorter in the groups treated with essential oil than in control group. Duration time for 5th stage of seizure at fully-kindled rats was significantly shorter in two experimental groups than control group. These results suggest that Rosa damascena essential oil significantly retarded the development of seizure stages and possesses the ability to counteract kindling acquisition. The flavonoids of Rosa damascena may act via GABAA receptors as previous studies have proposed for flavonoids of other medicinal plants. More detailed studies are recommended to define the effective component(s) of Rosa on different types of epilepsy.

  3. Investigating the Effects of Low Frequency rTMS on Kindled Seizure in Rats

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    Ali Yadollahpour

    2007-12-01

    Full Text Available Introduction: Neural stimulation is a promising new technology for the treatment of medically-intractable seizures.  Transcranial Magnetic Stimulation (TMS is a simple, non-invasive, low cost technique which is widely used in neurophysiology. In a few studies that have been performed at different frequencies the therapeutic effects of this technique were not obvious. Repetition of low frequencies TMS (≤1 Hz has inhibitory and quenching effects on neuron activities and it decreases the excitability of the cortex. In epilepsy, as a disease of the central nervous system, the excitability of the cortex increases. It seems that such a technique at its optimum frequencies has therapeutic potential in epilepsy. Materials and Methods: In this study, the effect of 0.1, 0.5, 1 and 2 Hz repetitive Transcranial Magnetic Stimulation (rTMS at an  intensity of  80% Resting Motor Threshold (RMT and at 1 Hz with an  intensity of  90 and 100% RMT  on Amygdala-kindling model in rats in optimum spatial coordinate was investigated. The procedure includes delivering a daily 5 minute rTMS stimulus using a butterfly figure coil having 25 mm in diameter and the coordinate which induces the maximum electrical field in Amygdala area.  The stimulus was given within five minutes after the electrical kindling stimulus was delivered.  The number of days to reach stage 1, 2, 3, 4 and 5 of kindling model After Discharge Duration (ADD in each day and the percentage of cumulative ADD between the treated and the control group was statistically compared.  Two groups were used to investigate the effect of the intensity of the magnetic field. A frequency of 1 Hz rTMS at an intensity of 90% and 100% RMT was delivered with the same physical parameters as before. Results: Using a frequency of 1 Hz rTMS at an intensity of 80% and RMT of 90% showed a significant inhibitory effect on the spread of seizure into other areas of brain in comparison to the control group. Increasing

  4. Hippocampal kindling alters the concentration of glial fibrillary acidic protein and other marker proteins in rat brain

    DEFF Research Database (Denmark)

    Hansen, A; Jørgensen, Ole Steen; Bolwig, T G

    1990-01-01

    The effect of hippocampal kindling on neuronal and glial marker proteins was studied in the rat by immunochemical methods. In hippocampus, pyriform cortex and amygdala there was an increase in glial fibrillary acidic protein (GFAP), indicating reactive gliosis, and an increase in the glycolytic...... enzyme NSE, suggesting increased anaerobic metabolism. Neuronal cell adhesion molecule (NCAM) decreased in pyriform cortex and amygdala of kindled rats, indicating neuronal degeneration....

  5. The behavioural depression of hippocampal kindled rats is attenuated by subcutaneous and intracerebroventricular naltrexone

    NARCIS (Netherlands)

    Cottrell, G.A.; Nyakas, C.; Bohus, B.

    1984-01-01

    1. Two questions were asked: Does naltrexone attenuate the behavioural depression (BD) in other models of limbic epilepsy besides amygdala kindling? Does intracerebroventricular (ICV) administration produce the same effects as subcutaneous injection i.e., attenuation of the BD. 2. Male wistar

  6. Kindling-Induced Changes in Plasticity of the Rat Amygdala and Hippocampus

    Science.gov (United States)

    Schubert, Manja; Siegmund, Herbert; Pape, Hans-Christian; Albrecht, Doris

    2005-01-01

    Temporal lobe epilepsy (TLE) is often accompanied by interictal behavioral abnormalities, such as fear and memory impairment. To identify possible underlying substrates, we analyzed long-term synaptic plasticity in two relevant brain regions, the lateral amygdala (LA) and the CA1 region of the hippocampus, in the kindling model of epilepsy. Wistar…

  7. Vigabatrin in Low doses Selectively Suppresses the Clonic Component of Audiogenically Kindled Seizures in Rats

    NARCIS (Netherlands)

    Vinogradova, L.V.; Kuznetsova, G.D.; Shatskova, A.B.; Rijn, C.M. van

    2005-01-01

    The effect of systemic administration of the gamma-aminobutyric acid (GABA)-transaminase inhibitor vigabatrin (VGB) on different components of convulsions was tested in the model of audiogenically kindled seizures, which consist of brainstem (running, tonus) and forebrain (clonus) elements. METHODS:

  8. Modulation of B1 and B2 kinin receptors expression levels in the hippocampus of rats after audiogenic kindling and with limbic recruitment, a model of temporal lobe epilepsy.

    Science.gov (United States)

    Pereira, Marilia G A G; Gitaí, Daniel L G; Paçó-Larson, Maria L; Pesquero, João B; Garcia-Cairasco, Norberto; Costa-Neto, Claudio M

    2008-02-01

    Epileptic seizures are hypersynchronous, paroxystic and abnormal neuronal discharges. Epilepsies are characterized by diverse mechanisms involving alteration of excitatory and inhibitory neurotransmission that result in hyperexcitability of the central nervous system (CNS). Enhanced neuronal excitability can also be achieved by inflammatory processes, including the participation of cytokines, prostaglandins or kinins, molecules known to be involved in either triggering or in the establishment of inflammation. Multiple inductions of audiogenic seizures in the Wistar audiogenic rat (WAR) strain are a model of temporal lobe epilepsy (TLE), due to the recruitment of limbic areas such as hippocampus and amygdala. In this study we investigated the modulation of the B1 and B2 kinin receptors expression levels in neonatal WARs as well as in adult WARs subjected to the TLE model. The expression levels of pro-inflammatory (IL-1 beta) and anti-inflammatory (IL-10) cytokines were also evaluated, as well as cyclooxygenase (COX-2). Our results showed that the B1 and B2 kinin receptors mRNAs were up-regulated about 7- and 4-fold, respectively, in the hippocampus of kindled WARs. On the other hand, the expressions of the IL-1 beta, IL-10 and COX-2 were not related to the observed increase of expression of kinin receptors. Based on those results we believe that the B1 and B2 kinin receptors have a pivotal role in this model of TLE, although their participation is not related to an inflammatory process. We believe that kinin receptors in the CNS may act in seizure mechanisms by participating in a specific kininergic neurochemical pathway.

  9. Kindling: A Model for the Development of Tardive Dyskinesia?

    Directory of Open Access Journals (Sweden)

    B. Glenthøj

    1988-01-01

    Full Text Available Tardive dyskinesia (TD from long-term neuroleptic treatment may be irreversible; therefore prevention has become a major concern. A controversial issue with regard to the clinical use of neuroleptic drugs is the possible influence on the development of TD of drug holidays. The major characteristics of kindling, theories of TD and the role of multiplicity in the development of TD are described. Some clinical studies point to interruption of neuroleptic therapy being a risk factor for development of irreversible TD. Induction of dyskinesia in non-human primates has been demonstrated after repeated administration of haloperidol. Rodent studies have not been conclusive. Several experimental results link TD with kindling: both conditions involve repeated stimulations, both seem to involve increased receptor responsiveness and in both conditions does depression in GABA transmission in SNR (substantia nigra; pars reticulata play an important role. It is concluded that the kindling hypothesis is relevant to the investigation of TD.

  10. Effects of Aqueous Matricaria Recutita extract on anxiety-like behavior in rat’s model kindled by Pentylenetetrazole

    Directory of Open Access Journals (Sweden)

    Gholamreza Komeili

    2016-04-01

    Full Text Available Background and Aim: Kindling can increase anxiety-like behavior in rodents. Oxidative stress has an important role in arousing anxiety. It is known that Matricaria Recutita has an antioxidant effect. Thus, the present study aimed at assessing the effects of this plant’s extract. on anxiety-like behavior induced by kindling in rats. Materials and Methods: In this experimental study, 40 male Wistar Albino rats (wt:200-250 g were randomly divided into 4 equal groups; namely control (intact, kindling, diazepam (2 mg/kg, and aqueous extract of Matricaria Recutita (30 mg/kg intrapertoneally. Kindling was done by a sub-convulsive dose of pentylenetetrazole (PTZ; 40 mg/kg, i.p. in the remainder . groups. Kindling parameters in all these animals were evaluated by a plus elevated maze. The percent of time spent in the open arms of maze (OAT % and percent of entries in the open arms (OAE % were accounted for anxiety evaluation. Increase in OAT % and OAE % indicated an anxiolytic effect. Finally,the obtained data was analyzed by means of Any-Maze software and P<0.05 was taken as the significant level. Results: Kindling significantly (P<0.05 increased anxiety response in rats for at least 24h following the last seizure (decrease in OAT % and OAE %. Administeration of diazepam and Matricaria Recutita induced a significant increase in OAT % and OAE %, thereby . displaying a decrease in the anxiety in the kindled rats (P<0.05. Activity rate of the animals increased in the extract-treated group. Conclusion: The results of the present study showed that Matricaria Recutita was able to improve elevated levels of anxiety in kindled rats. Therefore, further works are needed to elucidate the extent and mechanism of these effects.

  11. Z944, a Novel Selective T-Type Calcium Channel Antagonist Delays the Progression of Seizures in the Amygdala Kindling Model.

    Directory of Open Access Journals (Sweden)

    Pablo Miguel Casillas-Espinosa

    Full Text Available Temporal lobe epilepsy (TLE is the most common form of drug resistant epilepsy. Current treatment is symptomatic, suppressing seizures, but has no disease modifying effect on epileptogenesis. We examined the effects of Z944, a potent T-type calcium channel antagonist, as an anti-seizure agent and against the progression of kindling in the amygdala kindling model of TLE. The anti-seizure efficacy of Z944 (5mg/kg, 10mg/kg, 30mg/kg and 100mg/kg was assessed in fully kindled rats (5 class V seizures as compared to vehicle, ethosuximide (ETX, 100mg/kg and carbamazepine (30mg/kg. Each animal received the seven treatments in a randomised manner. Seizure class and duration elicited by six post-drug stimulations was determined. To investigate for effects in delaying the progression of kindling, naive animals received Z944 (30mg/kg, ETX (100mg/kg or vehicle 30-minutes prior to each kindling stimulation up to a maximum of 30 stimulations, with seizure class and duration recorded after each stimulation. At the completion of drug treatment, CaV3.1, CaV3.2 and CaV3.3 mRNA expression levels were assessed in the hippocampus and amygdala using qPCR. Z944 was not effective at suppressing seizures in fully kindled rats compared to vehicle. Animals receiving Z944 required significantly more stimulations to evoke a class III (p<0.05, IV (p<0.01 or V (p<0.0001 seizure, and to reach a fully kindled state (p<0.01, than animals receiving vehicle. There was no significant difference in the mRNA expression of the T-type Ca2+ channels in the hippocampus or amygdala. Our results show that selectively targeting T-type Ca2+ channels with Z944 inhibits the progression of amygdala kindling. This could be a potential for a new therapeutic intervention to mitigate the development and progression of epilepsy.

  12. Finasteride Inhibits the Disease-Modifying Activity of Progesterone in the Hippocampus Kindling Model of Epileptogenesis

    Science.gov (United States)

    Reddy, Doodipala Samba; Ramanathan, G.

    2012-01-01

    Progesterone (P) plays an important role in seizure susceptibility in women with epilepsy. Preclinical and experimental studies suggest that P appears to interrupt epileptogenesis, which is a process whereby a normal brain becomes progressively epileptic due to precipitating risk factors. P has not been investigated widely for its potential disease-modifying activity in epileptogenic models. Recently, P has been shown to exert disease-modifying effects in the kindling model of epileptogenesis. However, the mechanisms underlying the protective effects of P against epileptogenesis remain unclear. In this study, we investigated the role of P-derived neurosteroids in the disease-modifying activity of P. It is hypothesized that 5α-reductase converts P to allopregnanolone and related neurosteroids that retard epileptogenesis in the brain. To test this hypothesis, we utilized the mouse hippocampus kindling model of epileptogenesis and investigated the effect of finasteride, a 5α-reductase and neurosteroid synthesis inhibitor. P markedly retarded the development of epileptogenesis and inhibited the rate of kindling acquisition to elicit stage 5 seizures. Pretreatment with finasteride led to complete inhibition of the P-induced retardation of limbic epileptogenesis in mice. Finasteride did not significantly influence the acute seizure expression in fully-kindled mice expressing stage 5 seizures. Thus, neurosteroids that potentiate phasic and tonic inhibition in the hippocampus, such as allopregnanolone, may mediate the disease-modifying effect of P, indicating a new role of neurosteroids in acquired limbic epileptogenesis and temporal lobe epilepsy. PMID:22835430

  13. Corticosterone oscillations during mania induction in the lateral hypothalamic kindled rat—Experimental observations and mathematical modeling

    Science.gov (United States)

    Ho, Man Choi; Choi, Doo-Sup; Stanojević, Ana; Čupić, Željko; Kolar-Anić, Ljiljana

    2017-01-01

    Changes in the hypothalamic-pituitary-adrenal (HPA) axis activity constitute a key component of bipolar mania, but the extent and nature of these alterations are not fully understood. We use here the lateral hypothalamic-kindled (LHK) rat model to deliberately induce an acute manic-like episode and measure serum corticosterone concentrations to assess changes in HPA axis activity. A mathematical model is developed to succinctly describe the entwined biochemical transformations that underlay the HPA axis and emulate by numerical simulations the considerable increase in serum corticosterone concentration induced by LHK. Synergistic combination of the LHK rat model and dynamical systems theory allows us to quantitatively characterize changes in HPA axis activity under controlled induction of acute manic-like states and provides a framework to study in silico how the dynamic integration of neurochemical transformations underlying the HPA axis is disrupted in these states. PMID:28542167

  14. Radiation of the Rat Brain Suppresses Seizure-Induced Neurogenesis and Transiently Enhances Excitability during Kindling Acquisition.

    NARCIS (Netherlands)

    Raedt, R.; Boon, P.; Perssson, A.; Alborn, A.M.; Boterberg, T.; Van Dycke, A.; Linder, B.; De Smedt, T.; Wadman, W.J.; Ben-Menachem, E.; Eriksson, P.S.

    2007-01-01

    Purpose: Adult hippocampal neurogenesis is enhanced in several models for temporal lobe epilepsy (TLE). In this study, we used low-dose whole brain radiation to suppress hippocampal neurogenesis and then studied the effect of this treatment on epileptogenesis in a kindling model for TLE. Methods:

  15. Electrically evoked GABA release in rat hippocampus CA1 region and its changes during kindling epileptogenesis.

    NARCIS (Netherlands)

    Ghijsen, W.E.J.M.; Zuiderwijk, M.; Lopes da Silva, F.H.

    2007-01-01

    Previous findings on changes in K(+)-induced GABA release from hippocampal slices during kindling epileptogenesis were reinvestigated using physiological electrical stimulation. For that purpose, a procedure was developed enabling neurochemical monitoring of GABA release locally in the CA1 region of

  16. Ferulic acid exhibits antiepileptogenic effect and prevents oxidative stress and cognitive impairment in the kindling model of epilepsy.

    Science.gov (United States)

    Hassanzadeh, Parichehr; Arbabi, Elham; Atyabi, Fatemeh; Dinarvand, Rassoul

    2017-06-15

    Some conventional antiepileptic drugs induce oxidative stress and cognitive impairment which may limit their clinical applications. Ferulic acid is a phenolic phytochemical with antioxidant and neuroprotective properties that prompted us to evaluate its therapeutic potential in epilepsy which is usually associated with oxidative stress and cognitive decline. Male Wistar rats received 30mg/kg of pentylenetetrazole (PTZ) intraperitoneally (i.p.) once every alternate day until the development of kindling. The locomotor activity, elevated plus maze, and passive avoidance tests were performed. Oxidative stress was evaluated by the determination of brain malondialdehyde and reduced glutathione. The effects of pre-treatment with ferulic acid (25, 50, 75, and 100mg/kg, i.p.) against PTZ-kindled seizures, cognitive impairment, and oxidative stress were investigated. Kindling was developed 34.18±1.54days after PTZ treatment which was associated with generalized tonic-clonic seizures (GTCS), myoclonic jerks, cognitive deficit, and oxidative stress. Ferulic acid at doses of 75 and 100mg/kg significantly reduced the seizure score, number of myoclonic jerks, cognitive decline and oxidative stress. Spontaneous locomotor activity did not significantly differ between the groups. Ferulic acid exhibits antiepileptogenic effect and prevents oxidative stress and cognitive impairment induced by PTZ kindling. Therefore, this phenolic phytochemical appears as a promising adjuvant for antiepileptic drugs. Meanwhile, further experimental and clinical studies are required to provide insights into the cellular/molecular mechanism(s) underlying the action of ferulic acid. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. A Mouse Kindling Model of Perimenstrual Catamenial Epilepsy

    OpenAIRE

    Reddy, Doodipala Samba; Gould, Jordan; Gangisetty, O.

    2012-01-01

    Catamenial epilepsy is caused by fluctuations in progesterone-derived GABAA receptor-modulating anticonvulsant neurosteroids, such as allopregnanolone, that play a significant role in the pathophysiology of epilepsy. However, there is no specific mouse model of catamenial epilepsy. In this study, we developed and characterized a mouse model of catamenial epilepsy by using the neurosteroid-withdrawal paradigm. It is hypothesized that seizure susceptibility decreases when neurosteroid levels ar...

  18. Modeling structure and spectra of the kindling fluorescent protein asFP595

    Science.gov (United States)

    Collins, Jack R.; Topol, Igor A.; Savitsky, Alexander P.; Nemukhin, Alexander V.

    2011-03-01

    Modern computational approaches based on quantum mechanical methods to characterize structures and optical spectra of biological chromophores in proteins are intensively used to gain knowledge of events occurring upon of their photoexcitation. Primary attention is paid to the species from the family of the green fluorescent protein applied as biomarkers in living cells. We apply quantum chemical approaches for accurate calculations of the structures of the chromophore binding pockets and to estimate spectral bands corresponding to the S0-S1 optical transitions of the intriguing kindling protein asFP595. Its precursor, the chromoprotein asCP from the sea anemony Anemonia sulcata is characterized by distinctive spectral properties: at low light intensities the wild-type protein is weakly fluorescent with the very low quantum yield, however, high intensity irradiation with green light leads to a drastic increase of quantum yield. This phenomenon is now termed "kindling". In simulations, the model system is designed as a molecular cluster constructed on the basis of available crystal structures of the related protein. The equilibrium geometry of the cluster is optimized using density functional theory approximations. The vertical excitation energies corresponding to the S0-S1 transitions are computed by using the semiempirical ZINDO technique. A special attention is paid to evaluate effects of point mutations in the vicinity of the chromophore group. Theoretical data provide important information on the chromophore properties aiming to interpret the results of experimental studies and applications of this fluorescent protein.

  19. The effect of PTZ-induced epileptic seizures on hippocampal expression of PSA-NCAM in offspring born to kindled rats

    Directory of Open Access Journals (Sweden)

    Rajabzadeh Aliakbar

    2012-05-01

    Full Text Available Abstract Background Maternal epileptic seizures during pregnancy can affect the hippocampal neurons in the offspring. The polysialylated neural cell adhesion molecule (PSA-NCAM, which is expressed in the developing central nervous system, may play important roles in neuronal migration, synaptogenesis, and axonal outgrowth. This study was designed to assess the effects of kindling either with or without maternal seizures on hippocampal PSA-NCAM expression in rat offspring. Methods Forty timed-pregnant Wistar rats were divided into four groups: A Kind+/Seiz+, pregnant kindled (induced two weeks prior to pregnancy rats that received repeated intraperitoneal (i.p. pentylenetetrazol, PTZ injections on gestational days (GD 14-19; B Kind-/Seiz+, pregnant non-kindled rats that received PTZ injections on GD14-GD19; C Kind+/Seiz-, pregnant kindled rats that did not receive any PTZ injections; and D Kind-/Seiz-, the sham controls. Following birth, the pups were sacrificed on PD1 and PD14, and PSA-NCAM expression and localization in neonates’ hippocampi were analyzed by Western blots and immunohistochemistry. Results Our data show a significant down regulation of hippocampal PSA-NCAM expression in the offspring of Kind+/Seiz+ (p = 0.001 and Kind-/Seiz+ (p = 0.001 groups compared to the sham control group. The PSA-NCAM immunoreactivity was markedly decreased in all parts of the hippocampus, especially in the CA3 region, in Kind+/Seiz+ (p = 0.007 and Kind-/Seiz+ (p = 0.007 group’s newborns on both PD1 and 14. Conclusion Our findings demonstrate that maternal seizures but not kindling influence the expression of PSA-NCAM in the offspring’s hippocampi, which may be considered as a factor for learning/memory and cognitive impairments reported in children born to epileptic mothers.

  20. Amygdala-kindling induces a lasting reduction of GABA-immunoreactive neurons in a discrete area of the ipsilateral piriform cortex.

    Science.gov (United States)

    Lehmann, H; Ebert, U; Löscher, W

    1998-08-01

    Several lines of evidence indicate a critical role of the piriform cortex (PC) in the kindling model of temporal lobe epilepsy, suggesting that the PC is part of an epileptic network that is pivotal in the genesis of kindling, facilitating, and intensifying the spread of seizures from a focus in amygdala, hippocampus, or other limbic brain regions to cortical and subcortical regions. Kindling of the amygdala has been shown to induce long-lasting changes in synaptic efficacy in the ipsilateral PC comparable to abnormalities seen in epileptic foci, but the neurochemical alterations possibly underlying these functional changes are not known. The possibility that the enhanced excitability of the PC in response to kindling is related to a reduction of GABAergic neurotransmission prompted us to examine if a lasting reduction in GABA-immunoreactive PC neurons is detectable after kindling of the basolateral amygdala (BLA) in rats. Furthermore, GABA immunoreactivity was determined in the BLA in order to investigate whether GABAergic neurons decrease in focal tissue, as previously suggested by neurochemical and immunocytochemical studies in amygdala-kindled rats. Three groups of age-matched rats were used: (1) a group of rats that was kindled via electrical stimulation by a bipolar electrode implanted in the right BLA, (2) a group of BLA-implanted but nonstimulated rats, and (3) a group of non-implanted, naive control rats. The kindled rats were sacrificed 40 days after the last fully kindled seizure. The two other groups of rats were sacrificed together with the kindled rats on the same days, and tissues from kindled and control rats were treated concurrently throughout the immunohistochemical analysis. GABA neurons were stained by a monoclonal antibody to GABA. Kindling of the BLA led to a pronounced decrease in the number of GABA immunoreactive neurons in the ipsi- and contralateral BLA at all section levels examined. In the PC, no significant differences between groups

  1. Kindle Paperwhite for dummies

    CERN Document Server

    Nicoll, Leslie H

    2014-01-01

    Get the inside story on the all-new Kindle Paperwhite with help from For Dummies It reads like a book, but it's so much more. The Kindle Paperwhite is the ultimate e-reader, and this updated edition of Kindle Paperwhite For Dummies is your ultimate guide to getting more from this one-of-a-kind device. You'll learn to set up your Paperwhite, adjust the font to your liking, find your favorite books, magazines, and newspapers, and sync your Kindle content across devices before moving on to new Paperwhite features like Kindle FreeTime, Goodreads integration, Vocabulary Builder, In-line Footnotes

  2. An olfactory-limbic model of multiple chemical sensitivity syndrome: Possible relationships to kindling and affective spectrum disorders

    Energy Technology Data Exchange (ETDEWEB)

    Bell, I.R.; Miller, C.S.; Schwartz, G.E. (Univ. of Arizona Health Sciences Center, Tucson (United States))

    1992-08-01

    This paper reviews the clinical and experimental literature on patients with multiple adverse responses to chemicals (Multiple Chemical Sensitivity Syndrome-MCS) and develops a model for MCS based on olfactory-limbic system dysfunction that overlaps in part with Post's kindling model for affective disorders. MCS encompasses a broad range of chronic polysymptomatic conditions and complaints whose triggers are reported to include low levels of common indoor and outdoor environmental chemicals, such as pesticides and solvents. Other investigators have found evidence of increased prevalence of depression, anxiety, and somatization disorders in MCS patients and have concluded that their psychiatric conditions account for the clinical picture. However, none of these studies has presented any data on the effects of chemicals on symptoms or on objective measures of nervous system function. Synthesis of the MCS literature with large bodies of research in neurotoxicology, occupational medicine, and biological psychiatry, suggests that the phenomenology of MCS patients overlaps that of affective spectrum disorders and that both involve dysfunction of the limbic pathways. Animal studies demonstrate that intermittent repeated low level environmental chemical exposures, including pesticides, cause limbic kindling. Kindling (full or partial) is one central nervous system mechanism that could amplify reactivity to low levels of inhaled and ingested chemicals and initiate persistent affective, cognitive, and somatic symptomatology in both occupational and nonoccupational settings. As in animal studies, inescapable and novel stressors could cross-sensitize with chemical exposures in some individuals to generate adverse responses on a neurochemical basis. The olfactory-limbic model raises testable neurobiological hypotheses that could increase understanding of the multifactorial etiology of MCS and of certain overlapping affective spectrum disorders. 170 refs.

  3. Piperine-loaded chitosan-STPP nanoparticles reduce neuronal loss and astrocytes activation in chemical kindling model of epilepsy.

    Science.gov (United States)

    Anissian, Diana; Ghasemi-Kasman, Maryam; Khalili-Fomeshi, Mohsen; Akbari, Atefeh; Hashemian, Mona; Kazemi, Sohrab; Moghadamnia, Ali Akbar

    2017-09-20

    Recent evidence suggests that encapsulation of hydrophobic drugs in biodegradable polymers opens a new horizon in nanomedicine filed. Piperine, a main alkaloid form of black pepper possesses potent anticonvulsant activity. However, the low water solubility of piperine has limited its clinical application. In this study, piperine was loaded on chitosan-sodium tripolyphosphate nanoparticles (CS-STPP NPs) and the effect of piperine NPs on seizures behavior and astrocytes activation was assessed in pentylentetrazol (PTZ)-induced kindling model. Animals have received the daily injection of free piperine or piperine NPs at doses of 5 or 10mg/kg, 10days before PTZ injections and their intraperitoneally (i.p) administration continued until the last PTZ injection. The neuroprotective effects of piperine NPs were evaluated using nissl staining and immunostaining against NeuN. Astrocytes activation was examined by GFAP immunostaining. Behavioral data showed that piperine NPs have inhibited the development of seizure parameters compared to the free piperine groups. In addition, the levels of cell loss and astrocytes activation were reduced in piperine NPs groups. In conclusion, these data suggest that piperine NPs enhance the neuroprotection and ameliorate the astrocytes activation in chemical kindling model of epilepsy. This may provide an effective therapeutic strategy for the treatment of epilepsy disorder. Copyright © 2017. Published by Elsevier B.V.

  4. Galanin gene transfer curtails generalized seizures in kindled rats without altering hippocampal synaptic plasticity

    DEFF Research Database (Denmark)

    Kanter-Schlifke, I; Toft Sørensen, Andreas; Ledri, M

    2007-01-01

    Gene therapy-based overexpression of endogenous seizure-suppressing molecules represents a promising treatment strategy for epilepsy. Viral vector-based overexpression of the neuropeptide galanin has been shown to effectively suppress generalized seizures in various animal models of epilepsy. How...

  5. Thyrotropin-releasing hormone d,l polylactide nanoparticles (TRH-NPs) protect against glutamate toxicity in vitro and kindling development in vivo.

    Science.gov (United States)

    Veronesi, Michael C; Aldouby, Yanir; Domb, Abraham J; Kubek, Michael J

    2009-12-15

    Thyrotropin-releasing hormone (TRH) is reported to have anticonvulsant effects in animal seizure models and certain intractable epileptic patients. However, its duration of action is limited by rapid tissue metabolism and the blood brain barrier. Direct nose-brain delivery of neuropeptides in sustained-release biodegradable nanoparticles (NPs) is a promising mode of therapy for enhancing CNS bioavailability. Bioactivity/neuroprotection of d,l polylactide nanoparticles containing TRH was assessed against glutamate toxicity in cultured rat fetal hippocampal neurons. Subsequently, we utilized the kindling model of temporal lobe epilepsy to determine if intranasal administration of nanoparticles containing TRH (TRH-NPs) could inhibit kindling development. Animals received daily treatments of either blank (control) or TRH-NPs for 7 days before initiation of kindling. On day 8 and each day thereafter until either fully kindled or until day 20, the animals received daily treatments before receiving a kindling stimulus 3 h later. Afterdischarge duration (ADD) was assessed via electroencephalographs recorded from electrodes in the basolateral amygdalae and behavioral seizure stereotypy was simultaneously recorded digitally. Intranasal application of TRH-NPs resulted in a significant reduction in seizure ADD as kindling progressed, while the number of stimulations required to reach stage V seizures and to become permanently kindled was significantly greater in TRH-NP-treated subjects. Additionally, delay to clonus was significantly prolonged while clonus duration was reduced indicating a less severe seizure in TRH-NP-treated subjects. Our results provide proof of principle that intranasal delivery of sustained-release TRH-NPs may be neuroprotective and can be utilized to suppress seizures and perhaps epileptogenesis.

  6. Kindle Fire HDX for dummies

    CERN Document Server

    Muir, Nancy C

    2013-01-01

    Spark your interest in Kindle Fire HDX and start burning through books, movies, music, and more with this bestselling guide! The Kindle Fire HDX is Amazon's premiere tablet. With its new, more powerful Android operating system, this latest version has some exciting bells and whistles along with the features that have made the Fire a tablet fan favorite: access to the amazing Amazon Appstore, online music storage, a large music and video store, a huge e-book library, and easy one-step ordering from Amazon. This full-color, For Dummies guide shows you how to take advantage of all the Kindle Fi

  7. The origin of radiationless conversion of the excited state in the kindling fluorescent protein (KFP): femtosecond studies and quantum modeling

    Science.gov (United States)

    Shelaev, I.; Mironov, V.; Rusanov, A.; Gostev, F.; Bochenkova, A.; Sarkisov, O.; Nemukhin, A.; Savitsky, A.

    2011-06-01

    The Ala143Gly variant of the chromoprotein asCP from the sea anemony Anemonia sulcata, called the kindling fluorescent protein (KFP), is a promising candidate for the development of novel subdiffraction method of fluorescent microscopy. The pump-probe method with the delay times between the pump and probe pulses up to 5 ps was applied to study dynamics of the primary processes upon excitation of KFP. The differential absorption spectra at 80 fs delay showed the absorption peak in the range 450-510 nm with the maximum wavelength at 490 nm, which diminished almost twice by intensity by 400 fs and practically disappeared by 1.5 ps. The quantum calculations showed that upon photo-excitation of KFP to the first excited state S1, the fast radiationless relaxation occurred to the ground state S0 due to rotation of the phenolic fragment of the chromophore.

  8. Developmental exposure to an environmental PCB mixture delays the propagation of electrical kindling from the amygdala.

    Science.gov (United States)

    Bandara, Suren B; Sadowski, Renee N; Schantz, Susan L; Gilbert, Mary E

    2017-01-01

    Developmental PCB exposure impairs hearing and induces brainstem audiogenic seizures in adult offspring. The degree to which this enhanced susceptibility to seizure is manifest in other brain regions has not been examined. Thus, electrical kindling of the amygdala was used to evaluate the effect of developmental exposure to an environmentally relevant PCB mixture on seizure susceptibility in the rat. Female Long-Evans rats were dosed orally with 0 or 6mg/kg/day of the PCB mixture dissolved in corn oil vehicle 4 weeks prior to mating and continued through gestation and up until postnatal day (PND) 21. On PND 21, pups were weaned, and two males from each litter were randomly selected for the kindling study. As adults, the male rats were implanted bilaterally with electrodes in the basolateral amygdala. For each animal, afterdischarge (AD) thresholds in the amygdala were determined on the first day of testing followed by once daily stimulation at a standard 200μA stimulus intensity until three stage 5 generalized seizures (GS) ensued. Developmental PCB exposure did not affect the AD threshold or total cumulative AD duration, but PCB exposure did increase the latency to behavioral manifestations of seizure propagation. PCB exposed animals required significantly more stimulations to reach stage 2 seizures compared to control animals, indicating attenuated focal (amygdala) excitability. A delay in kindling progression in the amygdala stands in contrast to our previous finding of increased susceptibility to brainstem-mediated audiogenic seizures in PCB-exposed animals in response to a an intense auditory stimulus. These seemingly divergent results are not unexpected given the distinct source, type, and mechanistic underpinnings of these different seizure models. A delay in epileptogenesis following focal amygdala stimulation may reflect a decrease in neuroplasticity following developmental PCB exposure consistent with reductions in use-dependent synaptic plasticity that

  9. Comparison of the Effects of Adenosine A1 Receptors Activity in CA1 Region of the Hippocampus on Entorhinal Cortex and Amygdala Kindled Seizures in Rats

    Directory of Open Access Journals (Sweden)

    A. Heidarianpour

    2008-10-01

    Full Text Available Introduction & Objective: In the CNS, adenosine is known to suppress repetitive neuronal Firing, suggesting a role as an endogenous modifier of seizures. Indeed, intracerebral adenosine concentrations rise acutely during seizure activity and are thought to be responsible for terminating seizures and establishing a period of post-ictal refractoriness. However, it is unclear whether this suppression results from a general depression of brain excitability or through action on particular sites critical for the control of after discharge generation and/or seizure development and propagation. In this regard, comparison of the effects of adenosine A1 receptors of CA1 (region of the ‎hippocampus on entorhinal cortex and amygdala kindled seizures was ‎investigated in this study. Materials & Methods: In this experimental study, Animals were kindled by daily electrical stimulation of amygdale (group A or entorhinal cortex (group B. In the fully kindled animals, N6-‎cyclohexyladenosine (CHA;1 and 10 M; a selective adenosine A1 receptor ‎agonist and 1,3-dimethyl-8-cyclohexylxanthine(CPT;1 ‎µ‎M; a selective ‎adenosine A1 receptors antagonist were microinfused bilaterally into the CA1 ‎region of hippocampus (1l/2min and animals were stimulated at 5 and 15 minutes after drug ‎injection. All animals were received artificial cerebrospinal fluid, 24 h before ‎each drug injection and this result were used as control. Results: The seizure parameters were measured at 5 and 15min post injection. Obtained data showed that CHA at concentrations of 10 ‎µ‎M reduced ‎entorhinal cortex and amygdala after discharge and stage5 seizure durations and ‎increased stage4 latency. CHA at concentration 1‎µ‎M significantly alters ‎seizure parameters of group A but not effect on group B. Intrahippocampal (CA1 region pretreatment of CPT (1 ‎µ‎M before CHA abolished the effects of CHA on seizure parameters.Conclusion: It ‎may be

  10. Does brain slices from pentylenetetrazole-kindled mice provide a more predictive screening model for antiepileptic drugs?

    DEFF Research Database (Denmark)

    Hansen, Suzanne L.; Sterjev, Zoran; Werngreen, Marie

    2012-01-01

    The cortical wedge is a commonly applied model for in vitro screening of new antiepileptic drugs (AEDs) and has been extensively used in characterization of well-known AEDs. However, the predictive validity of this model as a screening model has been questioned as, e.g., carbamazepine has been re...

  11. Cerebral small vessel disease predisposes to temporal lobe epilepsy in spontaneously hypertensive rats.

    Science.gov (United States)

    Russo, Emilio; Leo, Antonio; Scicchitano, Francesca; Donato, Annalidia; Ferlazzo, Edoardo; Gasparini, Sara; Cianci, Vittoria; Mignogna, Chiara; Donato, Giuseppe; Citraro, Rita; Aguglia, Umberto; De Sarro, Giovambattista

    2017-04-01

    The link between cerebral small vessel disease (CSVD) and epilepsy has been poorly investigated. Some reports suggest that CSVD may predispose to temporal lobe epilepsy (TLE). Aim of this study was to evaluate whether spontaneously hypertensive rats (SHRs), an established model of systemic hypertension and CSVD, have a propensity to develop TLE more than generalized seizures. To this aim, amygdala kindling, as a model of TLE, and pentylenetetrazole (PTZ)-induced kindling, as a model of generalized seizures, have been used to ascertain whether SHRs are more prone to TLE as compared to Wistar Kyoto control rats. While young SHRs (without CSVD) do not differ from their age-matched controls in both models, old SHRs (with CSVD) develop stage 5 seizures in the amygdala kindling model (TLE) faster than age-matched control rats without CSVD. At odds, no differences between old SHRs and age-matched controls was observed in the development of PTZ kindling. Enalapril pre-treatment prevented the development of CSVD and normalized kindling development to control levels in SHRs. No difference was observed in the response to pharmacological treatment with carbamazepine or losartan. Overall, our study suggests that uncontrolled hypertension leading to CSVD might represent a risk factor for TLE. Further experimental studies are needed to unravel other risk factors that, along with CSVD, may predispose to TLE. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Improvement in hippocampal kindling analysis through computational processing data Aprimorando a análise do modelo de kindling hipocampal com o auxílio de processamento computacional

    Directory of Open Access Journals (Sweden)

    Joacir Graciolli Cordeiro

    2009-09-01

    Full Text Available The kindling phenomenon is classically investigated in epileptology research. The present study aims to provide further information about hippocampal kindling through computational processing data. Adult Wistar rats were implanted with dorsal hippocampal and frontal neocortical electrodes to perform the experiment. The processing data was obtained using the Spike2 and Matlab softwares. An inverse relationship between the number of "wet dog shakes" and the Racine's motor stages development was found. Moreover it was observed a significant increase in the afterdischarge (AD duration and its frequency content. The highest frequencies were, however, only reached at the beginning of behavioral seizures. During the primary AD, fast transients (ripples were registered in both hippocampi superimposed to slower waves. This experiment highlights the usefulness of computational processing applied to animal models of temporal lobe epilepsy and supports a relevant role of the high frequency discharges in temporal epileptogenesis.O fenômeno de kindling é classicamente utilizado no campo da epileptologia experimental. Este trabalho objetiva aprofundar a análise do modelo kindling hipocampal através de processamento computacional. Ratos wistar adultos receberam eletrodos hipocampais dorsais e neocorticais frontais para a realização do experimento. O processamento dos dados encontrados foi realizado pelos softwares Matlab e Spike2. Encontrou-se uma relação inversa entre wet dog shakes e o desenvolvimento dos estágios motores de Racine. A duração e o conteúdo de freqüência das pós-descargas hipocampais aumentaram durante o processo, sendo observadas descargas de alta freqüência (ripples em ambos os hipocampos durante as pós-descargas primárias, superimpostas a ondas lentas. As mais altas freqüências, entretanto, foram apenas atingidas com o início das crises epilépticas. A utilização de sistemas computacionais para a confecção e an

  13. Susceptibility to hippocampal kindling seizures is increased in aging C57 black mice

    Directory of Open Access Journals (Sweden)

    Kurt R. Stover

    2017-12-01

    Full Text Available The incidence of seizures increases with old age. Stroke, dementia and brain tumors are recognized risk factors for new-onset seizures in the aging populations and the incidence of these conditions also increased with age. Whether aging is associated with higher seizure susceptibility in the absence of the above pathologies remains unclear. We used classic kindling to explore this issue as the kindling model is highly reproducible and allows close monitoring of electrographic and motor seizure activities in individual animals. We kindled male young and aging mice (C57BL/6 strain, 2–3 and 18–22 months of age via daily hippocampal CA3 stimulation and monitored seizure activity via video and electroencephalographic recordings. The aging mice needed fewer stimuli to evoke stage-5 motor seizures and exhibited longer hippocampal afterdischarges and more frequent hippocampal spikes relative to the young mice, but afterdischarge thresholds and cumulative afterdischarge durations to stage 5 motor seizures were not different between the two age groups. While hippocampal injury and structural alterations at cellular and micro-circuitry levels remain to be examined in the kindled mice, our present observations suggest that susceptibility to hippocampal CA3 kindling seizures is increased with aging in male C57 black mice.

  14. Montelukast reduces seizures in pentylenetetrazol-kindled mice

    Science.gov (United States)

    Fleck, J.; Temp, F.R.; Marafiga, J.R.; Jesse, A.C.; Milanesi, L.H.; Rambo, L.M.; Mello, C.F.

    2016-01-01

    Cysteinyl leukotrienes (CysLTs) have been implicated in seizures and kindling; however, the effect of CysLT receptor antagonists on seizure frequency in kindled animals and changes in CysLT receptor expression after pentylenetetrazol (PTZ)-induced kindling have not been investigated. In this study, we evaluated whether the CysLT1 inverse agonist montelukast, and a classical anticonvulsant, phenobarbital, were able to reduce seizures in PTZ-kindled mice and alter CysLT receptor expression. Montelukast (10 mg/kg, sc) and phenobarbital (20 mg/kg, sc) increased the latency to generalized seizures in kindled mice. Montelukast increased CysLT1 immunoreactivity only in non-kindled, PTZ-challenged mice. Interestingly, PTZ challenge decreased CysLT2 immunoreactivity only in kindled mice. CysLT1 antagonists appear to emerge as a promising adjunctive treatment for refractory seizures. Nevertheless, additional studies are necessary to evaluate the clinical implications of this research. PMID:26909785

  15. How Kindle Could Change the Textbook Market

    Science.gov (United States)

    Young, Jeffrey R.

    2009-01-01

    Amazon is subsidizing pilot projects at six institutions--Arizona State, Case Western Reserve, Pace, and Princeton Universities, Reed College, and the University of Virginia's business school. It's picking up half the tab for the experiment on each campus, in which some sections of a few courses will be given the new Kindle DX, as the device is…

  16. Conceptual framework for the etiology of alcoholism: a "kindling"/stress hypothesis.

    Science.gov (United States)

    Breese, George R; Overstreet, David H; Knapp, Darin J

    2005-04-01

    The rationale for proposing the "kindling"/stress hypothesis is to provide a conceptual basis for the insidious development and maintenance of alcohol abuse. An objective of the hypothesis is to emphasize how continued alcohol abuse is linked to progressive neural adaptation. Work has shown that repeated withdrawals from chronic low levels of alcohol sensitize ("kindle") anxiety-like behavior ("anxiety") in rats, a finding consistent with multiple withdrawal kindling of seizure activity. Additionally, stress substitutes for initial cycles of the multiple withdrawal protocol to sensitize withdrawal-induced anxiety, which is indicative that stress is capable of facilitating neuroadaptive processes related to withdrawal. The persistence of adaptation caused by stress and multiple withdrawals is revealed by the appearance of withdrawal-induced anxiety following a future re-exposure to a single 5-day period of alcohol. This persisting adaptation also permits stress to induce anxiety during a period of abstinence--a response not observed in animals without previous exposure to alcohol. Furthermore, stress interacts with repeated withdrawals to enhance voluntary alcohol drinking. Results of other preclinical and clinical studies reported in the literature are integrated with these investigations in support of the proposed hypothesis. The "kindling"/stress hypothesis is based on the premise that repeated withdrawals from cycles of chronic alcohol exposure contribute to a progressive development of persisting adaptive change that sensitizes withdrawal-induced anxiety and allows stress to evoke symptoms associated with negative affect during abstinence. Thus, these consequences of repeated withdrawals account for the evolution of major characteristics of alcoholism, which include worsened acute withdrawal symptoms and increased stress-induced negative affect during abstinence, both of which enhance the likelihood of relapse--and with relapse an inability to limit an abusive

  17. Epileptic Pattern Recognition and Discovery of the Local Field Potential in Amygdala Kindling Process.

    Science.gov (United States)

    Wang, Yu-Lin; Chen, Yin-Lin; Su, Alvin Wen-Yu; Shaw, Fu-Zen; Liang, Sheng-Fu

    2016-03-01

    Epileptogenesis, which occurs in an epileptic brain, is an important focus for epilepsy. The spectral analysis has been popularly applied to study the electrophysiological activities. However, the resolution is dominated by the window function of the algorithm used and the sample size. In this report, a temporal waveform analysis method is proposed to investigate the relationship of electrophysiological discharges and motor outcomes with a kindling process. Wistar rats were subjected to electrical amygdala kindling to induce temporal lobe epilepsy. During the kindling process, different morphologies of afterdischarges (ADs) were found and a recognition method, using template matching techniques combined with morphological comparators, was developed to automatically detect the epileptic patterns. The recognition results were compared to manually labeled results, and 79%-91% sensitivity was found. In addition, the initial ADs (the first 10 s) of different seizure stages were specifically utilized for recognition, and an average of 85% sensitivity was achieved. Our study provides an alternative viewpoint away from frequency analysis and time-frequency analysis to investigate epileptogenesis in an epileptic brain. The recognition method can be utilized as a preliminary inspection tool to identify remarkable changes in a patient's electrophysiological activities for clinical use. Moreover, we demonstrate the feasibility of predicting behavioral seizure stages from the early epileptiform discharges.

  18. Up- and down-regulation of beta-adrenoreceptors in rat cerebral cortex following exposure to isomers of hexachlorocyclohexane

    Energy Technology Data Exchange (ETDEWEB)

    Stark, L.; Hollinger, M.; Joy, R.

    1986-03-01

    The authors have shown that the gamma (lindane) and beta isomers of hexachlorocyclohexane (HCH) have opposite effects on the kindling model of epilepsy (gamma facilitates, beta retards kindling acquisition). In the present study the authors determined the effects of these two isomers on ..beta..-adrenoreceptors in rat brain using /sup 3/H-dihydroalprenolol as the ligand following 10 days treatment with 10 mg/kg p.o. of isomers or corn oil. Results showed a statistically significant decrease in the number of ..beta..-adrenoreceptors in cortical tissue taken from lindane treated rats. In contrast, there was a significant increase in the number of ..beta..-adreno receptors in cortical tissue taken from beta-HCH treated rats. Neither treatment caused a significant change in Kd. It is concluded that the ..beta..-adrenoreceptor system in rat brain is differentially affected by the isomers of HCH. Since the kindling model of epilepsy is sensitive to modulation in adrenergic function, this system may be involved in the pro- and anticonvulsant effects of these HCH isomers on kindling acquisition.

  19. IPhone or Kindle: Competition of Electronic Books Sales

    Science.gov (United States)

    Chen, Li

    With the technical development of the reading equipment, e-books have witnessed a gradual and steady increase in sales in recent years. Last year, smart phones announced to be able to perform additional functions as e-book reading devices, making it possible for retailers selling e-books for smart phones (SPR) such as iPhone to differentiate with those selling e-books for specific reading equipment (SER) such as Amazon Kindle. We develop a game theory model to examine the competition between SER and SPR retailers. We derive the equilibrium price and analyze the factors that affect equilibrium outcomes under both scenarios of complete and incomplete information. Our results suggest that reduced cost due to inconvenience of reading e-books over iPhone lowers equilibrium prices, and reduced cost of specific reading equipment leads to more intense price competition. Under information asymmetry, we show that SER retailers will increase the price at equilibrium.

  20. Impaired recruitment of seizure-generated neurons into functional memory networks of the adult dentate gyrus following long-term amygdala kindling.

    Science.gov (United States)

    Fournier, Neil M; Botterill, Justin J; Marks, Wendie N; Guskjolen, Axel J; Kalynchuk, Lisa E

    2013-06-01

    Epileptic seizures increase the birth of new neurons in the adult hippocampus. Although the consequences of aberrant neurogenesis on behavior are not fully understood, one hypothesis is that seizure-generated neurons might form faulty circuits that disrupt hippocampal functions, such as learning and memory. In the present study, we employed long-term amygdala kindling (i.e., rats receive 99-electrical stimulations) to examine the effect of repeated seizures on hippocampal neurogenesis and behavior. We labeled seizure-generated cells with the proliferation marker BrdU after 30-stimulations and continued kindling for an additional 4weeks to allow newborn neurons to mature under conditions of repeated seizures. After kindling was complete, rats were tested in a trace fear conditioning task and sacrificed 2h later to examine if 4-week old newborn cells were recruited into circuits involved in the retrieval of emotional memory. Compared to non-kindled controls, long-term kindled rats showed significant impairments in fear memory reflected in a decrease in conditioned freezing to both tone and contextual cues during testing. Moreover, long-term kindling also prevented the activation of 4-week old newborn cells in response to fear memory retrieval. These results indicate that the presence of seizure activity during cell maturation impedes the ability of new neurons to integrate properly into circuits important in memory formation. Together, our findings suggest that aberrant seizure-induced neurogenesis might contribute to the development of learning impairments in chronic epilepsy and raise the possibility that targeting the reduced activation of adult born neurons could represent a beneficial strategy to reverse cognitive deficits in some epileptic patients. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Life stress and kindling in bipolar disorder: review of the evidence and integration with emerging biopsychosocial theories.

    Science.gov (United States)

    Bender, Rachel E; Alloy, Lauren B

    2011-04-01

    Most life stress literature in bipolar disorder (BD) fails to account for the possibility of a changing relationship between psychosocial context and episode initiation across the course of the disorder. According to Post's (1992) influential kindling hypothesis, major life stress is required to trigger initial onsets and recurrences of affective episodes, but successive episodes become progressively less tied to stressors and may eventually occur autonomously. Subsequent research on kindling has largely focused on unipolar depression (UD), and the model has been tested in imprecise and inconsistent ways. The aim of the present paper is to evaluate evidence for the kindling model as it applies to BD. We first outline the origins of the hypothesis, the evidence for the model in UD, and the issues needing further clarification. Next, we review the extant literature on the changing relationship between life stress and bipolar illness over time, and find that evidence from the methodologically strongest studies is inconsistent with the kindling hypothesis. We then integrate this existing body of research with two emerging biopsychosocial models of BD: the Behavioral Approach System dysregulation model, and the circadian and social rhythm theory. Finally, we present therapeutic implications and suggestions for future research. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Pro-epileptic effects of the cannabinoid receptor antagonist SR141716 in a model of audiogenic epilepsy

    NARCIS (Netherlands)

    Vinogradova, L.V.; Shatskova, A.B.; Rijn, C.M. van

    2011-01-01

    Endocannabinoid system and its CB1 receptors are suggested to provide endogeneous protection against seizures. The present study examines whether CB1 receptors contribute to resistance to seizures and kindling epileptogenesis in a model of audiogenic epilepsy. Three groups of Wistar rats were used:

  3. Chemical Kindling with Pentylenetetrazole and Effects of Equeous Extract of Humulus Lupulus Flowers on the Kindling Process in the Male Mice

    Directory of Open Access Journals (Sweden)

    S Namvar Aghdash

    2015-12-01

    Full Text Available Introduction: More than 1% of world population suffer from epilepsy, which affects many aspects of individuals’ life. In fact, multiple treatment methods are used for this disorder, among which treatment effects of herbal plants can be introduced. Humulus Lupulus has been utilized in the traditional medicine as an anti-convulsion herb. Therefore, this study aimed to investigate the anti-convulsive effect of Humulus Lupulus extract on the pentylenetetrazole (PTZ kindling model of epilepsy. Methods: The present experimental study (n=8 was carried out on 40 male mice which have been randomly chosen and divided into 5 groups (n=8, including 1-control group receiving only PTZ, 1 sham group receiving  distilled water  and 3  experimental groups which received equeous extract of Humulus lupulus in doses of 100, 200 and 300 mg/kg  30 minutes before PTZ injection via gavage tube. Chemical kindling was performed in all the groups by a total of 15 treatments with PTZ intraperitoneal injection of 35 mg/kg of body weight at every 48 hours. The data analysis was carried out by one-way ANOVA and Tukey post-hoc test. Results: The study results revealed that administration of Humulus Lupulus extract had a significant effect on the decrease of PTZ-induced seizures. Moreover, this extract can inhibit progress of seizure stages, decrease seizure duration and increase letency time of seizure onset. Conclusion: The findings of the present study demonstrated that aqueous extract of Hops plant has anticonvulsant effect on chemical kindling and as a result, it seems to be useful regarding the epilepsy treatment.

  4. Ketogenic Diet Prevents Epileptogenesis and Disease Progression in Adult Mice and Rats

    Science.gov (United States)

    Lusardi, Theresa A.; Akula, Kiran K.; Coffman, Shayla Q.; Ruskin, David; Masino, Susan A.; Boison, Detlev

    2015-01-01

    Epilepsy is a highly prevalent seizure disorder which tends to progress in severity and become refractory to treatment. Yet no therapy is proven to halt disease progression or to prevent the development of epilepsy. Because a high fat low carbohydrate ketogenic diet (KD) augments adenosine signaling in the brain and because adenosine not only suppresses seizures but also affects epileptogenesis, we hypothesized that a ketogenic diet might prevent epileptogenesis through similar mechanisms. Here, we tested this hypothesis in two independent rodent models of epileptogenesis. Using a pentylenetetrazole kindling paradigm in mice, we first show that a KD, but not a conventional antiepileptic drug (valproic acid), suppressed kindling-epileptogenesis. Importantly, after treatment reversal, increased seizure thresholds were maintained in those animals kindled in the presence of a KD, but not in those kindled in the presence of valproic acid. Next, we tested whether a KD can halt disease progression in a clinically relevant model of progressive epilepsy. Epileptic rats that developed spontaneous recurrent seizures after a pilocarpine-induced status epilepticus were treated with a KD or control diet (CD). Whereas seizures progressed in severity and frequency in the CD-fed animals, KD-fed animals showed a prolonged reduction of seizures, which persisted after diet reversal. KD-treatment was associated with increased adenosine and decreased DNA methylation, the latter being maintained after diet discontinuation. Our findings demonstrate that a KD prevented disease progression in two mechanistically different models of epilepsy, and suggest an epigenetic mechanism underlying the therapeutic effects. PMID:26256422

  5. A user experience evaluation of Amazon Kindle mobile application

    Science.gov (United States)

    Hussain, Azham; Mkpojiogu, Emmanuel O. C.; Musa, Ja'afaru; Mortada, Salah

    2017-10-01

    There is a dramatic increase in the development of mobile applications in recent years. This makes the usability evaluation of these mobile applications an important aspect in the advancement and application of technology. In this paper, a laboratory-based usability evaluation was carried out on the Amazon Kindle app using 15 users who performed 5 tasks on the Kindle e-book mobile app. A post-test questionnaire was administered to elicit users' perception on the usability of the application. The results demonstrate that almost all the participants were satisfied with services provided by the Amazon Kindle e-book mobile app. On all the four user experience factors examined, namely, perceived ease-of-use, perceived visibility, perceived enjoyabilty, and perceived efficiency, the evaluation outcome shows that the participants had a good and rich mobile experience with the application.

  6. Rat vagus nerve stimulation model of seizure suppression: nNOS and ΔFos B changes in the brainstem.

    Science.gov (United States)

    Rijkers, K; Majoie, H J M; Aalbers, M W; Philippens, M; Doenni, V M; Vles, J S H; Steinbusch, H M W; Moers-Hornikx, V M P; Hopkins, D A; Hoogland, G

    2012-12-01

    Vagus nerve stimulation (VNS) is a moderately effective treatment for intractable epilepsy. However, the mechanism of action is poorly understood. The effect of left VNS in amygdala kindled rats was investigated by studying changes in nNOS and ΔFos B expression in primary and secondary vagus nerve projection nuclei: the nucleus of the solitary tract (NTS), dorsal motor nucleus of the vagus nerve (DMV), parabrachial nucleus (PBN) and locus coeruleus (LC). Rats were fully kindled by stimulation of the amygdala. Subsequently, when the fully kindled state was reached and then maintained for ten days, rats received a single 3-min train of VNS starting 1min prior to the kindling stimulus and lasting for 2min afterwards. In control animals the vagus nerve was not stimulated. Animals were sacrificed 48h later. The brainstems were stained for neuronal nitric oxide synthase (nNOS) and ΔFos B. VNS decreased seizure duration with more than 25% in 21% of rats. No VNS associated changes in nNOS immunoreactivity were observed in the NTS and no changes in ΔFos B were observed in the NTS, PBN, or LC. High nNOS immunopositive cell densities of >300cells/mm(2) were significantly more frequent in the left DMV than in the right (χ(2)(1)=26.2, pvagus nerve was stimulated. We conclude that the observed nNOS immunoreactivity in the DMV suggests surgery-induced axonal damage. A 3-min train of VNS in fully kindled rats does not affect ΔFos B expression in primary and secondary projection nuclei of the vagus nerve. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Measurement equivalence of the KINDL questionnaire across child self-reports and parent proxy-reports: a comparison between item response theory and ordinal logistic regression.

    Science.gov (United States)

    Jafari, Peyman; Sharafi, Zahra; Bagheri, Zahra; Shalileh, Sara

    2014-06-01

    Measurement equivalence is a necessary assumption for meaningful comparison of pediatric quality of life rated by children and parents. In this study, differential item functioning (DIF) analysis is used to examine whether children and their parents respond consistently to the items in the KINDer Lebensqualitätsfragebogen (KINDL; in German, Children Quality of Life Questionnaire). Two DIF detection methods, graded response model (GRM) and ordinal logistic regression (OLR), were applied for comparability. The KINDL was completed by 1,086 school children and 1,061 of their parents. While the GRM revealed that 12 out of the 24 items were flagged with DIF, the OLR identified 14 out of the 24 items with DIF. Seven items with DIF and five items without DIF were common across the two methods, yielding a total agreement rate of 50 %. This study revealed that parent proxy-reports cannot be used as a substitute for a child's ratings in the KINDL.

  8. Kindling: The Amazon e-Reader as an Educational Tool

    Science.gov (United States)

    Brezicki, Colin

    2011-01-01

    The revolutionary electronic reading device, Amazon's Kindle, is already obsolete. Such is the breakneck speed of technology that the machine touted to spell the death of printed books is already heading for the scrap heap, replaced by e-readers like the iPad that access the Internet, make phone calls, download movies, and connect users with all…

  9. Kindling of Life Stress in Bipolar Disorder: Effects of Early Adversity.

    Science.gov (United States)

    Shapero, Benjamin G; Weiss, Rachel B; Burke, Taylor A; Boland, Elaine M; Abramson, Lyn Y; Alloy, Lauren B

    2017-05-01

    Most theoretical frameworks regarding the role of life stress in bipolar disorders (BD) do not incorporate the possibility of a changing relationship between psychosocial context and episode initiation across the course of the disorder. The kindling hypothesis theorizes that over the longitudinal course of recurrent affective disorders, the relationship between major life stressors and episode initiation declines (Post, 1992). The present study aimed to test an extension of the kindling hypothesis in BD by examining the effect of early life adversity on the relationship between proximal life events and prospectively assessed mood episodes. Data from 145 bipolar participants (59.3% female, 75.2% Caucasian, and mean age of 20.19 years; SD = 1.75 years) were collected as part of the Temple-Wisconsin Longitudinal Investigation of Bipolar Spectrum Project (112 Bipolar II; 33 Cyclothymic disorder). Participants completed a self-report measure of early adversity at baseline and interview-assessed mood episodes and life events at regular 4-month follow-ups. Results indicate that early childhood adversity sensitized bipolar participants to the effects of recent stressors only for depressive episodes and not hypomanic episodes within BD. This was particularly the case with minor negative events. The current study extends prior research examining the kindling model in BD using a methodologically rigorous assessment of life stressors and mood episode occurrence. Clinicians should assess experiences of early adversity in individuals with BD as it may impact reactivity to developing depressive episodes in response to future stressors. Copyright © 2017. Published by Elsevier Ltd.

  10. Estructura latente del KIDDO-KINDL en una muestra peruana / Latent structure of KIDDO-KINDL in a peruvian sample

    Directory of Open Access Journals (Sweden)

    Jhonatan S. Navarro Loli

    2016-06-01

    Full Text Available RESUMEN: El presente estudio evaluó las propiedades psicométricas del instrumento KIDDO-KINDL (Ravens-Sieberer y Bullinger, 1998, que cuantifica la calidad de vida relacionada a la salud en niños y adolescentes. En una muestra de 377 alumnos del primer al quinto grado de secundaria, el análisis factorial confirmatorio demostró que la estructura interna original de seis factores no es satisfactoria para representar los constructos cuantificados debido a que presenta inestabilidad dimensional a nivel de los ítems en los factores Familia, Emocional, Amigos y Escuela. Al aplicar el análisis factorial exploratorio se encontró una estructura de cuatro factores. Esta solución factorial obtuvo mejores indicadores de consistencia interna (valores entre 0.59 y 0.81 en comparación con la estructura original (valores entre 0.24 y 0.80, y cargas factoriales más elevadas. Se discuten los posibles cambios en la interpretación de KIDDO-KINDL ABSTRACT: The present study evaluated the psychometric properties of the KIDDO-KINDL instrument (Ravens-Sieberer & Bullinger, 1998, which quantifies the quality of life related to health in children and adolescents. In a sample of 377 secondary school students from first to fifth grade, the confirmatory factorial analysis showed that the original internal structure of six factors was not satisfactory in representing the quantified constructs, because it presents dimensional instability concerning the items in the Family, Emotional, Friends and School factors. When applying the factorial analysis we found a structure of four factors. This factorial solution obtained better internal consistency indicators (values between 0.59 and 0.81 in comparison with the original structure (values between 0.24 and 0.80, and higher factorial loads. We discuss the possible changes in the interpretation of KIDDO-KINDL.

  11. Advances on genetic rat models of epilepsy

    Science.gov (United States)

    Serikawa, Tadao; Mashimo, Tomoji; Kuramoto, Takashi; Voigt, Birger; Ohno, Yukihiro; Sasa, Masashi

    2014-01-01

    Considering the suitability of laboratory rats in epilepsy research, we and other groups have been developing genetic models of epilepsy in this species. After epileptic rats or seizure-susceptible rats were sporadically found in outbred stocks, the epileptic traits were usually genetically-fixed by selective breeding. So far, the absence seizure models GAERS and WAG/Rij, audiogenic seizure models GEPR-3 and GEPR-9, generalized tonic-clonic seizure models IER, NER and WER, and Canavan-disease related epileptic models TRM and SER have been established. Dissection of the genetic bases including causative genes in these epileptic rat models would be a significant step toward understanding epileptogenesis. N-ethyl-N-nitrosourea (ENU) mutagenesis provides a systematic approach which allowed us to develop two novel epileptic rat models: heat-induced seizure susceptible (Hiss) rats with an Scn1a missense mutation and autosomal dominant lateral temporal epilepsy (ADLTE) model rats with an Lgi1 missense mutation. In addition, we have established episodic ataxia type 1 (EA1) model rats with a Kcna1 missense mutation derived from the ENU-induced rat mutant stock, and identified a Cacna1a missense mutation in a N-Methyl-N-nitrosourea (MNU)-induced mutant rat strain GRY, resulting in the discovery of episodic ataxia type 2 (EA2) model rats. Thus, epileptic rat models have been established on the two paths: ‘phenotype to gene’ and ‘gene to phenotype’. In the near future, development of novel epileptic rat models will be extensively promoted by the use of sophisticated genome editing technologies. PMID:25312505

  12. Advances on genetic rat models of epilepsy.

    Science.gov (United States)

    Serikawa, Tadao; Mashimo, Tomoji; Kuramoro, Takashi; Voigt, Birger; Ohno, Yukihiro; Sasa, Masashi

    2015-01-01

    Considering the suitability of laboratory rats in epilepsy research, we and other groups have been developing genetic models of epilepsy in this species. After epileptic rats or seizure-susceptible rats were sporadically found in outbred stocks, the epileptic traits were usually genetically-fixed by selective breeding. So far, the absence seizure models GAERS and WAG/Rij, audiogenic seizure models GEPR-3 and GEPR-9, generalized tonic-clonic seizure models IER, NER and WER, and Canavan-disease related epileptic models TRM and SER have been established. Dissection of the genetic bases including causative genes in these epileptic rat models would be a significant step toward understanding epileptogenesis. N-ethyl-N-nitrosourea (ENU) mutagenesis provides a systematic approach which allowed us to develop two novel epileptic rat models: heat-induced seizure susceptible (Hiss) rats with an Scn1a missense mutation and autosomal dominant lateral temporal epilepsy (ADLTE) model rats with an Lgi1 missense mutation. In addition, we have established episodic ataxia type 1 (EA1) model rats with a Kcna1 missense mutation derived from the ENU-induced rat mutant stock, and identified a Cacna1a missense mutation in a N-Methyl-N-nitrosourea (MNU)-induced mutant rat strain GRY, resulting in the discovery of episodic ataxia type 2 (EA2) model rats. Thus, epileptic rat models have been established on the two paths: 'phenotype to gene' and 'gene to phenotype'. In the near future, development of novel epileptic rat models will be extensively promoted by the use of sophisticated genome editing technologies.

  13. Synaptic degeneration and remodelling after fast kindling of the olfactory bulb

    DEFF Research Database (Denmark)

    Woldbye, D P; Bolwig, T G; Kragh, J

    1996-01-01

    in the basolateral amygdala and dentate gyrus, suggesting that these regions may be functionally altered during the kindling process. In the piriform cortex and dentate gyrus increased NCAM/D3(SNAP-25) ratios found ipsilaterally at seven days after kindling probably reflect an elevated rate of synaptic remodelling...

  14. Optical teardown of a Kindle Paperwhite display by OCT

    CERN Document Server

    Johnson, Bart; Kuznetsov, Mark; Larson, Noble; McKenzie, Eric; Mathur, Vaibhav; Goldberg, Brian; Whitney, Peter

    2016-01-01

    An optical teardown, or reverse engineering, of an Amazon Kindle Paperwhite electrophoretic display was performed by Optical Coherence Tomography at 1060 nm. The display incorporates an optical diffuser, lightguide and scattering layers for white light illumination, capacitive touch sensing, and an electrophoretic display. All these layers can be imaged by OCT as well as the thin film transistor array on the back side for driving the pixels. Phase sensitive OCT is used to measure motion of the pigment particles as the display changes between black and white.

  15. The Psychoanalytic Concept ofJouissanceand the Kindling Hypothesis.

    Science.gov (United States)

    Dimitriadis, Yorgos

    2017-01-01

    This article aims to define the conceptual field of jouissance in Lacanian theory, and put forth the hypothesis of a relationship between certain neurophysiological mechanisms and specific clinical phenomena where jouissance is "kindled" and outside the control of the symbolic process. First, the author briefly introduces Lacan's notion of jouissance and the way it draws on Freud's theorization, and describes the preliminary stages of this conceptual field in Lacan's work. Then, the jouissance related to two other concepts: repetition, with its Freudian and Lacanian nuances, as well as the-exclusively-Lacanian concept of the object petit a . Lacan's later conceptualization of language as jouissance (the notion of lalangue ) is then discussed in relation to Freud's early ideas ("Letter 52") on the different kinds of inscriptions that help form the mental apparatus. Finally, the author tries to formulate a hypothesis regarding specific neurophysiological mechanisms, based on clinical situations where jouissance becomes "kindled" and escapes the control of the symbolic processes through the neurophysiological mechanisms of conditioning, "kindling-sensitization" and "excitotoxicity." In these cases, jouissance can have a destructive effect on the body and can affect, among others organs, the brain-a process the author has previously described heuristically as the "psychosomatic diseases of the brain." This would be a special mechanism of automatism that would be triggered under the specific conditions of the fragility of the signifying chain (foreclosure of the Name-of-the-Father or solidification of the signifying chain) in combination with biological factors, including genetic factors. In this process, signifiers are reduced to signals, which in turn may be reduced to stimuli, with a tendency toward self-perpetuation, while affects are reduced to emotions and moods. Thus, conditioning and kindling-sensitization could also be understood in terms of a "semiotic

  16. Rat penis as a replantation model.

    Science.gov (United States)

    Karamürsel, Sebat; Karamürsel, Tamer; Celebioğlu, Selim

    2005-11-01

    The aim of this study is to assess the feasibility of rat penile replantation as a new microsurgical training model. The study was performed in 2 parts. ANATOMIC STUDIES: Fifteen Wistar albino rats were used to study and document the penile vascular anatomy. In 5 rats, dissections were performed after colored silicone injections, while 5 rats were operated under anesthesia to develop the strategy of flap elevation. In the remaining 5 rats, microangiographic study was performed with silicone-lead oxide mixture. FLAP STUDIES: As flap studies in 5 rats, penis were elevated based on right-side internal pudendal artery and internal pudendal vein and resutured. In 6 rats, penis were elevated as free flaps, and in 3 rats the penis were implanted in right thigh of the rats being the femoral artery and vein recipient. In the remaining 3 rats, penis were resutured in their original place, with saphenous artery and vein being the recipient and rerouted to the pubic region. At postoperative fifth day, the penis were examined for viability, and selected ones were histologically examined. Rat penis has a dual blood supply from bilateral internal pudendal arteries. Venous drainage is via both crural veins and dorsal vein. One side of the internal pudendal artery and anastomotic vein (branch of pudendal plexus) may be used as the vascular pedicle of the flap. Rat penis may be successfully elevated as a free flap and also may be replanted in its original place.

  17. Ketogenic diet is antiepileptogenic in pentylenetetrazole kindled mice and decrease levels of N-acylethanolamines in hippocampus

    DEFF Research Database (Denmark)

    Hansen, Suzanne L; Nielsen, Ane H; Knudsen, Katrine E

    2009-01-01

    The ketogenic diet (KD) is used for the treatment of refractory epilepsy in children, however, the mechanism(s) remains largely unknown. Also, the antiepileptogenic potential in animal models of epilepsy has been poorly addressed. Activation of cannabinoid type-1 receptor (CB(1)-R) upon seizure...... activity or type of diet. The level of oleoylethanolamide as well as the sum of N-acylethanolamines were significantly decreased by the KD, but were unaffected by seizure activity. The study shows that the KD had clear antiepileptogenic properties in the pentylenetetrazole kindling model and does...

  18. Penile autotransplantation in rats: An animal model

    Directory of Open Access Journals (Sweden)

    Raouf M Seyam

    2013-01-01

    Conclusions: Penile autotransplantation in rats is feasible and provides the basis for evaluation of the corpora cavernosa in an allotransplantation model. Long-term urethral continuity and dorsal neurovascular bundle survival in this model is difficult to establish.

  19. The Spatiotemporal Dynamics of Phase Synchronization during Epileptogenesis in Amygdala-Kindling Mice.

    Directory of Open Access Journals (Sweden)

    Jia-Jia Li

    Full Text Available The synchronization among the activities of neural populations in functional regions is one of the most important electrophysiological phenomena in epileptic brains. The spatiotemporal dynamics of phase synchronization was investigated to reveal the reciprocal interaction between different functional regions during epileptogenesis. Local field potentials (LFPs were recorded simultaneously from the basolateral amygdala (BLA, the cornu ammonis 1 of hippocampus (CA1 and the mediodorsal nucleus of thalamus (MDT in the mouse amygdala-kindling models during the development of epileptic seizures. The synchronization of LFPs was quantified between BLA, CA1 and MDT using phase-locking value (PLV. During amygdala kindling, behavioral changes (from stage 0 to stage 5 of mice were accompanied by after-discharges (ADs of similar waveforms appearing almost simultaneously in CA1, MDT, as well as BLA. AD durations were positively related to the intensity of seizures. During seizures at stages 1~2, PLVs remained relatively low and increased dramatically shortly after the termination of the seizures; by contrast, for stages 3~5, PLVs remained a relatively low level during the initial period but increased dramatically before the seizure termination. And in the theta band, the degree of PLV enhancement was positively associated with seizure intensity. The results suggested that during epileptogenesis, the functional regions were kept desynchronized rather than hyper-synchronized during either the initial or the entire period of the seizures; so different dynamic patterns of phase synchronization may be involved in different periods of the epileptogenesis, and this might also reflect that during seizures at different stages, the mechanisms underlying the dynamics of phase synchronization were different.

