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Sample records for 6-ohda rat model

  1. Neurosteroid allopregnanolone attenuates cognitive dysfunctions in 6-OHDA-induced rat model of Parkinson's disease.

    Nezhadi, Akram; Sheibani, Vahid; Esmaeilpour, Khadijeh; Shabani, Mohammad; Esmaeili-Mahani, Saeed

    2016-05-15

    Cognitive deficits have an extensive influence on the quality of life of the Parkinson's disease (PD) patients. Previous studies have shown that lack of steroid hormones have an important role in the development of PD. Therefore, in this study the effects of neurosteroid allopregnanolone (Allo) on the PD-induced cognitive disorders were assessed. To simulate PD, 6-hydroxydopamine (6-OHDA) was injected into the rat's substantia nigra. Allo (5 and 20mg/kg, orally) were administered on the day after the 6-OHDA injection and continued during the entire treatment period (two months). Cognitive behaviors were assessed by Moris water maze (MWM), novel object recognition (NOR) and object location tasks. The data indicated that Allo significantly improved the 6-OHDA-induced cognitive impairment which revealed by the reduction of time spent to find out platform (escape latency) and the increase of retention time in MWM test and also with increase in the exploration index in NOR and object location tasks. Present study strongly supports the pro-cognitive property of allopregnanolone in PD. PMID:26970579

  2. Caffeine improves attention deficit in neonatal 6-OHDA lesioned rats, an animal model of attention deficit hyperactivity disorder (ADHD).

    Caballero, Miguel; Núñez, Fabiana; Ahern, Siobhán; Cuffí, Maria L; Carbonell, Lourdes; Sánchez, Silvia; Fernández-Dueñas, Víctor; Ciruela, Francisco

    2011-04-20

    Nowadays the pharmacological treatment of the attention deficit hyperactivity disorder (ADHD) is based on amphetamine derivatives (i.e. methylphenidate). However, these drugs induce a large array of adverse side effects, thus less aggressive psychostimulant drugs (i.e. caffeine) are being proposed in the management of ADHD. Following this tendency, we decided to study the possible therapeutic use of caffeine in an animal model of ADHD, namely the neonatal 6-hydroxy-dopamine (6-OHDA)-lesioned rat. Therefore, at postnatal day 7 rats were lesioned at the left striatum with 6-OHDA or with saline. Thereafter, at postnatal day 25 their activity and attention were measured with the Olton maze before caffeine was administered ad libitum in the drinking water. Next, after 14 days of caffeine treatment, we repeated these measurements to assess the effect of caffeine on motor activity and attention deficit. Interestingly, while no changes in the motor activity measurements were observed before and after caffeine administration, a significant improvement in the attention deficit of the 6-OHDA lesioned rats was achieved after caffeine treatment. Thus, our results led us to hypothesize that caffeine might be useful to manage the attention deficit during the prepubertal period of ADHD. PMID:21362462

  3. Behavioral and Neurochemical Effects of Alpha-Lipoic Acid in the Model of Parkinson’s Disease Induced by Unilateral Stereotaxic Injection of 6-Ohda in Rat

    Dayane Pessoa de Araújo; Caren Nádia Soares De Sousa; Paulo Victor Pontes Araújo; Carlos Eduardo de Souza Menezes; Francisca Taciana Sousa Rodrigues; Sarah de Souza Escudeiro; Nicole Brito Cortez Lima; Manoel Claúdio Azevedo Patrocínio; Lissiana Magna Vasconcelos Aguiar; Glauce Socorro de Barros Viana; Silvânia Maria Mendes Vasconcelos

    2013-01-01

    This study aimed to investigate behavioral and neurochemical effects of α -lipoic acid (100 mg/kg or 200 mg/kg) alone or associated with L-DOPA using an animal model of Parkinson's disease induced by stereotaxic injection of 6-hydroxydopamine (6-OHDA) in rat striatum. Motor behavior was assessed by monitoring body rotations induced by apomorphine, open field test and cylinder test. Oxidative stress was accessed by determination of lipid peroxidation using the TBARS method, concentration of ni...

  4. Behavioral and Neurochemical Effects of Alpha-Lipoic Acid in the Model of Parkinson’s Disease Induced by Unilateral Stereotaxic Injection of 6-Ohda in Rat

    Dayane Pessoa de Araújo

    2013-01-01

    Full Text Available This study aimed to investigate behavioral and neurochemical effects of α-lipoic acid (100 mg/kg or 200 mg/kg alone or associated with L-DOPA using an animal model of Parkinson’s disease induced by stereotaxic injection of 6-hydroxydopamine (6-OHDA in rat striatum. Motor behavior was assessed by monitoring body rotations induced by apomorphine, open field test and cylinder test. Oxidative stress was accessed by determination of lipid peroxidation using the TBARS method, concentration of nitrite and evaluation of catalase activity. α-Lipoic acid decreased body rotations induced by apomorphine, as well as caused an improvement in motor performance by increasing locomotor activity in the open field test and use of contralateral paw (in the opposite side of the lesion produced by 6-OHDA at cylinder test. α-lipoic acid showed antioxidant effects, decreasing lipid peroxidation and nitrite levels and interacting with antioxidant system by decreasing of endogenous catalase activity. Therefore, α-lipoic acid prevented the damage induced by 6-OHDA or by chronic use of L-DOPA in dopaminergic neurons, suggesting that α-lipoic could be a new therapeutic target for Parkinson's disease prevention and treatment.

  5. Reduced expression of choline acetyltransferase in vagal motoneurons and gastric motor dysfunction in a 6-OHDA rat model of Parkinson's disease.

    Zheng, Li-Fei; Wang, Zhi-Yong; Li, Xiao-feng; Song, Jin; Hong, Feng; Lian, Hui; Wang, Qian; Feng, Xiao-Yan; Tang, Yuan-yuan; Zhang, Yue; Zhu, Jin-Xia

    2011-10-28

    Parkinson's disease (PD) has been characterized by dopaminergic neuron degeneration in the substantia nigra (SN) accompanied by pathology of the dorsal motor nucleus of the vagus (DMV). PD patients have often experienced gastrointestinal dysfunctions, such as gastroparesis. However, the mechanism underlying these symptoms in PD patients is not clear. In the present study, we investigated alterations of cholinergic and catecholaminergic neurons in the DMV and gastric motor function in rats microinjected with 6-hydroxydopamine (6-OHDA) bilaterally into the SN (referred to as 6-OHDA rats) and explored possible mechanisms. A strain gauge force transducer was used to record gastric motility in vivo. Expression of choline acetyltransferase (ChAT) and tyrosine hydroxylase (TH) was evaluated by immunofluorescence and western blot analysis. Acetylcholine (Ach) content was measured using ultra-performance liquid chromatography tandem mass spectrometry (UPLC/MS/MS) analysis. After treatment with 6-OHDA for 6weeks, 6-OHDA rats exhibited decreased ChAT and enhanced TH expression in the DMV and decreased Ach content in the gastric muscular layer. Delayed gastric emptying and impaired gastric motility in vivo were observed in 6-OHDA rats. The results of the present study indicated that decreased ChAT and enhanced TH expression in the DMV may be correlated with the development of delayed gastric emptying and impaired gastric motility, which may be partly due to the decreased Ach release from the vagus. PMID:21955729

  6. 6-羟基多巴胺致帕金森病大鼠模型的建立与评价%The Establishment and Evaluation of Rats Model of the Parkinson's Disease Cased by 6-OHDA

    李泽鸿; 陶英楠; 刘继阳; 张帆

    2012-01-01

    应用6-羟基多巴胺(6-hydroxydopamine,6-OHDA)制造帕金森病(Parkinson,s disease,PD)大鼠模型,建模成功后采用组织化学方法检测模型黑质多巴胺能神经元变化,并从行为学及黑质多巴胺能神经元数目的变化对模型进行综合评价.取Wistar大鼠,采用立体定向法,进行右侧纹状体区6-OHDA双点注射.结果表明,6-OHDA纹状体注射可成功的诱导帕金森大鼠模型.%Appplicate the 6-hydroxydopanine (6-OHDA) to manufacture the rat's model of Parkinson's disease (PD), through the organizations of chemical method could dectect and evaluate the model comprehensivly from the changes of the behaviour and the number changes of dopaminergic neurons of nigra after the model succeed. Fetch Wistar rat by using stereotac-tic method, and then inject right striatum 6-OHDA into two-point. This study showed that 6-OHDA injection striatum could induce the rat model of Parkinson's sucessfully.

  7. Antagonism of quercetin against tremor induced by unilateral striatal lesion of 6-OHDA in rats.

    Mu, Xin; Yuan, Xia; Du, Li-Da; He, Guo-Rong; Du, Guan-Hua

    2016-01-01

    Quercetin, a flavonoid present in many plants, is reported to be effective in models of neurodegenerative diseases. The aim of the present study was to evaluate the anti-tremor effects of quercetin in 6-hydroxydopamine (6-OHDA)-induced rat model of Parkinson's disease. In rats, quercetin had no effect on apomorphine-induced rotations, but it could significantly attenuate muscle tremor of 6-OHDA lesioned rats. Interestingly, quercetin could decrease the burst frequency in a dose- and time-dependent manner. These results suggest that quercetin may have a protective effect on models to mimic muscle tremors of Parkinson's disease. This effect of quercetin may be associated with serotonergic system, but further study is needed. PMID:26217978

  8. Fetal Mesencephalic Neuron Transplantation and Tyrosine Hydroxylase Gene Therapy for Monkey and Rat Models of Parkinsonism Induced By MPTP or 6OHDA

    Shengdi Chen; Yingchun Zhao; Huizhen Yu; Zhenguo Liu; Lei Cao; hongcheng Zheng; Xingyuan Liu; Zhihua Jiang; Changfu Zhou

    2000-01-01

    @@The intracerebral transplantation and gene therapy may provide putative therapeutic approach to Parkinson′s disease. In the present study, implant of fetal mesencephalic dopamine neuron into I-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced hemiparkinsonian monkey model and in vivo and ex vivo tyrosine hydroxylase(TH) gene therapy for 6-hydroxydopamine(6-OHDA)-induced hemiparkinsonian rat model were investigated. The monkey model of hemiparkinsonism induced by unilateral administration of MPTP into the common carotid artery of three rhesus monkeys. The cell suspensions of substantia nigra obtained from human fetus of 11-12 weeks of gestation were injected stereotaxically into the caudate nucleus or substantia nigra of the lesioned side. The recipients were immunosuppressed by taking cyclosporine A for one month following the implant procedure. Apomorphine(APO)-induced motor asymmetry was significantly improved during the period of 18 weeks after graft. TH immunostaining assay demonstrated the surviving and sprouting of TH-immunoreactive cell bodies in the caudate nucleus for almost one year.

  9. Neuroprotective effect of Spirulina fusiform and amantadine in the 6-OHDA induced Parkinsonism in rats

    Chattopadhyaya, I.; Gupta, Sumeet; Mohammed, Asad; Mushtaq, N.; Chauhan, S.; Ghosh, Saikant

    2015-01-01

    Background Multi-factorial etiology exists in pathophysiology of neurodegenerative diseases. The imbalance of anti-oxidant enzymes and dopamine level leads to Parkinsonism. The objective of this study was to assess the protective effect of Spirulina fusiform alone and in combination with amantadine against Parkinsonism effect in 6-hydroxydopamine (6-OHDA) induced rat model. Methods S. fusiform was administered in different groups (500 mg/kg, once daily and twice daily) and a combination of sp...

  10. Transplantation of Deprenyl-Induced Tyrosine Hydroxylase-Positive Cells Improves 6-OHDA-Lesion Rat Model of Parkinson’s Disease: Behavioral and Immunohistochemical Evaluation

    Leili Hosseinpour

    2013-01-01

    Full Text Available Objective: There is longstanding experimental and clinical evidence that supports the idea that replacement of dopaminergic (DAergic neurons can ameliorate functional disabilities of Parkinson’s disease (PD. The purpose of the present study is to examine the efficacy of transplantation of rat bone marrow stromal cell (BMSCs-derived tyrosine hydroxylase-positive (TH+ cells induced by deprenyl into 6-hydroxydopamine (6-OHDA-lesioned rat models, using behavioral tests and immunohistochemical evaluations.Materials and Methods: In this experimental study, undifferentiated BrdU-labeled BMSCs were incubated in serum-free medium that contained 10-8 M deprenyl for 24 hours. Afterwards, BMSCs were cultured for 48 hours in α-minimal essential medium (α-MEM supplemented with 10% FBS, then differentiated into TH+ neurons. We randomly divided 24 hemiparkinsonian rats as follows: group 1 (control received only medium, while groups 2 and 3 were injected with 2×105 BMSCs and deprenyl-treated cells in 4 μl medium. Injections were made into the injured strata of the rats. Rotational behavior in response to apomorphine was tested before transplantation and at 2, 4, and 6 weeks post-graft. Animals were then sacrificed, and the brains were extracted for immunohistochemical and electron microscopic studies.Results: Apomorphine-induced rotation analysis indicated that animals with grafted cells in groups 2 and 3 exhibited significantly less rotational behavior than those in the control group at 2, 4, and 6 weeks after transplantation. Immunohistochemical analysis demonstrated that BrdU-labeled cells expressed specific neuronal markers, such as NF 200 and TH, at the implantation site. The presence of TH+ cells in conjunction with the reduction in rotation might show the capacity of grafted cells to release dopamine. Ultrastructural analysis revealed the presence of immature neurons and astrocyte-like cells at the graft site.Conclusion: TH+ neurons induced by

  11. Dopaminergic mechanisms underlying bladder hyperactivity in rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal pathway

    Yoshimura, Naoki; Kuno, Sadako; Chancellor, Michael B.; de Groat, William C.; Seki, Satoshi

    2003-01-01

    This study was undertaken to elucidate dopaminergic mechanisms underlying bladder hyperactivity in a rat model of Parkinson's disease (PD) induced by a unilateral 6-OHDA injection into the substantia nigra pars compacta.In 6-OHDA-lesioned rats, voided volume per micturition (0.41±0.04 ml, mean±s.e.m.) measured during 24 h in a metabolic cage was significantly smaller than in sham-operated rats (0.67±0.07 ml).Cystrometrograms (CMG) in conscious animals revealed significantly smaller bladder ca...

  12. Effects of L-Dopa on circadian rhythms of 6-OHDA striatal lesioned rats: a radiotelemetric study.

    Boulamery, Audrey; Simon, Nicolas; Vidal, Johanna; Bruguerolle, Bernard

    2010-01-01

    Temporal variation in the motor function of Parkinson's disease (PD) patients suggests the potential importance of a chronobiological and chronopharmacological approach in its clinical management. We previously documented the effects of striatal injection of 6-OHDA (as an animal model of PD) on the circadian rhythms of temperature (T), heart rate (HR), and locomotor activity (A). The present work assessed the possible influence of L-Dopa on these same rhythms in the 6-OHDA animal model of PD. The study began after a four-week recovery period following surgical implantation of telemetric devices to monitor the study variables and/or anaesthesia. The study was divided into an initial one-week control period (W1) for baseline measurement of T, HR, and A rhythms. Thereafter, stereotaxic 6-OHDA lesioning was done. and a second monitoring for two weeks followed (W2, W3). Rats were then randomly divided into two groups: eight control rats received, via a mini-osmotic pump implanted subcutaneously, the excipient saline; the other eight rats received L-Dopa (100 mg/kg SC/day). After a seven-day period (W4), the pumps were removed and the T, HR, and A rhythms were monitored for two weeks (W5 and W6). To control for 6-OHDA striatal dopamine-induced depletion, 12 other rats were injected by identical methods (eight rats with 6-OHDA and four controls with saline) and sacrificed at W1, W3, and W5 for dopamine striatal content determination. To verify the delivery of levodopa from the osmotic pumps, plasma levels of levodopa and its main metabolites 3-OMD, DOPAC, and HVA were determined on separate group of rats receiving the drug under the same experimental conditions (osmotic pumps delivering continuously 10 microl/h for seven days, 100 mg/kg/subcutaneously). Our results agree with previously reported rhythmic changes induced by 6-OHDA--loss of circadian rhythmicity or changes in the main parameters of the registered rhythms. When circadian rhythmicity was abolished, L

  13. Intranasal insulin protects against substantia nigra dopaminergic neuronal loss and alleviates motor deficits induced by 6-OHDA in rats.

    Pang, Y; Lin, S; Wright, C; Shen, J; Carter, K; Bhatt, A; Fan, L-W

    2016-03-24

    Protection of substantia nigra (SN) dopaminergic (DA) neurons by neurotrophic factors (NTFs) is one of the promising strategies in Parkinson's disease (PD) therapy. A major clinical challenge for NTF-based therapy is that NTFs need to be delivered into the brain via invasive means, which often shows limited delivery efficiency. The nose to brain pathway is a non-invasive brain drug delivery approach developed in recent years. Of particular interest is the finding that intranasal insulin improves cognitive functions in Alzheimer's patients. In vitro, insulin has been shown to protect neurons against various insults. Therefore, the current study was designed to test whether intranasal insulin could afford neuroprotection in the 6-hydroxydopamine (6-OHDA)-based rat PD model. 6-OHDA was injected into the right side of striatum to induce a progressive DA neuronal lesion in the ipsilateral SN pars compact (SNc). Recombinant human insulin was applied intranasally to rats starting from 24h post lesion, once per day, for 2 weeks. A battery of motor behavioral tests was conducted on day 8 and 15. The number of DA neurons in the SNc was estimated by stereological counting. Our results showed that 6-OHDA injection led to significant motor deficits and 53% of DA neuron loss in the ipsilateral side of injection. Treatment with insulin significantly ameliorated 6-OHDA-induced motor impairments, as shown by improved locomotor activity, tapered/ledged beam-walking performance, vibrissa-elicited forelimb-placing, initial steps, as well as methamphetamine-induced rotational behavior. Consistent with behavioral improvements, insulin treatment provided a potent protection of DA neurons in the SNc against 6-OHDA neurotoxicity, as shown by a 74.8% increase in tyrosine hydroxylase (TH)-positive neurons compared to the vehicle group. Intranasal insulin treatment did not affect body weight and blood glucose levels. In conclusion, our study showed that intranasal insulin provided strong

  14. Experimental Study on Early Parkinson's Disease Rat Model Induced by 6-OHDA%6-羟基多巴胺损伤早期帕金森病大鼠模型的实验研究

    沈福玉; 施建生

    2014-01-01

    目的:观察6-羟基多巴胺(6-hydroxydopamine,6-OHDA)损伤早期帕金森病(Parkinson's disease, PD)大鼠行为学及黑质部位组织学的变化特点。方法偏侧前脑内侧束注射6-OHDA,通过阿扑吗啡诱发旋转试验、跨步调节试验和姿势部对称试验评估注射后24 h、7 d及28 d大鼠行为学的变化;通过免疫组织化学染色观察黑质部位酪氨酸羟化酶(tyrosine hydroxylase, TH)阳性细胞计数的变化。结果6-OHDA组大鼠跨步调节试验评分减少,姿势不对称试验评分增加,阿扑吗啡诱发大鼠向损伤对侧旋转,与对照组和假手术组比较统计学差异显著(P<0.05);6-OHDA 7 d组、28 d组与24 h组比较,跨步调节试验评分进一步减少、姿势不对称试验评分进一步增加,阿扑吗啡诱发旋转次数增加,有统计学差异(P<0.05);6-OHDA 24 h组黑质TH阳性细胞减少,与对照组和假手术组比较有统计学差异(P<0.05),7 d组及28 d组TH阳性细胞进一步减少,与24 h组比较统计学差异显著(P<0.05)。结论通过阿扑吗啡诱发旋转结合非药物诱发试验进行行为学评估,可确定偏侧前脑内侧束注射6-OHDA损伤早期帕金森病动物模型。%ObjectiveTo observe the characteristic changes of behaviors and substantia nigra (SN) histology of Parkinson's disease (PD) rat model induced by 6-OHDA. Methods 6-hydroxydopamine (6-OHDA) was injected into the rats' unilateral medial forebrain bundle. The behaviors of the rats on the 24th hour ,7th day and 28th day were assessed by tests of the apomorphine induced rotations, the adjusting steps and the postural asymmetry.The forms and counts of tyrosine hydroxylase positive (TH) cells were surveyed by the immunohistochemistry staining. Results Rats of PD models appeared significant decrease in score of the adjusting steps test, while increase in score of the postural asymmetry test, and rotated to the uninjured side

  15. Gastric dysregulation induced by microinjection of 6-OHDA in the substantia nigra pars compacta of rats is determined by alterations in the brain-gut axis.

    Toti, Luca; Travagli, R Alberto

    2014-11-15

    Idiopathic Parkinson's disease (PD) is a late-onset, chronic, and progressive motor dysfunction attributable to loss of nigrostriatal dopamine neurons. Patients with PD experience significant gastrointestinal (GI) issues, including gastroparesis. We aimed to evaluate whether 6-hydroxy-dopamine (6-OHDA)-induced degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) induces gastric dysmotility via dysfunctions of the brain-gut axis. 6-OHDA microinjection into the SNpc induced a >90% decrease in tyrosine hydroxylase-immunoreactivity (IR) on the injection site. The [13C]-octanoic acid breath test showed a delayed gastric emptying 4 wk after the 6-OHDA treatment. In control rats, microinjection of the indirect sympathomimetic, tyramine, in the dorsal vagal complex (DVC) decreased gastric tone and motility; this inhibition was prevented by the fourth ventricular application of either a combination of α1- and α2- or a combination of D1 and D2 receptor antagonists. Conversely, in 6-OHDA-treated rats, whereas DVC microinjection of tyramine had reduced effects on gastric tone or motility, DVC microinjection of thyrotropin-releasing hormone induced a similar increase in motility as in control rats. In 6-OHDA-treated rats, there was a decreased expression of choline acetyl transferase (ChAT)-IR and neuronal nitric oxide synthase (NOS)-IR in DVC neurons but an increase in dopamine-β-hydroxylase-IR in the A2 area. Within the myenteric plexus of the esophagus, stomach, and duodenum, there were no changes in the total number of neurons; however, the percentage of NOS-IR neurons increased, whereas that of ChAT-IR decreased. Our data suggest that the delayed gastric emptying in a 6-OHDA rat model of PD may be caused by neurochemical and neurophysiological alterations in the brain-gut axis. PMID:25277799

  16. A biophysical model of the cortex-basal ganglia-thalamus network in the 6-OHDA lesioned rat model of Parkinson's disease.