  20. Gravitational Biology: The Rat Model

    Science.gov (United States)

    1997-01-01

    In this session, Session JP3, the discussion focuses on the following topics: Morphology of brain, pituitary and thyroid in the rats exposed to altered gravity; Biochemical Properties of B Adrenoceptors After Spaceflight (LMS-STS78) or Hindlimb Suspension in Rats; Influence of Hypergravity on the Development of Monoaminergic Systems in the Rat Spinal Cord; A Vestibular Evoked Potentials (VsEPs) Study of the Function of the Otolith Organs in Different Head Orientations with respect to Earth Gravity Vector in the Rat; Quantitative Observations on the Structure of Selected Proprioceptive Components in Adult Rats that Underwent About Half of their Fetal Development in Space; Effects of a Nine-Day Shuttle Mission on the Development of the Neonatal Rat Nervous System, A Behavioral Study; Muscle Atrophy Associated to Microgravity in Rat, Basic Data For Countermeasures; Simulated Weightlessness by Unloading in the Rat, Results of a Time Course Study of Biochemical Events Occurring During Unloading and Lack of Effect of a rhBNP-2 Treatment on Bone Formation and Bone Mineral Content in Unloading Rats; and Cytological Mechanism of the Osteogenesis Under Microgravity Conditions.

  1. The effective connectivity of the seizure onset zone and ictal perfusion changes in amygdala kindled rhesus monkeys.

    Science.gov (United States)

    Cleeren, Evy; Premereur, Elsie; Casteels, Cindy; Goffin, Karolien; Janssen, Peter; Van Paesschen, Wim

    2016-01-01

    Epileptic seizures are network-level phenomena. Hence, epilepsy may be regarded as a circuit-level disorder that cannot be understood outside this context. Better insight into the effective connectivity of the seizure onset zone and the manner in which seizure activity spreads could lead to specifically-tailored therapies for epilepsy. We applied the electrical amygdala kindling model in two rhesus monkeys until these animals displayed consistent stage IV seizures. At this stage, we investigated the effective connectivity of the amygdala by means of electrical microstimulation during fMRI (EM-fMRI). In addition, we imaged changes in perfusion during a seizure using ictal SPECT perfusion imaging. The spatial overlap between the connectivity network and the ictal perfusion network was assessed both at the regional level, by calculating Dice coefficients using anatomically defined regions of interest, and at the voxel level. The kindled amygdala was extensively connected to bilateral cortical and subcortical structures, which in many cases were connected multisynaptically to the amygdala. At the regional level, the spatial extents of many of these fMRI activations and deactivations corresponded to the respective increases and decreases in perfusion imaged during a stage IV seizure. At the voxel level, however, some regions showed residual seizure-specific activity (not overlapping with the EM-fMRI activations) or fMRI-specific activation (not overlapping with the ictal SPECT activations), indicating that frequently, only a part of a region anatomically connected to the seizure onset zone participated in seizure propagation. Thus, EM-fMRI in the amygdala of electrically-kindled monkeys reveals widespread areas that are often connected multisynaptically to the seizure focus. Seizure activity appears to spread, to a large extent, via these connected areas.

  2. model in female wistar rats

    African Journals Online (AJOL)

    2013-12-31

    Dec 31, 2013 ... cyclodextrin on wister rats : histopathologic analoges. Fundan Clin. Pharmacol.; 23(6) :747-755. Sandor, V., Cuparencu, B., Dumitrascu, L.D., Birt, A.M. and Krausz, L.T. (2006). Protective effects of amphetamine on gastric ulcerations induced by indomethacin in rats. World J. Gastroenterol.; 12(44): ...

  3. Experimental model to induce obesity in rats

    National Research Council Canada - National Science Library

    Vinicius Von Diemen; Eduardo Neubarth Trindade; Manoel Roberto Maciel Trindade

    2006-01-01

    .... Obesity can be induced in animals by neuroendocrine, dietary or genetic changes. The most widely used models to induce obesity in rats are a lesion of the ventromedial hypothalamic nucleus (VMH...

  4. ideal hepatotoxicity model in rats using carbon tetrachloride (ccl4)

    African Journals Online (AJOL)

    DR. AMINU

    ABSTRACT. A study to produce ideal Hepatotoxicity rats' models using varying concentrations of carbon tetrachloride (CCl4) was carried out. A total of seventy five rats were divided into five (5) groups of twenty five (25) rats each; rats in group I are negative control, were not induced with lipid peroxidation. Rats in groups II, ...

  5. Neuronal zinc-α2-glycoprotein is decreased in temporal lobe epilepsy in patients and rats.

    Science.gov (United States)

    Liu, Ying; Wang, Teng; Liu, Xi; Wei, Xin; Xu, Tao; Yin, Maojia; Ding, Xueying; Mo, Lijuan; Chen, Lifen

    2017-08-15

    Zinc-α2-glycoprotein (ZAG) is a 42-kDa protein encoded by the AZGP1 gene that is known as a lipid mobilizing factor and is highly homologous to major histocompatibility complex class I family molecules. Recently, transcriptomic research has shown that AZGP1 expression is reduced in the brain tissue of epilepsy patients. However, the cellular distribution and biological role of ZAG in the brain and epilepsy are unclear. Patients with refractory temporal lobe epilepsy (TLE) and brain trauma were included in this study, and pentylenetetrazole (PTZ)-kindled rats were also used. The existence and level of ZAG in the brain were identified using immunohistochemistry, double-labeled immunofluorescence and western blot, and the expression level of AZGP1 mRNA was determined with quantitative real-time polymerase chain reaction (qrt-PCR). To explore the potential biological role of ZAG in the brain, co-immunoprecipitation (Co-IP) of phosphorylated ERK (p-ERK), TGF-β1 and ZAG was also performed. ZAG was found in the cytoplasm of neurons in brain tissue from both patients and rats. The levels of AZGP1 mRNA and ZAG were lower in refractory TLE patients and PTZ-kindled rats than in controls. In addition, the ZAG level decreased as PTZ kindling continued. Co-IP identified direct binding between p-ERK, TGF-β1 and ZAG. ZAG was found to be synthesized in neurons, and both the AZGP1 mRNA and ZAG protein levels were decreased in epilepsy patients and rat models. The reduction in ZAG may participate in the pathogenesis and pathophysiology of epilepsy by interacting with p-ERK and TGF-β1, promoting inflammation, regulating the metabolism of ketone bodies, or affecting other epilepsy-related molecules. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  6. The Psychoanalytic Concept of Jouissance and the Kindling Hypothesis

    Directory of Open Access Journals (Sweden)

    Yorgos Dimitriadis

    2017-09-01

    Full Text Available This article aims to define the conceptual field of jouissance in Lacanian theory, and put forth the hypothesis of a relationship between certain neurophysiological mechanisms and specific clinical phenomena where jouissance is “kindled” and outside the control of the symbolic process. First, the author briefly introduces Lacan's notion of jouissance and the way it draws on Freud's theorization, and describes the preliminary stages of this conceptual field in Lacan's work. Then, the jouissance related to two other concepts: repetition, with its Freudian and Lacanian nuances, as well as the—exclusively—Lacanian concept of the object petit a. Lacan's later conceptualization of language as jouissance (the notion of lalangue is then discussed in relation to Freud's early ideas (“Letter 52” on the different kinds of inscriptions that help form the mental apparatus. Finally, the author tries to formulate a hypothesis regarding specific neurophysiological mechanisms, based on clinical situations where jouissance becomes “kindled” and escapes the control of the symbolic processes through the neurophysiological mechanisms of conditioning, “kindling-sensitization” and “excitotoxicity.” In these cases, jouissance can have a destructive effect on the body and can affect, among others organs, the brain—a process the author has previously described heuristically as the “psychosomatic diseases of the brain.” This would be a special mechanism of automatism that would be triggered under the specific conditions of the fragility of the signifying chain (foreclosure of the Name-of-the-Father or solidification of the signifying chain in combination with biological factors, including genetic factors. In this process, signifiers are reduced to signals, which in turn may be reduced to stimuli, with a tendency toward self-perpetuation, while affects are reduced to emotions and moods. Thus, conditioning and kindling-sensitization could also

  7. The Psychoanalytic Concept of Jouissance and the Kindling Hypothesis

    Science.gov (United States)

    Dimitriadis, Yorgos

    2017-01-01

    This article aims to define the conceptual field of jouissance in Lacanian theory, and put forth the hypothesis of a relationship between certain neurophysiological mechanisms and specific clinical phenomena where jouissance is “kindled” and outside the control of the symbolic process. First, the author briefly introduces Lacan's notion of jouissance and the way it draws on Freud's theorization, and describes the preliminary stages of this conceptual field in Lacan's work. Then, the jouissance related to two other concepts: repetition, with its Freudian and Lacanian nuances, as well as the—exclusively—Lacanian concept of the object petit a. Lacan's later conceptualization of language as jouissance (the notion of lalangue) is then discussed in relation to Freud's early ideas (“Letter 52”) on the different kinds of inscriptions that help form the mental apparatus. Finally, the author tries to formulate a hypothesis regarding specific neurophysiological mechanisms, based on clinical situations where jouissance becomes “kindled” and escapes the control of the symbolic processes through the neurophysiological mechanisms of conditioning, “kindling-sensitization” and “excitotoxicity.” In these cases, jouissance can have a destructive effect on the body and can affect, among others organs, the brain—a process the author has previously described heuristically as the “psychosomatic diseases of the brain.” This would be a special mechanism of automatism that would be triggered under the specific conditions of the fragility of the signifying chain (foreclosure of the Name-of-the-Father or solidification of the signifying chain) in combination with biological factors, including genetic factors. In this process, signifiers are reduced to signals, which in turn may be reduced to stimuli, with a tendency toward self-perpetuation, while affects are reduced to emotions and moods. Thus, conditioning and kindling-sensitization could also be understood in

  8. Genetically epilepsy-prone rats (GEPRs) and DBA/2 mice: Two animal models of audiogenic reflex epilepsy for the evaluation of new generation AEDs.

    Science.gov (United States)

    De Sarro, Giovambattista; Russo, Emilio; Citraro, Rita; Meldrum, Brian S

    2017-06-01

    This review summarizes the current knowledge about DBA/2 mice and genetically epilepsy-prone rats (GEPRs) and discusses the contribution of such animal models on the investigation of possible new therapeutic targets and new anticonvulsant compounds for the treatment of epilepsy. Also, possible chemical or physical agents acting as proconvulsant agents are described. Abnormal activities of enzymes involved in catecholamine and serotonin synthesis and metabolism were reported in these models, and as a result of all these abnormalities, seizure susceptibility in both animals is greatly affected by pharmacological manipulations of the brain levels of monoamines and, prevalently, serotonin. In addition, both genetic epileptic models permit the evaluation of pharmacodynamic and pharmacokinetic interactions among several drugs measuring plasma and/or brain level of each compound. Audiogenic models of epilepsy have been used not only for reflex epilepsy studies, but also as animal models of epileptogenesis. The seizure predisposition (epileptiform response to sound stimulation) and substantial characterization of behavioral, cellular, and molecular alterations in both acute and chronic (kindling) protocols potentiate the usefulness of these models in elucidating ictogenesis, epileptogenesis, and their mechanisms. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic". Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Hearing Voices in Different Cultures: A Social Kindling Hypothesis.

    Science.gov (United States)

    Luhrmann, Tanya M; Padmavati, R; Tharoor, Hema; Osei, Akwasi

    2015-10-01

    This study compares 20 subjects, in each of three different settings, with serious psychotic disorder (they meet inclusion criteria for schizophrenia) who hear voices, and compares their voice-hearing experience. We find that while there is much that is similar, there are notable differences in the kinds of voices that people seem to experience. In a California sample, people were more likely to describe their voices as intrusive unreal thoughts; in the South Indian sample, they were more likely to describe them as providing useful guidance; and in our West African sample, they were more likely to describe them as morally good and causally powerful. What we think we may be observing is that people who fall ill with serious psychotic disorder pay selective attention to a constant stream of many different auditory and quasi-auditory events because of different "cultural invitations"-variations in ways of thinking about minds, persons, spirits and so forth. Such a process is consistent with processes described in the cognitive psychology and psychiatric anthropology literature, but not yet described or understood with respect to cultural variations in auditory hallucinations. We call this process "social kindling." Copyright © 2015 Cognitive Science Society, Inc.

  10. Neuronal nitric oxide synthase contributes to pentylenetetrazole-kindling-induced hippocampal neurogenesis.

    Science.gov (United States)

    Zhu, Xinjian; Dong, Jingde; Shen, Kai; Bai, Ying; Chao, Jie; Yao, Honghong

    2016-03-01

    Neuronal nitric oxide synthase (nNOS), the major nitric oxide synthase isoform in the mammalian brain, is implicated in the pathophysiology of several neurological conditions, including epilepsy. Neurogenesis in hippocampal dentate gyrus (DG) persists throughout life in the adult brain. Alterations in this process occur in many neurological diseases, including epilepsy. Few studies, however, have addressed the role of nNOS in hippocampal DG neurogenesis in epileptic brain. The present study, therefore, investigated the role of nNOS in pentylenetetrazole (PTZ)-kindling-induced neurogenesis in hippocampal DG. Our results showed that nNOS expression and enzymatic activity were significantly increased in the hippocampus of PTZ-kindled mice. Meanwhile, these PTZ-kindled mice were characterized by significant enhancement of new born cells proliferation and survival in hippocampal DG, and these survived cells are co-labeled with NeuN and GFAP. Selective inhibition of nNOS by 7-NI, however, suppressed PTZ-kindling-induced hippocampal DG new born cells proliferation and survival, suggesting that nNOS contributes to PTZ-kindling-induced hippocampal neurogenesis. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. LIEER OF WISTAR RAT MODELS

    African Journals Online (AJOL)

    homeostasis synthesised in the liver, has been raised in cases of impaired liver. fimcflun. ... Bil rats served as co:|rtrols, while Eflmts more test animals. The .... between 13D-15tJg were used. These anin1alswe1'edividedlntotwo[2]n1eiJ1 groups: the control group and the test animals. Each group comprised sixty [60].

  12. Anticonvulsant effects of antiaris toxicaria aqueous extract: investigation using animal models of temporal lobe epilepsy.

    Science.gov (United States)

    Mante, Priscilla Kolibea; Adongo, Donatus Wewura; Woode, Eric

    2017-04-26

    Antiaris toxicaria has previously shown anticonvulsant activity in acute animal models of epilepsy. The aqueous extract (AAE) was further investigated for activity in kindling with pentylenetetrazole and administration of pilocarpine and kainic acid which mimic temporal lobe epilepsy in various animal species. ICR mice and Sprague-Dawley rats were pre-treated with AAE (200-800 mg kg(-1)) and convulsive episodes induced using pentylenetetrazole, pilocarpine and kainic acid. The potential of AAE to prevent or delay onset and alter duration of seizures were measured. In addition, damage to hippocampal cells was assessed in kainic acid-induced status epilepticus test. 800 mg kg(-1) of the extract suppressed the kindled seizure significantly (P toxicaria may be effective in controlling temporal lobe seizures in rodents.

  13. A rat model for hepatitis E virus

    Directory of Open Access Journals (Sweden)

    Yannick Debing

    2016-10-01

    Full Text Available Hepatitis E virus (HEV is one of the prime causes of acute viral hepatitis, and chronic hepatitis E is increasingly recognized as an important problem in the transplant setting. Nevertheless, the fundamental understanding of the biology of HEV replication is limited and there are few therapeutic options. The development of such therapies is partially hindered by the lack of a robust and convenient animal model. We propose the infection of athymic nude rats with the rat HEV strain LA-B350 as such a model. A cDNA clone, pLA-B350, was constructed and the infectivity of its capped RNA transcripts was confirmed in vitro and in vivo. Furthermore, a subgenomic replicon, pLA-B350/luc, was constructed and validated for in vitro antiviral studies. Interestingly, rat HEV proved to be less sensitive to the antiviral activity of α-interferon, ribavirin and mycophenolic acid than genotype 3 HEV (a strain that infects humans. As a proof-of-concept, part of the C-terminal polymerase sequence of pLA-B350/luc was swapped with its genotype 3 HEV counterpart: the resulting chimeric replicon replicated with comparable efficiency as the wild-type construct, confirming that LA-B350 strain is amenable to humanization (replacement of certain sequences or motifs by their counterparts from human HEV strains. Finally, ribavirin effectively inhibited LA-B350 replication in athymic nude rats, confirming the suitability of the rat model for antiviral studies.

  14. Indomethacin-Induced Gastric Ulcer: Model in Female Wistar Rats ...

    African Journals Online (AJOL)

    Indomethacin-Induced Gastric Ulcer: Model in Female Wistar Rats. ... In this regard, an animal model experiment was carried-out to determine the ulcer-dose of indomethacin on female Wistar rats. Based on this objective, ... from 32 Countries:.

  15. Simulations on the kindling mechanism of the asFP595 fluorescent protein

    Science.gov (United States)

    Grigorenko, Bella L.; Nemukhin, Alexander V.; Savitsky, Alexander P.

    2008-02-01

    We report the results of quantum mechanical - molecular mechanical (QM/MM) simulations aiming to elucidate the mechanism of kindling of the initially non-fluorescent protein asFP595, which is a mutated variant of the chromoprotein asCP from the sea anemone Anemonia sulcata. asFP595 becomes brightly fluorescent (kindles) with emission at 595 nm in response to intense light irradiation at 568 nm. In simulations, we use the flexible effective fragment QM/MM method with the complete active space self-consistent field (CASSCF) wavefunctions in the quantum part and the AMBER force field parameters in the molecular mechanical part. We analyze the computed scans over potential energy surfaces of the ground and excited electronic states and consider details of the working hypothesis that the trans-cis isomerization of the chromophore group inside the protein is responsible for kindling.

  16. Anticonvulsive evaluation of THIP in the murine pentylenetetrazole kindling model

    DEFF Research Database (Denmark)

    Simonsen, Charlotte; Boddum, Kim; von Schoubye, Nadia L

    2017-01-01

    THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) is a GABAA receptor agonist with varying potencies and efficacies at γ-subunit-containing receptors. More importantly, THIP acts as a selective superagonist at δ-subunit-containing receptors (δ-GABAA Rs) at clinically relevant concentrations. ...

  17. Developmental Exposure to an Environmental PCB Mixture Delays the Propagation of Kindling in the Amygdala

    Science.gov (United States)

    Developmental PCB exposure impairs hearing and induces brainstem audiogenic seizures in adult offspring. The degree to which this enhanced susceptibility to seizure is manifest in other brain regions has not been examined. Thus, electrical kindling of the amygdala was used to eva...

  18. Rat gastric banding model for bariatric surgery.

    Science.gov (United States)

    Kanno, Hitoshi; Kiyama, Teruo; Fujita, Itsuo; Kato, Shunji; Yoshiyuki, Toshiro; Tajiri, Takashi

    2008-08-01

    Adjustable gastric banding is a surgical approach to weight reduction. In this study we created a gastric banding model in rats to better understand the mechanism of body weight loss. Male Sprague-Dawley rats weighing 260 to 280 g were subjected to gastric banding (band group) (n=8) or to a sham operation (control group) (n=8). Body weights were monitored for 14 days, and daily food and water intake and nitrogen balance were monitored for 7 days. Two rats in the band group died of malnutrition due to gastric stomal stenosis and obstruction caused by the gastric banding. Body weight gain during the 14 days after the operation was less in the band group than in the control group (pwater intake during the 7 days after the operation was significantly less in the band group than in the control group (pbalance was significantly less in the band group than in the control group (p<0.01). Gastric banding decreased the body weight gain of rats by decreasing the amount of food intake because of the creation of a small gastric pouch.

  19. Possible nitric oxide mechanism in the protective effect of hesperidin against pentylenetetrazole (PTZ)-induced kindling and associated cognitive dysfunction in mice.

    Science.gov (United States)

    Kumar, Anil; Lalitha, Sree; Mishra, Jitendriya

    2013-10-01

    Epilepsy is a complex neurological disorder manifested by recurrent episodes of convulsive seizures, loss of consciousness, and sensory disturbances. Pentylenetetrazole (PTZ)-induced kindling primarily represents a model of generalized epilepsy. The present study has been undertaken to evaluate the neuroprotective potential of hesperidin and its interaction with nitric oxide modulators against PTZ-induced kindling and associated cognitive dysfunction in mice. The experimental protocol comprised of eleven groups (n=6), where a subconvulsive dose of PTZ (40 mg/kg, i.p.) had been administered every other day for a period of 12 days, and seizure episodes were noted after each PTZ injection over a period of 30 min. The memory performance tests were carried out on days 13 and 14 followed by the estimation of biochemical and mitochondrial parameters. Chronic administration of a subconvulsive dose of PTZ resulted in an increase in convulsive activity culminating in generalized clonic-tonic seizures, as revealed by a progressive increase in seizure score as well as alteration in antioxidant enzyme levels (lipid peroxidation, nitrite, glutathione, super oxide dismutase, and catalase) and mitochondrial complex (I, II, and IV) activities, whereas chronic treatment with hesperidin (200 mg/kg) significantly attenuated these behavioral, biochemical, and mitochondrial alterations. Further, treatment with l-arginine (100 mg/kg) or l-NAME (10 mg/kg) in combination with hesperidin significantly modulated the protective effect of hesperidin which was significant as compared to their effects per se in PTZ-treated animals. Thus, the present study suggests a possible involvement of the NO-cGMP pathway in the neuroprotective effect of hesperidin in PTZ-kindled mice. © 2013.

  20. Human fetal brain-derived neural stem/progenitor cells grafted into the adult epileptic brain restrain seizures in rat models of temporal lobe epilepsy.

    Science.gov (United States)

    Lee, Haejin; Yun, Seokhwan; Kim, Il-Sun; Lee, Il-Shin; Shin, Jeong Eun; Park, Soo Chul; Kim, Won-Joo; Park, Kook In

    2014-01-01

    Cell transplantation has been suggested as an alternative therapy for temporal lobe epilepsy (TLE) because this can suppress spontaneous recurrent seizures in animal models. To evaluate the therapeutic potential of human neural stem/progenitor cells (huNSPCs) for treating TLE, we transplanted huNSPCs, derived from an aborted fetal telencephalon at 13 weeks of gestation and expanded in culture as neurospheres over a long time period, into the epileptic hippocampus of fully kindled and pilocarpine-treated adult rats exhibiting TLE. In vitro, huNSPCs not only produced all three central nervous system neural cell types, but also differentiated into ganglionic eminences-derived γ-aminobutyric acid (GABA)-ergic interneurons and released GABA in response to the depolarization induced by a high K+ medium. NSPC grafting reduced behavioral seizure duration, afterdischarge duration on electroencephalograms, and seizure stage in the kindling model, as well as the frequency and the duration of spontaneous recurrent motor seizures in pilocarpine-induced animals. However, NSPC grafting neither improved spatial learning or memory function in pilocarpine-treated animals. Following transplantation, grafted cells showed extensive migration around the injection site, robust engraftment, and long-term survival, along with differentiation into β-tubulin III+ neurons (∼34%), APC-CC1+ oligodendrocytes (∼28%), and GFAP+ astrocytes (∼8%). Furthermore, among donor-derived cells, ∼24% produced GABA. Additionally, to explain the effect of seizure suppression after NSPC grafting, we examined the anticonvulsant glial cell-derived neurotrophic factor (GDNF) levels in host hippocampal astrocytes and mossy fiber sprouting into the supragranular layer of the dentate gyrus in the epileptic brain. Grafted cells restored the expression of GDNF in host astrocytes but did not reverse the mossy fiber sprouting, eliminating the latter as potential mechanism. These results suggest that human fetal

  1. Human fetal brain-derived neural stem/progenitor cells grafted into the adult epileptic brain restrain seizures in rat models of temporal lobe epilepsy.

    Directory of Open Access Journals (Sweden)

    Haejin Lee

    Full Text Available Cell transplantation has been suggested as an alternative therapy for temporal lobe epilepsy (TLE because this can suppress spontaneous recurrent seizures in animal models. To evaluate the therapeutic potential of human neural stem/progenitor cells (huNSPCs for treating TLE, we transplanted huNSPCs, derived from an aborted fetal telencephalon at 13 weeks of gestation and expanded in culture as neurospheres over a long time period, into the epileptic hippocampus of fully kindled and pilocarpine-treated adult rats exhibiting TLE. In vitro, huNSPCs not only produced all three central nervous system neural cell types, but also differentiated into ganglionic eminences-derived γ-aminobutyric acid (GABA-ergic interneurons and released GABA in response to the depolarization induced by a high K+ medium. NSPC grafting reduced behavioral seizure duration, afterdischarge duration on electroencephalograms, and seizure stage in the kindling model, as well as the frequency and the duration of spontaneous recurrent motor seizures in pilocarpine-induced animals. However, NSPC grafting neither improved spatial learning or memory function in pilocarpine-treated animals. Following transplantation, grafted cells showed extensive migration around the injection site, robust engraftment, and long-term survival, along with differentiation into β-tubulin III+ neurons (∼34%, APC-CC1+ oligodendrocytes (∼28%, and GFAP+ astrocytes (∼8%. Furthermore, among donor-derived cells, ∼24% produced GABA. Additionally, to explain the effect of seizure suppression after NSPC grafting, we examined the anticonvulsant glial cell-derived neurotrophic factor (GDNF levels in host hippocampal astrocytes and mossy fiber sprouting into the supragranular layer of the dentate gyrus in the epileptic brain. Grafted cells restored the expression of GDNF in host astrocytes but did not reverse the mossy fiber sprouting, eliminating the latter as potential mechanism. These results suggest

  2. Life Stress and Kindling in Bipolar Disorder: Review of the Evidence and Integration with Emerging Biopsychosocial Theories

    OpenAIRE

    Bender, Rachel E.; Alloy, Lauren B.

    2011-01-01

    Most life stress literature in bipolar disorder (BD) fails to account for the possibility of a changing relationship between psychosocial context and episode initiation across the course of the disorder. According to Post’s (1992) influential kindling hypothesis, major life stress is required to trigger initial onsets and recurrences of affective episodes, but successive episodes become progressively less tied to stressors and may eventually occur autonomously. Subsequent research on kindling...

  3. Striatal grafts in a rat model of Huntington's disease

    DEFF Research Database (Denmark)

    Guzman, R; Meyer, M; Lövblad, K O

    1999-01-01

    Survival and integration into the host brain of grafted tissue are crucial factors in neurotransplantation approaches. The present study explored the feasibility of using a clinical MR scanner to study striatal graft development in a rat model of Huntington's disease. Rat fetal lateral ganglionic...... eminences grown as free-floating roller-tube cultures can be successfully grafted in a rat Huntington model and that a clinical MR scanner offers a useful noninvasive tool for studying striatal graft development....

  4. Anticonvulsant and Neuroprotective Activities of Phragmanthera austroarabica Extract in Pentylenetetrazole-Kindled Mice

    Directory of Open Access Journals (Sweden)

    Hibah M. Aldawsari

    2017-01-01

    Full Text Available Anticonvulsant and neuroprotective activity of Phragmanthera austroarabica extract were tested in pentylenetetrazole-kindled mice. All the chemical constituents of the plant extract were identified. Additionally, the extract was standardized and proved to contain total phenolic contents equal to 379.92±1.32 mg gallic acid equivalents/g dry plant extract. Induction of kindling was achieved by repeated intraperitoneal administration of pentylenetetrazole (35 mg/kg twice weekly. Male albino mice were given P. austroarabica extract (200, 400, or 800 mg/kg. The two higher doses (400 or 800 mg/kg of the extract significantly caused notable reduction in seizure activity and hippocampal malondialdehyde level compared to pentylenetetrazole control group. The highest dose enhanced cortical GSH level and showed intact DNA in the laddering assay. Upon studying the neuroprotective effect, mice treated with the higher dose of the extract demonstrated an improvement in the percent of surviving neurons in the cortex and hippocampus. We concluded that P. austroarabica extract ameliorated seizure activity and protected cortical and hippocampal neurons against pentylenetetrazole-induced kindling in mice.

  5. Groove model of tibia-femoral osteoarthritis in the rat

    NARCIS (Netherlands)

    de Visser, H.M.; Weinans, H.H.; Coeleveld, K.; van Rijen, M.H.P.; Lafeber, F.P.J.G.; Mastbergen, S.C.

    2016-01-01

    Several experimental models of osteoarthritis in rats are used to study the pathophysiology of osteoarthritis. Many mechanically induced models have the limitation that permanent joint instability is induced by, for example, ligament transection or meniscal damage. This permanent instability will

  6. Effect of ozone on colon anastomoses in rat peritonitis model

    OpenAIRE

    Çakır,Tuğrul; Aslaner, Arif; Tekeli,Seçkin Özgür; Avcı,Sema; Doğan,Uğur; Tekeli,Feyza; Soylu,Hakan; Akyüz, Cebrail; Koç,Süleyman; Üstünel,İsmail; Yılmaz,Necat

    2016-01-01

    PURPOSE: To investigate the effects of medical ozone theraphy on the colon anastomosis of peritonitis model in rats. METHODS: Eighteen rats were randomly assigned into three equal groups; control, cecal punctuation and colon anastomosis and ozone theraphy. Sepsis was performed with a cecal punctuation in groups 2 and 3. The medical ozone theraphy was administered intraperitonealy for three weeks in group 3 while the other rats received saline injection. At the twenty second day serum were ob...

  7. Generation and characterization of rat liver stem cell lines and their engraftment in a rat model of liver failure

    NARCIS (Netherlands)

    Kuijk, Ewart W; Rasmussen, Shauna; Blokzijl, Francis; Huch, Meritxell; Gehart, Helmuth; Toonen, Pim; Begthel, Harry; Clevers, Hans; Geurts, Aron M; Cuppen, Edwin

    2016-01-01

    The rat is an important model for liver regeneration. However, there is no in vitro culture system that can capture the massive proliferation that can be observed after partial hepatectomy in rats. We here describe the generation of rat liver stem cell lines. Rat liver stem cells, which grow as

  8. Neuroprotective Effects of Liraglutide for Stroke Model of Rats

    Directory of Open Access Journals (Sweden)

    Kenichiro Sato

    2013-10-01

    Full Text Available The number of diabetes mellitus (DM patients is increasing, and stroke is deeply associated with DM. Recently, neuroprotective effects of glucagon-like peptide-1 (GLP-1 are reported. In this study, we explored whether liraglutide, a GLP-1 analogue exerts therapeutic effects on a rat stroke model. Wistar rats received occlusion of the middle cerebral artery for 90 min. At one hour after reperfusion, liraglutide or saline was administered intraperitoneally. Modified Bederson’s test was performed at 1 and 24 h and, subsequently, rats were euthanized for histological investigation. Peripheral blood was obtained for measurement of blood glucose level and evaluation of oxidative stress. Brain tissues were collected to evaluate the level of vascular endothelial growth factor (VEGF. The behavioral scores of liraglutide-treated rats were significantly better than those of control rats. Infarct volumes of liraglutide-treated rats at were reduced, compared with those of control rats. The level of derivatives of reactive oxygen metabolite was lower in liraglutide-treated rats. VEGF level of liraglutide-treated rats in the cortex, but not in the striatum significantly increased, compared to that of control rats. In conclusion, this is the first study to demonstrate neuroprotective effects of liraglutide on cerebral ischemia through anti-oxidative effects and VEGF upregulation.

  9. A Rat Excised Larynx Model of Vocal Fold Scar

    Science.gov (United States)

    Welham, Nathan V.; Montequin, Douglas W.; Tateya, Ichiro; Tateya, Tomoko; Choi, Seong Hee; Bless, Diane M.

    2009-01-01

    Purpose: To develop and evaluate a rat excised larynx model for the measurement of acoustic, aerodynamic, and vocal fold vibratory changes resulting from vocal fold scar. Method: Twenty-four 4-month-old male Sprague-Dawley rats were assigned to 1 of 4 experimental groups: chronic vocal fold scar, chronic vocal fold scar treated with 100-ng basic…

  10. Ovariectomized rats as a model of postmenopausal osteoarthritis

    DEFF Research Database (Denmark)

    Høegh-Andersen, Pernille; Tankó, László B; Andersen, Thomas L

    2004-01-01

    We aimed to assess the effect of ovariectomy on cartilage turnover and degradation, to evaluate whether ovariectomized (OVX) rats could form an experimental model of postmenopausal osteoarthritis. The effect of ovariectomy on cartilage was studied using two cohorts of female Sprague-Dawley rats...... a useful experimental model for the evaluation of the chondroprotective effects of estrogens and estrogen-like substances and the model may be an in vivo representation of osteoarthritis in postmenopausal women....

  11. Dietary models for inducing hypercholesterolemia in rats

    Directory of Open Access Journals (Sweden)

    Sheyla Leite Matos

    2005-03-01

    Full Text Available The present work aimed at finding a dietetical model capable of promoting the highest hypercholesterolemia without affecting the development of the rats. Sixty female Fisher rats were divided into five groups. The first one was fed a control diet; the remaining four were fed hypercholesterolemic diets with cholesterol and different contents of soybean oil, starch, casein, micronutrients and fiber and, consequently, different caloric values. After eight weeks animals were evaluated in relation to growth, fecal excretion, liver weight and fat, cholesterol and its fractions, serum biochemical parameters and sistolic pressure and compared with controls. The best result was obtained with the diet containing 25 % soybean oil, 1.0 % cholesterol, 13 % fiber and 4,538.4 Kcal/Kg, since it promoted an increase in LDL-cholesterol, a decrease in the HDL fraction and affected less the hepatic function of the animals.Modelos animais têm sido usados para investigar a relação entre desordens no metabolismo do colesterol e a aterogênese. A estratégia utilizada a fim de induzir hipercolesterolemia (dietas com alto teor de gordura e com colesterol adicionado leva à redução de sua ingestão pelos animais, o que induz desnutrição. O presente trabalho objetivou encontrar um modelo dietético capaz de promover a maior hipercolesterolemia, sem afetar o desenvolvimento dos animais. Sessenta ratas Fisher foram divididas em cinco grupos. O primeiro foi alimentado com uma dieta controle; os quatros restantes receberam dietas hipercolesterolêmicas, com colesterol e diferentes teores de óleo de soja, amido, caseína, micronutrientes e fibra e, conseqüentemente, diferentes valores calóricos. Após oito semanas os animais foram avaliados em relação ao crescimento, excreção fecal, peso e teor de gordura do fígado, colesterol e suas frações, parâmetros bioquímicos séricos e pressão sistólica. Os melhores resultados foram obtidos com a dieta contendo 25

  12. Phenotypic Characterization of LEA Rat: A New Rat Model of Nonobese Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Tadashi Okamura

    2013-01-01

    Full Text Available Animal models have provided important information for the genetics and pathophysiology of diabetes. Here we have established a novel, nonobese rat strain with spontaneous diabetes, Long-Evans Agouti (LEA rat derived from Long-Evans (LE strain. The incidence of diabetes in the males was 10% at 6 months of age and 86% at 14 months, while none of the females developed diabetes. The blood glucose level in LEA male rats was between 200 and 300 mg/dl at 120 min according to OGTT. The glucose intolerance in correspondence with the impairment of insulin secretion was observed in male rats, which was the main cause of diabetes in LEA rats. Histological examination revealed that the reduction of β-cell mass was caused by progressive fibrosis in pancreatic islets in age-dependent manner. The intracytoplasmic hyaline droplet accumulation and the disappearance of tubular epithelial cell layer associated with thickening of basement membrane were evident in renal proximal tubules. The body mass index and glycaemic response to exogenous insulin were comparable to those of control rats. The unique characteristics of LEA rat are a great advantage not only to analyze the progression of diabetes, but also to disclose the genes involved in type 2 diabetes mellitus.

  13. Phenotypic Characterization of LEA Rat: A New Rat Model of Nonobese Type 2 Diabetes

    Science.gov (United States)

    Okamura, Tadashi; Pei, Xiang Yuan; Miyoshi, Ichiro; Shimizu, Yukiko; Takanashi-Yanobu, Rieko; Mototani, Yasumasa; Kanai, Takao; Satoh, Jo; Kimura, Noriko; Kasai, Noriyuki

    2013-01-01

    Animal models have provided important information for the genetics and pathophysiology of diabetes. Here we have established a novel, nonobese rat strain with spontaneous diabetes, Long-Evans Agouti (LEA) rat derived from Long-Evans (LE) strain. The incidence of diabetes in the males was 10% at 6 months of age and 86% at 14 months, while none of the females developed diabetes. The blood glucose level in LEA male rats was between 200 and 300 mg/dl at 120 min according to OGTT. The glucose intolerance in correspondence with the impairment of insulin secretion was observed in male rats, which was the main cause of diabetes in LEA rats. Histological examination revealed that the reduction of β-cell mass was caused by progressive fibrosis in pancreatic islets in age-dependent manner. The intracytoplasmic hyaline droplet accumulation and the disappearance of tubular epithelial cell layer associated with thickening of basement membrane were evident in renal proximal tubules. The body mass index and glycaemic response to exogenous insulin were comparable to those of control rats. The unique characteristics of LEA rat are a great advantage not only to analyze the progression of diabetes, but also to disclose the genes involved in type 2 diabetes mellitus. PMID:23691528

  14. Effects of agomelatine on pentylenetetrazole-induced kindling, kindling-associated oxidative stress, and behavioral despair in mice and modulation of its actions by luzindole and 1-(m-chlorophenyl) piperazine.

    Science.gov (United States)

    Azim, M Suhaib; Agarwal, Nidhi B; Vohora, Divya

    2017-07-01

    In view of well-evidenced antiepileptic effects of melatonin and few reports of anticonvulsant action of agomelatine, the present study investigated whether agomelatine protects against pentylenetetrazole (PTZ)-induced kindling in mice and kindling-associated oxidative stress, depression, and impairment of spatial memory. In order to explore whether effects are mediated by melatonergic or serotonergic mechanisms, 1-(m-chlorophenyl) piperazine (mCPP), selective 5HT2c receptor agonist and luzindole, melatonergic receptor antagonist, were taken as pharmacological tools. In view of few hepatotoxic reports on agomelatine, the study evaluated effects on hepatic enzyme levels. Swiss strain albino mice were injected with PTZ (25mg/kg, i.p.) once every two days for 5weeks to induce kindling. The effects of agomelatine (10mg/kg, p.o.) alone and in combination with luzindole (2.5mg/kg, i.p.) or mCPP (7mg/kg, i.p.) on seizure severity during induction and % incidence of animals kindled at the end of 5weeks were recorded. Modified forced swim test was used for studying depression-like behavior while spontaneous alternation behavior was used for studying effects on spatial memory. Serum AST and ALT concentrations, cortical and hippocampal malondialdehyde, and reduced glutathione were measured. Agomelatine 10mg/kg, p.o. effectively delayed development of kindling, reduced seizure severity, and decreased % incidence. Luzindole reversed the protective effects of agomelatine while mCPP failed to show such a reversal, indicating melatonergic (and not serotonergic) mechanisms in the observed effects. Agomelatine also showed antioxidant effects that can partially contribute to its anticonvulsant action. In addition, it alleviated PTZ-kindling-associated behavioral despair and favorably modulated liver enzymes. Its effects on improvement of kindling-associated spatial memory could possibly be related to its effects on locomotor activity. Agomelatine, thus, could be explored as an

  15. Kindling-induced potentiation of excitatory and inhibitory inputs to hippocampal dentate granule cells. II. Effects of the NMDA antagonist MK-801.

    LENUS (Irish Health Repository)

    Robinson, G B

    1991-10-18

    The effect of the non-competitive N-methyl-D-aspartate antagonist MK-801 on the early development of kindling-induced potentiation was examined in the rabbit hippocampal dentate gyrus. MK-801 (0.5 mg\\/kg) was administered 2 h before each daily kindling stimulation was applied to the perforant path. This treatment continued for the first 10 days of kindling. MK-801 depressed the growth of the afterdischarge duration and suppressed development of behavioral seizures. MK-801 did not block kindling-induced potentiation of either the perforant path-dentate granule cell population spike or excitatory postsynaptic potential. Random impulse train stimulation and non-linear systems analytic techniques were used to examine kindling-induced potentiation of presumed GABAergic recurrent inhibitory circuits. Both the magnitude and duration of kindling-induced response inhibition, to the second of each pair of impulses within the train, were reduced in rabbits pretreated with MK-801. These results suggest that MK-801 differentially affects kindling-induced potentiation of excitatory and inhibitory circuits within the rabbit hippocampal dentate gyrus.

  16. Percutaneous Salivary Gland Ablation using Ethanol in a Rat Model

    Directory of Open Access Journals (Sweden)

    Emma Burch

    2017-12-01

    Full Text Available Objectives: Sialorrhea is a common health and psychosocial problem for children with neuromuscular dysfunction secondary to a variety of disorders such as cerebral palsy. Current accepted treatments include the injection of botulinum toxin into the submandibular glands for temporary symptom relief. The purpose of this study is to demonstrate the feasibility of percutaneous ethanol injection for longer lasting salivary gland ablation in an animal model. Material and Methods: Twenty rats were used in this study. In each rat, 98% ethanol was injected into the right submandibular gland under ultrasound guidance. No intervention was performed on the left gland, which served as the control. Ten rats were sacrificed and glands evaluated at three weeks, with the remaining 10 rats sacrificed and evaluated at three months. Unpaired, 1-tailed T-tests were used to analyse the data. Results: Ethanol injections induced a significant and sustained reduction in salivary gland size. Treated glands were 41% smaller by mass than untreated controls in the 10 rats sacrificed at three weeks (P < 0.001. Treated glands were 43% smaller by mass than untreated controls in the 10 rats sacrificed at three months (P < 0.001. Qualitative histologic analysis demonstrated extensive parenchymal damage, inflammation, and fibrosis at both three week and three month time points. Conclusions: Using a rat model, we demonstrated dramatic and sustained submandibular gland damage after percutaneous injection of ethanol.

  17. Effects of bee products on pentylenetetrazole-induced seizures in the rat.

    Science.gov (United States)

    Zárraga-Galindo, N; Vergara-Aragón, P; Rosales-Meléndez, S; Ibarra-Guerrero, P; Domínguez-Marrufo, L E; Oviedo-García, R E; Hernández-Ramírez, H; Hernández-Téllez, B; López-Martínez, I E; Sánchez-Cervantes, I; Vázquez-García, M; Santiago, J

    2011-01-01

    Bee products (BP) have been used for centuries as a diet complement with claimed curative properties. The aim of this study was to determine whether oral administration of BP prevented behavioral, histological, and biochemical alterations, caused by pentylenetetrazole (PTZ)-induced kindling in rats. Male Wistar rats were employed to evaluate seizure latency, number and duration, performance in the open field test, histological alterations and mortality following BP administration. Oral administration of BP at two doses, 30 and 60 mg/kg/day, significantly lengthened latency of both clonic and tonic PTZ-induced seizures, decreased the duration and frequency of seizures and reduced mortality. In the Open Field test, BP treated groups showed increases in the number of crossed squares and rearing counts, and on optimal dose, decreases in fecal boli. Histological analysis showed in PTZ (50 and 80 mg/kg) kindling rats, lungs with inflammatory peribronchiolar, and perialveolar infiltrates. In the liver, mild losses of trabeculae, multi-vesiculated hepatocytes (steatosis) and inflammatory infiltrates in hepatic parenchyma were observed. Interestingly, in the heart, fibers were markedly separated. In testis, stratified epithelium of seminal tubules lost its normal structure, tubules had epithelium loss, spermatids were absent, and spermatogonia and Leydig cells diminished. In PTZ kindling rats treated with BP, the lungs had no inflammatory infiltrates, although the heart showed some inflammatory infiltrates. Remaining structures had normal characteristics. These results, suggest that BP can protect rats from effects of PTZ-induced kindling.

  18. A rat model of early stage osteonecrosis induced by glucocorticoids

    Directory of Open Access Journals (Sweden)

    Kerachian Mohammad

    2011-12-01

    Full Text Available Abstract Background Glucocorticoid (GC-induced osteonecrosis (ON is an important complication of medical therapy. The exact pathomechanisms of ON has not been clearly elucidated. There is a need for a reproducible animal model that better approximates the clinical scenario. Methods To determine the genetic susceptibility of rats to develop GC-induced femoral head ON, we evaluated 5 different inbred strains of rats (Spontaneous Hypertensive Rat, Wistar Kyoto, Wistar Furth, SASCO Fisher and Lewis. Prednisone pellets (dosage of 1.82-2.56 mg/kg/day were implanted subcutaneously for 90. After 90 days, the femurs were resected and examined histologically and radiographically. Pathological and histological examination was performed. Hematoxylin and eosin (H & E staining was used to delineate the femoral head osteonecrosis lesions as well as abnormalities of articular cartilage and growth plate. Results The greatest differences in H & E staining were seen in the Wistar Kyoto and Wistar Furth groups. In these groups 4 out of 5 and 3 out of 5, respectively, steroid-induced rats revealed growth plate disruption with acellular areas. The TUNEL apoptosis staining assay for apoptosis revealed that 4 out of 5 of Wistar Kyoto rats, 5 out of 5 of Wistar Furth, 2 out of 4 of surviving Lewis and 2 out of 2 of the surviving spontaneous hypertensive rats had apoptotic osteocytes in trabeculae, whereas none of the Fisher rats showed apoptotic osteocytes. Conclusions We postulate that Wistar Kyoto, Wistar Furth and spontaneous hypertensive rats may be strains of rats more susceptible to develop ON of the femoral head while Fisher rats were the most resistant.

  19. Experimental model in rat for sentinel node biopsy

    Directory of Open Access Journals (Sweden)

    Oliveira Filho Renato Santos de

    2003-01-01

    Full Text Available Although sentinel node procedure has been used world wide, there are many aspects to be defined and better standardized. This study address if the experimental model in rats is appropriate for sentinel node biopsy. In this model, the lymph nodes are showed by lymphoscintigraphy, they are dyed by patent blue and identified by intraoperative gamma probe detection. It isn?t necessary to use magnification for the procedure. The model demonstrated that sentinel node biopsy in rats is feasible. So, besides allowing researches in this field, the model is useful for training and diffusing this technique.

  20. Role of stressful life events and kindling in bipolar disorder: Converging evidence from a mania-predominant illness course.

    Science.gov (United States)

    Subramanian, Karthick; Sarkar, Siddharth; Kattimani, Shivanand; Philip Rajkumar, Ravi; Penchilaiya, Venkatalakshmi

    2017-12-01

    Stressful life events can precipitate relapses and recurrences in bipolar disorder. Kindling in bipolar disorder has been linked to maladaptive psychological reactivity to minor stressful life events. Systematic studies on life events and kindling are rare in bipolar disorder with a manic predominant polarity. One hundred and forty-nine remitted patients with bipolar I disorder were recruited. The National Institute of Mental Health-Life Chart Methodology was used to depict the illness course retrospectively, and the Presumptive Stressful Life Events Scale-Lifetime version was used to record the stressful life events. The role of stressful life events and the probability of kindling were assessed using appropriate statistics. There was a mania-predominant course of bipolar disorder in the sample with 55.7% (n = 83) having only recurrent mania. Family conflict and altered sleep patterns were the commonly reported stressful life events. When controlled for the severity of the stressor, the stressful life events were often associated with the initial episodes rather than the latter ones. Kindling may occur in bipolar disorder with mania as the predominant polarity. However, retrospective recall bias and hospital-based sampling limit generalizability of such observations. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. The Kindles Are Coming: Ereaders and Tablets Are Springing up in Schools--And Librarians Are Leading the Way

    Science.gov (United States)

    Barack, Lauren

    2011-01-01

    Commonly spearheaded by librarians, Kindle pilot programs are springing up in schools around the country, bringing ereaders to K-12 students, who are cracking the spine, so to speak, on these alternative learning tools. From full adoption of the devices at Clearwater High School in Florida to tentative beta projects, educators are exploring how…

  2. Self-reported health-related quality of life in kindergarten children : psychometric properties of the Kiddy-KINDL

    NARCIS (Netherlands)

    Villalonga-Olives, E.; Kiese-Himmel, C.; Witte, C.; Almansa, J.; Dusilova, I.; Hacker, K.; von Steinbuechel, N.

    Objectives: To assess the psychometric properties of the German self-reported version of the Kiddy-KINDL that measures Health Related Quality of Life (HRQoL) in 3 to 5 year old kindergarten children. Study design: The population of the study comprised baseline data of a longitudinal study whose main

  3. Reversal of P-glycoprotein overexpression by Ginkgo biloba extract in the brains of pentylenetetrazole-kindled and phenytoin-treated mice.

    Science.gov (United States)

    Zhang, Ce; Fan, Qing; Chen, Shu-Liang; Ma, Hui

    2015-08-01

    The purpose of this study was to investigate the combined effects of Ginkgo biloba extract and phenytoin (PHT) sodium as a dose regimen simulating the clinical treatment of patients with epilepsy, on P-glycoprotein (P-GP) overexpression in a pentylenetetrazole-kindled mouse model of epilepsy. Epilepsy was induced by intraperitoneal administration of pentylenetetrazole (40 mg/kg) for 7 days followed by intragastric administration of PHT (40 mg/kg) for 14 days. Thirty mice that developed seizures were randomly divided into three groups and administered PHT as well as the following treatments: saline (negative control); verapamil (20 mg/kg, positive control); and G. biloba (30 mg/kg). Seizure severity was recorded 30 minutes after treatment on Day 4 of drug administration, after which the mice were euthanized, and their brains isolated. Western blots and immunohistochemistry were performed to analyze the expression of P-GP and caspase-3, respectively, in the brain tissue. High-performance liquid chromatography was used to measure the concentrations of PHT in the brains of the treated mice. After 4 consecutive days of treatment, the seizure severity in the mice in the G. biloba extract group was more significantly reduced than the seizure severity in the saline control group, and a significant difference was observed between the G. biloba extract and verapamil control groups (p biloba extract and verapamil than it did in the saline-treated control group (p biloba extract and verapamil showed significantly increased brain PHT concentrations (p biloba extract group was significantly lower than that in the vehicle control group (p biloba. Therefore, this study showed that treatment with G. biloba extract in combination with PHT prevented the upregulation of P-GP expression in mice. Moreover, G. biloba extract decreased seizure severity in pentylenetetrazole-kindled/PHT-treated mice through a mechanism that might be related to the reduction of P-GP expression in the brain

  4. Novel rat model for neurocysticercosis using Taenia solium.

    Science.gov (United States)

    Verastegui, Manuela R; Mejia, Alan; Clark, Taryn; Gavidia, Cesar M; Mamani, Javier; Ccopa, Fredy; Angulo, Noelia; Chile, Nancy; Carmen, Rogger; Medina, Roxana; García, Hector H; Rodriguez, Silvia; Ortega, Ynes; Gilman, Robert H

    2015-08-01

    Neurocysticercosis is caused by Taenia solium infecting the central nervous system and is the leading cause of acquired epilepsy and convulsive conditions worldwide. Research into the pathophysiology of the disease and appropriate treatment is hindered by lack of cost-effective and physiologically similar animal models. We generated a novel rat neurocysticercosis model using intracranial infection with activated T. solium oncospheres. Holtzman rats were infected in two separate groups: the first group was inoculated extraparenchymally and the second intraparenchymally, with different doses of activated oncospheres. The groups were evaluated at three different ages. Histologic examination of the tissue surrounding T. solium cysticerci was performed. Results indicate that generally infected rats developed cysticerci in the brain tissue after 4 months, and the cysticerci were observed in the parenchymal, ventricle, or submeningeal brain tissue. The route of infection did not have a statistically significant effect on the proportion of rats that developed cysticerci, and there was no dependence on infection dose. However, rat age was crucial to the success of the infection. Epilepsy was observed in 9% of rats with neurocysticercosis. In histologic examination, a layer of collagen tissue, inflammatory infiltrate cells, perivascular infiltrate, angiogenesis, spongy change, and mass effect were observed in the tissue surrounding the cysts. This study presents a suitable animal model for the study of human neurocysticercosis. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  5. Surgical Intervention to Rescue Hirschsprung Disease in a Rat Model

    Science.gov (United States)

    Stamp, Lincon A; Obermayr, Florian; Pontell, Louise; Young, Heather M; Xie, Dan; Croaker, David H; Song, Zan-Min; Furness, John B

    2015-01-01

    Background/Aims Rats with a spontaneous null mutation in endothelin receptor type B or Ednrb (sl/sl; spotting lethal) lack enteric neurons in the distal bowel and usually die within the first week after birth. This early postnatal lethality limits their use for examining the potential of cell therapy to treat Hirschsprung disease, and for studies of the influence of EDNRB on the mature CNS and vascular systems. Methods We have developed a surgical intervention to prolong the life of the spotting lethal sl/sl rat, in which we perform a colostomy on postnatal (P) day 4–6 rats to avoid the fatal obstruction caused by the lack of colonic enteric neurons. Results The stomas remained patent and functional and the rats matured normally following surgery. Weight gains were comparable between control and Hirschsprung phenotype (sl/sl) rats, which were followed until 4 weeks after surgery (5 weeks old). We confirmed the absence of enteric neurons in the distal colon of rats whose lives were saved by the surgical intervention. Conclusions This study provides a novel approach for studying EDNRB signalling in multiple organ systems in mature rats, including an animal model to study the efficacy of cell therapy to treat Hirschsprung disease. PMID:26424040

  6. Surgical Intervention to Rescue Hirschsprung Disease in a Rat Model.

    Science.gov (United States)

    Stamp, Lincon A; Obermayr, Florian; Pontell, Louise; Young, Heather M; Xie, Dan; Croaker, David H; Song, Zan-Min; Furness, John B

    2015-10-01

    Rats with a spontaneous null mutation in endothelin receptor type B or Ednrb (sl/sl; spotting lethal) lack enteric neurons in the distal bowel and usually die within the first week after birth. This early postnatal lethality limits their use for examining the potential of cell therapy to treat Hirschsprung disease, and for studies of the influence of EDNRB on the mature CNS and vascular systems. We have developed a surgical intervention to prolong the life of the spotting lethal sl/sl rat, in which we perform a colostomy on postnatal (P) day 4-6 rats to avoid the fatal obstruction caused by the lack of colonic enteric neurons. The stomas remained patent and functional and the rats matured normally following surgery. Weight gains were comparable between control and Hirschsprung phenotype (sl/sl) rats, which were followed until 4 weeks after surgery (5 weeks old). We confirmed the absence of enteric neurons in the distal colon of rats whose lives were saved by the surgical intervention. This study provides a novel approach for studying EDNRB signalling in multiple organ systems in mature rats, including an animal model to study the efficacy of cell therapy to treat Hirschsprung disease.

  7. Ameliorative effect of Curcumin on seizure severity, depression like behavior, learning and memory deficit in post-pentylenetetrazole-kindled mice.

    Science.gov (United States)

    Choudhary, Kailash M; Mishra, Awanish; Poroikov, Vladimir V; Goel, Rajesh Kumar

    2013-03-15

    Epilepsy is a chronic neurological disorder and generally associated with certain psychiatric comorbidities. Among several comorbidities depressive behavior and cognitive impairment has been reported to be most debilitating comorbidity associated with epilepsy. This study was envisaged to evaluate the ameliorative effect of Curcumin on depression like behavior and cognitive impairment observed in pentylenetetrazole kindled animals. Male Swiss Albino mice were kindled with subconvulsive dose of pentylenetetrazole (35 mg/kg, i.p.). Successfully kindled animals were used in the study to observe the effect of different treatments. Treatment groups received phenytoin (30 mg/kg) and Curcumin (50, 100 and 200mg/kg) for 15 days. The animals were challenged with pentylenetetrazole (35 mg/kg, i.p.) on day 5, 10 and 15 and seizure severity score, immobility period, number of mistakes and step down latency were recorded. On 15th day, all the animals were sacrificed after behavioral evaluations and their brain was isolated and homogenized to estimate brain norepinephrine, serotonin, total nitrite level and acetylcholinesterase activity. Phenytoin treatment significantly improved the depressive like behavior along with its anticonvulsant effect, however was unable to improve memory impairment. Curcumin significantly attenuated seizure severity, depression like behavior and memory impairment in kindled animals, in dose dependent manner. These results were supported by the biochemical modulation of brain monoamine, nitrosative stress level and acetylcholinesterase activity. Thus present study concluded that Curcumin has the ameliorative effect on seizure severity, depression like behavior and memory impairment in pentylenetetrazole kindled mice, possibly via central monoaminergic modulation and inhibitory effect on nitrosative stress and acetylcholinesterase activity. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Cannabis exacerbates depressive symptoms in rat model induced by reserpine.

    Science.gov (United States)

    Khadrawy, Yasser A; Sawie, Hussein G; Abdel-Salam, Omar M E; Hosny, Eman N

    2017-05-01

    Cannabis sativa is one of the most widely recreational drugs and its use is more prevalent among depressed patients. Some studies reported that Cannabis has antidepressant effects while others showed increased depressive symptoms in Cannabis users. Therefore, the present study aims to investigate the effect of Cannabis extract on the depressive-like rats. Twenty four rats were divided into: control, rat model of depression induced by reserpine and depressive-like rats treated with Cannabis sativa extract (10mg/kg expressed as Δ9-tetrahydrocannabinol). The depressive-like rats showed a severe decrease in motor activity as assessed by open field test (OFT). This was accompanied by a decrease in monoamine levels and a significant increase in acetylcholinesterase activity in the cortex and hippocampus. Na + ,K + -ATPase activity increased in the cortex and decreased in the hippocampus of rat model. In addition, a state of oxidative stress was evident in the two brain regions. This was indicated from the significant increase in the levels of lipid peroxidation and nitric oxide. No signs of improvement were observed in the behavioral and neurochemical analyses in the depressive-like rats treated with Cannabis extract. Furthermore, Cannabis extract exacerbated the lipid peroxidation in the cortex and hippocampus. According to the present findings, it could be concluded that Cannabis sativa aggravates the motor deficits and neurochemical changes induced in the cortex and hippocampus of rat model of depression. Therefore, the obtained results could explain the reported increase in the depressive symptoms and memory impairment among Cannabis users. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. A novel model of invasive fungal rhinosinusitis in rats.

    Science.gov (United States)

    Zhang, Fang; An, Yunfang; Li, Zeqing; Zhao, Changqing

    2013-01-01

    Invasive fungal rhinosinusitis (IFRS) is a life-threatening inflammatory disease that affects immunocompromised patients, but animal models of the disease are scarce. This study aimed to develop an IFRS model in neutropenic rats. The model was established in three consecutive steps: unilateral nasal obstruction with Merocel sponges, followed by administration of cyclophosphamide (CPA), and, finally, nasal inoculation with Aspergillus fumigatus. Fifty healthy Wistar rats were randomly divided into five groups, with group I as the controls, group II undergoing unilateral nasal obstruction alone, group III undergoing nasal obstruction with fungal inoculation, group IV undergoing nasal obstruction with administration of CPA, and group V undergoing nasal obstruction with administration of CPA and fungal inoculation. Hematology, histology, and mycology investigations were performed. The changes in the rat absolute neutrophil counts (ANCs) were statistically different across the groups. The administration of CPA decreased the ANCs, whereas nasal obstruction with fungal inoculation increased the ANCs, and nasal obstruction did not change them. Histological examination of the rats in group V revealed the hyphal invasion of sinus mucosa and bone, thrombosis, and tissue infarction. No pathology indicative of IFRS was observed in the remaining groups. Positive rates of fungal culture in tissue homogenates from the maxillary sinus (62.5%) and lung (25%) were found in group V, whereas groups I, II, III, and IV showed no fungal culture in the homogenates. A rat IFRS model was successfully developed through nasal obstruction, CPA-induced neutropenia, and fungal inoculation. The disease model closely mimics the pathophysiology of anthropic IFRS.

  10. Ototoxicity of boric acid powder in a rat animal model.

    Science.gov (United States)

    Salihoglu, Murat; Dogru, Salim; Cesmeci, Enver; Caliskan, Halil; Kurt, Onuralp; Kuçukodaci, Zafer; Gungor, Atila

    2017-04-22

    Boric acid, which has antiseptic and acidic properties, is used to treat external and middle ear infections. However, we have not found any literature about the effect of boric acid powder on middle ear mucosa and inner ear. The purpose of this study is to investigate possible ototoxic effects of boric acid powder (BAP) on cochlear outer hair cell function and histological changes in middle ear mucosa in a rat animal model. Twenty healthy, mature Wistar albino rats were used in this study. The rats were divided into two groups, Group A and Group B, each of which consisted of 10 rats. Initially, the animals in each group underwent distortion product otoacoustic emissions (DPOAE) testing of their right and left ears. After the first DPOAE test, a surgical microscope was used to make a small perforation in both ears of the rats in each group, and a second DPOAE test was used to measure both ears in all of the rats. BAP was applied to the right middle ear of the rats using tympanic membrane perforation, and the DPOAEs were measured immediately after the BAP application. The histological changes and DPOAEs were evaluated three days later in Group A and 40 days later in Group B. No significant differences were found at all of the DPOAE frequencies. In Group A, mild inflammation of the middle ear mucosa was found on the third day after BAP application. In Group B, BAP caused mild inflammatory changes on the 40th day, which declined over time. Those changes did not lead to significant fibrosis within the mucosa. In rats, BAP causes mild inflammation in middle ear mucosa and it has no ototoxic effects on cochlear outer hair cell function in the inner ear of rats. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  11. Establishment of a rat model for canine necrotizing meningoencephalitis (NME).

    Science.gov (United States)

    Park, E-S; Uchida, K; Nakayama, H

    2014-11-01

    The pathogenesis of necrotizing meningoencephalitis (NME), necrotizing leukoencephalitis (NLE), and granulomatous meningoencephalomyelitis (GME) is still uncertain, although they are considered immune-mediated diseases. The purpose of the present study is to generate a rodent model(s) of these diseases. Rats were injected with rat cerebral or cerebellar homogenate. Rats injected with cerebral homogenate (Cbr) exhibited vacuolar or malacic changes mainly in the cerebral cortex. CD3-positive T cells and Iba-1-positive and CD163-negative microglia infiltrated and activated around the lesions. IgG deposited in the glial fibrillary acid protein (GFAP)-positive glia limitans from the early phase, and CD3-positive T cells attached to GFAP-positive astrocytes. Autoantibodies against GFAP were detected in the sera. These pathological features of Cbr rats were consistent with those of canine NME. In contrast, rats injected with cerebral homogenate (Cbe) exhibited demyelinating lesions with inflammatory reactions in the cerebellum, brainstem, and spinal cord. The presence of demyelination and autoantibodies against myelin proteins in Cbe rats was similar to murine experimental autoimmune encephalitis and differed from NME, NLE, and GME. All the present findings indicate that autoantibodies together with microglia and T cells may play a major role in the pathogenesis of idiopathic canine meningoencephalomyelitis. © The Author(s) 2014.

  12. Bacterial otitis media: a new non-invasive rat model.

    NARCIS (Netherlands)

    Tonnaer, E.L.G.M.; Sanders, E.A.M.; Curfs, J.H.A.J.

    2003-01-01

    This study describes the development of a physiological rat model for otitis media. The model is based on the assumption that bacteria, intranasally introduced into the nasopharynx, will be transferred into the middle ear cavity during swallowing provided that the ambient air pressure is higher than

  13. Infrared Thermography in Serotonin-Induced Itch Model in Rats

    DEFF Research Database (Denmark)

    Jasemian, Yousef; Gazerani, Parisa; Dagnæs-Hansen, Frederik

    2012-01-01

    The study validated the application of infrared thermography in a serotonin-induced itch model in rats since the only available method in animal models of itch is the count of scratching bouts. Twenty four adult Sprague-Dawley male rats were used in 3 experiments: 1) local vasomotor response...... with no scratching reflex was investigated. Serotonin elicited significant scratching and lowered the local temperature at the site of injection. A negative dose-temperature relationship of serotonin was found by thermography. Vasoregulation at the site of serotonin injection took place in the absence of scratching...... reflexes. Thermography is a reliable, non-invasive, and objective method for assessment in serotonin-induced itch model in rat....

  14. Transgenic Rat Models for Breast Cancer Research

    Science.gov (United States)

    1999-10-01

    medium). Using bovine embryos, cytochalasin B has been shown to increase the rigidity of the membranes and to restrict the movement of the pronuclei with...non surgical transfer of frozen- thawed bovine embryos. Theriogenology 1984; 21: 767-790. 16. Papaioannou VE, Fox JG. Efficacy of tribromoethanol...0, Tsunoda Y. Cryopreservation of rat blastocysts by vitrification . Cryobiology 1988; 25: 170-173. 24 Helmuth and Griep FIGURE LEGENDS Figure 1

  15. Characterizing a Rat Brca2 Knockout Model

    Science.gov (United States)

    2007-05-01

    gel. m Yeast transformation and sequencing. yIG397 (ref. 15) yeast was cultured overnight at 30 OC in YPD medium supplemented with adenine (200...colonies when plated on selective medium . In the absence VOLUME 21 NUMBER 6 JUNE 2003 NATURE BIOTECHNOLOGY Table 2 ENU-induced heritable phenotypes mately...and a PCR product enriched for BrcaZfragment 2 (nucleotides 3518-5204) were plated on selective medium . When gDNA obtained from a rat (SD) with two

  16. Kindling and Oxidative Stress as Contributors to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

    Science.gov (United States)

    Jason, L A; Porter, N; Herrington, J; Sorenson, M; Kubow, S

    2009-01-01

    Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS) is one of the more complex illnesses involving multiple systems within the body. Onset of ME/CFS frequently occurs quickly, and many patients report a prior exposure to a viral infection. This debilitating illness can affect the immune, neuroendocrine, autonomic, and neurologic systems. Abnormal biological findings among some patients have included aberrant ion transport and ion channel activity, cortisol deficiency, sympathetic nervous system hyperactivity, EEG spike waves, left ventricular dysfunction in the heart, low natural killer cell cytotoxicity, and a shift from Th1 to Th2 cytokines. We propose that the kindling and oxidative stress theories provide a heuristic template for better understanding the at times conflicting findings regarding the etiology and pathophysiology of this illness.

  17. Kindling and second messengers: an approach to the neurobiology of recurrence in bipolar disorder.

    Science.gov (United States)

    Ghaemi, S N; Boiman, E E; Goodwin, F K

    1999-01-15

    Since bipolar disorder is inherently a longitudinal illness characterized by recurrence and cycling of mood episodes, neurobiological theories involving kindlinglike phenomena appear to possess a certain explanatory power. An approach to understanding kindlinglike phenomena at the molecular level has been made possible by advances in research on second-messenger systems in the brain. The time frame of interest has shifted from the microseconds of presynaptic events to hours, days, months, and even years in the longer duration of events beyond the synapse--through second messengers, gene regulation, and synthesis of long-acting trophic factors. These complex interlocking systems may explain how environmental stress could interact over time with genetic vulnerability to produce illness. In its two sections, this paper will review an approach to understanding two major aspects of the neurobiology of bipolar disorder: kindling phenomena and second-messenger mechanisms. We will suggest that these two fields of research together help explain the biology of recurrence.

  18. Experimental rat models of chronic allograft nephropathy: a review

    Directory of Open Access Journals (Sweden)

    Shrestha B

    2014-07-01

    Full Text Available Badri Shrestha, John HaylorSheffield Kidney Institute, Sheffield Teaching Hospitals NHS Trust, Sheffield, UKAbstract: Chronic allograft nephropathy (CAN is the leading cause of late allograft loss after renal transplantation (RT, which continues to remain an unresolved problem. A rat model of CAN was first described in 1969 by White et al. Although the rat model of RT can be technically challenging, it is attractive because the pathogenesis of CAN is similar to that following human RT and the pathological features of CAN develop within months as compared with years in human RT. The rat model of RT is considered as a useful investigational tool in the field of experimental transplantation research. We have reviewed the literature on studies of rat RT reporting the donor and recipient strain combinations that have investigated resultant survival and histological outcomes. Several different combinations of inbred and outbred rat combinations have been reported to investigate the multiple aspects of transplantation, including acute rejection, cellular and humoral rejection mechanisms and their treatments, CAN, and potential targets for its prevention.Keywords: interventions, therapy, late allograft loss, renal transplantation

  19. Ameliorative effect of lithium chloride on working and spatial memory deficit in a PTZ-induced seizure model

    Directory of Open Access Journals (Sweden)

    Marzieh Yazdani

    2017-06-01

    Full Text Available Background: The repetitive seizure attacks lead to widespread neuronal damage and cognitive deficit, e.g. memory and learning impairment. The single or repeated administration of pentylenetetrazole (PTZ can induce seizure in rat. This study evaluates the neuroprotective effect of lithium chloride (LiCl on PTZ-induced working and spatial memory deficit. Materials and Methods: To induce the PTZ-kindling model, repeated doses of PTZ (40mg/kg/BW/ip were injected for 5 consecutive days. After observing five stages of seizure, the PTZ+Li20, PTZ+Li40 and PTZ+Li80 groups received 20, 40 and 80 mg/kg/BW of LiCl, respectively and the PTZ+Saline group, received Saline for 14 days. The Morris water maze (MWM and Y maze tests were conducted in order to investigate the spatial and working memory. Results: Compared to Control group, the PTZ+Saline group showed a decrease in alteration behavior in Y maze and an increase in latency time and distance to hidden platform in MWM. LiCl-treated rats, especially in the lowest dose, showed a significant higher alteration behavior in Y maze and the lower latency time and distance to hidden platform in MWM than the PTZ+Saline group. Conclusion: The neuroprotective effects of LiCl can ameliorate the spatial and working memory impairment in a PTZ-kindling model.

  20. Decreases in 15-lipoxygenase metabolites in Olmsted syndrome model rats.

    Science.gov (United States)

    Wakabayashi, Masato; Yoshioka, Takeshi; Higashino, Kenichi; Numata, Yoshito; Igarashi, Yasuyuki; Kihara, Akio

    2017-03-01

    Olmsted syndrome (OS) is a congenital dermatosis characterized by palmoplantar keratoderma and periorificial keratotic plaque. TRPV3 (transient receptor potential vanilloid subtype 3) encodes a thermosensitive Ca 2+ channel and is the causative gene of OS. However, the molecular mechanism that causes the pathological development of OS is unclear. We aimed to investigate the molecular mechanisms underlying OS pathology from the perspective of lipid metabolism. Comprehensive lipidomics and microarray analyses were conducted on tissue samples from a non-lesional skin area of OS model rats (Ht rats) and from wild type (WT) rats as the control. Infiltration of leukocytes such as eosinophils and neutrophils and an increase in the fibrotic region were detected in the unaffected skin area of Ht rats compared with the WT rats. Among about 600 lipid species examined, the levels of 15-lipoxygenase (LOX) metabolites, the precursors of anti-inflammatory and pro-resolving lipid mediators, and dihydroceramides decreased by ≥16-fold in Ht rats compared with WT rats. Consistent with the decreases in the 15-LOX metabolites, expression levels of the genes that encode the 15-LOXs, Alox15 and Alox15b, were largely reduced. Conversely, increased expression levels were detected of Il36b, Ccl20, Cxcl1, and Cxcl2, which encode cytokines/chemokines, and S100a8 and S100a9, which encode the Ca 2+ binding proteins that are implicated in epidermal proliferation. The pro-inflammatory state in the unaffected skin of Ht rats caused by decreases in 15-LOX metabolites and increases in cytokines/chemokines may contribute to the pathogenesis of OS. Copyright © 2016 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

  1. A novel rat contact lens model for Fusarium keratitis.

    Science.gov (United States)

    Abou Shousha, Mohamed; Santos, Andrea Rachelle C; Oechsler, Rafael A; Iovieno, Alfonso; Maestre-Mesa, Jorge; Ruggeri, Marco; Echegaray, Jose J; Dubovy, Sander R; Perez, Victor L; Miller, Darlene; Alfonso, Eduardo C; Bajenaru, M Livia

    2013-01-01

    The aim of this study was to develop and characterize a new contact lens-associated fungal keratitis rat model and to assess the ability of non-invasive spectral-domain optical coherence tomography (SD-OCT) to detect pathological changes in vivo in fungal keratitis. We used SD-OCT to image and measure the cornea of Sprague Dawley rats. Fusarium infection was initiated in the rat eye by fitting Fusarium solani-soaked contact lenses on the experimental eye, while the control animals received contact lenses soaked in sterile saline. The fungal infection was monitored with periodic slit-lamp examination and in vivo SD-OCT imaging of the rat eye, and confirmed by histology, counting of viable fungi in the infected rat cornea, and PCR with specific primers for Fusarium sp. We imaged and measured the rat cornea with SD-OCT. Custom-made contact lenses were developed based on the OCT measurements. Incubation of contact lenses in a F. solani suspension resulted in biofilm formation. We induced contact lens-associated Fusarium keratitis by fitting the rat eyes for 4 h with the Fusarium-contaminated contact lenses. The SD-OCT images of the cornea correlated well with the slit-lamp and histopathological results and clearly defined clinical signs of infection, namely, increased corneal thickening, loss of epithelial continuity, hyper-reflective areas representing infiltrates, and endothelial plaques characteristic of fungal infection. Moreover, in three cases, SD-OCT detected the infection without any clear findings on slit-lamp examination. Infection was confirmed with histological fungal staining, PCR, and microbiological culture positivity. We developed a highly reproducible rat contact lens model and successfully induced contact lens-associated Fusarium keratitis in this model. The clinical presentation of contact lens-associated Fusarium keratitis in the rat model is similar to the human condition. SD-OCT is a valuable tool that non-invasively revealed characteristic signs

  2. A novel rat contact lens model for Fusarium keratitis

    Science.gov (United States)

    Abou Shousha, Mohamed; Santos, Andrea Rachelle C.; Oechsler, Rafael A.; Iovieno, Alfonso; Maestre-Mesa, Jorge; Ruggeri, Marco; Echegaray, Jose J.; Dubovy, Sander R.; Perez, Victor L.; Miller, Darlene; Alfonso, Eduardo C.

    2013-01-01

    Purpose The aim of this study was to develop and characterize a new contact lens–associated fungal keratitis rat model and to assess the ability of non-invasive spectral-domain optical coherence tomography (SD-OCT) to detect pathological changes in vivo in fungal keratitis. Methods We used SD-OCT to image and measure the cornea of Sprague Dawley rats. Fusarium infection was initiated in the rat eye by fitting Fusarium solani–soaked contact lenses on the experimental eye, while the control animals received contact lenses soaked in sterile saline. The fungal infection was monitored with periodic slit-lamp examination and in vivo SD-OCT imaging of the rat eye, and confirmed by histology, counting of viable fungi in the infected rat cornea, and PCR with specific primers for Fusarium sp. Results We imaged and measured the rat cornea with SD-OCT. Custom-made contact lenses were developed based on the OCT measurements. Incubation of contact lenses in a F. solani suspension resulted in biofilm formation. We induced contact lens–associated Fusarium keratitis by fitting the rat eyes for 4 h with the Fusarium-contaminated contact lenses. The SD-OCT images of the cornea correlated well with the slit-lamp and histopathological results and clearly defined clinical signs of infection, namely, increased corneal thickening, loss of epithelial continuity, hyper-reflective areas representing infiltrates, and endothelial plaques characteristic of fungal infection. Moreover, in three cases, SD-OCT detected the infection without any clear findings on slit-lamp examination. Infection was confirmed with histological fungal staining, PCR, and microbiological culture positivity. Conclusions We developed a highly reproducible rat contact lens model and successfully induced contact lens–associated Fusarium keratitis in this model. The clinical presentation of contact lens–associated Fusarium keratitis in the rat model is similar to the human condition. SD-OCT is a valuable tool that

  3. Antihyperalgesic Activity of Rhodiola rosea in a Diabetic Rat Model.

    Science.gov (United States)

    Déciga-Campos, Myrna; González-Trujano, Maria Eva; Ventura-Martínez, Rosa; Montiel-Ruiz, Rosa Mariana; Ángeles-López, Guadalupe Esther; Brindis, Fernando

    2016-02-01

    Preclinical Research Rhodiola rosea L. (Crassulaceae) is used for enhancing physical and mental performance. Recent studies demonstrated that R. rosea had anti-inflammatory activity in animal models, for example, carrageenan- and nystatin-induced edema in rats, possibly by inhibiting phospholipase A2 and cyclooxygenases-1 and -2. In addition, R. rosea had antinociceptive activity in thermal and chemical pain tests as well as mechanical hyperalgesia. The purpose of the present study was to assess the antihyperalgesic effect of an ethanol extract of Rhodiola rosea (R. rosea) in a diabetic rat model. Rats were administered a single dose of streptozotocin (STZ; 50 mg/kg, i.p.) and hyperalgesia was evaluated four weeks later. Formalin-evoked (0.5%) flinching was increased in diabetic rats compared with nondiabetic controls Systemic (1-100 mg/kg, i.p.) and local (0.1-10 mg/paw into the dorsal surface of the right hind paw) administration of R. rosea ethanol extract dose-dependently reduced formalin-induced hyperalgesia in diabetic rats. The antihyperalgesic effect of R. rosea was compared with gabapentin. These results suggest that R. rosea ethanol extract may have potential as a treatment for diabetic hyperalgesia. © 2016 Wiley Periodicals, Inc.

  4. Analgesic Effect of Xenon in Rat Model of Inflammatory Pain.

    Science.gov (United States)

    Kukushkin, M L; Igon'kina, S I; Potapov, S V; Potapov, A V

    2017-02-01

    The analgesic effects of inert gas xenon were examined on rats. The formalin model of inflammatory pain, tail-flick test, and hot-plate test revealed the antinociceptive effects of subanesthetizing doses of inhalation anesthetic xenon. Inhalation of 50/50 xenon/oxygen mixture moderated the nociceptive responses during acute and tonic phases of inflammatory pain.

  5. Cognitive symptoms in a rat model of Parkinson's Disease

    NARCIS (Netherlands)

    Holslag, Joost; Beck, Anne-Kathrin; Krauss, Joachim K.; Schwabe, K

    2017-01-01

    Objective: We here investigated the effect of bilateral 6-hydroxydopamine (6-OHDA) lesions, a rat model for Parkinson's disease (PD), on impulsivity and attention in an auditory oddball paradigm. In PD, the progressive loss of dopamine (DA) neurons in the substantia nigra leads to disturbed motor

  6. A rat model with an isolated bladder in situ

    DEFF Research Database (Denmark)

    Thulesen, J; Olsen, P S; Grevstad, J U

    1997-01-01

    This paper describes our method for producing a rat model with an isolated bladder in situ in which the bladder makes no contact with urine. First, the right kidney was removed, then an external catheter was placed in the right ureter for bladder infusions, and next the left ureter was anatomosed...

  7. A New Rat Model for Orthotopic Abdominal Wall Allotransplantation

    Directory of Open Access Journals (Sweden)

    William W. Lao, MD

    2014-04-01

    Conclusions: Technical, histological, and immunological aspects of a new rat model are described. These results give clues to what occurs in human abdominal wall transplantation. In addition, Th1, a proinflammatory cell, was found to be a potential biomarker for allograft rejection.

  8. [Biomarker screening of rat pulmonary hypertension model by transcriptome sequencing].

    Science.gov (United States)

    Hu, F; Xie, L; Yu, L; Chen, J; Liu, H M

    2016-04-01

    To screen relative gene and pathway of rat severe pulmonary hypertension by transcriptome sequencing. Pulmonary hypertension animal model of SD rats was established by left lung resection and hypodermic injection of monocrotaline.Monocrotaline was injected subcutaneously one week after left lung resection.Eight rats at 1, 3, 5 weeks after the injection of monocrotaline respectively were named group M1, group M2 and group M3.Eight normal rats were assigned into control group (group C). The right lung tissue was used for transcriptome sequencing to screen the differentially expressed genes.KEGG pathway analysis was performed to screen the pathways with enriched differentially expressed genes. The animal model was established successfully.The pulmonary artery pressure was as follows: group C (28.6±3.0) mmHg(1 mmHg=0.133 kPa), group M1 (38.9±3.3) mmHg, group M2 (50.8±3.9) mmHg, group M3 (51.5±3.5) mmHg.The pressure elevated in group M1 compared with group C (P=0.007). The pressure in M2 and M3 elevated compared with M1(P=0.002 and Ppulmonary hypertension were epithelial specific receptor tyrosine kinase(Tie2) and thrombospondin-1(TSP-1). Tie2 was down-regulated (qpulmonary hypertension and up-regulated (qpulmonary hypertension.TSP-1 was up-regulated (qpulmonary hypertension and down-regulated (qpulmonary hypertension.In the stage of severe pulmonary hypertension, the differentially expressed genes were enriched mainly in the pathways of phosphatidylinostitol 3-kinase, focal adhesion kinase and extracellular matrix receptor interaction. The study provides transcriptome information of rat pulmonary hypertension model and normal rat.Possible mechanisms of pulmonary hypertension are found.These genes and pathways might be new precursor for the diagnosis and treatment of pulmonary hypertension.

  9. Lessons from rat models of hypertension : from Goldblatt to genetic engineering

    NARCIS (Netherlands)

    Pinto, YM; Paul, M; Ganten, D

    Over the past 50 years various animal models of hypertension have been developed, predominantly in the rat. In this review we discuss the use of the rat as a model of hypertension, and evaluate what these models have taught us. Interestingly, the spontaneously hypertensive rat (SHR) is by far the

  10. Lessons from rat models of hypertension: from Goldblatt to genetic engineering

    NARCIS (Netherlands)

    Pinto, Y. M.; Paul, M.; Ganten, D.

    1998-01-01

    Over the past 50 years various animal models of hypertension have been developed, predominantly in the rat. In this review we discuss the use of the rat as a model of hypertension, and evaluate what these models have taught us. Interestingly, the spontaneously hypertensive rat (SHR) is by far the

  11. Simvastatin Exposure and Rotator Cuff Repair in a Rat Model.

    Science.gov (United States)

    Deren, Matthew E; Ehteshami, John R; Dines, Joshua S; Drakos, Mark C; Behrens, Steve B; Doty, Stephen; Coleman, Struan H

    2017-03-01

    Simvastatin is a common medication prescribed for hypercholesterolemia that accelerates local bone formation. It is unclear whether simvastatin can accelerate healing at the tendon-bone interface after rotator cuff repair. This study was conducted to investigate whether local and systemic administration of simvastatin increased tendon-bone healing of the rotator cuff as detected by maximum load to failure in a controlled animal-based model. Supraspinatus tendon repair was performed on 120 Sprague-Dawley rats. Sixty rats had a polylactic acid membrane overlying the repair site. Of these, 30 contained simvastatin and 30 did not contain medication. Sixty rats underwent repair without a polylactic acid membrane. Of these, 30 received oral simvastatin (25 mg/kg/d) and 30 received a regular diet. At 4 weeks, 5 rats from each group were killed for histologic analysis. At 8 weeks, 5 rats from each group were killed for histologic analysis and the remaining 20 rats were killed for biomechanical analysis. One rat that received oral simvastatin died of muscle necrosis. Average maximum load to failure was 35.2±6.2 N for those receiving oral simvastatin, 36.8±9.0 N for oral control subjects, 39.5±12.8 N for those receiving local simvastatin, and 39.1±9.3 N for control subjects with a polylactic acid membrane. No statistically significant differences were found between any of the 4 groups (P>.05). Qualitative histologic findings showed that all groups showed increased collagen formation and organization at 8 weeks compared with 4 weeks, with no differences between the 4 groups at each time point. The use of systemic and local simvastatin offered no benefit over control groups. [Orthopedics. 2017; 40(2):e288-e292.]. Copyright 2016, SLACK Incorporated.

  12. Rat Models of Ventricular Fibrillation Following Acute Myocardial Infarction

    DEFF Research Database (Denmark)

    Hundahl, Laura A.; Tfelt-Hansen, Jacob; Jespersen, Thomas

    2017-01-01

    A number of animal models have been designed in order to unravel the underlying mechanisms of acute ischemia-induced arrhythmias and to test compounds and interventions for antiarrhythmic therapy. This is important as acute myocardial infarction (AMI) continues to be the major cause of sudden...... cardiac death, and we are yet to discover safe and effective treatments of the lethal arrhythmias occurring in the acute setting. Animal models therefore continue to be relevant for our understanding and treatment of acute ischemic arrhythmias. This review discusses the applicability of the rat as a model...... for ventricular arrhythmias occurring during the acute phase of AMI. It provides a description of models developed, advantages and disadvantages of rats, as well as an overview of the most important interventions investigated and the relevance for human pathophysiology....

  13. Rat model of focal cerebral ischemia in the dominant hemisphere.

    Science.gov (United States)

    Zhang, Hua; Shen, Yan; Wang, Wei; Gao, Huanmin

    2015-01-01

    In the human brain, the dominant hemisphere is more complex than the non-dominant hemisphere. Hence, cerebral ischemia of the dominant hemisphere often leads to serious consequences. This study aims to establish a rodent model of focal cerebral ischemia in the dominant hemisphere. The quadruped feeding test was used to screen 70 male Sprague Dawley rats. From this test, 48 rats with right paw preference were selected and randomly assigned numbers. Half were assigned to the dominant hemisphere ischemia (DHI) group, and the other half were assigned to the non-dominant hemisphere ischemia (NDHI) group. The middle cerebral artery was occluded 2 h before reperfusion. Neurological functions were tested. TTC and HE staining were performed. The volume of cerebral infarction was calculated. Rats in the DHI group had significantly worse neurological scores than rats in the NDHI group (P dominant hemisphere than in the non-dominant hemisphere. The dominant hippocampus indicated severe neuronal loss and disorderly cellular arrangement. The volume of cerebral infarction was also greater in the DHI group compared to the NDHI group (P dominant hemisphere, MCA occlusion in the dominant hemisphere caused greater impairment in neurological functions. The proposed rodent model is reliable and has high levels of reproducibility. Therefore, his model can be reliably for investigating the mechanism of focal cerebral ischemia in the dominant hemisphere of human brains.

  14. Experimental model of heterotopic ossification in Wistar rats

    Energy Technology Data Exchange (ETDEWEB)

    Zotz, T.G.G. [Escola Politécnica, Programa de Pós-Graduação em Tecnologia em Saúde, Pontifícia Universidade Católica do Paraná, Curitiba, PR (Brazil); Paula, J.B. de [Médico,Doutor em Engenharia Biomédica, Curitiba, PR (Brazil); Moser, A.D.L. [Escola Politécnica, Programa de Pós-Graduação em Tecnologia em Saúde, Pontifícia Universidade Católica do Paraná, Curitiba, PR (Brazil)

    2012-04-05

    Heterotopic ossification (HO) is a metaplastic biological process in which there is newly formed bone in soft tissues adjacent to large joints, resulting in joint mobility deficit. In order to determine which treatment techniques are more appropriate for such condition, experimental models of induced heterotopic bone formation have been proposed using heterologous demineralized bone matrix implants and bone morphogenetic protein and other tissues. The objective of the present experimental study was to identify a reliable protocol to induce HO in Wistar rats, based on autologous bone marrow (BM) implantation, comparing 3 different BM volumes and based on literature evidence of this HO induction model in larger laboratory animals. Twelve male Wistar albino rats weighing 350/390 g were used. The animals were anesthetized for blood sampling before HO induction in order to quantify serum alkaline phosphatase (ALP). HO was induced by BM implantation in both quadriceps muscles of these animals, experimental group (EG). Thirty-five days after the induction, another blood sample was collected for ALP determination. The results showed a weight gain in the EG and no significant difference in ALP levels when comparing the periods before and after induction. Qualitative histological analysis confirmed the occurrence of heterotopic ossification in all 12 EG rats. In conclusion, the HO induction model was effective when 0.35 mL autologous BM was applied to the quadriceps of Wistar rats.

  15. A rat model of temporomandibular joint pain with histopathologic modifications.

    Science.gov (United States)

    Nicoll, Steven B; Hee, Christopher K; Davis, Martin B; Winkelstein, Beth A

    2010-01-01

    To develop a rat model of temporomandibular joint (TMJ) pain and to characterize in it the development and temporal response of behavioral hypersensitivity as well as to evaluate if and to what extent a loading protocol is associated with histological changes in the TMJ consistent with osteoarthritic pathology. A novel rat model of TMJ pain was developed using a noninvasive, mechanical loading protocol. Rats were exposed to steady mouth-opening for 7 days (2 N force, 1 hour/day), and mechanical hyperalgesia (increased pain response) was measured during the loading period and for 14 days thereafter. Histological modifications in the joint cartilage were also evaluated. Outcomes for the mouth-opening exposure were compared to age-matched controls. Thresholds for evoking responses were compared using a ranked ANOVA with repeated measures. Increased mechanical hypersensitivity in the temporomandibular region developed during daily loading and persisted even after the termination of the loading protocol. Histologic characterization revealed thinning of the cartilaginous structures of the joint and irregular zonal cellular arrangements in the condylar cartilage of rats subjected to the daily loading protocol. The injury model presented here is the first to demonstrate mechanically-induced behavioral hypersensitivity accompanied by osteoarthritic pathology in the TMJ.

  16. A rat model of pulmonary infection after cardiac transplant.

    Science.gov (United States)

    Chen, Hao; Yu, Weiyong; Lu, Chen; Zhan, Yanxia; Cheng, Yunfeng; Mei, Yunqing

    2015-04-01

    Cardiac allograft rejection and infection are leading causes of morbidity and mortality after transplant. The lack of an animal model has hindered related research. We have developed a rat model of pulmonary infection after cardiac transplant to address this issue. Lewis rats received Wistar rat heart allografts, cardiac rejection was induced by cessation of cyclosporine injection, and pulmonary infection was induced by Pseudomonas aeruginosa intrabronchial inoculation. Development of pulmonary infection and/or heart rejection was assessed by histopathology. Histopathologic findings showed that a dose of 2 × 108 colony forming units of Pseudomonas aeruginosa intrabronchial inoculation is sufficient to cause severe pneumonia without being lethal to transplanted animals. Daily administration of 10 mg/kg of cyclosporine reliably suppressed rejection, and withdrawal for 7 days can obtain a consistent International Society for Heart and Lung Transplantation 3R rejection. The current study represents a simple and effective rat model of pulmonary infection along, or in combination, with rejection after heart transplant, which can be used for research of infection-rejection in cardiac transplant settings.

  17. Groove model of tibia‐femoral osteoarthritis in the rat

    Science.gov (United States)

    de Visser, Huub M.; Weinans, Harrie; Coeleveld, Katja; van Rijen, Mattie H. P.; Lafeber, Floris P. J. G.

    2016-01-01

    ABSTRACT Several experimental models of osteoarthritis in rats are used to study the pathophysiology of osteoarthritis. Many mechanically induced models have the limitation that permanent joint instability is induced by, for example, ligament transection or meniscal damage. This permanent instability will counteract the potential beneficial effects of therapy. The groove model of osteoarthritis uses a one‐time trigger, surgically induced cartilage damage on the femoral condyles, and has been validated for the canine tibia‐femoral compartment. The present study evaluates this model for the rat knee joint. The articular cartilage of the weight bearing surface of both femoral condyles and trochlea were damaged (grooved) without damaging the underlying subchondral bone. Severity of joint degeneration was histologically assessed, in addition to patella cartilage damage, and subchondral bone characteristics by means of (contrast‐enhanced) micro‐CT. Mild histological degeneration of the surgically untouched tibial plateau cartilage was observed in addition to damage of the femoral condyles, without clear synovial tissue inflammation. Contrast enhanced micro‐CT demonstrated proteoglycan loss of the surgically untouched patella cartilage. Besides, a more sclerotic structure of the subchondral bone was observed. The tibia‐femoral groove model in a rat results in mild knee joint degeneration, without permanent joint instability and joint inflammation. This makes the rat groove model a useful model to study the onset and progression of post‐traumatic non‐inflammatory osteoarthritis, creating a relatively sensitive model to study disease modifying osteoarthritic drugs. © 2016 The Authors. Journal of Orthopaedic Research published by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. J Orthop Res 35:496–505, 2017. PMID:27183198

  18. Neonatal domoic acid decreases in vivo binding of [11C]yohimbine to α2 adrenoceptors in adult rat brain

    DEFF Research Database (Denmark)

    Thomsen, Majken; Lillethorup, Thea Pinholt; Jakobsen, Steen

    and the forced swim test at day 50, 75 and 98, respectively. At ~120 days of age 3-4 rats per group were injected with [11C]yohimbine, an α2 adrenergic receptor antagonist, and scanned in a Mediso micro positron emission tomography (PET) scanner, to measure α2 adrenoceptor binding. The volume of distribution (VT....... Barry, D.I., et al., Grafted noradrenergic neurons suppress seizure development in kindling-induced epilepsy. Proc Natl Acad Sci U S A, 1987. 84(23): p. 8712-5. 2. Loscher, W. and S.J. Czuczwar, Comparison of drugs with different selectivity for central alpha 1-and alpha 2-adrenoceptors in animal models...

  19. Signal attenuation as a rat model of obsessive compulsive disorder.

    Science.gov (United States)

    Goltseker, Koral; Yankelevitch-Yahav, Roni; Albelda, Noa S; Joel, Daphna

    2015-01-09

    In the signal attenuation rat model of obsessive-compulsive disorder (OCD), lever-pressing for food is followed by the presentation of a compound stimulus which serves as a feedback cue. This feedback is later attenuated by repeated presentations of the stimulus without food (without the rat emitting the lever-press response). In the next stage, lever-pressing is assessed under extinction conditions (i.e., no food is delivered). At this stage rats display two types of lever-presses, those that are followed by an attempt to collect a reward, and those that are not. The latter are the measure of compulsive-like behavior in the model. A control procedure in which rats do not experience the attenuation of the feedback cue serves to distinguish between the effects of signal attenuation and of extinction. The signal attenuation model is a highly validated model of OCD and differentiates between compulsive-like behaviors and behaviors that are repetitive but not compulsive. In addition the measures collected during the procedure eliminate alternative explanations for differences between the groups being tested, and are quantitative, unbiased and unaffected by inter-experimenter variability. The major disadvantages of this model are the costly equipment, the fact that it requires some technical know-how and the fact that it is time-consuming compared to other models of OCD (11 days). The model may be used for detecting the anti- or pro-compulsive effects of pharmacological and non-pharmacological manipulations and for studying the neural substrate of compulsive behavior.

  20. Acoustic noise improves motor learning in spontaneously hypertensive rats, a rat model of attention deficit hyperactivity disorder.

    Science.gov (United States)

    Söderlund, Göran B W; Eckernäs, Daniel; Holmblad, Olof; Bergquist, Filip

    2015-03-01

    The spontaneously hypertensive (SH) rat model of ADHD displays impaired motor learning. We used this characteristic to study if the recently described acoustic noise benefit in learning in children with ADHD is also observed in the SH rat model. SH rats and a Wistar control strain were trained in skilled reach and rotarod running under either ambient noise or in 75 dBA white noise. In other animals the effect of methylphenidate (MPH) on motor learning was assessed with the same paradigms. To determine if acoustic noise influenced spontaneous motor activity, the effect of acoustic noise was also determined in the open field activity paradigm. We confirm impaired motor learning in the SH rat compared to Wistar SCA controls. Acoustic noise restored motor learning in SH rats learning the Montoya reach test and the rotarod test, but had no influence on learning in Wistar rats. Noise had no effect on open field activity in SH rats, but increased corner time in Wistar. MPH completely restored rotarod learning and performance but did not improve skilled reach in the SH rat. It is suggested that the acoustic noise benefit previously reported in children with ADHD is shared by the SH rat model of ADHD, and the effect is in the same range as that of stimulant treatment. Acoustic noise may be useful as a non-pharmacological alternative to stimulant medication in the treatment of ADHD. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  1. Azithromycin reduces inflammation in a rat model of acute conjunctivitis

    Science.gov (United States)

    Fernandez-Robredo, Patricia; Recalde, Sergio; Moreno-Orduña, Maite; García-García, Laura; Zarranz-Ventura, Javier; García-Layana, Alfredo

    2013-01-01

    Purpose Macrolide antibiotics are known to have various anti-inflammatory effects in addition to their antimicrobial activity, but the mechanisms are still unclear. The effect of azithromycin on inflammatory molecules in the lipopolysaccharide-induced rat conjunctivitis model was investigated. Methods Twenty-four Wistar rats were divided into two groups receiving topical ocular azithromycin (15 mg/g) or vehicle. In total, six doses (25 µl) were administered as one dose twice a day for three days before subconjunctival lipopolysaccharide injection (3 mg/ml). Before the rats were euthanized, mucus secretion, conjunctival and palpebral edema and redness were evaluated. Real-time polymerase chain reaction was used to determine gene expression for interleukin-6, cyclooxygenase-2, tumor necrosis factor-α, matrix metalloproteinase (MMP)-2, and MMP-9. Interleukin-6 was determined with enzyme-linked immunosorbent assay, nuclear factor-kappa B with western blot, and MMP-2 activity with gelatin zymogram. Four eyes per group were processed for histology and subsequent periodic acid-Schiff staining and CD68 for immunofluorescence. The Student t test or the Wilcoxon test for independent samples was applied (SPSS v.15.0). Results Azithromycin-treated animals showed a significant reduction in all clinical signs (pazithromycin group (p=0.063). Mucus secretion by goblet cells and the macrophage count in conjunctival tissue were also decreased in the azithromycin group (pazithromycin administration ameliorates induced inflammation effects in a rat model of acute conjunctivitis. PMID:23378729

  2. Shaofu Zhuyu Decoction Regresses Endometriotic Lesions in a Rat Model

    Directory of Open Access Journals (Sweden)

    Guanghui Zhu

    2018-01-01

    Full Text Available The current therapies for endometriosis are restricted by various side effects and treatment outcome has been less than satisfactory. Shaofu Zhuyu Decoction (SZD, a classic traditional Chinese medicinal (TCM prescription for dysmenorrhea, has been widely used in clinical practice by TCM doctors to relieve symptoms of endometriosis. The present study aimed to investigate the effects of SZD on a rat model of endometriosis. Forty-eight female Sprague-Dawley rats with regular estrous cycles went through autotransplantation operation to establish endometriosis model. Then 38 rats with successful ectopic implants were randomized into two groups: vehicle- and SZD-treated groups. The latter were administered SZD through oral gavage for 4 weeks. By the end of the treatment period, the volume of the endometriotic lesions was measured, the histopathological properties of the ectopic endometrium were evaluated, and levels of proliferating cell nuclear antigen (PCNA, CD34, and hypoxia inducible factor- (HIF- 1α in the ectopic endometrium were detected with immunohistochemistry. Furthermore, apoptosis was assessed using the terminal deoxynucleotidyl transferase (TdT deoxyuridine 5′-triphosphate (dUTP nick-end labeling (TUNEL assay. In this study, SZD significantly reduced the size of ectopic lesions in rats with endometriosis, inhibited cell proliferation, increased cell apoptosis, and reduced microvessel density and HIF-1α expression. It suggested that SZD could be an effective therapy for the treatment and prevention of endometriosis recurrence.

  3. Rat tail revascularization model for advanced microsurgery training and research.

    Science.gov (United States)

    Sakrak, Tamer; Köse, A Aydan; Karabağli, Yakup; Koçman, A Emre; Ozbayoğlu, A Ceyla; Cetįn, Cengiz

    2011-09-01

    We describe a time-saving microsurgical exercise for continuing microsurgical training and research. The rat tail replantation model was simplified by excluding bone detachment. Rats were divided into two groups: devascularization only ( N = 3) and revascularization after devascularization ( N = 7). The tail was devascularized by ligation and division of artery and veins in the first group to reveal if a collateral circulation from bone existed. The divided vessels were reanastomosed in the second group. The circulation of the rat tails was followed for 1 week. The tails showed total necrosis in the devascularization group, whereas only two of seven tails showed partial necrosis in the revascularization group. Reexploration showed thrombosis narrowing the lumen at the anastomotic site of the partially necrosed tails, most likely due to an anastomotic insufficiency. The present study revealed that total amputation is not necessary for tail devascularization. The rat tail revascularization model provides a practical tool for advanced and continuing microsurgical training and research. © Thieme Medical Publishers.

  4. Genetic analysis of inherited hydrocephalus in a rat model.

    Science.gov (United States)

    Jones, Hazel C; Yehia, Baligh; Chen, Gin-Fu; Carter, Barbara J

    2004-11-01

    Congenital hydrocephalus is a serious neurological disorder with a diverse etiology. Although there is strong evidence for genetic causes, few genes have been identified in humans. The rodent model, the H-Tx rat, has hydrocephalus with an onset in late gestation and a complex mode of inheritance. Ventricular dilatation is associated with abnormalities in the cerebral aqueduct and subcommissural organ. Quantitative trait locus (QTL) mapping was performed on DNA from the progeny of a backcross with the non-hydrocephalic Fischer F344 strain, using DNA microsatellite markers. The hydrocephalus trait was quantified by measuring the severity of the ventricular dilatation. Four chromosomes, each with a locus for hydrocephalus (Chrs 9, 10, 11, and 17), were mapped using additional markers and DNA from four subsets of backcross progeny with allelic recombination at or near each locus. The genetic positions for the markers and the loci were located using the Ensemble Rat Genome Browser. For each chromosome studied, the interval containing the locus was examined for known rat genes and for human genes identified from human-rat homology. Genes expressed in brain and with a function associated with known causes of hydrocephalus were identified as possible candidate genes. Future studies to characterize the causative genes in this animal model will improve the understanding of genetic causes in humans.

  5. Experimental model of distraction osteogenesis in edentulous rats

    Directory of Open Access Journals (Sweden)

    Maria Montserrat Pujadas Bigi

    2011-06-01

    Full Text Available Distraction osteogenesis (DO is a surgical technique producing bone lengthening by distraction of the fracture callus. Although a large number of experimental studies on the events associated with DO of craniofacial skeleton have been reported, the few employing rat mandibular bone DO used complicated designs and produced a small volume of newly formed bone. Thus, this study aims to present an original experimental model of mandibular DO in edentulous rats that produces a sufficient quantity and quality of intramembranous bone. Eight male Wistar rats, weighing 75 g, underwent extraction of lower molars. With rats weighing 350 g, right mandibular osteotomy was performed and the distraction device was placed. The distraction device was custom made using micro-implants, expansion screws, and acrylic resin. Study protocol: latency: 6 days, distraction: ¼ turn (0.175 mm once a day during 6 d, consolidation: 28 d after distraction phase, sacrifice. DO-treated and contralateral hemimandibles were dissected and compared macroscopically and using radiographic studies. Histological sections were obtained and stained with H&E. A distraction gap filled with newly formed and mature bone tissue was obtained. This model of mandibular DO proved useful to obtain adequate quantity and quality of bone to study bone regeneration.

  6. Characterization of a frozen shoulder model using immobilization in rats.

    Science.gov (United States)

    Kim, Du Hwan; Lee, Kil-Ho; Lho, Yun-Mee; Ha, Eunyoung; Hwang, Ilseon; Song, Kwang-Soon; Cho, Chul-Hyun

    2016-12-08

    The objective of this study was to investigate serial changes for histology of joint capsule and range of motion of the glenohumeral joint after immobilization in rats. We hypothesized that a rat shoulder contracture model using immobilization would be capable of producing effects on the glenohumeral joint similar to those seen in patients with frozen shoulder. Sixty-four Sprague-Dawley rats were randomly divided into one control group (n = 8) and seven immobilization groups (n = 8 per group) that were immobilized with molding plaster for 3 days, or for 1, 2, 3, 4, 5, or 6 weeks. At each time point, eight rats were euthanized for histologic evaluation of the axillary recess and for measurement of the abduction angle. Infiltration of inflammatory cells was found in the synovial tissue until 2 weeks after immobilization. However, inflammatory cells were diminished and fibrosis was dominantly observed in the synovium and subsynovial tissue 3 weeks after immobilization. From 1 week after immobilization, the abduction angle of all immobilization groups at each time point was significantly lower than that of the control group. Our study demonstrated that a rat frozen shoulder model using immobilization generates the pathophysiologic process of inflammation leading to fibrosis on the glenohumeral joint similar to that seen in patients with frozen shoulder. This model was attained within 3 weeks after immobilization. It may serve as a useful tool to investigate pathogenesis at the molecular level and identify potential target genes that are involved in the development of frozen shoulder.

  7. Ranking candidate genes in rat models of type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Ståhl Fredrik

    2009-07-01

    Full Text Available Abstract Background Rat models are frequently used to find genomic regions that contribute to complex diseases, so called quantitative trait loci (QTLs. In general, the genomic regions found to be associated with a quantitative trait are rather large, covering hundreds of genes. To help selecting appropriate candidate genes from QTLs associated with type 2 diabetes models in rat, we have developed a web tool called Candidate Gene Capture (CGC, specifically adopted for this disorder. Methods CGC combines diabetes-related genomic regions in rat with rat/human homology data, textual descriptions of gene effects and an array of 789 keywords. Each keyword is assigned values that reflect its co-occurrence with 24 different reference terms describing sub-phenotypes of type 2 diabetes (for example "insulin resistance". The genes are then ranked based on the occurrences of keywords in the describing texts. Results CGC includes QTLs from type 2 diabetes models in rat. When comparing gene rankings from CGC based on one sub-phenotype, with manual gene ratings for four QTLs, very similar results were obtained. In total, 24 different sub-phenotypes are available as reference terms in the application and based on differences in gene ranking, they fall into separate clusters. Conclusion The very good agreement between the CGC gene ranking and the manual rating confirms that CGC is as a reliable tool for interpreting textual information. This, together with the possibility to select many different sub-phenotypes, makes CGC a versatile tool for finding candidate genes. CGC is publicly available at http://ratmap.org/CGC.

  8. Combating Combination of Hypertension and Diabetes in Different Rat Models

    Directory of Open Access Journals (Sweden)

    Talma Rosenthal

    2010-03-01

    Full Text Available Rat experimental models are used extensively for studying physiological mechanisms and treatments of hypertension and diabetes co-existence. Each one of these conditions is a major risk factor for cardiovascular disease (CVD, and the combination of the two conditions is a potent enhancer of CVD. Five major animal models that advanced our understanding of the mechanisms and therapeutic approaches in humans are discussed in this review: Zucker, Goto-Kakizaki, SHROB, SHR/NDmcr-cp and Cohen Rosenthal diabetic hypertensive (CRDH rats. The use of various drugs, such as angiotensin-converting enzyme (ACE inhibitors (ACEIs, various angiotensin receptor blockers (ARBs, and calcium channel blockers (CCBs, to combat the effects of concomitant pathologies on the combination of diabetes and hypertension, as well as the non-pharmacological approach are reviewed in detail for each rat model. Results from experiments on these models indicate that classical factors contributing to the pathology of hypertension and diabetes combination—Including hypertension, hyperglycemia, hyperinsulinemia and hyperlipidemia—can now be treated, although these treatments do not completely prevent renal complications. Animal studies have focused on several mechanisms involved in hypertension/diabetes that remain to be translated into clinical medicine, including hypoxia, oxidative stress, and advanced glycation. Several target molecules have been identified that need to be incorporated into a treatment modality. The challenge continues to be the identification and interpretation of the clinical evidence from the animal models and their application to human treatment.

  9. Particulate matter inhalation exacerbates cardiopulmonary injury in a rat model of isoproterenol-induced cardiomyopathy

    Science.gov (United States)

    Ambient particulate matter (PM) exposure is linked to cardiovascular events and death, especially among individuals with heart disease. A model of toxic cardiomyopathy was developed in Spontaneously Hypertensive Heart Failure (SHHF) rats to explore potential mechanisms. Rats were...

  10. [Effect of electroacupuncture on epileptic EEG and intracellular Ca2+ content in the hippocampus in epilepsy rats].

    Science.gov (United States)

    Yang, Fan; Xu, Guo-long; Yang, Yong-qing; Shen, De-kai; Feng, Pin-zhi; Wang, Pin; Liu, Xiang-guo

    2009-06-01

    To study the underlying mechanism of electroacupuncture (EA) in relieving epilepsy in pentylenetetrazole (PTZ)-induced epilepsy rats. Twenty SD rats were randomly divided into normal control, model, EA, Nimodipine groups, with 5 cases in each. Epilepsy model was established by intraperitoneal injection of PTZ (32.0 mg/kg), once daily for 28 days. EA (100 Hz, 0.6 mA) was applied to "Baihui" (GV 20) and "Dazhui" (GV 14), once daily for 7 days. For Nimodipine group, the rats were given with nimodipine (0.25 mg/kg, i.p.), once daily for 7 days. Electroencephalogram (EEG) was recorded and the fluorescence intensity of Ca2+ of the hippocampus tissue sections was detected by laser scanning confocal microscope (LSCM) after incubation in artificial cerebrospinal fluid containing Flou-3/AM (10 micromol/L) and pluronic F-127 (5 microl). Compared with model group, the latencies of epileptic EEG seizure prolonged obviously (P 0.05). EA has an obvious anti-epileptic effect, which may be closely related to its effect in downregulating the increased hippocampal Ca2+ level in PTZ-kindled epilepsy rats.

  11. Evaluation of two experimental models of hepatic encephalopathy in rats

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    L.M. García-Moreno

    2005-01-01

    Full Text Available The serious neuropsychological repercussions of hepatic encephalopathy have led to the creation of several experimental models in order to better understand the pathogenesis of the disease. In the present investigation, two possible causes of hepatic encephalopathy, cholestasis and portal hypertension, were chosen to study the behavioral impairments caused by the disease using an object recognition task. This working memory test is based on a paradigm of spontaneous delayed non-matching to sample and was performed 60 days after surgery. Male Wistar rats (225-250 g were divided into three groups: two experimental groups, microsurgical cholestasis (N = 20 and extrahepatic portal hypertension (N = 20, and a control group (N = 20. A mild alteration of the recognition memory occurred in rats with cholestasis compared to control rats and portal hypertensive rats. The latter group showed the poorest performance on the basis of the behavioral indexes tested. In particular, only the control group spent significantly more time exploring novel objects compared to familiar ones (P < 0.001. In addition, the portal hypertension group spent the shortest time exploring both the novel and familiar objects (P < 0.001. These results suggest that the existence of portosystemic collateral circulation per se may be responsible for subclinical encephalopathy.

  12. Effect of ozone on colon anastomoses in rat peritonitis model.

    Science.gov (United States)

    Çakır, Tuğrul; Aslaner, Arif; Tekeli, Seçkin Özgür; Avcı, Sema; Doğan, Uğur; Tekeli, Feyza; Soylu, Hakan; Akyüz, Cebrail; Koç, Süleyman; Üstünel, İsmail; Yılmaz, Necat

    2016-02-01

    To investigate the effects of medical ozone theraphy on the colon anastomosis of peritonitis model in rats. Eighteen rats were randomly assigned into three equal groups; control, cecal punctuation and colon anastomosis and ozone theraphy. Sepsis was performed with a cecal punctuation in groups 2 and 3. The medical ozone theraphy was administered intraperitonealy for three weeks in group 3 while the other rats received saline injection. At the twenty second day serum were obtained for TNF-α and IL-1β, the colonic burst pressures were measured and colonic tissue samples were obtained for MDA and MPO levels. Histolopatological examination was evaluated with H&E stain, and Ki-67, IL-1β and the VEGF immunostaining densities were also compared. Intraperitoneal ozone administration reversed TNF-α, IL-1β, MDA and MPO levels and the colonic burst pressures. There was also a significant difference at immunostaining densities of histopathological examination. Medical ozone therapy may contribute to tissue healing by affecting the proliferation and the vascularization thus has benefits on colonic anastomosis at peritonitis in rats.

  13. Genetics of hypertensive organ-damage in consomic rat models

    OpenAIRE

    Wendt, Norbert

    2010-01-01

    The clinical importance of hypertension is due to its high prevalence and the resulting hypertensive organ-damage (HOD). Especially salt-sensitive patients tend to develope increased levels of HOD. Aim of this thesis was to investigate the genetic basis of HOD in salt-sensitive hypertension. The salt-sensitive Dahl-rat (SS) was considered a suitable animal-model, which besides severe HOD like left-ventricular hypertrophy with fibrosis-deposition, also developes hypercholesteremia. By expe...

  14. Capsular Contracture In Silicone Breast Implants: Insights From Rat Models

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    VILBERTO J. VIEIRA

    Full Text Available ABSTRACT Breast augmentation with silicone implants is one of the most common procedures performed by plastic surgeons around the world. Capsular contracture is a frequent complication in breast augmentation and reconstructive surgery, that requires invasive intervention. The inflammatory response to implanted mammary prostheses appears to be directly associated to capsular contracture. This review discusses the evidences from rat models studies, on the role of inflammation and fibrosis in capsular contraction and its relation to silicone breast implants surface.

  15. Interaction between Thalamus and Hippocampus in Termination of Amygdala-Kindled Seizures in Mice

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    Zhen Zhang

    2016-01-01

    Full Text Available The thalamus and hippocampus have been found both involved in the initiation, propagation, and termination of temporal lobe epilepsy. However, the interaction of these regions during seizures is not clear. The present study is to explore whether some regular patterns exist in their interaction during the termination of seizures. Multichannel in vivo recording techniques were used to record the neural activities from the cornu ammonis 1 (CA1 of hippocampus and mediodorsal thalamus (MDT in mice. The mice were kindled by electrically stimulating basolateral amygdala neurons, and Racine’s rank standard was employed to classify the stage of behavioral responses (stage 1~5. The coupling index and directionality index were used to investigate the synchronization and information flow direction between CA1 and MDT. Two main results were found in this study. (1 High levels of synchronization between the thalamus and hippocampus were observed before the termination of seizures at stage 4~5 but after the termination of seizures at stage 1~2. (2 In the end of seizures at stage 4~5, the information tended to flow from MDT to CA1. Those results indicate that the synchronization and information flow direction between the thalamus and the hippocampus may participate in the termination of seizures.

  16. An improved experimental model for peripheral neuropathy in rats

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    Q.M. Dias

    Full Text Available A modification of the Bennett and Xie chronic constriction injury model of peripheral painful neuropathy was developed in rats. Under tribromoethanol anesthesia, a single ligature with 100% cotton glace thread was placed around the right sciatic nerve proximal to its trifurcation. The change in the hind paw reflex threshold after mechanical stimulation observed with this modified model was compared to the change in threshold observed in rats subjected to the Bennett and Xie or the Kim and Chung spinal ligation models. The mechanical threshold was measured with an automated electronic von Frey apparatus 0, 2, 7, and 14 days after surgery, and this threshold was compared to that measured in sham rats. All injury models produced significant hyperalgesia in the operated hind limb. The modified model produced mean ± SD thresholds in g (19.98 ± 3.08, 14.98 ± 1.86, and 13.80 ± 1.00 at 2, 7, and 14 days after surgery, respectively similar to those obtained with the spinal ligation model (20.03 ± 1.99, 13.46 ± 2.55, and 12.46 ± 2.38 at 2, 7, and 14 days after surgery, respectively, but less variable when compared to the Bennett and Xie model (21.20 ± 8.06, 18.61 ± 7.69, and 18.76 ± 6.46 at 2, 7, and 14 days after surgery, respectively. The modified method required less surgical skill than the spinal nerve ligation model.

  17. An improved experimental model for peripheral neuropathy in rats

    Energy Technology Data Exchange (ETDEWEB)

    Dias, Q.M.; Rossaneis, A.C.; Fais, R.S.; Prado, W.A. [Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2013-03-15

    A modification of the Bennett and Xie chronic constriction injury model of peripheral painful neuropathy was developed in rats. Under tribromoethanol anesthesia, a single ligature with 100% cotton glace thread was placed around the right sciatic nerve proximal to its trifurcation. The change in the hind paw reflex threshold after mechanical stimulation observed with this modified model was compared to the change in threshold observed in rats subjected to the Bennett and Xie or the Kim and Chung spinal ligation models. The mechanical threshold was measured with an automated electronic von Frey apparatus 0, 2, 7, and 14 days after surgery, and this threshold was compared to that measured in sham rats. All injury models produced significant hyperalgesia in the operated hind limb. The modified model produced mean ± SD thresholds in g (19.98 ± 3.08, 14.98 ± 1.86, and 13.80 ± 1.00 at 2, 7, and 14 days after surgery, respectively) similar to those obtained with the spinal ligation model (20.03 ± 1.99, 13.46 ± 2.55, and 12.46 ± 2.38 at 2, 7, and 14 days after surgery, respectively), but less variable when compared to the Bennett and Xie model (21.20 ± 8.06, 18.61 ± 7.69, and 18.76 ± 6.46 at 2, 7, and 14 days after surgery, respectively). The modified method required less surgical skill than the spinal nerve ligation model.

  18. Closed-loop seizure control on epileptic rat models

    Science.gov (United States)

    Liang, Sheng-Fu; Liao, Yi-Cheng; Shaw, Fu-Zen; Chang, Da-Wei; Young, Chung-Ping; Chiueh, Herming

    2011-08-01

    In this paper numerous alternative treatments in addition to pharmacological therapy are proposed for their use in epileptic patients. Epileptic animal models can play a crucial role in the performance evaluation of new therapeutic techniques. The objective of this research is to first develop various epileptic rat models; second, develop a portable wireless closed-loop seizure controller including on-line seizure detection and real-time electrical stimulation for seizure elimination; and third, apply the developed seizure controller to the animal models to perform on-line seizure elimination. The closed-loop seizure controller was applied to three Long-Evans rats with spontaneous spike-wave discharges (non-convulsive) and three Long-Evans rats with epileptiform activities induced by pentylenetetrazol (PTZ) injection (convulsive) for evaluation. The seizure detection accuracy is greater than 92% (up to 99%), and averaged seizure detection latency is less than 0.6 s for both spontaneous non-convulsive and PTZ-induced convulsive seizures. The average false stimulation rate is 3.1%. Near 30% of PTZ-induced convulsive seizures need more than two times of 0.5 s electrical stimulation for suppression and 90% of the non-convulsive seizures can be suppressed by only one 0.5 s electrical stimulation.

  19. The Fischer 344 rat as a model of presbycusis.

    Science.gov (United States)

    Syka, Josef

    2010-06-01

    Due to the rising number of the aged human population all over the world, presbycusis is a phenomenon that deserves the increasing attention of the medical community as regards to prevention and treatment. This requires finding appropriate animal models for human presbycusis that will be useful in future experiments. Among the available rat strains, the Fischer 344 (F344) strain promises to serve as a model producing prompt and profound presbycusis. Hearing thresholds begin to increase in this strain during the first year of life; toward the end of the second year, the thresholds are very high. The threshold shifts progress independently in both ears. The rapid deterioration of distortion product otoacoustic emissions, with the majority of outer hair cells (OHC) being present and morphologically intact, is apparently produced by the disruption of prestin. The age-related changes within inner ear function are accompanied by deterioration of acoustical signal processing within central auditory system, mainly due to impaired GABA inhibition. The loss of GABA inhibition in old animals is expressed primarily in the inferior colliculus but is also present in the cochlear nuclei and the auditory cortex. Sound-evoked behavioral reactions are also impaired in old F344 rats. Taken together, the described characteristics of the aging F344 rat auditory system supports the idea that this strain may serve as a suitable model for studying the mechanisms of presbycusis, its prevention and treatment. Copyright 2009 Elsevier B.V. All rights reserved.

  20. Reversal of P-glycoprotein overexpression by Ginkgo biloba extract in the brains of pentylenetetrazole-kindled and phenytoin-treated mice

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    Ce Zhang

    2015-08-01

    Full Text Available The purpose of this study was to investigate the combined effects of Ginkgo biloba extract and phenytoin (PHT sodium as a dose regimen simulating the clinical treatment of patients with epilepsy, on P-glycoprotein (P-GP overexpression in a pentylenetetrazole-kindled mouse model of epilepsy. Epilepsy was induced by intraperitoneal administration of pentylenetetrazole (40 mg/kg for 7 days followed by intragastric administration of PHT (40 mg/kg for 14 days. Thirty mice that developed seizures were randomly divided into three groups and administered PHT as well as the following treatments: saline (negative control; verapamil (20 mg/kg, positive control; and G. biloba (30 mg/kg. Seizure severity was recorded 30 minutes after treatment on Day 4 of drug administration, after which the mice were euthanized, and their brains isolated. Western blots and immunohistochemistry were performed to analyze the expression of P-GP and caspase-3, respectively, in the brain tissue. High-performance liquid chromatography was used to measure the concentrations of PHT in the brains of the treated mice. After 4 consecutive days of treatment, the seizure severity in the mice in the G. biloba extract group was more significantly reduced than the seizure severity in the saline control group, and a significant difference was observed between the G. biloba extract and verapamil control groups (p < 0.05. P-GP expression in the brain more significantly decreased in the mice treated with G. biloba extract and verapamil than it did in the saline-treated control group (p < 0.05. Compared with the saline-treated control group, the mice treated with G. biloba extract and verapamil showed significantly increased brain PHT concentrations (p < 0.05. Furthermore, caspase-3 expression in the brain tissue of the G. biloba extract group was significantly lower than that in the vehicle control group (p < 0.05; this finding demonstrated the neuroprotective effects of G. biloba

  1. A rat model for embolic encephalitis

    DEFF Research Database (Denmark)

    Astrup, Lærke Boye; Agerholm, Jørgen Steen; Aalbæk, Bent

    2011-01-01

    gain access to the brain by the circulation and, no foreign materials other than bacteria are implated in the brain. This ensures high face-validity and high construct-validity of the model for three reasons: 1) Cerebral infarction by thrombosis or disseminated intravascular coagulation is a key...

  2. Effects of JIP3 on epileptic seizures: Evidence from temporal lobe epilepsy patients, kainic-induced acute seizures and pentylenetetrazole-induced kindled seizures.

    Science.gov (United States)

    Wang, Z; Chen, Y; Lü, Y; Chen, X; Cheng, L; Mi, X; Xu, X; Deng, W; Zhang, Y; Wang, N; Li, J; Li, Y; Wang, X

    2015-08-06

    JNK-interacting protein 3 (JIP3), also known as JNK stress-activated protein kinase-associated protein 1 (JSAP1), is a scaffold protein mainly involved in the regulation of the pro-apoptotic signaling cascade mediated by c-Jun N-terminal kinase (JNK). Overexpression of JIP3 in neurons in vitro has been reported to lead to accelerated activation of JNK and enhanced apoptosis response to cellular stress. However, the occurrence and the functional significance of stress-induced modulations of JIP3 levels in vivo remain elusive. In this study, we investigated the expression of JIP3 in temporal lobe epilepsy (TLE) and in a kainic acid (KA)-induced mouse model of epileptic seizures, and determined whether down-regulation of JIP3 can decrease susceptibility to seizures and neuron damage induced by KA. We found that JIP3 was markedly increased in TLE patients and a mouse model of epileptic seizures; mice underexpressing JIP3 through lentivirus bearing LV-Letm1-RNAi showed decreased susceptibility, delayed first seizure and decreased seizure duration response to the epileptogenic properties of KA. Subsequently, a decreased activation of JNK following seizure induction was observed in mice underexpressing JIP3, which also exhibited less neuronal apoptosis in the CA3 region of the hippocampus, as assessed three days after KA administration. We also found that mice underexpressing JIP3 exhibited a delayed pentylenetetrazole (PTZ)-induced kindling seizure process. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  3. A rat model for embolic encephalitis

    DEFF Research Database (Denmark)

    Astrup, Lærke Boye; Rasmussen, Rune Skovgaard; Aalbæk, Bent

    2011-01-01

    have recently shown that sepsis is a common cause of microabscesses in the brain, and that S. aureus is one of the most common organisms isolated from these abscesses. This raises the question whether the blood-brain barrier truly makes the brain an immune-privileged organ or not. This makes the brain...... a most interesting organ in sepsis patients. However, symptoms of brain infection may be confused with systemic responses and gross neuropathologic lesions may be absent. Brain infection in sepsis patients is therefore prone to misclassification or diagnostic delay, and when the diagnosis is made...... coagulation is a key mechanism involved in neurologic complications to human bacteriaemia. 2: Human brain abscesses are primarily located in the same anatomical area that we target in our model. Our model therefore offers a tool for several scientific areas within research of brain infection and inflammation....

  4. Achilles tendinosis: a morphometrical study in a rat model.

    Science.gov (United States)

    Silva, Rafael Duarte; Glazebrook, Mark Anthony; Campos, Vinicius Castro; Vasconcelos, Anilton Cesar

    2011-01-01

    This study addresses the morphopathogenesis of Achilles tendinosis, using a rat model and presenting quantitative analysis of time-dependent histological changes. Thirty Wistar rats were used, randomly split in experimental and control groups. Animals of the experimental group were submitted to a treadmill running scheme. Five animals of each group were euthanized at four, eight and sixteen weeks. Achilles tendons were collected and processed routinely for histopath sections. Slides were stained by Hematoxylin-Eosin, Picrosirius Red, Alcian Blue, AgNOR, TUNEL and evaluated morphometrically. Cellular density decreased slightly along the time and was higher in the experimental group than in controls at fourth, eighth and sixteenth weeks. Fiber microtearing, percentual of reticular fibers and glycosaminoglycans content increased along the time and were higher in experimental group than in controls at all-time intervals. AgNOR labeling here interpreted as a marker of transcription activity was higher in the experimental groups than in controls at all-time intervals. Apoptotic cells were more frequent and diffusely distributed in tendinosis samples than in control groups. These results suggest that as mechanical overload is becoming chronic, cellular turnover and matrix deposition increases leading to tendinosis. The combination of staining techniques and morphometry used here to describe the evolution of lesions occurring in a rat model system has proved to be suited for the study of induced Achilles tendinosis.

  5. Respiratory deficits in a rat model of Parkinson's disease.

    Science.gov (United States)

    Tuppy, M; Barna, B F; Alves-Dos-Santos, L; Britto, L R G; Chiavegatto, S; Moreira, T S; Takakura, A C

    2015-06-25

    Parkinson's disease (PD) is a neurodegenerative disease characterized by loss of the dopaminergic nigrostriatal pathway. In addition to deficits in voluntary movement, PD involves a disturbance of breathing regulation. However, the cause and nature of this disturbance are not well understood. Here, we investigated breathing at rest and in response to hypercapnia (7% CO2) or hypoxia (8% O2), as well as neuroanatomical changes in brainstem regions essential for breathing, in a 6-hydroxydopamine (6-OHDA) rat model of PD. Bilateral injections of 6-OHDA (24μg/μl) into the striatum decreased tyrosine hydroxylase (TH(+))-neurons in the substantia nigra pars compacta (SNpc), transcription factor phox2b-expressing neurons in the retrotrapezoid nucleus and neurokinin-1 receptors in the ventral respiratory column. In 6-OHDA-lesioned rats, respiratory rate was reduced at rest, leading to a reduction in minute ventilation. These animals also showed a reduction in the tachypneic response to hypercapnia, but not to hypoxia challenge. These results suggest that the degeneration of TH(+) neurons in the SNpc leads to impairment of breathing at rest and in hypercapnic conditions. Our data indicate that respiratory deficits in a 6-OHDA rat model of PD are related to downregulation of neural systems involved in respiratory rhythm generation. The present study suggests a new avenue to better understand the respiratory deficits observed in chronic stages of PD. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  6. A rat model for muscle regeneration in the soft palate.

    Directory of Open Access Journals (Sweden)

    Paola L Carvajal Monroy

    Full Text Available BACKGROUND: Children with a cleft in the soft palate have difficulties with speech, swallowing, and sucking. Despite successful surgical repositioning of the muscles, optimal function is often not achieved. Scar formation and defective regeneration may hamper the functional recovery of the muscles after cleft palate repair. Therefore, the aim of this study is to investigate the anatomy and histology of the soft palate in rats, and to establish an in vivo model for muscle regeneration after surgical injury. METHODS: Fourteen adult male Sprague Dawley rats were divided into four groups. Groups 1 (n = 4 and 2 (n = 2 were used to investigate the anatomy and histology of the soft palate, respectively. Group 3 (n = 6 was used for surgical wounding of the soft palate, and group 4 (n = 2 was used as unwounded control group. The wounds (1 mm were evaluated by (immunohistochemistry (AZAN staining, Pax7, MyoD, MyoG, MyHC, and ASMA after 7 days. RESULTS: The present study shows that the anatomy and histology of the soft palate muscles of the rat is largely comparable with that in humans. All wounds showed clinical evidence of healing after 7 days. AZAN staining demonstrated extensive collagen deposition in the wound area, and initial regeneration of muscle fibers and salivary glands. Proliferating and differentiating satellite cells were identified in the wound area by antibody staining. CONCLUSIONS: This model is the first, suitable for studying muscle regeneration in the rat soft palate, and allows the development of novel adjuvant strategies to promote muscle regeneration after cleft palate surgery.

  7. Experience modulates vicarious freezing in rats: a model for empathy.

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    Piray Atsak

    Full Text Available The study of the neural basis of emotional empathy has received a surge of interest in recent years but mostly employing human neuroimaging. A simpler animal model would pave the way for systematic single cell recordings and invasive manipulations of the brain regions implicated in empathy. Recent evidence has been put forward for the existence of empathy in rodents. In this study, we describe a potential model of empathy in female rats, in which we studied interactions between two rats: a witness observes a demonstrator experiencing a series of footshocks. By comparing the reaction of witnesses with or without previous footshock experience, we examine the role of prior experience as a modulator of empathy. We show that witnesses having previously experienced footshocks, but not naïve ones, display vicarious freezing behavior upon witnessing a cage-mate experiencing footshocks. Strikingly, the demonstrator's behavior was in turn modulated by the behavior of the witness: demonstrators froze more following footshocks if their witness froze more. Previous experiments have shown that rats emit ultrasonic vocalizations (USVs when receiving footshocks. Thus, the role of USV in triggering vicarious freezing in our paradigm is examined. We found that experienced witness-demonstrator pairs emitted more USVs than naïve witness-demonstrator pairs, but the number of USVs was correlated with freezing in demonstrators, not in witnesses. Furthermore, playing back the USVs, recorded from witness-demonstrator pairs during the empathy test, did not induce vicarious freezing behavior in experienced witnesses. Thus, our findings confirm that vicarious freezing can be triggered in rats, and moreover it can be modulated by prior experience. Additionally, our result suggests that vicarious freezing is not triggered by USVs per se and it influences back onto the behavior of the demonstrator that had elicited the vicarious freezing in witnesses, introducing a paradigm

  8. Experience Modulates Vicarious Freezing in Rats: A Model for Empathy

    Science.gov (United States)

    Atsak, Piray; Orre, Marie; Bakker, Petra; Cerliani, Leonardo; Roozendaal, Benno

    2011-01-01

    The study of the neural basis of emotional empathy has received a surge of interest in recent years but mostly employing human neuroimaging. A simpler animal model would pave the way for systematic single cell recordings and invasive manipulations of the brain regions implicated in empathy. Recent evidence has been put forward for the existence of empathy in rodents. In this study, we describe a potential model of empathy in female rats, in which we studied interactions between two rats: a witness observes a demonstrator experiencing a series of footshocks. By comparing the reaction of witnesses with or without previous footshock experience, we examine the role of prior experience as a modulator of empathy. We show that witnesses having previously experienced footshocks, but not naïve ones, display vicarious freezing behavior upon witnessing a cage-mate experiencing footshocks. Strikingly, the demonstrator's behavior was in turn modulated by the behavior of the witness: demonstrators froze more following footshocks if their witness froze more. Previous experiments have shown that rats emit ultrasonic vocalizations (USVs) when receiving footshocks. Thus, the role of USV in triggering vicarious freezing in our paradigm is examined. We found that experienced witness-demonstrator pairs emitted more USVs than naïve witness-demonstrator pairs, but the number of USVs was correlated with freezing in demonstrators, not in witnesses. Furthermore, playing back the USVs, recorded from witness-demonstrator pairs during the empathy test, did not induce vicarious freezing behavior in experienced witnesses. Thus, our findings confirm that vicarious freezing can be triggered in rats, and moreover it can be modulated by prior experience. Additionally, our result suggests that vicarious freezing is not triggered by USVs per se and it influences back onto the behavior of the demonstrator that had elicited the vicarious freezing in witnesses, introducing a paradigm to study empathy

  9. Newly Developed Rat Model of Chronic Kidney Disease-Mineral Bone Disorder.

    Science.gov (United States)

    Watanabe, Kentaro; Fujii, Hideki; Goto, Shunsuke; Nakai, Kentaro; Kono, Keiji; Watanabe, Shuhei; Shinohara, Masami; Nishi, Shinichi

    2018-02-01

    Chronic kidney disease-mineral bone disorder (CKD-MBD) is associated with all-cause and cardiovascular morbidity and mortality in patients with CKD. Thus, elucidating its pathophysiological mechanisms is essential for improving the prognosis. We evaluated characteristics of CKD-MBD in a newly developed CKD rat model. We used male Sprague-Dawley (SD) rats and spontaneously diabetic Torii (SDT) rats, which are used as models for nonobese type 2 diabetes. CKD was induced by 5/6 nephrectomy (Nx). At 10 weeks, the rats were classified into six groups and administered with a vehicle or a low- or high-dose paricalcitol thrice a week. At 20 weeks, the rats were sacrificed; blood and urinary biochemical analyses and histological analysis of the aorta were performed. At 20 weeks, hemoglobin A1c (HbA1c) levels, blood pressure, and renal function were not significantly different among the six groups. Serum calcium and phosphate levels tended to be higher in SDT-Nx rats than in SD-Nx rats. The urinary excretion of calcium and phosphate was significantly greater in SDT-Nx rats than in SD-Nx rats. After administering paricalcitol, serum parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) levels were significantly higher in SDT-Nx rats than in SD-Nx rats. The degree of aortic calcification was significantly more severe and the aortic calcium content was significantly greater in SDT-Nx rats than in SD-Nx rats. We suggest that our new CKD rat model using SDT rats represents a useful CKD-MBD model, and this model was greatly influenced by paricalcitol administration. Further studies are needed to clarify the detailed mechanisms underlying this model.

  10. Studies on sensitivity of zebrafish as a model organism for Parkinson's disease: Comparison with rat model

    Science.gov (United States)

    Makhija, Dinesh T.; Jagtap, Aarti G.

    2014-01-01

    Objective: To determine the utility of zebra fish as an animal model for Parkinson's disease (PD) in comparison with rat model. Materials and Methods: MTT assay was performed on rat and zebrafish brain synaptosomal fractions using rotenone as a neurotoxic agent. Quercetin and resveratrol were used as standards to compare anti-apoptotic activity in both organisms. Catalepsy was induced in zebrafish by exposing them to haloperidol (9 μM) solution. Drug-treated groups were exposed to bromocriptine and pramipexole, 30 min prior to haloperidol exposure at the dose of 2, 5, and 10 μg/mL. Swimming speed, time spent in the bottom of the tank, and complete cataleptic time were evaluated to assess behavioral changes. In rats, catalepsy was induced using haloperidol (1.25 mg/kg i.p.). Drug-treated groups received bromocriptine (2.5 mg/kg.) and pramipexole (1 mg/kg) orally. Bar test, block test, and locomotor activity were carried out to assess behavioral changes. Results: Resveratrol and quercetin showed comparable inhibition of apoptosis in rats and zebrafish. In anti-cataleptic study, bromocriptine and pramipexole-treated groups showed significant difference (P behavioral parameters as compared to haloperidol control group in both the experimental organisms. Results obtained from fish model were in correlation with rat model. Conclusion: Findings of the present study revealed that zebrafish model is highly sensitive and can be used for basic screening of drugs against PD. PMID:24554909

  11. The utility of Apc-mutant rats in modeling human colon cancer

    Directory of Open Access Journals (Sweden)

    Amy A. Irving

    2014-11-01

    Full Text Available Prior to the advent of genetic engineering in the mouse, the rat was the model of choice for investigating the etiology of cancer. Now, recent advances in the manipulation of the rat genome, combined with a growing recognition of the physiological differences between mice and rats, have reignited interest in the rat as a model of human cancer. Two recently developed rat models, the polyposis in the rat colon (Pirc and Kyoto Apc Delta (KAD strains, each carry mutations in the intestinal-cancer-associated adenomatous polyposis coli (Apc gene. In contrast to mouse models carrying Apc mutations, in which cancers develop mainly in the small intestine rather than in the colon and there is no gender bias, these rat models exhibit colonic predisposition and gender-specific susceptibility, as seen in human colon cancer. The rat also provides other experimental resources as a model organism that are not provided by the mouse: the structure of its chromosomes facilitates the analysis of genomic events, the size of its colon permits longitudinal analysis of tumor growth, and the size of biological samples from the animal facilitates multiplexed molecular analyses of the tumor and its host. Thus, the underlying biology and experimental resources of these rat models provide important avenues for investigation. We anticipate that advances in disease modeling in the rat will synergize with resources that are being developed in the mouse to provide a deeper understanding of human colon cancer.

  12. The utility of Apc-mutant rats in modeling human colon cancer

    Science.gov (United States)

    Irving, Amy A.; Yoshimi, Kazuto; Hart, Marcia L.; Parker, Taybor; Clipson, Linda; Ford, Madeline R.; Kuramoto, Takashi; Dove, William F.; Amos-Landgraf, James M.

    2014-01-01

    Prior to the advent of genetic engineering in the mouse, the rat was the model of choice for investigating the etiology of cancer. Now, recent advances in the manipulation of the rat genome, combined with a growing recognition of the physiological differences between mice and rats, have reignited interest in the rat as a model of human cancer. Two recently developed rat models, the polyposis in the rat colon (Pirc) and Kyoto Apc Delta (KAD) strains, each carry mutations in the intestinal-cancer-associated adenomatous polyposis coli (Apc) gene. In contrast to mouse models carrying Apc mutations, in which cancers develop mainly in the small intestine rather than in the colon and there is no gender bias, these rat models exhibit colonic predisposition and gender-specific susceptibility, as seen in human colon cancer. The rat also provides other experimental resources as a model organism that are not provided by the mouse: the structure of its chromosomes facilitates the analysis of genomic events, the size of its colon permits longitudinal analysis of tumor growth, and the size of biological samples from the animal facilitates multiplexed molecular analyses of the tumor and its host. Thus, the underlying biology and experimental resources of these rat models provide important avenues for investigation. We anticipate that advances in disease modeling in the rat will synergize with resources that are being developed in the mouse to provide a deeper understanding of human colon cancer. PMID:25288683

  13. Effects of conventional anticonvulsant drugs on generalized tonic-clonic seizures in Noda epileptic rats.

    Science.gov (United States)

    Inoue, Maki; Yamamoto, Ayaka; Kaneko, Yuka; Noda, Atsushi; Naito, Hiroyuki

    2014-09-01

    Noda epileptic rats (NERs) present with clinico-pathological manifestations reminiscent of human generalized tonic-clonic epilepsy. Thus, this strain of rat has been a model of primary, generalized, tonic-clonic epilepsy. However, the infrequency of seizures in these rats makes the assessment of antiepileptic drugs (AEDs) difficult. Therefore, traditional AEDs have only been tested in NERs against audiogenic seizures evoked by weekly acoustic priming from 3 to 22 weeks of age or by using the kindling procedure in adult animals. Adult NERs are susceptible to changes in their environment, such as bedding replacement or unpleasant sensory stimuli. In the present study, traditional AEDs-phenobarbital (PB) and sodium valproate (VPA)-were evaluated against seizures evoked by strong environmental stimuli in mature NERs that had not been previously primed. The number of animals presenting with seizures decreased in a dose-dependent manner following administration of either PB (dose range 1.0-5.0mg/kg) or VPA (50 and 100mg/kg). Consequently, the utility of NERs as a model of generalized tonic-clonic epilepsy was confirmed. This type of protocol can be used to further evaluate AEDs and test effects of chronic administration of AEDs. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Self-reported health-related quality of life in kindergarten children: psychometric properties of the Kiddy-KINDL.

    Science.gov (United States)

    Villalonga-Olives, E; Kiese-Himmel, C; Witte, C; Almansa, J; Dusilova, I; Hacker, K; von Steinbuechel, N

    2015-07-01

    To assess the psychometric properties of the German self-reported version of the Kiddy-KINDL that measures Health Related Quality of Life (HRQoL) in 3 to 5 year old kindergarten children. The population of the study comprised baseline data of a longitudinal study whose main aim is to investigate self-reported health outcomes in young children (N = 317). Missing values, the distribution of data, internal consistency (Cronbach's alpha and Guttman's lambda), and reliability (split half and two weeks test-retest) were analysed. To assess discriminant validity, mean differences were tested splitting the sample regarding socio-emotional competences (VBV 3-6), age and gender. Structural validity was investigated with Confirmatory Factor Analysis (CFA). Mean HRQoL was 69.79 (SD 16.84). Overall missing values were 8.1%, overall Cronbach's alpha was 0.75 and overall Guttman's lambda was 0.77; for the whole scale Spearman-Brown test for split half reliability resulted in 0.80 and ICC for test-retest in 0.83. Discriminant validity investigation differentiated groups with high and low socio-emotional competence and those children who were 4.5 years or older, compared to the younger ones. Differences between boys and girls were also found. CFA suggested two main dimensions: physical and socio-emotional. This preliminary validation of the Kiddy-KINDL in very young children shows satisfactory psychometric properties. However, results of the Cronbach's alpha, Guttman's lambda and the CFA depicted problems, mainly in the psychological dimension. Due to these we recommend to use the Kiddy-KINDL as an instrument with only two dimensions. Further studies in general population samples are needed. Copyright © 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  15. [Establishment of rat model with diabetes mellitus and concomitant periodontitis and the carotid artery lesions in the model rats].

    Science.gov (United States)

    Ren, X Y; Wang, C; Liu, X; Li, H; Gao, J H; Ge, X J

    2017-12-09

    Objectives: To establish SD rat model with type 2 diabetes mellitus (DM) and concomitant chronic periodontitis (CP) and to evaluate the influence of periodontitis on the vascular lesions of type 2 diabetes rats. Methods: Totally 241 clean level SD rats were randomly divided into four groups, group A (normal control, NC, n= 27), group B (DM, n= 34), group C (CP, n= 90) and group D (DM+CP, n= 90). The rats of DM group were fed with high-fat and high-sugar diet for 8 to 10 weeks, and then were multiply injected with small dose streptozotocin under the condition of ice bath. Blood sugar levels after the injection were dynamically monitored at 72 h, 1 week, 2 weeks and 4 weeks, respectively. The CP model was established by means of ligation. Bilateral maxillary first and second molars were selected and ligated using 0.2 mm orthodontic wires binding with 4-0 surgical suture soaked with Porphyromonas gingivalis (Pg) suspension. After a period of 14 weeks, all the rats were put to death. Maxillary samples were subjected to methylene blue staining to observe alveolar bone loss. Bilateral carotid artery specimens were collected. The left carotid artery specimens were used to detect the prevalence of Pg using quantitative real-time PCR. The right carotid artery specimens were used to observe pathological changes. Results: Blood sugar levels of rats in group B and D increased and changed sharply after Streptozotocin injection with in 1 week. Symptoms of 'more drink, more food and body weight loss' appeared. The fasting blood glucose (FBG) was more than 7.8 mmol/L and (or) the random blood glucose (RBG) was more than 17.8 mmol/L. Both FBG and RBG became stable after 2 to 3 weeks. Levels of HbA1C in group B and D ([7.32±0.45]%, [9.41±0.45]%) were significantly higher than that of group A ([4.02±0.45]%) ( Pdiabetes vascular lesions.

  16. Behavioral and molecular responses to electroconvulsive shock differ between genetic and environmental rat models of depression.