    Kumaravelu, Karthik; Brocker, David T; Grill, Warren M

    2016-04-01

    Electrical stimulation of sub-cortical brain regions (the basal ganglia), known as deep brain stimulation (DBS), is an effective treatment for Parkinson's disease (PD). Chronic high frequency (HF) DBS in the subthalamic nucleus (STN) or globus pallidus interna (GPi) reduces motor symptoms including bradykinesia and tremor in patients with PD, but the therapeutic mechanisms of DBS are not fully understood. We developed a biophysical network model comprising of the closed loop cortical-basal ganglia-thalamus circuit representing the healthy and parkinsonian rat brain. The network properties of the model were validated by comparing responses evoked in basal ganglia (BG) nuclei by cortical (CTX) stimulation to published experimental results. A key emergent property of the model was generation of low-frequency network oscillations. Consistent with their putative pathological role, low-frequency oscillations in model BG neurons were exaggerated in the parkinsonian state compared to the healthy condition. We used the model to quantify the effectiveness of STN DBS at different frequencies in suppressing low-frequency oscillatory activity in GPi. Frequencies less than 40 Hz were ineffective, low-frequency oscillatory power decreased gradually for frequencies between 50 Hz and 130 Hz, and saturated at frequencies higher than 150 Hz. HF STN DBS suppressed pathological oscillations in GPe/GPi both by exciting and inhibiting the firing in GPe/GPi neurons, and the number of GPe/GPi neurons influenced was greater for HF stimulation than low-frequency stimulation. Similar to the frequency dependent suppression of pathological oscillations, STN DBS also normalized the abnormal GPi spiking activity evoked by CTX stimulation in a frequency dependent fashion with HF being the most effective. Therefore, therapeutic HF STN DBS effectively suppresses pathological activity by influencing the activity of a greater proportion of neurons in the output nucleus of the BG. PMID:26867734

  17. 高血糖对6-OHDA诱导的PD模型大鼠行为学的影响%The Effect of Hyperglycemia on the Ethology of 6-OHDA Induced PD Rat Model

    买尔哈巴; 孙景兰; 杨新玲; 贾玉敏; 耿飞飞

    2015-01-01

    Objective On the base of diabetic SD rat model, establish the Parkinson's disease(PD) rat model by two-spot u-nilaterally injection of 6-hydroxydopamine(6-OHDA) into the medial forebrain and evaluate this model in ethology. Meth-ods Ninety SD rats were randomly divided into five groups:normal group (n=5), physiological saline control group (n=10), diabetic group (n=20), PD group (n=20), and hyperglycemia-PD group (n=35). Establish diabetic rat model by high fat and high glucose diet and the intraperitoncal injection of streptozotocin. Establish PD hyperglycemia rat model by two-spot uni-laterally injection with 6-OHDA into the substanianigta parscompact(SNc) and ventral tegmental(VTA) stereotactically. And then ethology analysis (spontaneous behavioral lateralization, posture asymmetry, catalepsy test, revolving test) was conduct-ed at different time (the 7th, 14th, 21st and 28th day). Results There were significant differences in the parameters of spon-taneous behavioral lateralization, posture asymmetry, catalepsy test, revolving test between the PD group, hyperglycemia-PD group and normal group, physiological saline control group, diabetic group(P<0.01). There were significant differences in the parameters of spontaneous behavioral lateralization, catalepsy test between PD group and hyperglycemia-PD group. And the severity of spontaneous behavioral lateralization and rotating ring in PD group and hyperglycemia-PD group increased gradually with time. High blood sugar can not affect the re-volving test. Conclusion The ethological change of rats induced by injection of 6-OHDA increased with hyperglycemia and increased with time.%目的:在建立糖尿病SD大鼠模型的基础上,6-OHDA单侧毁损法建立高血糖-PD大鼠模型,探讨高血糖对PD大鼠行为学的影响。方法90只SD大鼠随机分为正常对照组(n=5),假手术组(n=10),糖尿病组(n=20),PD组(n=20)及高血糖-PD组(n=35)。采用高糖高脂饮食联合一次性腹腔注射链脲

  18. Pentoxifylline Neuroprotective Effects Are Possibly Related to Its Anti-Inflammatory and TNF-Alpha Inhibitory Properties, in the 6-OHDA Model of Parkinson’s Disease

    Kelly Rose Tavares Neves

    2015-01-01

    Full Text Available Pentoxifylline (PTX is a phosphodiesterase inhibitor with anti-TNF-alpha activity, associated with its anti-inflammatory action. Considering Parkinson’s disease (PD as a neuroinflammatory disorder, the objectives were to evaluate PTX neuroprotective properties, in a model of PD. Male Wistar rats, divided into sham-operated (SO, untreated 6-OHDA, and 6-OHDA treated with PTX (10, 25, and 50 mg/kg groups, received a unilateral 6-OHDA injection, except the SO group administered with saline. Treatments started 24 h after surgery and continued for 15 days when the animals were submitted to apomorphine-induced rotations, open field, and forced swimming tests. At the next day, they were euthanized and their striata processed for neurochemical (DA and DOPAC determinations, histological, and immunohistochemical (Fluoro-Jade, TH, DAT, OX-42, TNF-alpha, COX-2, and iNOS studies. PTX reversed the behavioral changes observed in the untreated 6-OHDA animals. Furthermore, PTX partially reversed the decrease in DA contents and improved neuronal viability. In addition, decreases in immunostaining for TH and dopamine transporter (DAT were reversed. The untreated 6-OHDA group showed intense OX-42, TNF-alpha, COX-2, and iNOS immunoreactivities, which were attenuated by PTX. In conclusion, we demonstrated a neuroprotective effect of PTX, possibly related to its anti-inflammatory and antioxidant actions, indicating its potential as an adjunct treatment for PD.

  19. Polysomnographic Features of Sleep Disturbances and REM Sleep Behavior Disorder in the Unilateral 6-OHDA Lesioned Hemiparkinsonian Rat

    Quynh Vo

    2014-01-01

    Full Text Available Sleep pattern disruption, specifically REM sleep behavior disorder (RBD, is a major nonmotor cause of disability in PD. Understanding the pathophysiology of these sleep pattern disturbances is critical to find effective treatments. 24-hour polysomnography (PSG, the gold standard for sleep studies, has never been used to test sleep dysfunction in the standard 6-OHDA lesioned hemiparkinsonian (HP rat PD model. In this study, we recorded 24-hour PSG from normal and HP rats. Recordings were scored into wake, rapid eye movement (REM, and non-REM (NREM. We then examined EEG to identify REM periods and EMG to check muscle activity during REM. Normal rats showed higher wakefulness (70–80% during the dark phase and lower wakefulness (20% during the light phase. HP rats showed 30–50% sleep in both phases, less modulation and synchronization to the light schedule (P<0.0001, and more long run lengths of wakefulness (P<0.05. HP rats also had more REM epochs with muscle activity than control rats (P<0.05. Our findings that the sleep architecture in the HP rat resembles that of PD patients demonstrate the value of this model in studying the pathophysiological basis of PD sleep disturbances and preclinical therapeutics for PD related sleep disorders including RBD.

  20. Valproic Acid Neuroprotection in the 6-OHDA Model of Parkinson's Disease Is Possibly Related to Its Anti-Inflammatory and HDAC Inhibitory Properties.

    Ximenes, José Christian Machado; Neves, Kelly Rose Tavares; Leal, Luzia Kalyne A M; do Carmo, Marta Regina Santos; Brito, Gerly Anne de Castro; Naffah-Mazzacoratti, Maria da Graça; Cavalheiro, Ésper Abrão; Viana, Glauce Socorro de Barros

    2015-01-01

    Parkinson's disease is a neurodegenerative disorder where the main hallmark is the dopaminergic neuronal loss. Besides motor symptoms, PD also causes cognitive decline. Although current therapies focus on the restoration of dopamine levels in the striatum, prevention or disease-modifying therapies are urgently needed. Valproic acid (VA) is a wide spectrum antiepileptic drug, exerting many biochemical and physiological effects. It has been shown to inhibit histone deacetylase which seems to be associated with the drug neuroprotective action. The objectives were to study the neuroprotective properties of VA in a model of Parkinson's disease, consisting in the unilateral striatal injection of the neurotoxin 6-OHDA. For that, male Wistar rats (250 g) were divided into the groups: sham-operated (SO), untreated 6-OHDA-lesioned, and 6-OHDA-lesioned treated with VA (25 or 50 mg/kg). Oral treatments started 24 h after the stereotaxic surgery and continued daily for 2 weeks, when the animals were subjected to behavioral evaluations (apomorphine-induced rotations and open-field tests). Then, they were sacrificed and had their mesencephalon, striatum, and hippocampus dissected for neurochemical (DA and DOPAC determinations), histological (Fluoro-Jade staining), and immunohistochemistry evaluations (TH, OX-42, GFAP, TNF-alpha, and HDAC). The results showed that VA partly reversed behavioral and neurochemical alterations observed in the untreated 6-OHDA-lesioned rats. Besides, VA also decreased neuron degeneration in the striatum and reversed the TH depletion observed in the mesencephalon of the untreated 6-OHDA groups. This neurotoxin increased the OX-42 and GFAP immunoreactivities in the mesencephalon, indicating increased microglia and astrocyte reactivities, respectively, which were reversed by VA. In addition, the immunostainings for TNF-alpha and HDAC demonstrated in the untreated 6-OHDA-lesioned rats were also decreased after VA treatments. These results were

  1. Valproic Acid Neuroprotection in the 6-OHDA Model of Parkinson’s Disease Is Possibly Related to Its Anti-Inflammatory and HDAC Inhibitory Properties

    José Christian Machado Ximenes

    2015-01-01

    Full Text Available Parkinson’s disease is a neurodegenerative disorder where the main hallmark is the dopaminergic neuronal loss. Besides motor symptoms, PD also causes cognitive decline. Although current therapies focus on the restoration of dopamine levels in the striatum, prevention or disease-modifying therapies are urgently needed. Valproic acid (VA is a wide spectrum antiepileptic drug, exerting many biochemical and physiological effects. It has been shown to inhibit histone deacetylase which seems to be associated with the drug neuroprotective action. The objectives were to study the neuroprotective properties of VA in a model of Parkinson’s disease, consisting in the unilateral striatal injection of the neurotoxin 6-OHDA. For that, male Wistar rats (250 g were divided into the groups: sham-operated (SO, untreated 6-OHDA-lesioned, and 6-OHDA-lesioned treated with VA (25 or 50 mg/kg. Oral treatments started 24 h after the stereotaxic surgery and continued daily for 2 weeks, when the animals were subjected to behavioral evaluations (apomorphine-induced rotations and open-field tests. Then, they were sacrificed and had their mesencephalon, striatum, and hippocampus dissected for neurochemical (DA and DOPAC determinations, histological (Fluoro-Jade staining, and immunohistochemistry evaluations (TH, OX-42, GFAP, TNF-alpha, and HDAC. The results showed that VA partly reversed behavioral and neurochemical alterations observed in the untreated 6-OHDA-lesioned rats. Besides, VA also decreased neuron degeneration in the striatum and reversed the TH depletion observed in the mesencephalon of the untreated 6-OHDA groups. This neurotoxin increased the OX-42 and GFAP immunoreactivities in the mesencephalon, indicating increased microglia and astrocyte reactivities, respectively, which were reversed by VA. In addition, the immunostainings for TNF-alpha and HDAC demonstrated in the untreated 6-OHDA-lesioned rats were also decreased after VA treatments. These

  2. EGCG Protects against 6-OHDA-Induced Neurotoxicity in a Cell Culture Model

    Dan Chen

    2015-01-01

    Full Text Available Background. Parkinson’s disease (PD is a progressive neurodegenerative disease that causes severe brain dopamine depletion. Disruption of iron metabolism may be involved in the PD progression. Objective. To test the protective effect of (−-epigallocatechin-3-gallate (EGCG against 6-hydroxydopamine- (6-OHDA- induced neurotoxicity by regulating iron metabolism in N27 cells. Methods. Protection by EGCG in N27 cells was assessed by SYTOX green assay, MTT, and caspase-3 activity. Iron regulatory gene and protein expression were measured by RT-PCR and Western blotting. Intracellular iron uptake was measured using 55Fe. The EGCG protection was further tested in primary mesencephalic dopaminergic neurons by immunocytochemistry. Results. EGCG protected against 6-OHDA-induced cell toxicity. 6-OHDA treatment significantly (p<0.05 increased divalent metal transporter-1 (DMT1 and hepcidin and decreased ferroportin 1 (Fpn1 level, whereas pretreatment with EGCG counteracted the effects. The increased 55Fe (by 96%, p<0.01 cell uptake confirmed the iron burden by 6-OHDA and was reduced by EGCG by 27% (p<0.05, supporting the DMT1 results. Pretreatment with EGCG and 6-OHDA significantly increased (p<0.0001 TH+ cell count (~3-fold and neurite length (~12-fold compared to 6-OHDA alone in primary mesencephalic neurons. Conclusions. Pretreatment with EGCG protected against 6-OHDA-induced neurotoxicity by regulating genes and proteins involved in brain iron homeostasis, especially modulating hepcidin levels.

  3. Striatal mRNA expression patterns underlying peak dose l-DOPA-induced dyskinesia in the 6-OHDA hemiparkinsonian rat.

    Smith, L M; Parr-Brownlie, L C; Duncan, E J; Black, M A; Gemmell, N J; Dearden, P K; Reynolds, J N J

    2016-06-01

    l-DOPA is the primary pharmacological treatment for relief of the motor symptoms of Parkinson's disease (PD). With prolonged treatment (⩾5years) the majority of patients will develop abnormal involuntary movements as a result of l-DOPA treatment, known as l-DOPA-induced dyskinesia. Understanding the underlying mechanisms of dyskinesia is a crucial step toward developing treatments for this debilitating side effect. We used the 6-hydroxydopamine (6-OHDA) rat model of PD treated with a three-week dosing regimen of l-DOPA plus the dopa decarboxylase inhibitor benserazide (4mg/kg and 7.5mg/kgs.c., respectively) to induce dyskinesia in 50% of individuals. We then used RNA-seq to investigate the differences in mRNA expression in the striatum of dyskinetic animals, non-dyskinetic animals, and untreated parkinsonian controls at the peak of dyskinesia expression, 60min after l-DOPA administration. Overall, 255 genes were differentially expressed; with significant differences in mRNA expression observed between all three groups. In dyskinetic animals 129 genes were more highly expressed and 14 less highly expressed when compared with non-dyskinetic and untreated parkinsonian controls. In l-DOPA treated animals 42 genes were more highly expressed and 95 less highly expressed when compared with untreated parkinsonian controls. Gene set cluster analysis revealed an increase in expression of genes associated with the cytoskeleton and phosphoproteins in dyskinetic animals compared with non-dyskinetic animals, which is consistent with recent studies documenting an increase in synapses in dyskinetic animals. These genes may be potential targets for drugs to ameliorate l-DOPA-induced dyskinesia or as an adjunct treatment to prevent their occurrence. PMID:26968766

  4. β-Asarone Inhibits IRE1/XBP1 Endoplasmic Reticulum Stress Pathway in 6-OHDA-Induced Parkinsonian Rats.

    Ning, Baile; Deng, Minzhen; Zhang, Qinxin; Wang, Nanbu; Fang, Yongqi

    2016-08-01

    Parkinson's disease (PD) is a neurodegenerative disease, with genetics and environment contributing to the disease onset. The limited pathological cognize of the disease restrained the approaches to improve the clinical treatment. Recently, studies showed that endoplasmic reticulum (ER) stress played an important role in the pathogenesis of PD. There was a neuroprotective effect partly mediated by modulating ER stress. β-Asarone is the essential constituent of Acorus tatarinowii Schott volatile oil. Our team observed that β-asarone could improve the behavior of parkinsonian rats; increase the HVA, Dopacl, and 5-HIAA levels; and reduce α-synuclein levels. Here we assumed that the protective role of β-asarone on parkinsonian rats was mediated via ER stress pathway. To prove the hypothesis we investigated the mRNA levels of glucose regulated protein 78 (GRP78) and C/EBP homologous binding protein (CHOP) in 6-hydroxy dopamine (6-OHDA) induced parkinsonian rats after β-asarone treatment. Furthermore, the inositol-requiring enzyme 1/X-Box Binding Protein 1 (IRE1/XBP1) ER stress pathway was also studied. The results showed that β-asarone inhibited the mRNA levels of GRP78 and CHOP, accompanied with the delined expressions of phosphorylated IER1 (p-IRE1) and XBP1. We deduced that β-asarone might have a protective effect on the 6-OHDA induced parkinsonian rats via IRE1/XBP1 Pathway. Collectively, all data indicated that β-asarone might be a potential candidate of medicine for clinical therapy of PD. PMID:27097550

  5. Effect of adenosine A(2A) receptor antagonists and L-DOPA on hydroxyl radical, glutamate and dopamine in the striatum of 6-OHDA-treated rats.

    Gołembiowska, Krystyna; Dziubina, Anna

    2012-02-01

    A(2A) adenosine receptor antagonists have been proposed as a new therapy of PD. Since oxidative stress plays an important role in the pathogenesis of PD, we studied the effect of the selective A(2A) adenosine receptor antagonists 8-(-3-chlorostyryl)caffeine (CSC) and 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM 241385) on hydroxyl radical generation, and glutamate (GLU) and dopamine (DA) extracellular level using a microdialysis in the striatum of 6-OHDA-treated rats. CSC (1 mg/kg) and ZM 241385 (3 mg/kg) given repeatedly for 14 days decreased the production of hydroxyl radical and extracellular GLU level, both enhanced by prior 6-OHDA treatment in dialysates from the rat striatum. CSC and ZM 241385 did not affect DA and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA) extracellular levels in the striatum of 6-OHDA-treated rats. L-DOPA (6 mg/kg) given twice daily for two weeks in the presence of benserazide (3 mg/kg) decreased striatal hydroxyl radical and glutamate extracellular level in 6-OHDA-treated rats. At the same time, L-DOPA slightly but significantly increased the extracellular levels of DOPAC and HVA. A combined repeated administration of L-DOPA and CSC or ZM 241385 did not change the effect of L-DOPA on hydroxyl radical production and glutamate extracellular level in spite of an enhancement of extracellular DA level by CSC and elevation of extracellular level of DOPAC and HVA by ZM 241385. The data suggest that the 6-OHDA-induced damage of nigrostriatal DA-terminals is related to oxidative stress and excessive release of glutamate. Administration of L-DOPA in combination with CSC or ZM 241385, by restoring striatal DA-glutamate balance, suppressed 6-OHDA-induced overproduction of hydroxyl radical. PMID:21830163

  6. ORALLY ACTIVE CARBAMATE PRODRUGS OF THE SELECTIVE DOPAMINE AGONIST N-0437 - INVIVO ACTIVITIES IN THE 6-OHDA TURNING MODEL AND INVITRO ACTIVITIES

    DENDAAS, [No Value; DEBOER, P; TEPPER, PG; ROLLEMA, H; HORN, AS

    1991-01-01

    The in-vivo activities of eight carbamate prodrugs of the D2-agonist N-0437 were determined by examining the effects of the prodrugs, after their oral administration in rats with unilateral 6-OHDA lesions of the striatum. The resulting contralateral turning was used as an index of the activity of th

  7. Hepcidin Plays a Key Role in 6-OHDA Induced Iron Overload and Apoptotic Cell Death in a Cell Culture Model of Parkinson's Disease

    Xu, Qi; Kanthasamy, Anumantha G.; Jin, Huajun; Reddy, Manju B.

    2016-01-01

    Background. Elevated brain iron levels have been implicated in the pathogenesis of Parkinson's disease (PD). However, the precise mechanism underlying abnormal iron accumulation in PD is not clear. Hepcidin, a hormone primarily produced by hepatocytes, acts as a key regulator in both systemic and cellular iron homeostasis. Objective. We investigated the role of hepcidin in 6-hydroxydopamine (6-OHDA) induced apoptosis in a cell culture model of PD. Methods. We downregulated hepcidin using siRNA interference in N27 dopaminergic neuronal cells and made a comparison with control siRNA transfected cells to investigate the role of hepcidin in 6-OHDA induced neurodegeneration. Results. Hepcidin knockdown (32.3%, P Hepcidin knockdown also reduced 6-OHDA induced caspase-3 activity by 42% (P hepcidin knockdown significantly attenuated 6-OHDA induced protein carbonyls by 52% (P hepcidin in oxidative stress. Conclusions. Our results demonstrate that hepcidin knockdown protected N27 cells from 6-OHDA induced apoptosis and that hepcidin plays a major role in reducing cellular iron burden and oxidative damage by possibly regulating cellular iron export mediated by ferroportin 1. PMID:27298749

  8. Hepcidin Plays a Key Role in 6-OHDA Induced Iron Overload and Apoptotic Cell Death in a Cell Culture Model of Parkinson’s Disease

    Qi Xu

    2016-01-01

    Full Text Available Background. Elevated brain iron levels have been implicated in the pathogenesis of Parkinson’s disease (PD. However, the precise mechanism underlying abnormal iron accumulation in PD is not clear. Hepcidin, a hormone primarily produced by hepatocytes, acts as a key regulator in both systemic and cellular iron homeostasis. Objective. We investigated the role of hepcidin in 6-hydroxydopamine (6-OHDA induced apoptosis in a cell culture model of PD. Methods. We downregulated hepcidin using siRNA interference in N27 dopaminergic neuronal cells and made a comparison with control siRNA transfected cells to investigate the role of hepcidin in 6-OHDA induced neurodegeneration. Results. Hepcidin knockdown (32.3%, P<0.0001 upregulated ferroportin 1 expression and significantly (P<0.05 decreased intracellular iron by 25%. Hepcidin knockdown also reduced 6-OHDA induced caspase-3 activity by 42% (P<0.05 and DNA fragmentation by 29% (P=0.086 and increased cell viability by 22% (P<0.05. In addition, hepcidin knockdown significantly attenuated 6-OHDA induced protein carbonyls by 52% (P<0.05 and intracellular iron by 28% (P<0.01, indicating the role of hepcidin in oxidative stress. Conclusions. Our results demonstrate that hepcidin knockdown protected N27 cells from 6-OHDA induced apoptosis and that hepcidin plays a major role in reducing cellular iron burden and oxidative damage by possibly regulating cellular iron export mediated by ferroportin 1.

  9. Spontaneous locomotor activity and L-DOPA-induced dyskinesia are not linked in 6-OHDA parkinsonian rats

    Stefania Sgroi

    2014-10-01

    Full Text Available Bradykinesia (slowness of movement and other characteristic motor manifestations of Parkinson’s disease (PD are alleviated by treatment with L-dihydroxyphenylalanine (L-DOPA. Long-term L-DOPA treatment, however, is associated with complications such as motor fluctuations and dyskinesia that severely impair the quality of life. It is unclear whether the effect of L-DOPA on spontaneous motor activity and its dyskinesia-inducing effect share a common mechanism. To investigate the possible connection between these two effects, we analyzed the spontaneous locomotor activity of parkinsonian rats before surgery (unilateral injection of 6-OHDA in the right medial forebrain bundle, before treatment with L-DOPA, during L-DOPA treatment (the “ON” phase, and after the end of L-DOPA treatment (the “OFF” phase. We correlated the severity of dyskinesia (AIM scores with locomotor responses in the ON/OFF phases of chronic L-DOPA treatment at two different doses. We treated three groups of parkinsonian animals with chronic injections of 8 mg/kg L-DOPA, 6 mg/kg L-DOPA, and saline solution and one group of non-lesioned animals with 8 mg/kg L-DOPA. At the end of the experiment, tyrosine hydroxylase (TH immunoreactivity was analyzed in the striatum of all parkinsonian rats. We found no correlation between the severity of dyskinesia and spontaneous locomotor activity in the ON or OFF phase of L-DOPA treatment. The only observed correlation was between the pathological rotation induced by L-DOPA at the highest dose and locomotor activity in the ON phase of L-DOPA treatment. In addition, a L-DOPA withdrawal effect was observed, with worse motor performance in the OFF phase than before the start of L-DOPA treatment. These findings suggest that different neural mechanisms underlie the effect of L-DOPA on spontaneous motor activity and its dyskinesia-inducing effect, with a different dose-response relationship for each of these two effects.

  10. Counteraction by nitric oxide synthase inhibitor of neurochemical alterations of dopaminergic system in 6-OHDA-lesioned rats under L-DOPA treatment.

    Del-Bel, Elaine; Padovan-Neto, Fernando Eduardo; Szawka, Raphael Escorsim; da-Silva, Célia Aparecida; Raisman-Vozari, Rita; Anselmo-Franci, Janete; Romano-Dutra, Angélica Caroline; Guimaraes, Francisco Silveira

    2014-01-01

    Nitric oxide synthase inhibitors reduce L-3, (Del-Bel et al., Cell Mol Neurobiol 25(2):371-392, 2005) 4-dihydroxyphenylalanine (L-DOPA)-induced abnormal motor effects subsequent to depletion of dopaminergic neurons in rodents and non-human primates. The present study used quantitative high-performance liquid chromatography to analyze, for the first time, dopamine metabolism in striatum of rats in order to elucidate the mechanism of action of the nitric oxide synthase inhibitors. Adult male Wistar rats received unilateral microinjection of saline (sham) or 6-hydroxydopamine (6-OHDA-lesioned) in the medial forebrain bundle. Past 3 weeks, rats were treated during 21 days with L-DOPA/benserazide (30 mg/kg/7.5 mg/kg, respectively, daily). On the 22nd day rats received an intraperitoneal (i.p.) injection of either vehicle or 7-nitroindazole, a preferential neuronal nitric oxide synthase inhibitor before L-DOPA. Abnormal involuntary movements and rotarod test were assessed as behavioral correlate of motor responses. Lesion intensity was evaluated through tyrosine hydroxylase immunohystochemical reaction. Dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), and an extent of dopamine striatal tissue levels/dopamine metabolism were measured in the striatum. Lesion with 6-OHDA decreased dopamine, DOPAC, and DOPAC/dopamine ratio in the lesioned striatum. L-DOPA treatment induced abnormal involuntary movements and increased DOPAC/dopamine ratio (nearly five times) in the lesioned striatum. L-DOPA-induced dyskinesia was mitigated by 7-nitroindazole, which also decreased dopamine turnover, dopamine and DOPAC levels. Our results revealed an almost two times increase in dopamine content in the non-lesioned striatum of 6-OHDA-lesioned rats. Reduction of striatal DOPAC/dopamine ratio in dyskinetic rats may suggest an increase in the dopamine availability. Our data confirm contribution of nitrergic transmission in the pathogenesis of L-DOPA-induced dyskinesia with potential

  11. Characterization of long-term motor deficits in the 6-OHDA model of Parkinson's disease in the common marmoset.

    Santana, M; Palmér, T; Simplício, H; Fuentes, R; Petersson, P

    2015-09-01

    Research aimed at developing new therapies for Parkinson's disease (PD) critically depend on valid animal models of the disease that allows for repeated testing of motor disabilities over extended time periods. We here present an extensive characterization of a wide range of motor symptoms in the 6-OHDA marmoset model of PD when tested over several months. The severity of motor deficits was quantified in two ways: (i) through manual scoring protocols appropriately adapted to include species specific motor behavior and (ii) using automated quantitative motion tracking based on image processing of the digital video recordings. We show that the automated methods allow for rapid and reliable characterization of motor dysfunctions, thus complementing the manual scoring procedures, and that robust motor symptoms lasting for several months could be induced when using a two-stage neurotoxic lesioning procedure involving one hemisphere at a time. This non-human primate model of PD should therefore be well suited for long-term evaluation of novel therapies for treatment of PD. PMID:25934488

  12. Hepcidin Plays a Key Role in 6-OHDA Induced Iron Overload and Apoptotic Cell Death in a Cell Culture Model of Parkinson's Disease.