    Science.gov (United States)

    Luo, Jie; Min, Su; Wei, Ke; Cao, Jun; Wang, Bin; Li, Ping; Dong, Jun; Liu, Yuanyuan

    2015-04-30

    Depression׳s causes play a role in individuals׳ different responses to antidepressant treatments, which require advancements. We investigated the mechanisms behind and responses to a highly effective antidepressant treatment, electroconvulsive therapy (ECT), in rat models with different (genetic or environmental) depression causes. Wistar Kyoto (WKY) rats and Wistar rats treated with chronic unpredictable mild stresses (CUMS) were used as genetic and environmental rat models of depression, respectively. The rats underwent electroconvulsive shock (ECS, the animal analog of ECT) or sham ECS. We performed a sucrose preference test, open field test, and Morris water maze to assess behavior. Hippocampal neuron numbers were measured with Nissl stain. Hippocampal BDNF, CREB, and p-CREB proteins were assayed with ELISA or western blotting. The main results showed that ECS impaired WKY rats׳ memories but improved CUMS rats׳ memories. It elevated hippocampal BDNF and CREB proteins only in CUMS rats, while it improved depressive behavior and hippocampal p-CREB protein levels in both rats, with more effective regulations in the CUMS rats. ECS did not change the hippocampal neuron number in both rats. These findings suggest that ECS exerted up-regulating effects on hippocampal BDNF and CREB (and its phosphorylation) in depressed rats, and the environmental model responded better. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. Surgery results in exaggerated and persistent cognitive decline in a rat model of the Metabolic Syndrome.

    Science.gov (United States)

    Feng, Xiaomei; Degos, Vincent; Koch, Lauren G; Britton, Steven L; Zhu, Yinggang; Vacas, Susana; Terrando, Niccolò; Nelson, Jeffrey; Su, Xiao; Maze, Mervyn

    2013-05-01

    Postoperative cognitive decline can be reproduced in animal models. In a well-validated rat model of the Metabolic Syndrome, we sought to investigate whether surgery induced a more severe and persistent form of cognitive decline similar to that noted in preliminary clinical studies. In rats that had been selectively bred for low and high exercise endurance, the low capacity runners (LCR) exhibited features of Metabolic Syndrome (obesity, dyslipidemia, insulin resistance, and hypertension). Tibial fracture surgery was performed under isoflurane anesthesia in LCR and high capacity runner (HCR) rats and cognitive function was assessed postoperatively in a trace-fear conditioning paradigm and Morris Water Maze; non-operated rats were exposed to anesthesia and analgesia (sham). Group sizes were n = 6. On postoperative D7, LCR rats had shorter freezing times than postoperative HCR rats. Five months postoperatively, LCR rats had a flatter learning trajectory and took longer to locate the submerged platform than postoperative HCR rats; dwell-time in the target quadrant in a probe trial was shorter in the postoperative LCR compared to HCR rats. LCR and HCR sham rats did not differ in any test. Postoperatively, LCR rats diverged from HCR rats exhibiting a greater decline in memory, acutely, with persistent learning and memory decline, remotely; this could not be attributed to changes in locomotor or swimming performance. This Metabolic Syndrome animal model of surgery-induced cognitive decline corroborates, with high fidelity, preliminary findings of postoperative cognitive dysfunction in Metabolic Syndrome patients.

  18. Establishment of animal model of dual liver transplantation in rat.

    Directory of Open Access Journals (Sweden)

    Ying Zhang

    Full Text Available The animal model of the whole-size and reduced-size liver transplantation in both rat and mouse has been successfully established. Because of the difficulties and complexities in microsurgical technology, the animal model of dual liver transplantation was still not established for twelve years since the first human dual liver transplantation has been made a success. There is an essential need to establish this animal model to lay a basic foundation for clinical practice. To study the physiological and histopathological changes of dual liver transplantation, "Y" type vein from the cross part between vena cava and two iliac of donor and "Y' type prosthesis were employed to recanalize portal vein and the bile duct between dual liver grafts and recipient. The dual right upper lobes about 45-50% of the recipient liver volume were taken as donor, one was orthotopically implanted at its original position, the other was rotated 180° sagitally and heterotopically positioned in the left upper quadrant. Microcirculation parameters, liver function, immunohistochemistry and survival were analyzed to evaluate the function of dual liver grafts. No significant difference in the hepatic microcirculatory flow was found between two grafts in the first 90 minutes after reperfusion. Light and electronic microscope showed the liver architecture was maintained without obvious features of cellular destruction and the continuity of the endothelium was preserved. Only 3 heterotopically positioned graft appeared patchy desquamation of endothelial cell, mitochondrial swelling and hepatocytes cytoplasmic vacuolization. Immunohistochemistry revealed there is no difference in hepatocyte activity and the ability of endothelia to contract and relax after reperfusion between dual grafts. Dual grafts made a rapid amelioration of liver function after reperfusion. 7 rats survived more than 7 days with survival rate of 58.3.%. Using "Y" type vein and bile duct prosthesis, we

  19. Sildenafil after cardiac arrest and infarction; an experimental rat model.

    Science.gov (United States)

    Mennander, Ari A; Vuohelainen, Vilma; Aanismaa, Riikka S; Narkilahti, Susanna; Paavonen, Timo; Tarkka, Matti

    2013-02-01

    Resuscitation after cardiac arrest may lead to ischemia-reperfusion injury and infarction. We evaluated whether sildenafil, a phosphodiesterase-5 inhibitor, has an impact on recovery after cardiac arrest in a rat cardiac transplantation model. Sixty-one Fischer344 rats underwent syngeneic heterotopic cardiac transplantation after ischemia and ligation of the left anterior coronary artery of the heart to yield myocardial infarction (IRI + MI). Of these, 22 rats received subcutaneously injected sildenafil (1 mg/kg/day) (IRI +MI + S). Twenty-three additional grafted animals with transplantation only served as controls with ischemia reperfusion injury (IRI). After 2 days, immunohistochemistry for eNOS, and RT-PCR for iNOS and Aquaporin-7 were performed after graft harvesting and histology. Two days after transplantation, remote intramyocardial arteries were more preserved in IRI + MI + S as compared with IRI +MI and IRI (0.74 ± 0.14, 0.56 ± 0.23 and 0.55 ± 0.22, PSU, p cardiac arrest and ischemia.

  20. Azithromycin reduces inflammation in a rat model of acute conjunctivitis.

    Science.gov (United States)

    Fernandez-Robredo, Patricia; Recalde, Sergio; Moreno-Orduña, Maite; García-García, Laura; Zarranz-Ventura, Javier; García-Layana, Alfredo

    2013-01-01

    Macrolide antibiotics are known to have various anti-inflammatory effects in addition to their antimicrobial activity, but the mechanisms are still unclear. The effect of azithromycin on inflammatory molecules in the lipopolysaccharide-induced rat conjunctivitis model was investigated. Twenty-four Wistar rats were divided into two groups receiving topical ocular azithromycin (15 mg/g) or vehicle. In total, six doses (25 µl) were administered as one dose twice a day for three days before subconjunctival lipopolysaccharide injection (3 mg/ml). Before the rats were euthanized, mucus secretion, conjunctival and palpebral edema and redness were evaluated. Real-time polymerase chain reaction was used to determine gene expression for interleukin-6, cyclooxygenase-2, tumor necrosis factor-α, matrix metalloproteinase (MMP)-2, and MMP-9. Interleukin-6 was determined with enzyme-linked immunosorbent assay, nuclear factor-kappa B with western blot, and MMP-2 activity with gelatin zymogram. Four eyes per group were processed for histology and subsequent periodic acid-Schiff staining and CD68 for immunofluorescence. The Student t test or the Wilcoxon test for independent samples was applied (SPSS v.15.0). Azithromycin-treated animals showed a significant reduction in all clinical signs (pconjunctivitis.

  1. Ozone enema: a model of microscopic colitis in rats.

    Science.gov (United States)

    Eliakim, R; Karmeli, F; Rachmilewitz, D; Cohen, P; Zimran, A

    2001-11-01

    Ozone is one of the most powerful oxidants available, with many applications in industry and medicine. Medically relevant features of ozone include bacterial and virucidal properties, disinfection, sterilization, circulatory stimulation, and disruption of malignant cells. Ozone therapy is administered in various ways, including intravenously, intramuscularly, and intrarectally. The latter modality is used for the treatment of colitis and hepatitis. Our aim was to examine the effect of ozone water enema on normal and inflamed rat colonic mucosa. Ozone water (20 microg/ml) was prepared via ozone generator and administered intrarectally (0.5 ml) daily. Rats were killed one, three, and seven days after rectal ozone water administration, and their colons resected, rinsed, and weighed (grams per 10 cm). Damage was assessed macro- and microscopically and tissue processed for myeloperoxidase and nitric oxide synthase activity. Rats receiving saline served as controls. In an additional experiment colitis was induced by intrarectal iodoacetamide. Ozone therapy caused no macroscopic damage. Ozone therapy induced microscopic colitis, which lasted for at least a week and was accompanied by increase in segmental weight, myeloperoxidase and nitric oxide activity, and prostaglandin E2 generation. Ozone therapy had no protective effect on inflamed mucosa. In conclusion, ozone water therapy had a deleterious effect on normal colonic mucosa, suggesting intrarectal administration be reevaluated. Ozone water enema may serve as a model of microscopic colitis.

  2. The Future of Reading/Thinking: Epistemological Construction in the Age of the Kindle

    Directory of Open Access Journals (Sweden)

    Benjamin J. Cline

    2012-08-01

    Full Text Available Whether as an application on our tablets (such as an I-pad or an Android device or as a single application piece of hardware such as a (Nook or Kindle, the handheld digital reading device is quickly becoming a fixture in contemporary life. It is not only changing the way in which books are bought and sold, but it is changing the nature of what it is to read and how our knowledge is constructed. Drawing on Walter Ong’s theories of secondary orality (2002 and McLuhan’s concepts of technologies as extensions of particular faculties with trade-offs in other areas (McLuhan, 1964, this paper argues that the handheld digital reader is not only a device which allows for reading of books, but it is also a rhetorical device. In order to accomplish this, the paper demonstrates that the handheld digital reader came as a response to a deviance amplifying rhetorical situation (Bitzer, 1968 brought on by the advent of easy duplication and a dwindling readership. This paper shows that the handheld digital reader functions as a social intervention (Brown, 1978; Opt & Gring, 2009 creating an attention shift (Brown W. R., 1982 which initially alters one’s epistemology, but with ontological and axiological repercussions. Finally, the paper discusses the potential ramifications of a rhetorical future populated by people whose worldviews have been heavily influenced by the inherent rhetoric of the handheld digital reading device and advising changes in rhetorical theory and practice which will have to be considered in light of these changes.

  3. Protective effect of chlorogenic acid on the focal cerebral ischemia reperfusion rat models

    Directory of Open Access Journals (Sweden)

    Mingsan Miao

    2017-05-01

    Conclusion: The results showed that chlorogenic acid could protect the focal cerebral ischemia reperfusion injury rat models by adjusting the inflammatory factor, hypoxia factor and nerve growth factor.

  4. Mechanism of auditory hypersensitivity in human autism using autism model rats.

    Science.gov (United States)

    Ida-Eto, Michiru; Hara, Nao; Ohkawara, Takeshi; Narita, Masaaki

    2017-04-01

    Auditory hypersensitivity is one of the major complications in autism spectrum disorder. The aim of this study was to investigate whether the auditory brain center is affected in autism model rats. Autism model rats were prepared by prenatal exposure to thalidomide on embryonic day 9 and 10 in pregnant rats. The superior olivary complex (SOC), a complex of auditory nuclei, was immunostained with anti-calbindin d28k antibody at postnatal day 50. In autism model rats, SOC immunoreactivity was markedly decreased. Strength of immunostaining of SOC auditory fibers was also weak in autism model rats. Surprisingly, the size of the medial nucleus of trapezoid body, a nucleus exerting inhibitory function in SOC, was significantly decreased in autism model rats. Auditory hypersensitivity may be, in part, due to impairment of inhibitory processing by the auditory brain center. © 2016 Japan Pediatric Society.

  5. Photon and electron absorbed fractions calculated from a new tomographic rat model

    Energy Technology Data Exchange (ETDEWEB)

    Peixoto, P H R [Departamento de Energia Nuclear, Universidade Federal de Pernambuco, Av. Prof. Luiz Freire 1000, Cidade Universitaria, CEP 50740-540, Recife, PE (Brazil); Vieira, J W [Centro Federal de Educacao Tecnologica de Pernambuco, Recife, PE (Brazil); Yoriyaz, H [Instituto de Pesquisas Energeticas e Nucleares, Sao Paulo, SP (Brazil); Lima, F R A [Centro Regional de Ciencias Nucleares-CNEN, Recife, PE (Brazil)], E-mail: phrpeixoto@yahoo.com.br

    2008-10-07

    This paper describes the development of a tomographic model of a rat developed using CT images of an adult male Wistar rat for radiation transport studies. It also presents calculations of absorbed fractions (AFs) under internal photon and electron sources using this rat model and the Monte Carlo code MCNP. All data related to the developed phantom were made available for the scientific community as well as the MCNP inputs prepared for AF calculations in that phantom and also all estimated AF values, which could be used to obtain absorbed dose estimates-following the MIRD methodology-in rats similar in size to the presently developed model. Comparison between the rat model developed in this study and that published by Stabin et al (2006 J. Nucl. Med. 47 655) for a 248 g Sprague-Dawley rat, as well as between the estimated AF values for both models, has been presented.

  6. A new rat model of neonatal bilirubin encephalopathy (kernicterus).

    Science.gov (United States)

    Amini, Naser; Vousooghi, Nasim; Soleimani, Mansoureh; Samadikuchaksaraei, Ali; Akbari, Mehdi; Safakheil, Hosein; Atafimanesh, Pezhman; Shahbazi, Ali; Brouki Milan, Peiman; Ramezani, Sara; Mozafari, Masoud; Joghataei, Mohammad Taghi

    Hemolytic kernicterus, an indirect bilirubin-induced brain dysfunction, is associated with hyper-bilirubinemia in mammalian neonates. In this study, a new model of kernicterus has been developed using intra-peritoneal injections of phenyl hydrazine and subcutaneous injections of sulfisoxazole. These drugs can potentially induce kernicterus in neonatal through changes in hemolysis and hypo-albumin. For this purpose, 7-day-old male Wistar rats (n=72; mean weight 11±1g) were used. The animals have been divided into six different groups which received the drugs alone and their combination, and the drugs' solvents and their combination. Biochemical parameters, brain iron and bilirubin, behavioural performance, auditory function and apoptosis were measured using auto-analyser instruments; atomic absorption spectroscopy, Sawasaki, footprint, auditory brainstem response (ABR) and TUNEL test, respectively. The drug-injected groups showed a significant reduction in serum haematocrit and an increase in the concentration of brain bilirubin, total and indirect bilirubin as well as TUNEL positive cells in basal ganglia. In addition, the obtained results showed that there was a significant increase in behavioural disturbance and auditory dysfunction in the group injected with the combination of two drugs. This kernicterus-induced rat model could perfectly mimic the common conditions of the hyperbilirubinemia in human neonates. This study offers an easy technique to develop more stable models for follow-up studies. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Implant-related infection model in rat spine.

    Science.gov (United States)

    Ofluoglu, Ender Ali; Zileli, Mehmet; Aydin, Derya; Baris, Yakup Sancar; Kuçukbasmaci, Omer; Gonullu, Nevriye; Ofluoglu, Onder; Toplamaoglu, Halil

    2007-07-01

    The rate of postoperative infections is approximately 1% in spine surgery. However, when metal implants are used, postoperative infection rates significantly increase and were reported between 2.1 and 8.5%. This study aim to set up an infection model in the rat spine with a metal implant. Forty white male Sprague Dawley rats were randomly divided in four groups. In all rats, under operation microscope, a 3 mm titanium microscrew was implanted in the thoracolumbar area (T10-L1) after laminar decortication. In Group I (control group), sterile isotonic solution and in other three groups, different concentrations of Staphylococcus aureus [Group II: (10(2)), Group III: (10(3)), Group IV: (10(6))] were squirted on the decorticated lamina site. All animals were sacrificed after 2 weeks, and then blood cultures and cultures from fascia, muscle and bone were obtained. Bacterial number in each tissue was measured as colony-forming unit per gram tissue. Titanium microscrews were placed in 0.5 ml tryptic soy broth and vortexed than plated on trypticase soy agar to determine bacterial growth. Two animals from each group were subjected to histological examination. Blood cultures obtained by intra-atrial puncture after 2 weeks were negative in all groups indicating no systemical infection developed. Bacterial cultures were negative in all specimens of Group I (control group). A significant osseous infection was confirmed in Groups II, III and IV. Comparison of bacterial counts in bone cultures showed no significant difference between Group III (10(3) CFU/10 microl) and Group IV (10(6) CFU/10 microl) (P > 0.05), while both groups had significantly higher counts than Group II (10(2) CFU/10 microl) (P > 0.05). Microscopic findings of supurrative inflammation were present only in Group IV (10(6) CFU/10 microl). This study shows that inoculation of S. aureus in 10(6) CFU/10 microl concentration at the decorticated lamina after implantation of a titanium screw in rat spine is a

  8. Rehabilitative exercise in a rat model of doxorubicin cardiotoxicity.

    Science.gov (United States)

    Hydock, David S; Lien, Chia-Ying; Jensen, Brock T; Parry, Traci L; Schneider, Carole M; Hayward, Reid

    2012-12-01

    The use of exercise to minimize doxorubicin (DOX)-induced cardiotoxicity is gaining attention. However, very few clinically relevant reports exist investigating the effects of exercise performed during and following DOX treatments. The purpose of this study, therefore, was to examine the effects of voluntary wheel running during and following DOX treatment using two models of late-onset DOX cardiotoxicity in the rat. Female Sprague-Dawley rats received either DOX or saline injections using one of two separate treatment regimens. These regimens involved either daily or weekly DOX injections with cumulative doses for both protocols totaling 15 mg/kg. Daily DOX injections were 1 mg/kg and lasted for 15 consecutive days while weekly DOX injections were 2.5 mg/kg and lasted for six consecutive weeks with control animals receiving matched saline injection regimens. Immediately following the initial DOX/saline injection, animals were randomly housed in cages with voluntary running wheels or standard rat cages throughout DOX/saline treatments and continued until reaching 10 weeks. Cardiac function was then assessed using echocardiography and an isolated working heart model, and myosin heavy chain (MHC) isoform distribution was assessed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. When compared wth controls, daily DOX treatment resulted in reduced running wheel distances at weeks 2-10 (P running wheel distances at weeks 2, 6 and 10 (P running during and following daily and weekly DOX dosing protected against DOX-induced cardiotoxicity by preserving maximal mitral and aortic blood flow velocities, left ventricular developed pressure and MHC isoform expression. In conclusion, the overall reduced volume of activity during and following daily and weekly DOX treatments attenuated DOX-induced cardiac dysfunction suggesting that low-volume endurance training may be an effective rehabilitative approach in minimizing DOX cardiotoxicity in cancer patients.

  9. A SIMPLE EXPERIMENTAL MODEL OF HEAT SHOCK RESPONSE IN RATS

    Directory of Open Access Journals (Sweden)

    Tufi Neder Meyer

    1998-10-01

    Full Text Available Objective: To obtain a simple model for the elicitation of the heat shock response in rats. Design: Laboratory study. Setting: University research laboratories. Sample: Seventy-nine adult male albino rats (weight range 200 g to 570 g. Procedures: Exposure to heat stress by heating animals in a warm bath for 5 min after their rectal temperatures reached 107.60 F (420 C. Liver and lung samples were collected for heat-shock protein 70 (HSP70 detection (Western analysis. Results: Western analysis was positive for HSP70 in the liver and in the lungs of heated animals. There was a temporal correlation between heating and HSP70 detection: it was strongest 1 day after heating and reduced afterwards. No heated animals died. Conclusion: These data show that heating rats in a warm (45o C bath, according to parameters set in this model, elicits efficiently the heat shock response.OBJETIVO: Obter um modelo simples para tentar esclarecer a resposta ao choque térmico em ratos. LOCAL: Laboratório de pesquisa da Universidade. MÉTODO: Amostra: 79 ratos albinos, adultos, entre 200g a 570g. Procedimentos: Exposição ao calor, em banho quente, por 5 minutos, após a temperatura retal chegar a 42 graus centigrados. Biópsias de fígado e pulmão foram obtidas para detectar a proteina 70 (HSP 70, pelo "Western blot". RESULTADOS: As análises foram positivas nos animais aquecidos, com uma correlação entre aquecimento e constatação da HSP 70. Foi mais elevada no primeiro dia e não houve óbitos nos animais aquecidos. CONCLUSÃO: Os ratos aquecidos a 45 graus centígrados respondem eficientemente ao choque térmico.

  10. New rat model that phenotypically resembles autosomal recessive polycystic kidney disease

    NARCIS (Netherlands)

    J. Nauta (Jeroen); M.A. Goedbloed (Miriam); H.V. Herck; D.A. Hesselink (Dennis); P. Visser (Pim); R. Willemsen (Rob); R.P.E. van Dokkum (Richard); C.J. Wright; L.M. Guay-Woodford

    2000-01-01

    textabstractNumerous murine models of polycystic kidney disease (PKD) have been described. While mouse models are particularly well suited for investigating the molecular pathogenesis of PKD, rats are well established as an experimental model of renal physiologic

  11. A revised Racine's scale for PTZ-induced seizures in rats

    NARCIS (Netherlands)

    Luttjohann, A.K.; Fabene, P.F.; Luijtelaar, E.L.J.M. van

    2009-01-01

    Behavioral scoring is commonly used to access seizure intensity in different seizure models. Racine's scale, originally developed for the amygdala-kindling model, is also frequently used as an intensity measurement in other experimental seizure or epilepsy models. The aim of the present study is to

  12. A Case Study of Mobile Technology-enabled English Language Learning: the Amazon Kindle e-Reader Initiative in Palestine

    Directory of Open Access Journals (Sweden)

    Khitam Yousuf Shraim

    2014-06-01

    Full Text Available The proliferation of increasingly interactive e-reader devices such as the Amazon Kindle represents an opportunity to explore their evolving pedagogical value. This study aims to investigate how use of the Kindle can enhance individuals’ English language learning—more specifically their attitudes, reading comprehension, vocabulary development and pronunciation performance—in the context of informal and lifelong learning in Palestine, and to explore the further potential of scaling up the use of e-readers at a national level. At the piloting stage of this initiative, the study operated at two levels (micro and meso of the M3 evaluation framework. Mixed methods were used: qualitative data were obtained through a case study of the practices and perceptions of two teachers in two classrooms in the Qalqilia center and quantitative data were collected through a survey of 114 learners. The study shows that the Kindle’s technological affordances are effective in creating a flexible, authentic and interactive environment for English language learning, provided that teachers change their teaching methods to take full advantage of the features of mobile technologies to create innovative learning approaches aligned with the needs of the e-generation. It was also found that despite some concerns with the usability issue, attitudes towards learning English changed positively and learners’ vocabulary and pronunciation improved.

  13. Correction of liver disease following transplantation of normal rat hepatocytes into Long-Evans Cinnamon rats modeling Wilson's disease.

    Science.gov (United States)

    Irani, A N; Malhi, H; Slehria, S; Gorla, G R; Volenberg, I; Schilsky, M L; Gupta, S

    2001-03-01

    To establish the efficacy of cell therapy in Wilson's disease, we used the Long-Evans Cinnamon (LEC) rat model with atp7b gene mutation and copper toxicosis. Several groups of LEC rats were established, including animals pretreated with retrorsine to exacerbate copper toxicosis and inhibit proliferation in native hepatocytes followed by partial hepatectomy to promote liver repopulation. Hepatocytes from normal, syngeneic LEA rats were transplanted intrasplenically. Animal survival, biliary copper excretion, and hepatic copper were determined. The magnitude of liver repopulation was demonstrated by measuring serum ceruloplasmin and hepatic atp7b mRNA. Long-term survival in LEC rats treated with retrorsine, partial hepatectomy, and cell transplantation was up to 90%, whereas fewer than 10% of animals pretreated with retrorsine, without cell therapy, survived, P Wilson's disease.

  14. iPhone, Android, or Kindle: The Emma S. Clark Memorial Library Has an App for That and So Can You

    Science.gov (United States)

    Johnson, Bob; Gutmann, Ted

    2013-01-01

    If you are like the millions of people buying the latest smartphone, iPhone 5, or Samsung Galaxy S III, your local library should have something to offer you. The Emma S. Clark Memorial Library, for one, has an app for that! Dubbed "Emma Mobile," the library's application works with iOS (Apple), Android (Google), and Amazon Kindle Fire…

  15. Face Graft Scaffold Production in a Rat Model.

    Science.gov (United States)

    Duisit, Jérôme; Amiel, Hadrien; Orlando, Giuseppe; Dedriche, Adeline; Behets, Catherine; Gianello, Pierre; Lengelé, Benoît

    2018-01-01

    As a route toward face bioengineering, the authors previously reported the production of a complete scaffold by perfusion-decellularization of a porcine ear subunit graft and partial recellularization. To extend the scaffold to the whole face and to down-scale it, they applied their findings to a rodent hemifacial graft model. After the animals were killed, seven full-thickness rat hemiface grafts were harvested with the common carotid artery and the external jugular vein as a pedicle, and cannulated. Grafts were decellularized by a detergent-based protocol: either by perfusion through the common carotid artery, or by mechanical agitation. After decellularization, samples were analyzed for DNA quantification and histology by hematoxylin and eosin, Masson trichrome, Sirius red, or Safranin O staining. Vascular tree patency was assessed by microangiographic computed tomography after contrast injection. Cell-friendly extracellular matrix was assessed by seeding of human adipose-derived stem cells and vital staining after 7 days of culture. Decellularization was effective in both groups, with a cell clearance at all levels, with the exception of cartilage areas in the agitation-treated groups. Microscopic assessment found a well-preserved extracellular matrix in both groups. Vascular contrast was found in all regions of the scaffolds. After the animals were killed, seeded cells were found viable and well distributed on all scaffolds. The authors successfully decellularized face grafts in a rodent model, with a preserved vascular tree. Perfusion-decellularization led to better and faster results compared with mechanical agitation but is not mandatory in this model. The rat face is an interesting scaffold model for further recellularization studies, in the final goal of human face bioengineering.

  16. Metformin and atorvastatin reduce adhesion formation in a rat uterine horn model.

    Science.gov (United States)

    Yilmaz, Bulent; Aksakal, Orhan; Gungor, Tayfun; Sirvan, Levent; Sut, Necdet; Kelekci, Sefa; Soysal, Sunullah; Mollamahmutoglu, Leyla

    2009-03-01

    The aim of the present study was to determine whether atorvastatin and metformin are effective in preventing adhesions in a rat uterine horn model. A total of 40 non-pregnant, female Wistar albino rats, weighing 180-210 g, were used as a model for post-operative adhesion formation. The rats were randomized into four groups after seven standard lesions were inflicted in each uterine horn and lower abdominal sidewall using bipolar cauterization. The rats were given atorvastatin 2.5 mg/kg/day, p.o. (10 rats), atorvastatin 30 mg/kg/day, p.o. (10 rats), metformin 50 mg/kg/day, p.o. (10 rats) and no treatment was applied in the control group (10 rats). The animals were killed 2 weeks later and adhesions were scored both clinically and pathologically by authors blinded to groups. One rat in the control group died before the end of the 2 week period. Total clinical adhesion scores regarding extent, severity and degree of adhesions and histopathological findings including inflammation and fibrosis were significantly lower in the metformin (P < 0.001 and P < 0.01, respectively) and atorvastatin 30 mg/kg/day (P < 0.001 and P < 0.01, respectively) groups when compared with control group. Metformin and atorvastatin are both effective for prevention of adhesion formation in a rat uterine horn model.

  17. Teriparatide and the treatment of bisphosphonate-related osteonecrosis of the jaw: a rat model

    NARCIS (Netherlands)

    Ersan, N.; van Ruijven, L.J.; Bronckers, A.L.J.J.; Olgaç, V.; Ìlgüy, D.; Everts, V.

    2014-01-01

    Objectives: The objectives of this study were to establish a bisphosphonate-related osteonecrosis of the jaw (BRONJ) rat model and to analyse the effects of teriparatide (TP) on this model. Methods: Sprague-Dawley rats were divided into three groups: I—zoledronic acid (ZA, n = 10); II—ZA and

  18. Validation of infrared thermography in serotonin-induced itch model in rats

    DEFF Research Database (Denmark)

    Dagnæs-Hansen, Frederik; Jasemian, Yousef; Gazerani, Parisa

    The number of scratching bouts is generally used as a standard method in animal models of itch. The aim of the present study was to validate the application of infrared thermography (IR-Th) in a serotonin-induced itch model in rats. Adult Sprague-Dawley male rats (n = 24) were used in 3 consecutive...

  19. Respiratory tract lung geometry and dosimetry model for male Sprague-Dawley rats.

    Energy Technology Data Exchange (ETDEWEB)

    Miller, Frederick J.; Asgharian, Bahman; Schroeter, Jeffry D.; Price, Owen; Corley, Richard A.; Einstein, Daniel R.; Jacob, Rick E.; Cox, Timothy C.; Kabilan, Senthil; Bentley, Timothy

    2014-08-26

    While inhalation toxicological studies of various compounds have been conducted using a number of different strains of rats, mechanistic dosimetry models have only had tracheobronchial (TB) structural data for Long-Evans rats, detailed morphometric data on the alveolar region of Sprague-Dawley rats and limited alveolar data on other strains. Based upon CT imaging data for two male Sprague-Dawley rats, a 15-generation, symmetric typical path model was developed for the TB region. Literature data for the alveolar region of Sprague-Dawley rats were analyzed to develop an eight-generation model, and the two regions were joined to provide a complete lower respiratory tract model for Sprague-Dawley rats. The resulting lung model was used to examine particle deposition in Sprague-Dawley rats and to compare these results with predicted deposition in Long-Evans rats. Relationships of various physiologic variables and lung volumes were either developed in this study or extracted from the literature to provide the necessary input data for examining particle deposition. While the lengths, diameters and branching angles of the TB airways differed between the two Sprague- Dawley rats, the predicted deposition patterns in the three major respiratory tract regions were very similar. Between Sprague-Dawley and Long-Evans rats, significant differences in TB and alveolar predicted deposition fractions were observed over a wide range of particle sizes, with TB deposition fractions being up to 3- to 4-fold greater in Sprague-Dawley rats and alveolar deposition being significantly greater in Long-Evans rats. Thus, strain-specific lung geometry models should be used for particle deposition calculations and interspecies dose comparisons.

  20. Respiratory Tract Lung Geometry and Dosimetry Model for Male Sprague-Dawley Rats

    Energy Technology Data Exchange (ETDEWEB)

    Miller, Frederick J.; Asgharian, Bahman; Schroeter, Jeffry D.; Price, Owen; Corley, Richard A.; Einstein, Daniel R.; Jacob, Rick E.; Cox, Timothy C.; Kabilan, Senthil; Bentley, Timothy

    2015-07-24

    While inhalation toxicological studies of various compounds have been conducted using a number of different strains of rats, mechanistic dosimetry models have only had tracheobronchial (TB) structural data for Long-Evans rats, detailed morphometric data on the alveolar region of Sprague-Dawley rats and limited alveolar data on other strains. Based upon CT imaging data for two male Sprague-Dawley rats, a 15-generation, symmetric typical path model was developed for the TB region. Literature data for the alveolar region of Sprague-Dawley rats were analyzed to develop an eight-generation model, and the two regions were joined to provide a complete lower respiratory tract model for Sprague-Dawley rats. The resulting lung model was used to examine particle deposition in Sprague-Dawley rats and to compare these results with predicted deposition in Long-Evans rats. Relationships of various physiologic variables and lung volumes were either developed in this study or extracted from the literature to provide the necessary input data for examining particle deposition. While the lengths, diameters and branching angles of the TB airways differed between the two Sprague-Dawley rats, the predicted deposition patterns in the three major respiratory tract regions were very similar. Between Sprague-Dawley and Long-Evans rats, significant differences in TB and alveolar predicted deposition fractions were observed over a wide range of particle sizes, with TB deposition fractions being up to 3- to 4-fold greater in Sprague-Dawley rats and alveolar deposition being significantly greater in Long-Evans rats. Thus, strain-specific lung geometry models should be used for particle deposition calculations and interspecies dose comparisons.

  1. Rheumatoid arthritis: identifying and characterising polymorphisms using rat models

    Science.gov (United States)

    2016-01-01

    ABSTRACT Rheumatoid arthritis is a chronic inflammatory joint disorder characterised by erosive inflammation of the articular cartilage and by destruction of the synovial joints. It is regulated by both genetic and environmental factors, and, currently, there is no preventative treatment or cure for this disease. Genome-wide association studies have identified ∼100 new loci associated with rheumatoid arthritis, in addition to the already known locus within the major histocompatibility complex II region. However, together, these loci account for only a modest fraction of the genetic variance associated with this disease and very little is known about the pathogenic roles of most of the risk loci identified. Here, we discuss how rat models of rheumatoid arthritis are being used to detect quantitative trait loci that regulate different arthritic traits by genetic linkage analysis and to positionally clone the underlying causative genes using congenic strains. By isolating specific loci on a fixed genetic background, congenic strains overcome the challenges of genetic heterogeneity and environmental interactions associated with human studies. Most importantly, congenic strains allow functional experimental studies be performed to investigate the pathological consequences of natural genetic polymorphisms, as illustrated by the discovery of several major disease genes that contribute to arthritis in rats. We discuss how these advances have provided new biological insights into arthritis in humans. PMID:27736747

  2. Modafinil improves monocrotaline-induced pulmonary hypertension rat model.

    Science.gov (United States)

    Lee, Hyeryon; Kim, Kwan Chang; Cho, Min-Sun; Suh, Suk-Hyo; Hong, Young Mi

    2016-07-01

    Pulmonary arterial hypertension (PAH) progressively leads to increases in pulmonary vasoconstriction. Modafinil plays a role in vasorelaxation and blocking KCa3.1 channel with a result of elevating intracellular cyclic adenosine monophosphate (cAMP) levels. The purpose of this study is to evaluate the effects on modafinil in monocrotaline (MCT)-induced PAH rat. The rats were separated into three groups: the control group, the monocrotaline (M) group (MCT 60 mg/kg), and the modafinil (MD) group (MCT 60 mg/kg + modafinil). Reduced right ventricular pressure (RVP) was observed in the MD group. Right ventricular hypertrophy was improved in the MD group. Reduced number of intra-acinar pulmonary arteries and medial wall thickness were noted in the MD group. After the administration of modafinil, protein expressions of endothelin-1 (ET-1), endothelin receptor A (ERA) and KCa3.1 channel were significantly reduced. Modafinil suppressed pulmonary artery smooth muscle cell (PASMC) proliferation via cAMP and KCa3.1 channel. Additionally, we confirmed protein expressions such as Bcl-2-associated X, vascular endothelial growth factor, tumor necrosis factor-α, and interleukin-6 were reduced in the MD group. Modafinil improved PAH by vasorelaxation and a decrease in medial thickening via ET-1, ERA, and KCa3.1 down regulation. This is a meaningful study of a modafinil in PAH model.

  3. Neuroprotective mechanism of Coenzyme Q10 (CoQ10) against PTZ induced kindling and associated cognitive dysfunction: Possible role of microglia inhibition.

    Science.gov (United States)

    Bhardwaj, Manveen; Kumar, Anil

    2016-12-01

    Neuroinflammation, oxidative stress and mitochondrial dysfunction play a significant role to explain the pathophysiology of epilepsy. Neuroinflammation through microglia activation has been documented in epileptogenesis. Compounds which inhibit activation of glial cells have been suggested as one of the treatment approaches for the effective treatment of epilepsy. The present study has been designed to investigate the role of coenzyme Q10 and its interaction with minocycline (microglia inhibitor) against pentylenetetrazol (PTZ) induced kindling epilepsy. Laca mice received Coenzyme Q10 and minocycline for a period of 29 days. PTZ (40mg/kg ip) injection has been given on alternate days. Various behavioural parameters (kindling score and elevated plus maze), biochemical parameters (lipid peroxidation, superoxide dismutase, reduced glutathione, catalase, nitrite and acetylcholinesterase) and mitochondrial enzyme complex activities of (I, II and IV) were assessed in the discrete areas of the brain. Administration of a subconvulsive dose of PTZ (40mg/kg) repeatedly increased significantly kindling score, oxidative damage and impaired mitochondrial enzyme complex activities (I, II and IV) and pro-inflammatory marker (TNF-α) as compared to naive animals. Coenzyme Q10 (10, 20 and 40mg/kg) and minocycline (50 and 100mg/kg) for a duration of 29days significantly attenuated kindling score, reversed oxidative damage, TNF-α and restored mitochondrial enzyme complex activities (I, II and IV) as compared to control. Further, combinations of CoQ10 (10, 20mg/kg) with minocycline (50 and 100mg/kg) significantly modulate the protective effect of CoQ10 which was significant as compared to their effect per se in PTZ treated animals. The present study suggests the involvement of microglia inhibition in the protective effect of CoQ10 in PTZ induced kindling in mice. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o

  4. Curative effect of sesame oil in a rat model of chronic kidney disease.

    Science.gov (United States)

    Liu, Chuan-Teng; Chien, Se-Ping; Hsu, Dur-Zong; Periasamy, Srinivasan; Liu, Ming-Yie

    2015-12-01

    Chronic kidney disease causes a progressive and irreversible loss of renal function. We investigated the curative effect of sesame oil, a natural, nutrient-rich, potent antioxidant, in a rat model of chronic kidney disease. Chronic kidney disease was induced by subcutaneously injecting uni-nephrectomized rats with deoxycorticosterone acetate (DOCA) and 1% NaCl [DOCA/salt] in drinking water. Four weeks later, the rats were gavaged with sesame oil (0.5 or 1 mL/kg per day) for 7 days. Renal injury, histopathological changes, hydroxyl radical, peroxynitrite, lipid peroxidation, Nrf2, osteopontin expression, and collagen were assessed 24 h after the last dose of sesame oil. Blood urea nitrogen, creatinine, urine volume, and albuminuria were significantly higher in the DOCA/salt treated rats than in control rats. Sesame oil significantly decreased these four tested parameters in DOCA/salt treated rats. In addition, creatinine clearance rate and nuclear Nrf2 expression were significantly decreased in the DOCA/salt treated rats compared to control rats. Sesame oil significantly decreased hydroxyl radical, peroxynitrite level, lipid peroxidation, osteopontin, and renal collagen deposition, but increased creatinine clearance rate and nuclear Nrf2 expression in DOCA/salt treated rats. We conclude that supplementation of sesame oil mitigates DOCA/salt induced chronic kidney disease in rats by activating Nrf2 and attenuating osteopontin expression and inhibiting renal fibrosis in rats. © 2015 Asian Pacific Society of Nephrology.

  5. Altered explorative strategies and reactive coping style in the FSL rat model of depression

    Directory of Open Access Journals (Sweden)

    Salvatore eMagara

    2015-04-01

    Full Text Available Modeling depression in animals is based on the observation of behaviors interpreted as analogue to human symptoms. Typical tests used in experimental depression research are designed to evoke an either-or outcome. It is known that explorative and coping strategies are relevant for depression, however these aspects are generally not considered in animal behavioral testing. Here we investigate the Flinders Sensitive Line (FSL, a rat model of depression, compared to the Sprague-Dawley (SD rat in three independent tests where the animals are allowed to express a more extensive behavioral repertoire. The multivariate concentric square field™ (MCSF and the novel cage tests evoke exploratory behaviors in a novel environment and the home cage change test evokes social behaviors in the re-establishment of a social hierarchy. In the MCSF test, FSL rats exhibited less exploratory drive and more risk-assessment behavior compared to SD rats. When re-exposed to the arena, FSL, but not SD rats, increased their exploratory behavior compared to the first trial and displayed risk-assessment behavior to the same extent as SD rats. Thus, the behavior of FSL rats was more similar to that of SDs when the rats were familiar with the arena. In the novel cage test FSL rats exhibited a reactive coping style, consistent with the reduced exploration observed in the MCSF. Reactive coping is associated with less aggressive behavior. Accordingly, FSL rats displayed less aggressive behavior in the home cage change test. Taken together, our data show that FSL rats express altered explorative behavior and reactive coping style. Reduced interest is a core symptom of depression, and individuals with a reactive coping style are more vulnerable to the disease. Our results support the use of FSL rats as an animal model of depression and increase our understanding of the FSL rat beyond the behavioral dimensions targeted by the traditional depression-related tests.

  6. Impaired voluntary wheel running behavior in the unilateral 6-hydroxydopamine rat model of Parkinson's disease.

    Science.gov (United States)

    Pan, Qi; Zhang, Wangming; Wang, Jinyan; Luo, Fei; Chang, Jingyu; Xu, Ruxiang

    2015-02-01

    The aim of this study was to investigate voluntary wheel running behavior in the unilateral 6-hydroxydopamine (6-OHDA) rat model. Male Sprague-Dawley rats were assigned to 2 groups : 6-OHDA group (n=17) and control group (n=8). The unilateral 6-OHDA rat model was induced by injection of 6-OHDA into unilateral medial forebrain bundle using a stereotaxic instrument. Voluntary wheel running activity was assessed per day in successfully lesioned rats (n=10) and control rats. Each behavioral test lasted an hour. The following parameters were investigated during behavioral tests : the number of running bouts, the distance moved in the wheel, average peak speed in running bouts and average duration from the running start to the peak speed. The number of running bouts and the distance moved in the wheel were significantly decreased in successfully lesioned rats compared with control rats. In addition, average peak speed in running bouts was decreased, and average duration from the running start to the peak speed was increased in lesioned animals, which might indicate motor deficits in these rats. These behavioral changes were still observed 42 days after lesion. Voluntary wheel running behavior is impaired in the unilateral 6-OHDA rat model and may represent a useful tool to quantify motor deficits in this model.

  7. Antiulcer activity and the mechanism of action of magaldrate in gastric ulceration models of rat

    National Research Council Canada - National Science Library

    Patel, A V; Santani, D D; Goyal, R K

    2000-01-01

    The present study was undertaken to investigate the mechanism of cytoprotective effects of magaldrate in aspirin plus pylorus-ligation model and ethanol-induced gastric ulcer model in rats. Magaldrate (60 mg/kg, p.o...

  8. Sleep Changes in a Rat Prenatal Stress Model of Depression

    DEFF Research Database (Denmark)

    Skoven, Christian; Sickman, Helle M.; Bastlund, Jesper Frank

    determination of sleep-wakefulness state. As traumatic episodes can trigger episodes of clinical depression, we also investigated effects of an acute stressor during the recording period. PNS animals (n=21) had an 82% increase in amount of REMS (11.6±1.4% vs 6.3±0.9%; phours of the dark......Major depression is one of the most frequently occurring mental health disorders, but is characterized by diverse symptomatology. Sleep disturbances, however, are commonplace in depressive patients. These alterations include increased duration of Rapid Eye Movement Sleep (REMS) and increased sleep...... fragmentation. Stressful life events during the second trimester of human pregnancy increase the risk of depression in the offspring. Similarly, rodents exposed to prenatal stress (PNS) during gestation express depression- like behavioral changes. Accordingly, we investigated sleep changes in a rat PNS model...

  9. A model of calcium homeostasis in the rat.

    Science.gov (United States)

    Granjon, David; Bonny, Olivier; Edwards, Aurélie

    2016-11-01

    We developed a model of calcium homeostasis in the rat to better understand the impact of dysfunctions such as primary hyperparathyroidism and vitamin D deficiency on calcium balance. The model accounts for the regulation of calcium intestinal uptake, bone resorption, and renal reabsorption by parathyroid hormone (PTH), vitamin D 3 , and Ca 2+ itself. It is the first such model to incorporate recent findings regarding the role of the calcium-sensing receptor (CaSR) in the kidney, the presence of a rapidly exchangeable pool in bone, and the delayed response of vitamin D 3 synthesis. Accounting for two (fast and slow) calcium storage compartments in bone allows the model to properly predict the effects of bisphophonates on the plasma levels of Ca 2+ ([Ca 2+ ] p ), PTH, and vitamin D 3 Our model also suggests that Ca 2+ exchange rates between plasma and the fast pool vary with both sex and age, allowing [Ca 2+ ] p to remain constant in spite of sex- and age-based hormonal and other differences. Our results suggest that the inconstant hypercalciuria that is observed in primary hyperparathyroidism can be attributed in part to counterbalancing effects of PTH and CaSR in the kidney. Our model also correctly predicts that calcimimetic agents such as cinacalcet bring down [Ca 2+ ] p to within its normal range in primary hyperparathyroidism. In addition, the model provides a simulation of CYP24A1 inactivation that leads to a situation reminiscent of infantile hypercalcemia. In summary, our model of calcium handling can be used to decipher the complex regulation of calcium homeostasis. Copyright © 2016 the American Physiological Society.

  10. Modeling interpopulation dispersal by banner-tailed kangaroo rats

    Science.gov (United States)

    Skvarla, J.L.; Nichols, J.D.; Hines, J.E.; Waser, P.M.

    2004-01-01

    Many metapopulation models assume rules of population connectivity that are implicitly based on what we know about within-population dispersal, but especially for vertebrates, few data exist to assess whether interpopulation dispersal is just within-population dispersal "scaled up." We extended existing multi-stratum mark-release-recapture models to incorporate the robust design, allowing us to compare patterns of within- and between-population movement in the banner-tailed kangaroo rat (Dipodomys spectabilis). Movement was rare among eight populations separated by only a few hundred meters: seven years of twice-annual sampling captured >1200 individuals but only 26 interpopulation dispersers. We developed a program that implemented models with parameters for capture, survival, and interpopulation movement probability and that evaluated competing hypotheses in a model selection framework. We evaluated variants of the island, stepping-stone, and isolation-by-distance models of interpopulation movement, incorporating effects of age, season, and habitat (short or tall grass). For both sexes, QAICc values clearly favored isolation-by-distance models, or models combining the effects of isolation by distance and habitat. Models with probability of dispersal expressed as linear-logistic functions of distance and as negative exponentials of distance fit the data equally well. Interpopulation movement probabilities were similar among sexes (perhaps slightly biased toward females), greater for juveniles than adults (especially for females), and greater before than during the breeding season (especially for females). These patterns resemble those previously described for within-population dispersal in this species, which we interpret as indicating that the same processes initiate both within- and between-population dispersal.

  11. Cyclosporin safety in a simplified rat brain tumor implantation model

    Directory of Open Access Journals (Sweden)

    Francisco H. C. Felix

    2012-01-01

    Full Text Available Brain cancer is the second neurological cause of death. A simplified animal brain tumor model using W256 (carcinoma 256, Walker cell line was developed to permit the testing of novel treatment modalities. Wistar rats had a cell tumor solution inoculated stereotactically in the basal ganglia (right subfrontal caudate. This model yielded tumor growth in 95% of the animals, and showed absence of extracranial metastasis and systemic infection. Survival median was 10 days. Estimated tumor volume was 17.08±6.7 mm³ on the 7th day and 67.25±19.8 mm³ on 9th day post-inoculation. Doubling time was 24.25 h. Tumor growth induced cachexia, but no hematological or biochemical alterations. This model behaved as an undifferentiated tumor and can be promising for studying tumor cell migration in the central nervous system. Dexamethasone 3.0 mg/kg/day diminished significantly survival in this model. Cyclosporine 10 mg/kg/day administration was safely tolerated.

  12. A rat model for determining the postprandial response to foods.

    Science.gov (United States)

    Belobrajdic, Damien P; Wei, Jiangqin; Bird, Anthony R

    2017-03-01

    The use of small animal models for studying postprandial changes in circulating nutrients, hormones and metabolic biomarkers is hampered by the limited quantity of blood that can be withdrawn for analysis. Here, we describe the development of an unrestrained, meal-fed rat model, having a permanent or temporary vascular cannula that permits repeated blood sampling. The applicability and performance of the model were evaluated in a series of experiments on acute glycaemic and insulinaemic responses to carbohydrate-based test meals. A test food containing 0.4 g carbohydrate raised blood glucose by 1.5 mmol L -1 . Postprandial blood glucose levels peaked at 15 min and returned to baseline at 180 min, whereas they remained elevated for longer when the test meal contained 1.25 g carbohydrate. The glycaemic response tended (P = 0.063) to be higher when the meal tolerance test was conducted at the start rather than the end of the dark period, but the insulinaemic response was unaffected. The magnitude of the glycaemic response was less for blood collected from the caudal vein compared to that from the jugular vein. Both cannulation strategies were equally effective in enabling return of red blood cells, thus preserving blood volume. This improved small animal model affords new opportunities to screen foods for nutrient bioavailability and explore metabolic mechanisms mediating responses to food consumption. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  13. Circadian urinary citrate excretion in a rat model of exercise.

    Science.gov (United States)

    Nuñez, Paula; Diaz, Irene; Perillan, Carmen; Arguelles, Juan; Diaz, Elena

    2017-01-15

    Circadian rhythms are the approximate 24h biological cycles that function to prepare an organism for daily environmental changes. Circadian rhythms unquestionably play critical roles in metabolic homeostasis and the exercise has emerged as a strong non-photic time cue or zeitgeber in animal models and humans. Numerous studies about the effects of exercise on the citrate synthase activity have been published. Citrate is used to assess energy production or expenditure because it is a substrate of the Krebs Cycle, a cycle for oxidative energy production. We tested the existence of a rhythmic urinary citrate excretion in a rat model that is made to exercise at six different points during the day. The data obtained by the enzyme assays were fitted to a mathematical model (Fourier series), showing for the first time, the existence of a distinct ultradian rhythm in the urinary citrate excretion. The aerobic exercise led to the increase in the period length of the ultradian rhythm and raised the acrophase value of the urinary citrate excretion. Therefore, the urinary citrate excretion pattern changed after exercise, showing a clear circadian rhythm fitted to the mathematical model. The citrate urine samples could provide accurate data for ranking an individual's metabolic status. Using exercise to maintain the circadian clock at an appropriate phase and amplitude might be effective to prevent cardiometabolic disease development. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Differentiated analysis of orthodontic tooth movement in rats with an improved rat model and three-dimensional imaging.

    Science.gov (United States)

    Kirschneck, Christian; Proff, Peter; Fanghaenel, Jochen; Behr, Michael; Wahlmann, Ulrich; Roemer, Piero

    2013-12-01

    Rat models currently available for analysis of orthodontic tooth movement often lack differentiated, reliable and precise measurement systems allowing researchers to separately investigate the individual contribution of tooth tipping, body translation and root torque to overall displacement. Many previously proposed models have serious limitations such as the rather inaccurate analysis of the effects of orthodontic forces on rat incisors. We therefore developed a differentiated measurement system that was used within a rat model with the aim of overcoming the limitations of previous studies. The first left upper molar and the upper incisors of 24 male Wistar rats were subjected to a constant orthodontic force of 0.25 N by means of a NiTi closed coil spring for up to four weeks. The extent of the various types of tooth movement was measured optometrically with a CCD microscope camera and cephalometrically by means of cone beam computed tomography (CBCT). Both types of measurement proved to be reliable for consecutive measurements and the significant tooth movement induced had no harmful effects on the animals. Movement kinetics corresponded to known physiological processes and tipping and body movement equally contributed to the tooth displacement. The upper incisors of the rats were significantly deformed and their natural eruption was effectively halted. The results showed that our proposed measurement systems used within a rat model resolved most of the inadequacies of previous studies. They are reliable, precise and physiological tools for the differentiated analysis of orthodontic tooth movement while simultaneously preserving animal welfare. Copyright © 2013 Elsevier GmbH. All rights reserved.

  15. In Situ Perfusion Model in Rat Colon for Drug Absorption Studies: Comparison with Small Intestine and Caco-2 Cell Model.

    Science.gov (United States)

    Lozoya-Agullo, Isabel; González-Álvarez, Isabel; González-Álvarez, Marta; Merino-Sanjuán, Matilde; Bermejo, Marival

    2015-09-01

    Our aim is to develop and to validate the in situ closed loop perfusion method in rat colon and to compare with small intestine and Caco-2 cell models. Correlations with human oral fraction absorbed (Fa) and human colon fraction absorbed (Fa_colon) were developed to check the applicability of the rat colon model for controlled release (CR) drug screening. Sixteen model drugs were selected and their permeabilities assessed in rat small intestine and colon, and in Caco-2 monolayers. Correlations between colon/intestine/Caco-2 permeabilities versus human Fa and human Fa_colon have been explored to check model predictability and to apply a BCS approach in order to propose a cut off value for CR screening. Rat intestine perfusion with Doluisio's method and single-pass technique provided a similar range of permeabilities demonstrating the possibility of combining data from different laboratories. Rat colon permeability was well correlated with Caco-2 cell-4 days model reflecting a higher paracellular permeability. Rat colon permeabilities were also higher than human colon ones. In spite of the magnitude differences, a good sigmoidal relationship has been shown between rat colon permeabilities and human colon fractions absorbed, indicating that rat colon perfusion can be used for compound classification and screening of CR candidates. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  16. Rat model of cancer-induced bone pain: changes in nonnociceptive sensory neurons in vivo.

    Science.gov (United States)

    Zhu, Yong Fang; Ungard, Robert; Zacal, Natalie; Huizinga, Jan D; Henry, James L; Singh, Gurmit

    2017-07-01

    Clinical data on cancer-induced bone pain (CIBP) suggest extensive changes in sensory function. In a previous investigation of an animal model of CIBP, we have observed that changes in intrinsic membrane properties and excitability of dorsal root ganglion (DRG) nociceptive neurons correspond to mechanical allodynia and hyperalgesia. To investigate the mechanisms underlying changes in nonnociceptive sensory neurons in this model, we have compared the electrophysiological properties of primary nonnociceptive sensory neurons at 2 weeks after CIBP model induction with properties in sham control animals. Copenhagen rats were injected with 10 6 MAT-LyLu rat prostate cancer cells into the distal femur epiphysis to generate a model of CIBP. After von Frey tactile measurement of mechanical withdrawal thresholds, the animals were prepared for acute electrophysiological recordings of mechanically sensitive neurons in the DRG in vivo. The mechanical withdrawal threshold progressively decreased in CIBP model rats. At neurons between CIBP model rats and sham rats. However, at >2 weeks, the Aβ-fiber low-threshold mechanoreceptors (LTMs) in CIBP model rats exhibited a slowing of the dynamics of action potential (AP) genesis, including wider AP duration and lower AP amplitude compared with sham rats. Furthermore, enhanced excitability of Aβ-fiber LTM neurons was observed as an excitatory discharge in response to intracellular injection of depolarizing current into the soma. After induction of the CIBP model, Aβ-fiber LTMs at >2 weeks but not sensory neurons might be involved in the peripheral sensitization and tumor-induced tactile hypersensitivity in CIBP.

  17. Rat indwelling urinary catheter model of Candida albicans biofilm infection.

    Science.gov (United States)

    Nett, Jeniel E; Brooks, Erin G; Cabezas-Olcoz, Jonathan; Sanchez, Hiram; Zarnowski, Robert; Marchillo, Karen; Andes, David R

    2014-12-01

    Indwelling urinary catheters are commonly used in the management of hospitalized patients. Candida can adhere to the device surface and propagate as a biofilm. These Candida biofilm communities differ from free-floating Candida, exhibiting high tolerance to antifungal therapy. The significance of catheter-associated candiduria is often unclear, and treatment may be problematic considering the biofilm drug-resistant phenotype. Here we describe a rodent model for the study of urinary catheter-associated Candida albicans biofilm infection that mimics this common process in patients. In the setting of a functioning, indwelling urinary catheter in a rat, Candida proliferated as a biofilm on the device surface. Characteristic biofilm architecture was observed, including adherent, filamentous cells embedded in an extracellular matrix. Similar to what occurs in human patients, animals with this infection developed candiduria and pyuria. Infection progressed to cystitis, and a biofilmlike covering was observed over the bladder surface. Furthermore, large numbers of C. albicans cells were dispersed into the urine from either the catheter or bladder wall biofilm over the infection period. We successfully utilized the model to test the efficacy of antifungals, analyze transcriptional patterns, and examine the phenotype of a genetic mutant. The model should be useful for future investigations involving the pathogenesis, diagnosis, therapy, prevention, and drug resistance of Candida biofilms in the urinary tract. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  18. Rapamycin is neuroprotective in a rat chronic hypertensive glaucoma model.

    Directory of Open Access Journals (Sweden)

    Wenru Su

    Full Text Available Glaucoma is a leading cause of irreversible blindness. Injury of retinal ganglion cells (RGCs accounts for visual impairment of glaucoma. Here, we report rapamycin protects RGCs from death in experimental glaucoma model and the underlying mechanisms. Our results showed that treatment with rapamycin dramatically promote RGCs survival in a rat chronic ocular hypertension model. This protective action appears to be attributable to inhibition of neurotoxic mediators release and/or direct suppression of RGC apoptosis. In support of this mechanism, in vitro, rapamycin significantly inhibits the production of NO, TNF-α in BV2 microglials by modulating NF-κB signaling. In experimental animals, treatment with rapamycin also dramatically inhibited the activation of microglials. In primary RGCs, rapamycin was capable of direct suppression the apoptosis of primary RGCs induced by glutamate. Mechanistically, rapamycin-mediated suppression of RGCs apoptosis is by sparing phosphorylation of Akt at a site critical for maintenance of its survival-promoting activity in cell and animal model. These results demonstrate that rapamycin is neuroprotective in experimental glaucoma, possibly via decreasing neurotoxic releasing and suppressing directly apoptosis of RGCs.

  19. Standardised Models for Inducing Experimental Peritoneal Adhesions in Female Rats

    Directory of Open Access Journals (Sweden)

    Bernhard Kraemer

    2014-01-01

    Full Text Available Animal models for adhesion induction are heterogeneous and often poorly described. We compare and discuss different models to induce peritoneal adhesions in a randomized, experimental in vivo animal study with 72 female Wistar rats. Six different standardized techniques for peritoneal trauma were used: brushing of peritoneal sidewall and uterine horns (group 1, brushing of parietal peritoneum only (group 2, sharp excision of parietal peritoneum closed with interrupted sutures (group 3, ischemic buttons by grasping the parietal peritoneum and ligating the base with Vicryl suture (group 4, bipolar electrocoagulation of the peritoneum (group 5, and traumatisation by electrocoagulation followed by closure of the resulting peritoneal defect using Vicryl sutures (group 6. Upon second look, there were significant differences in the adhesion incidence between the groups (P<0.01. Analysis of the fraction of adhesions showed that groups 2 (0% and 5 (4% were significantly less than the other groups (P<0.01. Furthermore, group 6 (69% was significantly higher than group 1 (48% (P<0.05 and group 4 (47% (P<0.05. There was no difference between group 3 (60% and group 6 (P=0.2. From a clinical viewpoint, comparison of different electrocoagulation modes and pharmaceutical adhesion barriers is possible with standardised models.

  20. Thujone corrects cholesterol and triglyceride profiles in diabetic rat model.

    Science.gov (United States)

    Baddar, Nour W Al-Haj; Aburjai, Talal A; Taha, Mutasem O; Disi, Ahmad M

    2011-07-01

    Thujone, which is the major constituent in Salvia sp. (Lamiaceae), was found to correct the lipid profile (cholesterol and triglycerides) in diabetic rats. Oral treatment with thujone (5 mg kg⁻¹ body weight dose) significantly adjusted cholesterol and triglyceride levels in diabetic rats (p ≤ 0.05) to normal levels compared to diabetic untreated rats. This provides a premise in the field of finding new agents to treat diabetic complications.

  1. Osteoprotective effect of Monascus-fermented dioscorea in ovariectomized rat model of postmenopausal osteoporosis.

    Science.gov (United States)

    Chiang, Shen-Shih; Chang, Shang-Ping; Pan, Tzu-Ming

    2011-09-14

    This experiment established the ovariectomized (OVX) rat model of postmenopausal osteoporosis and examined the effect of the oral administration of different dosages of dioscorea, red mold dioscorea (RMD), and soy isoflavones on bone mineral density (BMD). Three months after osteoporosis had been induced and 4 weeks after feeding had begun, the tibia and femur BMD of OVX rats administered RMD showed significant increases compared with that of all other groups of OVX rats. Closer examination using microcomputed tomography also revealed that the RMD-administered rats had denser trabecular bone volume and a higher trabecular number compared to all other rat groups. Reconstructed 3D imaging indicated increases in cancellous bone mineral content, cancellous bone mineral density, and cortical bone mineral content of the proximal tibia in OVX rats. These findings indicate that administration of monacolin K and phytoestrogen diosgenin could prevent bone loss induced by estrogen deficiency.

  2. A RAT MODEL OF HEART FAILURE INDUCED BY ISOPROTERENOL AND A HIGH SALT DIET

    Science.gov (United States)

    Rat models of heart failure (HF) show varied pathology and time to disease outcome, dependent on induction method. We found that subchronic (4wk) isoproterenol (ISO) infusion in Spontaneously Hypertensive Heart Failure (SHHF) rats caused cardiac injury with minimal hypertrophy. O...

  3. Fenugreek Prevents the Development of STZ-Induced Diabetic Nephropathy in a Rat Model of Diabetes

    Directory of Open Access Journals (Sweden)

    Yingli Jin

    2014-01-01

    evidently reduced by fenugreek treatment. Furthermore, the upregulation of TGF-β1 and CTGF at a transcriptional and translational level in DN rats was distinctly inhibited by fenugreek. Consequently, fenugreek prevents DN development in a STZ-induced diabetic rat model.

  4. Effects of Ecballium elaterium on brain in a rat model of sepsis ...

    African Journals Online (AJOL)

    Demet Arslan

    2017-08-31

    Aug 31, 2017 ... model of sepsis-associated encephalopathy (SAE) [induced by cecal ligation and puncture. (CLP)]. Thirty rats were divided into three groups of 10 each: control, sepsis, and treatment. Rats were subjected to CLP except for the control group, which underwent laparatomy only. The treatment group received ...

  5. Evaluation of novel resorbable membranes for bone augmentation in a rat model

    NARCIS (Netherlands)

    Zeng, N.; van Leeuwen, A.C.; Yuan, Huipin; Bos, R.R.M.; Grijpma, Dirk W.; Kuijer, R.

    2016-01-01

    Objectives Our study compared two novel, biodegradable poly(trimethylene carbonate) (PTMC) barrier membranes to clinically applied barrier membranes in maintaining volume of block autologous bone grafts in a rat mandible model. Material and methods Two hundred and forty rats were included in this

  6. Plasma hormones facilitated the hypermotility of the colon in a chronic stress rat model.

    Directory of Open Access Journals (Sweden)

    Chengbai Liang

    Full Text Available OBJECTIVE: To study the relationship between brain-gut peptides, gastrointestinal hormones and altered motility in a rat model of repetitive water avoidance stress (WAS, which mimics the irritable bowel syndrome (IBS. METHODS: Male Wistar rats were submitted daily to 1-h of water avoidance stress (WAS or sham WAS (SWAS for 10 consecutive days. Plasma hormones were determined using Enzyme Immunoassay Kits. Proximal colonic smooth muscle (PCSM contractions were studied in an organ bath system. PCSM cells were isolated by enzymatic digestion and IKv and IBKca were recorded by the patch-clamp technique. RESULTS: The number of fecal pellets during 1 h of acute restraint stress and the plasma hormones levels of substance P (SP, thyrotropin-releasing hormone (TRH, motilin (MTL, and cholecystokinin (CCK in WAS rats were significantly increased compared with SWAS rats, whereas vasoactive intestinal peptide (VIP, calcitonin gene-related peptide (CGRP and corticotropin releasing hormone (CRH in WAS rats were not significantly changed and peptide YY (PYY in WAS rats was significantly decreased. Likewise, the amplitudes of spontaneous contractions of PCSM in WAS rats were significantly increased comparing with SWAS rats. The plasma of WAS rats (100 µl decreased the amplitude of spontaneous contractions of controls. The IKv and IBKCa of PCSMs were significantly decreased in WAS rats compared with SWAS rats and the plasma of WAS rats (100 µl increased the amplitude of IKv and IBKCa in normal rats. CONCLUSION: These results suggest that WAS leads to changes of plasma hormones levels and to disordered myogenic colonic motility in the short term, but that the colon rapidly establishes a new equilibrium to maintain the normal baseline functioning.

  7. The characterization of obese polycystic ovary syndrome rat model suitable for exercise intervention.

    Directory of Open Access Journals (Sweden)

    Chuyan Wu

    Full Text Available To develop a new polycystic ovary syndrome (PCOS rat model suitable for exercise intervention.Thirty six rats were randomly divided into three experimental groups: PCOS rats with high-fat diet (PF, n = 24, PCOS rats with ordinary diet (PO, n = 6, and control rats with ordinary diet (CO, n = 6. Two kinds of PCOS rat model were made by adjustment diet structure and testosterone injection for 28 days. After a successful animal model, PF model rats were randomly assigned to three groups: exercise with a continuation of high-fat diet (PF-EF, n = 6, sedentary with a continuation of high-fat diet (PF-SF, n = 6, exercise with an ordinary diet (PF-EO, n = 6. Fasting blood glucose (FBG and insulin (FINS, estrogen (E2, progesterone (P, and testosterone (T in serum were determined by RIA, and ovarian morphology was evaluated by Image-Pro plus 6.0.Body weight, Lee index, FINS increased significantly in PF rat model. Serum levels of E2 and T were significantly higher in PF and PO than in CO. Ovary organ index and ovarian areas were significant lower in PF than in CO. After intervention for 2 weeks, the levels of 1 h postprandial blood glucose (PBG1, 2 h postprandial blood glucose (PBG2, FINS and the serum levels of T decreased significantly in PF-EF rats and PF-EO rats. The ratio of FBG/FINS was significant higher in PF-EO rats than in PF-SF rats. Ovarian morphology showed that the numbers of preantral follicles and atretic follicles decreased significantly, and the numbers of antral follicles and corpora lutea increased significantly in the rats of PF-EF and PF-EO.By combination of high-fat diet and testosterone injection, the obese PCOS rat model is conformable with the lifestyle habits of fatty foods and insufficient exercise, and has metabolic and reproductive characteristics of human PCOS. This model can be applied to study exercise intervention.

  8. A Novel Model of Intravital Platelet Imaging Using CD41-ZsGreen1 Transgenic Rats.

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    Makoto Mizuno

    Full Text Available Platelets play pivotal roles in both hemostasis and thrombosis. Although models of intravital platelet imaging are available for thrombosis studies in mice, few are available for rat studies. The present effort aimed to generate fluorescent platelets in rats and assess their dynamics in a rat model of arterial injury. We generated CD41-ZsGreen1 transgenic rats, in which green fluorescence protein ZsGreen1 was expressed specifically in megakaryocytes and thus platelets. The transgenic rats exhibited normal hematological and biochemical values with the exception of body weight and erythroid parameters, which were slightly lower than those of wild-type rats. Platelet aggregation, induced by 20 μM ADP and 10 μg/ml collagen, and blood clotting times were not significantly different between transgenic and wild-type rats. Saphenous arteries of transgenic rats were injured with 10% FeCl3, and the formation of fluorescent thrombi was evaluated using confocal microscopy. FeCl3 caused time-dependent increases in the mean fluorescence intensity of injured arteries of vehicle-treated rats. Prasugrel (3 mg/kg, p.o., administered 2 h before FeCl3, significantly inhibited fluorescence compared with vehicle-treated rats (4.5 ± 0.4 vs. 14.9 ± 2.4 arbitrary fluorescence units at 30 min, respectively, n = 8, P = 0.0037. These data indicate that CD41-ZsGreen1 transgenic rats represent a useful model for intravital imaging of platelet-mediated thrombus formation and the evaluation of antithrombotic agents.

  9. Functional gait analysis in a spinal contusion rat model.

    Science.gov (United States)

    Bhimani, Abhiraj D; Kheirkhah, Pouyan; Arnone, Gregory D; Nahhas, Cindy R; Kumar, Prateek; Wonais, Matt; Hidrogo, Hugo; Aguilar, Eddy; Spalinski, Daniel; Gopalka, Mahie; Roth, Steven; Mehta, Ankit I

    2017-09-08

    Evaluating functional performance of spinal cord injury (SCI) rat models is essential for the development of novel treatments and breakthroughs. However, due to the variety of functional analysis methods available - each with its own strengths and weaknesses - it can be challenging to choose the most appropriate functional analysis test for the animal model. Therefore, we analyzed the strengths and weaknesses of five methods in order to determine which test is not only accurate and easily reproducible, but also relatively inexpensive so that it can be adopted universally. When comparing the Basso, Beattie, and Bresnahan (BBB) test, Ladder walking test, CatWalk test, Rotating Rod test, Microsoft Kinect system and VICON, we used the criteria of sensitivity, quality of data generated, statistical analysis of data, and rate of human error. These specific tests were chosen in order to compare the advantages and disadvantages of simple yet effective methods (BBB, Ladder test, and Rotating Rod test) to more complex and computerized methods (Catwalk, Microsoft Kinect and VICON). Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Mathematical Model of Ammonia Handling in the Rat Renal Medulla

    Science.gov (United States)

    Noiret, Lorette; Baigent, Stephen; Jalan, Rajiv; Thomas, S. Randall

    2015-01-01

    The kidney is one of the main organs that produces ammonia and release it into the circulation. Under normal conditions, between 30 and 50% of the ammonia produced in the kidney is excreted in the urine, the rest being absorbed into the systemic circulation via the renal vein. In acidosis and in some pathological conditions, the proportion of urinary excretion can increase to 70% of the ammonia produced in the kidney. Mechanisms regulating the balance between urinary excretion and renal vein release are not fully understood. We developed a mathematical model that reflects current thinking about renal ammonia handling in order to investigate the role of each tubular segment and identify some of the components which might control this balance. The model treats the movements of water, sodium chloride, urea, NH3 and NH4+, and non-reabsorbable solute in an idealized renal medulla of the rat at steady state. A parameter study was performed to identify the transport parameters and microenvironmental conditions that most affect the rate of urinary ammonia excretion. Our results suggest that urinary ammonia excretion is mainly determined by those parameters that affect ammonia recycling in the loops of Henle. In particular, our results suggest a critical role for interstitial pH in the outer medulla and for luminal pH along the inner medullary collecting ducts. PMID:26280830

  11. CM 40907: a structurally novel anticonvulsant in mice, rats and baboons

    Energy Technology Data Exchange (ETDEWEB)

    Chambon, J.P.; Brochard, J.; Hallot, A.; Heaulme, M.; Brodin, R.; Roncucci, R.; Biziere, K.

    1985-06-01

    CM 40907 (3-(4-hydroxypiperidyl)-6-(2'-chlorophenyl)-pyridazine) is a chemically original compound which possesses the pharmacological properties of a potent, p.o. active anticonvulsant. The anticonvulsant activity of CM 40907 was examined in mice, rats and photosensitive Papio-papio baboons and compared to that of phenobarbital, diphenylhydantoin, carbamazepine, sodium valproate and ethosuximide. In mice, CM 40907 antagonized electroconvulsive shock and chemically induced seizures with an overall potency comparable to that of carbamazepine and a therapeutic ratio (ED50 rotorod/ED50 electroshock) superior to that of ethosuximide, sodium valproate, phenobarbital and carbamazepine. In the rat CM 40907 suppressed completed kindled amygdaloid seizures and was approximately as active as phenobarbital. In naturally photosensitive Senegalese Papio-papio baboons CM 40907 antagonized myoclonus and cortical paroxysmal discharges. In this model CM 40907 was approximately one-fourth as potent as phenobarbital, twice as potent as carbamazepine and 6 times more potent than sodium valproate. In mice CM 40907, at anticonvulsant doses, increased the affinity of (/sup 3/H)flunitrazepam for its central receptor site. Based on these results it is postulated that CM 40907 is a potent and relatively nonsedative anticonvulsant and may be of therapeutic benefit in epileptic disorders.

  12. Presence of lymphatics in a rat tendon lesion model.

    Science.gov (United States)

    Tempfer, Herbert; Kaser-Eichberger, Alexandra; Korntner, Stefanie; Lehner, Christine; Kunkel, Nadja; Traweger, Andreas; Trost, Andrea; Strohmaier, Clemens; Bogner, Barbara; Runge, Christian; Bruckner, Daniela; Krefft, Karolina; Heindl, Ludwig M; Reitsamer, Herbert A; Schrödl, Falk

    2015-04-01

    Tendons lack sufficient blood supply and represent a bradytroph tissue with prolonged healing time under pathological conditions. While the role of lymphatics in wound/defect healing in tissues with regular blood supply is well investigated, its involvement in tendon defects is not clear. We here try to identify the role of the lymphatic system in a tendon lesion model with morphological methods. A rat Achilles tendon lesion model (n = 5) was created via surgical intervention. Two weeks after surgery, animals were killed and lesioned site removed and prepared for polarization microscopy (picrosirius red) and immunohistochemistry using the lymphatic markers PROX1, VEGFR3, CCL21, LYVE-1, PDPN, and the vascular marker CD31. Additionally, DAPI was applied. Untreated tendons served as controls, confocal laser-scanning microscopy was used for documentation. At the lesion site, polarization microscopy revealed a structural reintegration while immunohistochemistry detected band-like profiles immunoreactive for PDPN, VEGFR3, CCL21, LYVE1, and CD31, surrounding DAPI-positive nuclei. PROX1-positive nuclei were detected within the lesion forming lines and opposed to each other. These PROX1-positive nuclei were surrounded by LYVE-1- or VEGFR3-positive surfaces. Few CD31-positive profiles contained PROX1-positive nuclei, while the majority of CD31-positive profiles lacked PROX1-positive nuclei. VEGFR3-, PDPN-, and LYVE-1-positive profiles were numerous within the lesion site, but absent in control tissue. Within 2 weeks, a structural rearrangement takes place in this lesion model, with dense lymphatic supply. The role of lymphatics in tendon wound healing is unclear, and proposed model represents a good possibility to study healing dynamics and lymphangiogenesis in a tissue almost completely lacking lymphatics in physiological conditions.

  13. Virgin Coconut Oil Supplementation Prevents Bone Loss in Osteoporosis Rat Model

    Science.gov (United States)

    Hayatullina, Zil; Muhammad, Norliza; Mohamed, Norazlina; Soelaiman, Ima-Nirwana

    2012-01-01

    Oxidative stress and free radicals have been implicated in the pathogenesis of osteoporosis. Therefore, antioxidant compounds have the potential to be used in the prevention and treatment of the disease. In this study, we investigated the effects of virgin coconut oil (VCO) on bone microarchitecture in a postmenopausal osteoporosis rat model. VCO is a different form of coconut oil as it is rich with antioxidants. Three-month-old female rats were randomly grouped into baseline, sham-operated, ovariectomized control (Ovx), and ovariectomized rats fed with 8% VCO in their diet for six weeks (Ovx+VCO). Bone histomorphometry of the right femora was carried out at the end of the study. Rats supplemented with VCO had a significantly greater bone volume and trabecular number while trabecular separation was lower than the Ovx group. In conclusion, VCO was effective in maintaining bone structure and preventing bone loss in estrogen-deficient rat model. PMID:23024690

  14. A reproducible in-vivo model of lymphatic malformation in rats.

    Science.gov (United States)

    Sun, Y; Jia, J; Zhang, W; Liu, B; Zhang, Z; Zhao, Y

    2011-11-01

    The aim of this study was to develop a reproducible rat model of lymphatic malformation. Different types of adjuvant, with and without vascular endothelial growth factor (VEGF)-C, was injected into the neck and floor of the mouth of rats. The rats were killed 2 months after the injection. Injected rats developed cystic lesions in the neck and floor of the mouth. Immunohistochemical examination revealed that the cysts were lined by endothelium, which expressed the lymphatic endothelial markers LYVE-1 and VEGF receptor-3. Raman spectra of the liquid contents of the cysts were similar in all injected rats. Transmission electron microscopy revealed that the endothelial cells had no basement membrane or surrounding pericytes. The cystic lesions were consistent with human lymphatic malformation. This animal model could be used to investigate pathogenesis of lymphatic malformation and its responses to candidate therapies. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. The Influence of a High Salt Diet on a Rat Model of Isoproterenol-Induced Heart Failure

    Science.gov (United States)

    Rat models of heart failure (HF) show varied pathology and time to disease outcome, dependent on induction method. We found that subchronic (4 weeks) isoproterenol (ISO) infusion exacerbated cardiomyopathy in Spontaneously Hypertensive Heart Failure (SHHF) rats. Others have shown...

  16. Induced hypothermia is protective in a rat model of pneumococcal pneumonia associated with increased adenosine triphosphate availability and turnover

    NARCIS (Netherlands)

    Beurskens, Charlotte J. P.; Aslami, Hamid; Kuipers, Maria T.; Horn, Janneke; Vroom, Margreeth B.; van Kuilenburg, André B. P.; Roelofs, Joris J. T. H.; Schultz, Marcus J.; Juffermans, Nicole P.

    2012-01-01

    Objective: To determine the effect of induced hypothermia on bacterial growth, lung injury, and mitochondrial function in a rat model of pneumococcal pneumosepsis. Design: Animal study. Setting: University research laboratory. Subjects: Male Sprague-Dawley rats. Interventions: Subjects were

  17. DEFEROXAMINE ACCELERATED HEALING IN OPEN EXCISION WOUND MODEL IN RATS

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    Mahendra Ram

    2016-06-01

    Full Text Available Forty apparently healthy male Wister rats were used in this study and full thickness cutaneous wounds were created under pentobarbitone anesthesia. All the rats were divided into two groups, of which one (control was treated with ointment base and other with DFO ointment (0.1%. Wound size measurement and tissue collection were done on days 3, 7, 11 and 14 post-wounding. Histopathological changes were assessed by H&E staining. The percent wound healing was significantly higher on days 7, 11 and 14 in DFO-treated rats as compared to control. DFO markedly facilitated cutaneous wound healing in rats by recruitment of inflammatory cells, deposition of fibroblasts, formation of new blood vessels and epithelialization to the wound site. Therefore, topical application of DFO ointment might be of great use in cutaneous wound healing in rats.

  18. A novel newborn rat kernicterus model created by injecting a bilirubin solution into the cisterna magna.

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    Sijie Song

    Full Text Available BACKGROUND: Kernicterus still occurs around the world; however, the mechanism of bilirubin neurotoxicity remains unclear, and effective treatment strategies are lacking. To solve these problems, several kernicterus (or acute bilirubin encephalopathy animal models have been established, but these models are difficult and expensive. Therefore, the present study was performed to establish a novel kernicterus model that is simple and affordable by injecting unconjugated bilirubin solution into the cisterna magna (CM of ordinary newborn Sprague-Dawley (SD rats. METHODS: On postnatal day 5, SD rat pups were randomly divided into bilirubin and control groups. Then, either bilirubin solution or ddH2O (pH = 8.5 was injected into the CM at 10 µg/g (bodyweight. For model characterization, neurobehavioral outcomes were observed, mortality was calculated, and bodyweight was recorded after bilirubin injection and weaning. Apoptosis in the hippocampus was detected by H&E staining, TUNEL, flow cytometry and Western blotting. When the rats were 28 days old, learning and memory ability were evaluated using the Morris water maze test. RESULTS: The bilirubin-treated rats showed apparently abnormal neurological manifestations, such as clenched fists, opisthotonos and torsion spasms. Bodyweight gain in the bilirubin-treated rats was significantly lower than that in the controls (P<0.001. The early and late mortality of the bilirubin-treated rats were both dramatically higher than those of the controls (P = 0.004 and 0.017, respectively. Apoptosis and necrosis in the hippocampal nerve cells in the bilirubin-treated rats were observed. The bilirubin-treated rats performed worse than the controls on the Morris water maze test. CONCLUSION: By injecting bilirubin into the CM, we successfully created a new kernicterus model using ordinary SD rats; the model mimics both the acute clinical manifestations and the chronic sequelae. In particular, CM injection is easy

  19. Lemon juice has protective activity in a rat urolithiasis model

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    Oussama Abdelkhalek

    2007-10-01

    Full Text Available Abstract Background The use of herbal medicines (medicinal plants or phytotherapy has recently gained popularity in Europe and the United States. Nevertheless the exact mechanism of the preventive effects of these products is still far to be clearly established, being its knowledge necessary to successfully apply these therapies to avoid stone formation. Methods The effect of oral lemon juice administration on calcium oxalate urolithiasis was studied in male Wistar rats. Rats were rendered nephrolithic by providing drinking water containing 0.75% ethylene glycol [v/v] (EG and 2% ammonium chloride [w/v] (AC for 10 days. In addition to EG/AC treatment, three groups of rats were also gavage-administered solutions containing 100%, 75% or 50% lemon juice [v/v] (6 μl solution/g body weight. Positive control rats were treated with EG/AC but not lemon juice. Negative control rats were provided with normal drinking water, and were administered normal water by gavage. Each group contained 6 rats. After 10 days, serum samples were collected for analysis, the left kidney was removed and assessed for calcium levels using flame spectroscopy, and the right kidney was sectioned for histopathological analysis using light microscopy. Results Analysis showed that the rats treated with EG/AC alone had higher amounts of calcium in the kidneys compared to negative control rats. This EG/AC-induced increase in kidney calcium levels was inhibited by the administration of lemon juice. Histology showed that rats treated with EG/AC alone had large deposits of calcium oxalate crystals in all parts of the kidney, and that such deposits were not present in rats also treated with either 100% or 75% lemon juice. Conclusion These data suggest that lemon juice has a protective activity against urolithiasis.

  20. Young Sprague Dawley rats infected by Plasmodium berghei: A relevant experimental model to study cerebral malaria.

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    Sokhna Keita Alassane

    Full Text Available Cerebral malaria (CM is the most severe manifestation of human malaria yet is still poorly understood. Mouse models have been developed to address the subject. However, their relevance to mimic human pathogenesis is largely debated. Here we study an alternative cerebral malaria model with an experimental Plasmodium berghei Keyberg 173 (K173 infection in Sprague Dawley rats. As in Human, not all infected subjects showed cerebral malaria, with 45% of the rats exhibiting Experimental Cerebral Malaria (ECM symptoms while the majority (55% of the remaining rats developed severe anemia and hyperparasitemia (NoECM. These results allow, within the same population, a comparison of the noxious effects of the infection between ECM and severe malaria without ECM. Among the ECM rats, 77.8% died between day 5 and day 12 post-infection, while the remaining rats were spontaneously cured of neurological signs within 24-48 hours. The clinical ECM signs observed were paresis quickly evolving to limb paralysis, global paralysis associated with respiratory distress, and coma. The red blood cell (RBC count remained normal but a drastic decrease of platelet count and an increase of white blood cell numbers were noted. ECM rats also showed a decrease of glucose and total CO2 levels and an increase of creatinine levels compared to control rats or rats with no ECM. Assessment of the blood-brain barrier revealed loss of integrity, and interestingly histopathological analysis highlighted cyto-adherence and sequestration of infected RBCs in brain vessels from ECM rats only. Overall, this ECM rat model showed numerous clinical and histopathological features similar to Human CM and appears to be a promising model to achieve further understanding the CM pathophysiology in Humans and to evaluate the activity of specific antimalarial drugs in avoiding/limiting cerebral damages from malaria.

  1. Young Sprague Dawley rats infected by Plasmodium berghei: A relevant experimental model to study cerebral malaria.

    Science.gov (United States)

    Keita Alassane, Sokhna; Nicolau-Travers, Marie-Laure; Menard, Sandie; Andreoletti, Olivier; Cambus, Jean-Pierre; Gaudre, Noémie; Wlodarczyk, Myriam; Blanchard, Nicolas; Berry, Antoine; Abbes, Sarah; Colongo, David; Faye, Babacar; Augereau, Jean-Michel; Lacroux, Caroline; Iriart, Xavier; Benoit-Vical, Françoise

    2017-01-01

    Cerebral malaria (CM) is the most severe manifestation of human malaria yet is still poorly understood. Mouse models have been developed to address the subject. However, their relevance to mimic human pathogenesis is largely debated. Here we study an alternative cerebral malaria model with an experimental Plasmodium berghei Keyberg 173 (K173) infection in Sprague Dawley rats. As in Human, not all infected subjects showed cerebral malaria, with 45% of the rats exhibiting Experimental Cerebral Malaria (ECM) symptoms while the majority (55%) of the remaining rats developed severe anemia and hyperparasitemia (NoECM). These results allow, within the same population, a comparison of the noxious effects of the infection between ECM and severe malaria without ECM. Among the ECM rats, 77.8% died between day 5 and day 12 post-infection, while the remaining rats were spontaneously cured of neurological signs within 24-48 hours. The clinical ECM signs observed were paresis quickly evolving to limb paralysis, global paralysis associated with respiratory distress, and coma. The red blood cell (RBC) count remained normal but a drastic decrease of platelet count and an increase of white blood cell numbers were noted. ECM rats also showed a decrease of glucose and total CO2 levels and an increase of creatinine levels compared to control rats or rats with no ECM. Assessment of the blood-brain barrier revealed loss of integrity, and interestingly histopathological analysis highlighted cyto-adherence and sequestration of infected RBCs in brain vessels from ECM rats only. Overall, this ECM rat model showed numerous clinical and histopathological features similar to Human CM and appears to be a promising model to achieve further understanding the CM pathophysiology in Humans and to evaluate the activity of specific antimalarial drugs in avoiding/limiting cerebral damages from malaria.

  2. The rat: a laboratory model for studies of the diving response

    Science.gov (United States)

    Gan, Qi; Juric, Rajko

    2010-01-01

    Underwater submersion in mammals induces apnea, parasympathetically mediated bradycardia, and sympathetically mediated peripheral vasoconstriction. These effects are collectively termed the diving response, potentially the most powerful autonomic reflex known. Although these physiological responses are directed by neurons in the brain, study of neural control of the diving response has been hampered since 1) it is difficult to study the brains of animals while they are underwater, 2) feral marine mammals are usually large and have brains of variable size, and 3) there are but few references on the brains of naturally diving species. Similar responses are elicited in anesthetized rodents after stimulation of their nasal mucosa, but this nasopharyngeal reflex has not been compared directly with natural diving behavior in the rat. In the present study, we compared hemodynamic responses elicited in awake rats during volitional underwater submersion with those of rats swimming on the water's surface, rats involuntarily submerged, and rats either anesthetized or decerebrate and stimulated nasally with ammonia vapors. We show that the hemodynamic changes to voluntary diving in the rat are similar to those of naturally diving marine mammals. We also show that the responses of voluntary diving rats are 1) significantly different from those seen during swimming, 2) generally similar to those elicited in trained rats involuntarily “dunked” underwater, and 3) generally different from those seen from dunking naive rats underwater. Nasal stimulation of anesthetized rats differed most from the hemodynamic variables of rats trained to dive voluntarily. We propose that the rat trained to dive underwater is an excellent laboratory model to study neural control of the mammalian diving response, and also suggest that some investigations may be done with nasal stimulation of decerebrate preparations to decipher such control. PMID:20093670

  3. Diet-induced metabolic syndrome model in rats

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    Reza Homayounfar

    2013-03-01

    Full Text Available Background & Objective: Risk for heart disease, diabetes, and stroke increases with the number of the metabolic risk factors. In general, a person who has the metabolic syndrome is twice as likely to develop heart disease and five times as likely to develop diabetes as someone who does not have the metabolic syndrome. High-calorie-diet rodent models have contributed significantly to the analysis of the pathophysiology of the metabolic syndrome, but their phenotype varies distinctly between different studies and maybe is not very similar to a model of the metabolic syndrome in humans. We sought to create a model in this study close to the disease in humans.   Materials & Methods: Twenty male, Wistar rats were randomly assigned to the high-calorie diet group with 416 calories per 100 grams (researcher made or the control diet group for 12 weeks. Weight changes, lipid profile, glucose, insulin levels, and QUICKI index (an indicator of insulin sensitivity were measured. Weight changes were compared using the repeated measures and the independent t-test, and serum factors were compared using the independent t-test.   Results: There was a significant change in weight, glucose, insulin, and lipid profile except for HDL at the end of the study. The QUICKI index (0.34 ± 0.02 vs. 0.40 ± 0.01; p value <0.0001 suggested that insulin resistance had been created in the high-calorie diet group.   Conclusion: The present study demonstrates the ability to make diet-induced metabolic syndrome domestically.

  4. Additive effects of dietary glycotoxins and androgen excess on the kidney of a female rat model

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    Sotiria Palimeri

    2016-06-01

    Conclusions: The above mentioned data suggest that dietary glycotoxins, in combination with increased androgen exposure, exert a more profound negative impact on the kidney of an androgenized female rat model that mimics the metabolic characteristics of polycystic ovary syndrome.

  5. Efficacious rat model displays non-toxic effect with Korean beechwood creosote: a possible antibiotic substitute

    National Research Council Canada - National Science Library

    Quynh, Anh Nguyen Thai; Sharma, Neelesh; Cho, Kwang Keun; Yeo, Tae Jong; Kim, Ki Beom; Jeong, Chul Yon; Min, Tae Sun; Young, Kim Jae; Kim, Jin Nam; Jeong, Dong-Kee

    2014-01-01

    Wood creosote, an herbal anti-diarrheal and a mixture of major volatile compounds, was tested for its non-toxicological effects, using a rat model, with the objective to use the creosote as an antibiotic substitute...

  6. Pulmonary Transcriptional Response to Ozone in Healthy and Cardiovascular Compromised Rat Models

    Science.gov (United States)

    The genetic cardiovascular disease (CVD) and associated metabolic impairments can influence the lung injury from inhaled pollutants. We hypothesized that comparative assessment of global pulmonary expression profile of healthy and CVD-prone rat models will provide mechanistic ins...

  7. Association between probiotics and enteral nutrition in an experimental acute pancreatitis model in rats

    NARCIS (Netherlands)

    Baal, M.C.P.M. van; Rens, M.J. van; Geven, C.B.; Pol, F.M. van de; Brink, I. van den; Hannink, G.J.; Nagtegaal, I.D.; Peters, W.H.M.; Rijkers, G.T.; Gooszen, H.G.

    2014-01-01

    BACKGROUND/OBJECTIVES: Recently, a randomized controlled trial showed that probiotic prophylaxis was associated with an increased mortality in enterally fed patients with predicted severe pancreatitis. In a rat model for acute pancreatitis, we investigated whether an association between probiotic

  8. Assessment of pharmacokinetic interaction of spirulina with glitazone in a type 2 diabetes rat model.

    Science.gov (United States)

    Gupta, Annu; Nair, Anroop; Kumria, Rachna; Al-Dhubiab, Bandar-E; Chattopadhyaya, Ipshita; Gupta, Sumeet

    2013-12-01

    The objective of the current study was to assess the possible pharmacokinetic interactions of spirulina with glitazones in an insulin resistance rat model. Wistar male albino rats were equally divided into five groups: insulin resistant rats+spirulina (500 mg/kg)+pioglitazone (10 mg/kg), insulin resistant rats+pioglitazone (10 mg/kg), insulin resistant rats+spirulina (500 mg/kg)+rosiglitazone (10 mg/kg), insulin resistant rats+rosiglitazone (10 mg/kg), and insulin resistant rats+spirulina (500 mg/kg). Described doses of pioglitazone, rosiglitazone, or spirulina were per orally administered and the plasma drug concentrations were determined. The pharmacokinetic parameters such as Tmax, Cmax, AUC(0-α), t1/2, and Kel were determined by plotting the drug concentration as a function of time. The data observed in this acute study indicated that there was no statistically significant difference in any of the pharmacokinetic parameters (Tmax, Cmax, AUC(0-α), t1/2, and Kel) of glitazones (pioglitazone, rosiglitazone) or spirulina, when they were coadministered. Given the promising results, this study concludes that the coadministration of spirulina does not influence the pharmacokinetics of glitazones in a type 2 diabetes rat model. Further chronic in vivo studies are recommended to assess the real time effect.

  9. Degraded neural and behavioral processing of speech sounds in a rat model of Rett syndrome.

    Science.gov (United States)

    Engineer, Crystal T; Rahebi, Kimiya C; Borland, Michael S; Buell, Elizabeth P; Centanni, Tracy M; Fink, Melyssa K; Im, Kwok W; Wilson, Linda G; Kilgard, Michael P

    2015-11-01

    Individuals with Rett syndrome have greatly impaired speech and language abilities. Auditory brainstem responses to sounds are normal, but cortical responses are highly abnormal. In this study, we used the novel rat Mecp2 knockout model of Rett syndrome to document the neural and behavioral processing of speech sounds. We hypothesized that both speech discrimination ability and the neural response to speech sounds would be impaired in Mecp2 rats. We expected that extensive speech training would improve speech discrimination ability and the cortical response to speech sounds. Our results reveal that speech responses across all four auditory cortex fields of Mecp2 rats were hyperexcitable, responded slower, and were less able to follow rapidly presented sounds. While Mecp2 rats could accurately perform consonant and vowel discrimination tasks in quiet, they were significantly impaired at speech sound discrimination in background noise. Extensive speech training improved discrimination ability. Training shifted cortical responses in both Mecp2 and control rats to favor the onset of speech sounds. While training increased the response to low frequency sounds in control rats, the opposite occurred in Mecp2 rats. Although neural coding and plasticity are abnormal in the rat model of Rett syndrome, extensive therapy appears to be effective. These findings may help to explain some aspects of communication deficits in Rett syndrome and suggest that extensive rehabilitation therapy might prove beneficial. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Mesozeaxanthin Protects Retina from Oxidative Stress in a Rat Model.

    Science.gov (United States)

    Orhan, Cemal; Akdemir, Fatih; Tuzcu, Mehmet; Sahin, Nurhan; Yilmaz, Ismet; Deshpande, Jayant; Juturu, Vijaya; Sahin, Kazim

    2016-11-01

    Mesozeaxanthin (MZ) is able to protect against chronic and cumulative eye damage and neutralize free radicals produced by oxidative stress. The objective of the present study was to evaluate the protective potential of MZ against retinal oxidative damage and growth and transcription factors of the retina in rats fed with high-fat diet (HFD). Twenty-eight Sprague Dawley rats were randomly divided into the following 4 groups: (1) Control, (2) MZ (100 mg/kg bw/d), (3) HFD (42% of calories as fat), and (4) HFD+MZ (100 mg/kg bw/d) group rats were administered daily as supplement for 12 weeks. Consumption of HFD was associated with hyperglycemia and oxidative stress as reflected by increased serum MDA concentration (P retina of rats fed with HFD had increased levels of vascular endothelial growth factor (VEGF), inducible nitric oxide (iNOS), intercellular adhesion molecule-1 (ICAM-1), and nuclear factor-kappa B (NF-κB) levels and decreased nuclear factor erythroid 2-related factor 2 (Nrf2) and heme-oxygenase 1(HO-1) levels compared to the healthy rat retina (P retina of rats fed (P retina and the ability to modulate oxidative stress of retina in rats fed an HFD by suppressing retinal lipid peroxidation and regulating growth and transcription factors.

  11. The JCR:LA-cp rat: a novel rodent model of cystic medial necrosis.

    Science.gov (United States)

    Pung, Yuh Fen; Chilian, William M; Bennett, Martin R; Figg, Nichola; Kamarulzaman, Mohd Hamzah

    2017-03-01

    Although there are multiple rodent models of the metabolic syndrome, very few develop vascular complications. In contrast, the JCR:LA-cp rat develops both metabolic syndrome and early atherosclerosis in predisposed areas. However, the pathology of the normal vessel wall has not been described. We examined JCR:LA control (+/+) or cp/cp rats fed normal chow diet for 6 or 18 mo. JCR:LA-cp rats developed multiple features of advanced cystic medial necrosis including "cysts," increased collagen formation and proteoglycan deposition around cysts, apoptosis of vascular smooth muscle cells, and spotty medial calcification. These appearances began within 6 mo and were extensive by 18 mo. JCR:LA-cp rats had reduced medial cellularity, increased medial thickness, and vessel hypoxia that was most marked in the adventitia. In conclusion, the normal chow-fed JCR:LA-cp rat represents a novel rodent model of cystic medial necrosis, associated with multiple metabolic abnormalities, vascular smooth muscle cell apoptosis, and vessel hypoxia.NEW & NOTEWORTHY Triggers for cystic medial necrosis (CMN) have been difficult to study due to lack of animal models to recapitulate the pathologies seen in humans. Our study is the first description of CMN in the rat. Thus the JCR:LA-cp rat represents a useful model to investigate the underlying molecular changes leading to the development of CMN. Copyright © 2017 the American Physiological Society.

  12. Evaluating resveratrol as a therapeutic bone agent: preclinical evidence from rat models of osteoporosis.

    Science.gov (United States)

    Tou, Janet C

    2015-08-01

    Resveratrol (RSV) is a naturally occurring plant polyphenol that has potential to attenuate osteoporosis with distinct pathologies. This review evaluates preclinical evidence regarding the efficacy and safety of RSV as a therapeutic bone agent using different rat models. Limitations of these animal models are discussed, and suggestions for strengthening the experimental design of future studies are provided. The ovariectomized rat model of postmenopausal osteoporosis reported that RSV supplementation attenuated estrogen deficiency-induced bone loss and trabecular structural deterioration. RSV safety was indicated by the absence of stimulation of estrogen-sensitive tissue. Providing RSV to rats aged >6 months attenuated age-related bone mass loss and structural deterioration but produced inconsistent effects on bones in rats aged osteoporosis reported that RSV attenuated bone loss in old rats, but higher doses and longer duration supplementation before mechanical loading were required for younger rats. Limitations common to studies using rat models of osteoporosis include requirements to include animals that are skeletally mature, longer study durations, and to adjust for potential confounding effects due to altered body weight and endocrine function. Strengthening experimental design can contribute to translation of animal results to clinically relevant recommendations for humans. Published 2015. This article is U.S. Government work and is in the public domain in the USA.

  13. A novel newborn rat kernicterus model created by injecting a bilirubin solution into the cisterna magna.

    Science.gov (United States)

    Song, Sijie; Hu, Ying; Gu, Xianfang; Si, Feifei; Hua, Ziyu

    2014-01-01

    Kernicterus still occurs around the world; however, the mechanism of bilirubin neurotoxicity remains unclear, and effective treatment strategies are lacking. To solve these problems, several kernicterus (or acute bilirubin encephalopathy) animal models have been established, but these models are difficult and expensive. Therefore, the present study was performed to establish a novel kernicterus model that is simple and affordable by injecting unconjugated bilirubin solution into the cisterna magna (CM) of ordinary newborn Sprague-Dawley (SD) rats. On postnatal day 5, SD rat pups were randomly divided into bilirubin and control groups. Then, either bilirubin solution or ddH2O (pH = 8.5) was injected into the CM at 10 µg/g (bodyweight). For model characterization, neurobehavioral outcomes were observed, mortality was calculated, and bodyweight was recorded after bilirubin injection and weaning. Apoptosis in the hippocampus was detected by H&E staining, TUNEL, flow cytometry and Western blotting. When the rats were 28 days old, learning and memory ability were evaluated using the Morris water maze test. The bilirubin-treated rats showed apparently abnormal neurological manifestations, such as clenched fists, opisthotonos and torsion spasms. Bodyweight gain in the bilirubin-treated rats was significantly lower than that in the controls (Pkernicterus model using ordinary SD rats; the model mimics both the acute clinical manifestations and the chronic sequelae. In particular, CM injection is easy to perform; thus, more stable models for follow-up study are available.

  14. Reproduction and evaluation of a rat model of inhalation lung injury caused by black gunpowder smog

    OpenAIRE

    Yi-fan LIU; Hong-wei TANG; Xiao-li WU; Yin-jing XIE; Hong-rui ZHANG; Jin-yan DUAN; Dai-jun XIANG; Xiao-mei LAN; Mian-yang LI; Cheng-bin WANG; Deng-qing LI

    2013-01-01

    Objective To reproduce and evaluate a rat model of inhalation lung injury caused by black gunpowder smog. Methods The smog composition was analyzed and a rat model of inhalation lung injury was reproduced. Forty two healthy male Wistar rats were randomly divided into normal control (NC) group and 1h, 2h, 6h, 24h, 48h and 96h after inhalation group (n=6). The arterial blood gas, wet to dry weight ratio (W/D) of lung, leukocyte count, and protein concentration in broncho-alveolar lavage fluid (...

  15. Modeling CICR in rat ventricular myocytes: voltage clamp studies

    Directory of Open Access Journals (Sweden)

    Palade Philip T

    2010-11-01

    Full Text Available Abstract Background The past thirty-five years have seen an intense search for the molecular mechanisms underlying calcium-induced calcium-release (CICR in cardiac myocytes, with voltage clamp (VC studies being the leading tool employed. Several VC protocols including lowering of extracellular calcium to affect Ca2+ loading of the sarcoplasmic reticulum (SR, and administration of blockers caffeine and thapsigargin have been utilized to probe the phenomena surrounding SR Ca2+ release. Here, we develop a deterministic mathematical model of a rat ventricular myocyte under VC conditions, to better understand mechanisms underlying the response of an isolated cell to calcium perturbation. Motivation for the study was to pinpoint key control variables influencing CICR and examine the role of CICR in the context of a physiological control system regulating cytosolic Ca2+ concentration ([Ca2+]myo. Methods The cell model consists of an electrical-equivalent model for the cell membrane and a fluid-compartment model describing the flux of ionic species between the extracellular and several intracellular compartments (cell cytosol, SR and the dyadic coupling unit (DCU, in which resides the mechanistic basis of CICR. The DCU is described as a controller-actuator mechanism, internally stabilized by negative feedback control of the unit's two diametrically-opposed Ca2+ channels (trigger-channel and release-channel. It releases Ca2+ flux into the cyto-plasm and is in turn enclosed within a negative feedback loop involving the SERCA pump, regulating[Ca2+]myo. Results Our model reproduces measured VC data published by several laboratories, and generates graded Ca2+ release at high Ca2+ gain in a homeostatically-controlled environment where [Ca2+]myo is precisely regulated. We elucidate the importance of the DCU elements in this process, particularly the role of the ryanodine receptor in controlling SR Ca2+ release, its activation by trigger Ca2+, and its

  16. Translational mixed-effects PKPD modelling of recombinant human growth hormone - from hypophysectomized rat to patients

    DEFF Research Database (Denmark)

    Thorsted, A; Thygesen, P; Agersø, H

    2016-01-01

    and validated through simulations relative to patient data. KEY RESULTS: The final model described rhGH PK as a two compartmental model with parallel linear and non-linear elimination terms, parallel first-order absorption with a total s.c. bioavailability of 87% in rats. Induction of IGF-1 was described...... s.c. administration was over predicted. After correction of the human s.c. absorption model, the induction model for IGF-1 well described the human PKPD data. CONCLUSIONS: A translational mechanistic PKPD model for rhGH was successfully developed from experimental rat data. The model links...

  17. Dynamics of myelin content decrease in the rat stroke model

    Science.gov (United States)

    Kisel, A.; Khodanovich, M.; Atochin, D.; Mustafina, L.; Yarnykh, V.

    2017-08-01

    The majority of studies were usually focused on neuronal death after brain ischemia; however, stroke affects all cell types including oligodendrocytes that form myelin sheath in the CNS. Our study is focused on the changes of myelin content in the ischemic core and neighbor structures in early terms (1, 3 and 10 days) after stroke. Stroke was modeled with middle cerebral artery occlusion (MCAo) in 15 male rats that were divided into three groups by time points after operation. Brain sections were histologically stained with Luxol Fast Blue (LFB) for myelin quantification. The significant demyelination was found in the ischemic core, corpus callosum, anterior commissure, whereas myelin content was increased in caudoputamen, internal capsule and piriform cortex compared with the contralateral hemisphere. The motor cortex showed a significant increase of myelin content on the 1st day and a significant decrease on the 3rd and 10th days after MCAo. These results suggest that stroke influences myelination not only in the ischemic core but also in distant structures.

  18. A novel experimental model of erectile dysfunction in rats with heart failure using volume overload.

    Directory of Open Access Journals (Sweden)

    Fábio Henrique Silva

    Full Text Available Patients with heart failure (HF display erectile dysfunction (ED. However, the pathophysiology of ED during HF remains poorly investigated.This study aimed to characterize the aortocaval fistula (ACF rat model associated with HF as a novel experimental model of ED. We have undertaken molecular and functional studies to evaluate the alterations of the nitric oxide (NO pathway, autonomic nervous system and oxidative stress in the penis.Male rats were submitted to ACF for HF induction. Intracavernosal pressure in anesthetized rats was evaluated. Concentration-response curves to contractile (phenylephrine and relaxant agents (sodium nitroprusside; SNP, as well as to electrical field stimulation (EFS, were obtained in the cavernosal smooth muscle (CSM strips from sham and HF rats. Protein expression of endothelial NO synthase (eNOS and neuronal NO synthase (nNOS and phosphodiestarese-5 in CSM were evaluated, as well as NOX2 (gp91phox and superoxide dismutase (SOD mRNA expression. SOD activity and thiobarbituric acid reactive substances (TBARs were also performed in plasma.HF rats display erectile dysfunction represented by decreased ICP responses compared to sham rats. The neurogenic contractile responses elicited by EFS were greater in CSM from the HF group. Likewise, phenylephrine-induced contractions were greater in CSM from HF rats. Nitrergic response induced by EFS were decreased in the cavernosal tissue, along with lower eNOS, nNOS and phosphodiestarese-5 protein expressions. An increase of NOX2 and SOD mRNA expression in CSM and plasma TBARs of HF group were detected. Plasma SOD activity was decreased in HF rats.ED in HF rats is associated with decreased NO bioavailability in erectile tissue due to eNOS/nNOS dowregulation and NOX2 upregulation, as well as hypercontractility of the penis. This rat model of ACF could be a useful tool to evaluate the molecular alterations of ED associated with HF.

  19. Antimicrobial Activity of Artemisia absinthium Against Surgical Wounds Infected by Staphylococcus aureus in a Rat Model.

    Science.gov (United States)

    Moslemi, Hamid Reza; Hoseinzadeh, Hesamoddin; Badouei, Mahdi Askari; Kafshdouzan, Khatereh; Fard, Ramin Mazaheri Nezhad

    2012-12-01

    The wound infection is one of the frequent complications in patients undergoing surgical operations. Staphylococcus aureus is the most common cause of surgical wounds. Artemisia absinthium has been shown to bear strong antimicrobial activity, especially against Gram-positive pathogens. This study was designed to investigate the antimicrobial effects of A. absinthium against surgical wounds infected by S. aureus in a rat model. Twenty male Sprague-Dawley rats were divided randomly into two equal groups of treated and control rats. A circular incision was created on the dorsal inter-scapular region of each rat. After skin wounding, rats were inoculated locally with 1 × 10(4) CFU of S. aureus at sites of skin wounds. The extract was applied topically twice a day throughout the experiment. Animals of the control group were left untreated. Results have revealed that topical application of A. absinthium extract on the infected wound sites produced significant antibacterial activity against S. aureus.

  20. The protective effect of losartan on diabetic neuropathy in a diabetic rat model.

    Science.gov (United States)

    Cavusoglu, T; Karadeniz, T; Cagiltay, E; Karadeniz, M; Yigitturk, G; Acikgoz, E; Uyanikgil, Y; Ates, U; Tuglu, M I; Erbas, O

    2015-09-01

    Involvement of the peripheral and autonomic nervous systems is possibly the most frequent complication of diabetes. Important risk factors included hyperglycemia, dyslipidemia, hypertension, and smoking. Angiotensin-converting-enzyme inhibitor (ACE) inhibitors should be beneficial in all vascular beds, including neuropathy and retinopathy. In this study we aimed to evaluate the effect of the angiotensin receptor blocker losartan on diabetic neuropathy in a diabetic rat model. 24 male, Sprague Dawley albino mature rats were divided into 3 groups; (1) control group: No drug was administered to the remainder of rats which blood glucose levels were under 120 mg/dl, (2) diabetic control: rats were given no medication, but 4 ml per day of tap water was given by oral gavage, (3) losartan groups: rats were given 10 mg/kg/day oral of losartan for 4 weeks. Electromyography (EMG) was applied to anesthetized rats at the end of 4(th) weekend. Then, the animals were euthanized and sciatic nerve was performed for histopathological examination. Compound Muscle Action Potential (CMAP) amplitude of diabetic rats receiving the Saline in the EMG was significantly reduced when compared to the control group. Distal latency value and CMAP duration of diabetic rats receiving the saline were meaningfully increased when compared to the control group. CMAP amplitude and CMAP duration of diabetic rats receiving the Losartan treatment in the EMG were meaningfully reduced when compared to diabetic rats receiving the Saline.Perineural thickness in the rats receiving the Losartan treatment was found to be significantly reduced when compared to the group receiving the Saline. As a result, it has been shown in this study that perineural thickness of the Losartan treatment was significantly reduced when compared to saline receiving group, significantly increased the immunoexpression of NGF, and also provided a significantly recovery in EMG when compared to Saline receiving group. © Georg

  1. Novel Rat Model of Repetitive Portal Venous Embolization Mimicking Human Non-Cirrhotic Idiopathic Portal Hypertension

    DEFF Research Database (Denmark)

    Klein, Sabine; Hinüber, Christian; Hittatiya, Kanishka

    2016-01-01

    BACKGROUND: Non-cirrhotic idiopathic portal hypertension (NCIPH) is characterized by splenomegaly, anemia and portal hypertension, while liver function is preserved. However, no animal models have been established yet. This study assessed a rat model of NCIPH and characterized the hemodynamics......, and compared it to human NCIPH. METHODS: Portal pressure (PP) was measured invasively and coloured microspheres were injected in the ileocecal vein in rats. This procedure was performed weekly for 3 weeks (weekly embolization). Rats without and with single embolization served as controls. After four weeks (one...... in the weekly embolization group. Fibrotic markers αSMA and Desmin were upregulated in weekly embolized rats. DISCUSSION: This study establishes a model using repetitive embolization via portal veins, comparable with human NCIPH and may serve to test new therapies....

  2. Long-term characterization of the diet-induced obese and diet-resistant rat model

    DEFF Research Database (Denmark)

    Madsen, Andreas Nygaard; Hansen, Gitte; Paulsen, Sarah Juel

    2010-01-01

    The availability of useful animal models reflecting the human obesity syndrome is crucial in the search for novel compounds for the pharmacological treatment of obesity. In the current study, we have performed an extensive characterization of the obesity syndrome in a polygenetic animal model......, namely the selectively bred diet-induced obese (DIO) and diet-resistant (DR) rat strains. We show that they constitute useful models of the human obesity syndrome. DIO and DR rats were fed either a high-energy (HE) or a standard chow (Chow) diet from weaning to 9 months of age. Metabolic characterization...... including blood biochemistry and glucose homeostasis was examined at 2, 3, 6, and 9 months of age. Furthermore, in 6-month-old HE-fed DIO rats, the anti-obesity effects of liraglutide and sibutramine were examined in a 28-day study. Only HE-fed DIO rats developed visceral obesity, hyperleptinemia...

  3. Characterization of primary rat nasal epithelial cultures in CFTR knockout rats as a model for CF sinus disease.

    Science.gov (United States)

    Tipirneni, Kiranya E; Cho, Do-Yeon; Skinner, Daniel F; Zhang, Shaoyan; Mackey, Calvin; Lim, Dong-Jin; Woodworth, Bradford A

    2017-11-01

    The objectives of the current experiments were to develop and characterize primary rat nasal epithelial cultures and evaluate their usefulness as a model of cystic fibrosis (CF) sinonasal transepithelial transport and CF transmembrane conductance regulator (CFTR) function. Laboratory in vitro and animal studies. CFTR+/+ and CFTR-/- rat nasal septal epithelia (RNSE) were cultured on semipermeable supports at an air-liquid interface to confluence and full differentiation. Monolayers were mounted in Ussing chambers for pharmacologic manipulation of ion transport and compared to similar filters containing murine (MNSE) and human (HSNE) epithelia. Histology and scanning electron microscopy (SEM) were completed. Real-time polymerase chain reaction of CFTR+/+ RNSE, MNSE, and HSNE was performed to evaluate relative CFTR gene expression. Forskolin-stimulated anion transport (ΔIsc in μA/cm2 ) was significantly greater in epithelia derived from CFTR+/+ when compared to CFTR-/- animals (100.9 ± 3.7 vs. 10.5 ± 0.9; P rats at 4 months. CFTR expression was similar among species. The successful development of the CFTR-/- rat enables improved evaluation of CF sinus disease based on characteristic abnormalities of ion transport. NA. Laryngoscope, 127:E384-E391, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  4. Candida albicans Airway Colonization Facilitates Subsequent Acinetobacter baumannii Pneumonia in a Rat Model.

    Science.gov (United States)

    Tan, Xiaojiang; Chen, Ruilan; Zhu, Song; Wang, Huijun; Yan, Dongxing; Zhang, Xiangdong; Farmakiotis, Dimitrios; Mylonakis, Eleftherios

    2016-06-01

    The objective of the study was to determine the effects of Candida albicans respiratory tract colonization on Acinetobacter baumannii pneumonia in a rat model. Rats were colonized with C. albicans by instillation of 3 × 10(6) CFU into their airways, while sterile saline was instilled in the control group. The colonized rats were further divided into two groups: treated with amphotericin B or not. The rats were subsequently infected with A. baumannii (10(8) CFU by tracheobronchial instillation). A. baumannii lung CFU counts, cytokine lung levels, and rates of A. baumannii pneumonia were compared between groups. In vitro expression of A. baumannii virulence genes was measured by reverse transcription (RT)-PCR after 24-hour incubation with C. albicans or with Mueller-Hinton (MH) broth alone. Rats with Candida colonization developed A. baumannii pneumonia more frequently and had higher A. baumannii CFU burdens and heavier lungs than controls. After A. baumannii infection, lung interleukin 17 (IL-17) concentrations were lower and gamma interferon (IFN-γ) concentrations were higher in Candida-colonized rats than in controls. Candida-colonized rats treated with amphotericin B had a decreased rate of A. baumannii pneumonia and lower IFN-γ levels but higher IL-17 levels than untreated rats. Expression of basC, barB, bauA, ptk, plc2, and pld2 was induced while expression of ompA and abaI was suppressed in A. baumannii cultured in the presence of C. albicans C. albicans colonization facilitated the development of A. baumannii pneumonia in a rat model. Among Candida-colonized rats, antifungal treatment lowered the incidence of A. baumannii pneumonia. These findings could be due to modification of the host immune response and/or expression of A. baumannii virulence genes by Candida spp. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  5. Naringin prevents bone loss in a rat model of type 1 Diabetes mellitus.

    Science.gov (United States)

    Rivoira, M; Rodríguez, V; Picotto, G; Battaglino, R; Tolosa de Talamoni, N

    2018-01-01

    The aim of this work was to know whether naringin (NA) could prevent the bone complications in a model of streptozotocin (STZ) induced diabetes. Rats were divided in: 1) controls, 2) STZ-rats, 3) STZ-rats treated with 40 mg NA/kg, and 4) STZ-rats treated with 80 mg NA/kg. BMD and BMC were performed by DEXA. Bone histomorphometry and histology as well as TRAP staining were done in tibia. Osteocalcin (OCN) was determined in bone and serum. Glutathione content and SOD and catalase activities were assayed in bone marrow from femur. The data showed that NA80 increased the BMD and BMC from the long bones of STZ-rats. Both NA40 and NA80 normalized the trabecular number and the trabecular separations. An increase in the number of adipocytes and TRAP(+) cells in tibia from STZ-rats was blocked by NA. NA40 treatment increased the number of OCN(+) cells, but only the NA80 treatment allowed to reach the control values. NA normalized the SOD and catalase activities in bone marrow of femur from STZ-rats. In conclusion, NA avoids alterations in the physical properties and microstructure of bone from STZ-rats probably by stimulation of osteoblastogenesis, inhibition of the osteoclastogenesis and adipogenesis via blocking the oxidative stress. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Lycopene in the prevention of renal cell cancer in the TSC2 mutant Eker rat model.

    Science.gov (United States)

    Sahin, Kazim; Cross, Brian; Sahin, Nurhan; Ciccone, Karina; Suleiman, Shadeah; Osunkoya, Adeboye O; Master, Viraj; Harris, Wayne; Carthon, Bradley; Mohammad, Ramzi; Bilir, Birdal; Wertz, Karin; Moreno, Carlos S; Walker, Cheryl L; Kucuk, Omer

    2015-04-15

    Renal cell carcinoma (RCC) is the most frequent upper urinary tract cancer in humans and accounts for 80-85% of malignant renal tumors. Eker rat represents a unique animal model to study RCC since these rats develop spontaneous renal tumors and leiomyoma, which may be due to tuberous sclerosis 2 (TSC2) mutation resulting in the activation of the mammalian target of rapamycin (mTOR) pathway. This study examines the role of a lycopene-rich diet in the development of RCC in the TSC2 mutant Eker rat model. Ten-week old female Eker rats (n=90) were assigned in equal numbers to receive 0, 100 or 200mg/kg of lycopene as part of their daily diet. After 18 months the rats were sacrificed and the kidneys were removed. Immunohistochemical staining with antibodies against mTOR, phospho-S6 and EGFR were performed, as well as hematoxylin-eosin staining for histologic examination of the tumors. Tumors were counted and measured in individual kidneys. Presence of tumor decreased from 94% in control animals to 65% in the experimental group, but the difference was not statistically significant (Plycopene-treated rats (Plycopene group, tumor numbers decreased (Plycopene increased from 0 to 200. Control rats fed only basal diet had a greater length of tumors (23.98 mm) than rats fed lycopene supplement groups (12.90 mm and 11.07 mm) (Plycopene increased from 0 to 200mg/kg. All tumors showed strong staining with antibodies against mTOR, phospho-S6 and EGFR. In conclusion, dietary supplementation with lycopene attenuates the development of renal cell cancers in the predisposed TSC2 mutant Eker rat model. These results suggest that lycopene may play a role in the prevention of RCC. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Voluntary Alcohol Intake following Blast Exposure in a Rat Model of Mild Traumatic Brain Injury.

    Directory of Open Access Journals (Sweden)

    Yi Wei Lim

    Full Text Available Alcoholism is a frequent comorbidity following mild traumatic brain injury (mTBI, even in patients without a previous history of alcohol dependence. Despite this correlational relationship, the extent to which the neurological effects of mTBI contribute to the development of alcoholism is unknown. In this study, we used a rodent blast exposure model to investigate the relationship between mTBI and voluntary alcohol drinking in alcohol naïve rats. We have previously demonstrated in Sprague Dawley rats that blast exposure leads to microstructural abnormalities in the medial prefrontal cortex (mPFC and other brain regions that progress from four to thirty days. The mPFC is a brain region implicated in alcoholism and drug addiction, although the impact of mTBI on drug reward and addiction using controlled models remains largely unexplored. Alcohol naïve Sprague Dawley rats were subjected to a blast model of mTBI (or sham conditions and then tested in several common measures of voluntary alcohol intake. In a seven-week intermittent two-bottle choice alcohol drinking test, sham and blast exposed rats had comparable levels of alcohol intake. In a short access test session at the conclusion of the two-bottle test, blast rats fell into a bimodal distribution, and among high intake rats, blast treated animals had significantly elevated intake compared to shams. We found no effect of blast when rats were tested for an alcohol deprivation effect or compulsive drinking in a quinine adulteration test. Throughout the experiment, alcohol drinking was modest in both groups, consistent with other studies using Sprague Dawley rats. In conclusion, blast exposure had a minimal impact on overall alcohol intake in Sprague Dawley rats, although intake was increased in a subpopulation of blast animals in a short access session following intermittent access exposure.

  8. Bone healing around titanium implants in two rat colitis models.

    Science.gov (United States)

    Kuchler, Ulrike; Luvizuto, Eloa R; Muñoz, Fernando; Hofbauer, Julia; Watzek, Georg; Gruber, Reinhard

    2013-02-01

    Crohn's disease is a chronic inflammatory process that has recently been associated with a higher risk of early implant failure. Herein we provide information on the impact of colitis on peri-implant bone formation using preclinical models of chemically induced colitis. Colitis was induced by intrarectal instillation of 2,4,6-trinitro-benzene-sulfonic-acid (TNBS). Colitis was also induced by feeding rats dextran-sodium-sulfate (DSS) in drinking water. One week after disease induction, titanium miniscrews were inserted into the tibia. Four weeks after implantation, peri-implant bone volume per tissue volume (BV/TV) and bone-to-implant contacts (BIC) were determined by histomorphometric analysis. Cortical histomorphometric parameters were similar in the control (n = 10), DSS (n = 10) and TNBS (n = 8) groups. Cortical BV/TV was 92.2 ± 3.7%, 92.0 ± 3.0% and 92.6 ± 2.7%. Cortical BIC was 81.3 ± 8.8%, 83.2 ± 8.4% and 84.0 ± 7.0%, respectively. No significant differences were observed when comparing the medullary BV/TV and BIC (19.5 ± 6.4%, 16.2 ± 5.6% and 15.4 ± 9.0%) and (48.8 ± 12.9%, 49.2 ± 6.2 and 41.9 ± 11.7%), respectively. Successful induction of colitis was confirmed by loss of body weight and colon morphology. The results suggest bone regeneration around implants is not impaired in chemically induced colitis models. Considering that Crohn's disease can affect any part of the gastrointestinal tract including the mouth, our model only partially reflects the clinical situation. © 2012 John Wiley & Sons A/S.

  9. Cardiovascular disease-related parameters and oxidative stress in SHROB rats, a model for metabolic syndrome.

    Directory of Open Access Journals (Sweden)

    Eunice Molinar-Toribio

    Full Text Available SHROB rats have been suggested as a model for metabolic syndrome (MetS as a situation prior to the onset of CVD or type-2 diabetes, but information on descriptive biochemical parameters for this model is limited. Here, we extensively evaluate parameters related to CVD and oxidative stress (OS in SHROB rats. SHROB rats were monitored for 15 weeks and compared to a control group of Wistar rats. Body weight was recorded weekly. At the end of the study, parameters related to CVD and OS were evaluated in plasma, urine and different organs. SHROB rats presented statistically significant differences from Wistar rats in CVD risk factors: total cholesterol, LDL-cholesterol, triglycerides, apoA1, apoB100, abdominal fat, insulin, blood pressure, C-reactive protein, ICAM-1 and PAI-1. In adipose tissue, liver and brain, the endogenous antioxidant systems were activated, yet there was no significant oxidative damage to lipids (MDA or proteins (carbonylation. We conclude that SHROB rats present significant alterations in parameters related to inflammation, endothelial dysfunction, thrombotic activity, insulin resistance and OS measured in plasma as well as enhanced redox defence systems in vital organs that will be useful as markers of MetS and CVD for nutrition interventions.

  10. Alpha adrenergic receptors in renal pelvis and calyces: can rat models be used?

    Directory of Open Access Journals (Sweden)

    Osman Raif Karabacakb

    2014-10-01

    Full Text Available We aimed, in this study, to determine the distribution of α-1 AR subtypes in rat and human pelvis and calyces, and to evaluate, by comparing these two species, the possibility of rats to be used as models for humans. Twenty patients with renal carcinoma were included into the study. The patients underwent radical nephrectomy for renal cell carcinoma (RCC. After nephrectomy, specimens were evaluated and excisional biopsies from healthy pelvis and calyces tissues were performed. When pathology confirmed the non-invasion of RCC, specimen was included into the study. A total of 7 adult Wistar Albino (250-300 g female rats were used in this study. Specimens included renal pelvis and calyces. All specimens were evaluated under light microscope histopathologically. The concentrations of the receptor densities did not differ between the two groups. With the demonstration of the α receptors in rat kidneys and calyces, many receptor-based studies concerning both humans and rats can take place. Novel medication targeting these subtypes -in this matter α1A and α1D for renal pelvis and calyces- may be helpful for expulsive therapy and/or pain relief. With the demonstration of similar receptor densities between human and rat tissues, rat model may be useful for α-receptor trials for renal pelvis and calyces.

  11. Impaired Decision Making and Loss of Inhibitory-Control in a Rat Model of Huntington Disease.

    Science.gov (United States)

    El Massioui, Nicole; Lamirault, Charlotte; Yagüe, Sara; Adjeroud, Najia; Garces, Daniel; Maillard, Alexis; Tallot, Lucille; Yu-Taeger, Libo; Riess, Olaf; Allain, Philippe; Nguyen, Huu Phuc; von Hörsten, Stephan; Doyère, Valérie

    2016-01-01

    Cognitive deficits associated with Huntington disease (HD) are generally dominated by executive function disorders often associated with disinhibition and impulsivity/compulsivity. Few studies have directly examined symptoms and consequences of behavioral disinhibition in HD and its relation with decision-making. To assess the different forms of impulsivity in a transgenic model of HD (tgHD rats), two tasks assessing cognitive/choice impulsivity were used: risky decision-making with a rat gambling task (RGT) and intertemporal choices with a delay discounting task (DD). To assess waiting or action impulsivity the differential reinforcement of low rate of responding task (DRL) was used. In parallel, the volume as well as cellular activity of the amygdala was analyzed. In contrast to WT rats, 15 months old tgHD rats exhibited a poor efficiency in the RGT task with difficulties to choose advantageous options, a steep DD curve as delays increased in the DD task and a high rate of premature and bursts responses in the DRL task. tgHD rats also demonstrated a concomitant and correlated presence of both action and cognitive/choice impulsivity in contrast to wild type (WT) animals. Moreover, a reduced volume associated with an increased basal cellular activity of the central nucleus of amygdala indicated a dysfunctional amygdala in tgHD rats, which could underlie inhibitory dyscontrol. In conclusion, tgHD rats are a good model for impulsivity disorder that could be used more widely to identify potential pharmacotherapies to treat these invasive symptoms in HD.

  12. In vivo micro-CT analysis of bone remodeling in a rat calvarial defect model

    Energy Technology Data Exchange (ETDEWEB)

    Umoh, Joseph U; Holdsworth, David W [Pre-Clinical Imaging Research Centre, Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario, PO Box 5015, 100 Perth Drive, London, ON N6A 5K8 (Canada); Sampaio, Arthur V; Underhill, T Michael [Laboratory of Molecular Skeletogenesis, Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC (Canada); Welch, Ian [Animal Care and Veterinary Services, University of Western Ontario, London, ON (Canada); Pitelka, Vasek; Goldberg, Harvey A [CIHR Group in Skeletal Development and Remodelling, University of Western Ontario, London, ON (Canada)], E-mail: jumoh@imaging.robarts.ca, E-mail: asampaio@interchange.ubc.ca, E-mail: tunderhi@interchange.ubc.ca, E-mail: iwelch@uwo.ca, E-mail: vasek.pitelka@schulich.uwo.ca, E-mail: hagoldbe@uwo.ca, E-mail: david.holdsworth@imaging.robarts.ca

    2009-04-07

    The rodent calvarial defect model is commonly used to investigate bone regeneration and wound healing. This study presents a micro-computed tomography (micro-CT) methodology for measuring the bone mineral content (BMC) in a rat calvarial defect and validates it by estimating its precision error. Two defect models were implemented. A single 6 mm diameter defect was created in 20 rats, which were imaged in vivo for longitudinal experiments. Three 5 mm diameter defects were created in three additional rats, which were repeatedly imaged ex vivo to determine precision. Four control rats and four rats treated with bone morphogenetic protein were imaged at 3, 6, 9 and 12 weeks post-surgery. Scan parameters were 80 kVp, 0.45 mA and 180 mAs. Images were reconstructed with an isotropic resolution of 45 {mu}m. At 6 weeks, the BMC in control animals (4.37 {+-} 0.66 mg) was significantly lower (p < 0.05) than that in treated rats (11.29 {+-} 1.01 mg). Linear regression between the BMC and bone fractional area, from 20 rats, showed a strong correlation (r{sup 2} = 0.70, p < 0.0001), indicating that the BMC can be used, in place of previous destructive analysis techniques, to characterize bone growth. The high precision (2.5%) of the micro-CT methodology indicates its utility in detecting small BMC changes in animals.

  13. Characterization of the rat pneumonic plague model: infection kinetics following aerosolization of Yersinia pestis CO92.

    Science.gov (United States)

    Agar, Stacy L; Sha, Jian; Foltz, Sheri M; Erova, Tatiana E; Walberg, Kristin G; Baze, Wallace B; Suarez, Giovanni; Peterson, Johnny W; Chopra, Ashok K

    2009-02-01

    Yersinia pestis, the causative agent of human bubonic and pneumonic plague, is spread during natural infection by the fleas of rodents. Historically associated with infected rat fleas, studies on the kinetics of infection in rats are surprisingly few, and these reports have focused mainly on bubonic plague. Although the natural route of primary infection results in bubonic plague in humans, it is commonly thought that aerosolized Y. pestis will be utilized during a biowarfare attack. Accordingly, based on our previous characterization of the mouse model of pneumonic plague, we sought to examine the progression of infection in rats exposed in a whole-body Madison chamber to aerosolized Y. pestis CO92. Following an 8.6 LD(50) dose of Y. pestis, injury was apparent in the rat tissues based on histopathology, and chemokines and cytokines rose above control levels (1h post infection [p.i.]) in the sera and organ homogenates over a 72-h infection period. Bacteria disseminated from the lungs to peripheral organs, with the largest increases in the spleen, followed by the liver and blood at 72h p.i. compared to the 1h controls. Importantly, rats were as sensitive to pneumonic plague as mice, having a similar LD(50) dose by the intranasal and aerosolized routes. Further, we showed direct transmission of plague bacteria from infected to uninfected rats. Taken together, the data allowed us to characterize for the first time a rat pneumonic plague model following aerosolization of Y. pestis.

  14. Availability of Acute and/or Subacute Toxicokinetic Data for Select Compounds for the Rat and Physiologically Based Pharmacokinetic (PBPK) Models for Rats and Humans for Those Compounds

    Science.gov (United States)

    2017-05-04

    adolescents and adults Route(s) Oral (AsV) Duration Chronic Tissue dosimetry No dose metrics used for calibration or validation Model language Not...and iron deficient diets (fed to maternal rats starting on gestation day [GD] 20 and to young rats). Table B16. Tissue distribution of cadmium in

  15. Effects of nicotine on a rat model of early stage osteoarthritis.

    Science.gov (United States)

    Gu, Qiangrong; Li, Dong; Wei, Bo; Guo, Yang; Yan, Junwei; Mao, Fengyong; Zhang, Xiang; Wang, Liming

    2015-01-01

    The objective of the study was to investigate the effects of nicotine on articular cartilage degeneration and inflammation in a rat model of early stage osteoarthritis (OA), using T2 mapping. In this study, a rat model of early stage OA was established by immobilizing the left knee joints of adult male rats for two weeks. Subsequently, rats were fed with nicotine for two and four weeks. Changes in the articular cartilage from the medial femoral condylar region of the knee were evaluated by gross observation and histological grading with the contents of cartilage matrix detected. T2 values of the articular cartilage were estimated through high-field magnetic resonance imaging (MRI) (7.0 T). Levels of serum tumor necrosis factor-α (TNF-α) were assessed by ELISA. The expression of TNF-α and the cholinergic receptor, α7nAChR, in the synovial tissue was measured by RT-PCR. Nicotine treatment ameliorated cartilage destruction, promoted matrix production, reduced the serum level of TNF-α and the expression of TNF-α in the synovial tissue, and increased the expression of α7nAChR in the synovial tissue in the rat model of early stage OA. In conclusion, nicotine prevented cartilage damage and had an anti-inflammatory effect in a rat model of early stage OA. Thus nicotine may have potential as a therapeutic strategy for early stage OA.

  16. Anti-inflammatory activity of methyl palmitate and ethyl palmitate in different experimental rat models

    Energy Technology Data Exchange (ETDEWEB)

    Saeed, Noha M. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Egyptian Russian University, Cairo (Egypt); El-Demerdash, Ebtehal [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt); Abdel-Rahman, Hanaa M. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Egyptian Russian University, Cairo (Egypt); Algandaby, Mardi M. [Department of Biology (Botany), Faculty of Science, King Abdulaziz University, Jeddah (Saudi Arabia); Al-Abbasi, Fahad A. [Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah (Saudi Arabia); Abdel-Naim, Ashraf B., E-mail: abnaim@pharma.asu.edu.eg [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt)

    2012-10-01

    Methyl palmitate (MP) and ethyl palmitate (EP) are naturally occurring fatty acid esters reported as inflammatory cell inhibitors. In the current study, the potential anti-inflammatory activity of MP and EP was evaluated in different experimental rat models. Results showed that MP and EP caused reduction of carrageenan-induced rat paw edema in addition to diminishing prostaglandin E2 (PGE2) level in the inflammatory exudates. In lipopolysaccharide (LPS)-induced endotoxemia in rats, MP and EP reduced plasma levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). MP and EP decreased NF-κB expression in liver and lung tissues and ameliorated histopathological changes caused by LPS. Topical application of MP and EP reduced ear edema induced by croton oil in rats. In the same animal model, MP and EP reduced neutrophil infiltration, as indicated by decreased myeloperoxidase (MPO) activity. In conclusion, this study demonstrates the effectiveness of MP and EP in combating inflammation in several experimental models. -- Highlights: ► Efficacy of MP and EP in combating inflammation was displayed in several models. ► MP and EP reduced carrageenan-induced rat paw edema and prostaglandin E2 level. ► MP and EP decreased TNF-α and IL-6 levels in experimental endotoxemia. ► MP and EP reduced NF-κB expression and histological changes in rat liver and lung. ► MP and EP reduced croton oil-induced ear edema and neutrophil infiltration.

  17. A nonlinear model of stress hormone levels in rats-the interaction between pollution and parasites.

    Science.gov (United States)

    Klar, B; Sures, B

    2004-09-01

    The impact of an infection with a parasite and a simultaneous cadmium exposure on the stress hormone levels of rats was studied. To this end, we introduce a nonlinear heteroscedastic model, which is able to describe the temporal evolution of cortisol concentrations in groups of rats treated by cadmium or parasite infection. A thorough analysis gives strong evidence that parasitic infection and cadmium exposure affect the stress hormone level of rats in an additive manner. Therefore, the host's response to environmental pollution should be studied in relation to parasite infections. Copyright 2003 Elsevier Inc.

  18. COMP-Angiopoietin-1 Promotes Cavernous Angiogenesis in a Type 2 Diabetic Rat Model

    OpenAIRE

    Kim, Sun-Ouck; Lee, Hyun-Suk; Ahn, Kyuyoun; Park, Kwangsung

    2013-01-01

    Cartilage oligomeric matrix protein-angiopoietin-1 (COMP-Ang1) is an angiogenic factor for vascular angiogenesis. The aim was to investigate the effect of an intracavernosal injection of COMP-Ang1 on cavernosal angiogenesis in a diabetic rat model. Male Otsuka Long-Evans Tokushima Fatty (OLETF) rats made up the experimental group (1 yr old) and Long-Evans Tokushima Otsuka (LETO) rats made up the control group. The experimental group was divided into vehicle only, 10 ?g COMP-Ang1, and 20 ?g CO...

  19. A novel knee prosthesis model of implant-related osteo- myelitis in rats

    DEFF Research Database (Denmark)

    Søe, Niels H.; Jensen, Nina Vendel; Nürnberg, Birgit Meinecke

    2012-01-01

    There have been numerous reports of animal models of osteomyelitis. Very few of these have been prosthesis models that imitate human conditions. We have developed a new rat model of implant-related osteomyelitis that mimics human osteomyelitis, to investigate the pathology of infection after...

  20. Work performance evaluation using the exercising rat model

    Energy Technology Data Exchange (ETDEWEB)

    Stavert, D.M.; Lehnert, B.E.

    1987-01-01

    A treadmill-metabolic chamber system and a stress testing protocol have been developed to evaluate aerobic work performance on exercising rats that have inhaled toxic substances. The chamber with an enclosed treadmill provides the means to measure the physiologic status of rats during maximal work intensities in terms of O/sub 2/ consumption (V/sub 02/) and CO/sub 2/ production (V/sub c02/). The metabolic chamber can also accommodate instrumented rats for more detailed analyses of their cardiopulmonary status, e.g., ECG, cardiac output, arterial blood gases and pH, and arterial and venous blood pressures. For such studies, an arterial/venous catheter preparation is required. Because of the severe metabolic alterations after such surgery, a post surgical recovery strategy using hyperalimentation was developed to ensure maximal performance of instrumented animals during stress testing. Actual work performance studies are conducted using an eight minute stress test protocol in which the rat is subjected to increasing external work. The metabolic state of the animal is measured from resting levels to maximum oxygen consumption (V/sub 02max/). V/sub 02max/ has been shown to be reproducible in individual rats and is a sensitive indicator of oxidant gas-induced pulmonary damage. 3 tabs.

  1. Rat models of spinal cord injury: from pathology to potential therapies

    Directory of Open Access Journals (Sweden)

    Jacob Kjell

    2016-10-01

    Full Text Available A long-standing goal of spinal cord injury research is to develop effective spinal cord repair strategies for the clinic. Rat models of spinal cord injury provide an important mammalian model in which to evaluate treatment strategies and to understand the pathological basis of spinal cord injuries. These models have facilitated the development of robust tests for assessing the recovery of locomotor and sensory functions. Rat models have also allowed us to understand how neuronal circuitry changes following spinal cord injury and how recovery could be promoted by enhancing spontaneous regenerative mechanisms and by counteracting intrinsic inhibitory factors. Rat studies have also revealed possible routes to rescuing circuitry and cells in the acute stage of injury. Spatiotemporal and functional studies in these models highlight the therapeutic potential of manipulating inflammation, scarring and myelination. In addition, potential replacement therapies for spinal cord injury, including grafts and bridges, stem primarily from rat studies. Here, we discuss advantages and disadvantages of rat experimental spinal cord injury models and summarize knowledge gained from these models. We also discuss how an emerging understanding of different forms of injury, their pathology and degree of recovery has inspired numerous treatment strategies, some of which have led to clinical trials.

  2. Rat models of spinal cord injury: from pathology to potential therapies

    Science.gov (United States)

    2016-01-01

    ABSTRACT A long-standing goal of spinal cord injury research is to develop effective spinal cord repair strategies for the clinic. Rat models of spinal cord injury provide an important mammalian model in which to evaluate treatment strategies and to understand the pathological basis of spinal cord injuries. These models have facilitated the development of robust tests for assessing the recovery of locomotor and sensory functions. Rat models have also allowed us to understand how neuronal circuitry changes following spinal cord injury and how recovery could be promoted by enhancing spontaneous regenerative mechanisms and by counteracting intrinsic inhibitory factors. Rat studies have also revealed possible routes to rescuing circuitry and cells in the acute stage of injury. Spatiotemporal and functional studies in these models highlight the therapeutic potential of manipulating inflammation, scarring and myelination. In addition, potential replacement therapies for spinal cord injury, including grafts and bridges, stem primarily from rat studies. Here, we discuss advantages and disadvantages of rat experimental spinal cord injury models and summarize knowledge gained from these models. We also discuss how an emerging understanding of different forms of injury, their pathology and degree of recovery has inspired numerous treatment strategies, some of which have led to clinical trials. PMID:27736748

  3. [Effects of myxoma virus on gliomas of rats models in vivo].

    Science.gov (United States)

    Zhang, Qiu-Sheng; Zhang, Meng; Liang, Shi-Jie; Lin, Heng-Zhou; Ji, Tao; Li, Wei-Ping

    2012-04-01

    To explore the in vivo effects of myxoma virus (MV) on gliomas of rat model. Methods C6 glioma cells were implanted into the frontal lobe of SD rats using stereotactic methods to establish animal models of glioma. C6 glioma cells were implanted into the frontal lobe of SD rats using stereotactic methods to establish animal models of glioma. Models were divided into 4 groups randomly after tumor growth was affirmed, and MV, 5-FU, MV + 5-FU, and denatured myxoma virus (DV) were implanted into the tumors using stereotactic methods, bodyweight, tumor size, expression of glial fibrillary acidic protein (GFAP), Akt of each model were observed. The gliomas in all SD rats were established successfully. And tumor growth in MV, 5-FU, MV + 5-FU were significantly decreased as compared with DV group after injection, sizes of some tumors were lessened, and GFAP expression decreased in MV, 5-FU and MV +5-FU groups. The expression of PI3k, Akt and mTOR were decreased in MV and MV +5-FU groups. C6 glioma SD rat models could be established successfully using stereotactic methods. MV may enhance biological activity of chemotherapeutic drugs on tumor cells of animal models in vivo by regulating some genes of PI3K-Akt-mTOR signal pathway.

  4. Refinement of the Collagen Induced Arthritis Model in Rats by Infrared Thermography

    DEFF Research Database (Denmark)

    Jasemian, Yousef; Deleuran, Bent Winding; Svendsen, Pia

    2011-01-01

    Aims: Collagen induced arthritis in rats is an important model for human rheumatoid arthritis. This study was designed to improve and refine this model by use of infrared thermography by measuring surface temperature of hind feet. Our hypothesis is that the local temperature on the feet correlates....... Methodology: Arthritis was induced with collagen immunization in sixteen Lewis rats. Four of the animals were treated with dexamethasone to function as negative controls. Clinical scores were based on the magnitude of paw edema. The mean temperature of the hind feet (region covering the metatarsus and tarsus......) was normalized with a reference area on the back of the same rat. The temperature index were compared with the clinical score index, edema index, and bodyweight of the rats Results: The mean hind feet temperatures increased with increasing clinical severity in the acute stage of the disease. There were positive...

  5. Efficacy of Intrathecal Morphine in a Model of Surgical Pain in Rats.

    Directory of Open Access Journals (Sweden)

    Aurelie Thomas

    Full Text Available Concerns over interactions between analgesics and experimental outcomes are a major reason for withholding opioids from rats undergoing surgical procedures. Only a fraction of morphine injected intravenously reaches receptors responsible for analgesia in the central nervous system. Intrathecal administration of morphine may represent a way to provide rats with analgesia while minimizing the amount of morphine injected. This study aimed to assess whether morphine injected intrathecally via direct lumbar puncture provides sufficient analgesia to rats exposed to acute surgical pain (caudal laparotomy.In an initial blinded, randomised study, pain-free rats received morphine subcutaneously (MSC, 3mg.kg-1, N = 6, intrathecally (MIT, 0.2mg.kg-1, N = 6; NaCl subcutaneously (NSC, N = 6 or intrathecally (NIT, N = 6. Previously validated pain behaviours, activity and Rat Grimace Scale (RGS scores were recorded at baseline, 1, 2, 4 and 8h post-injection. Morphine-treated rats had similar behaviours to NaCl rats, but their RGS scores were significantly different over time and between treatments. In a second blinded study, rats (N = 28 were randomly allocated to one of the following four treatments (N = 7: MSC, 3mg.kg-1, surgery; MIT, 0.2mg.kg-1, surgery; NIT, surgery; NSC, sham surgery. Composite Pain Behaviours (CPB and RGS were recorded as previously. CPB in MIT and MSC groups were not significantly different to NSC group. MSC and MIT rats displayed significantly lower RGS scores than NIT rats at 1 and 8h postoperatively. RGS scores for MIT and MSC rats were not significantly different at 1, 2, and 8h postoperatively. Intraclass correlation value amongst operators involved in RGS scoring (N = 9 was 0.913 for total RGS score. Intrathecal morphine was mostly indistinguishable from its subcutaneous counterpart, providing pain relief lasting up to 8 hours in a rat model of surgical pain. Further studies are warranted to clarify the relevance of the rat grimace

  6. Generation of rat-induced pluripotent stem cells from a new model of metabolic syndrome.

    Directory of Open Access Journals (Sweden)

    Nana Takenaka-Ninagawa

    Full Text Available We recently characterized DahlS.Z-Leprfa/Leprfa (DS/obese rats, derived from a cross between Dahl salt-sensitive rats and Zucker rats, as a new animal model of metabolic syndrome (MetS. Although the phenotype of DS/obese rats is similar to that of humans with MetS, the pathophysiological and metabolic characteristics in each cell type remain to be clarified. Hence, the establishment of induced pluripotent stem cells (iPSCs derived from MetS rats is essential for investigations of MetS in vitro. Reports of rat iPSCs (riPSCs, however, are few because of the difficulty of comparing to other rodents such as mouse. Recently, the advantage of using mesenchymal stromal cells (MSCs as a cell source for generating iPSCs was described. We aimed to establish riPSCs from MSCs in adipose tissues of both DS/obese rats and their lean littermates, DahlS.Z-Lepr+/Lepr+ (DS/lean rats using lentivirus vectors with only three factors Oct4, Klf4, and Sox2 without c-Myc. The morphology, gene expression profiles, and protein expression of established colonies showed embryonic stem cell (ESCs-like properties, and the differentiation potential into cells from all three germ layers both in vitro and in vivo (teratomas. Both riPSCs became adipocytes after induction of adipogenesis by insulin, T3, and dexamethasone. Real-time PCR analysis also revealed that both riPSCs and the adipose tissue from DS/obese and DS/lean rats possess similar expression patterns of adipocyte differentiation-related genes. We succeeded in generating riPSCs effectively from MSCs of both DS/obese and DS/lean rats. These riPSCs may well serve as highly effective tools for the investigation of MetS pathophysiology in vitro.