    Xu, Qi; Kanthasamy, Anumantha G; Jin, Huajun; Reddy, Manju B

    2016-01-01

    Background. Elevated brain iron levels have been implicated in the pathogenesis of Parkinson's disease (PD). However, the precise mechanism underlying abnormal iron accumulation in PD is not clear. Hepcidin, a hormone primarily produced by hepatocytes, acts as a key regulator in both systemic and cellular iron homeostasis. Objective. We investigated the role of hepcidin in 6-hydroxydopamine (6-OHDA) induced apoptosis in a cell culture model of PD. Methods. We downregulated hepcidin using siRNA interference in N27 dopaminergic neuronal cells and made a comparison with control siRNA transfected cells to investigate the role of hepcidin in 6-OHDA induced neurodegeneration. Results. Hepcidin knockdown (32.3%, P export mediated by ferroportin 1. PMID:27298749

  13. COMPARISON OF THE D1-DOPAMINE AGONIST SKF-38393 AND A-68930 IN NEONATAL 6-OHDA-LESIONED RATS: BEHAVIORAL EFFECTS AND INDUCTION OF C-FOS-LIKE IMMUNOREACTIVITY

    Previous studies from this laboratory and others have found that neonatal 6-OHDA-lesioned rats exhibit profound behavioral manifestations, and significant induction of striatal c-fos-like immunoreactivity (FLI), when administered the selective D1-dopamine agonist SKF-38393. ith t...

  14. Inhibition of Endoplasmic Reticulum Stress is Involved in the Neuroprotective Effect of bFGF in the 6-OHDA-Induced Parkinson's Disease Model.

    Cai, Pingtao; Ye, Jingjing; Zhu, Jingjing; Liu, Dan; Chen, Daqing; Wei, Xiaojie; Johnson, Noah R; Wang, Zhouguang; Zhang, Hongyu; Cao, Guodong; Xiao, Jian; Ye, Junming; Lin, Li

    2016-08-01

    Parkinson's disease (PD) is a progressive neurodegenerative disorder with complicated pathophysiologic mechanisms. Endoplasmic reticulum (ER) stress appears to play a critical role in the progression of PD. We demonstrated that basic fibroblast growth factor (bFGF), as a neurotropic factor, inhibited ER stress-induced neuronal cell apoptosis and that 6-hydroxydopamine (6-OHDA)-induced ER stress was involved in the progression of PD in rats. bFGF administration improved motor function recovery, increased tyrosine hydroxylase (TH)-positive neuron survival, and upregulated the levels of neurotransmitters in PD rats. The 6-OHDA-induced ER stress response proteins were inhibited by bFGF treatment. Meanwhile, bFGF also increased expression of TH. The administration of bFGF activated the downstream signals PI3K/Akt and Erk1/2 in vivo and in vitro. Inhibition of the PI3K/Akt and Erk1/2 pathways by specific inhibitors partially reduced the protective effect of bFGF. This study provides new insight towards bFGF translational drug development for PD involving the regulation of ER stress. PMID:27493838

  15. A partial lesion model of Parkinson's disease in mice--characterization of a 6-OHDA-induced medial forebrain bundle lesion.

    Boix, Jordi; Padel, Thomas; Paul, Gesine

    2015-05-01

    The most frequently used animal models for Parkinson's disease (PD) utilize unilateral injection of 6-hydroxydopamine (6-OHDA) in the medial forebrain bundle (MFB), which results in total denervation of the dopaminergic nigrostriatal pathway. However, neuroprotective interventions in PD require models resembling earlier stages of PD, where some dopaminergic cells and fibres remain. The aim of the present study was therefore to establish a MFB partial lesion model in mice. We tested four different 6-OHDA doses, and our results show a dose-dependent loss of nigral dopaminergic cells and striatal fibres that correlated with behavioural impairment in several behavioural tests. Specifically, doses of 0.7 μg and 1 μg of 6-OHDA induced a partial denervation of the nigrostriatal pathway, associated with a mild but quantifiable behavioural impairment. We identified the amphetamine-induced rotation, stepping, corridor and cylinder test to be sensitive enough to select partial lesion animals. Based on our data, we proposed a range of cut-off values for these different behavioural tests to select partial lesion mice. Using a statistical prediction model we identified two behavioural tests (the stepping test and amphetamine-induced rotation test) that with a high sensitivity and specificity predict the extent of nigral dopaminergic cell loss and select mice with a partial nigrostriatal lesion prior to further interventions. This model can serve as an important tool to study neuroprotective therapies for PD in mouse models, especially when the treatment targets the substantia nigra and/or the striatum. PMID:25698603

  16. Striatal Injury with 6-OHDA Transiently Increases Cerebrospinal GFAP and S100B.

    Batassini, Cristiane; Broetto, Núbia; Tortorelli, Lucas Silva; Borsoi, Milene; Zanotto, Caroline; Galland, Fabiana; Souza, Tadeu Mello; Leite, Marina Concli; Gonçalves, Carlos-Alberto

    2015-01-01

    Both glial fibrillary acidic protein (GFAP) and S100B have been used as markers of astroglial plasticity, particularly in brain injury; however, they do not necessarily change in the same time frame or direction. Herein, we induced a Parkinson's disease (PD) model via a 6-OHDA intrastriatal injection in rats and investigated the changes in GFAP and S100B using ELISA in the substantia nigra (SN), striatum, and cerebrospinal fluid on the 1st, 7th, and 21st days following the injection. The model was validated using measurements of rotational behaviour induced by methylphenidate and tyrosine hydroxylase in the dopaminergic pathway. To our knowledge, this is the first measurement of cerebrospinal fluid S100B and GFAP in the 6-OHDA model of PD. Gliosis (based on a GFAP increase) was identified in the striatum, but not in the SN. We identified a transitory increment of cerebrospinal fluid S100B and GFAP on the 1st and 7th days, respectively. This initial change in cerebrospinal fluid S100B was apparently related to the mechanical lesion. However, the 6-OHDA-induced S100B secretion was confirmed in astrocyte cultures. Current data reinforce the idea that glial changes precede neuronal damage in PD; however, these findings also indicate that caution is necessary regarding the interpretation of data in this PD model. PMID:26090233

  17. Cardiac sympathetic denervation in 6-OHDA-treated nonhuman primates.

    Valerie Joers

    Full Text Available Cardiac sympathetic neurodegeneration and dysautonomia affect patients with sporadic and familial Parkinson's disease (PD and are currently proposed as prodromal signs of PD. We have recently developed a nonhuman primate model of cardiac dysautonomia by iv 6-hydroxydopamine (6-OHDA. Our in vivo findings included decreased cardiac uptake of a sympathetic radioligand and circulating catecholamines; here we report the postmortem characterization of the model. Ten adult rhesus monkeys (5-17 yrs old were used in this study. Five animals received 6-OHDA (50 mg/kg i.v. and five were age-matched controls. Three months post-neurotoxin the animals were euthanized; hearts and adrenal glands were processed for immunohistochemistry. Quantification of immunoreactivity (ir of stainings was performed by an investigator blind to the treatment group using NIH ImageJ software (for cardiac bundles and adrenals, area above threshold and optical density and MBF StereoInvestigator (for cardiac fibers, area fraction fractionator probe. Sympathetic cardiac nerve bundle analysis and fiber area density showed a significant reduction in global cardiac tyrosine hydroxylase-ir (TH; catecholaminergic marker in 6-OHDA animals compared to controls. Quantification of protein gene protein 9.5 (pan-neuronal marker positive cardiac fibers showed a significant deficit in 6-OHDA monkeys compared to controls and correlated with TH-ir fiber area. Semi-quantitative evaluation of human leukocyte antigen-ir (inflammatory marker and nitrotyrosine-ir (oxidative stress marker did not show significant changes 3 months post-neurotoxin. Cardiac nerve bundle α-synuclein-ir (presynaptic protein was reduced (trend in 6-OHDA treated monkeys; insoluble proteinase-K resistant α-synuclein (typical of PD pathology was not observed. In the adrenal medulla, 6-OHDA monkeys had significantly reduced TH-ir and aminoacid decarboxylase-ir. Our results confirm that systemic 6-OHDA dosing to nonhuman primates

  18. 6-OHDA-induced apoptosis and mitochondrial dysfunction are mediated by early modulation of intracellular signals and interaction of Nrf2 and NF-κB factors

    6-Hydroxydopamine (6-OHDA) is a neurotoxin that generates an experimental model of Parkinson's disease in rodents and is commonly employed to induce a lesion in dopaminergic pathways. The characterization of those molecular mechanisms linked to 6-OHDA-induced early toxicity is needed to better understand the cellular events further leading to neurodegeneration. The present work explored how 6-OHDA triggers early downstream signaling pathways that activate neurotoxicity in the rat striatum. Mitochondrial function, caspases-dependent apoptosis, kinases signaling (Akt, ERK 1/2, SAP/JNK and p38) and crosstalk between nuclear factor kappa B (NF-κB) and nuclear factor-erythroid-2-related factor 2 (Nrf2) were evaluated at early times post-lesion. We found that 6-OHDA initiates cell damage via mitochondrial complex I inhibition, cytochrome c and apoptosis-inducing factor (AIF) release, as well as activation of caspases 9 and 3 to induce apoptosis, kinase signaling modulation and NF-κB-mediated inflammatory responses, accompanied by inhibition of antioxidant systems regulated by the Nrf2 pathway. Our results suggest that kinases SAP/JNK and p38 up-regulation may play a role in the early stages of 6-OHDA toxicity to trigger intrinsic pathways for apoptosis and enhanced NF-κB activation. In turn, these cellular events inhibit the activation of cytoprotective mechanisms, thereby leading to a condition of general damage

  19. Striatal Injury with 6-OHDA Transiently Increases Cerebrospinal GFAP and S100B

    Cristiane Batassini; Núbia Broetto; Lucas Silva Tortorelli; Milene Borsoi; Caroline Zanotto; Fabiana Galland; Tadeu Mello Souza; Marina Concli Leite; Carlos-Alberto Gonçalves

    2015-01-01

    Both glial fibrillary acidic protein (GFAP) and S100B have been used as markers of astroglial plasticity, particularly in brain injury; however, they do not necessarily change in the same time frame or direction. Herein, we induced a Parkinson’s disease (PD) model via a 6-OHDA intrastriatal injection in rats and investigated the changes in GFAP and S100B using ELISA in the substantia nigra (SN), striatum, and cerebrospinal fluid on the 1st, 7th, and 21st days following the injection. The mode...

  20. Effect and mechanism of homocysteine on Parkinson's disease induced by 6-OHDA

    Hongxia Xing; Hai Peng; Xuebing Cao; Shenggang Sun

    2008-01-01

    Objective: To study the effects and mechanism of homocysteine(Hey) on Parkinson's disease(PD) induced by 6-hydroxydopamine (6-OHDA) in vivo. Methods:Forty rats were divided into 4 groups. 6-OHDA or the solvent of 6-OHDA was focally administrated to induce PD, 2 h later Hey or 0.9% sodium chloride was administrated in the ipsolateral substantial nigra(SN). We used behavioral testing, Immolunohistochemical techniques, biochemistry techniques to detect the injury of SN. Results:The rotary turns of PD rats induced by 6-OHDA showed significant increase after treatment with Hey compared with the controls(P < 0.05). Also the numbers of tyrosine hydroxylase(TH)-stained neurons were decreased, and dendrites were fragmented and truncated. Free radicals were increased and antioxidant enzymes decreased. Conclusion:Focal infusion of Hey into the SN increased the vulnerability of the dopaminergic neurons to 6-OHDA-induced degeneration, it seems that the endangering effect of Hey is due to exacerbating oxidative stress.

  1. Retigabine, a K(V)7 (KCNQ) potassium channel opener, attenuates L-DOPA-induced dyskinesias in 6-OHDA-lesioned rats.

    Sander, S E; Lemm, C; Lange, N; Hamann, M; Richter, A

    2012-02-01

    L-DOPA-induced dyskinesias (LID) represent a severe complication of long-time pharmacotherapy in Parkinson's disease that necessitates novel therapeutics. The acute and chronic effects of K(V)7.2-7.5 channel openers (retigabine, flupirtine) on the severity of LID and parkinsonian signs were examined in comparison to the glutamate receptor antagonist amantadine (positive control) in a rat model of LID. Acute treatment with retigabine (2.5, 5 mg/kg i.p.) and flupirtine (5, 10 mg/kg i.p.) significantly reduced the severity of abnormal involuntary movements (AIM) to a comparable extent as amantadine (20, 40 mg/kg s.c.), but flupirtine delayed the disappearance of AIM. Chronic treatment with retigabine (daily 5 mg/kg i.p. over 19 days combined with l-DOPA 10 mg i.p.) did not prevent or delay the development of LID, but reduced the severity of AIM, while antidyskinetic effects of amantadine (40 mg/kg i.p.) were restricted to the first day of treatment. Retigabine caused sedation and ataxia which declined during the chronic treatment, but did not reduce the antiparkinsonian effects of l-DOPA in these experiments. Acute co-injections of retigabine (5 mg) together with l-DOPA (10 mg/kg) neither reduced the motor performance in the rotarod test nor exerted negative effects on the antiparkinsonian efficacy of l-DOPA in the block and stepping test. Nevertheless, the sedative effects of retigabine may limit its therapeutic potential for the treatment of LID. The present data indicate that K(V)7 channels deserve attention in the research of the pathophysiology of dyskinesias. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'. PMID:22079161

  2. RNAi-mediated silencing of HLA A2 suppressed acute rejection against human fibroblast xenografts in the striatum of 6-OHDA lesioned rats.

    Liang, Caixia; Xu, Yunzhi; Zheng, Deyu; Sun, Xiaohong; Xu, Qunyuan; Duan, Deyi

    2016-08-15

    Major histocompatibility complex class l (MHC I) molecules play a role in determining whether transplanted cells will be accepted or rejected, and masking of MHC I on donor cells has been found useful for immunoprotection of neural xenografts. In the present study, primary human embryonic lung fibroblasts (HELF), HELF treated with lentivirus-mediated small interfering RNAs (siRNAs) targeting human leukocyte antigen A2 (HLA A2, MHC I in humans) (siHELF), and rat embryonic lung fibroblasts (RELF) were stereotaxically grafted into the striatum of 6-hydroxydopamine lesioned rats to explore whether knockdown of HLA A2 could reduce host immune responses against xenografts. Before lentiviral infection, the cells were transduced with retroviruses harboring tyrosine hydroxylase cDNA. Knockdown of HLA A2 protein was examined by Western blotting. The immune responses (the number of CD4 and CD8 T-cells in the brain and peripheral blood), glial reaction, and survival of human fibroblasts were quantitatively evaluated by flow cytometry and immunohistochemistry at 4d, 2w, and 6w post-graft. Animal behaviors were assessed by counting apomorphine-induced rotations pre- and post-grafts. It was shown that a lower level of HLA A2 was observed in siHELF grafts than in HELF grafts, and knockdown of HLA A2 decreased rat immune responses, as indicated by less remarkable increases in the number of CD8 and CD4 T-cells in the brain and the ratio of CD4:CD8 T-cells in the peripheral blood in rats grafted with siHELF. Rats grafted with siHELF exhibited a significant improvement in motor asymmetry post-transplantation and a better survival of human fibroblasts at 2w. The increasing number of activated microglia and the decreasing number of astrocytes were found in three groups of rats post-implantation. These data suggested that RNAi-mediated knockdown of HLA A2 could suppress acute rejection against xenogeneic human cell transplants in the rat brain. PMID:27397073

  3. Systemic administration of 6-OHDA to rhesus monkeys upregulates HLA-DR expression in brain microvasculature

    Joers V

    2014-09-01

    Full Text Available Valerie Joers,1,2 Scott Vermilyea,1,2 Kristine Dilley,1 Marina E Emborg1–3 1Preclinical Parkinson's Research Program, Wisconsin National Primate Research Center, 2Neuroscience Training Program, 3Department of Medical Physics, University of Wisconsin-Madison, Madison, WI, USA Background: We recently developed a nonhuman primate model of cardiac dysautonomia by systemic dosing of the catecholaminergic neurotoxin 6-hydroxydopamine (6-OHDA. The aim of this study was to assess whether systemic 6-OHDA affects the central nervous system of nonhuman primates, in particular the dopaminergic nigrostriatal system. Methods: Brain sections from adult rhesus monkeys that received systemic 6-OHDA (50 mg/kg intravenously; n=5 and were necropsied 3 months later, as well as normal controls (n=5 were used in this study. Tissue was cut frozen at 40 µm on a sliding microtome, processed for immunohistochemistry, and blindly evaluated. Results: Neither the optical density of tyrosine hydroxylase immunoreactivity (TH-ir; a dopaminergic neuronal marker in the caudate and putamen nucleus nor the TH-ir cell number and volume in the substantia nigra showed significant differences between groups. Yet within groups, statistical analysis revealed significant individual differences in the 6-OHDA-treated group, with two animals showing a lower cell count and volume. Optical density quantification of α-synuclein-ir in the substantia nigra did not show differences between groups. As α-synuclein intracellular distribution was noted to vary between animals, it was further evaluated with a semiquantitative scale. A greater intensity and presence of α-synuclein-positive nigral cell bodies was associated with larger TH-positive nigral cell volumes. Increased human leukocyte antigen (HLA-DR; a microglial marker expression was observed in 6-OHDA-treated animals compared with controls. HLA-DR-ir was primarily localized in endothelial cells and perivascular spaces throughout

  4. The preferential nNOS inhibitor 7-nitroindazole and the non-selective one N(G)-nitro-L-arginine methyl ester administered alone or jointly with L-DOPA differentially affect motor behavior and monoamine metabolism in sham-operated and 6-OHDA-lesioned rats.

    Czarnecka, Anna; Konieczny, Jolanta; Lenda, Tomasz; Lorenc-Koci, Elżbieta

    2015-11-01

    Reciprocal interactions between nitrergic and dopaminergic systems play a key role in the control of motor behavior. In the present study, we performed a comparative analysis of motor behavior (locomotor activity, catalepsy, rotational behavior) and monoamine metabolism in the striatum and substantia nigra of unilaterally sham-operated and 6-OHDA-lesioned rats treated with the preferential neuronal nitric oxide synthase (nNOS) inhibitor 7-nitroindazole (7-NI) or the non-selective one N(G)-nitro-L-arginine methyl ester (L-NAME), alone or in combination with L-DOPA. Each NOS inhibitor given alone (50mg/kg) induced a distinct catalepsy 30 min after injection but only 7-NI impaired spontaneous locomotion after 10 min. In 6-OHDA-lesioned rats, chronic L-DOPA (25mg/kg) induced 2.5-h long contralateral rotations. 7-NI (30 and 50mg/kg) markedly reduced the intensity of L-DOPA-induced contralateral rotations while extending their duration until 4.5h whereas L-NAME (50 and 100mg/kg) only tended to attenuate their intensity without affecting the duration. 7-NI but not L-NAME significantly increased endogenous tissue DA levels in the nigrostriatal system of both sham-operated and 6-OHDA-lesioned rats. In L-DOPA-treated group, 7-NI significantly enhanced the L-DOPA-derived tissue DA content in this system and decreased the level of the intracellular DA metabolite DOPAC produced by monoamine oxidase (MAO). In contrast to 7-NI, L-NAME decreased markedly DA content and did not affect DOPAC level in the ipsilateral striatum. It means that the differences in 7-NI and L-NAME-mediated modulation of L-DOPA-induced behavioral and biochemical effects resulted not only from the inhibition of NOS activity but also from differences in their ability to inhibit MAO. PMID:26319690

  5. Systemic administration of 6-OHDA to rhesus monkeys upregulates HLA-DR expression in brain microvasculature

    Joers V; Vermilyea S; Dilley K; Emborg ME

    2014-01-01

    Valerie Joers,1,2 Scott Vermilyea,1,2 Kristine Dilley,1 Marina E Emborg1–3 1Preclinical Parkinson's Research Program, Wisconsin National Primate Research Center, 2Neuroscience Training Program, 3Department of Medical Physics, University of Wisconsin-Madison, Madison, WI, USA Background: We recently developed a nonhuman primate model of cardiac dysautonomia by systemic dosing of the catecholaminergic neurotoxin 6-hydroxydopamine (6-OHDA). The aim of this study was to assess whether ...

  6. Apomorphine induced c-fos expression in the striatum of 6-OHDA-lesioned rats%阿朴吗啡诱导黑质毁损大鼠纹状体c-fos表达

    冯定庆; 陈晓蓉

    2005-01-01

    目的观察6-羟基多巴胺(6-OHDA)毁损黑质后,不同时间点腹腔注射阿朴吗啡(APO)大鼠纹状体c-fos表达情况,探讨其可能机制.方法利用6-OHDA单侧一点注射大鼠黑质致密区(SNc),特异毁损DA能神经元;术后1、7、14、21 d腹腔注射APO,观察旋转行为;利用免疫组织化学和电镜的方法,观察各时间点黑质DA能神经元形态学变化和纹状体c-fos表达情况.结果毁损侧DA能神经元逐渐减少,超微结构损伤逐渐加重;DA神经元丢失≥80%时,APO诱导的旋转实验>7 r·min-1,纹状体毁损侧c-fos表达.结论 APO能诱导毁损侧纹状体表达c-fos,c-fos表达与DA能神经元毁损程度有一定的关系.

  7. Deep brain stimulation of the subthalamic nucleus reestablishes neuronal information transmission in the 6-OHDA rat model of parkinsonism

    Dorval, Alan D.; Grill, Warren M.

    2014-01-01

    Pathophysiological activity of basal ganglia neurons accompanies the motor symptoms of Parkinson's disease. High-frequency (>90 Hz) deep brain stimulation (DBS) reduces parkinsonian symptoms, but the mechanisms remain unclear. We hypothesize that parkinsonism-associated electrophysiological changes constitute an increase in neuronal firing pattern disorder and a concomitant decrease in information transmission through the ventral basal ganglia, and that effective DBS alleviates symptoms by de...

  8. 阿朴吗啡诱导黑质毁损大鼠腹侧被盖区c-jun表达%Apomorphine induce c-jun expression in ventral tagmental area of 6-OHDA-lesioned rats

    陈晓宇; 姚玉芹; 沈韶辉; 韩卉

    2006-01-01

    目的:观察6-羟基多巴胺(6-hydroxydopamine,6-OHDA)毁损黑质DA能神经元后,不同时间点腹腔注射阿朴吗啡(Apomorphine,APO)大鼠行为学及中脑腹侧被盖区(ventraltagmental area,VTA)形态学、c-jun表达情况,探讨其可能机制.方法:6-OHDA单侧一点注射大鼠右黑质致密区(substantianigracompacta,SNc),特异性毁损DA能神经元;术后1、3、7、14、21d腹腔注射APO,观察旋转行为;利用电镜、尼氏染色、免疫组织化学ABC法,观察各时间点VTA DA能神经元形态学变化和酪氨酸羟化酶(TH)、c-jun表达情况.结果:毁损侧VTA DA能神经元逐渐减少,超微结构损伤逐渐加重;DA神经元丢失≥75%时,APO诱导的旋转实验≥7r/min,VTA毁损侧c-jun表达.结论:APO能诱导毁损侧VTA表达c-jun;c-jun表达与DA能神经元毁损程度有一定的关系.

  9. Neurotoxic effects of berberine on long-term L-DOPA administration in 6-hydroxydopamine-lesioned rat model of Parkinson's disease.