  7. Rats

    Directory of Open Access Journals (Sweden)

    Alexey Kondrashov

    2012-01-01

    Full Text Available We aimed to perform a chemical analysis of both Alibernet red wine and an alcohol-free Alibernet red wine extract (AWE and to investigate the effects of AWE on nitric oxide and reactive oxygen species production as well as blood pressure development in normotensive Wistar Kyoto (WKY and spontaneously hypertensive rats (SHRs. Total antioxidant capacity together with total phenolic and selected mineral content was measured in wine and AWE. Young 6-week-old male WKY and SHR were treated with AWE (24,2 mg/kg/day for 3 weeks. Total NOS and SOD activities, eNOS and SOD1 protein expressions, and superoxide production were determined in the tissues. Both antioxidant capacity and phenolic content were significantly higher in AWE compared to wine. The AWE increased NOS activity in the left ventricle, aorta, and kidney of SHR, while it did not change NOS activity in WKY rats. Similarly, increased SOD activity in the plasma and left ventricle was observed in SHR only. There were no changes in eNOS and SOD1 expressions. In conclusion, phenolics and minerals included in AWE may contribute directly to increased NOS and SOD activities of SHR. Nevertheless, 3 weeks of AWE treatment failed to affect blood pressure of SHR.

  8. MMC controlled-release membranes attenuate epidural scar formation in rat models after laminectomy

    OpenAIRE

    Xie, Hao; Wang, Binbin; Shen, Xun; Qin, Jian; Jiang, Longhai; Yu, Chen; Geng, Dawei; Yuan, Tangbo; Wu, Tao; Cao, Xiaojian; Liu, Jun

    2017-01-01

    Epidural scar formation after laminectomy impede surgical outcomes of decompression. Mitomycin C (MMC) has been demonstrated to have significant inhibitory effects on epidural scar. This study was undertaken to develop an effective MMC controlled-release membrane and to investigate its effects on epidural scar in rat models of laminectomy. A total of 72 rats that underwent laminectomy were divided into three groups. Among them, 24 were treated with mitomycin C-polylactic acid (MMC-PLA) contro...

  9. The Healing Effect of Licorice on Pseudomonas aeruginosa Infected Burn Wounds in Experimental Rat Model

    OpenAIRE

    Tanideh, Nader; Rokhsari, Pedram; Mehrabani, Davood; Mohammadi Samani, Soleiman; Sabet Sarvestani, Fatemeh; Ashraf, Mohammad Javad; Koohi Hosseinabadi, Omid; Shamsian, Shahram; AHMADI, Nasrollah

    2014-01-01

    BACKGROUND Burn is still one of the most devastating injuries in emergency medicine while improvements in wound healing knowledge and technology have resulted into development of new dressings. This study was undertaken to evaluate the healing effect of licorice in Pseudomonas aeruginosa infected burn wounds of experimental rat model. METHODS One hundred and twenty female Sprague-Dawley rats were randomly allocated to 4 equal groups. Group A received silver sulfadiazine ointment, Group B rece...

  10. Deep brain stimulation exacerbates hypokinetic dysarthria in a rat model of Parkinson's disease.

    Science.gov (United States)

    King, Nathaniel O; Anderson, Collin J; Dorval, Alan D

    2016-02-01

    Motor symptoms of Parkinson's disease (PD) follow the degeneration of dopaminergic neurons in the substantia nigra pars compacta. Deep brain stimulation (DBS) treats some parkinsonian symptoms, such as tremor, rigidity, and bradykinesia, but may worsen certain medial motor symptoms, including hypokinetic dysarthria. The mechanisms by which DBS exacerbates dysarthria while improving other symptoms are unclear and difficult to study in human patients. This study proposes an animal model of DBS-exacerbated dysarthria. We use the unilateral, 6-hydroxydopamine (6-OHDA) rat model of PD to test the hypothesis that DBS exacerbates quantifiable aspects of vocalization. Mating calls were recorded from sexually experienced male rats under healthy and parkinsonian conditions and during DBS of the subthalamic nucleus. Relative to healthy rats, parkinsonian animals made fewer calls with shorter and less complex vocalizations. In the parkinsonian rats, putatively therapeutic DBS further reduced call frequency, duration, and complexity. The individual utterances of parkinsonian rats spanned a greater bandwidth than those of healthy rats, potentially reducing the effectiveness of the vocal signal. This utterance bandwidth was further increased by DBS. We propose that the parkinsonism-associated changes in call frequency, duration, complexity, and dynamic range combine to constitute a rat analog of parkinsonian dysarthria. Because DBS exacerbates the parkinsonism-associated changes in each of these metrics, the subthalamic stimulated 6-OHDA rat is a good model of DBS-induced hypokinetic dysarthria in PD. This model will help researchers examine how DBS alleviates many motor symptoms of PD while exacerbating parkinsonian speech deficits that can greatly diminish patient quality of life. © 2015 Wiley Periodicals, Inc.

  11. Endometriose: modelo experimental em ratas Endometriosis: experimental model in rats

    Directory of Open Access Journals (Sweden)

    Eduardo Schor

    1999-06-01

    that the free portion of the endometrium was directed towards the lumen of the abdominal cavity. After 21 days the animals were again operated to observe the size of the implants and to remove the ectopic endometrium for microscopic analysis. Results: we macroscopically observed a significant growth of the endometrial implants. Microscopic examination showed presence of glandular epithelium and stroma similar to topic epithelium. Conclusion: this model reproduces endometriosis in the female rat allowing a better study of this pathology, mainly the action of drugs on these implants.

  12. Effect of Ozone on Intestinal Epithelial Homeostasis in a Rat Model

    Directory of Open Access Journals (Sweden)

    Igor Sukhotnik

    2015-01-01

    Full Text Available Background: The positive effects of ozone therapy have been described in many gastrointestinal disorders. The mechanisms of this positive effect of ozone therapy are poorly understood. The purpose of the present study was to investigate whether the use of ozone may potentiate the gut intestinal mucosal homeostasis in a rat model. Methods: Adult rats weighing 250–280 g were randomly assigned to one of three experimental groups of 8 rats each: 1 Control rats were given 2 mL of water by gavage and intraperitoneally (IP for 5 days; 2 O3-PO rats were treated with 2 mL of ozone/oxygen mixture by gavage and 2 mL of water IP for 5 days; 3 O3-IP rats were treated with 2 mL of water by gavage and 2 mL of ozone/oxygen mixture IP for 5 days. Rats were sacrificed on day 6. Bowel and mucosal weight, mucosal DNA and protein, villus height and crypt depth, and cell proliferation and apoptosis were evaluated following sacrifice. Results: The group of O3-IP rats demonstrated a greater jejunal and ileal villus height and crypt depth, a greater enterocyte proliferation index in jejunum, and lower enterocyte apoptosis in ileum compared to control animals. Oral administration of the ozone/oxygen mixture resulted in a less significant effect on cell turnover. Conclusions: Treatment with an ozone/oxygen mixture stimulates intestinal cell turnover in a rat model. Intraperitoneal administration of ozone resulted in a more significant intestinal trophic effect than oral administration.

  13. Hearing impairment in the P23H-1 retinal degeneration rat model

    Directory of Open Access Journals (Sweden)

    Jorge V. Sotoca

    2014-09-01

    Full Text Available The transgenic P23H line 1 (P23H-1 rat expresses a variant of rhodopsin with a mutation that leads to loss of visual function. This rat strain is an experimental model usually employed to study photoreceptor degeneration. Although the mutated protein should not interfere with other sensory functions, observing severe loss of auditory reflexes in response to natural sounds led us to study auditory brain response (ABR recording. Animals were separated into different hearing levels following the response to natural stimuli (hand clapping and kissing sounds. Of all the analyzed animals, 25.9% presented auditory loss before 50 days of age (P50 and 45% were totally deaf by P200. ABR recordings showed that all the rats had a higher hearing threshold than the control Sprague-Dawley (SD rats, which was also higher than any other rat strains. The integrity of the central and peripheral auditory pathway was analyzed by histology and immunocytochemistry. In the cochlear nucleus (CN, statistical differences were found between SD and P23H-1 rats in VGluT1 distribution, but none were found when labeling all the CN synapses with anti-Syntaxin. This finding suggests anatomical and/or molecular abnormalities in the auditory downstream pathway. The inner ear of the hypoacusic P23H-1 rats showed several anatomical defects, including loss and disruption of hair cells and spiral ganglion neurons. All these results can explain, at least in part, how hearing impairment can occur in a high percentage of P23H-1 rats. P23H-1 rats may be considered an experimental model with visual and auditory dysfunctions in future research.

  14. Effect of Ozone on Intestinal Epithelial Homeostasis in a Rat Model

    Science.gov (United States)

    Sukhotnik, Igor; Starikov, Alona; Coran, Arnold G.; Pollak, Yulia; Sohotnik, Rima; Shaoul, Ron

    2015-01-01

    Background: The positive effects of ozone therapy have been described in many gastrointestinal disorders. The mechanisms of this positive effect of ozone therapy are poorly understood. The purpose of the present study was to investigate whether the use of ozone may potentiate the gut intestinal mucosal homeostasis in a rat model. Methods: Adult rats weighing 250–280 g were randomly assigned to one of three experimental groups of 8 rats each: 1) Control rats were given 2 mL of water by gavage and intraperitoneally (IP) for 5 days; 2) O3-PO rats were treated with 2 mL of ozone/oxygen mixture by gavage and 2 mL of water IP for 5 days; 3) O3-IP rats were treated with 2 mL of water by gavage and 2 mL of ozone/oxygen mixture IP for 5 days. Rats were sacrificed on day 6. Bowel and mucosal weight, mucosal DNA and protein, villus height and crypt depth, and cell proliferation and apoptosis were evaluated following sacrifice. Results: The group of O3-IP rats demonstrated a greater jejunal and ileal villus height and crypt depth, a greater enterocyte proliferation index in jejunum, and lower enterocyte apoptosis in ileum compared to control animals. Oral administration of the ozone/oxygen mixture resulted in a less significant effect on cell turnover. Conclusions: Treatment with an ozone/oxygen mixture stimulates intestinal cell turnover in a rat model. Intraperitoneal administration of ozone resulted in a more significant intestinal trophic effect than oral administration. PMID:25717388

  15. Heterogeneous stock rats: a model to study the genetics of despair-like behavior in adolescence.

    Science.gov (United States)

    Holl, K; He, H; Wedemeyer, M; Clopton, L; Wert, S; Meckes, J K; Cheng, R; Kastner, A; Palmer, A A; Redei, E E; Solberg Woods, L C

    2017-08-22

    Major depressive disorder (MDD) is a complex illness caused by both genetic and environmental factors. Antidepressant resistance also has a genetic component. To date, however, very few genes have been identified for major depression or antidepressant resistance. In this study, we investigated whether outbred heterogeneous stock (HS) rats would be a suitable model to uncover the genetics of depression and its connection to antidepressant resistance. The Wistar Kyoto (WKY) rat, one of the eight founders of the HS, is a recognized animal model of juvenile depression and is resistant to fluoxetine antidepressant treatment. We therefore hypothesized that adolescent HS rats would exhibit variation in both despair-like behavior and response to fluoxetine treatment. We assessed heritability of despair-like behavior and response to sub-acute fluoxetine using a modified forced swim test (FST) in 4-week-old HS rats. We also tested whether blood transcript levels previously identified as depression biomarkers in adolescent human subjects are differentially expressed in HS rats with high vs. low FST immobility. We demonstrate heritability of despair-like behavior in 4-week-old HS rats and show that many HS rats are resistant to fluoxetine treatment. In addition, blood transcript levels of Amfr, Cdr2 and Kiaa1539, genes previously identified in human adolescents with MDD, are differentially expressed between HS rats with high vs. low immobility. These data demonstrate that FST despair-like behavior will be amenable to genetic fine-mapping in adolescent HS rats. The overlap between human and HS blood biomarkers suggest that these studies may translate to depression in humans. © 2017 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  16. Hydrogen sulfide prevents postoperative adhesion in a rat uterine horn model.

    Science.gov (United States)

    Xia, Ye; Zhu, Yi Zhun; Xu, Congjian

    2017-02-01

    Abdominal adhesions are primarily severe postoperative complications that can cause gynecological problems such as infertility and chronic pelvic pain. Inflammatory mediators are significantly related to adhesion formation, and hydrogen sulfide plays a significant anti-inflammatory role in multiple physiological processes. Therefore, the effect of NaHS, a hydrogen sulfide donor, on postoperative adhesion formation was examined in a rat uterine horn model. A rat uterine horn model was created to evaluate whether NaHS, a hydrogen sulfide donor, could decrease postoperative adhesion formation. Rats were randomly grouped and administrated with different doses of NaHS, where DL-propargylglycine and low-molecular-weight heparin acted as negative and positive controls, respectively. The extent and severity of adhesions were assessed on the 14th postoperative day. Serum of rats was sampled for the determination of 27 cytokines using a chip. The severity and total scores of adhesion in rats given 112μM/kg and 56μM/kg NaHS were significantly less compared with those of the control group (p0.05). At least six cytokines were involved in the procedures for the prevention of adhesion formation, as they varied significantly among different groups. Administration of NaHS could apparently reduce postoperative adhesion in the rat uterine horn model. This preventive effect may be associated with the variation of cytokine that is related to inflammatory. Copyright © 2017 Taiwan Association of Obstetrics & Gynecology. Published by Elsevier B.V. All rights reserved.

  17. Beneficial effects of melatonin in a rat model of sporadic Alzheimer's disease.

    Science.gov (United States)

    Rudnitskaya, Ekaterina A; Maksimova, Kseniya Yi; Muraleva, Natalia A; Logvinov, Sergey V; Yanshole, Lyudmila V; Kolosova, Nataliya G; Stefanova, Natalia A

    2015-06-01

    Melatonin synthesis is disordered in patients with Alzheimer's disease (AD). To determine the role of melatonin in the pathogenesis of AD, suitable animal models are needed. The OXYS rats are an experimental model of accelerated senescence that has also been proposed as a spontaneous rat model of AD-like pathology. In the present study, we demonstrate that disturbances in melatonin secretion occur in OXYS rats at 4 months of age. These disturbances occur simultaneously with manifestation of behavioral abnormalities against the background of neurodegeneration and alterations in hormonal status but before the signs of amyloid-β accumulation. We examined whether oral administration of melatonin could normalize the melatonin secretion and have beneficial effects on OXYS rats before progression to AD-like pathology. The results showed that melatonin treatment restored melatonin secretion in the pineal gland of OXYS rats as well as the serum levels of growth hormone and IGF-1, the level of BDNF in the hippocampus and the healthy state of hippocampal neurons. Additionally, melatonin treatment of OXYS rats prevented an increase in anxiety and the decline of locomotor activity, of exploratory activity, and of reference memory. Thus, melatonin may be involved in AD progression, whereas oral administration of melatonin could be a prophylactic strategy to prevent or slow down the progression of some features of AD pathology.

  18. Characterization of dystrophin deficient rats: a new model for Duchenne muscular dystrophy.

    Science.gov (United States)

    Larcher, Thibaut; Lafoux, Aude; Tesson, Laurent; Remy, Séverine; Thepenier, Virginie; François, Virginie; Le Guiner, Caroline; Goubin, Helicia; Dutilleul, Maéva; Guigand, Lydie; Toumaniantz, Gilles; De Cian, Anne; Boix, Charlotte; Renaud, Jean-Baptiste; Cherel, Yan; Giovannangeli, Carine; Concordet, Jean-Paul; Anegon, Ignacio; Huchet, Corinne

    2014-01-01

    A few animal models of Duchenne muscular dystrophy (DMD) are available, large ones such as pigs or dogs being expensive and difficult to handle. Mdx (X-linked muscular dystrophy) mice only partially mimic the human disease, with limited chronic muscular lesions and muscle weakness. Their small size also imposes limitations on analyses. A rat model could represent a useful alternative since rats are small animals but 10 times bigger than mice and could better reflect the lesions and functional abnormalities observed in DMD patients. Two lines of Dmd mutated-rats (Dmdmdx) were generated using TALENs targeting exon 23. Muscles of animals of both lines showed undetectable levels of dystrophin by western blot and less than 5% of dystrophin positive fibers by immunohistochemistry. At 3 months, limb and diaphragm muscles from Dmdmdx rats displayed severe necrosis and regeneration. At 7 months, these muscles also showed severe fibrosis and some adipose tissue infiltration. Dmdmdx rats showed significant reduction in muscle strength and a decrease in spontaneous motor activity. Furthermore, heart morphology was indicative of dilated cardiomyopathy associated histologically with necrotic and fibrotic changes. Echocardiography showed significant concentric remodeling and alteration of diastolic function. In conclusion, Dmdmdx rats represent a new faithful small animal model of DMD.

  19. [Effects of biotin on blood glucose regulation in type 2 diabetes rat model].

    Science.gov (United States)

    Xiang, Xuesong; Liu, Yan; Zhang, Xuesong; Zhang, Wenzong; Wang, Zhu

    2015-03-01

    To explore the effect of biotin on blood glucose regulation in rats and its possible mechanism. According to initial body weight and blood glucose, we randomly divided the 90 Wistar rats into 5 groups: the normal control group, model group, biotin low-dose group (0. 6mg/kg BW), biotin medium-dose group (3. 0 mg/kg BW) and biotin high-dose group (6. 0 mg/kg BW). After 2 months, the rats with HFS feed were injected with STZ (25 mg/kg BW) to manufacture diabetic rat model. After the OGTT experiment at 10th week, the blood glucose, insulin, liver/muscle glycogen and other biochemical indexes were detected. The GCK, PCK1 mRNA expression were measured with RT-PCR method. Biotin has a certain improvement on postprandial glucose in diabetic rats. Compared with the model group, the AUC and the 30min postprandial blood glucose of biotin high-dose group were significantly decreased (P Biotin can affect some key enzyme gene in glucose metabolism, such as GCK, PCK1. The possible mechanism of the decreasing biotin blood sugar in diabetic rats may by promoting the synthesis of glycogenand reducing gluconeogenesis.

  20. The Effects of Methylphenidate on Goal-Directed Behavior in a Rat Model of ADHD

    Directory of Open Access Journals (Sweden)

    Joman Y. Natsheh

    2015-11-01

    Full Text Available Although attentional and motor alterations in Attention Deficit Hyperactivity Disorder (ADHD have been well characterized, less is known about how this disorder impacts goal-directed behavior. To investigate whether there is a misbalance between goal-directed and habitual behaviors in an animal model of ADHD, we tested adult [P75-P105] Spontaneously Hypertensive Rats (SHR (ADHD rat model and Wistar-Kyoto rats (WKY, the normotensive control strain, on an instrumental conditioning paradigm with two phases: a free-operant training phase in which rats separately acquired two distinct action-outcome contingencies, and a choice test conducted in extinction prior to which one of the food outcomes was devalued through specific satiety. To assess the effects of Methylphenidate, a commonly used ADHD medication, on goal-directed behavior, we injected rats with either Methylphenidate or saline prior to the choice test. Both rat strains acquired an instrumental response, with SHR responding at greater rates over the course of training. During the choice test WKY demonstrated goal-directed behavior, responding more frequently on the lever that delivered, during training, the still-valued outcome. In contrast, SHR showed no goal-directed behavior, responding equally on both levers. However, methylphenidate administration prior to the choice test restored goal-directed behavior in SHR, and disrupted this behavior in WKY rats. This study provides the first experimental evidence for selective impairment in goal-directed behavior in rat models of ADHD, and how methylphenidate acts differently on SHR and WKY animals to restore or impair this behavior, respectively.

  1. Endoscopic Evaluation of Esophago-Gastro-Jejunostomy in Rat Model of Barrett’s Esophagus

    Science.gov (United States)

    Lu, Shaoying; Lowe, Anson W; Triadafilopoulos, George; Hsiung, Pei-Lin; Hao, Ying; Crawford, James M; Wang, Thomas D

    2011-01-01

    Background and aims Endoscopy can be used to monitor the onset of metaplastic transformation and to observe the progression of neoplasia in small animal models of Barrett’s esophagus. By avoiding animal sacrifice, the natural history of this disease can be studied in a longitudinal fashion. We aim to characterize the endoscopic features of esophageal mucosa at various stages of the metaplasia-dysplasia-carcinoma sequence in a rat reflux model of Barrett’s for comparison with histology. Methods Acid and bile reflux was produced by introducing a side-to-side esophago-gastro-jejunostomy in Sprague-Dawley rats. Endoscopic examination of the distal esophagus was performed in 24 surgically-altered and 4 control rats, between weeks 24 to 36 after the operation in 4 week intervals, and all rats were biopsied and sacrificed at 36 weeks. Endoscopic images were classified based on the surface mucosal patterns of the distal esophagus and then compared to histology. The endoscopic appearance were classified as: 1) normal, characterized by a smooth surface; 2) intestinal metaplasia, defined as elevated plaques/ridges, deep grooves and thin linear folds; 3) dysplasia, indicated by coarse folds/grooves, mesh-like villi, and foveolar appearance, and 4) carcinoma, suggested by irregular shaped mass lesions with ulcerations. Results The endoscopic criteria for intestinal metaplasia yielded a sensitivity of 100% in comparison to histology. Intestinal metaplasia with high-grade dysplasia was found in 2 rats and with low-grade dysplasia in 3 rats. Both focally-invasive squamous cell carcinoma and invasive adenocarcinoma were found in 1 rat. Conclusions Small animal endoscopy in a rat model of Barrett’s esophagus can be used to perform surveillance, classify mucosal patterns, observe the onset of intestinal metaplasia, and monitor the progression of neoplastic transformation, representing a useful tool for studying the natural history of this disease. PMID:19473210

  2. Efficacy and Safety of Echinacoside in a Rat Osteopenia Model

    Directory of Open Access Journals (Sweden)

    Xiaolin Yang

    2013-01-01

    parameters without the overall incidences of adverse events of uterus and mammary gland compared to OVX and SHAM groups. This study demonstrated that administration of ECH for 12 weeks can effectively and safely prevent OVX-induced osteoporosis in rats via increasing the OPG/RANKL ratio.

  3. The F8(-/-) rat as a model of hemophilic arthropathy

    DEFF Research Database (Denmark)

    Christensen, Kristine Rothaus; Roepstorff, K.; Wiinberg, B.

    2016-01-01

    . Methods Wild-type and F8(-/-) rats were treated with vehicle or recombinant human factor VIII (rhFVIII) prior to a needle-induced joint bleed. Joint swelling was measured prior to injury, the following 7 days and upon euthanasia. Histologic sections of the joint were stained, and athropathic changes...

  4. Analgesic synergism of gabapentin and carbamazepine in rat model ...

    African Journals Online (AJOL)

    Purpose: To evaluate synergy in the analgesic effects of a combination therapy of carbamazepine (CBZ) and gabapentin (GBP) in diabetic neuropathic pain. Methods: Neuropathic pain was produced in rats by a single intraperitoneal injection of streptozotocin (STZ) at 60 mg/kg. CBZ, GBP, and their combination were orally ...

  5. Neuroprotective effect corilagin in spinal cord injury rat model by ...

    African Journals Online (AJOL)

    Background: Neurological functions get altered in a patient suffering from spinal cord injury (SCI). Present study evaluates the neuroprotective effect of corilagin in spinal cord injury rats by inhibiting nuclear factor-kappa B (NF-κB), inflammatory mediators and apoptosis. Materials and method: Spinal cord injury was ...

  6. [Analysis on establishment and affecting factors of qi stagnation and blood stasis rat model].

    Science.gov (United States)

    Wang, Tingting; Jia, Cheng; Chen, Yu; Li, Xin; Cheng, Jiayi

    2012-06-01

    To study on the method for establishing the Qi stagnation and blood stasis rat model and analyze the affecting factors. The orthogonal design was adopted to study the influences of joint stimulations including noise, light, electricity, ice water bath, tail-clamping on model rats. The 'flying spot' method was used to dynamically simulate blood flow velocity in microcirculation. the pressure sensing technology of MOTO was adopted to detect hemorheology-related indicators. And the coagulation method was used to detect blood coagulation-related indicators. Compared with the negative control group, all model groups showed significant reduction in the blood flow velocity in mesenteric microcirculation and increase in the whole blood viscosity at high, medium and low shear rate, the plasma viscosity and the fibrinogen content in four blood coagulation indicators. Noise, light, electricity, tail-clamping, bondage and icewater-bath make significant impact on model rats.

  7. Development and pharmacologic characterization of the rat 6 Hz model of partial seizures.

    Science.gov (United States)

    Metcalf, Cameron S; West, Peter J; Thomson, Kyle E; Edwards, Sharon F; Smith, Misty D; White, H Steve; Wilcox, Karen S

    2017-06-01

    The mouse 6 Hz model of psychomotor seizures is a well-established and commonly used preclinical model for antiseizure drug (ASD) discovery. Despite its widespread use both in the identification and differentiation of novel ASDs in mice, a corresponding assay in rats has not been developed. We established a method for 6 Hz seizure induction in rats, with seizure behaviors similar to those observed in mice including head nod, jaw clonus, and forelimb clonus. A convulsive current that elicits these seizure behaviors in 97% of rats (CC97 ) was determined using a Probit analysis. Numerous prototype ASDs were evaluated in this model using stimulus intensities of 1.5× and 2× the CC97 , which is comparable to the approach used in the mouse 6 Hz seizure model (e.g., 32 and 44 mA stimulus intensities). The ASDs evaluated include carbamazepine, clobazam, clonazepam, eslicarbazepine, ethosuximide, ezogabine, gabapentin, lacosamide, lamotrigine, levetiracetam, phenobarbital, phenytoin, rufinamide, tiagabine, topiramate, and sodium valproate. Median effective dose (ED50 ) and median toxic (motor impairment) dose (TD50 ) values were obtained for each compound. Compounds that were effective at the 1.5 × CC97 stimulus intensity at protective index (PI) values >1 included clobazam, ethosuximide, ezogabine, levetiracetam, phenobarbital, and sodium valproate. Compounds that were effective at the 2 × CC97 stimulus intensity at PI values >1 included ezogabine, phenobarbital, and sodium valproate. In a manner similar to the use of the mouse 6 Hz model, development of a rat 6 Hz test will aid in the differentiation of ASDs, as well as in study design and dose selection for chronic rat models of pharmacoresistant epilepsy. The limited number of established ASDs with demonstrable efficacy at the higher stimulus intensity suggests that, like the mouse 6 Hz 44 mA model, the rat 6 Hz seizure model may be a useful screening tool for pharmacoresistant seizures. Wiley Periodicals, Inc.

  8. Carcinogenically relevant split dose repair increased with age in rat skin model.

    Science.gov (United States)

    Burns, Fredric; Tang, Moon-Shong Eric; Wu, Feng; Uddin, Ahmed

    2012-07-01

    These experiments utilize cancer induction to evaluate cancer-relevant repair during the interval between dose fractions. Low LET electron radiation(LET ~ 0.34 keV/u) were utilized in experiments that involved exposing rat dorsal skin to 2 equal 8 Gy dose fractions separated at various intervals from 0.25 h to 24 h. Cancer onset was established for 80 weeks after the exposures and only histologically verified cancers were included in the analysis. This experiment involved a total of 540 rats and 880 induced cancers. In the youngest rats (irradiated at 28 days of age) the cancer yield declined with a halftime of approximately 3.5 hrs. In 113 day old rats the cancer yield halftime was shortened to 1.3 hrs. In the oldest rats (182 days of age), the halftime could not be established quantitatively, because it was less than the shortest interval (15 min) utilized in the protocol (best estimate ~5 min). In the oldest rats the cancer yields for all fractionated exposures dropped essentially to the expected level of 2 single fractions, below which theoretically no further reduction is possible. The follow-up times for obtaining cancer yields were the same for all exposure groups in spite of the differing ages at exposure. These results indicate that repair of carcinogenically-relevant damage accelerates with age of the rat. No information is available on the possible mechanistic basis for this finding, although the model might be useful for delineating which of the many postulated split dose repair pathways is the correct one. The finding indicates that older rats should be less susceptible to the carcinogenic action of single doses of low LET radiation in comparison to younger rats, which has been verified in separate studies.

  9. Effect of TheraCyte-encapsulated parathyroid cells on lumbar fusion in a rat model.

    Science.gov (United States)

    Chen, Sung-Hsiung; Huang, Shun-Chen; Lui, Chun-Chung; Lin, Tzu-Ping; Chou, Fong-Fu; Ko, Jih-Yang

    2012-09-01

    Implantation of TheraCyte 4 × 10(6) live parathyroid cells can increase the bone marrow density of the spine of ovariectomized rats. There has been no published study examining the effect of such implantation on spinal fusion outcomes. The purpose of this study was to examine the effect of TheraCyte-encapsulated parathyroid cells on posterolateral lumbar fusions in a rat model. Forty Sprague-Dawley rats underwent single-level, intertransverse process spinal fusions using iliac crest autograft. The rats were randomly assigned to two groups: Group 1 rats received sham operations on their necks (control; N = 20); Group 2 rats were implanted with TheraCyte-encapsulated 4 × 10(6) live parathyroid cells into the subcutis of their necks (TheraCyte; N = 20). Six weeks after surgery the rats were killed. Fusion was assessed by inspection, manual palpation, radiography, and histology. Blood was drawn to measure the serum levels of calcium, phosphorus, and intact parathyroid hormone (iPTH). Based on manual palpation, the control group had a fusion rate of 33 % (6/18) and the TheraCyte group had a fusion rate of 72 % (13/18) (P = 0.044). Histology confirmed the manual palpation results. Serum iPTH levels were significantly higher in the TheraCyte group compared with the control group (P animal study revealed that there were more fusions in rats that received TheraCyte-encapsulated 4 × 10(6) live parathyroid cells than in control rats without significant change in serum calcium or phosphorus concentrations. As with any animal study, the results may not extrapolate to a higher species. Further studies are needed to determine if these effects are clinically significant.

  10. Betulinic acid attenuates renal fibrosis in rat chronic kidney disease model.

    Science.gov (United States)

    Sharma, Anshuk; Thakur, Richa; Lingaraju, Madhu C; Kumar, Dhirendra; Mathesh, Karikalan; Telang, Avinash G; Singh, Thakur Uttam; Kumar, Dinesh

    2017-05-01

    Most chronic kidney diseases (CKDs), regardless of the nature of the initial injury, progress to end-stage renal disease (ESRD) characterized by fibrosis with irreversible loss of tissue and function. Thus, improved and more effective therapies are critical. Betulinic acid (BA), a pentacyclic triterpene is a compound in the pipeline of anti-cancer drug development. It has been shown to a possess variety of beneficial effects in many disease conditions. However, its efficacy against CKD is yet to be explored. The present study was undertaken to investigate the effect of BA on renal fibrosis in the rat model of adenine-induced CKD. CKD rats gained significantly less weight during the experimental period when compared to control rats and BA treatment did not significantly increase the weight gain in CKD rats. CKD rats showed elevated levels of serum blood urea nitrogen (BUN), creatinine and uric acid along with increased levels of kidney injury markers such as cystatin C and neutrophil gelatinase-associated lipocalin (NGAL). Further, in comparison to control rats, kidney samples from CKD rats revealed increased profibrotic protein levels like transforming growth factor-beta (TGF-β), connective tissue growth factor (CTGF), fibronectin, collagen type I and hydroxyproline indicating a progressive fibrotic response. These data are further fortified by histological findings where kidney damage and fibrosis are clearly evident as dilatation of tubules, glomerular degeneration and vacuolation along with deposition of collagen fibers. However, the above-mentioned findings in CKD rats were significantly reversed by BA-treatment revealing its nephroprotective potential and anti-fibrotic activity. The biochemical mechanism of the nephroprotective and anti-fibrotic effect of BA in the adenine-induced CKD rats might be mediated by inhibition of pro-fibrotic protein production thereby hindering the kidney tissue damage along with improvement in kidney function. Thus, BA could be

  11. A Novel Rat Model of Hereditary Hemochromatosis Due to a Mutation in Transferrin Receptor 2

    Science.gov (United States)

    Bartnikas, Thomas B; Wildt, Sheryl J; Wineinger, Amy E; Schmitz-Abe, Klaus; Markianos, Kyriacos; Cooper, Dale M; Fleming, Mark D

    2013-01-01

    Sporadic iron overload in rats has been reported, but whether it is due to genetic or environmental causes is unknown. In the current study, phenotypic analysis of Hsd:HHCL Wistar rats revealed a low incidence of histologically detected liver iron overload. Here we characterized the pathophysiology of the iron overload and showed that the phenotype is heritable and due to a mutation in a single gene. We identified a single male rat among the 132 screened animals that exhibited predominantly periportal, hepatocellular iron accumulation. This rat expressed low RNA levels of the iron regulatory hormone hepcidin and low protein levels of transferrin receptor 2 (Tfr2), a membrane protein essential for hepcidin expression in humans and mice and mutated in forms of hereditary hemochromatosis. Sequencing of Tfr2 in the iron-overloaded rat revealed a novel Ala679Gly polymorphism in a highly conserved residue. Quantitative trait locus mapping indicated that this polymorphism correlated strongly with serum iron and transferrin saturations in male rats. Expression of the Gly679 variant in tissue culture cell lines revealed decreased steady-state levels of Tfr2. Characterization of iron metabolism in the progeny of polymorphic rats suggested that homozygosity for the Ala679Gly allele leads to a hemochromatosis phenotype. However, we currently cannot exclude the possibility that a polymorphism or mutation in the noncoding region of Tfr2 contributes to the iron-overload phenotype. Hsd:HHCL rats are the first genetic rat model of hereditary hemochromatosis and may prove useful for understanding the molecular mechanisms underlying the regulation of iron metabolism. PMID:23582421

  12. Loss of Parvalbumin in the Hippocampus of MAM Schizophrenia Model Rats Is Attenuated by Peripubertal Diazepam.

    Science.gov (United States)

    Du, Yijuan; Grace, Anthony A

    2016-11-01

    Loss of parvalbumin interneurons in the hippocampus is a robust finding in schizophrenia brains. Rats exposed during embryonic day 17 to methylazoxymethanol acetate exhibit characteristics consistent with an animal model of schizophrenia, including decreased parvalbumin interneurons in the ventral hippocampus. We reported previously that peripubertal administration of diazepam prevented the emergence of pathophysiology in adult methylazoxymethanol acetate rats. We used an unbiased stereological method to examine the impact of peripubertal diazepam treatment on parvalbumin interneuron number in the ventral subiculum, dentate gyrus of the hippocampus and the basolateral amygdala. Methylazoxymethanol acetate rats with peripubertal diazepam showed significantly more parvalbumin interneurons (3355±173 in the ventral subiculum, 1211±76 in the dentate gyrus) than methylazoxymethanol acetate without diazepam (2375±109 and 824±54, respectively). No change was found in the basolateral amygdala. Peripubertal diazepam attenuated the decrease of parvalbumin in the ventral hippocampus of methylazoxymethanol acetate rats. © The Author 2016. Published by Oxford University Press on behalf of CINP.

  13. Speech sound discrimination training improves auditory cortex responses in a rat model of autism

    Directory of Open Access Journals (Sweden)

    Crystal T Engineer

    2014-08-01

    Full Text Available Children with autism often have language impairments and degraded cortical responses to speech. Extensive behavioral interventions can improve language outcomes and cortical responses. Prenatal exposure to the antiepileptic drug valproic acid (VPA increases the risk for autism and language impairment. Prenatal exposure to VPA also causes weaker and delayed auditory cortex responses in rats. In this study, we document speech sound discrimination ability in VPA exposed rats and document the effect of extensive speech training on auditory cortex responses. VPA exposed rats were significantly impaired at consonant, but not vowel, discrimination. Extensive speech training resulted in both stronger and faster anterior auditory field responses compared to untrained VPA exposed rats, and restored responses to control levels. This neural response improvement generalized to non-trained sounds. The rodent VPA model of autism may be used to improve the understanding of speech processing in autism and contribute to improving language outcomes.

  14. Liver fibrosis impairs hepatic pharmacokinetics of liver transplant drugs in the rat model.

    Science.gov (United States)

    Zou, Yu-Hong; Liu, Xin; Khlentzos, Alexander M; Asadian, Peyman; Li, Peng; Thorling, Camilla A; Robertson, Thomas A; Fletcher, Linda M; Crawford, Darrell H G; Roberts, Michael S

    2010-01-01

    This study aims to investigate hepatic pharmacokinetics of the four most common drugs (metoprolol, omeprazole, spironolactone, and furosemide) given to patients undergoing liver transplantation before surgery. The investigation was carried out in CCl(4)-induced fibrotic perfused rat livers and the results were compared to those in normal rat liver. Drug outflow fraction-time profiles were obtained after bolus injection into a single-pass-perfused normal or fibrotic rat liver. The pharmacokinetic parameters were estimated using previously developed barrier-limited and space-distributed models. The results showed a marked increase in the liver fibrosis index for CCl(4)-treated rats compared to controls (pdrugs were significantly lower (pdrugs were significantly longer (pdrugs across the basolateral membrane and their metabolic clearance and were in a manner similar to those previously found for another group of drugs.

  15. Effect of sodium aescinate treatment on PCOS rat model with insulin resistance.

    Science.gov (United States)

    Chen, L; Hu, L M; Wang, Y F; Yang, H Y; Huang, X Y; Zhou, W; Sun, H X

    2017-01-01

    Recent studies indicated that insulin resistance may contribute to the pathogenesis of polycystic ovary syndrome (PCOS); however, the specific mechanism is still unclear. To investigate the effect of sodium aescinate (SA) on PCOS-IR rat models. Sixty rats were randomly divided into the five groups: un-treated rats (n = 12), PCOS-IR group (n = 12), PCOS-IR group plus 50 mg/kg SA (n = 12), PCOS-IR group plus 10 mg/kg SA (n = 12), PCOS-IR group plus 150 mg/kg metformin (n = 12). On day 21, rats were sacrificed, and H(and)E staining was performed for histopathologic examination of the ovaries; moreover, the serum level of follicle-stimulating hormone (FSH), testosterone, and luteotropic hormone (LH) were measured, and the expression as well as phosphorylation of PI3K, Akt and Gsk-3β were examined using western blot assay. High dosage of SA treatment improved the morphological features of the ovaries in PCOS rats, and also induced significant decrease in serum expression of testosterone and LH/FSH ratio and significant decrease in the expression of p-PI3K, p-Akt and p-Gsk-3β. Our results demonstrated that SA treatment could alleviate the symptom of PCOS in rat model through regulating the PI3K/Akt/GSK3-β pathway (Fig. 4, Ref. 22).

  16. Step training in a rat model for complex aneurysmal vascular microsurgery

    Directory of Open Access Journals (Sweden)

    Martin Dan

    2015-12-01

    Full Text Available Introduction: Microsurgery training is a key step for the young neurosurgeons. Both in vascular and peripheral nerve pathology, microsurgical techniques are useful tools for the proper treatment. Many training models have been described, including ex vivo (chicken wings and in vivo (rat, rabbit ones. Complex microsurgery training include termino-terminal vessel anastomosis and nerve repair. The aim of this study was to describe a reproducible complex microsurgery training model in rats. Materials and methods: The experimental animals were Brown Norway male rats between 10-16 weeks (average 13 and weighing between 250-400g (average 320g. We performed n=10 rat hind limb replantations. The surgical steps and preoperative management are carefully described. We evaluated the vascular patency by clinical assessment-color, temperature, capillary refill. The rats were daily inspected for any signs of infections. The nerve regeneration was assessed by foot print method. Results: There were no case of vascular compromise or autophagia. All rats had long term survival (>90 days. The nerve regeneration was clinically completed at 6 months postoperative. The mean operative time was 183 minutes, and ischemia time was 25 minutes.

  17. Radiation-induced cognitive dysfunction: An experimental model in the old rat

    Energy Technology Data Exchange (ETDEWEB)

    Lamproglou, I. [Laboratoire de Biophysique, Paris (France); Chen, Q.M.; Poisson, M. [Hopital de la Salpetriere, Paris (France)] [and others

    1995-01-01

    To develop a model of radiation-induced behavioral dysfunction. A course of whole brain radiation therapy (30 Gy/10 fractions/12 days) was administered to 26 Wistar rats ages 16-27 months, while 26 control rats received sham irradiation. Sequential behavioral studies including one-way avoidance, two-way avoidance, and a standard operant conditioning method (press-lever avoidance) were undertaken. In addition, rats were studied in a water maze 7 months postradiation therapy. Prior to radiation therapy, both groups were similar. No difference was found 1 and 3 months postradiation therapy. At 6-7 months postradiation therapy, irradiated rats had a much lower percentage of avoidance than controls for one-way avoidance (23% vs. 55%, p {le} 0.001) and two-way avoidance (18% vs. 40%, p {le} 0.01). Seven months postradiation therapy the reaction time was increased (press-lever avoidance, 11.20 s vs. 8.43 s, p {le} 0.05) and the percentage of correct response was lower (water maze, 53% vs. 82%) in irradiated rats compared with controls. Pathological examination did not demonstrate abnormalities of the irradiated brains at the light microscopic level. Behavioral dysfunction affecting mainly memory can be demonstrated following conventional radiation therapy in old rats. This model can be used to study the pathogenesis of radiation-induced cognitive changes. 15 refs., 3 figs., 1 tab.

  18. The groove model of tibia-femoral osteoarthritis in the rat

    NARCIS (Netherlands)

    de Visser, Huub M|info:eu-repo/dai/nl/41398561X; Weinans, Harrie|info:eu-repo/dai/nl/087198622; Coeleveld, Katja; van Rijen, Mattie Hp|info:eu-repo/dai/nl/304817856; Lafeber, Floris Pjg; Mastbergen, Simon C|info:eu-repo/dai/nl/290932599

    Several experimental models of osteoarthritis in rats are used to study the pathophysiology of osteoarthritis. Many mechanically induced models have the limitation that permanent joint instability is induced by e.g. ligament transection or meniscal damage. This permanent instability will counteract

  19. Development and identification of a multicompartment model for the distribution of adriamycin in the rat

    NARCIS (Netherlands)

    Sonneveld, P.; Mulder, J.A.

    1981-01-01

    The distribution kinetics of adriamycin in the rat were analyzed by using a multicompartment mathematical model. The set of a priori unknown model parameters, the drug rate constants, were estimated from 48 hr multicompartment drug distribution data by applying multivariate system identification

  20. Genetic animal models for Absence epilepsy: a review of the WAG/Rij strain of rats

    NARCIS (Netherlands)

    Coenen, A.M.L.; Luijtelaar, E.L.J.M. van

    2003-01-01

    Based on the reviewed literature and the data presented in this paper, conclusions can be drawn with respect to the validity of the WAG/Rij strain of rats as a model for absence epilepsy in humans. The view that the WAG/Rij model has "face validity" is supported by the simultaneous presence of

  1. Prevention of injury by resveratrol in a rat model of adenine-induced ...

    African Journals Online (AJOL)

    cartilage degradation in animal models of arthritis. [11]. This study examined the utility of resveratrol for treating CKD by suppressing the expression of inorganic phosphate, parathyroid hormone, and FGF-23 in a rat model. METHODS. Chemicals and reagents. The adenine and resveratrol used in this study were obtained ...

  2. Differential effects of B7-1 blockade in the rat experimental autoimmune encephalomyelitis model

    DEFF Research Database (Denmark)

    Gallon, L; Chandraker, A; Issazadeh-Navikas, Shohreh

    1997-01-01

    Blocking the CD28-B7 T cell costimulatory activation pathway protects animals from developing experimental autoimmune encephalomyelitis (EAE). In the mouse EAE model, selective blockade of B7-1 by specific mAbs has been shown to protect animals from EAE. In the Lewis rat model, we have shown that...

  3. Tissue reactions to lead samples in a late infection rat model

    NARCIS (Netherlands)

    VanWachem, PB; VanLuyn, MJA; DeWit, AW; Raatjes, D; Verhoeven, MLPM; Hendriks, M; Cahalan, PT

    Tissue reactions to rat lead samples, model ii ng for clinically used leads, were investigated in a late infection model, in which injection of bacteria was performed after a 3-week encapsulation process. At the site of injection, detachment of the original fibrous capsule, wound fluid infiltration,

  4. Repeated Moderate Noise Exposure in the Rat--an Early Adulthood Noise Exposure Model.

    Science.gov (United States)

    Mannström, Paula; Kirkegaard, Mette; Ulfendahl, Mats

    2015-12-01

    In this study, we investigated the effects of varying intensity levels of repeated moderate noise exposures on hearing. The aim was to define an appropriate intensity level that could be repeated several times without giving rise to a permanent hearing loss, and thus establish a model for early adulthood moderate noise exposure in rats. Female Sprague-Dawley rats were exposed to broadband noise for 90 min, with a 50 % duty cycle at levels of 101, 104, 107, or 110 dB sound pressure level (SPL), and compared to a control group of non-exposed animals. Exposure was repeated every 6 weeks for a maximum of six repetitions or until a permanent hearing loss was observed. Hearing was assessed by the auditory brainstem response (ABR). Rats exposed to the higher intensities of 107 and 110 dB SPL showed permanent threshold shifts following the first exposure, while rats exposed to 101 and 104 dB SPL could be exposed at least six times without a sustained change in hearing thresholds. ABR amplitudes decreased over time for all groups, including the non-exposed control group, while the latencies were unaffected. A possible change in noise susceptibility following the repeated moderate noise exposures was tested by subjecting the animals to high-intensity noise exposure of 110 dB for 4 h. Rats previously exposed repeatedly to 104 dB SPL were slightly more resistant to high-intensity noise exposure than non-exposed rats or rats exposed to 101 dB SPL. Repeated moderate exposure to 104 dB SPL broadband noise is a viable model for early adulthood noise exposure in rats and may be useful for the study of noise exposure on age-related hearing loss.

  5. Bilateral Cavernous Nerve Crush Injury in the Rat Model: A Comparative Review of Pharmacologic Interventions.

    Science.gov (United States)

    Haney, Nora M; Nguyen, Hoang M T; Honda, Matthew; Abdel-Mageed, Asim B; Hellstrom, Wayne J G

    2017-08-18

    It is common for men to develop erectile dysfunction after radical prostatectomy. The anatomy of the rat allows the cavernous nerve (CN) to be identified, dissected, and injured in a controlled fashion. Therefore, bilateral CN injury (BCNI) in the rat model is routinely used to study post-prostatectomy erectile dysfunction. To compare and contrast the available literature on pharmacologic intervention after BCNI in the rat. A literature search was performed on PubMed for cavernous nerve and injury and erectile dysfunction and rat. Only articles with BCNI and pharmacologic intervention that could be grouped into categories of immune modulation, growth factor therapy, receptor kinase inhibition, phosphodiesterase type 5 inhibition, and anti-inflammatory and antifibrotic interventions were included. To assess outcomes of pharmaceutical intervention on erectile function recovery after BCNI in the rat model. The ratio of maximum intracavernous pressure to mean arterial pressure was the main outcome measure chosen for this analysis. All interventions improved erectile function recovery after BCNI based on the ratio of maximum intracavernous pressure to mean arterial pressure results. Additional end-point analysis examined the corpus cavernosa and/or the major pelvic ganglion and CN. There was extreme heterogeneity within the literature, making accurate comparisons between crush injury and therapeutic interventions difficult. BCNI in the rat is the accepted animal model used to study nerve-sparing post-prostatectomy erectile dysfunction. However, an important limitation is extreme variability. Efforts should be made to decrease this variability and increase the translational utility toward clinical trials in humans. Haney NM, Nguyen HMT, Honda M, et al. Bilateral Cavernous Nerve Crush Injury in the Rat Model: A Comparative Review of Pharmacologic Interventions. Sex Med Rev 2017;X:XXX-XXX. Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier

  6. Experimental tuberculosis in the Wistar rat: a model for protective immunity and control of infection.

    Directory of Open Access Journals (Sweden)

    Amit Singhal

    Full Text Available BACKGROUND: Despite the availability of many animal models for tuberculosis (TB research, there still exists a need for better understanding of the quiescent stage of disease observed in many humans. Here, we explored the use of the Wistar rat model for the study of protective immunity and control of Mycobacterium tuberculosis (Mtb infection. METHODOLOGY/PRINCIPAL FINDINGS: The kinetics of bacillary growth, evaluated by the colony stimulating assay (CFU and the extent of lung pathology in Mtb infected Wistar rats were dependent on the virulence of the strains and the size of the infecting inoculums. Bacillary growth control was associated with induction of T helper type 1 (Th1 activation, the magnitude of which was also Mtb strain and dose dependent. Histopathology analysis of the infected lungs demonstrated the formation of well organized granulomas comprising epithelioid cells, multinucleated giant cells and foamy macrophages surrounded by large numbers of lymphocytes. The late stage subclinical form of disease was reactivated by immunosuppression leading to increased lung CFU. CONCLUSION: The Wistar rat is a valuable model for better understanding host-pathogen interactions that result in control of Mtb infection and potentially establishment of latent TB. These properties together with the ease of manipulation, relatively low cost and well established use of rats in toxicology and pharmacokinetic analyses make the rat a good animal model for TB drug discovery.

  7. Lung and Intestine: A Specific Link in an Ulcerative Colitis Rat Model

    Directory of Open Access Journals (Sweden)

    Yuan Liu

    2013-01-01

    Full Text Available Background. To investigate the link and mechanisms between intestine and lung in the ulcerative colitis (UC rat model. Materials and Methods. We used the UC rat model by immunological sensitization combined with local 2, 4, 6-trinitrobenzene sulfonic acid (TNBS in 50% ethanol enema, observed dynamically animal general state and body weight, examined the histological and functional changes in the colon, lung, liver, and kidney tissues, and detected microvascular endothelium response towards inflammation characterized with the expression of iNOS, TXB2, P-selectin, ICAM-1, and vascular endothelial growth factor A (VEGF-A in the colon and lung tissue. Results. Pulmonary function results suggested ventilator disorder, and pathological findings showed interstitial pneumonia. There were no significant changes in the liver and kidney function and histopathology. The colon and lung tissue iNOS, TXB2, P-selectin, ICAM-1, and VEGF-A expression of the model rats was significantly higher than the normal rats at both time points. Conclusions. Our study is the first to demonstrate the close association between the large intestine and lung in the immune-TNBS-ethanol-induced UC rat model. Different organs and tissues with the same embryonic origin may share the same pathological specificities in a disease. The present study provided a new way of thinking for pathological changes in clinical complex diseases manifested with multiorgan damage.

  8. Catalpol regulates function of hypothalamic-pituitary-adrenocortical-axis in an Alzheimer's disease rat model.

    Science.gov (United States)

    Wang, Jin-Hong; Li, Wen-Tao; Yu, Shu-Tian; Xie, Hai; Han, Hui-Rong

    2014-09-01

    To investigate the regulating effects of catalpol on the hypothalamic-pituitary- adrenocortical-axis (HPA) in an Alzheimer's disease (AD) rat model. Healthy male Wistar Rats were selected. The AD model was generated by orthotopic injection of beta-amyloid 25-35 (Abeta25-35) into the right lateral ventricle. The animals were divided into five study groups: Catalpol at low dose (5 mg/kg), Catalpol at high dose (10 mg/kg), model control group and sham surgery control group, n = 9 respectively. The serum concentration of hydrocortisone (HYD), adrenocorticotropin (ACTH) and corticotropin releasing hormone (CRH) determined by Enzyme-Linked Immunosorbent Assay (ELISA). Structural alterations of the hypothalamus were examined by H&E stain and electron microscope. The CRH receptor 1 (CRHR1) positive neurons were detected with immunohistochemistry. Serum HYD level was significantly increased (p endocrine function of the HPA and alleviate the structural damage of hypothalamus in AD rats.

  9. Improvement of Radiation-Mediated Immunosuppression of Human NSCLC Tumour Xenografts in a Nude Rat Model

    Directory of Open Access Journals (Sweden)

    Sergey V. Tokalov

    2010-01-01

    Full Text Available Human tumour xenografts in a nude rat model have consistently been used as an essential part of preclinical studies for anticancer drugs activity in human. Commonly, these animals receive whole body irradiation to assure immunosuppression. But whole body dose delivery might be inhomogeneous and the resulting incomplete bone marrow depletion may modify tumour behaviour. To improve irradiation-mediated immunosuppression of human non-small cell lung cancer (NSCLC xenografts in a nude rat model irradiation (2 + 2 Gy from opposite sides of animals has been performed using a conventional X-ray tube. The described modification of whole body irradiation improves growth properties of human NSCLC xenografts in a nude rat model. The design of the whole body irradiation mediated immunosuppression described here for NSCLC xenografts may be useful for research applications involving other types of human tumours.

  10. Acetic acid bacterial lipids improve cognitive function in dementia model rats.

    Science.gov (United States)

    Fukami, Hiroyuki; Tachimoto, Hideki; Kishi, Mikiya; Kaga, Takayuki; Tanaka, Yasukazu

    2010-04-14

    Acetic acid bacteria, fermentative microorganisms of traditional foods, have unique alkali-stable lipids (ASL), such as dihydroceramide which is a precursor of sphingolipids. Sphingolipids are important components of the brain tissue. We examined the effect of oral administration of ASL in a rat model of dementia (7-week-old, male) with a basal forebrain lesion. In a water maze test, the dementia model rats demonstrated poor spatial orientation. The administration of ASL (165 or 1650 mg/kg of body weight per day, for 14 days) produced a significant improvement in learning ability in the dementia model rats. In vitro experiments showed ASL had the ability to promote neurite outgrowth in pheochromocytoma (PC12) cells. Among the ASL components, dihydroceramide has the most potent effect on the differentiation of PC12 cells. It is highly possible that oral administration of dihydroceramide-containing ASL reverses the decline in cognitive function in dementia.

  11. [Effects of Salidroside on Tic Behavior of Tourette Syndrome Model Rats].

    Science.gov (United States)

    Xie, Hui; Wang, Zhen; Ji, Yan; Yin, Jing; Yang, Wen-hao; Ren, Li-min

    2016-01-01

    To observe the effect of salidroside on tic behavior and in vivo dopamine DA) and serotonin (5-HT) levels in Tourette syndrome (TS) model rats. Forty rats were randomly divided into the blank control group, the TS model group, the haloperidol-treated group (0.5 mg/kg x d(-1)), and the salidroside-treated group (50 mg/kg x d(-1)), 10 in each group. TS rat model was induced by imino-dipropio-nitrile (IDPN). Peritoneal injection of haloperidol and salidroside was started from the 4th day of modeling in the haloperidol-treated group and the salidroside-treated group respectively. Normal saline was peritoneally injected to rats in the blank control group and the TS model group respectively. Stereotyped behavior was scored, and changes of DA and 5-HT levels in blood and striatum were measured before modeling, after modeling, and after intervention. Compared with the blank control group, the score of the tic behavior was elevated (P salidroside-treated group (P salidroside-treated group and the haloperidol-treated group. Compared with the haloperidol-treated group, the tic behavior score increased (P salidroside-treated group. In the salidroside-treated group, the tic behavior was significantly reduced, and DA levels in plasma and striatum were elevated. Its mechanism might be related to regulating activities of dopamine neurons in striatum.

  12. Glutamatergic signaling and low prodynorphin expression are associated with intact memory and reduced anxiety in rat models of healthy aging

    Directory of Open Access Journals (Sweden)

    Caroline eMenard

    2014-05-01

    Full Text Available The LOU/C/Jall (LOU rat strain is considered a model of healthy aging due to its increased longevity, maintenance of stable body weight (BW throughout life and low incidence of age-related diseases. However, aging LOU rat cognitive and anxiety status has yet to be investigated. In the present study, male and female LOU rat cognitive performances (6-42 months were assessed using novel object recognition and Morris Water Maze tasks. Recognition memory remained intact in all LOU rats up to 42 months of age. As for spatial memory, old LOU rat performed similarly as young animals for learning acquisition, reversal learning and retention. While LOU rat BW remained stable despite aging, 20-month-old ad-libitum-fed (OAL male Sprague Dawley rats become obese. We determined if long-term caloric restriction (LTCR prevents age-related BW increase and cognitive deficits in this rat strain, as observed in the obesity-resistant LOU rats. Compared to young animals, recognition memory was impaired in OAL but intact in 20-month-old calorie-restricted (OCR rats. Similarly, OAL spatial learning acquisition was impaired but LTCR prevented the deficits. Exacerbated stress responses may favor age-related cognitive decline. In the elevated plus maze and open field tasks, LOU and OCR rats exhibited high levels of exploratory activity whereas OAL rats displayed anxious behaviors. Expression of prodynorphin (Pdyn, an endogenous peptide involved in stress-related memory impairments, was increased in the hippocampus of OAL rats. Group 1 metabotropic glutamate receptor 5 and immediate early genes Homer 1a and Arc expression, both associated with successful cognitive aging, were unaltered in aging LOU rats but lower in OAL than OCR rats. Altogether, our results, supported by principal component analysis and correlation matrix, suggest that intact memory and low anxiety are associated with glutamatergic signaling and low Pdyn expression in the hippocampus of non obese aging

  13. Glutamatergic signaling and low prodynorphin expression are associated with intact memory and reduced anxiety in rat models of healthy aging

    Science.gov (United States)

    Ménard, Caroline; Quirion, Rémi; Bouchard, Sylvain; Ferland, Guylaine; Gaudreau, Pierrette

    2014-01-01

    The LOU/C/Jall (LOU) rat strain is considered a model of healthy aging due to its increased longevity, maintenance of stable body weight (BW) throughout life and low incidence of age-related diseases. However, aging LOU rat cognitive and anxiety status has yet to be investigated. In the present study, male and female LOU rat cognitive performances (6–42 months) were assessed using novel object recognition and Morris Water Maze tasks. Recognition memory remained intact in all LOU rats up to 42 months of age. As for spatial memory, old LOU rat performed similarly as young animals for learning acquisition, reversal learning, and retention. While LOU rat BW remained stable despite aging, 20-month-old ad-libitum-fed (OAL) male Sprague Dawley rats become obese. We determined if long-term caloric restriction (LTCR) prevents age-related BW increase and cognitive deficits in this rat strain, as observed in the obesity-resistant LOU rats. Compared to young animals, recognition memory was impaired in OAL but intact in 20-month-old calorie-restricted (OCR) rats. Similarly, OAL spatial learning acquisition was impaired but LTCR prevented the deficits. Exacerbated stress responses may favor age-related cognitive decline. In the elevated plus maze and open field tasks, LOU and OCR rats exhibited high levels of exploratory activity whereas OAL rats displayed anxious behaviors. Expression of prodynorphin (Pdyn), an endogenous peptide involved in stress-related memory impairments, was increased in the hippocampus of OAL rats. Group 1 metabotropic glutamate receptor 5 and immediate early genes Homer 1a and Arc expression, both associated with successful cognitive aging, were unaltered in aging LOU rats but lower in OAL than OCR rats. Altogether, our results, supported by principal component analysis and correlation matrix, suggest that intact memory and low anxiety are associated with glutamatergic signaling and low Pdyn expression in the hippocampus of non-obese aging rats. PMID

  14. Hormone-induced rat model of polycystic ovary syndrome: A systematic review.

    Science.gov (United States)

    Noroozzadeh, Mahsa; Behboudi-Gandevani, Samira; Zadeh-Vakili, Azita; Ramezani Tehrani, Fahimeh

    2017-12-15

    Despite polycystic ovary syndrome (PCOS) being one of the most common endocrine disorders affecting reproductive-aged women, the etiopathogenesis and mechanisms of this syndrome remain unclear. Considering the ethical limitations in human studies, animal models that reflect many features of PCOS are crucial resources to investigate this syndrome. We aimed to introduce the most suitable rat model of PCOS that closely mimics the endocrine, ovarian and metabolic disturbances of human PCOS phenotype, while maintaining normal reproductive system morphology in adulthood, in order to further more detailed investigations about PCOS. We searched Pubmed, Science direct, and Web of science between 1990 and 2016, for relevant English manuscripts, using keywords including the "Polycystic Ovary Syndrome AND Rat Model" to generate a subset of citations relevant to our research. Included were those articles that compared at least both ovarian histology or estrous cycle and reproductive hormonal profiles in hormone-induced rat model of PCOS and controls. Differences in the findings between hormone-induced PCOS rats appear to be a result of the degree of transplacental transfer of the steroid administered into the fetus, dose and type of hormone, route of administration and timing and duration of exposure. We conclude that prenatal hormone-induced rat model with a lower dose and shorter time of exposure during the critical period of fetal development that exhibits endocrine, ovarian and metabolic disturbances similar to PCOS in women, while maintaining normal reproductive system morphology in adulthood is more suitable than postnatal hormone-induced rat model to facilitate studies regarding PCOS. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. The BSSG rat model of Parkinson's disease: progressing towards a valid, predictive model of disease.

    Science.gov (United States)

    Van Kampen, Jackalina M; Robertson, Harold A

    2017-09-01

    Parkinson's disease (PD) is a neurodegenerative disorder, classically considered a movement disorder. A great deal is known about the anatomical connections and neuropathology and pharmacological changes of PD, as they relate to the loss of dopaminergic function and the appearance of cardinal motor symptoms. Our understanding of the role of dopamine in PD has led to the development of effective pharmacological treatments of the motor symptoms in the form of dopamine replacement therapy using levodopa and dopaminergic agonists. Much of the information concerning these drug treatments has been obtained using classical neurotoxic models that mimic dopamine depletion (e.g., 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine or MPTP, 6-hydroxydopamine, reserpine). However, PD is more than a disorder of the nigrostriatal dopamine pathway. Our understanding of the neuropathology of PD has undergone massive changes, with the discovery that mutations in α-synuclein cause a familial form of PD and that PD pathology may spread, affecting multiple neurotransmitter systems and brain regions. These new developments in our understanding of PD demand that we reconsider our animal models. While classic neurotoxin models have been useful for the development of effective symptomatic treatments for motor manifestations, the paucity of a valid animal model exhibiting the progressive development of multiple key features of PD pathophysiology and phenotype has impeded the search for neuroprotective therapies, capable of slowing or halting disease progression. What characteristics would a good animal model of human PD have? In so much as is possible, a good model would exhibit as many behavioral, anatomical, biochemical, immunological, and pathological changes as are observed in the human condition, developing progressively, with clear, identifiable biomarkers along the way. Here, we review the BSSG rat model of PD, a novel environmental model of PD, with strong construct, face, and predictive

  16. A Novel Rat Model of Polymicrobial Peri-Implantitis: A Preliminary Study.

    Science.gov (United States)

    Koutouzis, Theofilos; Eastman, Christie; Chukkapalli, Sasanka; Larjava, Hannu; Kesavalu, Lakshmyya

    2017-02-01

    Peri-implantitis is a complex polymicrobial biofilm-induced inflammatory osteolytic gingival infection that results in orofacial implant failures. To the best knowledge of the authors, there are no preclinical in vivo studies in implant dentistry that have investigated the inflammatory response to known microbial biofilms observed in humans. The aim of this study is to develop a novel peri-implant rat model using an established model of polymicrobial periodontitis. Wistar rats were used for the study of experimental peri-implantitis. One month after extraction of maxillary first molars, a titanium mini-implant was inserted. Two months after implant healing, implants were uncovered, and abutment fixing was done using cyanoacrylate to prevent abutment loosening. Rats were separated into two groups (group A: polymicrobial-infected and group B: sham-infected). One week after healing of abutments, rats were infected with Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia for 12 weeks. Bacterial colonization, bone resorption, and implant inflammation were evaluated by polymerase chain reaction (PCR), microcomputed tomography, and histology, respectively. Three rats with four implants in the infection group and two rats with three implants in the sham-infection group were analyzed. PCR analysis revealed presence of bacterial genomic DNA, and infection elicited significant immunoglobulin (Ig)G and IgM antibody responses, indicating bacterial colonization/infection around implants. Infection induced an enhanced mean distance from implant platform to the first bone-to-implant contact, extensive peri-implantitis with advanced bone resorption, and extensive inflammation with granulation tissue and polymorphonuclear leukocytes. To the best knowledge of the authors, this is the first study to develop a novel rat model of polymicrobial peri-implantitis. With modifications to improve implant retention it could offer significant advantages for studies of

  17. General developmental health in the VPA-rat model of autism

    DEFF Research Database (Denmark)

    Favre, Mônica R; Rinaldi Barkat, Tania; Lamendola, Deborah

    2013-01-01

    Autism is a neurodevelopmental condition diagnosed by impaired social interaction, abnormal communication and, stereotyped behaviors. While post-mortem and imaging studies have provided good insights into the neurobiological symptomology of autism, animal models can be used to study...... with VPA during early pregnancy show an increased risk for giving birth to an autistic child. In rats, early embryonic exposure, around the time of neural tube closure, leads to autism-like anatomical and behavioral abnormalities in the offspring. Considering the increasing use of the VPA rat model, we...

  18. Establishing a rat model of spastic cerebral palsy by targeted ethanol injection

    Science.gov (United States)

    Yu, Yadong; Li, Liang; Shao, Xinzhong; Tian, Fangtao; Sun, Qinglu

    2013-01-01

    Spastic cerebral palsy is generally considered to result from cerebral cortical or pyramidal tract damage. Here, we precisely targeted the left pyramidal tract of 2-month-old Sprague-Dawley rats placed on a stereotaxic instrument under intraperitoneal anesthesia. Based on the rat brain stereotaxic map, a 1-mm hole was made 10 mm posterior to bregma and 0.8 mm left of sagittal suture. A microsyringe was inserted perpendicularly to the surface of the brain to a depth of 9.7 mm, and 15 μL of ethanol was slowly injected to establish a rat model of spastic cerebral palsy. After modeling, the rats appeared to have necrotic voids in the pyramidal tract and exhibited typical signs and symptoms of flexion spasms that lasted for a long period of time. These findings indicate that this is an effective and easy method of establishing a rat model of spastic cerebral palsy with good re-producibility. Ethanol as a chemical ablation agent specifically and thoroughly damages the pyramidal tract, and therefore, the animals display flexion spasms, which are a typical symptom of the disease. PMID:25206647

  19. Rat model of influenza-associated encephalopathy (IAE): studies of electroencephalogram (EEG) in vivo.

    Science.gov (United States)

    Cissé, Y; Wang, S; Inoue, I; Kido, H

    2010-02-17

    Influenza-associated encephalopathy (IAE) is characterized by severe neurological complications during high-grade fever with high morbidity and mortality in children. The major neurological complications during high-grade fever include convulsive seizures, loss of consciousness, neuropsychiatric behavior (hallucination, meaningless speech, disorientation, laughing alone); high voltage amplitude slow waves and the occurrence of theta oscillation are depicted on the electroencephalogram (EEG) in the IAE patients. At the early phase of the disease, the cytokines levels increase in severe cases. To understand the neuronal properties in the CNS leading to these neurological complications in IAE patients, we recorded EEG signals from the hippocampus and cortex of rats infected with influenza A/WSN/33 H1N1 virus (IAV) strain. Abnormal EEG activities were observed in all infected rats under anesthesia, including high voltage EEG burst amplitude and increased EEG spikes in the early phase (8 h-day 2) of infection, and these increases at the early phase were in parallel with a significant increase level of interleukin-6 (IL-6) in the serum. When the infected rats were heat-stressed by elevating the rat body core temperature to 39-41 degrees C, these abnormal EEG activities were enhanced, and the oscillation pattern shifted in most of rats from slow bursting waves (EEG activities in IAE patients could be well reproduced in anesthetized IAV infected rats under hyperthermia, hence this animal model will be useful for further understandings the mechanism of neuronal complications in IAE patient during high-grade fever.

  20. Hepatoprotective Effects of Swimming Exercise against D-Galactose-Induced Senescence Rat Model

    Directory of Open Access Journals (Sweden)

    Chi-Chang Huang

    2013-01-01

    Full Text Available This study investigates whether a 12-week swimming exercise training can prevent liver damage or senescence associated biomarkers in an experimental aging model in rats. Twenty-three male Sprague-Dawley rats were divided into four groups: vehicle treatment with sedentary control (C, , aging induction with sedentary (A, , vehicle treatment with swimming exercise (SW, , and aging induction with swimming exercise (A + SW, . Rats in groups A and AS received intraperitoneal D-galactose injections (150 mg/kg/day for 12 weeks to induce aging. Rats in groups SW and A + SW were subjected to swimming exercise training for 12 weeks. Body weight, liver weight, epididymal fat mass, blood biochemistry, and liver pathology were performed at the end of the experiment. Hepatic senescence protein markers such as β-galactosidase, p53, and p21, as well as the inflammatory mediator, IL-6, were examined. The D-galactose-treated rats exhibited increases in AST and γ-GT plasma levels and β-galactosidase protein expression compared to the control group. Swimming exercise significantly reduced BW, epididymal fat mass, γ-GT activity, and p53, p21, and IL-6 protein levels compared to the aging group. These results suggest that a 12-week swimming exercise program suppresses senescence markers and downregulates inflammatory mediator in the liver tissues of D-galactose-induced aging rats.

  1. Strong interactions between learned helplessness and risky decision-making in a rat gambling model.

    Science.gov (United States)

    Nobrega, José N; Hedayatmofidi, Parisa S; Lobo, Daniela S

    2016-11-18

    Risky decision-making is characteristic of depression and of addictive disorders, including pathological gambling. However it is not clear whether a propensity to risky choices predisposes to depressive symptoms or whether the converse is the case. Here we tested the hypothesis that rats showing risky decision-making in a rat gambling task (rGT) would be more prone to depressive-like behaviour in the learned helplessness (LH) model. Results showed that baseline rGT choice behaviour did not predict escape deficits in the LH protocol. In contrast, exposure to the LH protocol resulted in a significant increase in risky rGT choices on retest. Unexpectedly, control rats subjected only to escapable stress in the LH protocol showed a subsequent decrease in riskier rGT choices. Further analyses indicated that the LH protocol affected primarily rats with high baseline levels of risky choices and that among these it had opposite effects in rats exposed to LH-inducing stress compared to rats exposed only to the escape trials. Together these findings suggest that while baseline risky decision making may not predict LH behaviour it interacts strongly with LH conditions in modulating subsequent decision-making behaviour. The suggested possibility that stress controllability may be a key factor should be further investigated.