    Shin, Keon Sung; Choi, Hyun Sook; Zhao, Ting Ting; Suh, Kwang Hoon; Kwon, Ik Hyun; Choi, Soon Ok; Lee, Myung Koo

    2013-06-01

    The effects of berberine on long-term administration of L-DOPA in 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease (PD) were investigated. Rat models of PD were prepared by 6-OHDA lesions in the ipsilateral sides, and then were treated with berberine (5 and 15 mg/kg) and/or L-DOPA (10 mg/kg) once daily for 21 days. Treatments with either concentration of berberine (5 and 15 mg/kg) in 6-OHDA-lesioned groups decreased the numbers of tyrosine hydroxylase (TH)-immunopositive neurons in the substantia nigra and the levels of dopamine, norepinephrine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum as compared to 6-OHDA-lesioned groups. In addition, dopaminergic neuronal cell death of the ipsilateral sides in 6-OHDA-lesioned groups was attenuated by L-DOPA administration. However, both concentrations of berberine in 6-OHDA-lesioned groups treated with L-DOPA aggravated the numbers of TH-immunopositive neurons in the substantia nigra and the levels of dopamine, norepinephrine, DOPAC and HVA in the striatum as compared to rats not treated with berberine. These results suggest that berberine leads to the degeneration of dopaminergic neuronal cells in the substantia nigra in the rat model of PD with chronic L-DOPA administration. Long-term L-DOPA therapy that may involve possibly neurotoxic isoquinoline agents including berberine should involve monitoring for adverse symptoms. PMID:23539311

  10. 纹状体内注射6-羟基多巴胺制备兔帕金森病模型%Making Parkinsonian model of rabbit by injecting 6-OHDA into corpus striatum

    刘晓静; 尹逊河; 王宪龙; 郭丽红

    2012-01-01

    The aim of this research was to study the method of modeling Parkinson disease(PD) by injecting 6-hydroxydopamine(6-OHDA) into right side of rabbit corpus striatum.After the surgery,the change of behavior induced by apomorphine was observed every week.The rabbits were sacrificed after six weeks and the change of morphology,structure,amount of TH positive neurons were observed in substantia nigra part using SABC immunohistochemical technique.The results showed that the abnormal behaviors,including moving stiffly,seeking for food,appeared in a part of the rabbits after operation.The rate of the apomorphin-induced rotation was over 7 r/min among 16 rabbits(80%) after 6 weeks of the injection.The rabbit with more than 7 rotation per minute was regarded as a successful PD model.TH immunohistochemical staining showed that the TH positive neurons were seen within the nigral in normal control group,sham surgery group,and the unlesioned side of model group.They had the hyperchromic cytoplasm,the clear tubers,numerous positive cells and the long axons,which had no noble diversity among above three groups(P〉0.05).While in the opposite area of the model group TH positive neuron staining became lighter,cell body and tuber got blurrier,especially,the number and the axons length of the TH-positive neurons decreased and got shorter dramatically than that in the unlesioned side of the model group and the other two groups(P〈0.05).The results suggest that injecting 6-OHDA into the unilateral striatum was a feasible method for establishing rabbit model of PD,which is simple manipulation with satisfying achievement ratio and lower mortality.%应用脑立体定位技术微量注射6-OHDA于兔右侧纹状体内。术后每周观察以阿扑吗啡(Apomorphin,APO)诱导的旋转行为,并于术后6周处死兔,以黑质酪氨酸羟化酶(Tyrosine hydroxylase,TH)免疫组化染色,观察黑质多巴胺能神经元的形态、结构及数量变化。结果

  11. Exercise partially reverses the effect of maternal separation on hippocampal proteins in 6-hydroxydopamine lesioned rat brain

    Dimatelis, JJ; Hendricks, S.; Hsieh, J; Vlok, NM; Bugarith, K; Daniels, WMU; Russell, VA

    2012-01-01

    Animals subjected to maternal separation stress during the early stages of development display behavioural, endocrine and growth factor abnormalities that mirror the clinical findings in anxiety/depression. In addition, maternal separation has been shown to exacerbate the behavioural deficits induced by 6-hydroxydopamine (6-OHDA) in a rat model of Parkinson's disease. In contrast, voluntary exercise reduced the detrimental effects of 6-OHDA in the rat model. The beneficial effects of exercise...

  12. Selective COX-2 inhibition prevents progressive dopamine neuron degeneration in a rat model of Parkinson's disease

    Yu Meixiang

    2004-05-01

    Full Text Available Abstract Several lines of evidence point to a significant role of neuroinflammation in Parkinson's disease (PD and other neurodegenerative disorders. In the present study we examined the protective effect of celecoxib, a selective inhibitor of the inducible form of cyclooxygenase (COX-2, on dopamine (DA cell loss in a rat model of PD. We used the intrastriatal administration of 6-hydroxydopamine (6-OHDA that induces a retrograde neuronal damage and death, which progresses over weeks. Animals were randomized to receive celecoxib (20 mg/kg/day or vehicle starting 1 hour before the intrastriatal administration of 6-OHDA. Evaluation was performed in vivo using micro PET and selective radiotracers for DA terminals and microglia. Post mortem analysis included stereological quantification of tyrosine hydroxylase, astrocytes and microglia. 12 days after the 6-OHDA lesion there were no differences in DA cell or fiber loss between groups, although the microglial cell density and activation was markedly reduced in animals receiving celecoxib (p

  13. Curcumin protects nigral dopaminergic neurons by iron-chelation in the 6-hydroxydopamine rat model of Parkinson's disease

    Xi-Xun Du; Hua-Min Xu; Hong Jiang; Ning Song; Jun Wang; Jun-Xia Xie

    2012-01-01

    [Objective] Curcumin is a plant polyphenolic compound and a major component of spice turmeric (Curcuma longa).It has been reported to possess free radical-scavenging,iron-chelating,and anti-inflammatory properties in different tissues.Our previous study showed that curcumin protects MES23.5 dopaminergic cells from 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in vitro.The present study aimed to explore this neuroprotective effect in the 6-OHDAlesioned rat model of Parkinson's disease in vivo.[Methods] Rats were given intragastric curcumin for 24 days.6-OHDA lesioning was conducted on day 4 of curcumin treatment.Dopamine content was assessed by high-performance liquid chromatography with electrochemical detection,tyrosine hydroxylase (TH)-containing neurons by immunohistochemistry,and iron-containing cells by Perls' iron staining.[Results] The dopamine content in the striatum and the number of THimmunoreactive neurons decreased after 6-OHDA treatment.Curcumin pretreatment reversed these changes.Further studies demonstrated that 6-OHDA treatment increased the number of iron-staining cells,which was dramatically decreased by curcumin pretreatment.[Conclusion]The protective effects of curcumin against 6-OHDA may be attributable to the ironchelating activity of curcumin to suppress the iron-induced degeneration of nigral dopaminergic neurons.

  14. Subtle Cardiovascular Dysfunction in the Unilateral 6-Hydroxydopamine-Lesioned Rat

    K. Slack

    2010-01-01

    Full Text Available The present study evaluated whether the unilateral 6-hydroxydopamine (6-OHDA model of Parkinson's disease produces autonomic deficits. Autonomic parameters were assessed by implanting a small radiofrequency telemetry device which measured heart rate variability (HRV, diurnal rhythms of heart rate (HR, core body temperature (cBT and locomotor activity (LA. Rats then received 6-OHDA lesion or sham surgery. 6-OHDA lesioned rats exhibited head and body axis biases, defective sensorimotor function (“disengage” test, and prominent apomorphine rotation (all P<.05 versus controls. Diurnal rhythm of HR was lower for 6-OHDA lesioned rats (n=8 versus controls (n=6; P<.05. Whilst HR decreased similarly in both groups during the day, there was a greater decrease in HR for the 6-OHDA lesioned rats at night (by 38 b.p.m. relative to 17 b.p.m. for controls. LA and cBT did not differ between surgery groups. This study indicates the unilateral 6-OHDA model of PD shows subtle signs of cardiovascular autonomic dysfunction.

  15. Metabolic-dopaminergic mapping of the 6-hydroxydopamine rat model for Parkinson's disease

    The unilateral 6-hydroxydopamine (6-OHDA) lesion rat model is a well-known acute model for Parkinson's disease (PD). Its validity has been supported by invasive histology, behavioral studies and electrophysiology. Here, we have characterized this model in vivo by multitracer imaging [glucose metabolism and dopamine transporter (DAT)] in relation to behavioral and histological parameters. Eighteen female adult Wistar rats (eight 6-OHDA-lesioned, ten controls) were investigated using multitracer [18F]-fluoro-2-deoxy-D-glucose (FDG) and [18F]-FECT 2'-[18F]-fluoroethyl-(1R-2-exo-3-exe)-8-methyl-3-(4-chlorophenyl)- 8-azabicyclo (3.2.1)-octane-2-carboxylate small animal positron emission tomography (PET). Relative glucose metabolism and parametric DAT binding images were anatomically standardized to Paxinos space and analyzed on a voxel-basis using SPM2, supplemented by a template-based predefined volumes-of-interest approach. Behavior was characterized by the limb-use asymmetry test; dopaminergic innervation was validated by in vitro tyrosine hydroxylase staining. In the 6-OHDA model, significant glucose hypometabolism is present in the ipsilateral sensory-motor cortex (-6.3%; p = 4 x 10 -6). DAT binding was severely decreased in the ipsilateral caudate-putamen, nucleus accumbens and substantia nigra (all p -9), as confirmed by the behavioral and histological outcomes. Correlation analysis revealed a positive relationship between the degree of DAT impairment and the change in glucose metabolism in the ipsilateral hippocampus (p = 3 x 10 -5), while cerebellar glucose metabolism was inversely correlated to the level of DAT impairment (p -4). In vivo cerebral mapping of 6-OHDA-lesioned rats using [ 18F ]-FDG and [ 18F ]-FECT small animal PET shows molecular-functional correspondence to the cortico-subcortical network impairments observed in PD patients. This provides a further molecular validation supporting the validity of the 6-OHDA lesion model to mimic multiple aspects

  16. Changes of norepinephrine and tumor necrosis factor in submandibular gland of rats with sympathetic nerve injury and the protective effect of 17 beta-estradiol

    Yagao Feng; Suya Deng; Zhenqi Liu; Min Hu; Houjun Yan; Qiusheng Wang

    2006-01-01

    BACKGROUND: Recent researches have indicated that estrogen has extensive neuroprotective effects. So some studies designed ovariectomized animal models and administrated with estrogen, so as to verify its neuroprotective effects.OBJECTIVE: To observe the effect of 17 beta-estradiol on the content of norepinephrine (NE) and level of tumor necrosis factor (TNF) in submandibular glands of rats with sympathetic nerve injury, and analyze the dose-dependence and pathway of action.DESIGN: A randomized control animal study.SETTINGS: Department of Hand Surgery, the 252 Hospital of Chinese PLA; Department of Hand Surgery,Union Hospital affiliated to Tongji Medical College, Huazhong University of Science and Technology.MATERIALS: Fifty healthy female Wistar rats were randomly divided into 5 groups with 10 rats in each group: sham-operated group, ovariectomy+6-OHDA+saline group, ovariectomy+6-OHDA+17β-estradiol 50,200 and 500 μg/kg groups.METHODS: The experiments were carried out in Tongji Medical College, Huazhong University of Science and Technology between October 2005 and March 2006. Bilateral ovaries were only exposed but not resected for the rats in the sham-operated group, but bilateral ovaries were resected in all the other groups. In the ovariectomy+6-OHDA+17β-estradiol 50, 200 and 500 μg/kg groups, the rats were administrated with intraperitoneal injection of 6-OHDA (8 mg/kg), and then immediately given 17β-estradiol of corresponding dosages respectively, once a day for 10 days continuously. Rats in the sham-operated group and ovariectomy+6-OHDA+saline group were administrated with saline of the same volume. After administration, 5 rats in each group were killed to determine the NE contents in bilateral submandibular glands with high performance liquid chromatography-electrochemical detector (HPLC-ECD), and the other 5 rats were used to determine the TNF levels in submandibular glands with enzyme-linked immunosorbant assay.MATN OUTCOME MEASURES: The NE contents

  17. Carnosic acid protects against 6-hydroxydopamine-induced neurotoxicity in in vivo and in vitro model of Parkinson's disease: involvement of antioxidative enzymes induction.

    Wu, Chi-Rei; Tsai, Chia-Wen; Chang, Shu-Wei; Lin, Chia-Yuan; Huang, Li-Chun; Tsai, Chia-Wen

    2015-01-01

    The neuroprotective effects of carnosic acid (CA), a phenolic diterpene isolated from rosemary (Rosmarinus officinalis), have been widely investigated in recent years, however, its protection in in vivo still unclear. In this study, we investigated the behavioral activity and neuroprotective effects of CA in a rat model of Parkinson's disease (PD) induced by 6-hydroxydopamine (6-OHDA). Rats were treated with 20mg/kg body weight of CA for 3 weeks before 6-OHDA exposure. Results indicated that CA improved the locomotor activity and reduced the apomorphine-caused rotation in 6-OHDA-stimulated rats. Significant protection against lipid peroxidation and GSH reduction was observed in the 6-OHDA rats pretreated with CA. Pretreatment with CA increased the protein expression of γ-glutamate-cysteine ligase catalytic subunit, γ-glutamate-cysteine ligase modifier subunit, superoxide dismutase, and glutathione reductase compared with 6-OHDA-stimulated rats and SH-SY5Y cells. Immunoblots showed that the reduction of the Bcl-2/Bax ratio, the induction of caspase 3 cleavage, and the induction of poly(ADP-ribose) polymerase (PARP) cleavage by 6-OHDA was reversed in the presence of SB203580 (a p38 inhibitor) or SP600125 (a JNK inhibitor) in SH-SY5Y cells. Rats treated with CA reversed the 6-OHDA-mediated the activation of c-Jun NH2-terminal kinase and p38, the down-regulation of the Bcl-2/Bax ratio, the up-regulation of cleaved caspase 3/caspase 3 and cleaved PARP/PARP ratio, and the down-regulation of tyrosine hydroxylase protein. However, BAM7, an activator of Bax, attenuated the effect of CA on apoptosis in SH-SY5Y cells. These results suggest that CA protected against 6-OHDA-induced neurotoxicity is attributable to its anti-apoptotic and anti-oxidative action. The present findings may help to clarify the possible mechanisms of rosemary in the neuroprotection of PD. PMID:25446857

  18. Neuroprotective effect of ketamine/xylazine on two rat models of Parkinson's disease

    M.M. Ferro

    2007-01-01

    Full Text Available There is a great concern in the literature for the development of neuroprotectant drugs to treat Parkinson's disease. Since anesthetic drugs have hyperpolarizing properties, they can possibly act as neuroprotectants. In the present study, we have investigated the neuroprotective effect of a mixture of ketamine (85 mg/kg and xylazine (3 mg/kg (K/X on the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP or 6-hydroxydopamine (6-OHDA rat models of Parkinson's disease. The bilateral infusion of MPTP (100 µg/side or 6-OHDA (10 µg/side into the substantia nigra pars compacta of adult male Wistar rats under thiopental anesthesia caused a modest (~67% or severe (~91% loss of tyrosine hydroxylase-immunostained cells, respectively. On the other hand, an apparent neuroprotective effect was observed when the rats were anesthetized with K/X, infused 5 min before surgery. This treatment caused loss of only 33% of the nigral tyrosine hydroxylase-immunostained cells due to the MPTP infusion and 51% due to the 6-OHDA infusion. This neuroprotective effect of K/X was also suggested by a less severe reduction of striatal dopamine levels in animals treated with these neurotoxins. In the working memory version of the Morris water maze task, both MPTP- and 6-OHDA-lesioned animals spent nearly 10 s longer to find the hidden platform in the groups where the neurotoxins were infused under thiopental anesthesia, compared to control animals. This amnestic effect was not observed in rats infused with the neurotoxins under K/X anesthesia. These results suggest that drugs with a pharmacological profile similar to that of K/X may be useful to delay the progression of Parkinson's disease.

  19. Tetraspanin (TSP-17 protects dopaminergic neurons against 6-OHDA-induced neurodegeneration in C. elegans.

    Neda Masoudi

    2014-12-01

    Full Text Available Parkinson's disease (PD, the second most prevalent neurodegenerative disease after Alzheimer's disease, is linked to the gradual loss of dopaminergic neurons in the substantia nigra. Disease loci causing hereditary forms of PD are known, but most cases are attributable to a combination of genetic and environmental risk factors. Increased incidence of PD is associated with rural living and pesticide exposure, and dopaminergic neurodegeneration can be triggered by neurotoxins such as 6-hydroxydopamine (6-OHDA. In C. elegans, this drug is taken up by the presynaptic dopamine reuptake transporter (DAT-1 and causes selective death of the eight dopaminergic neurons of the adult hermaphrodite. Using a forward genetic approach to find genes that protect against 6-OHDA-mediated neurodegeneration, we identified tsp-17, which encodes a member of the tetraspanin family of membrane proteins. We show that TSP-17 is expressed in dopaminergic neurons and provide genetic, pharmacological and biochemical evidence that it inhibits DAT-1, thus leading to increased 6-OHDA uptake in tsp-17 loss-of-function mutants. TSP-17 also protects against toxicity conferred by excessive intracellular dopamine. We provide genetic and biochemical evidence that TSP-17 acts partly via the DOP-2 dopamine receptor to negatively regulate DAT-1. tsp-17 mutants also have subtle behavioral phenotypes, some of which are conferred by aberrant dopamine signaling. Incubating mutant worms in liquid medium leads to swimming-induced paralysis. In the L1 larval stage, this phenotype is linked to lethality and cannot be rescued by a dop-3 null mutant. In contrast, mild paralysis occurring in the L4 larval stage is suppressed by dop-3, suggesting defects in dopaminergic signaling. In summary, we show that TSP-17 protects against neurodegeneration and has a role in modulating behaviors linked to dopamine signaling.

  20. Dual SPECT of dopamine system using [99mTc]TRODAT-1 and [123I]IBZM in normal and 6-OHDA-lesioned formosan rock monkeys

    Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by a severe loss of the dopaminergic neurons in the substantia nigra pars compacta. In this study, we evaluated pre- and post-synaptic binding sites of the dopamine system in three normal and one parkinsonian monkeys using simultaneous [99mTc]TRODAT-1 and [123I]IBZM imaging. The parkinsonian monkey was induced by injecting 6-hydroxydopamine (6-OHDA) bilaterally into the medial forebrain bundle under MRI guidance. [99mTc]TRODAT-1 (targeting dopamine transporters) and [123I]IBZM (targeting D2/D3 receptors) were administered almost simultaneously and the SPECT images were acquired over 4 h using a dual-headed gamma camera equipped with ultra-high resolution fan-beam collimators. Data were obtained using energy window of 15% centered on 140 keV for 99mTc in conjunction with 10% asymmetric energy window in a lower bound at 159 keV for 123I. Single SPECT studies of [99mTc]TRODAT-1 and [123I]IBZM were also performed. We found a comparable image quality and uptake ratios between single- and dual-isotope studies. There are higher TRODAT-1 uptakes in the control monkeys than the 6-OHDA-lesioned monkey. The uptake of [123I] IBZM showed no significant difference between controls and 6-OHDA-lesioned monkey. Our results suggest that dual isotope imaging using [99mTc]TRODAT-1 and [123I]IBZM may be a useful means in evaluating the changes of both pre- and post-synaptic dopamine system in a primate model of parkinsonism

  1. Characterization of liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, in rat partial and full nigral 6-hydroxydopamine lesion models of Parkinson's disease.

    Hansen, Henrik H; Fabricius, Katrine; Barkholt, Pernille; Mikkelsen, Jens D; Jelsing, Jacob; Pyke, Charles; Knudsen, Lotte Bjerre; Vrang, Niels

    2016-09-01

    Exendin-4, a glucagon-like peptide-1 (GLP-1) receptor agonist, have been demonstrated to promote neuroprotection in the rat 6-hydroxydopamine (6-OHDA) neurotoxin model of Parkinson's disease (PD), a neurodegenerative disorder characterized by progressive nigrostriatal dopaminergic neuron loss. In this report, we characterized the effect of a long-acting GLP-1 receptor agonist, liraglutide (500µg/kg/day, s.c.) in the context of a partial or advanced (full) 6-OHDA induced nigral lesion in the rat. Rats received a low (3µg, partial lesion) or high (13.5µg, full lesion) 6-OHDA dose stereotaxically injected into the right medial forebrain bundle (n=17-20 rats per experimental group). Six weeks after induction of a partial nigral dopaminergic lesion, vehicle or liraglutide was administered for four weeks. In the full lesion model, vehicle dosing or liraglutide treatment was applied for a total of six weeks starting three weeks pre-lesion, or administered for three weeks starting on the lesion day. Quantitative stereology was applied to assess the total number of midbrain tyrosine hydroxylase (TH) positive dopaminergic neurons. As compared to vehicle controls, liraglutide had no effect on the rotational responsiveness to d-amphetamine or apomorphine, respectively. In correspondence, while numbers of TH-positive nigral neurons were significantly reduced in the lesion side (partial lesion ≈55%; full lesion ≈90%) liraglutide administration had no influence dopaminergic neuronal loss in either PD model setting. In conclusion, liraglutide showed no neuroprotective effects in the context of moderate or substantial midbrain dopaminergic neuronal loss and associated functional motor deficits in the rat 6-OHDA lesion model of PD. PMID:27233809

  2. Differential pattern of motor impairments in neurotoxic, environmental and inflammation-driven rat models of Parkinson's disease.

    Naughton, Carol; Moriarty, Niamh; Feehan, Jennifer; O'Toole, Daniel; Dowd, Eilís

    2016-01-01

    One of the reasons proposed for the paucity of drug discovery for Parkinson's disease is the lack of relevant animal models of the condition. Parkinson's disease has been modelled extensively using the selective neurotoxin, 6-hydroxydopamine (6-OHDA). However, as this model bears little etiological resemblance to the human condition, there has been a drive to develop models with improved etiological validity. Two such models are those induced by the pesticide, rotenone, and the inflammagen, lipopolysaccharide (LPS). However, to date, these models have been poorly characterised in terms of their motor profiles and have never been directly compared to the more established models. Thus, the aim of this study was to characterise the behavioural profile of the rotenone and LPS models, and to compare them with the 6-OHDA model. Animals underwent baseline testing on the Stepping, Whisker, Corridor and Cylinder Tests of motor function. They were then grouped for unilateral intra-striatal infusion of 6-OHDA, rotenone or LPS. Motor testing continued for ten weeks after which the rats were processed for immunohistochemical analysis of nigrostriatal integrity. We found that, although all neurotoxins induced a similar level of nigrostriatal neurodegeneration, neither the rotenone nor LPS models were associated with amphetamine-induced rotation, and they were associated with significantly less pronounced and stable impairments in the spontaneous tasks than the 6-OHDA model. In conclusion, this study demonstrates key differences in the pattern of motor dysfunction induced by Parkinsonian neurotoxins which should be taken into consideration when selecting the most appropriate model for Parkinson's disease preclinical studies. PMID:26393432

  3. Intracranial application of near-infrared light in a hemi-parkinsonian rat model: the impact on behavior and cell survival.

    Reinhart, Florian; Massri, Nabil El; Chabrol, Claude; Cretallaz, Celine; Johnstone, Daniel M; Torres, Napoleon; Darlot, Fannie; Costecalde, Thomas; Stone, Jonathan; Mitrofanis, John; Benabid, Alim-Louis; Moro, Cécile

    2016-06-01

    OBJECT The authors of this study used a newly developed intracranial optical fiber device to deliver near-infrared light (NIr) to the midbrain of 6-hydroxydopamine (6-OHDA)-lesioned rats, a model of Parkinson's disease. The authors explored whether NIr had any impact on apomorphine-induced turning behavior and whether it was neuroprotective. METHODS Two NIr powers (333 nW and 0.16 mW), modes of delivery (pulse and continuous), and total doses (634 mJ and 304 J) were tested, together with the feasibility of a midbrain implant site, one considered for later use in primates. Following a striatal 6-OHDA injection, the NIr optical fiber device was implanted surgically into the midline midbrain area of Wistar rats. Animals were tested for apomorphine-induced rotations, and then, 23 days later, their brains were aldehyde fixed for routine immunohistochemical analysis. RESULTS The results showed that there was no evidence of tissue toxicity by NIr in the midbrain. After 6-OHDA lesion, regardless of mode of delivery or total dose, NIr reduced apomorphine-induced rotations at the stronger, but not at the weaker, power. The authors found that neuroprotection, as assessed by tyrosine hydroxylase expression in midbrain dopaminergic cells, could account for some, but not all, of the observed behavioral improvements; the groups that were associated with fewer rotations did not all necessarily have a greater number of surviving cells. There may have been other "symptomatic" elements contributing to behavioral improvements in these rats. CONCLUSIONS In summary, when delivered at the appropriate power, delivery mode, and dosage, NIr treatment provided both improved behavior and neuroprotection in 6-OHDA-lesioned rats. PMID:26613166

  4. Nrf2 signaling contributes to the neuroprotective effects of urate against 6-OHDA toxicity.

    Ning Zhang

    Full Text Available BACKGROUND: Mounting evidence shows that urate may become a biomarker of Parkinson's disease (PD diagnosis and prognosis and a neuroprotectant candidate for PD therapy. However, the cellular and molecular mechanisms underlying its neuroprotective actions remain poorly understood. RESULTS: In this study, we showed that urate pretreatment protected dopaminergic cell line (SH-SY5Y and MES23.5 against 6-hydroxydopamine (6-OHDA- and hydrogen peroxide- induced cell damage. Urate was found to be accumulated into SH-SY5Y cells after 30 min treatment. Moreover, urate induced NF-E2-related factor 2 (Nrf2 accumulation by inhibiting its ubiquitinationa and degradation, and also promoted its nuclear translocation; however, it did not modulate Nrf2 mRNA level or Kelch-like ECH-associated protein 1 (Keap1 expression. In addition, urate markedly up-regulated the transcription and protein expression of γ-glutamate-cysteine ligase catalytic subunit (γ-GCLC and heme oxygenase-1 (HO-1, both of which are controlled by Nrf2 activity. Furthermore, Nrf2 knockdown by siRNA abolished the intracellular glutathione augmentation and the protection exerted by urate pretreatment. CONCLUSION: Our findings demonstrated that urate treatment may result in Nrf2-targeted anti-oxidant genes transcription and expression by reducing Nrf2 ubiquitination and degradation and promoting its nuclear translocation, and thus offer neuroprotection on dopaminergic cells against oxidative stresses.