  2. Thrombolytic effects in vivo of nattokinase in a carrageenan-induced rat model of thrombosis.

    Science.gov (United States)

    Xu, Jianping; Du, Ming; Yang, Xiulin; Chen, Qingquan; Chen, Hong; Lin, Dong-Hong

    2014-01-01

    Nattokinase is a serine protease produced by Bacillus subtilis during the fermentation of the soybean product natto. The fibrinolytic activity and thrombolytic effects of nattokinase have been observed in vitro, but the effect in vivo has still to be researched. The objective of this study was to demonstrate the activity of nattokinase in vivo. To establish a rat model of thrombosis, κ-carrageenan was injected subcutaneously into the toes of Sprague-Dawley (SD) rats. Histological examination confirmed thrombosis. The rats were then treated with varying doses of nattokinase and the resulting thrombolysis was histologically assessed. ELISA was used to determine the levels of the fibrin/fibrinogen degradation products (FDPs) and D-dimer, which are sensitive indices of fibrinolytic activity. Vermis kinase, a known thrombolytic agent, was used as a positive control. Biopsy results revealed partial thrombolysis in the tail vessels of the rats treated with nattokinase or vermis kinase. FDP and D-dimer levels were higher in rats treated with high-dose nattokinase than in those treated with saline. No difference in FDP or D-dimer levels was observed between rats treated with high-dose nattokinase and those treated with vermis kinase. Both the histological and physiological evidence from this study indicate that nattokinase exerts thrombolytic effects in vivo.

  3. COMP-angiopoietin-1 promotes cavernous angiogenesis in a type 2 diabetic rat model.

    Science.gov (United States)

    Kim, Sun-Ouck; Lee, Hyun-Suk; Ahn, Kyuyoun; Park, Kwangsung

    2013-05-01

    Cartilage oligomeric matrix protein-angiopoietin-1 (COMP-Ang1) is an angiogenic factor for vascular angiogenesis. The aim was to investigate the effect of an intracavernosal injection of COMP-Ang1 on cavernosal angiogenesis in a diabetic rat model. Male Otsuka Long-Evans Tokushima Fatty (OLETF) rats made up the experimental group (1 yr old) and Long-Evans Tokushima Otsuka (LETO) rats made up the control group. The experimental group was divided into vehicle only, 10 µg COMP-Ang1, and 20 µg COMP-Ang1. COMP-Ang1 was injected into the corpus cavernosum of the penis. After 4 weeks, the penile tissues of the rats were obtained for immunohistochemistry and Western blot analysis. The immunoreactivity of PECAM-1 and VEGF was increased in the COMP-Ang1 group compared with the vehicle only group. Moreover, the expression of PECAM-1 and VEGF was notably augmented in the 20 µg Comp Ang-1 group. In the immunoblotting study, the expression of PECAM-1 and VEGF protein was significantly less in the OLEFT rats than in the control LETO rats. However, this expression was restored to control level after intracavernosal injection of COMP-Ang1. These results show that an intracavernosal injection of COMP-Ang1 enhances cavernous angiogenesis by structurally reinforcing the cavernosal endothelium.

  4. Auditory evoked potentials in a newborn Wistar rat model of hyperbilirubinemia.

    Science.gov (United States)

    Gökdoğan, Çağıl; Genç, Aydan; Gülbahar, Özlem; Gökdoğan, Ozan; Helvacı, Ayşe; Bezgin, Selin Üstün; Memiş, Leyla

    2016-01-01

    Hyperbilirubinemia is a common health problem in newborns. Its effects can be different according to the level and duration of the hyperbilirubinemia. The toxic effect of bilirubin on the auditory system can be seen as a sensory neural hearing loss or auditory neuropathy spectrum disorder (ANSD). The purpose of our study was to determine the effects of toxic bilirubin level on the auditory system by using Auditory Brainstem Response audiometry. Rats are used as animal models due to their low cost and easy attainability. Auditory Brainstem Response was used for auditory assessment. In this study, three groups were established: experimental, control and placebo groups. In the experimental group, which consists of rats with hyperbilirubinemia, sensory neural hearing loss was found bilaterally in 4 rats (66.67%) and unilaterally in 2 rats (16.67%) and auditory neuropathy spectrum disorder was found unilaterally in 1 rat (8.33%). Auditory Brainstem Response thresholds were significantly elevated compared to control and placebo groups (p<0.05). Hyperbilirubinemia of newborn rats may result both in sensory neural hearing loss and auditory neuropathy spectrum disorder. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  5. Auditory evoked potentials in a newborn Wistar rat model of hyperbilirubinemia

    Directory of Open Access Journals (Sweden)

    Çagil Gökdogan

    2016-04-01

    Full Text Available ABSTRACT INTRODUCTION: Hyperbilirubinemia is a common health problem in newborns. Its effects can be different according to the level and duration of the hyperbilirubinemia. The toxic effect of bilirubin on the auditory system can be seen as a sensory neural hearing loss or auditory neuropathy spectrum disorder (ANSD. OBJECTIVE: The purpose of our study was to determine the effects of toxic bilirubin level on the auditory system by using Auditory Brainstem Response audiometry. METHODS: Rats are used as animal models due to their low cost and easy attainability. Auditory Brainstem Response was used for auditory assessment. In this study, three groups were established: experimental, control and placebo groups. RESULTS: In the experimental group, which consists of rats with hyperbilirubinemia, sensory neural hearing loss was found bilaterally in 4 rats (66.67% and unilaterally in 2 rats (16.67% and auditory neuropathy spectrum disorder was found unilaterally in 1 rat (8.33%. Auditory Brainstem Response thresholds were significantly elevated compared to control and placebo groups (p < 0.05. CONCLUSION: Hyperbilirubinemia of newborn rats may result both in sensory neural hearing loss and auditory neuropathy spectrum disorder.

  6. Vagus nerve stimulation delivered during motor rehabilitation improves recovery in a rat model of stroke.

    Science.gov (United States)

    Khodaparast, Navid; Hays, Seth A; Sloan, Andrew M; Fayyaz, Tabbassum; Hulsey, Daniel R; Rennaker, Robert L; Kilgard, Michael P

    2014-09-01

    Neural plasticity is widely believed to support functional recovery following brain damage. Vagus nerve stimulation paired with different forelimb movements causes long-lasting map plasticity in rat primary motor cortex that is specific to the paired movement. We tested the hypothesis that repeatedly pairing vagus nerve stimulation with upper forelimb movements would improve recovery of motor function in a rat model of stroke. Rats were separated into 3 groups: vagus nerve stimulation during rehabilitation (rehab), vagus nerve stimulation after rehab, and rehab alone. Animals underwent 4 training stages: shaping (motor skill learning), prelesion training, postlesion training, and therapeutic training. Rats were given a unilateral ischemic lesion within motor cortex and implanted with a left vagus nerve cuff. Animals were allowed 1 week of recovery before postlesion baseline training. During the therapeutic training stage, rats received vagus nerve stimulation paired with each successful trial. All 17 trained rats demonstrated significant contralateral forelimb impairment when performing a bradykinesia assessment task. Forelimb function was recovered completely to prelesion levels when vagus nerve stimulation was delivered during rehab training. Alternatively, intensive rehab training alone (without stimulation) failed to restore function to prelesion levels. Delivering the same amount of stimulation after rehab training did not yield improvements compared with rehab alone. These results demonstrate that vagus nerve stimulation repeatedly paired with successful forelimb movements can improve recovery after motor cortex ischemia and may be a viable option for stroke rehabilitation. © The Author(s) 2014.

  7. A physiologically based pharmacokinetic model for valnemulin in rats and extrapolation to pigs.

    Science.gov (United States)

    Yuan, L G; Luo, X Y; Zhu, L X; Wang, R; Liu, Y H

    2011-06-01

    A flow-limited, physiologically based pharmacokinetic (PBPK) model for predicting the plasma and tissue concentrations of valnemulin after a single oral administration to rats was developed, and then the data were extrapolated to pigs so as to predict withdrawal interval in edible tissues. Blood/tissue pharmacokinetic data and blood/tissue partition coefficients for valnemulin in rats and pigs were collected experimentally. Absorption, distribution and elimination of the drug were characterized by a set of mass-balance equations. Model simulations were achieved using a commercially available software program. The rat PBPK model better predicted plasma and tissue concentrations. The correlation coefficients of the predicted and experimentally determined values for plasma, liver, kidney, lung and muscle were 0.96, 0.94, 0.96, 0.91 and 0.91, respectively. The rat model parameters were extrapolated to pigs to estimate valnemulin residue withdrawal interval in edible tissues. Correlation (R(2) ) between predicted and observed liver, kidney and muscle were 0.95, 0.97 and 0.99, respectively. Based on liver tissue residue profiles, the pig model estimated a withdrawal interval of 10 h under a multiple oral dosing schedule (5.0 mg/kg, twice daily for 7.5 days). PBPK models, such as this one, provide evidence of the usefulness in interspecies PK data extrapolation over a range of dosing scenarios and can be used to predict withdrawal interval in pigs. © 2010 Blackwell Publishing Ltd.

  8. Genotypic and phenotypic characterization of P23H line 1 rat model.

    Directory of Open Access Journals (Sweden)

    Elise Orhan

    Full Text Available Rod-cone dystrophy, also known as retinitis pigmentosa (RP, is the most common inherited degenerative photoreceptor disease, for which no therapy is currently available. The P23H rat is one of the most commonly used autosomal dominant RP models. It has been created by incorporation of a mutated mouse rhodopsin (Rho transgene in the wild-type (WT Sprague Dawley rat. Detailed genetic characterization of this transgenic animal has however never been fully reported. Here we filled this knowledge gap on P23H Line 1 rat (P23H-1 and provide additional phenotypic information applying non-invasive and state-of-the-art in vivo techniques that are relevant for preclinical therapeutic evaluations. Transgene sequence was analyzed by Sanger sequencing. Using quantitative PCR, transgene copy number was calculated and its expression measured in retinal tissue. Full field electroretinography (ERG and spectral domain optical coherence tomography (SD-OCT were performed at 1-, 2-, 3- and 6-months of age. Sanger sequencing revealed that P23H-1 rat carries the mutated mouse genomic Rho sequence from the promoter to the 3' UTR. Transgene copy numbers were estimated at 9 and 18 copies in the hemizygous and homozygous rats respectively. In 1-month-old hemizygous P23H-1 rats, transgene expression represented 43% of all Rho expressed alleles. ERG showed a progressive rod-cone dysfunction peaking at 6 months-of-age. SD-OCT confirmed a progressive thinning of the photoreceptor cell layer leading to the disappearance of the outer retina by 6 months with additional morphological changes in the inner retinal cell layers in hemizygous P23H-1 rats. These results provide precise genotypic information of the P23H-1 rat with additional phenotypic characterization that will serve basis for therapeutic interventions, especially for those aiming at gene editing.

  9. Development of a sleeve gastrectomy weight-loss model in obese Zucker rats

    Science.gov (United States)

    Lopez, Peter P.; Nicholson, Susannah E.; Burkhardt, Gabriel E.; Johnson, Robert A.; Johnson, Fruzsina K.

    2009-01-01

    Background: Obesity promotes the development of diabetes and cardiovascular disease. The most effective weight-loss treatment is bariatric surgery, but results greatly vary depending on the procedure. Sleeve gastrectomy (SG) has recently emerged as a reduced risk weight-loss procedure for super obese patients. However, the mechanism of weight-loss from SG and its effects on obesity-induced complications are yet to be determined. Our goal was to develop an experimental model of SG in genetically obese rats. Materials and Methods: Male obese Zucker rats (400-500g, leptin-insensitive) were anesthetized with isoflurane. After a midline laparotomy, the stomach was clamped, the greater curvature was excised and a triple suture line was used to close the gastric remnant. Sham rats underwent laparotomy only. Metabolic parameters were followed for 14 days after surgery. Results: Caloric intake and body weight decreased in SG rats over 14 days by 98±10kcal/day and 74±14g, respectively. Blood total cholesterol levels were lower in rats that lost weight. Furthermore, blood glucose levels were lower in rats that lost weight. Active ghrelin levels were unchanged in SG rats 14 days after surgery. Conclusions: These results show that SG promotes weight-loss in obese Zucker rats. Furthermore, SG-induced weight-loss is accompanied by improved plasma cholesterol and glucose profile. However, SG does not promote a prolonged decrease in ghrelin levels. These results suggest that SG is an effective weight-loss procedure in leptin-insensitivity to improve the lipid profile and decrease insulin resistance and these effects might be independent of changes in ghrelin levels. PMID:19394650

  10. Atrial fibrillation promotion with long-term repetitive obstructive sleep apnea in a rat model.

    Science.gov (United States)

    Iwasaki, Yu-Ki; Kato, Takeshi; Xiong, Feng; Shi, Yan-Fen; Naud, Patrice; Maguy, Ange; Mizuno, Kyoichi; Tardif, Jean-Claude; Comtois, Philippe; Nattel, Stanley

    2014-11-11

    Obstructive sleep apnea (OSA) importantly contributes to the occurrence of atrial fibrillation (AF) in humans, but the mechanisms are poorly understood. Experimental research has provided insights into AF promotion by acute OSA episodes. However, patients with OSA usually have frequent nocturnal episodes for some time before manifesting AF. The goal of this study was to test the hypothesis that repetitive OSA causes cardiac remodeling that predisposes to AF. We mimicked OSA by using a mechanical ventilator and closing the airway at end-expiration with a 3-way stopcock (OSA rats). Matched control groups included rats with the ventilator stopped but airway left open (open airway rats) and continuously ventilated rats (sham rats). OSA rats were exposed to 20 consecutive 2-min cycles of 40 s of apnea/80 s of ventilation per day, 5 days per week for 4 weeks. OSA significantly increased the duration of AF from (median [interquartile range]) 2.6 s [1.9 s to 8.9 s] (shams) and 16 s [1.8 s to 93 s] (open airway) to 49s [34 s to 444 s]. AF inducibility increased to 56% (9 of 16) of OSA rats; this is up from 15% (2 of 13) and 13% (2 of 15) in open airway and sham rats, respectively (p promoting cardiac remodeling, with conduction abnormalities related to connexin dysregulation and fibrosis playing a prominent role. This novel animal model provides mechanistic insights into an important clinical problem and may be useful for further exploration of underlying mechanisms and therapeutic approaches. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  11. Phenotypic modulation of corpus cavernosum smooth muscle cells in a rat model of cavernous neurectomy.

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    Fan Yang

    Full Text Available Patients undergoing radical prostatectomy (RP are at high risk for erectile dysfunction (ED due to potential cavernous nerve (CN damage during surgery. Penile hypoxia after RP is thought to significantly contribute to ED pathogenesis.We previously showed that corpora cavernosum smooth muscle cells (CCSMCs undergo phenotypic modulation under hypoxic conditions in vitro. Here, we studied such changes in an in vivo post-RP ED model by investigating CCSMCs in bilateral cavernous neurectomy (BCN rats.Sprague-Dawley rats underwent sham (n = 12 or BCN (n = 12 surgery. After 12 weeks, they were injected with apomorphine to determine erectile function. The penile tissues were harvested and assessed for fibrosis using Masson trichrome staining and for molecular markers of phenotypic modulation using immunohistochemistry and western blotting. CCSMC morphological structure was evaluated by hematoxylin-eosin (H&E staining and transmission electron microscopy (TEM.Erectile function was significantly lower in BCN rats than in sham rats. BCN increased hypoxia-inducible factor-1α and collagen protein expression in corpora cavernous tissue. H&E staining and TEM showed that CCSMCs in BCN rats underwent hypertrophy and showed rough endoplasmic reticulum formation. The expression of CCSMC phenotypic markers, such as smooth muscle α-actin, smooth muscle myosin heavy chain, and desmin, was markedly lower, whereas vimentin protein expression was significantly higher in BCN rats than in control rats.CCSMCs undergo phenotype modulation in rats with cavernous neurectomy. The results have unveiled physiological transformations that occur at the cellular and molecular levels and have helped characterize CN injury-induced ED.

  12. Phenotypic modulation of corpus cavernosum smooth muscle cells in a rat model of cavernous neurectomy.

    Science.gov (United States)

    Yang, Fan; Zhao, Jian F; Shou, Qi Y; Huang, Xiao J; Chen, Gang; Yang, Ke B; Zhang, Shi G; Lv, Bo D; Fu, Hui Y

    2014-01-01

    Patients undergoing radical prostatectomy (RP) are at high risk for erectile dysfunction (ED) due to potential cavernous nerve (CN) damage during surgery. Penile hypoxia after RP is thought to significantly contribute to ED pathogenesis. We previously showed that corpora cavernosum smooth muscle cells (CCSMCs) undergo phenotypic modulation under hypoxic conditions in vitro. Here, we studied such changes in an in vivo post-RP ED model by investigating CCSMCs in bilateral cavernous neurectomy (BCN) rats. Sprague-Dawley rats underwent sham (n = 12) or BCN (n = 12) surgery. After 12 weeks, they were injected with apomorphine to determine erectile function. The penile tissues were harvested and assessed for fibrosis using Masson trichrome staining and for molecular markers of phenotypic modulation using immunohistochemistry and western blotting. CCSMC morphological structure was evaluated by hematoxylin-eosin (H&E) staining and transmission electron microscopy (TEM). Erectile function was significantly lower in BCN rats than in sham rats. BCN increased hypoxia-inducible factor-1α and collagen protein expression in corpora cavernous tissue. H&E staining and TEM showed that CCSMCs in BCN rats underwent hypertrophy and showed rough endoplasmic reticulum formation. The expression of CCSMC phenotypic markers, such as smooth muscle α-actin, smooth muscle myosin heavy chain, and desmin, was markedly lower, whereas vimentin protein expression was significantly higher in BCN rats than in control rats. CCSMCs undergo phenotype modulation in rats with cavernous neurectomy. The results have unveiled physiological transformations that occur at the cellular and molecular levels and have helped characterize CN injury-induced ED.

  13. Copper balance and ceruloplasmin in chronic hepatitis in a Wilson disease animal model, LEC rats

    Energy Technology Data Exchange (ETDEWEB)

    Komatsu, Yutaka; Ogra, Yasumitsu; Suzuki, Kazuo T. [Graduate School of Pharmaceutical Sciences, Chiba University, Inage, Chiba 263-8522 (Japan)

    2002-09-01

    In an animal model of Wilson disease, Long-Evans rats with cinnamon-colored coat (LEC rats), copper (Cu) accumulates in the liver with age up to the onset of acute hepatitis owing to a hereditary defective transporter for the efflux of Cu, ATP7B. The plasma Cu concentration is low in LEC rats because of the excretion of apo-ceruloplasmin (apo-Cp). However, toward and after the onset of chronic hepatitis, plasma Cu concentration increases in the form of holo-Cp, while the liver Cu concentration is maintained at a constant level without the occurrence of fulminant hepatitis. In the present study, the material balance of Cu was studied in LEC rats with chronic hepatitis in order to elucidate the mechanisms underlying the increase of holo-Cp in plasma and the maintenance of Cu at a constant level in the liver. The relationship between the Cu concentration and ferroxidase activity of Cp was analyzed in the plasma of LEC rats of different ages and of Wistar rats fed a Cu-deficient diet for different durations. Cu was suggested to be delivered to Cp in an all-or-nothing manner, resulting in the excretion of fully Cu-occupied holo-Cp (Cu{sub 6}-Cp) or totally Cu-unoccupied Cu{sub 0}-Cp (apo-Cp), but not partially Cu-occupied Cu{sub n}-Cp (where n=1-5). The increase of holo-Cp in acute and chronic hepatitis in LEC rats was explained by the delivery of Cu, accumulating in the non-metallothionein-bound form, to Cp outside the Golgi apparatus of the liver. The plasma Cu concentration and ferroxidase activity were proposed to be specific indicators of the appearance of non-metallothionein-bound Cu in the liver of LEC rats. (orig.)

  14. Polycystic kidney rat is a novel animal model of Caroli's disease associated with congenital hepatic fibrosis.

    Science.gov (United States)

    Sanzen, T; Harada, K; Yasoshima, M; Kawamura, Y; Ishibashi, M; Nakanuma, Y

    2001-05-01

    Caroli's disease (congenital intrahepatic biliary dilatation) associated with congenital hepatic fibrosis is an autosomal recessive polycystic kidney disease. Recently, the polycystic kidney (PCK) rat, a spontaneous mutant derived from a colony of CRJ:CD rats with polycystic lesions in the liver and an autosomal recessive mode of inheritance, was reported. In the present study, the pathology of the hepatobiliary system and the biliary cell-kinetics were evaluated in fetuses (day 18 to 21 of gestation) and neonates and adults (1 day to 4 months after delivery) of PCK rats. CRJ:CD rats were used as a control. Multiple segmental and saccular dilatations of intrahepatic bile ducts were first observed in fetuses at 19 days of gestation. The dilatation spread throughout the liver and the degree of dilatation increased with aging. Gross and histological features characterizing ductal plate malformation were common in the intrahepatic bile ducts. Overgrowth of portal connective tissue was evident and progressive after delivery. These features were very similar to those of Caroli's disease with congenital hepatic fibrosis. Proliferative activity in the biliary epithelial cells was greater in PCK rats than controls during the development. In contrast, the biliary epithelial apoptosis was less extensive in PCK rats than the controls until 1 week after delivery, but greater after 3 weeks, suggesting that the remodeling defect in immature bile ducts associated with the imbalance of cell kinetics plays a role in the occurrence of intrahepatic biliary anomalies in PCK rats. The PCK rat could be a useful and promising animal model of Caroli's disease with congenital hepatic fibrosis.

  15. Analgesic effect of Minocycline in rat model of inflammation-induced visceral pain

    Science.gov (United States)

    Kannampalli, Pradeep; Pochiraju, Soumya; Bruckert, Mitchell; Shaker, Reza; Banerjee, Banani; Sengupta, Jyoti N.

    2014-01-01

    The present study investigates the analgesic effect of minocycline, a semi-synthetic tetracycline antibiotic, in a rat model of inflammation-induced visceral pain. Inflammation was induced in male rats by intracolonic administration of tri-nitrobenzenesulphonic acid (TNBS). Visceral hyperalgesia was assessed by comparing the viscero-motor response (VMR) to graded colorectal distension (CRD) prior and post 7 days after TNBS treatment. Electrophysiology recordings from CRD-sensitive pelvic nerve afferents (PNA) and lumbo-sacral (LS) spinal neurons were performed in naïve and inflamed rats. Colonic inflammation produced visceral hyperalgesia characterized by increase in the VMRs to CRD accompanied with simultaneous activation of microglia in the spinal cord and satellite glial cells (SGCs) in the dorsal root ganglions (DRGs). Selectively inhibiting the glial activation following inflammation by araC (Arabinofuranosyl Cytidine) prevented the development of visceral hyperalgesia. Intrathecal minocycline significantly attenuated the VMR to CRD in inflamed rats, whereas systemic minocycline produced a delayed effect. In electrophysiology experiments, minocycline significantly attenuated the mechanotransduction of CRD-sensitive PNAs and the responses of CRD-sensitive LS spinal neurons in TNBS-treated rats. While the spinal effect of minocycline was observed within 5 min of administration, systemic injection of the drug produced a delayed effect (60 min) in inflamed rats. Interestingly, minocycline did not exhibit analgesic effect in naïve, non-inflamed rats. The results demonstrate that intrathecal injection of minocycline can effectively attenuate inflammation-induced visceral hyperalgesia. Minocycline might as well act on neuronal targets in the spinal cord of inflamed rats, in addition to the widely reported glial inhibitory action to produce analgesia. PMID:24485889

  16. Quercetin Decreases Insulin Resistance in a Polycystic Ovary Syndrome Rat Model by Improving Inflammatory Microenvironment.

    Science.gov (United States)

    Wang, Zhenzhi; Zhai, Dongxia; Zhang, Danying; Bai, Lingling; Yao, Ruipin; Yu, Jin; Cheng, Wen; Yu, Chaoqin

    2017-05-01

    Insulin resistance (IR) is a clinical feature of polycystic ovary syndrome (PCOS). Quercetin, derived from Chinese medicinal herbs such as hawthorn, has been proven practical in the management of IR in diabetes. However, whether quercetin could decrease IR in PCOS is unknown. This study aims to observe the therapeutic effect of quercetin on IR in a PCOS rat model and explore the underlying mechanism. An IR PCOS rat model was established by subcutaneous injection with dehydroepiandrosterone. The body weight, estrous cycle, and ovary morphology of the quercetin-treated rats were observed. Serum inflammatory cytokines were analyzed using enzyme-linked immunosorbent assay. In ovarian tissues, the expression of key genes involved in the inflammatory signaling pathway was detected through Western blot, real-time polymerase chain reaction, or immunohistochemistry. The nuclear translocation of nuclear factor κB (NF-κB) was also observed by immunofluorescence. The estrous cycle recovery rate of the insulin-resistant PCOS model after quercetin treatment was 58.33%. Quercetin significantly reduced the levels of blood insulin, interleukin 1β, IL-6, and tumor necrosis factor α. Quercetin also significantly decreased the granulosa cell nuclear translocation of NF-κB in the insulin-resistant PCOS rat model. The treatment inhibited the expression of inflammation-related genes, including the nicotinamide adenine dinucleotide phosphate oxidase subunit p22phox, oxidized low-density lipoprotein, and Toll-like receptor 4, in ovarian tissue. Quercetin improved IR and demonstrated a favorable therapeutic effect on the PCOS rats. The underlying mechanism of quercetin potentially involves the inhibition of the Toll-like receptor/NF-κB signaling pathway and the improvement in the inflammatory microenvironment of the ovarian tissue of the PCOS rat model.

  17. The rat as a model for orthodontic tooth movement--a critical review and a proposed solution

    NARCIS (Netherlands)

    Ren, Yijin; Maltha, Jaap C; Kuijpers-Jagtman, Anne Marie

    2004-01-01

    The aims of this study were to perform a systematic review of the use of rats as a model for experimental tooth movement, to give a critical evaluation of the use of elastics as a force delivery system, and to describe a newly designed well-defined model for tooth movement in rats. The literature

  18. The rat as a model for orthodontic tooth movement--a critical review and a proposed solution.

    NARCIS (Netherlands)

    Ren, Y.; Maltha, J.C.; Kuijpers-Jagtman, A.M.

    2004-01-01

    The aims of this study were to perform a systematic review of the use of rats as a model for experimental tooth movement, to give a critical evaluation of the use of elastics as a force delivery system, and to describe a newly designed well-defined model for tooth movement in rats. The literature

  19. Metabolomics of cerebrospinal fluid reveals changes in the central nervous system metabolism in a rat model of multiple sclerosis

    NARCIS (Netherlands)

    Noga, M.J.; Dane, A.; Shi, S.; Attali, A.; Aken, H. van; Suidgeest, E.; Tuinstra, T.; Muilwijk, B.; Coulier, L.; Luider, T.; Reijmers, T.H.; Vreeken, R.J.; Hankemeier, T.

    2012-01-01

    Experimental Autoimmune Encephalomyelitis (EAE) is the most commonly used animal model for Multiple Sclerosis (MScl). CSF metabolomics in an acute EAE rat model was investigated using targetted LC-MS and GC-MS. Acute EAE in Lewis rats was induced by co-injection of Myelin Basic Protein with Complete

  20. Metabolomics of cerebrospinal fluid reveals changes in the central nervous system metabolism in a rat model of multiple sclerosis

    NARCIS (Netherlands)

    M. Noga (Marek); A. Dane (Adrie); S. Shi (Shanna); A. Attali (Amos); H. van Aken (Hans); E. Suidgeest (Ernst); T. Tuinstra (Tinka); B. Muilwijk (Bas); L. Coulier (Leon); T.M. Luider (Theo); R.M. Reijmers (Rogier); R. Vreeken (Rob); T. Hankemeier (Thomas)

    2012-01-01

    textabstractExperimental Autoimmune Encephalomyelitis (EAE) is the most commonly used animal model for Multiple Sclerosis (MScl). CSF metabolomics in an acute EAE rat model was investigated using targetted LC-MS and GC-MS. Acute EAE in Lewis rats was induced by co-injection of Myelin Basic Protein

  1. Generation of gene knockouts and mutant models in the laboratory rat by ENU-driven target-selected mutagenesis

    NARCIS (Netherlands)

    Smits, Bart M G; Mudde, Josine B; van de Belt, Jose; Verheul, Mark; Olivier, Jocelien; Homberg, Judith; Guryev, Victor; Cools, Alexander R; Ellenbroek, Bart A; Plasterk, Ronald H A; Cuppen, Edwin

    OBJECTIVE: The rat is one of the most important model organisms for biomedical and pharmacological research. However, the generation of novel models for studying specific aspects of human diseases largely depends on selection for specific traits using existing rat strains, thereby solely depending

  2. Caloric restriction protects against electrical kindling of the amygdala by inhibiting the mTOR signaling pathway

    Directory of Open Access Journals (Sweden)

    Bryan Victor Phillips-Farfan

    2015-03-01

    Full Text Available Caloric restriction (CR has been shown to possess antiepileptic properties; however its mechanism of action is poorly understood. CR might inhibit the activity of the mammalian or mechanistic target of rapamycin (mTOR signaling cascade, which seems to participate crucially in the generation of epilepsy. Thus, we investigated the effect of CR on the mTOR pathway and whether CR modified epilepsy generation due to electrical amygdala kindling. The former was studied by analyzing the phosphorylation of adenosine monophosphate-activated protein kinase, protein kinase B and the ribosomal protein S6. The mTOR cascade is regulated by energy and by insulin levels, both of which may be changed by CR; thus we investigated if CR altered the levels of energy substrates in the blood or the level of insulin in plasma. Finally, we studied if CR modified the expression of genes that encode proteins participating in the mTOR pathway. CR increased the after-discharge threshold and tended to reduce the after-discharge duration, indicating an anti-convulsive action. CR diminished the phosphorylation of protein kinase B and ribosomal protein S6, suggesting an inhibition of the mTOR cascade. However, CR did not change glucose, β-hydroxybutyrate or insulin levels; thus the effects of CR were independent from them. Interestingly, CR also did not modify the expression of any investigated gene. The results suggest that the anti-epileptic effect of CR may be partly due to inhibition of the mTOR pathway.

  3. [The replacement therapy of rPTH(1-84) in established rat model of hypothyroidism].

    Science.gov (United States)

    Ding, Zhiwei; Li, Tiancheng; Liu, Yuhe; Xiao, Shuifang

    2015-12-01

    To investigate the replacement therapy of rPTH(1-84) (recombinant human parathyroid hormone (1-84)) to hypothyroidism in established rat model. Rat model of hypothyroidism was established by resecting parathyroids. A total of 30 rats with removal of parathyroids were divided into 6 groups randomly, 5 in each group, and applied respectively with saline injection (negative control group), calcitriol treatment (positive control group) and quadripartite PTH administration with dose of 20, 40, 80 and 160 µg/kg (experimental groups). Saline and rPTH(1-84) were injected subcutaneously daily. Calcitriol was gavaged once a day. Sham-operation was conducted in 5 rats of negative control group. To verify the authenticity of the rat model with hypothyroidism, the serum was insolated centrifugally from rat blood that was obtained from angular vein at specific time to measure calcium and phosphorus concentration. Urine in 12 hours was collected by metabolic cages and the calcium concentration was measured. After 10-week drug treatment, the experiment was terminated and bilateral femoral bone and L2-5 lumbar vertebra were removed from rats. Bone mineral density (BMD)of bilateral femoral bone and lumbar vertebra was analyzed by dual X-ray absorptiometry (DXA). The concentration of bone alkaline phosphatase (BALP) in serum was determined by radioimmunoassay. The rat model with hypothyroidism was obtained by excising parathyroid gland and was verified by monitoring calcium and phosphorus concentration subsequently. Administration of rPTH(1-84) in the dose of 80 or 160 µg/kg made serum calcium and phosphorus back to normal levels, with no significant difference between the doses (P>0.05). The BMD in each group of rats with rPTH(1-84) administration was increased significantly (Prats of maximum rPTH(1-84) injection group (160 µg/kg) were higher than those of normal control group (Prats treated with calcitriol had normal calcium levels and showed the increase of BMD and phosphorus

  4. Freshly isolated hepatocyte transplantation in acetaminophen-induced hepatotoxicity model in rats

    Directory of Open Access Journals (Sweden)

    Daniela Rodrigues

    2012-12-01

    Full Text Available CONTEXT: Hepatocyte transplantation is an attractive therapeutic modality for liver disease as an alternative for orthotopic liver transplantation. OBJECTIVE: The aim of the current study was to investigate the feasibility of freshly isolated rat hepatocyte transplantation in acetaminophen-induced hepatotoxicity model. METHODS: Hepatocytes were isolated from male Wistar rats and transplanted 24 hours after acetaminophen administration in female recipients. Female rats received either 1x10(7 hepatocytes or phosphate buffered saline through the portal vein or into the spleen and were sacrificed after 48 hours. RESULTS: Alanine aminotransferase levels measured within the experiment did not differ between groups at any time point. Molecular analysis and histology showed presence of hepatocytes in liver of transplanted animals injected either through portal vein or spleen. CONCLUSION: These data demonstrate the feasibility and efficacy of hepatocyte transplantation in the liver or spleen in a mild acetaminophen-induced hepatotoxicity model.

  5. Rubidium-82 PET imaging is feasible in a rat myocardial infarction model

    DEFF Research Database (Denmark)

    Ghotbi, Adam Ali; Clemmensen, Andreas; Kyhl, Kasper

    2017-01-01

    BACKGROUND: Small-animal myocardial infarct models are frequently used in the assessment of new cardioprotective strategies. A validated quantification of perfusion using a non-cyclotron-dependent PET tracer would be of importance in monitoring response to therapy. We tested whether myocardial PET...... perfusion imaging is feasible with Rubidium-82 ((82)Rb) in a small-animal scanner using a rat myocardial infarct model. METHODS: 18 Sprague-Dawley rats underwent permanent coronary artery ligation (infarct group), and 11 rats underwent ischemia-reperfusion (reperfusion group) procedure. (82)Rb......-PET and magnetic resonance imaging (MRI) were conducted before and after the intervention. Perfusion was compared to both left ventricle ejection fraction (LVEF) and infarct size assessed by MRI. RESULTS: Follow-up global (82)Rb-uptake correlated significantly with infarct size (infarct group: r = -0.81, P

  6. Ranitidine reduced levodopa-induced dyskinesia in a rat model of Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Cui G

    2013-12-01

    Full Text Available Guiyun Cui,1,* Xinxin Yang,1,* Xiaoying Wang,2,* Zunsheng Zhang,1 Xuanye Yue,1 Hongjuan Shi,1 Xia Shen11Department of Neurology, 2Department of Ultrasound, the Affiliated Hospital of Xuzhou Medical College, Jiangsu, People’s Republic of China *These authors contributed equally to this workBackground: Chronic administration of levodopa in Parkinson’s disease leads to debilitating involuntary movements, termed levodopa-induced dyskinesia (LID. The pathogenesis of LID is poorly understood. Previous research has shown that histamine H2 receptors are highly expressed in the input (striatum and output (globus pallidus, substantia nigra regions of the basal ganglia, particularly in the GABAergic striatopallidal and striatonigral pathways. Therefore, a histamine H2 receptor antagonist could be used to reduce LID. In the present work, we investigated whether ranitidine has the potential to diminish LID in rats with dyskinesia and explored the underlying mechanisms involved.Methods: A rat model of PD was induced by 6-hydroxydopamine. Valid PD rats were then treated with levodopa (25 mg/kg, intraperitoneally and benserazide (12.5 mg/kg, intraperitoneally for 21 days to induce a rat model of LID. The acute and chronic effects of administration of ranitidine at different doses (5 mg/kg, 10 mg/kg, and 20 mg/kg on abnormal involuntary movements, levodopa-induced rotations, and the forelimb adjusting steps test were investigated in LID rats. The chronic effect of ranitidine (10 mg/kg on the expression of Arc and proenkephalin was also evaluated.Results: Levodopa elicited increased dyskinesia in PD rats. Acute ranitidine treatment had no effect on LID, but chronic ranitidine administration (10 mg/kg, 20 mg/kg reduced LID in rats with dyskinesia. Importantly, levodopa-induced rotations were not affected by chronic treatment with ranitidine. In addition, chronic ranitidine (10 mg/kg, 20 mg/kg significantly improved stepping of the lesioned forepaw. Real

  7. Cyclosporin A significantly improves preeclampsia signs and suppresses inflammation in a rat model.

    Science.gov (United States)

    Hu, Bihui; Yang, Jinying; Huang, Qian; Bao, Junjie; Brennecke, Shaun Patrick; Liu, Huishu

    2016-05-01

    Preeclampsia is associated with an increased inflammatory response. Immune suppression might be an effective treatment. The aim of this study was to examine whether Cyclosporin A (CsA), an immunosuppressant, improves clinical characteristics of preeclampsia and suppresses inflammation in a lipopolysaccharide (LPS) induced preeclampsia rat model. Pregnant rats were randomly divided into 4 groups: group 1 (PE) rats each received LPS via tail vein on gestational day (GD) 14; group 2 (PE+CsA5) rats were pretreated with LPS (1.0 μg/kg) on GD 14 and were then treated with CsA (5mg/kg, ip) on GDs 16, 17 and 18; group 3 (PE+CsA10) rats were pretreated with LPS (1.0 μg/kg) on GD 14 and were then treated with CsA (10mg/kg, ip) on GDs 16, 17 and 18; group 4 (pregnant control, PC) rats were treated with the vehicle (saline) used for groups 1, 2 and 3. Systolic blood pressure, urinary albumin, biometric parameters and the levels of serum cytokines were measured on day 20. CsA treatment significantly reduced LPS-induced systolic blood pressure and the mean 24-h urinary albumin excretion. Pro-inflammatory cytokines IL-6, IL-17, IFN-γ and TNF-α were increased in the LPS treatment group but were reduced in (LPS+CsA) group (Ppreeclampsia signs and attenuated inflammatory responses in the LPS induced preeclampsia rat model which suggests that immunosuppressant might be an alternative management option for preeclampsia. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Cavernous smooth muscle hyperplasia in a rat model of hyperlipidaemia-associated erectile dysfunction.

    Science.gov (United States)

    Qiu, Xuefeng; Fandel, Thomas M; Lin, Guiting; Huang, Yun-Ching; Dai, Yu-Tian; Lue, Tom F; Lin, Ching-Shwun

    2011-12-01

    What's known on the subject? and what does the study add? Increased cavernous smooth muscle content has been repeatedly observed in rat models of hyperlipidaemia - associated erectile dysfunction. This study shows that the increased smooth muscle content is due to hyperplasia. • To investigate the structural changes, including possible smooth muscle hyperplasia, in the penis of a hyperlipidaemia-associated erectile dysfunction (ED) animal model. • Hyperlipidaemia was induced in rats through a high-fat diet. • Penile tissues of normal and hyperlipidaemic rats were stained with Alexa-488-conjugated phalloidin and/or with antibodies against rat endothelial cell antigen, neuronal nitric oxide synthase (nNOS), and collagen type IV (Col-IV) before image and statistical analyses were carried out. • The main outcome measures were the smooth muscle, endothelial, Col-IV and nNOS content of the corpus cavernosum. • Phalloidin intensely stained all smooth muscle in the penis, revealing the circular and longitudinal components of cavernous smooth muscle (CSM). • The CSM content was significantly higher in the hyperlipidaemic than in the normal rats (P Cavernous endothelial content was significantly lower in hyperlipidaemic than in normal rats (P < 0.05). • nNOS-positive nerves within the dorsal nerves, around the dorsal arteries, and in the corpora cavernosa were all significantly lower in the hyperlipidaemic than in the normal rats (P < 0.05). • Hyperlipidaemia is associated with reduced nNOS-positive nerves, reduced endothelium, and increased CSM in the penis. • The increased CSM is attributable to hyperplasia. • These structural changes may explain why hyperlipidaemic men are more likely to develop ED. © 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.

  9. A New Rat Model of Epileptic Spasms Based on Methylazoxymethanol-Induced Malformations of Cortical Development

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    Eun-Hee Kim

    2017-06-01

    Full Text Available Malformations of cortical development (MCDs can cause medically intractable epilepsies and cognitive disabilities in children. We developed a new model of MCD-associated epileptic spasms by treating rats prenatally with methylazoxymethanol acetate (MAM to induce cortical malformations and postnatally with N-methyl-d-aspartate (NMDA to induce spasms. To produce cortical malformations to infant rats, two dosages of MAM (15 mg/kg, intraperitoneally were injected to pregnant rats at gestational day 15. In prenatally MAM-exposed rats and the controls, spasms were triggered by single (6 mg/kg on postnatal day 12 (P12 or 10 mg/kg on P13 or 15 mg/kg on P15 or multiple doses (P12, P13, and P15 of NMDA. In prenatally MAM-exposed rats with single NMDA-provoked spasms at P15, we obtain the intracranial electroencephalography and examine the pretreatment response to adrenocorticotropic hormone (ACTH or vigabatrin. Rat pups prenatally exposed to MAM exhibited a significantly greater number of spasms in response to single and multiple postnatal NMDA doses than vehicle-exposed controls. Vigabatrin treatment prior to a single NMDA dose on P15 significantly suppressed spasms in MAM group rats (p < 0.05, while ACTH did not. The MAM group also showed significantly higher fast oscillation (25–100 Hz power during NMDA-induced spasms than controls (p = 0.047. This new model of MCD-based epileptic spasms with corresponding features of human spasms will be valuable for future research of the developmental epilepsy.

  10. Royal Jelly Prevents Osteoporosis in Rats: Beneficial Effects in Ovariectomy Model and in Bone Tissue Culture Model

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    Saburo Hidaka

    2006-01-01

    Full Text Available Royal jelly (RJ has been used worldwide for many years as medical products, health foods and cosmetics. Since RJ contains testosterone and has steroid hormone-type activities, we hypothesized that it may have beneficial effects on osteoporosis. We used both an ovariectomized rat model and a tissue culture model. Rats were divided into eight groups as follows: sham-operated (Sham, ovariectomized (OVX, OVX given 0.5% (w/w raw RJ, OVX given 2.0% (w/w RJ, OVX given 0.5% (w/w protease-treated RJ (pRJ, OVX given 2.0% (w/w pRJ, OVX given 17β-estradiol and OVX given its vehicle, respectively. The Ovariectomy decreased tibial bone mineral density (BMD by 24%. Administration of 17β-estradiol to OVX rats recovered the tibial BMD decrease by 100%. Administration of 2.0% (w/w RJ and 0.5–2.0% (w/w pRJ to OVX rats recovered it by 85% or more. These results indicate that both RJ and pRJ are almost as effective as 17β-estradiol in preventing the development of bone loss induced by ovariectomy in rats. In tissue culture models, both RJ and pRJ increased calcium contents in femoral-diaphyseal and femoral-metaphyseal tissue cultures obtained from normal male rats. However, in a mouse marrow culture model, they neither inhibited the parathyroid hormone (PTH-induced calcium loss nor affected the formation of osteoclast-like cells induced by PTH in mouse marrow culture system. Therefore, our results suggest that both RJ and pRJ may prevent osteoporosis by enhancing intestinal calcium absorption, but not by directly antagonizing the action of PTH.

  11. Sodium ferulate inhibits neointimal hyperplasia in rat balloon injury model.

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    Jing Zhang

    Full Text Available BACKGROUND/AIM: Neointimal formation after vessel injury is a complex process involving multiple cellular and molecular processes. Inhibition of intimal hyperplasia plays an important role in preventing proliferative vascular diseases, such as restenosis. In this study, we intended to identify whether sodium ferulate could inhibit neointimal formation and further explore potential mechanisms involved. METHODS: Cultured vascular smooth muscle cells (VSMCs isolated from rat thoracic aorta were pre-treated with 200 µmol/L sodium ferulate for 1 hour and then stimulated with 1 µmol/L angiotensin II (Ang II for 1 hour or 10% serum for 48 hours. Male Sprague-Dawley rats subjected to balloon catheter insertion were administrated with 200 mg/kg sodium ferulate (or saline for 7 days before sacrificed. RESULTS: In presence of sodium ferulate, VSMCs exhibited decreased proliferation and migration, suppressed intracellular reactive oxidative species production and NADPH oxidase activity, increased SOD activation and down-regulated p38 phosphorylation compared to Ang II-stimulated alone. Meanwhile, VSMCs treated with sodium ferulate showed significantly increased protein expression of smooth muscle α-actin and smooth muscle myosin heavy chain protein. The components of Notch pathway, including nuclear Notch-1 protein, Jagged-1, Hey-1 and Hey-2 mRNA, as well as total β-catenin protein and Cyclin D1 mRNA of Wnt signaling, were all significantly decreased by sodium ferulate in cells under serum stimulation. The levels of serum 8-iso-PGF2α and arterial collagen formation in vessel wall were decreased, while the expression of contractile markers was increased in sodium ferulate treated rats. A decline of neointimal area, as well as lower ratio of intimal to medial area was observed in sodium ferulate group. CONCLUSION: Sodium ferulate attenuated neointimal hyperplasia through suppressing oxidative stress and phenotypic switching of VSMCs.

  12. Isolation of primary osteoblast cell lines from adult rat and rat embryos and their use as models for in vitro biocompatibility tests of nanostructured titanium-based implants.

    Science.gov (United States)

    Khrunyk, Y Y; Vyalykh, I V; Korelin, A V; Belikov, S V; Karabanalov, M S; Rakitin, S B; Kamalov, R V; Popov, A A

    2017-07-01

    Methods for obtaining osteoblast cultures from the calvaria of adult Wistar rats and 12-day-old embryos of these rats have been adapted for studying the biocompatibility and ossointegration of titanium-based implants. The osteoblast morphology and their differentiation into osteocytes on a titanium matrix with specially treated surface have been studied. It has been confirmed that two cultures of diploid rat cells obtained in the study can serve as efficient models for preclinical in vitro testing of nanostructured titanium implants for biocompatibility and osseointegration.

  13. Depressive-like symptoms in a reserpine-induced model of fibromyalgia in rats.

    Science.gov (United States)

    Blasco-Serra, Arantxa; Escrihuela-Vidal, Francesc; González-Soler, Eva M; Martínez-Expósito, Fernando; Blasco-Ausina, M Carmen; Martínez-Bellver, Sergio; Cervera-Ferri, Ana; Teruel-Martí, Vicent; Valverde-Navarro, Alfonso A

    2015-11-01

    Since the pathogenesis of fibromyalgia is unknown, treatment options are limited, ineffective and in fact based on symptom relief. A recently proposed rat model of fibromyalgia is based on central depletion of monamines caused by reserpine administration. This model showed widespread musculoskeletal pain and depressive-like symptoms, but the methodology used to measure such symptoms has been criticized. Evidence relates the high prevalence of pain and depression in fibromyalgia to common pathogenic pathways, most probably focused on the monoaminergic system. The present study aims at a validation of the reserpine model of fibromyalgia. For this purpose, rats undergoing this model have been tested for depressive-like symptoms with a Novelty-Suppressed Feeding Test adaptation. Animals administered with reserpine and subjected to forced food deprivation performed a smaller number of incursions to the center of the open field, evidenced by a decrease in the per-minute rate of the rats' approaching, smelling or touching the food. They also took more time to eat from the central food than control rats. These NSFT findings suggest the presence of depressive-like disorders in this animal model of fibromyalgia. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Comparison of anterior segment structures in two rat glaucoma models: an ultrasound biomicroscopic study.

    Science.gov (United States)

    Nissirios, Nikolaos; Chanis, Raul; Johnson, Elaine; Morrison, John; Cepurna, William O; Jia, Lijun; Mittag, Thomas; Danias, John

    2008-06-01

    Optic nerve disease in chronic IOP elevation rat glaucoma models develops at different rates. This study was undertaken to investigate whether anterior chamber (AC) changes develop in two popular models in vivo and whether the changes are related to IOP. Ten female Wistar rats and 12 male Brown-Norway rats were subjected to episcleral vein cauterization (EVC) and hypertonic saline episcleral vein sclerosis (HSEVS), respectively. Contralateral untreated eyes served as controls. IOP was recorded for a period of 5 to 6 weeks, and with the rats under anesthesia, the eyes were imaged with an ultrasound biomicroscope. Measurements of the AC depth (ACD), trabecular-iris angle (TIA), iris thickness at the thickest point near the pupillary margin (IT), angle opening distance (AOD; at 200 microm from the scleral spur), and ciliary body area (CBA) were compared between control eyes of the two strains and between experimental and control eyes within each strain. The differences were correlated with IOP history. Eyes subjected to EVC demonstrated greater increases in IOP than eyes subjected to HSEVS. Between rat strains, control eyes differed significantly in all the parameters studied, except for ACD. No difference was detected between experimental and control eyes in the EVC group. In contrast, experimental eyes in the HSEVS group had approximately 71% larger ACDs and approximately 32% smaller CBAs than did the contralateral control eyes (P EVC rat model of glaucoma do not undergo changes in the AC. In contrast, eyes subjected to HSEVS display deepening of the AC and reduction in size of the ciliary body within 5 to 6 weeks. These changes correlate to IOP exposure and may be the result of specific changes induced by the experimental intervention. These models are likely to rely on different mechanisms of pressure elevation and cannot be used interchangeably.

  15. A novel knee prosthesis model of implant-related osteo- myelitis in rats

    OpenAIRE

    Søe, Niels H; Jensen, Nina Vendel; Nürnberg, Birgit Meinecke; Jensen, Asger Lundorff; Koch, Janne; Poulsen, Steen Seier; Pier, Gerald B.; Johansen, Helle Krogh

    2013-01-01

    Background and purpose: There have been numerous reports of animal models of osteomyelitis. Very few of these have been prosthesis models that imitate human conditions. We have developed a new rat model of implant-related osteomyelitis that mimics human osteomyelitis, to investigate the pathology of infection after orthop edic implant surgery. Methods: 2 wild-type strains of Staphylococcus aureus, MN8 and UAMS-1, and their corresponding mutants that are unable to produce poly-N-acetyl glucosa...

  16. Porphyromonas gingivalis and Treponema denticola Mixed Microbial Infection in a Rat Model of Periodontal Disease

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    Raj K. Verma

    2010-01-01

    Full Text Available Porphyromonas gingivalis and Treponema denticola are periodontal pathogens that express virulence factors associated with the pathogenesis of periodontitis. In this paper we tested the hypothesis that P. gingivalis and T. denticola are synergistic in terms of virulence; using a model of mixed microbial infection in rats. Groups of rats were orally infected with either P. gingivalis or T. denticola or mixed microbial infections for 7 and 12 weeks. P. gingivalis genomic DNA was detected more frequently by PCR than T. denticola. Both bacteria induced significantly high IgG, IgG2b, IgG1, IgG2a antibody levels indicating a stimulation of Th1 and Th2 immune response. Radiographic and morphometric measurements demonstrated that rats infected with the mixed infection exhibited significantly more alveolar bone loss than shaminfected control rats. Histology revealed apical migration of junctional epithelium, rete ridge elongation, and crestal alveolar bone resorption; resembling periodontal disease lesion. These results showed that P. gingivalis and T. denticola exhibit no synergistic virulence in a rat model of periodontal disease.

  17. Manifestation of Hyperandrogenism in the Continuous Light Exposure-Induced PCOS Rat Model

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    Xuezhi Kang

    2015-01-01

    Full Text Available Polycystic ovary syndrome (PCOS is a complex endocrine and metabolic disorder, and its pathogenesis has yet to be completely clarified. A fully convincing animal model has not been established for PCOS. In earlier studies, researchers have shown that the exposure of rats to continuous light can induce PCOS; nevertheless, hyperandrogenism, a key characteristic observed in human PCOS, has not been reported previously. In the present study, we found that (1 body weights decreased in female rats in a continuous light environment with both ovarian and uterine augmentation; (2 the estrous cycle in rats under continuous light environment was disordered, and polycystic ovary-like changes occurred, accompanied with fur loss and lethargy; and (3 serum testosterone levels in rats in a continuous light environment significantly increased. Our data suggest that continuous light can lead to the occurrence of PCOS in female rats without the need for drugs; this is a reasonable PCOS animal model that is more consistent with the natural disease state in humans; and poor sleep habits or negligence of sleep hygiene may be an important lifestyle factor in pathogenesis of PCOS.

  18. ARISTOLOCHIA BRACTEOLATE RETZ. ATTENUATES HYPERURICEMIA IN A METABOLIC ARTHRITIS RAT MODEL.

    Science.gov (United States)

    Li, Yun-Peng; Wu, Shuang; Ran, Afou; Xu, Da-Yong; Wei, Jing-Mei; Zhao, Zi-Long

    2017-01-01

    The leaves of Aristolochia bracteolata Retz. has been documented in the folk medicine literature for its anti-arthritic activity. The target of the research envisaged was to elucidate the activity of A. bracteolata extract on hyperuricemic condition in arthritis rat model. Dried and powdered plant leaves were extracted using ether and chloroform. Potassium oxonate was injected intra-articularly to produce arthritis. The hyperuricemic effect, of A. bracteolate was analyzed by studying levels of uric acid in serum as well as in urine of arthritis induced rats. Effects of plant extracts were also studied on BUN (blood urea nitrogen) levels and fraction of uric acid excreted. Results indicate that administration of A. bracteolata presented substantial change in uric acid concentration, augmented by potassium oxonate administration in rats. The reduction in levels of uric acid levels was nearly same as allopurinol. The investigation also revealed that the primary plant extract has nephroprotective effect by enhancing the production of Prostaglandin E2 and Interleukin-1. Histological studies of rat kidney slices indicated the safety of the present plant extract. The crude extract of A. bracteolate can be used to reduce hyperuricemia in metabolic arthritis produced in rat model, without inducing any potential damaging effects.

  19. Neuroprotective and behavioral efficacy of intravenous transplanted adipose stem cells in experimental Parkinsonian rat models

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    Malihe Nakhaeifard

    2016-02-01

    Full Text Available Background: Parkinson's disease is a deficiency of dopamine in the striatum, characterized by bradykinesis, rigidity and resting tremor. Adipose tissue-Derived Stem Cells (ADSCs have many advantages for cell therapy because of the easy availability and pluripotency without ethical problems. In this research, the effects of ADSCs transplantation on motor impairment of rat Parkinsonian models were evaluated. Materials and Methods: Parkinson model was constructed by the unilateral lesion of striatum of male Wistar rats using 20µg of 6-hydroxydopamine (6-OHDA as lesion group. Cell and α-MEM (α-minimal essential medium groups were lesioned animals that received intravenous injection of 3×106 cells suspended in medium and medium repectively. All rats were evaluated behaviorally with rotarod and apomorphine-induced rotation tests, at 4 and 8 weeks after cell transplantation. Results: Lesion and α-MEM groups showed increased contralateral turns while cell group significantly ameliorated both in rotarod and apomorphine-induced rotation tests. There was a significant difference of contralateral turns between cell and lesioned groups at 8 weeks after transplantation. Lesioned rats showed significant decrease of staying on the rod as compared to control, but in cell group there was a significant increase in comparision with the lesioned animals. Conclusion: ADSCs injected intravenously promote functional recovery in Parkinsonian rats.

  20. Small Animal Models for Human Metapneumovirus: Cotton Rat is More Permissive than Hamster and Mouse

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    Yu Zhang

    2014-07-01

    Full Text Available Human metapneumovirus (hMPV is the second most prevalent causative agent of pediatric respiratory infections worldwide. Currently, there are no vaccines or antiviral drugs against this virus. One of the major hurdles in hMPV research is the difficulty to identify a robust small animal model to accurately evaluate the efficacy and safety of vaccines and therapeutics. In this study, we compared the replication and pathogenesis of hMPV in BALB/c mice, Syrian golden hamsters, and cotton rats. It was found that BALB/c mice are not permissive for hMPV infection despite the use of a high dose (6.5 log10 PFU of virus for intranasal inoculation. In hamsters, hMPV replicated efficiently in nasal turbinates but demonstrated only limited replication in lungs. In cotton rats, hMPV replicated efficiently in both nasal turbinate and lung when intranasally administered with three different doses (4, 5, and 6 log10 PFU of hMPV. Lungs of cotton rats infected by hMPV developed interstitial pneumonia with mononuclear cells infiltrates and increased lumen exudation. By immunohistochemistry, viral antigens were detected at the luminal surfaces of the bronchial epithelial cells in lungs. Vaccination of cotton rats with hMPV completely protected upper and lower respiratory tract from wildtype challenge. The immunization also elicited elevated serum neutralizing antibody. Collectively, these results demonstrated that cotton rat is a robust small animal model for hMPV infection.

  1. Bamboo leaf extract improves spatial learning ability in a rat model with senile dementia.

    Science.gov (United States)

    Liu, Jian-xiang; Zhu, Min-ying; Feng, Ci-yuan; Ding, Hai-bin; Zhan, Ying; Zhao, Zhan; Ding, Yue-min

    2015-07-01

    Senile dementia (SD) is a syndrome characterized by progressive neurological deterioration. Treatment for the disease is still under investigation. Bamboo leaf extract (B-extract) has been known for its biological efficacy in anti-oxidant and anti-cancer activities. However, study on B-extract for its protection against dementia is very limited. The effect of B-extract on a rat model with SD was examined. B-extract improved spatial learning ability of the dementia rats. The hippocampus of dementia model rats showed reduced levels of acetylcholine (ACh), epinephrine (E), norepinephrine (NE), and dopamine (DA), and increased activities of acetylcholine esterase (AChE) and monoamine oxidase (MAO). Treatment with B-extract 20 mg/(kg·d) for 7 weeks significantly inhibited the enzyme activity compared with untreated dementia rats, and raised the levels of ACh, E, and DA in the hippocampus. In addition, treatment with B-extract elevated the level of γ-aminobutyric acid (GABA), but reduced the level of glutamate (Glu) in the brain. These data suggest that B-extract might be a potential drug in treating impairment of spatial memory in dementia rats by regulating the central neurotransmitter function.

  2. White matter atrophy and myelinated fiber disruption in a rat model of depression.

    Science.gov (United States)

    Gao, Yuan; Ma, Jing; Tang, Jing; Liang, Xin; Huang, Chun-Xia; Wang, San-Rong; Chen, Lin-Mu; Wang, Fei-Fei; Tan, Chuan-Xue; Chao, Feng-Lei; Zhang, Lei; Qiu, Xuan; Luo, Yan-Min; Xiao, Qian; Du, Lian; Xiao, Qian; Tang, Yong

    2017-06-01

    Brain imaging and postmortem studies have indicated that white matter abnormalities may contribute to the pathology and pathogenesis of depression. However, until now, no study has quantitatively investigated white matter changes in depression in rats. The current study used the chronic unpredictable stress (CUS) model of depression. Body weight and sucrose preference test (SPT) scores were assessed weekly. Upon successfully establishing the CUS animal model, all animals were tested using the SPT and the open field test (OFT). Then, transmission electron microscopy and unbiased stereological methods were used to investigate white matter changes in the rats. Compared with the control group, the body weight and sucrose preference of the CUS rats were significantly decreased (p matter volume, the total volume, and the total length and mean diameter of myelinated fibers in the white matter of the CUS rats were significantly decreased compared to the control rats (p = .042, p = .038, p = .035, p = .019, respectively). The results of this study suggested that white matter atrophy and disruption of myelinated fibers in the white matter may contribute to the pathophysiology underlying depression, which might provide new targets for the development of novel therapeutic interventions for depression. © 2017 Wiley Periodicals, Inc.

  3. A two-state stochastic model of REM sleep architecture in the rat.

    Science.gov (United States)

    Gregory, Gavin G; Cabeza, Rafael

    2002-11-01

    Rapid eye movement (REM) sleep is a recurring state throughout the sleeping period. Based on the examination of 45 sleep records of 3-mo-old male rats during the middle of the light phase, a stochastic model is proposed for the sequence X(1),Y(2), X(2),Y(2),. of REM sleep durations X and inter-REM sleep waiting times Y experienced by a rat during a sleeping period. In our model the probability distribution of any variable in the sequence, given the past, is allowed to depend on only the immediately previous variable. The conditional distributions f(y(i) | x(i)) and g(x(i+1) | y(i)) do not depend on the index i. It is shown that the marginal distributions tend to stationarity. Aggregations of the data on a discrete time scale suggest that the conditional distributions be formulated as two-component mixtures. These component distributions are modeled as Poisson and their means are called the means of short and long waiting time and the means of short and long REM sleep duration. Associated with each mean is a probability weight. Parametric forms are given to the means and probability weights. The model estimated by maximum likelihood shows a good fit to data of the 3-mo-old rats. The model fit to a smaller data set obtained from rats aged 15-22 mo shows a significant shortening of the means for both short and long REM sleep bout durations compared with the means of the 3-mo-old rats. Neuronal correlates for the behavior of the model are discussed in the context of the reciprocal interaction model of REM sleep regulation.

  4. Establishment of 9L/F344 rat intracerebral glioma model of brain tumor stem cells

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    Zong-yu XIAO

    2015-04-01

    Full Text Available Objective To establish the 9L/F344 rat intracerebral glioma model of brain tumor stem cells.  Methods Rat 9L gliosarcoma stem-like cells were cultured in serum-free suspension. The expression of CD133 and nestin were tested by immunohistochemistry. A total of 48 inbredline male F344 rats were randomly divided into 2 groups, and 9L tumor sphere cells and 9L monolayer cells were respectively implanted into the right caudate nucleus of F344 rats in 2 groups. Survival time was observed and determined using the method of Kaplan-Meier survival analysis. Fourteen days after implantation or when the rats were dying, their brains were perfused and sectioned for HE staining, and CD133 and nestin were detected by immunohistochemistry.  Results Rat 9L tumor spheres were formed with suspension culture in serum-free medium. The gliomas formed in both groups were invasive without obvious capsule. More new vessels, bleeding and necrosis could be detected in 9L tumor spheres group. The tumor cells in both groups were positive for CD133 and nestin. There was no significant difference in the expression of CD133 and nestin between 2 groups (P > 0.05, for all. According to the expression of nestin, the tumors formed by 9L tumor sphere cells were more invasive. The median survival time of the rats bearing 9L tumor sphere cells was 15 d (95%CI: 15.219-15.781, and the median survival time of the rats bearing 9L monolayer cells was 21 d (95%CI: 20.395-21.605. There was significant difference between 2 groups (χ2 = 12.800, P = 0.000.  Conclusions 9L/F344 rat intracerebral glioma model of brain tumor stem cells is successfully established, which provides a glioma model for the future research. DOI: 10.3969/j.issn.1672-6731.2015.04.012

  5. Luteolin ameliorates colistin-induced nephrotoxicity in the rat models.

    Science.gov (United States)

    Arslan, Birsen Yigit; Arslan, Ferhat; Erkalp, Kerem; Alagöl, Ayşin; Sevdi, Mehmet Salih; Yıldız, Güneş; Küçük, Suat Hayri; Altınay, Serdar

    2016-11-01

    To study the protective, preventive effect of luteolin from colistin-induced nephrotoxicity. Four different treatment options were tested on rats: colistin, luteolin, and a combination of colistin and luteolin, intraperitoneally as two doses a day, for seven days. Another group of rats were used as the control and treated with sterile saline. Serum creatinine levels were measured before and after treatment. Histological changes and colistin-induced apoptosis (Insitu BrdU-red DNA Fragmentation Assay Kit) of the renal tissues were examined after the scarification procedure. In the Colistin Group, post-treatment creatinine levels were statistically higher than the pretreatment levels (p = .001). In the remaining groups, no significant changes were observed. Cells that undergo apoptosis were counted and it was shown that all groups except the colistin-treated group had a similar number of apoptotic cells, whereas the colistin-treated group had statistically higher number of apoptotic cells compared to other groups (p = .0001). Renal histological damage was also measured and the score of the colistin treated group was higher as compared to other groups. The results obtained from this study demonstrated us that luteolin was capable of preventing colistin-induced nephrotoxicity and that this effect was significant at histopathological level.

  6. Application of Mathematical Modelling as a Tool to Analyze the EEG Signals in Rat Model of Focal Cerebral Ischemia

    Science.gov (United States)

    Paul, S.; Bhattacharya, P.; Pandey, A. K.; Patnaik, R.

    2014-01-01

    The present paper envisages the application of mathematical modelling with the autoregressive (AR) model method as a tool to analyze electroencephalogram data in rat subjects of transient focal cerebral ischemia. This modelling method was used to determine the frequencies and characteristic changes in brain waveforms which occur as a result of disorders or fluctuating physiological states. This method of analysis was utilized to ensure actual correlation of the different mathematical paradigms. The EEG data was obtained from different regions of the rat brain and was modelled by AR method in a MATLAB platform. AR modelling was utilized to study the long-term functional outcomes of a stroke and also is preferable for EEG signal analysis because the signals consist of discrete frequency intervals. Modern spectral analysis, namely AR spectrum analysis, was used to correlate the conditional and prevalent changes in brain function in response to a stroke.

  7. Comparison of Goto-Kakizaki rats and high fat diet-induced obese rats: Are they reliable models to study Type 2 Diabetes mellitus?

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    Wilson Mitsuo Tatagiba Kuwabara

    Full Text Available Type 2 Diabetes mellitus (T2DM is an evident growing disease that affects different cultures throughout the world. T2DM occurs under the influence of three main factors: the genetic background, environmental and behavioral components. Obesity is strongly associated to the development of T2DM in the occident, while in the orient most of the diabetic patients are considered lean. Genetics may be a key factor in the development of T2DM in societies where obesity is not a recurrent public health problem. Herein, two different models of rats were used to understand their differences and reliability as experimental models to study the pathophysiology of T2DM, in two different approaches: the genetic (GK rats and the environmental (HFD-induced obese rats influences. GK rats were resistant to weight gain even though food/energy consumption (relative to body weight was higher in this group. HFD, on the other hand, induced obesity in Wistar rats. White adipose tissue (WAT expansion in this group was accompanied by immune cells infiltration, inflammation and insulin resistance. GK rats also presented WAT inflammation and insulin resistance; however, no immune cells infiltration was observed in the WAT of this group. Liver of HFD group presented fat accumulation without differences in inflammatory cytokines content, while liver of GK rats didn't present fat accumulation, but showed an increase of IL-6 and IL-10 content and glycogen. Also, GK rats showed increased plasma GOT and GPT. Soleus muscle of HFD presented normal insulin signaling, contrary to GK rats, which presented higher content of basal phosphorylation of GSK-3β. Our results demonstrated that HFD developed a mild insulin resistance in Wistar rats, but was not sufficient to develop T2DM. In contrast, GK rats presented all the typical hallmarks of T2DM, such as insulin resistance, defective insulin production, fasting hyperglycemia/hyperinsulinemia and lipid plasma alteration. Thus, on the given

  8. 5-Hydroxytryptamine Changes under Different Pretreatments on Rat Models of Myocardial Infarction and/or Depression

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    Mei-Yan Liu

    2017-01-01

    Conclusions: By elevating the amount of 5-HT and modulating 5-HT2AR and SERT levels in serum and platelets, XinLingWan and sertraline were found to exert pretreatment effect on rat models of MI and/or depression.

  9. Influence of fluid resuscitation on renal microvascular PO2 in a normotensive rat model of endotoxemia

    NARCIS (Netherlands)

    Johannes, Tanja; Mik, Egbert G.; Nohé, Boris; Raat, Nicolaas J. H.; Unertl, Klaus E.; Ince, Can

    2006-01-01

    INTRODUCTION: Septic renal failure is often seen in the intensive care unit but its pathogenesis is only partly understood. This study, performed in a normotensive rat model of endotoxemia, tests the hypotheses that endotoxemia impairs renal microvascular PO2 (microPO2) and oxygen consumption

  10. Translational mixed-effects PKPD modelling of recombinant human growth hormone - from hypophysectomized rat to patients

    DEFF Research Database (Denmark)

    Thorsted, Anders; Thygesen, Peter; Agersø, Henrik

    2016-01-01

    was developed from experimental PKPD studies of rhGH and effects of long-term treatment as measured by insulin-like growth factor 1 (IGF-1) and bodyweight gain in rats. Modelled parameter values were scaled to human values using the allometric approach with fixed exponents for PKs and unscaled for PDs...

  11. Impaired coronary endothelial function in a rat model of spontaneous albuminuria

    NARCIS (Netherlands)

    Gschwend, Simone; Pinto-Sietsma, Sara-Joan; Buikema, Hendrik; Pinto, Yigal M.; van Gilst, Wiek H.; Schulz, Angela; de Zeeuw, Dick; Kreutz, Reinhold

    2002-01-01

    BACKGROUND: Albuminuria is an independent risk factor of coronary artery disease and has been proposed to reflect a general endothelial disorder. The Munich Wistar Frömter (MWF) rat strain develops spontaneous albuminuria and, therefore, may be an interesting experimental model to study alterations

  12. Prevention of injury by resveratrol in a rat model of adenine-induced ...

    African Journals Online (AJOL)

    Purpose: To investigate the preventive effect of resveratrol against renal pathological changes in a rat model of chronic kidney disease (CKD). Methods: CKD was induced by daily intragastric administration of adenine (200 mg/kg) for 1 month. The effect of 10, 15, and 20 mg/kg doses of resveratrol on the levels of ...

  13. Effects of Ecballium elaterium on brain in a rat model of sepsis ...

    African Journals Online (AJOL)

    Here we examined the anti-inflammatory and antioxidant effects of Ecballium elaterium (EE) on brain, and explored its therapeutic potential in an animal model of sepsis-associated encephalopathy (SAE) [induced by cecal ligation and puncture (CLP)]. Thirty rats were divided into three groups of 10 each: control, sepsis, ...

  14. Ultrastructure of basement membranes of peritoneal capillaries in a chronic peritoneal infusion model in the rat

    NARCIS (Netherlands)

    Zweers, M. M.; Splint, L. J.; Krediet, R. T.; Struijk, D. G.

    2001-01-01

    BACKGROUND: Long-term peritoneal dialysis with glucose- based dialysis solutions has been associated with diabetiform alterations of peritoneal tissue. A peritoneal infusion model in the rat was developed to study the effect of chronic infusion of a glucose-based dialysis solution and an isotonic

  15. Whole mitochondrial genome sequence and mutations of the hypertension model inbred rat strain (Muridae; Rattus).

    Science.gov (United States)

    Song, Wei; Gao, Lin-lin; Zhen, Lin-lin

    2016-01-01

    We reported the complete mitochondrial genome sequencing of a important hypertension model inbred rat strain for the first time. The total length of the mitogenome was 16,310 bp. It harbored 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes and 1 non-coding control region. The mutation events contained in this strain were also reported.

  16. Assessing Autophagy in Sciatic Nerves of a Rat Model that Develops Inflammatory Autoimmune Peripheral Neuropathies

    Directory of Open Access Journals (Sweden)

    Susana Brun

    2017-09-01

    Full Text Available The rat sciatic nerve has attracted widespread attention as an excellent model system for studying autophagy alterations in peripheral neuropathies. In our laboratory, we have developed an original rat model, which we used currently in routine novel drug screening and to evaluate treatment strategies for chronic inflammatory demyelinating polyneuropathy (CIDP and other closely related diseases. Lewis rats injected with the S-palmitoylated P0(180-199 peptide develop a chronic, sometimes relapsing-remitting type of disease. Our model fulfills electrophysiological criteria of demyelination with axonal degeneration, confirmed by immunohistopathology and several typical features of CIDP. We have set up a series of techniques that led us to examine the failures of autophagy pathways in the sciatic nerve of these model rats and to follow the possible improvement of these defects after treatment. Based on these newly introduced methods, a novel area of investigation is now open and will allow us to more thoroughly examine important features of certain autophagy pathways occurring in sciatic nerves.

  17. Elastic Changes of Capsule in a Rat Knee Contracture Model Assessed by Scanning Acoustic Microscopy

    Science.gov (United States)

    Hagiwara, Y.; Chimoto, E.; Ando, A.; Saijo, Y.; Itoi, E.

    Sound speed of a capsule in a rat knee contracture model was measured by scanning acoustic microscopy. There was no statistical significant difference in the anterior capsule compared with the control group. However, the sound speed of the posterior capsule was significantly greater compared with the control group after prolonged immobilization.

  18. RAT Selection and Resource Allocation in Heterogeneous Networks - OPNET Modeler in Optimization Studies

    DEFF Research Database (Denmark)

    Zakrzewska, Anna; Ruepp, Sarah Renée; Berger, Michael Stübert

    2013-01-01

    The paper addresses the problem of optimal selection of Radio Access Technology (RAT) and assignment of resources in a multistandard wireless network scenario. It is shown how OPNET Modeler can be used to perform optimization studies using Integer Linear Programming (ILP) solvers. In this way...