  5. Lesion of the subthalamic nucleus reverses motor deficits but not death of nigrostriatal dopaminergic neurons in a rat 6-hydroxydopamine-lesion model of Parkinson's disease

    V. Rizelio

    2010-01-01

    Full Text Available The objective of the present study was to determine whether lesion of the subthalamic nucleus (STN promoted by N-methyl-D-aspartate (NMDA would rescue nigrostriatal dopaminergic neurons after unilateral 6-hydroxydopamine (6-OHDA injection into the medial forebrain bundle (MFB. Initially, 16 mg 6-OHDA (6-OHDA group or vehicle (artificial cerebrospinal fluid - aCSF; Sham group was infused into the right MFB of adult male Wistar rats. Fifteen days after surgery, the 6-OHDA and SHAM groups were randomly subdivided and received ipsilateral injection of either 60 mM NMDA or aCSF in the right STN. Additionally, a control group was not submitted to stereotaxic surgery. Five groups of rats were studied: 6-OHDA/NMDA, 6-OHDA/Sham, Sham/NMDA, Sham/Sham, and Control. Fourteen days after injection of 6-OHDA, rats were submitted to the rotational test induced by apomorphine (0.1 mg/kg, ip and to the open-field test. The same tests were performed again 14 days after NMDA-induced lesion of the STN. The STN lesion reduced the contralateral turns induced by apomorphine and blocked the progression of motor impairment in the open-field test in 6-OHDA-treated rats. However, lesion of the STN did not prevent the reduction of striatal concentrations of dopamine and metabolites or the number of nigrostriatal dopaminergic neurons after 6-OHDA lesion. Therefore, STN lesion is able to reverse motor deficits after severe 6-OHDA-induced lesion of the nigrostriatal pathway, but does not protect or rescue dopaminergic neurons in the substantia nigra pars compacta.

  6. Alterations in primary motor cortex neurotransmission and gene expression in hemi-parkinsonian rats with drug-induced dyskinesia.

    Lindenbach, D; Conti, M M; Ostock, C Y; Dupre, K B; Bishop, C

    2015-12-01

    Treatment of Parkinson's disease (PD) with dopamine replacement relieves symptoms of poverty of movement, but often causes drug-induced dyskinesias. Accumulating clinical and pre-clinical evidence suggests that the primary motor cortex (M1) is involved in the pathophysiology of PD and that modulating cortical activity may be a therapeutic target in PD and dyskinesia. However, surprisingly little is known about how M1 neurotransmitter tone or gene expression is altered in PD, dyskinesia or associated animal models. The present study utilized the rat unilateral 6-hydroxydopamine (6-OHDA) model of PD/dyskinesia to characterize structural and functional changes taking place in M1 monoamine innervation and gene expression. 6-OHDA caused dopamine pathology in M1, although the lesion was less severe than in the striatum. Rats with 6-OHDA lesions showed a PD motor impairment and developed dyskinesia when given L-DOPA or the D1 receptor agonist, SKF81297. M1 expression of two immediate-early genes (c-Fos and ARC) was strongly enhanced by either L-DOPA or SKF81297. At the same time, expression of genes specifically involved in glutamate and GABA signaling were either modestly affected or unchanged by lesion and/or treatment. We conclude that M1 neurotransmission and signal transduction in the rat 6-OHDA model of PD/dyskinesia mirror features of human PD, supporting the utility of the model to study M1 dysfunction in PD and the elucidation of novel pathophysiological mechanisms and therapeutic targets. PMID:26363150

  7. Neuroprotective Properties of a Standardized Extract from Myracrodruon urundeuva Fr. All. (Aroeira-Do-Sertão, as Evaluated by a Parkinson’s Disease Model in Rats

    Iana Calou

    2014-01-01

    Full Text Available Myracrodruon urundeuva Fr. All. (Anacardiaceae is a Brazilian medicinal species, which is common to the Northeastern Brazilian semiarid region, whose stem-bark is widely used in folk medicine. It is an endangered species, presenting as main bioactive components tannins and chalcones. In this work, we studied the neuroprotective effects of a standardized extract from cultivated M. urundeuva (SEMU, in a model of Parkinson’s disease. Thus, a unilateral injection of 6-OHDA was done into the rat right stratum. The animals were submitted to stereotaxic surgery, then treated with SEMU (5, 10, 20, or 40 mg/kg, p.o. for 2 weeks, subjected to behavioral tests, and euthanized for striata dissections and neurochemical, histological, and immunohistochemical analyses. We showed, for the first time, that SEMU reverted behavioral alterations seen in the 6-OHDA-lesioned group and partially blocked the decrease in DA and DOPAC contents. The numbers of viable neurons and TH immunopositive cells were increased by SEMU. In addition, the SEMU-treated 6-OHDA groups showed lower numbers of GFAP and OX-42 immunopositive cells. The neuroprotective action of SEMU is possibly related to the antioxidant and anti-inflammatory properties of M. urundeuva, pointing out to its potential use in the prevention or treatment of neurodegenerative conditions, such as Parkinson’s disease.

  8. The Effect of Chronic Administration of Buspirone on 6-Hydroxydopamine-Induced Catalepsy in Rats

    Hamdolah Sharifi

    2012-06-01

    Full Text Available Purpose: Several evidences show that serotonergic neurons play a role in the regulation of movements executed by the basal ganglia. Recently we have reported that single dose of buspirone improved 6-hydroxydopamine (6-OHDA and haloperidol-induced catalepsy. This study is aimed to investigate effect of chronic intraperitoneal (i.p. administration of buspirone on 6-OHDA-induced catalepsy in male Wistar rats. Methods: Catalepsy was induced by unilateral infusion of 6-OHDA (8 μg/2 μl/rat into the central region of the SNc and was assayed by the bar-test method 5, 60, 120 and 180 min after drugs administration in 10th day. The effect of buspirone (0.5, 1 and 2 mg/kg, i.p. for 10 days was assessed in 6-OHDA-lesioned rats. Results: The results showed that chronic injection of buspirone (0.5, 1 and 2 mg/kg, i.p. for 10 days decreased catalepsy when compared with the control group. The best anticataleptic effect was observed at the dose of 1 mg/kg. The catalepsy-improving effect of buspirone was reversed by 1-(2-methoxyphenyl- 4-[4-(2-phthalimido butyl]piperazine hydrobromide (NAN-190, 0.5 mg/kg, i.p.,as a 5-HT1A receptor antagonist. Conclusion: Our study indicates that chronic administration of buspirone improves catalepsy in a 6-OHDA-induced animal model of parkinson's disease (PD. We also suggest that buspirone may be used as an adjuvant therapy to increase effectiveness of antiparkinsonian drugs. In order to prove this hypothesis, further clinical studies should be done.

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

    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. PMID:26498277

  10. The beneficial effect of the flavonoid quercetin on behavioral changes in hemi-Parkinsonian rats

    Mehdi Mehdizadeh

    2010-01-01

    Full Text Available   Abstract   Introduction: A large body of experimental evidence supports a role for oxidative stress as a mediator of nerve cell death in Parkinson's disease (PD. Flavonoids like quercetin have been reported to prevent neuronal degeneration caused by increased oxidative burden, therefore, this study examined whether quercetin administration at a high dose would attenuate behavioral abnormalities in experimental model of PD in rat.   Methods: For this purpose, unilateral intrastriatal 6-hydroxydopamine (6-OHDA-lesioned rats were pretreated with quercetin (20 mg/kg; i.p. 1 hour before surgery and treated once a day for one month. After one month, apomorphine-induced rotational behavior was measured postlesion.   Results: Apomorphine-induced rotations were counted after 4 weeks. Quercetin administration could attenuate the rotational behavior in treated lesioned rats as compared to untreated ones.   Discussion: Flavonoid quercetin administration for one month could attenuate behavioral abnormalities in 6-OHDA model of PD.

  11. Effect of Chronic L-Dopa or Melatonin Treatments after Dopamine Deafferentation in Rats: Dyskinesia, Motor Performance, and Cytological Analysis

    Ana Luisa Gutierrez-Valdez; Verónica Anaya-Martínez; José Luis Ordoñez-Librado; Ricardo García-Ruiz; Carmen Torres-Esquivel; Montserrat Moreno-Rivera; Javier Sánchez-Betancourt; Enrique Montiel-Flores; Maria Rosa Avila-Costa

    2012-01-01

    The present study examines the ability of melatonin to protect striatal dopaminergic loss induced by 6-OHDA in a rat model of Parkinson's disease, comparing the results with L-DOPA-treated rats. The drugs were administered orally daily for a month, their therapeutic or dyskinetic effects were assessed by means of abnormal involuntary movements (AIMs) and stepping ability. At the cellular level, the response was evaluated using tyrosine hydroxylase immunoreactivity and striatal ultrastructural...

  12. Establishment of a Parkinson's disease model in rats via striatal one-site double injection Feasibility observation

    Bing Liu; Li Ma; Yulong Shi; Boli Zhang

    2008-01-01

    BACKGROUND: To date, many 6-hydroxydopamine (6-OHDA)-lesioned rat models have been established by injecting 6-OHDA into two or more sites in the substantia nigra pars compacta, striatum or median forebrain bundle. The success rate of models established by this method is satisfactory, but it can raise the death rate, and is elaborate and tedious to perform.OBJECTIVE: To observe the difference between injections of 6-OHDA into the striatum from one site and two sites, and to explore the feasibility of establishing Parkinson's disease rat models via striatal one-site double injection.DESIGN, TIME AND SETTING: A randomized, controlled animal experiment based on a modeling comparison was performed at the Pharmacology Laboratory of Traditional Chinese Medicine, Academy of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine between August 2005 and April 2006.MATERIALS: A total of 46 male Wistar rats were purchased from Beijing Weitong Lihua Experimental Animal Technical Co., Ltd., China. 6-OHDA hydrogen bromide was sourced from Sigma Co., Ltd., USA.METHODS: All 46 rats were randomized to three groups: one-site injection (n = 18), two-site injection (n = 18), and control (n = 10). Lesions in rat brains were established by infusing 5 p g 6-OHDA into the striatum at the following coordinates: anteroposterior (AP) 1.0 ram, mediolateral (ML) 2.7 mm,dorsoventral (DV) -5.2 or -6.0 mm for the one-site injection group, and AP 1.0 mm, ML 2.5 ram, DV -4.5 mm/AP -0.4 ram, ML 3.5 mm, DV -4.5 mm for the two-site injection group, respectively. Rats in the control group were injected with the same volume of 0.01% ascorbic acid as above.MAIN OUTCOME MEASURES: Tyrosine hydroxylase-positive neurons were detected by immunohistochemistry. Success rates of PD models established by one-site and two-site injection techniques were examined.RESULTS: One rat died in the one-site injection group and four in the two-site injection group. Thus behavioral testing was

  13. Transplantation of ES cells to Parkinson model rat irradiated with carbon ion beam

    The present study was designed to make a new Parkinson disease model using carbon ion beam. We irradiated right medial forebrain bundle of adult SD rats with charged carbon particles (290 MeV/nucleon, Mono peak, 150 Gy) and damaged right dopaminergic neurons pathway. To irradiate precisely, rats were set in the stereotactic frame with ear bars. Four weeks after the irradiation, behavioral test and in vitro autoradiography showed hemi-Parkinson model as well as 6-OHDA lesioned rats. Pathological examinations showed cell death, gliosis and inflammations at the irradiated area. However, no obvious alteration was observed at the surrounding normal tissue. These results indicated utility and validity of this method. (author)

  14. Expression of calbindin D28K in substantia nigra of model rats with Parkinson disease

    Dianshuai Gao; Hongmei Liu; Yanxia Ding; Hongjun Wang; Yanqiang Wang

    2006-01-01

    BACKGROUND: Previous researches suggested that expression level of calbindin D28K mRNA decreased in substantia nigra (SN) of model rats with Parkinson disease (PD), and this might be related to the decrease of anti-degeneration potentials of dopaminergic neurons.OBJECTIVE: To observe expression changes of calbindin D28K in SN dopaminergic neurons during their degeneration and death in midbrain of PD model rats.DESIGN: Completely randomized grouping design.SETTING: Department of Neurobiology, Xuzhou Medical College.MATERIALS: A total of 92 healthy male SD rats, with the age of 3 months, weighing 200-250 g, were selected from Experimental Animal Center of Xuzhou Medical College [certification: SCXK (su) 2003-0003].Calbindin D28K(CB), tyroxine hydroxylase (TH), ABC kit, 6-hydroxydopamine (6-OHDA) and Nissl dyes were provided by Sigma Company, and sheep serum was provided by Beijing Zhongshan Company.METHODS: The experiment was carried out in the Neurobiological Center of Xuzhou Medical College from October 2003 to October 2004. ① With lot method, rats were divided into blank control group (n=28), experimental control group (n=28) and experimental group (n=36). Rats in experimental group were injected with 6-OHDA at right corpus striatum for PD modeling; rats in experimental control group were injected with saline at the same site; rats in blank control group did not give any injections. ② On the 7th, 14th, 21st and 28th days, SN segments on right midbrain from every 5 rats in experimental group were fixed, embedded with paraffin and cut into successively coronary pieces. Rats in other two groups were treated with the same methods and then stained with Nissl to show neuronal form. Meanwhile, CB and TH antibodies staining with immunohistochemistry were used to show CB containing dopaminergic neurons and dopaminergic neurons,and cells were calculated and observed under optic microscope. ③ On the 14th and 28th days, every 4 rats in experimental group and every 4

  15. Exposure to Early Life Stress Results in Epigenetic Changes in Neurotrophic Factor Gene Expression in a Parkinsonian Rat Model

    Thabisile Mpofana

    2016-01-01

    Full Text Available Early life adversity increases the risk of mental disorders later in life. Chronic early life stress may alter neurotrophic factor gene expression including those for brain derived neurotrophic factor (BDNF and glial cell derived neurotrophic factor (GDNF that are important in neuronal growth, survival, and maintenance. Maternal separation was used in this study to model early life stress. Following unilateral injection of a mild dose of 6-hydroxydopamine (6-OHDA, we measured corticosterone (CORT in the blood and striatum of stressed and nonstressed rats; we also measured DNA methylation and BDNF and GDNF gene expression in the striatum using real time PCR. In the presence of stress, we found that there was increased corticosterone concentration in both blood and striatal tissue. Further to this, we found higher DNA methylation and decreased neurotrophic factor gene expression. 6-OHDA lesion increased neurotrophic factor gene expression in both stressed and nonstressed rats but this increase was higher in the nonstressed rats. Our results suggest that exposure to early postnatal stress increases corticosterone concentration which leads to increased DNA methylation. This effect results in decreased BDNF and GDNF gene expression in the striatum leading to decreased protection against subsequent insults later in life.

  16. Heat shock protein 60 affects behavioral improvement in a rat model of Parkinson's disease grafted with human umbilical cord mesenchymal stem cell-derived dopaminergic-like neurons.

    Zhao, Can; Li, Hui; Zhao, Xian-Jing; Liu, Zheng-Xia; Zhou, Ping; Liu, Ying; Feng, Mei-Jiang

    2016-06-01

    Parkinson's disease (PD) is a neurodegenerative disorder that is caused by a loss of dopaminergic (DAergic) neurons in mesencephalic substantia nigra (SN). Human umbilical cord mesenchymal stem cells (hUC-MSCs) are capable of self-renewal and differentiation into multiple cell lineages, including DAergic neurons. Thus, hUC-MSCs could be a promising alternative to compensate for the loss of DAergic neurons in PD. In the current study, hUC-MSCs and hUC-MSCs-derived DAergic-like neurons were transplanted into the striatum and SN of a rat model of PD that is induced by 6-hydroxydopamine (6-OHDA). We evaluated their therapeutic effects on improving rotation behavior in the rat and on modulating the level of heat shock protein 60 (Hsp60) expression in the brain. After transplantation, an amelioration of rotation behavior was observed in rats that underwent cell grafting, and hUC-MSCs-derived DAergic-like neurons were superior to hUC-MSCs at inducing behavioral improvement. Western blot and immunohistochemistry analysis indicated significantly elevated levels of Hsp60 in cell-grafted rats compared to 6-OHDA-lesioned (PD) rats. These results demonstrate that hUC-MSCs-based cell transplantation is potential therapeutic treatment for PD, and hUC-MSCs-derived DAergic-like neurons appear to be favorable candidates for cell replacement therapy in PD. Finally, Hsp60 could be involved in a mechanism of behavioral recovery. PMID:26758268

  17. Neuroprotection in a rat Parkinson model by GDNF gene therapy using EIAV vector.

    Azzouz, Mimoun; Ralph, Scott; Wong, Liang-Fong; Day, Denise; Askham, Zoe; Barber, Robert D; Mitrophanous, Kyriacos A; Kingsman, Susan M; Mazarakis, Nicholas D

    2004-04-29

    Vectors based on lentiviruses are opening up new approaches for the treatment of neurodegenerative diseases. Currently, the equine infectious anaemia virus (EIAV) vector is one of the most attractive gene delivery systems with respect to neuronal tropism. The aim was to validate EIAV-lentiviral vectors as a gene delivery system for neurotrophic factor genes in an animal model of Parkinson's disease. EIAV carrying the glial cell line-derived neurotrophic factor (GDNF) gene was unilaterally injected into rat striatum and above the substantia nigra (SN). One week later, the rats received a 6-OHDA lesion into the ipsilateral striatum. GDNF delivery led to extensive expression of GDNF protein within the striatum. In addition, near complete protection against dopaminergic cell death was observed in the GDNF-treated group. PMID:15076720

  18. Intrastriatal GDNF gene transfer by inducible lentivirus vectors protects dopaminergic neurons in a rat model of parkinsonism.

    Chen, Sha-Sha; Yang, Chun; Hao, Fei; Li, Chen; Lu, Tao; Zhao, Li-Ru; Duan, Wei-Ming

    2014-11-01

    Glial cell line-derived neurotrophic factor (GDNF) has neuroprotective effects on dopaminergic (DA) neurons both in vivo and in vitro. However, substantial evidence has shown that a long-term overexpression of GDNF gene is often associated with side effects. We previously improved tetracycline (Tet)-On lentivirus system carrying human GDNF (hGDNF) gene, and demonstrated that hGDNF gene expression was tightly regulated and functional in vitro. Here we further examined the efficiency and neuroprotection of Tet-On lentivirus-mediated hGDNF gene regulation in neural progenitor cells (NPCs) and a rat model of parkinsonism. The results showed that hGDNF gene expression was tightly regulated in transduced NPCs. Doxycycline (Dox)-induced hGDNF protected DA neurons from 6-hydroxydopamine (6-OHDA)-induced toxicity in vitro. Intrastriatal injections of Tet-On lentivirus vectors resulted in dramatically increased levels of hGDNF protein in the striatum of rats with Dox-drinking water, when compared to lentivirus-injected and saline-injected rats with normal drinking water, respectively. In addition, hGDNF protected nigral DA neurons and striatal DA fibers, and attenuated d-amphetamine-induced rotational asymmetry in the 6-OHDA lesioned rats. To the best of our knowledge, this is the first report that hGDNF gene transfer by Tet-On lentivirus vectors is tightly regulated in rat brain, and Dox-induced hGDNF is functional in neuroprotection of nigral DA neurons in a rat model of parkinsonism. PMID:24997241

  19. CX3CL1 reduces neurotoxicity and microglial activation in a rat model of Parkinson's disease

    Hudson Charles E

    2011-01-01

    Full Text Available Abstract Background Parkinson's disease is characterized by a progressive loss of dopaminergic neurons in the substantia nigra. The cause of the neurodegeneration is unknown. Neuroinflammation has been clearly shown in Parkinson's disease and may be involved in the progressive nature of the disease. Microglia are capable of producing neuronal damage through the production of bioactive molecules such as cytokines, as well as reactive oxygen species (ROS, and nitric oxide (NO. The inflammatory response in the brain is tightly regulated at multiple levels. One form of immune regulation occurs via neurons. Fractalkine (CX3CL1, produced by neurons, suppresses the activation of microglia. CX3CL1 is constitutively expressed. It is not known if addition of exogenous CX3CL1 beyond otherwise physiologically normal levels could decrease microglia activation and thereby minimize the secondary neurodegeration following a neurotoxic insult. Methods The intrastriatal 6-hydroxydopamine (6-OHDA rat model of Parkinson disease, was used to test the hypothesis that exogenous CX3CL1 could be neuroprotective. Treatment with recombinant CX3CL1 was delivered to the striatum by an osmotic minipump for 28 days beginning 7 days after the initial insult. Unbiased stereological methods were used to quantify the lesion size in the striatum, the amount of neuronal loss in the substantia nigra, and the amount of microglia activation. Results As hypothesized, CX3CL1 was able to suppress this microglia activation. The reduced microglia activation was found to be neuroprotective as the CX3CL1 treated rats had a smaller lesion volume in the striatum and importantly significantly fewer neurons were lost in the CX3CL1 treated rats. Conclusion These findings demonstrated that CX3CL1 plays a neuroprotective role in 6-OHDA-induced dopaminergic lesion and it might be an effective therapeutic target for many neurodegenerative diseases, including Parkinson disease and Alzheimer disease

  20. Functional characterization and expression of thalamic GABAB receptors in a rodent model of Parkinson’s disease

    de Groote, C; Wüllner, U; Löschmann, P.-A.; Luiten, P.G.M.; Klockgether, T

    1999-01-01

    Increased GABAergic neurotransmission of the basal ganglia output nuclei projecting to the motor thalamus is thought to contribute to the pathophysiology of Parkinson’s disease. We investigated the functional role of thalamic GABAB receptors in a rodent model of Parkinson’s disease. First, we examined the effects of blockade of GABAB receptors in the ventromedial thalamic nucleus of rats with a unilateral 6-OHDA lesion of the substantia nigra on locomotor activity. In addition we studied the ...

  1. Ellagic acid improves hyperalgesia and cognitive deficiency in 6-hydroxidopamine induced rat model of Parkinson’s disease

    Mojtaba Dolatshahi

    2015-01-01

    Conclusion: 6-OHDA can induce oxidative stress and can disrupt the neural mechanisms underlying proper integration of painful stimuli and cognitive processes in MFB-lesioned rats. Consequently, nigrostriatal pathway can play possible role in nociception and cognition. EA, a natural antioxidant, has neuroprotective effect on this pathway and can ameliorate this defect and be considered in PD management.

  2. Serotonergic modulation of receptor occupancy in rats treated with L-DOPA after unilateral 6-OHDA lesioning

    Nahimi, Adjmal; Høltzermann, Mette; Landau, Anne M.;

    2012-01-01

    Recent studies suggest that l-3,4 dihydroxyphenylalanine (L-DOPA)-induced dyskinesia (LID), a severe complication of conventional L-DOPA therapy of Parkinson's disease, may be caused by dopamine (DA) release originating in serotonergic neurons. To evaluate the in vivo effect of a 5-HT(1A) agonist...

  3. Transplantation of human umbilical cord blood-derived mononuclear cells induces recovery of motor dysfunction in a rat model of Parkinson's disease

    Chen C

    2016-04-01

    Full Text Available Chao Chen,1,* Jing Duan,1,* Aifang Shen,2,* Wei Wang,1 Hao Song,1 Yanming Liu,1 Xianjie Lu,1 Xiaobing Wang,2 Zhiqing You,1 Zhongchao Han,3,4 Fabin Han1 1Center for Stem Cells and Regenerative Medicine, The Liaocheng People's Hospital, Affiliated Liaocheng Hospital, Taishan Medical University, Shandong, People's Republic of China; 2Department of Gynecology and Obstetrics, The Liaocheng People's Hospital, Affiliated Liaocheng Hospital, Taishan Medical University, Shandong, People's Republic of China; 3The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences, Peking Union of Medical College, Tianjin, People's Republic of China; 4National Engineering Research Center of Cell Products, AmCellGene Co. Ltd., TEDA, Tianjin, People's Republic of China*These authors contributed equally to this workAbstract: Human umbilical cord blood-derived mononuclear cells (hUCB-MNCs were reported to have neurorestorative capacity for neurological disorders such as stroke and traumatic brain injury. This study was performed to explore if hUCB-MNC transplantation plays any therapeutic effects for Parkinson's disease (PD in a 6-OHDA-lesioned rat model of PD. hUCB-MNCs were isolated from umbilical cord blood and administered to the striatum of the 6-OHDA-lesioned rats. The apomorphine-induced locomotive turning-overs were measured to evaluate the improvement of motor dysfunctions of the rats after administration of hUCB-MNCs. We observed that transplanted hUCB-MNCs significantly improve the motor deficits of the PD rats and that grafted hUCB-MNCs integrated to the host brains and differentiated to neurons and dopamine neurons in vivo after 16 weeks of transplantation. Our study provided evidence that transplanted hUCB-MNCs play therapeutic effects in a rat PD model by differentiating to neurons and dopamine neurons. Keywords: hUCB-MNCs, Parkinson's disease, transplantation

  4. Multicistronic lentiviral vector-mediated striatal gene transfer of aromatic L-amino acid decarboxylase, tyrosine hydroxylase, and GTP cyclohydrolase I induces sustained transgene expression, dopamine production, and functional improvement in a rat model of Parkinson's disease.

    Azzouz, Mimoun; Martin-Rendon, Enca; Barber, Robert D; Mitrophanous, Kyriacos A; Carter, Emma E; Rohll, Jonathan B; Kingsman, Susan M; Kingsman, Alan J; Mazarakis, Nicholas D

    2002-12-01

    Parkinson's disease (PD) is a neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in the substantia nigra. This loss leads to complete dopamine depletion in the striatum and severe motor impairment. It has been demonstrated previously that a lentiviral vector system based on equine infectious anemia virus (EIAV) gives rise to highly efficient and sustained transduction of neurons in the rat brain. Therefore, a dopamine replacement strategy using EIAV has been investigated as a treatment in the 6-hydroxydopamine (6-OHDA) animal model of PD. A self-inactivating EIAV minimal lentiviral vector that expresses tyrosine hydroxylase (TH), aromatic amino acid dopa decarboxylase (AADC), and GTP cyclohydrolase 1 (CH1) in a single transcription unit has been generated. In cultured striatal neurons transduced with this vector, TH, AADC, and CH1 proteins can all be detected. After stereotactic delivery into the dopamine-denervated striatum of the 6-OHDA-lesioned rat, sustained expression of each enzyme and effective production of catecholamines were detected, resulting in significant reduction of apomorphine-induced motor asymmetry compared with control animals (p < 0.003). Expression of each enzyme in the striatum was observed for up to 5 months after injection. These data indicate that the delivery of three catecholaminergic synthetic enzymes by a single lentiviral vector can achieve functional improvement and thus open the potential for the use of this vector for gene therapy of late-stage PD patients. PMID:12451130

  5. Naringin treatment induces neuroprotective effects in a mouse model of Parkinson's disease in vivo, but not enough to restore the lesioned dopaminergic system.

    Kim, Heung Deok; Jeong, Kyoung Hoon; Jung, Un Ju; Kim, Sang Ryong

    2016-02-01

    We recently reported that treatment with naringin, a major flavonoid found in grapefruit and citrus fruits, attenuated neurodegeneration in a rat model of Parkinson's disease (PD) in vivo. In order to investigate whether its effects are universally applied to a different model of PD and whether its treatment induces restorative effects on the lesioned nigrostriatal dopaminergic (DA) projection, we observed the effects of pre-treatment or post-treatment with naringin in a mouse model of PD. For neuroprotective effects, 6-hydroxydopamine (6-OHDA) was unilaterally injected into the striatum of mouse brains for a neurotoxin model of PD in the presence or absence of naringin by daily intraperitoneal injection. Our results showed that naringin protected the nigrostriatal DA projection from 6-OHDA-induced neurotoxicity. Moreover, similar to the effects in rat brains, this treatment induced the activation of mammalian target of rapamycin complex 1 (mTORC1), which is well known as an important survival factor for DA neurons, and inhibited microglial activation in the substantia nigra (SN) of mouse brains treated with 6-OHDA. However, there was no significant change of DA phenotypes in the SN and striatum post-treated with naringin compared with 6-OHDA-lesioned mice, despite the treatment being continued for 12 weeks. These results suggest that post-treatment with naringin alone may not be enough to restore the nigrostriatal DA projection in a mouse model of PD. However, our results apparently suggest that naringin is a beneficial natural product to prevent DA degeneration, which is involved in PD. PMID:26878791

  6. Exercise exerts neuroprotective effects on Parkinson's disease model of rats.

    Tajiri, Naoki; Yasuhara, Takao; Shingo, Tetsuro; Kondo, Akihiko; Yuan, Wenji; Kadota, Tomohito; Wang, Feifei; Baba, Tanefumi; Tayra, Judith Thomas; Morimoto, Takamasa; Jing, Meng; Kikuchi, Yoichiro; Kuramoto, Satoshi; Agari, Takashi; Miyoshi, Yasuyuki; Fujino, Hidemi; Obata, Futoshi; Takeda, Isao; Furuta, Tomohisa; Date, Isao

    2010-01-15

    Recent studies demonstrate that rehabilitation ameliorates physical and cognitive impairments of patients with stroke, spinal cord injury, and other neurological diseases and that rehabilitation also has potencies to modulate brain plasticity. Here we examined the effects of compulsive exercise on Parkinson's disease model of rats. Before 6-hydroxydopamine (6-OHDA, 20 microg) lesion into the right striatum of female SD rats, bromodeoxyuridine (BrdU) was injected to label the proliferating cells. Subsequently, at 24 h after the lesion, the rats were forced to run on the treadmill (5 days/week, 30 min/day, 11 m/min). As behavioral evaluations, cylinder test was performed at 1, 2, 3, and 4 weeks and amphetamine-induced rotational test was performed at 2 and 4 weeks with consequent euthanasia for immunohistochemical investigations. The exercise group showed better behavioral recovery in cylinder test and significant decrease in the number of amphetamine-induced rotations, compared to the non-exercise group. Correspondingly, significant preservation of tyrosine hydroxylase (TH)-positive fibers in the striatum and TH-positive neurons in the substantia nigra pars compacta (SNc) was demonstrated, compared to the non-exercise group. Additionally, the number of migrated BrdU- and Doublecortin-positive cells toward the lesioned striatum was increased in the exercise group. Furthermore, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor increased in the striatum by exercise. The results suggest that exercise exerts neuroprotective effects or enhances the neuronal differentiation in Parkinson's disease model of rats with subsequent improvement in deteriorated motor function. PMID:19900418

  7. Trans-blood brain barrier delivery of dopamine-loaded nanoparticles reverses functional deficits in parkinsonian rats.

    Pahuja, Richa; Seth, Kavita; Shukla, Anshi; Shukla, Rajendra Kumar; Bhatnagar, Priyanka; Chauhan, Lalit Kumar Singh; Saxena, Prem Narain; Arun, Jharna; Chaudhari, Bhushan Pradosh; Patel, Devendra Kumar; Singh, Sheelendra Pratap; Shukla, Rakesh; Khanna, Vinay Kumar; Kumar, Pradeep; Chaturvedi, Rajnish Kumar; Gupta, Kailash Chand

    2015-05-26

    Sustained and safe delivery of dopamine across the blood brain barrier (BBB) is a major hurdle for successful therapy in Parkinson's disease (PD), a neurodegenerative disorder. Therefore, in the present study we designed neurotransmitter dopamine-loaded PLGA nanoparticles (DA NPs) to deliver dopamine to the brain. These nanoparticles slowly and constantly released dopamine, showed reduced clearance of dopamine in plasma, reduced quinone adduct formation, and decreased dopamine autoxidation. DA NPs were internalized in dopaminergic SH-SY5Y cells and dopaminergic neurons in the substantia nigra and striatum, regions affected in PD. Treatment with DA NPs did not cause reduction in cell viability and morphological deterioration in SH-SY5Y, as compared to bulk dopamine-treated cells, which showed reduced viability. Herein, we report that these NPs were able to cross the BBB and capillary endothelium in the striatum and substantia nigra in a 6-hydroxydopamine (6-OHDA)-induced rat model of PD. Systemic intravenous administration of DA NPs caused significantly increased levels of dopamine and its metabolites and reduced dopamine-D2 receptor supersensitivity in the striatum of parkinsonian rats. Further, DA NPs significantly recovered neurobehavioral abnormalities in 6-OHDA-induced parkinsonian rats. Dopamine delivered through NPs did not cause additional generation of ROS, dopaminergic neuron degeneration, and ultrastructural changes in the striatum and substantia nigra as compared to 6-OHDA-lesioned rats. Interestingly, dopamine delivery through nanoformulation neither caused alterations in the heart rate and blood pressure nor showed any abrupt pathological change in the brain and other peripheral organs. These results suggest that NPs delivered dopamine into the brain, reduced dopamine autoxidation-mediated toxicity, and ultimately reversed neurochemical and neurobehavioral deficits in parkinsonian rats. PMID:25825926

  8. Intravenous administration of mesenchymal stem cells exerts therapeutic effects on parkinsonian model of rats: Focusing on neuroprotective effects of stromal cell-derived factor-1α

    Tayra Judith

    2010-04-01

    Full Text Available Abstract Background Mesenchymal stem cells (MSCs are pluripotent stem cells derived from bone marrow with secretory functions of various neurotrophic factors. Stromal cell-derived factor-1α (SDF-1α is also reported as one of chemokines released from MSCs. In this research, the therapeutic effects of MSCs through SDF-1α were explored. 6-hydroxydopamine (6-OHDA, 20 μg was injected into the right striatum of female SD rats with subsequent administration of GFP-labeled MSCs, fibroblasts, (i.v., 1 × 107 cells, respectively or PBS at 2 hours after 6-OHDA injection. All rats were evaluated behaviorally with cylinder test and amphetamine-induced rotation test for 1 month with consequent euthanasia for immunohistochemical evaluations. Additionally, to explore the underlying mechanisms, neuroprotective effects of SDF-1α were explored using 6-OHDA-exposed PC12 cells by using dopamine (DA assay and TdT-mediated dUTP-biotin nick-end labeling (TUNEL staining. Results Rats receiving MSC transplantation significantly ameliorated behaviorally both in cylinder test and amphetamine-induced rotation test compared with the control groups. Correspondingly, rats with MSCs displayed significant preservation in the density of tyrosine hydroxylase (TH-positive fibers in the striatum and the number of TH-positive neurons in the substantia nigra pars compacta (SNc compared to that of control rats. In the in vitro study, SDF-1α treatment increased DA release and suppressed cell death induced by 6-OHDA administration compared with the control groups. Conclusions Consequently, MSC transplantation might exert neuroprotection on 6-OHDA-exposed dopaminergic neurons at least partly through anti-apoptotic effects of SDF-1α. The results demonstrate the potentials of intravenous MSC administration for clinical applications, although further explorations are required.

  9. Striatal adenosine A{sub 2A} receptor-mediated positron emission tomographic imaging in 6-hydroxydopamine-lesioned rats using [{sup 18}F]-MRS5425

    Bhattacharjee, Abesh Kumar; Lang Lixin; Jacobson, Orit [Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892 (United States); Shinkre, Bidhan [Chemical Biology Unit, Laboratory of Cell Biochemistry and Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 (United States); Ma Ying [Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892 (United States); Niu Gang [Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892 (United States); Department of Radiology and Imaging Sciences, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892 (United States); Trenkle, William C. [Chemical Biology Unit, Laboratory of Cell Biochemistry and Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 (United States); Jacobson, Kenneth A. [Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 (United States); Chen Xiaoyuan [Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892 (United States); Kiesewetter, Dale O., E-mail: dk7k@nih.gov [Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892 (United States)

    2011-08-15

    Introduction: A{sub 2A} receptors are expressed in the basal ganglia, specifically in striatopallidal GABAergic neurons in the striatum (caudate-putamen). This brain region undergoes degeneration of presynaptic dopamine projections and depletion of dopamine in Parkinson's disease. We developed an {sup 18}F-labeled A{sub 2A} analog radiotracer ([{sup 18}F]-MRS5425) for A{sub 2A} receptor imaging using positron emission tomography (PET). We hypothesized that this tracer could image A{sub 2A} receptor changes in the rat model for Parkinson's disease, which is created following unilateral injection of the monoaminergic toxin 6-hydroxydopamine (6-OHDA) into the substantia nigra. Methods: [{sup 18}F]-MRS5425 was injected intravenously in anesthetized rats, and PET imaging data were collected. Image-derived percentage injected doses per gram (%ID/g) in regions of interest was measured in the striatum of normal rats and in rats unilaterally lesioned with 6-OHDA after intravenous administration of saline (baseline), D{sub 2} agonist quinpirole (1.0 mg/kg) or D{sub 2} antagonist raclopride (6.0 mg/kg). Results: Baseline %ID/g reached a maximum at 90 s and maintained plateau for 3.5 min, and then declined slowly thereafter. In 6-OHDA-lesioned rats, %ID/g was significantly higher in the lesioned side compared to the intact side, and the baseline total %ID/g (data from both hemispheres were combined) was significantly higher compared to quinpirole stimulation starting from 4.5 min until the end of acquisition at 30 min. Raclopride did not produce any change in uptake compared to baseline or between the hemispheres. Conclusion: Thus, increase of A{sub 2A} receptor-mediated uptake of radioactive MRS5425 could be a superior molecular target for Parkinson's imaging.

  10. Striatal adenosine A2A receptor-mediated positron emission tomographic imaging in 6-hydroxydopamine-lesioned rats using [18F]-MRS5425

    Introduction: A2A receptors are expressed in the basal ganglia, specifically in striatopallidal GABAergic neurons in the striatum (caudate-putamen). This brain region undergoes degeneration of presynaptic dopamine projections and depletion of dopamine in Parkinson's disease. We developed an 18F-labeled A2A analog radiotracer ([18F]-MRS5425) for A2A receptor imaging using positron emission tomography (PET). We hypothesized that this tracer could image A2A receptor changes in the rat model for Parkinson's disease, which is created following unilateral injection of the monoaminergic toxin 6-hydroxydopamine (6-OHDA) into the substantia nigra. Methods: [18F]-MRS5425 was injected intravenously in anesthetized rats, and PET imaging data were collected. Image-derived percentage injected doses per gram (%ID/g) in regions of interest was measured in the striatum of normal rats and in rats unilaterally lesioned with 6-OHDA after intravenous administration of saline (baseline), D2 agonist quinpirole (1.0 mg/kg) or D2 antagonist raclopride (6.0 mg/kg). Results: Baseline %ID/g reached a maximum at 90 s and maintained plateau for 3.5 min, and then declined slowly thereafter. In 6-OHDA-lesioned rats, %ID/g was significantly higher in the lesioned side compared to the intact side, and the baseline total %ID/g (data from both hemispheres were combined) was significantly higher compared to quinpirole stimulation starting from 4.5 min until the end of acquisition at 30 min. Raclopride did not produce any change in uptake compared to baseline or between the hemispheres. Conclusion: Thus, increase of A2A receptor-mediated uptake of radioactive MRS5425 could be a superior molecular target for Parkinson's imaging.

  11. Neuroprotective Properties of Mildronate, a Small Molecule, in a Rat Model of Parkinson’s Disease

    Harry V. Vinters

    2010-11-01

    Full Text Available Previously, we have found that mildronate [3-(2,2,2-trimethylhydrazinium propionate dihydrate], a small molecule with charged nitrogen and oxygen atoms, protects mitochondrial metabolism that is altered by inhibitors of complex I and has neuroprotective effects in an azidothymidine-neurotoxicity mouse model. In the present study, we investigated the effects of mildronate in a rat model of Parkinson’s disease (PD that was generated via a unilateral intrastriatal injection of the neurotoxin 6-hydroxydopamine (6‑OHDA. We assessed the expression of cell biomarkers that are involved in signaling cascades and provide neural and glial integration: the neuronal marker TH (tyrosine hydroxylase; ubiquitin (a regulatory peptide involved in the ubiquitin-proteasome degradation system; Notch-3 (a marker of progenitor cells; IBA-1 (a marker of microglial cells; glial fibrillary acidic protein, GFAP (a marker of astrocytes; and inducible nitric oxide synthase, iNOS (a marker of inflammation. The data show that in the 6-OHDA-lesioned striatum, mildronate completely prevented the loss of TH, stimulated Notch-3 expression and decreased the expression of ubiquitin, GFAP and iNOS. These results provide evidence for the ability of mildronate to control the expression of an array of cellular proteins and, thus, impart multi-faceted homeostatic mechanisms in neurons and glial cells in a rat model of PD. We suggest that the use of mildronate provides a protective effect during the early stages of PD that can delay or halt the progression of this neurodegenerative disease.

  12. Autoradiographic study of dopamine transporter in rat Model of Parkinson' s disease with 125I-β-CIT

    Liu Zhenguo; Chen Shengdi; Shum Wenshan

    2000-01-01

    Objective To evaluate the value of iaaging for dopamine transpter(DAT) wi th 125I- β-CIT. Methods The partial and complete lesioned rat models of hemiparkinsonism were rendered with 6- hydroxy-dopamine (6-OHDA). Each rat was injected intravenously with 1251-β-CIT containing 40 μ Ci. Coronal t issue sections were imaged by autoradiography. The levets of dopamine (DA)and its metabolites were measured by high performance 1iquid choromatography and electro-chemical detection (HPLC-ECD). The t yros i nc hydroxylase(Tll)-positive cells and fibres in substantia nigra and striatum of the rats were observed by immunohistochemieal staining. Results The radioactivities in the lesioned striatum of both partial and complete lesioned hemiparkinsonian rats were 2.67±0.25 and O. 98±0.29 respectively , and were singificantly decreased by.18% and 72% respectively, as compared with those of unlesioned side. The levels of DA in the lesioned striatum of partial and complete lesioned models were decreased by 39% and 98% respectively. The loss of TH-positive eells and fibres in the substantia nigra and striatum was found in the lesioned striatum of both partial and complete-lesioned models. Conclusion The imaging study of DAT may be helpful for the early diagnosis of Parkinson's disease and for the monitor of the progression of this discaose;.

  13. Nonuniform cardiac denervation observed by 11C-meta-hydroxyephedrine PET in 6-OHDA-treated monkeys.

    Valerie Joers

    Full Text Available Parkinson's disease presents nonmotor complications such as autonomic dysfunction that do not respond to traditional anti-parkinsonian therapies. The lack of established preclinical monkey models of Parkinson's disease with cardiac dysfunction hampers development and testing of new treatments to alleviate or prevent this feature. This study aimed to assess the feasibility of developing a model of cardiac dysautonomia in nonhuman primates and preclinical evaluations tools. Five rhesus monkeys received intravenous injections of 6-hydroxydopamine (total dose: 50 mg/kg. The animals were evaluated before and after with a battery of tests, including positron emission tomography with the norepinephrine analog (11C-meta-hydroxyephedrine. Imaging 1 week after neurotoxin treatment revealed nearly complete loss of specific radioligand uptake. Partial progressive recovery of cardiac uptake found between 1 and 10 weeks remained stable between 10 and 14 weeks. In all five animals, examination of the pattern of uptake (using Logan plot analysis to create distribution volume maps revealed a persistent region-specific significant loss in the inferior wall of the left ventricle at 10 (P<0.001 and 14 weeks (P<0.01 relative to the anterior wall. Blood levels of dopamine, norepinephrine (P<0.05, epinephrine, and 3,4-dihydroxyphenylacetic acid (P<0.01 were notably decreased after 6-hydroxydopamine at all time points. These results demonstrate that systemic injection of 6-hydroxydopamine in nonhuman primates creates a nonuniform but reproducible pattern of cardiac denervation as well as a persistent loss of circulating catecholamines, supporting the use of this method to further develop a monkey model of cardiac dysautonomia.

  14. Nonuniform cardiac denervation observed by 11C-meta-hydroxyephedrine PET in 6-OHDA-treated monkeys.

    Joers, Valerie; Seneczko, Kailie; Goecks, Nichole C; Kamp, Timothy J; Hacker, Timothy A; Brunner, Kevin G; Engle, Jonathan W; Barnhart, Todd E; Nickles, R Jerome; Holden, James E; Emborg, Marina E

    2012-01-01

    Parkinson's disease presents nonmotor complications such as autonomic dysfunction that do not respond to traditional anti-parkinsonian therapies. The lack of established preclinical monkey models of Parkinson's disease with cardiac dysfunction hampers development and testing of new treatments to alleviate or prevent this feature. This study aimed to assess the feasibility of developing a model of cardiac dysautonomia in nonhuman primates and preclinical evaluations tools. Five rhesus monkeys received intravenous injections of 6-hydroxydopamine (total dose: 50 mg/kg). The animals were evaluated before and after with a battery of tests, including positron emission tomography with the norepinephrine analog (11)C-meta-hydroxyephedrine. Imaging 1 week after neurotoxin treatment revealed nearly complete loss of specific radioligand uptake. Partial progressive recovery of cardiac uptake found between 1 and 10 weeks remained stable between 10 and 14 weeks. In all five animals, examination of the pattern of uptake (using Logan plot analysis to create distribution volume maps) revealed a persistent region-specific significant loss in the inferior wall of the left ventricle at 10 (P<0.001) and 14 weeks (P<0.01) relative to the anterior wall. Blood levels of dopamine, norepinephrine (P<0.05), epinephrine, and 3,4-dihydroxyphenylacetic acid (P<0.01) were notably decreased after 6-hydroxydopamine at all time points. These results demonstrate that systemic injection of 6-hydroxydopamine in nonhuman primates creates a nonuniform but reproducible pattern of cardiac denervation as well as a persistent loss of circulating catecholamines, supporting the use of this method to further develop a monkey model of cardiac dysautonomia. PMID:22539969

  15. Noisy galvanic vestibular stimulation promotes GABA release in the substantia nigra and improves locomotion in hemiparkinsonian rats.

    Ghazaleh Samoudi

    Full Text Available BACKGROUND: The vestibular system is connected to spinal, cerebellar and cerebral motor control structures and can be selectively activated with external electrodes. The resulting sensation of disturbed balance can be avoided by using stochastic stimulation patterns. Adding noise to the nervous system sometimes improves function. Small clinical trials suggest that stochastic vestibular stimulation (SVS may improve symptoms in Parkinson's disease. We have investigated this claim and possible mechanisms using the 6-hydroxydopamine (6-OHDA hemilesion model of Parkinson's disease. METHODOLOGY/PRINCIPAL FINDINGS: Animals were tested in the accelerating rod test and the Montoya staircase test of skilled forelimb use. In 6-OHDA hemilesioned animals, SVS improved rod performance by 56±11 s. At group level L-DOPA treatment had no effect, but positive responders improved time on rod by 60±19 s. Skilled forelimb use was not altered by SVS. To investigate how SVS may influence basal ganglia network activity, intracerebral microdialysis was employed in four regions of interest during and after SVS. In presence of the γ-amino buturic acid (GABA transporter inhibitor NNC 711, SVS induced an increase in GABA to 150±15% of baseline in the substantia nigra (SN of unlesioned animals, but had no effect in the pedunculopontine nucleus (PPN, the striatum or the ventromedial thalamus (VM. Dopamine release remained stable in all areas, as did GABA and amine concentrations in the SN of unstimulated controls. Following SVS, a sustained increase in GABA concentrations was observed in the ipsilesional, but not in the contralesional SN of 6-OHDA hemilesioned rats. In contrast, L-DOPA treatment produced a similar increase of GABA in the ipsi- and contra-lesional SN. CONCLUSIONS/SIGNIFICANCE: SVS improves rod performance in a rat model of Parkinson's disease, possibly by increasing nigral GABA release in a dopamine independent way. We propose that SVS could be useful for

  16. Experimental Study on Heterograft of Glomus Ccl ls of Carotid Body for Hemioarkinsonian Rats

    曹学兵; 孙圣刚; 童萼塘

    2002-01-01

    Summary: To observe the effects of heterograft of glomus cells of carotid body on hemiparkinsonian rat models, rats with unilateral 6-hydroxydopamine (6-OHDA)-induced lesions of the right dopamin ergic neurons of substantia nigra received intrastriatal glomus cells heterograft. Apomorphine-induced rotation was monitored for 30 rmin at various time points after grafting. The striata were cut and ex-amined for dopamine content by HPLC and for immunohistochemical staining of tyrosine hydroxylase positive neurons (TH+ ) at the end of the experiments. The results showed that apomorphine-induced rotational behavior was significantly reduced for 12 weeks and the dopamine contents were signifi cantly elevated after grafting (P<0.01), and TH+ cells survived better. The present study demon strates that intrastriatal heterograft of glomus cells within carotid body in rats with 6-OHDA-elicited lesions could reduce apomorphine-induced rotational behavior and elevate the dopamine contents and numbers of TH+ cell surviving within striatum, and can serve as a new and effective alternative for Parkinson disease.