  19. Variability in Ozone-Induced Pulmonary Injury and Inflammation in Healthy and Cardiovascular Compromised Rat Models

    Science.gov (United States)

    The molecular bases for variability in air pollutant-induced pulmonary injury due to underlying cardiovascular (CVD) and/or metabolic diseases are unknown. We hypothesized that healthy and genetic CVD-prone rat models will exhibit exacerbated response to acute ozone exposure depe...

  20. Oxidative stress in a rat model of cotton smoke inhalation-induced ...

    African Journals Online (AJOL)

    Background: Smoke inhalation injury refers to airway and lung parenchyma injury and general chemical damage caused by inhaling toxic gases and substances. The aim of this study was to explore the oxidative stress mechanism of cotton smoke inhalation-induced pulmonary injury in a rat model. Materials and Methods: ...

  1. Strain Differences in Antioxidants in Rat Models of Cardiovascular Disease Exposed to Ozone

    Science.gov (United States)

    We examined the hypothesis that antioxidant substances and enzymes in lung, heart and in bronchoalveolar lavage fluid (BALF) are altered in response to 03 in cardiovascular disease and/or metabolic syndrome (CVD)-prone rat models. CVD strains [spontaneously hypertensive (SH), SH ...

  2. Impaired coronary endothelial function in a rat model of spontaneous albuminuria

    NARCIS (Netherlands)

    Gschwend, S; Pinto-Sietsma, SJ; Buikema, H; Pinto, YM; van Gilst, WH; Schulz, A; de Zeeuw, D; Kreutz, R

    Background. Albuminuria is an independent risk factor of coronary artery disease and has been proposed to reflect a general endothelial disorder. The Munich Wistar Fromter (MWF) rat strain develops spontaneous albuminuria and, therefore, may be an interesting experimental model to study alterations

  3. Induction of model time-related airway inflammation in Wistar rats ...

    African Journals Online (AJOL)

    Induction of model time-related airway inflammation in Wistar rats with crude extract of Periplaneta americana. M E Eko, M U Eteng, D N Omokaro, I B Umoh. Abstract. No Abstract. Global Journal of Pure and Applied Physics Vol. 14 (1) 2008 pp. 49-54. Full Text: EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL ...

  4. Effects of yokukansan on anxiety-like behavior in a rat model of cerebrovascular dementia.

    Science.gov (United States)

    Nogami, Ai; Sakata, Yuri; Uchida, Naoki; Yamaguchi, Kazuko; Kawasaki, Chihiro; Shindo, Taro; Kubota, Kaori; Katsurabayashi, Shutaro; Takasaki, Kotaro; Mishima, Kenichi; Nishimura, Ryoji; Fujiwara, Michihiro; Iwasaki, Katsunori

    2011-04-01

    Behavioral and psychological symptoms of dementia (BPSD) are commonly seen in patients with dementia. Current pharmacological approaches to treatment are inadequate, despite the availability of serotonergic agents to ameliorate anxiety, one of the symptoms of BPSD. The herbal medicine yokukansan has been demonstrated to improve BPSD in a randomized, single-blinded, placebo-controlled study. However, the mechanisms of the anxiolytic effect of yokukansan have not been clarified. There are also no reports on the anxiolytic effect of yokukansan in cerebrovascular ischemia models. In this study, we examined whether rats subjected to repeated cerebral ischemia exhibited anxiety-like behavior in a plus-maze task, a light/dark box test and an open-field task. We then investigated the effect of yokukansan on anxiety-like behavior in ischemic rats. Repeated ischemia was induced by the four-vessel occlusion method in which a 10-min ischemic episode was repeated once after 60 min. Yokukansan was orally administered once a day for 14 days from 7 days before ischemia induction. The last administration was performed 1 h before the behavioral experiments. The ischemic rats showed anxiety-like behavior in all three tasks, suggesting that this rat may be a good model for anxiety in cerebrovascular dementia. Yokukansan exhibited anxiolytic effects on the anxiety-like behavior in rats subjected to repeated cerebral ischemia, and exerted antagonistic effects on the wet-dog shakes induced by 1-(2,5-dimethoxy-4-indophenyl)-2-amino propane, a serotonin receptor (5-HT(2A)) agonist. This study revealed that yokukansan shows anxiolytic effects not only in normal animals but also in cerebrovascular model rats.

  5. [Foshouningshen decoction improves sleeping via the serotonergic system in a rat model of insomnia].

    Science.gov (United States)

    Huang, Jie-Cong; Xie, Wei; Deng, Ning; Liang, Wen-Lin; Hu, Dong-Rong; Hong, Yu; Zhou, Yang

    2017-08-20

    To evaluate the sedative and hypnotic effects of Foshouningshen decoction (FSNSD) and study its effects on expressions of 5-hydroxy tryptamine (5-HT) and 5-HT1A receptor (5-HT1AR) in the hippocampus in a rat model of insomnia. Male KM mice were divided into control group, estazolam (0.4 mg/kg daily) group, and low-, moderate-, and high-dose FSNSD groups (daily dose of 12, 24, and 48 g/kg, respectively). After corresponding treatments for 1 week, the mice underwent sleep-inducing test with subthreshold and threshold doses of sodium pentobarbital. Forty-eight male SD rats were randomized into control group, insomnia model group, estazolam group (0.2 mg/kg daily), and low-, moderate-, and high-dose FSNSD groups (with daily dose of 6, 12, and 24 g/kg, respectively). Rat models of insomnia were established by intraperitoneal injection of 4-cholro-dl-phenylalanine (PCPA) at the daily dose of 350 mg/kg for 3 days, after which the rats received corresponding treatments via gavage for 1 week. The performance of the rats in open field test was recorded and the hippocampal expression of 5-HT was detected using ELISA; the expressions of 5-HT1AR protein and mRNA in the hippocampus were detected using immunohistochemistry and real-time PCR, respectively. In the sleep-inducing test with a subthreshold dose of sodium pentobarbital, the mice treated with high-dose FSNSD showed a significantly higher rate of sleep onset than the control mice (Pmodel group showed increased total distance in open field test (Popen field test (P<0.05) and increased the content of 5-HT (P<0.05) and expressions of 5-HT1AR (P<0.01) in the hippocampus of rats with insomnia. FSNSD can produce therapeutic effects on insomnia possibly by increasing 5-HT content and expressions of 5-HT1AR in the hippocampus.

  6. High Resolution Ultrasonography for Assessment of Renal Cysts in the PCK Rat Model of Autosomal Recessive Polycystic Kidney Disease.

    OpenAIRE

    Kapoor Sarika; Rodriguez Daniel; Mitchell Katharyn; Wüthrich Rudolf P

    2016-01-01

    BACKGROUND/AIMS: The PCK rat model of polycystic kidney disease is characterized by the progressive development of renal medullary cysts. Here, we evaluated the suitability of high resolution ultrasonography (HRU) to assess the kidney and cyst volume in PCK rats, testing three different ultrasound image analysis methods, and correlating them with kidneys weights and histological examinations. METHODS: After inducing anesthesia, PCK rats (n=18) were subjected to HRU to visualize the kidneys...

  7. Decreased exposure of simvastatin and simvastatin acid in a rat model of type 2 diabetes

    Science.gov (United States)

    Xu, Dan; Li, Feng; Zhang, Mian; Zhang, Ji; Liu, Can; Hu, Meng-yue; Zhong, Ze-yu; Jia, Ling-ling; Wang, Da-wei; Wu, Jie; Liu, Li; Liu, Xiao-dong

    2014-01-01

    Aim: Simvastatin is frequently administered to diabetic patients with hypercholesterolemia. The aim of the study was to investigate the pharmacokinetics of simvastatin and its hydrolysate simvastatin acid in a rat model of type 2 diabetes. Methods: Diabetes was induced in 4-week-old rats by a treatment of high-fat diet combined with streptozotocin. After the rats received a single dose of simvastatin (20 mg/kg, po, or 2 mg/kg, iv), the plasma concentrations of simvastatin and simvastatin acid were determined. Simvastatin metabolism and cytochrome P4503A (Cyp3a) activity were assessed in hepatic microsomes, and its uptake was studied in freshly isolated hepatocytes. The expression of Cyp3a1, organic anion transporting polypeptide 2 (Oatp2), multidrug resistance-associated protein 2 (Mrp2) and breast cancer resistance protein (Bcrp) in livers was measured using qRT-PCR. Results: After oral or intravenous administration, the plasma concentrations and areas under concentrations of simvastatin and simvastatin acid were markedly decreased in diabetic rats. Both simvastatin metabolism and Cyp3a activity were markedly increased in hepatocytes of diabetic rats, accompanied by increased expression of hepatic Cyp3a1 mRNA. Furthermore, the uptake of simvastatin by hepatocytes of diabetic rats was markedly increased, which was associated with increased expression of the influx transporter Oatp2, and decreased expression of the efflux transporters Mrp2 and Bcrp. Conclusion: Diabetes enhances the metabolism of simvastatin and simvastatin acid in rats via up-regulating hepatic Cyp3a activity and expression and increasing hepatic uptake. PMID:25152023

  8. Is montelukast effective in regression of endometrial implants in an experimentally induced endometriosis model in rats?

    Science.gov (United States)

    Kiykac Altinbas, Sadiman; Tapisiz, Omer Lutfi; Cavkaytar, Sabri; Simsek, Gulcin; Oguztuzun, Serpil; Goktolga, Umit

    2015-01-01

    Montelukast, a selective antagonist of Type 1 cysteinyl leukotriene receptors (CysLT1Rs), antagonizes the proinflammatory and proasthmatic activities of CysLT1Rs. We investigated the effect of montelukast on a surgically induced endometriosis rat model. Thirty-two sexually mature, cycling, female Wistar-Albino rats, in which endometriotic implants were surgically induced, were randomly divided into three groups. Group I [Montelukast (M), 10 rats)] was given 1.6 mg/kg/day of oral montelukast sodium. Group II [Leuprolide acetate (L), 11 rats] was given 1 mg/kg single dose of s.c.leuprolide acetate. Group III [Control (C), 11 rats] received saline solution through an orogastric tube and served as controls. After a 3-weeks medication, the rats were sacrificed to investigate the endometriotic implants for size and morphological and histological characteristics, including immunoreactivity of MMP-2 and VEGF. The mean area of implants decreased from 48.2 ± 24.7 to 29.3 ± 15.8mm(2) in Group I (M) (P = 0.008) and from 62 ± 32.1 to 39.9 ± 18.1mm(2) in Group II (L) (P=0.003). In Group III (C), the mean area increased from 41.1 ± 31.1 to 60.4 ± 37.1mm(2) (P = 0.025). Histopathological analysis showed statistically significant lower scores in rats treated with montelukast compared to leuprolide and controls. MMP H scores were not different between the groups in both epithelial and stromal MMP-2 immunostaining. VEGF H scores were statistically lower in Group 1 (M) in epithelial VEGF immunostaining when compared to Group II (L) and Group III (C) (P=0.006). Montelukast may effectively cause a significant decrease in the area of endometriotic implants. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. Endothelin B receptors contribute to retinal ganglion cell loss in a rat model of glaucoma.

    Directory of Open Access Journals (Sweden)

    Alena Z Minton

    Full Text Available Glaucoma is an optic neuropathy, commonly associated with elevated intraocular pressure (IOP characterized by optic nerve degeneration, cupping of the optic disc, and loss of retinal ganglion cells which could lead to loss of vision. Endothelin-1 (ET-1 is a 21-amino acid vasoactive peptide that plays a key role in the pathogenesis of glaucoma; however, the receptors mediating these effects have not been defined. In the current study, endothelin B (ET(B receptor expression was assessed in vivo, in the Morrison's ocular hypertension model of glaucoma in rats. Elevation of IOP in Brown Norway rats produced increased expression of ET(B receptors in the retina, mainly in retinal ganglion cells (RGCs, nerve fiber layer (NFL, and also in the inner plexiform layer (IPL and inner nuclear layer (INL. To determine the role of ET(B receptors in neurodegeneration, Wistar-Kyoto wild type (WT and ET(B receptor-deficient (KO rats were subjected to retrograde labeling with Fluoro-Gold (FG, following which IOP was elevated in one eye while the contralateral eye served as control. IOP elevation for 4 weeks in WT rats caused an appreciable loss of RGCs, which was significantly attenuated in KO rats. In addition, degenerative changes in the optic nerve were greatly reduced in KO rats compared to those in WT rats. Taken together, elevated intraocular pressure mediated increase in ET(B receptor expression and its activation may contribute to a decrease in RGC survival as seen in glaucoma. These findings raise the possibility of using endothelin receptor antagonists as neuroprotective agents for the treatment of glaucoma.

  10. Comparative Metabolism of Carbon Tetrachloride in Rats, Mice and Hamsters Using Gas Uptake and PBPK Modeling

    Energy Technology Data Exchange (ETDEWEB)

    Thrall, Karla D.(BATTELLE (PACIFIC NW LAB)); Vucelick, Mark E.(FLUOR HANFORD, INC); Gies, Richard A.(BATTELLE (PACIFIC NW LAB)); Zangar, Richard C.(BATTELLE (PACIFIC NW LAB)); Weitz, Karl K.(BATTELLE (PACIFIC NW LAB)); Poet, Torka S.(BATTELLE (PACIFIC NW LAB)); Springer, David L.(BATTELLE (PACIFIC NW LAB)); Grant, Donna M.(BATTELLE (PACIFIC NW LAB)); Benson, Janet M.(Inhalation Toxicology Research Institute)

    2000-08-25

    No study has comprehensively compared the rate of metabolism of carbon tetrachloride (CCl4) across species. Therefore, the in vivo metabolism of CCl4 was evaluated using groups of male animals (F344 rats, B6C3F1 mice, and Syrian hamsters) exposed to 40-1800 ppm CCl4 in a closed, recirculating gas-uptake system. For each species, an optimal fit of the family of uptake curves was obtained by adjusting Michaelis-Menten metabolic constants Km (affinity) and Vmax (capacity) using a physiologically based pharmacokinetic (PBPK) model. The results show that the mouse has a slightly higher capacity and lower affinity for metabolizing CCl4 compared to the rat, while the hamster has a higher capacity and lower affinity than either rat or mouse. A comparison of the Vmax to Km ratio, normalized for mg of liver protein (L/hr/mg) across species indicates that hamsters metabolize more CCl4 than either rats or mice, and should be more susceptible to CCl4-induced hepatotoxicity. These species comparisons were evaluated against toxicokinetic studies conducted in animals exposed by nose-only inhalation to 20 ppm 14C-labeled CCl4 for 4 hours. The toxicokinetic study results are consistent with the in vivo rates of metabolism, with rats eliminating less radioactivity associated with metabolism (14CO2 and urine/feces) and more radioactivity associated with the parent compound (radioactivity trapped on charcoal) compared to either hamsters or mice. The in vivo metabolic constants determined here, together with in vitro constants determined using rat, mouse, hamster and human liver microsomes, were used to estimate human in vivo metabolic rates of 1.49 mg/hr/kg body weight and 0.25 mg/L for Vmax and Km, respectively. Normalizing the rate of metabolism (Vmax/Km) by mg liver protein, the rate of metabolism of CCl4 differs across species, with hamster > mouse& > rat > human.

  11. Effects of DPP-4 inhibitors on the heart in a rat model of uremic cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Lyubov Chaykovska

    Full Text Available BACKGROUND: Uremic cardiomyopathy contributes substantially to mortality in chronic kidney disease (CKD patients. Glucagon-like peptide-1 (GLP-1 may improve cardiac function, but is mainly degraded by dipeptidyl peptidase-4 (DPP-4. METHODOLOGY/PRINCIPAL FINDINGS: In a rat model of chronic renal failure, 5/6-nephrectomized [5/6N] rats were treated orally with DPP-4 inhibitors (linagliptin, sitagliptin, alogliptin or placebo once daily for 4 days from 8 weeks after surgery, to identify the most appropriate treatment for cardiac dysfunction associated with CKD. Linagliptin showed no significant change in blood level AUC(0-∞ in 5/6N rats, but sitagliptin and alogliptin had significantly higher AUC(0-∞ values; 41% and 28% (p = 0.0001 and p = 0.0324, respectively. No correlation of markers of renal tubular and glomerular function with AUC was observed for linagliptin, which required no dose adjustment in uremic rats. Linagliptin 7 µmol/kg caused a 2-fold increase in GLP-1 (AUC 201.0 ng/l*h in 5/6N rats compared with sham-treated rats (AUC 108.6 ng/l*h (p = 0.01. The mRNA levels of heart tissue fibrosis markers were all significantly increased in 5/6N vs control rats and reduced/normalized by linagliptin. CONCLUSIONS/SIGNIFICANCE: DPP-4 inhibition increases plasma GLP-1 levels, particularly in uremia, and reduces expression of cardiac mRNA levels of matrix proteins and B-type natriuretic peptides (BNP. Linagliptin may offer a unique approach for treating uremic cardiomyopathy in CKD patients, with no need for dose-adjustment.

  12. Basement membrane chondroitin sulfate proteoglycan alterations in a rat model of polycystic kidney disease

    DEFF Research Database (Denmark)

    Ehara, T; Carone, F A; McCarthy, K J

    1994-01-01

    Alterations in basement membrane components, notably proteoglycans, in a rat model of polycystic kidney disease have been investigated. Rats were fed phenol II (2-amino-4-hydroxyphenyl-5-phenyl thiazole) for 4 days and then changed to normal diet for a 7-day recovery period. Marked dilation...... membrane heparan sulfate proteoglycan core protein related to perlecan did not diminish but rather stained affected tubules intensely, whereas laminin, on the other hand, was apparently diminished in the basement membranes of the cystic tubules. Type IV collagen staining did not change through disease...... in this disease....

  13. Intermittent Fasting Pretreatment Prevents Cognitive Impairment in a Rat Model of Chronic Cerebral Hypoperfusion.

    Science.gov (United States)

    Hu, Yuan; Yang, Ying; Zhang, Miao; Deng, Min; Zhang, Jun-Jian

    2017-07-01

    Background: Whether intermittent fasting (IF) pretreatment can prevent vascular cognitive dysfunction remains unknown to our knowledge.Objective: We investigated the effects and underlying mechanisms of IF pretreatment on cognitive dysfunction in a permanent 2-vessel occlusion (2VO) vascular dementia rat model.Methods: Male Wistar rats weighing 200 g were subjected to either IF or ad libitum feeding for 12 wk before 2VO surgery. Rats in the IF protocol underwent alternative-day feed deprivation (FD). Memory of the animals was assessed by using the Morris water maze (MWM) and the novel object recognition (NOR) test 6 wk after the surgery. After behavioral testing, malondialdehyde and glutathione concentrations, superoxide dismutase (SOD) activity, gene expression of antioxidative enzymes, inflammatory protein concentrations, and microglia density were determined in the hippocampus of rats.Results: 2-vessel occlusion operation ad libitum (2VO-AL) rats had significantly longer escape latencies on day 4 of the training phase and spent a lower percentage of time in the target quadrant (25% compared with 38% and 41%) in the MWM, and had lower discrimination ratios (47% compared with 65% and 67%) in the NOR test than 2-vessel operation and alternate-day feed deprivation (2VO-FD) and sham operation ad libitum (Sham-AL) rats, respectively (P < 0.05). This indicates that IF helps to prevent vascular cognitive deficits. 2VO-AL rats also had higher malondialdehyde (3.54 compared with 2.15 and 1.66 nmol/mg protein) and lower glutathione concentrations (53.25 compared with 66.41 and 91.71 nmol/mg protein), lower SOD activity (100.1 compared with 133.3 and 138.5 U/mg protein), lower gene expression of antioxidative enzymes, higher expression of inflammatory proteins, and higher microglia density in the hippocampus than 2VO-FD and Sham-AL rats, respectively (P < 0.05). This suggests that IF has antioxidative and anti-inflammatory effects.Conclusions: IF pretreatment provided

  14. Early Fesoterodine Fumarate Administration Prevents Neurogenic Detrusor Overactivity in a Spinal Cord Transected Rat Model.

    Directory of Open Access Journals (Sweden)

    Xavier Biardeau

    Full Text Available In spinal cord injury, onset of detrusor overactivity (DO is detrimental for quality of life (incontinence and renal risk. Prevention has only been achieved with complex sophisticated electrical neuromodulation techniques.To assess the efficacy of early fesoterodine fumarate (FF administration in preventing bladder overactivity in a spinal cord transected (SCT rat model.33 Sprague-Dawley rats were allocated to 6 groups-Group 1: 3 normal controls; Group 2: 6 SCT controls; Group 3: 6 SCT rats + FF 0.18 mg/kg/d; Group 4: 6 SCT rats + FF 0.12 mg/kg/d; Group 5: 6 SCT rats + FF 0.18 mg/kg/d + 72-h wash-out period; Group 6: 6 SCT rats + FF 0.12 mg/kg/d + 72-h wash-out period. SCT was performed at T10. FF was continuously administered. Cystometry was undertaken 6 weeks after SCT in awake rats recording intermicturition pressure (IMP, baseline pressure, threshold pressure (Pthres and maximum pressure (Pmax. Normal controls and SCT controls were initially compared using the Mann-Whitney U tests in order to confirm the SCT effect on cystometric parameters. The comparisons in cystometric and metabolic cage parameters between SCT controls and treated rats were done using post-hoc Dunn's tests for Kruskal-Wallis analysis. Statistical testing was conducted at the two-tailed α-level of 0.05.Pressure parameters were significantly higher in SCT control group compared to normal controls. Six weeks after SCT, IMP was significantly lower in low dose treated group than in SCT controls. Pmax was significantly lower in 3 treated groups compared to SCT controls. Pthres was significantly lower in full time treated groups than in SCT controls.Early administration of FF modulates bladder overactivity in a SCT rat model. Whereas short-term prevention has been demonstrated, the long-term should be further analyzed. Clinical application of these results should confirm this finding through randomized research protocols.

  15. Cariogenic potential of foods. I. Caries in the rat model.

    Science.gov (United States)

    Mundorff, S A; Featherstone, J D; Bibby, B G; Curzon, M E; Eisenberg, A D; Espeland, M A

    1990-01-01

    As part of a major study to identify cariogenic elements of foods, the cariogenic potential of 22 foods relative to sucrose (confectioners' sugar) was determined over six intubation rat caries experiments. Cariogenic potential indices were calculated for each food from sulcal and buccal-lingual caries based on both number and severity. Those foods with the lowest cariogenic potential indices were peanuts, gelatin dessert, corn chips, yoghurt, and bologna; with the highest cariogenic potential indices were sucrose, granola cereal, french fries, bananas, cupcakes, and raisins. There was no simple relationship between food sucrose content and caries. Enhanced cariogenic potential was associated with foods containing approximately 1% or more hydrolyzable starch in combination with sucrose or other sugars.

  16. Modeling diabetes disease progression and salsalate intervention in Goto-Kakizaki rats.

    Science.gov (United States)

    Cao, Yanguang; Dubois, Debra C; Sun, Hao; Almon, Richard R; Jusko, William J

    2011-12-01

    Type 2 diabetes mellitus (T2DM) arises owing to insulin resistance and β-cell dysfunction. Chronic inflammation is widely identified as a cause of T2DM. The Goto-Kakizaki (GK) rat is a spontaneous rodent model for T2DM with chronic inflammation. The purpose of this study was to characterize diabetes progression in GK rats and evaluate the potential role of the anti-inflammatory agent salsalate. The GK rats were divided into control groups (n = 6) and salsalate treatment groups (n = 6), which were fed a salsalate-containing diet from 5 to 21 weeks of age. Blood glucose and salicylate concentrations were measured once a week. Glucose concentrations showed a biphasic increase in which the first phase started at approximately 5 weeks, resulting in an increase by 15 to 25 mg/dl and a second phase at 14 to 15 weeks with an upsurge of more than 100 mg/dl. A mechanism-based model was proposed to describe the natural diabetes progression and salsalate pharmacodynamics by using a population method in S-ADAPT. Two transduction cascades were applied to mimic the two T2DM components: insulin resistance and β-cell dysfunction. Salsalate suppressed both disease factors by a fraction of 0.622 on insulin resistance and 0.134 on β-cell dysfunction. The substantial alleviation of diabetes by salsalate supports the hypothesis that chronic inflammation is a pathogenic factor of diabetes in GK rats. In addition, body weight and food intake were measured and further modeled by a mechanism-based growth model. Modeling results suggest that salsalate reduces weight gain by enhancing metabolic rate and energy expenditure in both GK and Wister-Kyoto rats.

  17. Comparison of pharyngocutaneous fistula closure with and without bacterial cellulose in a rat model.

    Science.gov (United States)

    Demir, Berat; Sarı, Murat; Binnetoglu, Adem; Yumusakhuylu, Ali Cemal; Filinte, Deniz; Tekin, İshak Özel; Bağlam, Tekin; Batman, Abdullah Çağlar

    2018-04-01

    The present study aimed to compare the effects of bacterial cellulose used for closure of pharyngocutaneous fistulae, a complication of total laryngectomy, with those of primary sutures in a rat model. Thirty female Sprague-Dawley underwent experimental pharyngoesophagotomy and were grouped depending on the material used for pharyngocutaneous fistula closure: group I, which received primary sutures alone, group II, which received bacterial cellulose alone; and group III, which received both. After 7 days, the rats were sacrificed. Pharyngocutaneous fistula development was assessed, the gross wound was inspected, and histological examination was conducted. Pharyngocutaneous fistulae developed in 12 rats (41%) in all: 6 from group I (21%), 4 from group II (14%) and 2 from group III (7%). Fibroblast density and inflammatory cell infiltration were significantly greater in group III than group I. We concluded that bacterial cellulose may be useful for pharyngocutaneous fistula closure. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Health biomarkers in a rat model after intake of organically grown carrots

    DEFF Research Database (Denmark)

    Melballe Jensen, Maja; Jørgensen, Henry; Halekoh, Ulrich

    2012-01-01

    BACKGROUND:Organic foodis perceived as beingofbetter quality andhealthier than conventional foods although the scientific research on organic foodstuffs is highly contradictory. The aim of the present study was to investigate if intake of carrots from four different cultivation systems grown in two...... consecutive years would influence various biomarkers of health in a rat model. All rats were fed a diet with 40% carrot content. The carrots were grown under conventional (C), ‘minimalistic’ organic (O1), organic (O2), or ‘very’ organic cultivation systems (O3). A control group (CO) being fed standard rat...... chow was included. RESULTS: The plasma α-tocopherol concentration was higher in the O2 carrot-based diet group than in the C carrot based-diet group in one year, while all other health biomarkers or nutrient content differences were observed between the CO diet and the carrot-based diets. CONCLUSION...

  19. Dentate granule cells form hilar basal dendrites in a rat model of hypoxia-ischemia.

    Science.gov (United States)

    Díaz-Cintra, Sofia; Xue, Baogang; Spigelman, Igor; Van, K; Wong, Alan M; Obenaus, Andre; Ribak, Charles E

    2009-08-18

    Hilar basal dendrites form on dentate granule cells following seizures. To determine whether other brain insults cause the formation of hilar basal dendrites, a model of global cerebral hypoxia/ischemia was used. Rats underwent a transient induction of ischemia by occlusion of both common carotid arteries followed by reperfusion. Hippocampal slices were prepared from these animals 1 month after the ischemic insult, and granule cells were labeled with a retrograde tracing technique after biocytin injections into stratum lucidum of CA3b. Ischemic rats had numerous biocytin-labeled granule cells with hilar basal dendrites located at the hilar border of the granule cell layer. Quantitative analysis of ischemic rats compared to controls showed a significant increase in the percentage of biocytin-labeled granule cells with hilar basal dendrites. These data demonstrate that other brain insults in addition to epilepsy may result in the formation of hilar basal dendrites on granule cells.

  20. Establishment of a novel rat model without blood priming during normothermic cardiopulmonary bypass.

    Science.gov (United States)

    Zhu, X; Ji, B; Liu, J; Sun, Y; Wu, S; Zheng, Z; Long, C; Tang, Y

    2014-01-01

    An effective animal model was needed for research on the pathophysiology of cardiopulmonary bypass (CPB). Rat models were considered suitable for research into CPB, recently. The aim of the article is to establish a simple and safe CPB model without blood priming in rats, containing the advantages of controlling temperature precisely, being similar to the clinical process and laying the foundation for the further study of a deep hypothermic circulatory arrest (DHCA) model. Ten Sprague-Dawley rats, divided into a CPB group (n=7) and a sham group (n=3), received sevoflurane inhalation anesthesia and were maintained in an anesthesia state by intubation. The entire CPB circuit consisted of a reservoir, a membrane oxygenator, a roller pump, a heat exchanger and a heat cooler, all of which were connected via silicon tubes. The volume of the priming solution, composed of 6% HES130/0.4 and 125 IU heparin, was less than 12 ml. In the CPB group, a 22G catheter was placed in the left femoral artery for monitoring arterial blood pressure, a 20G catheter was placed in a tail artery for arterial inflow and a homemade, multiorificed catheter was inserted into a right jugular vein for venous drainage. After 90 minutes, the CPB process was terminated when vital signs were stable. In the sham group, the same surgical process was conducted except for the venous drainage. Post-oxygenator blood gas and hemodynamic parameters were measured at each time point before CPB, during CPB and after CPB. All CPB processes were successfully achieved. Blood gas analysis and hemodynamic parameters of each time point were in accordance with normal ranges. The vital signs of all rats were stable. The establishment of CPB without blood priming in rats can be achieved successfully. The rat model could be used to study short-term or long-term organ injury mechanisms caused by CPB. Furthermore, on the basis of the precise control of temperature and the depth of anesthesia, the DHCA model in rats could be

  1. Weight loss and brown adipose tissue reduction in rat model of sleep apnea

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    de Oliveira Patricia G

    2008-07-01

    Full Text Available Abstract Background - Obesity is related to obstructive sleep apnea-hypopnea syndrome (OSAHS, but its roles in OSAHS as cause or consequence are not fully clarified. Isocapnic intermittent hypoxia (IIH is a model of OSAHS. We verified the effect of IIH on body weight and brown adipose tissue (BAT of Wistar rats. Methods Nine-month-old male breeders Wistar rats of two groups were studied: 8 rats submitted to IIH and 5 control rats submitted to sham IIH. The rats were weighed at the baseline and at the end of three weeks, after being placed in the IIH apparatus seven days per week, eight hours a day, in the lights on period, simulating an apnea index of 30/hour. After experimental period, the animals were weighed and measured as well as the BAT, abdominal, perirenal, and epididymal fat, the heart, and the gastrocnemius muscle. Results Body weight of the hypoxia group decreased 17 ± 7 grams, significantly different from the variation observed in the control group (p = 0,001. The BAT was 15% lighter in the hypoxia group and reached marginally the alpha error probability (p = 0.054. Conclusion Our preliminary results justify a larger study for a longer time in order to confirm the effect of isocapnic intermittent hypoxia on body weight and BAT.

  2. Inflammation and Atrophy Precede Prostate Neoplasia in PhIP Induced Rat Model

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    Borowsky, A D; Dingley, K; Ubick, E; Turteltaub, K; Cardiff, R D; DeVere-White, R

    2006-06-01

    2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) has been implicated as a major mutagenic heterocyclic amine in the human diet and is carcinogenic in the rat prostate. In order to validate PhIP induced rat prostate neoplasia as a model of human prostate cancer progression, we sought to study the earliest histologic and morphologic changes in the prostate and to follow the progressive changes over time. We fed 67 male Fischer F344 5 week old rats with PhIP (400 PPM) or control diets for 20 weeks, and then sacrificed animals for histomorphologic examination at age 25 weeks, 45 weeks, and 65 weeks. Animals treated with PhIP showed significantly more inflammation (P=.002 (25wk), >.001(45wk), .016(65wk)) and atrophy (P=.003(25wk), >.001(45wk), .006 (65wk)) in their prostate glands relative to controls. Prostatic intraepithelial neoplasia (PIN) occurred only in PhIP treated rats. PIN lesions arose in areas of glandular atrophy, most often in the ventral prostate. Atypical cells in areas of atrophy show loss of glutathione S-transferase pi immunostaining preceding development of PIN. None of the animals in this study developed invasive carcinomas differing from previous reports. Overall, these findings suggest that the pathogenesis of prostatic neoplasia in the PhIP treated rat prostate proceeds from inflammation to post-inflammatory proliferative atrophy to PIN.

  3. Late onset deficits in synaptic plasticity in the valproic acid rat model of autism

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    Henry Giles Stratten Martin

    2014-01-01

    Full Text Available Valproic acid (VPA is a frequently used drug in the treatment of epilepsy, bipolar disorders and migraines; however it is also a potent teratogen. Prenatal exposure increases the risk of childhood malformations and can result in cognitive deficits. In rodents in utero exposure to VPA also causes neurodevelopmental abnormalities and is an important model of autism. In early postnatal life VPA exposed rat pups show changes in medial prefrontal cortex (mPFC physiology and synaptic connectivity. Specifically, principal neurons show decreased excitability but increased local connectivity, coupled with an increase in long-term potentiation (LTP due to an up-regulation of NMDA receptor (NMDAR expression. However recent evidence suggests compensatory homeostatic mechanisms lead to normalization of synaptic NMDA receptors during later postnatal development. Here we have extended study of mPFC synaptic physiology into adulthood to better understand the longitudinal consequences of early developmental abnormalities in VPA exposed rats. Surprisingly in contrast to early postnatal life and adolescence, we find that adult VPA exposed rats show reduced synaptic function. Both NMDAR mediated currents and LTP are lower in adult VPA rats, although spontaneous activity and endocannabinoid dependent long-term depression are normal. We conclude that rather than correcting, synaptic abnormalities persist into adulthood in VPA exposed rats, although a quite different synaptic phenotype is present. This switch from hyper to hypo function in mPFC may be linked to some of the neurodevelopmental defects found in prenatal VPA exposure and autism spectrum disorders in general.

  4. Reduced expression of perlecan in the aorta of secondary hyperparathyroidism model rats with medial calcification.

    Science.gov (United States)

    Shibata, Maki; Shigematsu, Takashi; Hatamura, Ikuji; Saji, Fumie; Mune, Sachiko; Kunimoto, Ken; Hanba, Yoshiyuki; Shiizaki, Kazuhiro; Sakaguchi, Toshifumi; Negi, Shigeo

    2010-01-01

    Vascular calcification is an important complication that worsens the prognosis for dialysis patients, although its detailed molecular mechanisms are still unknown. We produced a rat model for vascular calcification with hyperphosphatasemia and hyperparathyroidism, performing a 5/6 nephrectomy and providing a high-phosphorus, low-calcium diet for eight weeks. We examined mRNA obtained from the calcified aortae using microarray analysis, and searched for alterations in gene expression specifically in the calcified lesions. Medial calcification was demonstrated in the abdominal aorta of 12 out of 42 hyperparathyroidism rats. In the aortae of hyperparathyroid rats with vascular calcification, the genes for heparan sulfate proteoglycans, including perlecan, were found to be down-regulated using microarray analysis and real time PCR. Immunohistochemistry also demonstrated reduced production of perlecan in the aortae of hyperparathyroid rats. Perlecan is a major component of the vascular wall basement membrane and may play a role in protecting vascular smooth muscle cells from inflammatory cells and various toxins. It has also been reported that heparan sulfate chains may inhibit osteogenesis. Our findings indicate that perlecan may protect vascular smooth muscle cells from various factors that promote vascular calcification. It may be that reduced expression of perlecan in the calcified aortae of hyperparathyroid rats is a risk factor for vascular calcification.

  5. Effects of electroacupuncture on capsaicin-induced model of atopic dermatitis in rats.

    Science.gov (United States)

    Jung, Dal-Lim; Lee, Seung-Deok; Choi, In-Hwa; Na, Heung-Sik; Hong, Seung-Ug

    2014-04-01

    Electroacupuncture (EA) is used as a prescription to treat pruritus and atopic dermatitis. Whether EA affects experimental itch in rat models of immunologic or neuronal damages, however, is unknown. The present study was designed to determine the therapeutic effects of high-frequency EA on atopic dermatitis-like lesions in rats. Capsaicin (50mg/kg) was subcutaneously administered rat pups within 48h after birth. Rats then underwent 30min of EA at six acupoints (bilateral BL13, and unilateral LI11, ST36, SP10, SP6) every other day (EA group) for 3 weeks. Measurements of IgE, mast cells, scratching behavior, dynorphin release, skin thickness and dermatitis score were obtained. Only the dermatitis score and dynorphin expression were decreased in the EA group compared with the control non-EA group. We suggest that high-frequency EA alleviates pruritus of atopic dermatitis-like lesions in rats induced by capsaicin injection, via the release of dynorphin. These findings indicate a new potential therapeutic approach for the amelioration of symptoms of atopic dermatitis. Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  6. Inflammation and Atrophy Precede Prostatic Neoplasia in a PhIP-Induced Rat Model

    Directory of Open Access Journals (Sweden)

    Alexander D. Borowsky

    2006-09-01

    Full Text Available 2-Amino-1-methyl-6-phenylimidazo(4,5-bpyridine (PhIP has been implicated as a major mutagenic heterocyclicamine in the human diet and is carcinogenic in the rat prostate. To validate PhIP-induced rat prostatic neoplasia as a model of human prostate cancer progression, we sought to study the earliest histologic and morphologic changes in the prostate and to follow progressive changes over time. We fed sixty-seven 5-week-old male Fischer F344 rats with PhIP (400 ppm or control diets for 20 weeks, and then sacrificed animals for histomorphologic examination at the ages of 25, 45, and 65 weeks. Animals treated with PhIP showed significantly more inflammation (P = .002, > .001, and .016 for 25, 45, and 65 weeks, respectively and atrophy (P = .003, > .001, and .006 for 25, 45, and 65 weeks, respectively in their prostate glands relative to controls. Prostatic intraepithelial neoplasia (PIN occurred only in PhIP-treated rats. PIN lesions arose in areas of glandular atrophy, most often in the ventral prostate. Atypical cells in areas of atrophy show loss of glutathione S-transferase π immunostaining preceding the development of PIN.None of the animals in this study developed invasive carcinomas, differing from those in previous reports. Overall, these findings suggest that the pathogenesis of prostatic neoplasia in the PhIP-treated rat prostate proceeds from inflammation to postinflammatory proliferative atrophy to PIN.

  7. Green and Black Cardamom in a Diet-Induced Rat Model of Metabolic Syndrome

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    Maharshi Bhaswant

    2015-09-01

    Full Text Available Both black (B and green (G cardamom are used as flavours during food preparation. This study investigated the responses to B and G in a diet-induced rat model of human metabolic syndrome. Male Wistar rats were fed either a corn starch-rich diet (C or a high-carbohydrate, high-fat diet with increased simple sugars along with saturated and trans fats (H for 16 weeks. H rats showed signs of metabolic syndrome leading to visceral obesity with hypertension, glucose intolerance, cardiovascular remodelling and nonalcoholic fatty liver disease. Food was supplemented with 3% dried B or G for the final eight weeks only. The major volatile components were the closely related terpenes, 1,8-cineole in B and α-terpinyl acetate in G. HB (high-carbohydrate, high-fat + black cardamom rats showed marked reversal of diet-induced changes, with decreased visceral adiposity, total body fat mass, systolic blood pressure and plasma triglycerides, and structure and function of the heart and liver. In contrast, HG (high-carbohydrate, high-fat + green cardamom rats increased visceral adiposity and total body fat mass, and increased heart and liver damage, without consistent improvement in the signs of metabolic syndrome. These results suggest that black cardamom is more effective in reversing the signs of metabolic syndrome than green cardamom.

  8. Alterations in the vascular architecture of the dorsal root ganglia in a rat neuropathic pain model.

    Science.gov (United States)

    Kubícek, Lubos; Kopácik, Roman; Klusáková, Ilona; Dubový, Petr

    2010-04-20

    An alteration in the structural arrangement of blood vessels identified by RECA immunohistochemistry was studied in a rat L4 dorsal root ganglia (L4-DRG) neuropathic pain model. We compared a three-dimensional (3-D) reconstruction of the vascular architecture surrounding bodies of the primary sensory neurons in the L4-DRG of naïve rats with that of rats that had surgically undergone unilateral sciatic nerve ligature. Rhodamine-conjugated dextran (Fluoro-Ruby) was used for retrograde labelling of neurons, the axons of which had been injured by nerve ligature. In contrast to DRG from naïve rats and contralateral DRG from operated rats, an increased proportion of RECA+ vascular area and the appearance of nest-like arrangements of blood vessels around neuronal bodies with injured axons were observed in L4-DRG ipsilateral to the sciatic nerve ligature. Fractal analysis confirmed a higher degree of vascular branching, irregularity, and tortuosity in L4-DRG related with sciatic nerve injury. The results suggest that nerve injury induces changes in vascular architecture in associated DRG. Copyright 2010 Elsevier GmbH. All rights reserved.

  9. Postdependent state in rats as a model for medication development in alcoholism.

    Science.gov (United States)

    Meinhardt, Marcus W; Sommer, Wolfgang H

    2015-01-01

    Rational development of novel therapeutic strategies for alcoholism requires understanding of its underlying neurobiology and pathophysiology. Obtaining this knowledge largely relies on animal studies. Thus, choosing the appropriate animal model is one of the most critical steps in pre-clinical medication development. Among the range of animal models that have been used to investigate excessive alcohol consumption in rodents, the postdependent model stands out. It was specifically developed to test the role of negative affect as a key driving force in a perpetuating addiction cycle for alcoholism. Here, we will describe our approach to make rats dependent via chronic intermittent exposure to alcohol, discuss the validity of this model, and compare it with other commonly used animal models of alcoholism. We will summarize evidence that postdependent rats fulfill several criteria of a 'Diagnostic and Statistical Manual of Mental Disorders IV/V-like' diagnostic system. Importantly, these animals show long-lasting excessive consumption of and increased motivation for alcohol, and evidence for loss of control over alcohol intake. Our conclusion that postdependent rats are an excellent model for medication development for alcoholism is underscored by a summary of more than two dozen pharmacological tests aimed at reversing these abnormal alcohol responses. We will end with open questions on the use of this model. In the tradition of the Sanchis-Segura and Spanagel review, we provide comic strips that illustrate the postdependent procedure and relevant phenotypes in this review. © 2014 Society for the Study of Addiction.

  10. Chronic ocular hypertensive rat model using microbead injection: comparison of polyurethane, polymethylmethacrylate, silica and polystyene microbeads.

    Science.gov (United States)

    Rho, Seungsoo; Park, Insung; Seong, Gong Je; Lee, Naeun; Lee, Chang-Kyu; Hong, Samin; Kim, Chan Yun

    2014-09-01

    To establish and assess an ocular hypertensive rat model using intracameral injection with various microbeads of different sizes and materials. Chronic elevation of intraocular pressure (IOP) was induced by the injection of various microbeads into the anterior chamber of Sprague-Dawley rat eyes. We compared the IOPs induced by the injection of different microbeads [7- and 17-µm polyurethane (PU), 7- and 15-µm polymethylmethacrylate (PMMA), 13-µm silica, and 15-µm polystyrene (PS)] and selected the appropriate microbeads for a chronic ocular hypertensive model in terms of IOP elevation and adverse events. IOP changes were observed for 4 weeks after microbead injections. Axonal degeneration was assessed with transmission electron microscopic photographs and RGC loss was assessed with retrograde labeling. Seventy-eight rats were included. Three days after a single injection of microbeads, IOPs were increased by 24.0% by 7-µm PU microbeads, 101.8% by 17-µm PU microbeads, 56.6% by 7-µm PMMA microbeads, 22.0% by 15-µm PMMA microbeads, 153.0% by 13-µm silica microbeads, and 34.7% by 15-µm PS microbeads. 17-µm PU microbeads produced constant IOP elevation with good reproducibility (standard deviation of ocular hypertensive model in rats. Among several biomaterials, PU microbeads produced a more stable IOP elevation without adverse events.

  11. A novel rat model of catheter-associated urinary tract infection.

    Science.gov (United States)

    Kim, Hee Youn; Choe, Hyun-Sop; Lee, Dong Sup; Yoo, Jae Mo; Lee, Seung-Ju

    2015-08-01

    The authors aimed to establish a rat model of catheter-associated UTIs using a complete urethral catheter. Bacterial growth in biofilms on urethral catheters was analyzed using standard culture methods to validate this model. A total of 15 rats were divided into the following three groups according to the duration of indwelling catheter placement: a 2-week group (n = 5, group 1), a 4-week group (n = 5, group 2), and a 6-week group (n = 5, group 3). A urethral catheter was inserted with the distal end buried just beneath the urethra, and it was fixed inside of the urethra with a single suture starting at the vagina so that the suture knot was hidden inside of the vagina, preventing the rats from biting it off. A standard culture method was used to analyze bacterial growth in the biofilms. All 15 urethral catheters were intact at the end of the experiment. Pseudomonas aeruginosa, Escherichia coli, Enterococcus spp., Enterococcus faecalis, and Corynebacterium spp. were identified in the biofilms on the urethral catheters. Our rat UTI model consisting of a complete urinary catheter is feasible. Our study may provide fundamental data for future biofilm studies incorporating molecular techniques, and even clinical studies.

  12. Adeno-associated viral vector serotype 5 poorly transduces liver in rat models.

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    Paula S Montenegro-Miranda

    Full Text Available Preclinical studies in mice and non-human primates showed that AAV serotype 5 provides efficient liver transduction and as such seems a promising vector for liver directed gene therapy. An advantage of AAV5 compared to serotype 8 already shown to provide efficient correction in a phase 1 trial in patients suffering from hemophilia B, is its lower seroprevalence in the general population. Our goal is liver directed gene therapy for Crigler-Najjar syndrome type I, inherited severe unconjugated hyperbilirubinemia caused by UGT1A1 deficiency. In a relevant animal model, the Gunn rat, we compared the efficacy of AAV 5 and 8 to that of AAV1 previously shown to be effective. Ferrying a construct driving hepatocyte specific expression of UGT1A1, both AAV8 and AAV1 provided an efficient correction of hyperbilirubinemia. In contrast to these two and to other animal models AAV5 failed to provide any correction. To clarify whether this unexpected finding was due to the rat model used or due to a problem with AAV5, the efficacy of this serotype was compared in a mouse and two additional rat strains. Administration of an AAV5 vector expressing luciferase under the control of a liver specific promoter confirmed that this serotype poorly performed in rat liver, rendering it not suitable for proof of concept studies in this species.

  13. Hyperphosphatemia-induced hyperparathyroidism in 5/6 nephrectomized rats: development of a new animal model.

    Science.gov (United States)

    Jiang, Ying; Wang, Mei

    2008-12-05

    We require a stable model to understand the molecular mechanism by which isolated hyperphosphatemia induces hyperparathyroidism secondary to chronic renal failure. The present study established a rat model of hyperphosphatemia-induced secondary hyperparathyroidism in chronic renal failure. Twenty-nine rats with 5/6 nephrectomy (Nx) were divided into three groups and were fed for 10 weeks on a high phosphate diet (1.2% phosphate) starting from three different post-Nx time points. Parathyroid hormone mRNA in parathyroid gland was measured by real-time PCR and parathyroid cell hyperplasia was tested by proliferating cell nuclear antigen (PCNA) assay. The 10 rats fed a high phosphate diet starting from the fourth week post-Nx had isolated hyperphosphatemia and excess synthesis/secretion of parathyroid hormone, and hyperplasia of the parathyroid glands were induced (r = 0.86 - 0.97, P rat model of hyperphosphatemia-induced secondary hyperparathyroidism in chronic renal failure was established by 5/6 Nx and 10 weeks-high phosphate diet starting from the fourth week post-Nx.

  14. Human Umbilical Cord Mesenchymal Stem Cells Therapy in Cyclophosphamide-Induced Premature Ovarian Failure Rat Model

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    Dan Song

    2016-01-01

    Full Text Available Premature ovarian failure (POF is one of the most common causes of infertility in women. In our present study, we established cyclophosphamide- (CTX- induced POF rat model and elucidated its effect on ovarian function. We detected the serum estrogen, follicle stimulating hormone, and anti-Müllerian hormone of mice models by ELISA and evaluated their folliculogenesis by histopathology examination. Our study revealed that CTX administration could severely disturb hormone secretion and influence folliculogenesis in rat. This study also detected ovarian cells apoptosis by deoxy-UTP-digoxigenin nick end labeling (TUNEL and demonstrated marked ovarian cells apoptosis in rat models following CTX administration. In order to explore the potential of human umbilical cord mesenchymal stem cells (UCMSCs in POF treatment, the above indexes were used to evaluate ovarian function. We found that human UCMSCs transplantation recovered disturbed hormone secretion and folliculogenesis in POF rat, in addition to reduced ovarian cell apoptosis. We also tracked transplanted UCMSCs in ovaries by fluorescence in situ hybridization (FISH. The results manifested that the transplanted human UCMSCs could reside in ovarian tissues and could survive for a comparatively long time without obvious proliferation. Our present study provides new insights into the great clinical potential of human UCMSCs in POF treatment.

  15. A novel experimental model for studying transverse orthodontic tooth movement in the rat mandible.

    Science.gov (United States)

    Alsagheer, Ayad; Kline, Loren W; Doschak, Michael R; Major, Paul W

    2013-09-01

    To establish a rat model of a one-piece mandible using the principles of gingivoperiosteoplasty and guided bone regeneration to fuse the midline symphyseal area. Twenty-four Sprague-Dawley female rats were divided into two groups: 12 experimental and 12 control. Both groups were imaged using in vivo micro-computed tomography at baseline and at end point (5 months). The experimental group received regenerative surgery at the symphysis area; the control group received no treatment. Outcomes were evaluated by radiographic examination of gross and volumetric bony changes in the symphyseal region of interest marked between the mental foramina bilaterally and the two central incisors near the most coronal margin of the alveolar crests. These landmarks were chosen as they can be reproduced on the computed tomography images at baseline and end point. Histologic examination was performed on all samples at a level 5 mm apical to the alveolar bone crest. Radiologic and histologic examinations of the experimental group revealed complete bony fusion of the symphyseal area in three subjects, partial fusion in five subjects, and thickening of the alveolar bony socket in three subjects; one rat died of anesthesia-related complications. No evidence of fusion or alveolar bone thickening was found in any of the controls. This surgical animal model demonstrates that a rat mandible can be surgically manipulated to mimic the one-piece human mandible. This novel model may prove useful in studying mandibular bone remodeling and orthodontic mandibular tooth movement.

  16. Transplantation of induced pluripotent stem cells improves functional recovery in Huntington's disease rat model.

    Science.gov (United States)

    Mu, Shuhua; Wang, Jiachuan; Zhou, Guangqian; Peng, Wenda; He, Zhendan; Zhao, Zhenfu; Mo, CuiPing; Qu, Junle; Zhang, Jian

    2014-01-01

    The purpose of this study was to determine the functional recovery of the transplanted induced pluripotent stem cells in a rat model of Huntington's disease with use of 18F-FDG microPET/CT imaging. In a quinolinic acid-induced rat model of striatal degeneration, induced pluripotent stem cells were transplanted into the ipsilateral lateral ventricle ten days after the quinolinic acid injection. The response to the treatment was evaluated by serial 18F-FDG PET/CT scans and Morris water maze test. Histological analyses and Western blotting were performed six weeks after stem cell transplantation. After induced pluripotent stem cells transplantation, higher 18F-FDG accumulation in the injured striatum was observed during the 4 to 6-weeks period compared with the quinolinic acid-injected group, suggesting the metabolic recovery of injured striatum. The induced pluripotent stem cells transplantation improved learning and memory function (and striatal atrophy) of the rat in six week in the comparison with the quinolinic acid-treated controls. In addition, immunohistochemical analysis demonstrated that transplanted stem cells survived and migrated into the lesioned area in striatum, and most of the stem cells expressed protein markers of neurons and glial cells. Our findings show that induced pluripotent stem cells can survive, differentiate to functional neurons and improve partial striatal function and metabolism after implantation in a rat Huntington's disease model.

  17. Flow diverter implantation in a rat model of sidewall aneurysm: a feasibility study.

    Science.gov (United States)

    Aquarius, René; Smits, Debby; Gounis, Matthew J; Leenders, William P J; de Vries, Joost

    2018-01-01

    More challenging animal models are needed to elucidate the efficacy of flow diverter (FD) designs and the mechanisms behind observed complications. The purpose of this study is to demonstrate the feasibility of implanting a FD in a sidewall aneurysm rat model. An end-to-side anastomosis was created in the abdominal aorta of 36 rats using a decellularized donor pouch. A FD was subsequently implanted. After up to 3 months of follow-up, we observed that rats displayed normal growth and behavior. Mortality within the groups was low (2 rats, 5.6%). All aneurysms thrombosed after FD implantation and showed progressive soft tissue replacement of the thrombus during follow-up. The abdominal aortas remained patent. This model can be used to test the effects of FDs in future studies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  18. [Effects of milkvetch root on neuro-endocrino-immune network in asthma model rat].

    Science.gov (United States)

    Dong, Jing-cheng; Zhao, Fu-dong; Xie, Jin-yu

    2007-07-01

    To study the change and the effect of milkvetch root (MR) on neuro-endocrino-immune (NEI) network related indexes in repeated asthmatic attack model rats. Rats were randomly divided into five groups: the normal group (A), the model group (B), and the three treated groups (C, D, E) treated with low, medium and high dose of the MR by gastrogavage. The corticotropin releasing hormone (CRH) mRNA expression in hypothalamus was tested by Realtime-PCR, serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were detected with radioimmunoassay, serum IL-6, IL-4, IFN-gamma determined with enzyme-linked immunosorbent assay, and the lung tissue pathology was examined by hematoxylin and eosin staining. As compared with the normal group, in the rats 3 weeks after modeling, CRH mRNA expression, blood IFN-gamma and plasma ACTH were unchanged, serum level of CORT raised significantly (P<0.05), IL-6 and IL-4 showed an increasing trend but without significance. Low dose of MR could promote the production of serum CORT, and hight dose of MR could down-regulate the concentrations of IL-4 and IL-6 (P<0.01). No significant difference was found in comparison of pathological changes of lung tissue among the groups. Rats suffered from repeated asthmatic attack have some disorders in indexes of NEI, MR could enhance the function of hypothalamic-pituitary-adrenal cortex axis and adjust the balance of Th1 and Th2 cytokines to alleviate the inflammation of asthma.

  19. Comparison between resveratrol and cabergoline in preventing ovarian hyperstimulation syndrome in a rat model.

    Science.gov (United States)

    Kasap, Esin; Turan, Gülizar Arzu; Eskicioğlu, Fatma; Cengiz, Hakan; Gur, Esra Bahar; Sivrikoz, Oya Nermin; Genc, Mine; Yılmaz, Osman

    2016-08-01

    The aim of this study is to investigate the effects of resveratrol in a rat model of ovarian hyperstimulation syndrome (OHSS) and compare with cabergoline. Randomized controlled, animal study. Female Wistar rats. A rat OHSS model was used to investigate the effects of resveratrol compare with cabergoline administration for preventing OHSS. Body weight, ovary weight, diameter, vascular permeability (VP), vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2) expression (immunohistochemistry), and serum estradiol (E2) levels were then compared. The ovarian VEGF concentration was significantly increased in the OHSS Groups (Groups 3-5) compared with the control groups (1 and 2). But vascular permeability, VEGF, and COX-2 expressions were reduced in animals treated with the resveratrol group compared with the cabergoline group (group 5) and the severe OHSS (group 3) group. Blood E2 levels were decreased in group treated with the resveratrol group compared with the cabergoline group (group 5) and severe the OHSS (group 3) group. Our results in a rat model suggest that resveratrol has a beneficial effect on OHSS by reducing the increases in ovarian daimeter, VP, and VEGF expression associated with OHSS. These effects may be mediated by the COX-2 inhibitory capacity of resveratrol.

  20. Neuroprotective Effects of Ellagic Acid in a Rat Model of Parkinson's Disease

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    Alireza Sarkaki

    2016-09-01

    Full Text Available Antioxidants have protective effects against free radicals-induced neural damage in Parkinson's disease (PD. We examined the effects of ellagic acid (EA on locomotion, pallidal local EEG, and its frequency bands' power and also cerebral antioxidant contents in a rat model of PD induced by 6-hydroxidopamine (6-OHDA. 6-OHDA (16 µg/2µ l was injected into the right medial forebrain bundle (MFB in MFB-lesioned rat's brain. Sham group received vehicle instead of 6-OHDA. PD-model was confirmed by rotational test using apomorphine injection. EA (50 mg/kg/2 ml, by gavages was administered in PD+EA group. One group of MFB-lesioned rats received pramipexole (PPX; 2 mg/kg/2 ml, by gavages as a positive control group (PD+PPX group. Motor activity was assessed by stride length, rotarod, and cylinder tests. Pallidal local EEG was recorded in freely moving rats. The levels of malondialdehyde (MDA besides Glutathione peroxidase (GPx and superoxide dismutase (SOD activities were measured in both striatum and hippocampus tissues. MFB lesion caused significant reduction of stride-length (P<0.001, bar decent latency (P<0.001 and frequency bands' power of pallidal EEG (P<0.001. Use of 6-OHDA caused a reduction in the GPx (P<0.001 and SOD (P<0.001 activities while increased significantly the levels of MDA (P<0.001 in MFB-lesioned rats. EA significantly restored all above parameters. The results show that EA can improve the motor impairments and electrophysiological performance in the MFB-lesioned rats via raising the cerebral antioxidant contents. Therefore, EA can protect the brain against free radicals-induced neural damage and may be beneficial in the treatment of PD.

  1. Exercises in hot and humid environment caused liver injury in a rat model.

    Directory of Open Access Journals (Sweden)

    DongLiang Li

    Full Text Available To investigate injury pattern during intense exercises in hot and humid environment particularly on liver in a rat exertional heat stroke model.We randomly divided 30 rats into a control group (CG, a normal temperature (25±2°C, 60%±5% humidity exercise group (NTEG and a high temperature and high humidity (35±2°C, 80%±10% humidity exercising group (HTEG, each comprising 10 animals. The NTEG and HTEG rats were forced to run in a treadmill for 1 hour maximum at 20 rpm. We analyzed liver cells of all three groups with JC-1 dye and flow cytometry for apoptosis rates in addition to liver tissue 8 - hydroxy deoxyguanosine (8 - OhdG and blood serum IL-6, tumor necrosis factor alpha (TNF-α, alanine aminotransferase ALT, aspartate amino transferase (AST, serum creatinine (CREA, blood urea nitrogen (BUN, lactate dehydrogenase (LDH, creatine phosphate kinase (CK concentrations.Compared with NTEG rats, beside reduced exercise tolerance (60±5 vs. 15±3 minutes (p = 0.002 the 8-OhdG liver tissue concentrations were significantly higher (p = 0.040 in the HTEG rats. The HTEG developed more organ tissue damage and cellular fragmentations of liver cells. In both exercise groups TNF-α and IL-6 serum concentrations were enhanced significantly (p<0.001 being highest in the HTEG animals. Serum ALT, AST, LDH, CREA, BUN and CK concentrations were significantly enhance in both exercise groups.In our exertional heat stroke rat model, we found tissue damage particularly in livers during exercises in hot and humid environment that was related to inflammation, oxidative stress and apoptosis.

  2. Wistar rats: A forgotten model of age-related hearing loss

    Directory of Open Access Journals (Sweden)

    Juan Carlos eAlvarado

    2014-03-01

    Full Text Available Age-related hearing loss (ARHL is one of the most frequent sensory impairments in senescence and is a source of important socio-economic consequences. Understanding the pathological responses that occur in the central auditory pathway of patients who suffer from this disability is vital to improve its diagnosis and treatment. Therefore, the goal of this study was to characterize age-related modifications in auditory brainstem responses (ABR and to determine whether these functional responses might be accompanied by an imbalance between excitation and inhibition in the cochlear nucleus of Wistar rats. To do so, ABR recordings at different frequencies and immunohistochemistry for the vesicular glutamate transporter 1 (VGLUT1 and the vesicular GABA transporter (VGAT in the ventral cochlear nucleus (VCN were performed in young, middle-aged and old male Wistar rats. The results demonstrate that there was a significant increase in the auditory thresholds, a significant decrease in the amplitudes and an increase in the latencies of the ABR waves as the age of the rat increased. Additionally, there were decreases in VGLUT1 and VGAT immunostaining in the VCN of older rats compared to younger rats. Therefore, the observed age-related decline in the magnitude of auditory evoked responses might be due in part to a reduction in markers of excitatory function; meanwhile, the concomitant reduction in both excitatory and inhibitory markers might reflect a common central alteration in animal models of ARLH. Together, these findings highlight the suitability of the Wistar rat as an excellent model to study ARHL.

  3. Neuroprotective Effects of Ellagic Acid in a Rat Model of Parkinson's Disease.

    Science.gov (United States)

    Sarkaki, Alireza; Farbood, Yaghoob; Dolatshahi, Mojtaba; Mansouri, Seyed Mohammad Taqhi; Khodadadi, Ali

    2016-08-01

    Antioxidants have protective effects against free radicals-induced neural damage in Parkinson's disease (PD). We examined the effects of ellagic acid (EA) on locomotion, pallidal local EEG, and its frequency bands' power and also cerebral antioxidant contents in a rat model of PD induced by 6-hydroxidopamine (6-OHDA). 6-OHDA (16 µg/2µ l) was injected into the right medial forebrain bundle (MFB) in MFB-lesioned rat's brain. Sham group received vehicle instead of 6-OHDA. PD-model was confirmed by rotational test using apomorphine injection. EA (50 mg/kg/2 ml, by gavages) was administered in PD+EA group. One group of MFB-lesioned rats received pramipexole (PPX; 2 mg/kg/2 ml, by gavages) as a positive control group (PD+PPX group). Motor activity was assessed by stride length, rotarod, and cylinder tests. Pallidal local EEG was recorded in freely moving rats. The levels of malondialdehyde (MDA) besides Glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were measured in both striatum and hippocampus tissues. MFB lesion caused significant reduction of stride-length (P<0.001), bar decent latency (P<0.001) and frequency bands' power of pallidal EEG (P<0.001). Use of 6-OHDA caused a reduction in the GPx (P<0.001) and SOD (P<0.001) activities while increased significantly the levels of MDA (P<0.001) in MFB-lesioned rats. EA significantly restored all above parameters. The results show that EA can improve the motor impairments and electrophysiological performance in the MFB-lesioned rats via raising the cerebral antioxidant contents. Therefore, EA can protect the brain against free radicals-induced neural damage and may be beneficial in the treatment of PD.

  4. Antiallodynic effects of vitamin C and vitamin E in chronic post-ischemia pain rat model

    Science.gov (United States)

    Park, Jun-Mo; Kim, Chae Kyung; Lee, Hyung Chul; Jung, Hoon; Choi, Kwang-Uk; Hong, Seong Wook; Lim, Dong Gun; Baek, Woon-Yi

    2013-01-01

    Background Recent research has shown that reactive oxygen species (ROS) play a significant role in the development and persistence of neuropathic pain through central sensitization via N-methyl-D-aspartate (NMDA) receptor activation. In the present study, we examined whether the intraperitoneal administration of vitamins C and E alone or together could alleviate mechanical allodynia in a chronic post-ischemia pain (CPIP) rat model. Methods Vitamins C and E were administered intraperitoneally to 48 male Sprague Dawley rats once per day for 3 days before hindpaw ischemia-reperfusion (I/R) injury was induced. On the third day, the CPIP rat model was produced by inducing ischemia in the left hindpaw by applying an O-ring for 3 h, followed by reperfusion. Three days after reperfusion, hindpaw mechanical allodynia was assessed by measuring the withdrawal response to von Frey filament stimulation. The rats were sacrificed immediately after behavioral testing to determine the phosphorylated NMDA receptor subunit 1 (pNR1) and extracellular-signal-regulated kinases (pERK) levels in the spinal cord. Results When the antioxidant vitamins C and E were administered intraperitoneally to CPIP rats, I/R injury-induced mechanical allodynia was attenuated, and pNR1 and pERK levels were decreased in the rat spinal cord. Additionally, the co-administration of both vitamins had an increased antiallodynic effect. Conclusions The reduced phosphorylated NR1 and ERK levels indicate that vitamins C and E inhibit the modulation of spinal cord neuropathic pain processing. Co-administration of vitamins C and E had a greater antiallodynic effect. PMID:24363848

  5. mRNA expression profile of prostaglandin D2 receptors in rat trigeminovascular system, and effect of prostaglandins in rat migraine models

    DEFF Research Database (Denmark)

    Sekeroglu, A.; Jansen-Olesen, I.; Gupta, S.

    2015-01-01

    processing structures in rat brain; 2.) To study the effect of the DP1 receptor antagonist, MK-0524, on PGD2-induced vasodilation of middle meningeal artery (MMA) in rat closed cranial window (CCW) model; 3.) To investigate if an i.v. infusion of prostaglandin (PG) mix, PGD2, PGE2 and PGI2 (iloprost...... receptor was highly expressed in trigeminal ganglion and dorsal rootganglion. MK-0524 significantly (62%, pMMA. No increase in p-ERK protein level was observed in the TVS after infusion of PG mix in awake rats. Neuronal activation markers, cFOS and EGR-1, were...... not changed in the trigeminal nucleus caudalis. Conclusions: PGD2 induced vasodilation of MMA is mainly mediated by activation of DP1 receptors. Furthermore, high expression of DP1 mRNA in TG and DRG suggest that PGD2 might play a role in migraine pathophysiology. However, infusion of PG mix in awake rats did...

  6. Involvement of NGF in the Rat Model of Persistent Muscle Pain Associated With Taut Band

    OpenAIRE

    Li, Jun; Yi, Shuang-Qin; Wang, Heng-Xiao; Yi, Nozomi; Ogawa, Yuki; OZAKI, NORIYUKI; Itoh, Masahiro

    2011-01-01

    Myofascial pain syndrome (MPS) is an important clinical condition characterized by chronic muscle pain and a myofascial trigger point (MTrP) located in a taut band (TB). However, its pathogenic mechanism is still unclear. We developed an animal model relevant to conditions of MPS, and analyzed the mechanism of the muscle pain in this model. We applied eccentric contraction (EC) to a rat's gastrocnemius muscle (GM) for 2 weeks, and examined the mechanical withdrawal thresholds, histological ch...

  7. A cell culture model using rat coronary artery adventitial fibroblasts to measure collagen production

    OpenAIRE

    Meszaros Gary; Doane Kathleen; Milsted Amy; Jenkins Cathleen; Toot Jonathan; Ely Daniel

    2007-01-01

    Abstract Background We have developed a rat cell model for studying collagen type I production in coronary artery adventitial fibroblasts. Increased deposition of adventitial collagen type I leads to stiffening of the blood vessel, increased blood pressure, arteriosclerosis and coronary heart disease. Although the source and mechanism of collagen deposition is yet unknown, the adventitia appears to play a significant role. To demonstrate the application of our cell model, cultured adventitial...

  8. The rat as a model to evaluate the gastric irritation potential of alkaline products.

    Science.gov (United States)

    Sauers, L J; Maurer, J K; Reer, P J

    1994-01-01

    Animal models historically used to assess the acute gastric irritation potential of accidental ingestion of consumer products include the dog, pig, rabbit, and cat. In looking at alternative methods that are of shorter duration and more cost-effective, the rat is being evaluated as a potential model. Acute gastric irritation is known to increase as the reserve alkalinity of the formulation increases. In initial experiments to assess the rat as a potential model, animals were dosed via oral gavage with 1 of 4 formulations ranging in reserve alkalinity from 4.0 to 10.8. Necropsies were performed at 15 and 60 min after dosing. Macroscopic and microscopic evaluations of the stomach revealed morphological differences in the various treatment groups that distinguish granular formulations having either a low (R.A. = 4.0), moderate (R.A. = 7.1), or higher (R.A. = 10.8) reserve alkalinity. Additionally, it was observed that the acute gastric changes in rats dosed with a liquid formulation having a low (R.A. = 4.2) reserve alkalinity were similar to those in rats dosed with a granular formulation having a moderate reserve alkalinity (R.A. = 7.1). This suggests that other factors such as types of ingredients, pH, and physical form influence the extent of acute gastric irritation and demonstrates that an evaluation of only reserve alkalinity is not sufficient to ensure the safety of these products. This preliminary work supports the rat as a potential model to assess the acute gastric irritation potential of alkaline formulations or substances.

  9. Effect of exercise on learning and memory in a rat model of developmental stress.

    Science.gov (United States)

    Grace, Laurian; Hescham, Sarah; Kellaway, Lauriston A; Bugarith, Kishor; Russell, Vivienne A

    2009-12-01

    Adverse life events occurring in early development can result in long-term effects on behavioural, physiological and cognitive processes. In particular, perinatal stressors impair neurogenesis in the hippocampus which consequently impairs memory formation. Exercise has previously been shown to have antidepressant effects and to increase cognitive functioning by increasing neurogenesis and neurotrophins in the hippocampus. The current study examined the effects of maternal separation, which has been shown to model anxiety in animals, and the effects of exercise on learning and memory. Forty-five male Sprague-Dawley rats were divided into four groups, maternally separated / non-runners, maternally separated / runners, non-separated / runners and non-separated / non-runners. Maternal separation occurred from postnatal day 2 (P2) to 14 (P14) for 3 h per day. Exercised rats were given voluntary access to individual running wheels attached to their cages from P29 to P49. Behavioural testing (Morris water maze (MWM) and object recognition tests) took place from P49 to P63. Maternally separated rats showed no significant difference in anxiety levels in the elevated plus maze and the open field compared to the normally reared controls. However, rats that were allowed voluntary access to running wheels showed increased levels of anxiety in the elevated plus maze and in the open field. Maternal separation did not have any effect on memory performance in the MWM or the object recognition tasks. Exercise increased spatial learning and memory in the MWM with the exercised rats displaying a decreased latency in locating the hidden platform than the non-exercised rats. The exercised rats spent significantly less time exploring the most recently encountered object in the temporal order task in comparison to the non-exercised controls, therefore showing improved temporal recognition memory. All groups performed the same on the other recognition tasks, with all rats showing intact

  10. Development of a Stepping Force Analgesic Meter for a Rat Arthritic Model

    Directory of Open Access Journals (Sweden)

    Sook Yee Hor

    2011-05-01

    Full Text Available Behavioural assessment of experimental pain is an essential method for analysing and measuring pain levels. Rodent models, which are widely used in behavioural tests, are often subject to external forces and stressful manipulations that cause variability of the parameters measured during the experiment. Therefore, these parameters may be inappropriate as indicators of pain. In this article, a stepping-force analgesimeter was designed to investigate the variations in the stepping force of rats in response to pain induction. The proposed apparatus incorporates new features, namely an infrared charge-coupled device (CCD camera and a data acquisition system. The camera was able to capture the locomotion of the rats and synchronise the stepping force concurrently so that each step could be identified. Inter-day and intra-day precision and accuracy of each channel (there were a total of eight channels in the analgesimeter and each channel was connected to one load cell and one amplifier were studied using different standard load weights. The validation studies for each channel also showed convincing results whereby intra-day and inter-day precision were less than 1% and accuracy was 99.36–100.36%. Consequently, an in vivo test was carried out using 16 rats (eight females and eight males. The rats were allowed to randomly walk across the sensor tunnel (the area that contained eight channels and the stepping force and locomotion were recorded. A non-expert, but from a related research domain, was asked to differentiate the peaks of the front and hind paw, respectively. The results showed that of the total movement generated by the rats, 50.27 ± 3.90% in the case of the male rats and 62.20 ± 6.12% in that of the female rats had more than two peaks, a finding which does not substantiate the assumptions made in previous studies. This study also showed that there was a need to use the video display frame to distinguish between the front and hind paws in