  17. CART modulates the effects of levodopa in rat model of Parkinson's disease.

    Upadhya, Manoj A; Shelkar, Gajanan P; Subhedar, Nishikant K; Kokare, Dadasaheb M

    2016-03-15

    Parkinson's disease (PD) is an age-related disorder characterized by a progressive degeneration of dopaminergic neurons of substantia nigra (SN). The neuropeptide cocaine- and amphetamine-regulated transcript (CART) is known to closely interact with the dopamine system and regulate psychomotor activity. We screened the effectiveness of CART in reversing the symptoms of PD in a rat model. PD like condition was induced by administering 6-hydroxydopamine (6-OHDA) directly in the SN of the right side. Fifteen days later, intraperitoneal (IP) treatment with apomorphine hydrochloride to these rats, resulted in contralateral rotations in the rotation test chamber suggesting induction of PD-like symptoms. This action of apomorphine was significantly attenuated by intracerebroventricular (ICV) treatment with CART and potentiated by CART antibody. IP treatment with levodopa also produced contralateral rotation in PD induced rats, and showed anti-Parkinson-like action. Prior treatment with CART via ICV route potentiated the anti-Parkinsonian effects of levodopa, while CART antibody produced opposite effects. CART treatment per se, to PD induced rats produced ipsilateral rotations, suggesting that the peptide may promote the endogenous release of dopamine from intact neurons. While CART-immunoreactivity in arcuate nucleus, paraventricular nucleus, striatum, substantia nigra, ventral tegmental area and locus coeruleus was reduced in the PD induced rats, levodopa treatment restored the expression of CART-immunoreactivity in these nuclei. These results suggest that endogenous CART might closely interact with the dopamine containing SN-striatal pathway which is known to profoundly influence the motor system. The study underscores the importance of CART as a potential therapeutic agent in the treatment of PD. PMID:26771081

  18. In vivo studies of the SERT-selective [{sup 18}F]FPBM and VMAT2-selective [{sup 18}F]AV-133 radiotracers in a rat model of Parkinson's disease

    Wang, Julie L. [Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 (United States); Oya, Shunichi; Parhi, Ajit K.; Lieberman, Brian P.; Ploessl, Karl; Hou, Catherine [Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 (United States); Kung, Hank F. [Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 (United States); Department of Radiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 (United States)], E-mail: kunghf@sunmac.spect.upenn.edu

    2010-05-15

    Introduction: The utility of [{sup 18}F]FPBM [2-(2'-((dimethylamino)methyl)-4'-(3-[{sup 18}F] -fluoropropoxy)phenylthio)benzenamine], a selective serotonin transporter (SERT) tracer, and [{sup 18}F]AV-133 [(+)-2-Hydroxy-3-isobutyl-9-(3-fluoropropoxy)-10-methoxy-1,2,3,4,6, 7-hexahydro-11bH-benzo[a]quinolizine], a selective vesicular monoamine transporter 2 (VMAT2) tracer, were tested in the 6-hydroxydopamine (6-OHDA) unilateral lesioned rat model. Methods: Positron emission tomography (PET) imaging of three 6-OHDA unilateral lesioned male Sprague Dawley rats (Rats 1-3) were performed with [{sup 18}F]FPBM and [{sup 18}F]AV-133 to examine whether changes in SERT and VMAT2 binding, respectively, could be detected in the brain. The brains of the three rats were then removed and examined by in vitro autoradiography with [{sup 18}F]FPBM and the dopamine transporter ligand, [{sup 125}I]IPT [N-(3'-[{sup 125}I]-iodopropen-2'-yl)-2-beta-carbomethoxy-3-beta-(4-chloro phenyl) tropane, for confirmation. Biodistribution of [{sup 18}F]FPBM in a separate group of p-chloroamphetamine (PCA) treated rats were also performed. Results: PET image analysis showed varying levels of SERT binding reduction (Rat 1=-11%, Rat 2=-4%, Rat 3=-43%; n=2) and a clear and definitive loss of VMAT2 binding (Rat 1=-87%, Rat 2=-72%, and Rat 3=-91%; n=1) in the left striatum when compared to the right (non-lesioned side) striatum. The results from PET imaging were corroborated with quantitative in vitro autoradiography. Rats treated with a selective serotonin toxin (p-chloroamphetamine) showed a significant reduction of [{sup 18}F]FPBM uptake in the cortex and hypothalamus regions of the brain. Conclusion: The preliminary data suggest that [{sup 18}F]FPBM and [{sup 18}F]AV-133 may be useful for the examination of serotonergic and dopaminergic neuron integrity, respectively, in the living brain.

  19. Assessment of the Protection of Dopaminergic Neurons by an α7 Nicotinic Receptor Agonist, PHA 543613 Using [18F]LBT-999 in a Parkinson’s Disease Rat Model

    Sérrière, Sophie; Doméné, Aurélie; Vercouillie, Johnny; Mothes, Céline; Bodard, Sylvie; Rodrigues, Nuno; Guilloteau, Denis; Routier, Sylvain; Page, Guylène; Chalon, Sylvie

    2015-01-01

    The inverse association between nicotine intake and Parkinson’s disease (PD) is well established and suggests that this molecule could be neuroprotective through anti-inflammatory action mediated by nicotinic receptors, including the α7-subtype (α7R). The objective of this study was to evaluate the effects of an agonist of α7R, PHA 543613, on striatal dopaminergic neurodegeneration and neuroinflammation in a rat model of PD induced by 6-hydroxydopamine (6-OHDA) lesion. Adult male Wistar rats were lesioned in the right striatum and assigned to either the PHA group (n = 7) or the Sham group (n = 5). PHA 543613 hydrochloride at the concentration of 6 mg/kg (PHA group) or vehicle (Sham group) was intra-peritoneally injected 2 h before 6-OHDA lesioning and then at days 2, 4, and 6 post-lesion. Positron emission tomography (PET) imaging was performed at 7 days post-lesion using [18F]LBT-999 to quantify the striatal dopamine transporter (DAT). After PET imaging, neuroinflammation was evaluated in same animals in vitro through the measurement of the microglial activation marker 18 kDa translocator protein (TSPO) by quantitative autoradiography with [3H]PK-11195. The DAT density reflecting the integrity of dopaminergic neurons was significantly decreased while the intensity of neuroinflammation measured by TSPO density was significantly increased in the lesioned compared to intact striatum in both groups. However, these both modifications were partially reversed in the PHA group compared to Sham. In addition, a significant positive correlation between the degree of lesion and the intensity of neuroinflammation was evidenced. These findings indicate that PHA 543613 exerts neuroprotective effects on the striatal dopaminergic neurons associated with a reduction in microglial activation in this model of PD. This reinforces the hypothesis that an α7R agonist could provide beneficial effects for the treatment of PD. PMID:26389120

  20. Phytic Acid Protects against 6-Hydroxydopamine-Induced Dopaminergic Neuron Apoptosis in Normal and Iron Excess Conditions in a Cell Culture Model

    Qi Xu; Kanthasamy, Anumantha G.; Reddy, Manju B.

    2011-01-01

    Iron may play an important role in Parkinson's disease (PD) since it can induce oxidative stress-dependent neurodegeneration. The objective of this study was to determine whether the iron chelator, phytic acid (IP6) can protect against 6-hydroxydopamine- (6-OHDA-) induced apoptosis in immortalized rat mesencephalic dopaminergic cells under normal and iron-excess conditions. Caspase-3 activity was increased about 6-fold after 6-OHDA treatment (compared to control; < . 0 0 1 ) and 30 μmol/L I...

  1. Preparation of 6—[18F]fluoro—L—DOPA and its biodistribution in normal and unilateral PD model rats

    ZHANGLan; TANGGang-Hua; 等

    2002-01-01

    No-carrier-added 6-[18F] fluoro-L-DOPA(6-FDOPA) was synthesized via a multistep procedure from a commercial available precursor,6-nitroveratraldehyde,The total synthesis time was 75min,with a radiochemical yield of (10±3)%,high radiochemical purity(>99%) and high enantiomeric purity(>95%).The biodistributions of 6-FDOPA in normal and unilateral PD model rats were measured.The results from normal rats showed the expected high concentration of radioactivity in striatum and low distrbutions in cerebrum,cortex and cerebellum.The ration of the radioactivity in striatum to cerebellum reached a peak value(5.9) at 60 min.In unilateral PD model rate.whose substania nigra of the right side had been damaged by pre-treated with 6-OHDA,the radioactive concentration in striatum of the damaged side was significantly lower than that of the undamaged side or that of both sides in striatum of control groups.

  2. Cardiac Dysregulation and Myocardial Injury in a 6-Hydroxydopamine-Induced Rat Model of Sympathetic Denervation.

    Yue-Hua Jiang

    Full Text Available Cardiac sympathetic denervation is found in various cardiac pathologies; however, its relationship with myocardial injury has not been thoroughly investigated.Twenty-four rats were assigned to the normal control group (NC, sympathectomy control group (SC, and a sympathectomy plus mecobalamin group (SM. Sympathectomy was induced by injection of 6-OHDA, after which, the destruction and distribution of sympathetic and vagal nerve in the left ventricle (LV myocardial tissue were determined by immunofluorescence and ELISA. Heart rate variability (HRV, ECG and echocardiography, and assays for myocardial enzymes in serum before and after sympathectomy were examined. Morphologic changes in the LV by HE staining and transmission electron microscope were used to estimate levels of myocardial injury and concentrations of inflammatory cytokines were used to reflect the inflammatory reaction.Injection of 6-OHDA decreased NE (933.1 ± 179 ng/L for SC vs. 3418.1± 443.6 ng/L for NC, P < 0.01 and increased NGF (479.4± 56.5 ng/mL for SC vs. 315.85 ± 28.6 ng/mL for NC, P < 0.01 concentrations. TH expression was reduced, while ChAT expression showed no change. Sympathectomy caused decreased HRV and abnormal ECG and echocardiography results, and histopathologic examinations showed myocardial injury and increased collagen deposition as well as inflammatory cell infiltration in the cardiac tissue of rats in the SC and SM groups. However, all pathologic changes in the SM group were less severe compared to those in the SC group.Chemical sympathectomy with administration of 6-OHDA caused dysregulation of the cardiac autonomic nervous system and myocardial injuries. Mecobalamin alleviated inflammatory and myocardial damage by protecting myocardial sympathetic nerves.

  3. PET Imaging of Serotonin Transporters With 4-[(18)F]-ADAM in a Parkinsonian Rat Model With Porcine Neural Xenografts.

    Chiu, Chuang-Hsin; Li, I-Hsun; Weng, Shao-Ju; Huang, Yuahn-Sieh; Wu, Shinn-Chih; Chou, Ta-Kai; Huang, Wen-Sheng; Liao, Mei-Hsiu; Shiue, Chyng-Yann; Cheng, Cheng-Yi; Ma, Kuo-Hsing

    2016-01-01

    Parkinson's disease (PD) is a neurodegenerative disease characterized by a loss of dopaminergic neurons in the nigrostriatal pathway. Apart from effective strategies to halt the underlying neuronal degeneration, cell replacement now offers novel prospects for PD therapy. Porcine embryonic neural tissue has been considered an alternative source to human fetal grafts in neurodegenerative disorders because its use avoids major practical and ethical issues. This study was undertaken to evaluate the effects of embryonic day 27 (E27) porcine mesencephalic tissue transplantation in a PD rat model using animal positron emission tomography (PET) coupled with 4-[(18)F]-ADAM, a serotonin transporter (SERT) imaging agent. The parkinsonian rat was induced by injecting 6-hydroxydopamine into the medial forebrain bundle (MFB) of the right nigrostriatal pathway. The apomorphine-induced rotation behavioral test and 4-[(18)F]-ADAM/animal PET scanning were carried out following 6-OHDA lesioning. At the second week following 6-OHDA lesioning, the parkinsonian rat rotates substantially on apomorphine-induced contralateral turning. In addition, the mean striatal-specific uptake ratio (SUR) of 4-[(18)F]-ADAM decreased by 44%. After transplantation, the number of drug-induced rotations decreased markedly, and the mean SUR of 4-[(18)F]-ADAM and the level of SERT immunoreactivity (SERT-ir) in striatum were partially restored. The mean SUR level was restored to 71% compared to that for the contralateral intact side, which together with the abundant survival of tyrosine hydroxylase (TH) neurons accounted for functional recovery at the fourth week postgraft. In regard to the extent of donor-derived cells, we found the neurons of the xenografts from E27 transgenic pigs harboring red fluorescent protein (RFP) localized with TH-ir cells and SERT-ir in the grafted area. Thus, transplanted E27 porcine mesencephalic tissue may restore dopaminergic and serotonergic systems in the parkinsonian rat

  4. Effects of unilateral 6-OHDA lesions on [3H]-N-propylnorapomorphine binding in striatum ex vivo and vulnerability to amphetamine-evoked dopamine release in rat

    Palner, Mikael; Kjaerby, Celia; Knudsen, Gitte M; Cumming, Paul

    2011-01-01

    It has been argued that agonist ligands for dopamine D(2/3) receptors recognize a privileged subset of the receptors in living striatum, those which are functionally coupled to intracellular G-proteins. In support of this claim, the D(2/3) agonist [(3)H]-N-propylnorapomorphine ([(3)H]NPA) proved to...

  5. Microencapsulated Dopamine (DA)-Induced Restitution of Function in 6-OHDA-Denervated Rat Striatum in vivo: Comparison Between Two Microsphere Excipients

    McRae, Amanda; Hjorth, Stephan; Mason, David W.; Dillon, Lynn; Tice, Thomas R.

    1991-01-01

    Biodegradable controlled-release microsphere systems made with the biocompatible biodegradable polyester excipient poly [DL lactide-co-glycolide] constitute an exciting new technology for drug delivery to the central nervous system (CNS). The present study describes functional observations indicating that implantation of dopamine (DA) microspheres encapsulated within two different polymer excipients into denervated- striatal tissue assures a prolonged release of the transmitter in vivo. Moreo...

  6. Roles of dopaminergic innervation of nucleus accumbens shell and dorsolateral caudate-putamen in cue-induced morphine seeking after prolonged abstinence and the underlying D1- and D2-like receptor mechanisms in rats

    Gao, Jun; Li, Yonghui; Zhu, Ning; Brimijoin, Stephen; Sui, Nan

    2013-01-01

    Drug-associated cues can elicit relapse to drug seeking after abstinence. Studies with extinction–reinstatement models implicate dopamine (DA) in the nucleus accumbens shell (NAshell) and dorsolateral caudate-putamen (dlCPu) in cocaine seeking. However, less is known about their roles in cue-induced opiate seeking after prolonged abstinence. Using a morphine self-administration and abstinence–relapse model, we explored the roles of NAshell and dlCPu DA and the D1/D2-like receptor mechanisms underlying morphine rewarding and/or seeking. Acquisition of morphine self-administration was examined following 6-Hydroxydopamine hydrobromide (6-OHDA) lesions of the NAshell and dlCPu. For morphine seeking, rats underwent 3 weeks’ morphine self-administration followed by 3 weeks’ abstinence from morphine and the training environment. Prior to testing, 6-OHDA, D1 antagonist SCH23390, or D2 antagonist eticlopride was locally injected; then rats were exposed to morphine-associated contextual and discrete cues. Results show that acquisition of morphine self-administration was inhibited by NAshell (not dlCPu) lesions, while morphine seeking was attenuated by lesions of either region, by D1 (not D2) receptor blockade in NAshell, or by blockade of either D1 or D2 receptors in dlCPu. These data indicate a critical role of dopaminergic transmission in the NAshell (via D1-like receptors) and dlCPu (via D1- and D2-like receptors) in morphine seeking after prolonged abstinence. PMID:23151613

  7. Dorsal striatal dopamine depletion impairs both allocentric and egocentric navigation in rats.

    Braun, Amanda A; Graham, Devon L; Schaefer, Tori L; Vorhees, Charles V; Williams, Michael T

    2012-05-01

    Successful navigation requires interactions among multiple but overlapping neural pathways mediating distinct capabilities, including egocentric (self-oriented, route-based) and allocentric (spatial, map-based) learning. Route-based navigation has been shown to be impaired following acute exposure to the dopaminergic (DA) drugs (+)-methamphetamine and (+)-amphetamine, but not the serotoninergic (5-HT) drugs (±)-3,4-methylenedioxymethamphetamine or (±)-fenfluramine. The dopaminergic-rich neostriatum is involved in both allocentric and egocentric navigation. This experiment tested whether dorsal striatal DA loss using bilateral 6-hydroxydopamine (6-OHDA) injections impaired one or both types of navigation. Two weeks following 6-OHDA injections, rats began testing in the Cincinnati water maze (CWM) followed by the Morris water maze (MWM) for route-based and spatial navigation, respectively. 6-OHDA treatment significantly increased latency and errors in the CWM and path length, latency, and cumulative distance in the MWM with no difference on cued MWM trials. Neostriatal DA levels were reduced by 80% at 2 and 7 weeks post-treatment. In addition, 6-OHDA increased DA turnover and decreased norepinephrine (NE) levels. 6-OHDA injections did not alter monoamine levels in the prefrontal cortex. The data support that neostriatal DA modulates both types of navigation. PMID:22465436

  8. Altered neuronal activity in the pedunculopontine nucleus: An electrophysiological study in a rat model of Parkinson's disease.

    Geng, Xiwen; Xie, Jinlu; Wang, Xuenan; Wang, Xiusong; Zhang, Xiao; Hou, Yabing; Lei, Chengdong; Li, Min; Qu, Qingyang; He, Tingting; Han, Hongyu; Yao, Xiaomeng; Wang, Min

    2016-05-15

    The pedunculopontine nucleus (PPN) is a new deep brain stimulation target for treating Parkinson's disease (PD). But the alterations of the PPN electrophysiological activities in PD are still debated. To investigate these potential alterations, extracellular single unit and local field potential (LFP) activities in the PPN were recorded in unilateral hemispheric 6-hydroxydopamine (6-OHDA) lesioned rats and in control rats, respectively. The spike activity results revealed two types of neurons (Type I and Type II) with distinct electrophysiological characteristics in the PPN. Both types of neurons had increased firing rate and changed firing pattern in lesioned rats when compared to control rats. Specifically, Type II neurons showed an increased firing rate when the rat state was switched from rest to locomotion. The LFP results demonstrated that lesioned rats had lower LFP power at 0.7-12Hz and higher power at 12-30Hz than did control animals in either resting or locomotor state. These findings provide a better understanding of the effects of 6-OHDA lesion on neuronal activities in the PPN and also provide a proof of the link between this structure and locomotion, which contributes to better understanding the mechanisms of the PPN functioning in the pathophysiology of PD. PMID:26924016

  9. 7-nitroindazole attenuates 6-hydroxydopamine-induced spatial learning deficits and dopamine neuron loss in a presymptomatic animal model of Parkinson's disease.

    Haik, Kristi L; Shear, Deborah A; Hargrove, Chad; Patton, Jared; Mazei-Robison, Michelle; Sandstrom, Michael I; Dunbar, Gary L

    2008-04-01

    Parkinson's disease (PD) is a neurodegenerative disorder in which loss of dopaminergic (DA) neurons (>50%) in the substantia nigra (SN) precedes most of the overt motor symptoms, making early diagnosis and treatment interventions difficult. Because PD has been associated with free radicals generated by nitric oxide, this study tested whether treatments of 7-nitroindazole (7NI), a nitric-oxide-synthase inhibitor, could reduce cognitive deficits that often emerge before overt motor symptoms in a presymptomatic rat model of PD. Rats were given intraperitoneal injections of 50 mg/kg 7NI (or vehicle) just before receiving bilateral, intrastriatal injections of the DA-toxin, 6-hydroxydopamine (6-OHDA). The rats were then given a battery of motor tasks, and their learning ability was assessed using a spatial reversal task in a water-T maze. Results indicate that 7NI treatments attenuate 6-OHDA-induced spatial learning deficits and protect against DA cell loss in the SN, suggesting that 7NI may have potential as an early, presymptomatic pharmacotherapy for PD. PMID:18489022

  10. Comparative Analysis of the Effects of Neurotrophic Factors CDNF and GDNF in a Nonhuman Primate Model of Parkinson’s Disease

    Garea-Rodríguez, Enrique; Eesmaa, Ave; Lindholm, Päivi; Schlumbohm, Christina; König, Jessica; Meller, Birgit; Krieglstein, Kerstin; Helms, Gunther; Saarma, Mart; Fuchs, Eberhard

    2016-01-01

    Cerebral dopamine neurotrophic factor (CDNF) belongs to a newly discovered family of evolutionarily conserved neurotrophic factors. We demonstrate for the first time a therapeutic effect of CDNF in a unilateral 6-hydroxydopamine (6-OHDA) lesion model of Parkinson’s disease in marmoset monkeys. Furthermore, we tested the impact of high chronic doses of human recombinant CDNF on unlesioned monkeys and analyzed the amino acid sequence of marmoset CDNF. The severity of 6-OHDA lesions and treatmen...

  11. Laser Acupuncture at HT7 Acupoint Improves Cognitive Deficit, Neuronal Loss, Oxidative Stress, and Functions of Cholinergic and Dopaminergic Systems in Animal Model of Parkinson’s Disease

    Jintanaporn Wattanathorn

    2014-01-01

    Full Text Available To date, the therapeutic strategy against cognitive impairment in Parkinson’s disease (PD is still not in satisfaction level and requires novel effective intervention. Based the oxidative stress reduction and cognitive enhancement induced by laser acupuncture at HT7, the beneficial effect of laser acupuncture at HT7 against cognitive impairment in PD has been focused. In this study, we aimed to determine the effect of laser acupuncture at HT7 on memory impairment, oxidative stress status, and the functions of both cholinergic and dopaminergic systems in hippocampus of animal model of PD. Male Wistar rats, weighing 180–220 g, were induced unilateral lesion at right substantianigra by 6-OHDA and were treated with laser acupuncture continuously at a period of 14 days. The results showed that laser acupuncture at HT7 enhanced memory and neuron density in CA3 and dentate gyrus. The decreased AChE, MAO-B, and MDA together with increased GSH-Px in hippocampus of a 6-OHDA lesion rats were also observed. In conclusion, laser acupuncture at HT7 can improve neuron degeneration and memory impairment in animal model of PD partly via the decreased oxidative stress and the improved cholinergic and dopaminergic functions. More researches concerning effect of treatment duration are still required.

  12. [18F]desmethoxyfallypride as a novel PET radiotracer for quantitative in vivo dopamine D2/D3 receptor imaging in rat models of neurodegenerative diseases

    Introduction: [18F]desmethoxyfallypride ([18F]DMFP) is a promising tracer for longitudinal assessment of striatal dopamine D2/D3-receptor (D2R) availability by positron emission tomography (PET) in small animal models. We explored the feasibility of [18F]DMFP-PET to image D2R availability in rat models of Huntington's (HD) and Parkinson's disease (PD). Methods: Animals received either unilateral intrastriatal quinolinic acid lesions or medial forebrain bundle injections of 6-OHDA to produce the loss of striatal projection neurones or deplete the striatal dopamine, corresponding to established animal models for HD and PD, respectively. Three weeks after lesioning, PET scans were acquired on a microPET Focus 120 system following the tail vein injection of [18F]DMFP. Results: [18F]DMFP-PET clearly visualized lesion induced decreases and increases of D2R availability. In vivo estimates of D2R binding and changes thereof gained by pharmacokinetic analyses correlated significantly with D2R density and its change provided by in vitro [3H]raclopride-autoradiography. Conclusions: In conclusion, [18F]DMFP-PET is a suitable method for in vivo D2R-assessment in preclinical research, e.g for monitoring cell-based therapies.

  13. Effect of siRNA-induced silencing of cellular prion protein on tyrosine hydroxylase expression in the substantia nigra of a rat model of Parkinson's disease.

    Wang, X; Yang, H A; Wang, X N; Du, Y F

    2016-01-01

    The most significant pathological feature of Parkinson's disease (PD) is the progressive degeneration of dopaminergic (DA) neurons in the substantia nigra. Currently, available treatments for PD cannot prevent the loss of DA neurons. Tyrosine hydroxylase (TH) expressed in substantia nigra neurons catalyzes the conversion of tyrosine to L-3,4-dihydroxyphenylalanine (L-DOPA), which is the rate-limiting step of DA biosynthesis. Major reasons for PD occurrence include decreased TH activity in the substantia nigra and secondary DA suppression. Decreased TH activity and the resulting suppression of DA synthesis (or neurotransmission) in the substantia nigra are key factors underlying the development of PD. Cellular prion protein (PRP) is a membrane glycoprotein expressed in the central nervous system. Although the sequence of PRP is highly conserved, its physiological function is unclear. The purpose of this study was to investigate the effect of PRP-targeted small interfering RNA (siRNA) on TH expression in a rat model of PD. Thirty male Wistar rats were injected with 6-hydroxydopamine (6-OHDA) to generate a model of PD. The rats then received injections of PRP-siRNA or nonsense siRNA in the lateral ventricles. Substantia nigra samples were collected for quantification of PRP and TH expression using real-time polymerase chain reaction and western blotting. PRP-siRNA decreased PRP expression in the substantia nigra. TH expression was decreased in PD model rats but was increased after PRP silencing. We conclude that PRP-siRNA may increase TH expression in vivo and may therefore exert protective effects on neurons in a model of PD. PMID:27173342

  14. Rat Endovascular Perforation Model

    Sehba, Fatima A.

    2014-01-01

    Experimental animal models of aneurysmal subarachnoid hemorrhage (SAH) have provided a wealth of information on the mechanisms of brain injury. The Rat endovascular perforation model (EVP) replicates the early pathophysiology of SAH and hence is frequently used to study early brain injury following SAH.

  15. Vocal training, levodopa, and environment effects on ultrasonic vocalizations in a rat neurotoxin model of Parkinson disease.

    Kelm-Nelson, Cynthia A; Brauer, Alexander F L; Ciucci, Michelle R

    2016-07-01

    Levodopa does not improve dysarthria in patients with Parkinson Disease (PD), although vocal exercise therapy, such as "LSVT/LOUD(®)", does improve vocal communication. Most patients receive vocal exercise therapy while concurrently being treated with levodopa, although the interaction between levodopa and vocal exercise therapy on communication in PD is relatively unknown. Further, carryover of vocal exercise therapy to novel situations is critical for successful outcomes, but the influence of novel situations on rehabilitated vocal communication is not well understood. To address the influence of exercise, medications, and environment on vocal communication with precise experimental control, we employed the widely used 6-OHDA rat neurotoxin model of PD (infusion to the medial forebrain bundle), and assessed ultrasonic vocalizations after: vocal exercise, vocal exercise with levodopa, levodopa alone, and control conditions. We tested USVs in the familiar training environment of the home cage and a novel cage. We hypothesized that parkinsonian rats that undergo vocal exercise would demonstrate significant improvement of ultrasonic vocalization (USV) acoustic parameters as compared to the control exercise and levodopa-only treatment groups. We further hypothesized that vocal exercise in combination with levodopa administration, similar to what is common in humans, would lead to improvement in USV outcomes, particularly when tested in a familiar versus a novel environment. We found that the combination of exercise and levodopa lead to some improvement in USV acoustic parameters and these effects were stronger in a familiar vs. a novel environment. Our results suggest that although treatment can improve aspects of communication, environment can influence the benefits of these effects. PMID:27025445

  16. Vocal training, levodopa, and environment effects on ultrasonic vocalizations in a rat neurotoxin model of Parkinson disease

    Kelm-Nelson, Cynthia A.; Brauer, Alexander F.L.; Ciucci, Michelle R.

    2016-01-01

    Levodopa does not improve dysarthria in patients with Parkinson Disease (PD), although vocal exercise therapy, such as “LSVT/LOUD®”, does improve vocal communication. Most patients receive vocal exercise therapy while concurrently being treated with levodopa, although the interaction between levodopa and vocal exercise therapy on communication in PD is relatively unknown. Further, carryover of vocal exercise therapy to novel situations is critical for successful outcomes, but the influence of novel situations on rehabilitated vocal communication is not well understood. To address the influence of exercise, medications, and environment on vocal communication with precise experimental control, we employed the widely used 6-OHDA rat neurotoxin model of PD (infusion to the medial forebrain bundle), and assessed ultrasonic vocalizations after: vocal exercise, vocal exercise with levodopa, levodopa alone, and control conditions. We tested USVs in the familiar training environment of the home cage and a novel cage. We hypothesized that parkinsonian rats that undergo vocal exercise would demonstrate significant improvement of ultrasonic vocalization (USV) acoustic parameters as compared to the control exercise and levodopa-only treatment groups. We further hypothesized that vocal exercise in combination with levodopa administration, similar to what is common in humans, would lead to improvement in USV outcomes, particularly when tested in a familiar versus a novel environment. We found that the combination of exercise and levodopa lead to some improvement in USV acoustic parameters and these effects were stronger in a familiar vs. a novel environment. Our results suggest that although treatment can improve aspects of communication, environment can influence the benefits of these effects. PMID:27025445

  17. DEVELOPMENT OF SEROTONERGIC AND ADRENERGIC RECEPTORS IN THE RAT SPINAL CORD: EFFECTS OF NEONATAL CHEMICAL LESIONS AND HYPERTHYROIDISM

    The ontogeny of serotonergic receptors and alpha- and beta-adrenergic receptors in thoracolumbar spinal cord of rats given neurotoxins which destroy serotonergic (5,7-dihydroxytryptamine (5,7-DHT) or noradrenergic (6-hydroxydopamine (6-OHDA)) nerve terminals was examined. Intraci...

  18. Intranigral administration of substance P receptor antagonist attenuated levodopa-induced dyskinesia in a rat model of Parkinson's disease.

    Yang, Xinxin; Zhao, Hui; Shi, Hongjuan; Wang, Xiaoying; Zhang, Shenyang; Zhang, Zunsheng; Zu, Jie; Zhang, Wei; Shen, Xia; Cui, Guiyun; Hua, Fang

    2015-09-01

    Levodopa (L-dopa) remains the most effective drug in the treatment of Parkinson's disease (PD). However, L-dopa-induced dyskinesia (LID) has hindered its use for PD patients. The mechanisms of LID are not fully understood. Substance P (SP) receptor antagonist has been shown to reduce parkinsonism in animal models of PD, and ameliorate LID in PD rats. But the concrete mechanism is not fully understood. To address this issue, we produced a rat model of PD using 6-hydroxydompamine (6-OHDA) injections, and valid PD rats were intranigrally administrated with different doses of SP receptor antagonist LY303870 (5 nmol/day, 10 nmol/day and 20 nmol/day) following L-dopa (6 mg/kg/day, i.p.) plus benserazide (12 mg/kg/day, i.p.) for 23 days. We found that nigral SP levels were increased on days 3, 7 and 14 and decreased on day 21 after 6-hydroxydompamine lesions. But nigral SP levels kept increasing after repeated L-dopa administration in PD rats. Intranigral administration of low and moderate LY303870 reduced abnormal involuntary movements (AIMs) while improving motor deficits in PD rats treated with L-dopa plus benserazide. Microdialysis revealed that LY303870 (10 nmol/day) treatment attenuated the increase of striatal dopamine and the reduction of γ-aminobutyric acid in ventromedial thalamus of PD rats primed with L-dopa. Additionally, LY303870 (10 nmol/day) treatment prior to L-dopa administration reduced the phosphorylated levels of dopamine- and cyclic adenosine monophosphate-regulated phosphoprotein of 32 kDa at Thr 34 and extracellular signal-regulated kinases 1/2 as well as the levels of activity-regulated cytoskeleton-associated protein and Penk in L-dopa-primed PD rats. Taken together, these data showed that low and moderate SP receptor antagonists LY303870 could ameliorate LID via neurokinin 1 receptor without affecting therapeutic effect of L-dopa. PMID:26001615

  19. The Effect of Ethanolic The effect of ethanolic extract of Saffron (Crocus sativus L. on improving the spatial memory parameters in the experimental models of Parkinson disease in male rats

    Homeyra Hatami

    2016-03-01

    Full Text Available Background & Objective: The axial role of the oxidative stress in the pathophysiology of Parkinson disease has been identified. On the other hand, the learning and memory impairment in Parkinson disease has a distinguished outlook. Since Saffron has antioxidative stress effects, the aim of the present study is to investigate the improving effects of Saffron extract on the spatial memory parameters in the experimental models of Parkinson disease in male rats. Methods & Materials: In this experimental study, 35 male rats weighing approximately 250±50 gram were randomly divided in five equal groups: control, sham (saline + ascorbat, Parkinson's model (injection of 6-OHDA, 2/5 μg/ μl and 2 groups of Parkinson's model + saffron extract pretreatment (5 and 10 μg/rat for 5 days. The Parkinson’s induction model was made by intracerebral injection of 6 – hydroxy dopamine. The Morris Water maze was used for studying the spatial learning and memory.  The data analysis was performed by using One-Way ANOVA. Results: Intracerebral injection of 6- hydroxy dopamine increased the time latency required for finding the hidden platform and damaged the spatial memory (P<0.05. The pretreatment of Saffron extract (5 and 10 μg/rat, 5 days improved the reduced spatial memory in Parkinson's rats (P < 0.05. Conclusion: The Saffron extract is able to restore the spatial memory parameters such as the time latency and the distance travelled for finding the hidden platform in Parkinson's rats as compared to the level of the control group.

  20. Imaging DA release in a rat model of L-DOPA-induced dyskinesias: a longitudinal in vivo PET investigation of the antidyskinetic effect of MDMA.

    Lettfuss, Nadine Y; Fischer, Kristina; Sossi, Vesna; Pichler, Bernd J; von Ameln-Mayerhofer, Andreas

    2012-10-15

    In the context of Parkinson's disease, motor symptoms result from the degeneration of nigrostriatal neurons. Dopamine (DA) replacement using l-3,4-dihydroxyphenylalanine (L-DOPA) has been the treatment of choice in the early stages of the disease. However, with disease progression, patients suffer from motor complications, which have been suggested to arise from DA released from serotonergic terminals according to the false neurotransmitter hypothesis. The synthetic amphetamine derivative (±) 3,4-methylenedioxymethamphetamine (MDMA) has been shown to significantly inhibit dyskinesia in humans and in animal models of PD. In this study, we examined the effect of MDMA on L-DOPA-induced DA release by using [(11)C]raclopride kinetic modeling to assess alterations in DA neurotransmission in a rat model of L-DOPA-induced dyskinesia (LID) in a longitudinal in vivo PET study. Rats were submitted to 6-OHDA lesions, and the lesions were confirmed to be sufficiently severe based on the performance during stepping tests and [(11)C]methylphenidate PET scans. The rats underwent two [(11)C]raclopride PET sessions before (baseline) and after two weeks of chronic L-DOPA treatment (priming). L-DOPA priming led to strong abnormal involuntary movements (AIMs). In group 1, L-DOPA priming reduced L-DOPA-induced DA release in the lesioned striatum with no effect on the healthy side, while the concomitant administration of L-DOPA and MDMA (group 2) increased the DA levels in the lesioned and healthy striatum. In addition, behavioral analysis, which was performed two weeks after the second PET session, confirmed the antidyskinetic effect of MDMA. Our data show that L-DOPA-induced DA release is attenuated in the Parkinsonian striatum after chronic L-DOPA pretreatment and that the antidyskinetic mechanism of MDMA does not depend primarily on dopaminergic neurotransmission. PMID:22766162

  1. Major Alterations of Phosphatidylcholine and Lysophosphotidylcholine Lipids in the Substantia Nigra Using an Early Stage Model of Parkinson's Disease.

    Farmer, Kyle; Smith, Catherine A; Hayley, Shawn; Smith, Jeffrey

    2015-01-01

    Parkinson's disease (PD) is a progressive neurodegenerative disease affecting the nigrostriatal pathway, where patients do not manifest motor symptoms until >50% of neurons are lost. Thus, it is of great importance to determine early neuronal changes that may contribute to disease progression. Recent attention has focused on lipids and their role in pro- and anti-apoptotic processes. However, information regarding the lipid alterations in animal models of PD is lacking. In this study, we utilized high performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) and novel HPLC solvent methodology to profile phosphatidylcholines and sphingolipids within the substantia nigra. The ipsilateral substantia nigra pars compacta was collected from rats 21 days after an infusion of 6-hydroxydopamine (6-OHDA), or vehicle into the anterior dorsal striatum. We identified 115 lipid species from their mass/charge ratio using the LMAPS Lipid MS Predict Database. Of these, 19 lipid species (from phosphatidylcholine and lysophosphotidylcholine lipid classes) were significantly altered by 6-OHDA, with most being down-regulated. The two lipid species that were up-regulated were LPC (16:0) and LPC (18:1), which are important for neuroinflammatory signalling. These findings provide a first step in the characterization of lipid changes in early stages of PD-like pathology and could provide novel targets for early interventions in PD. PMID:26274953

  2. Behavioural effects of basal ganglia rho-kinase inhibition in the unilateral 6-hydroxydopamine rat model of Parkinson's disease.

    Inan, Salim Yalcin; Soner, Burak Cem; Sahin, Ayse Saide

    2016-08-01

    Parkinson's disease (PD) is one of the most common neurodegenerative disorders, which affects more than six million people in the world. While current available pharmacological therapies for PD in the early stages of the disease usually improve motor symptoms, they cause side effects, such as fluctuations and dyskinesias in the later stages. In this later stage, high frequency deep brain stimulation of the subthalamic nucleus (STN-DBS) is a treatment option which is most successful to treat drug resistant advanced PD. It has previously been demonstrated that activation of Rho/Rho-kinase pathway is involved in the dopaminergic cell degeneration which is one of the main characteristics of PD pathology. In addition, the involvement of this pathway has been suggested in diverse cellular events in the central nervous system; such as epilepsy, anxiety-related behaviors, regulation of dendritic and axonal morphology, antinociception, subarachnoid haemorrhage, spinal cord injury and amyotrophic lateral sclerosis. However, up to date, to our knowledge there are no previous reports showing the beneficial effects of the potent Rho-kinase inhibitor Y-27632 in the 6-hydroxydopamine (6-OHDA) rat model of PD. Therefore, in the present study, we investigated the behavioural effects of basal ganglia Y-27632 microinjections in this PD model. Our results indicated that basal ganglia Y-27632 microinjections significantly decreased the number of contralateral rotations-induced by apomorphine, significantly increased line crossings in the open-field test, contralateral forelimb use in the limb-use asymmetry test and contralateral tape playing time in the somatosensory asymmetry test, which may suggest that Y-27632 could be a potentially active antiparkinsonian agent. PMID:26996632

  3. Major Alterations of Phosphatidylcholine and Lysophosphotidylcholine Lipids in the Substantia Nigra Using an Early Stage Model of Parkinson’s Disease

    Farmer, Kyle; Smith, Catherine A.; Hayley, Shawn; Smith, Jeffrey

    2015-01-01

    Parkinson’s disease (PD) is a progressive neurodegenerative disease affecting the nigrostriatal pathway, where patients do not manifest motor symptoms until >50% of neurons are lost. Thus, it is of great importance to determine early neuronal changes that may contribute to disease progression. Recent attention has focused on lipids and their role in pro- and anti-apoptotic processes. However, information regarding the lipid alterations in animal models of PD is lacking. In this study, we utilized high performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) and novel HPLC solvent methodology to profile phosphatidylcholines and sphingolipids within the substantia nigra. The ipsilateral substantia nigra pars compacta was collected from rats 21 days after an infusion of 6-hydroxydopamine (6-OHDA), or vehicle into the anterior dorsal striatum. We identified 115 lipid species from their mass/charge ratio using the LMAPS Lipid MS Predict Database. Of these, 19 lipid species (from phosphatidylcholine and lysophosphotidylcholine lipid classes) were significantly altered by 6-OHDA, with most being down-regulated. The two lipid species that were up-regulated were LPC (16:0) and LPC (18:1), which are important for neuroinflammatory signalling. These findings provide a first step in the characterization of lipid changes in early stages of PD-like pathology and could provide novel targets for early interventions in PD. PMID:26274953

  4. Major Alterations of Phosphatidylcholine and Lysophosphotidylcholine Lipids in the Substantia Nigra Using an Early Stage Model of Parkinson’s Disease

    Kyle Farmer

    2015-08-01

    Full Text Available Parkinson’s disease (PD is a progressive neurodegenerative disease affecting the nigrostriatal pathway, where patients do not manifest motor symptoms until >50% of neurons are lost. Thus, it is of great importance to determine early neuronal changes that may contribute to disease progression. Recent attention has focused on lipids and their role in pro- and anti-apoptotic processes. However, information regarding the lipid alterations in animal models of PD is lacking. In this study, we utilized high performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS and novel HPLC solvent methodology to profile phosphatidylcholines and sphingolipids within the substantia nigra. The ipsilateral substantia nigra pars compacta was collected from rats 21 days after an infusion of 6-hydroxydopamine (6-OHDA, or vehicle into the anterior dorsal striatum. We identified 115 lipid species from their mass/charge ratio using the LMAPS Lipid MS Predict Database. Of these, 19 lipid species (from phosphatidylcholine and lysophosphotidylcholine lipid classes were significantly altered by 6-OHDA, with most being down-regulated. The two lipid species that were up-regulated were LPC (16:0 and LPC (18:1, which are important for neuroinflammatory signalling. These findings provide a first step in the characterization of lipid changes in early stages of PD-like pathology and could provide novel targets for early interventions in PD.

  5. Co-transplantation of GDNF-overexpressing neural stem cells and fetal dopaminergic neurons mitigates motor symptoms in a rat model of Parkinson's disease.

    Xingli Deng

    Full Text Available Striatal transplantation of dopaminergic (DA neurons or neural stem cells (NSCs has been reported to improve the symptoms of Parkinson's disease (PD, but the low rate of cell survival, differentiation, and integration in the host brain limits the therapeutic efficacy. We investigated the therapeutic effects of intracranial co-transplantation of mesencephalic NSCs stably overexpressing human glial-derived neurotrophic factor (GDNF-mNSCs together with fetal DA neurons in the 6-OHDA rat model of PD. Striatal injection of mNSCs labeled by the contrast enhancer superparamagnetic iron oxide (SPIO resulted in a hypointense signal in the striatum on T2-weighted magnetic resonance images that lasted for at least 8 weeks post-injection, confirming the long-term survival of injected stem cells in vivo. Co-transplantation of GDNF-mNSCs with fetal DA neurons significantly reduced apomorphine-induced rotation, a behavioral endophenotype of PD, compared to sham-treated controls, rats injected with mNSCs expressing empty vector (control mNSCs plus fetal DA neurons, or rats injected separately with either control mNSCs, GDNF-mNSCs, or fetal DA neurons. In addition, survival and differentiation of mNSCs into DA neurons was significantly greater following co-transplantation of GDNF-mNSCs plus fetal DA neurons compared to the other treatment groups as indicated by the greater number of cell expressing both the mNSCs lineage tracer enhanced green fluorescent protein (eGFP and the DA neuron marker tyrosine hydroxylase. The success of cell-based therapies for PD may be greatly improved by co-transplantation of fetal DA neurons with mNSCs genetically modified to overexpress trophic factors such as GDNF that support differentiation into DA cells and their survival in vivo.

  6. Antidyskinetic Effect of 7-Nitroindazole and Sodium Nitroprusside Associated with Amantadine in a Rat Model of Parkinson's Disease.

    Bortolanza, Mariza; Bariotto-Dos-Santos, Keila D; Dos-Santos-Pereira, Maurício; da-Silva, Célia Aparecida; Del-Bel, Elaine

    2016-07-01

    Amantadine is the noncompetitive antagonist of N-methyl-D-aspartate, receptor activated by the excitatory neurotransmitter glutamate. It is the only effective medication used to alleviate dyskinesia induced by L-3,4-dihydroxyphenylalanine (L-DOPA) in Parkinson's disease patients. Unfortunately, adverse effects as abnormal involuntary movements (AIMs) known as L-DOPA-induced dyskinesia limit its clinical utility. Combined effective symptomatic treatment modalities may lessen the liability to undesirable events. Likewise drugs known to interfere with nitrergic system reduce AIMs in animal models of Parkinson's disease. We aimed to analyze an interaction between amantadine, neuronal nitric oxide synthase inhibitor (7-nitroindazole, 7NI), and nitric oxide donor (sodium nitroprusside, SNP) in 6-hydroxydopamine-(6-OHDA)-lesioned rats (microinjection in the medial forebrain bundle) presenting L-DOPA-induced dyskinesia (20 mg/kg, gavage, during 21 days). We confirm that 7NI-30 mg/kg, SNP-2/4 mg/kg and amantadine-40 mg/kg, individually reduced AIMs. Our results revealed that co-administration of sub-effective dose of amantadine (10 mg/kg) plus sub-effective dose of 7NI (20 mg/kg) potentiates the effect of reducing AIMs scores when compared to the effect of the drugs individually. No superior benefit on L-DOPA-induced AIMs was observed with the combination of amantadine and SNP. The results revealed that combination of ineffective doses of amantadine and 7NI represents a new strategy to increase antidyskinetic effect in L-DOPA-induced AIMs. It may provide additional therapeutic benefits to Parkinson's disease patients from these disabling complications at lower and thus safer and more tolerable doses than required when either drug is used alone. To close, we discuss the paradox of both nitric oxide synthase inhibitor and/or donor produced AIMs reduction by targeting nitric oxide synthase. PMID:27053252

  7. Hypericum Perforatum Hydroalcoholic Extract Mitigates Motor Dysfunction and is Neuroprotective in Intrastriatal 6-Hydroxydopamine Rat Model of Parkinson's Disease.

    Kiasalari, Zahra; Baluchnejadmojarad, Tourandokht; Roghani, Mehrdad

    2016-05-01

    Parkinson's disease is the second most common neurodegenerative disorder with selective and progressive decline of nigral dopaminergic neurons. Hypericum perforatum L. (H. perforatum, St. John's wort) has been traditionally used for management of different disorders, especially mild-to-moderate depression. This study was conducted to evaluate the effect of H. perforatum extract against unilateral striatal 6-hydroxydopamine (6-OHDA) toxicity and to unmask some involved mechanisms. Intrastriatal 6-OHDA-lesioned rats were treated with H. perforatum hydroalcoholic extract at a dose of 200 mg/kg/day started 1 week pre-surgery for 1 week post-surgery. The extract attenuated apomorphine-induced rotational behavior, decreased the latency to initiate and the total time on the narrow beam task, lowered striatal level of malondialdehyde and enhanced striatal catalase activity and reduced glutathione content, normalized striatal expression of glial fibrillary acidic protein, tumor necrosis factor α with no significant effect on mitogen-activated protein kinase, lowered nigral DNA fragmentation, and prevented damage of nigral dopaminergic neurons with a higher striatal tyrosine hydroxylase immunoreactivity. These findings reveal the beneficial effect of H. perforatum via attenuation of DNA fragmentation, astrogliosis, inflammation, and oxidative stress. PMID:26119304

  8. Effect of Passive Smoking on the Rotational Behavior and Striatal Dopamine Content of 6-hydroxydopamine-induced Rat Model of Parkinson Disease%被动吸烟对帕金森病大鼠旋转行为和纹状体多巴胺含量的影响

    董宁; 孙圣刚; 陈吉相; 王涛

    2001-01-01

    目的 观察被动吸烟对帕金森病(PD)大鼠的影响,以验证流行病学研究的结论,为PD研究提供一条新的线索。方法 用6-羟基多巴胺(6-OHDA)立体定向注入大鼠一侧黑质致密部和中脑被盖腹侧区建立偏侧PD模型,观察术前4周开始给予的被动吸烟(持续6周)和术后2周对成功模型给予的被动吸烟(持续2周)对阿朴吗啡诱发的旋转行为及纹状体DA含量的影响。结果 术前4周开始被动吸烟的大鼠旋转行为有减少趋势,受损侧纹状体DA含量较对照组升高。术后2周,成功模型给予的被动吸烟对PD大鼠的旋转行为及纹状体DA含量均无影响。结论 被动吸烟可减轻6-OHDA对黑质DA能神经元的损伤。%Objective To observe the effect of passive smoking on therotational behavior and striatal dopamine content of the rat Parkinson disease (PD) model. Methods Creating the PD rat model by unilaterally injecting 6-hydroxydopamine(6-OHDA) into the substantia nigra pars compacta(SNpc) and the ventral tegmental area(VTA), the effects of passive smoking on the apomorphine-induced rotation behavior and the dopamine content of striatum beginning four weeks before the operation(lasting six weeks) or two weeks after the operation(lasting two weeks) in the successful models were observed. Results Rats received passive smoking beginning four weeks before the operation had a tendency to decrease the apomorphine-induced rotation behavior. The dopamine content of the striatum was elevated as compared to the control group. Passive smoking beginning two weeks after the operation in the successful models did not alter either the rotation behavior or the DA content of striatum. Conclusions Passive smoking can partially protect DA neurons of substantia nigra from the damage of 6-OHDA.

  9. 6-羟多巴胺诱导帕金森病大鼠模型行为学评价方法的探讨%Assessment of 6-hydroxydopamine-Lesion Induced Behavioral Alteration as a Rat Model of Parkinson’s Disease

    杨谦谦; 孙芳龄; 艾厚喜; 张丽; 王文

    2013-01-01

    Objective:To systematically evaluate 6-hydroxydopamine(6-OHDA)-induced behavioral alteration as a rat model of Parkinson’s disease. Methods:6-OHDA was microinjected into the left side of the substantia nigra striatum to damage the dopaminergic neurons in the SD rats. Three weeks later,intraperitoneal injection of apomorphine(APO)to observe the rotational behavior. The motoric function of animals was analyzed with rotarod test and open field test, and the rat’s muslce vibration frequency and amplitude were determined using the myoelectricity test. The severity of the behavioral alterations of the individual animals was also categorized. Results:The time of rats that remained on the rotarod was significantly reduced in model group as compared to sham group. In the open field test,the horizontal travel distance was decreased in the model group. The myoelectricity test result showed that the muscle vibration frequency and amplitude was increased in animals receiving 6-OHDA microinjection. Conclusion:These results provided behavioral evidence in future studies to evaluate and categorize Parkinson-like behaviors in rats.%目的:复制帕金森病(Parkinsonʼs disease,PD)大鼠模型并根据行为学检查结果对此模型进行较为全面的评价,以期建立治疗此疾病的新型实验平台。方法:运用6-羟多巴胺(6-hydroxydopamine)单点定向注射黑质-纹状体的方法,损毁SD大鼠左侧中脑多巴胺能神经元,动物术后3周腹腔注射(intrapertioneal injection,ip)阿扑吗啡(apomorphine,APO)观察是否诱导动物向健侧旋转行为,复制PD模型。分别应用转棒实验和旷场实验分析测定动物的运动功能,应用肌电测试实验测定大鼠的震颤频率和幅度,并据此对动物模型进行评价和分类。结果:造模后,部分大鼠转棒实验在棒时间显著缩短,旷场实验横向跨格次数减少,出现运动功能障碍;肌电检测结果显示部分

  10. Enhanced function in the good forelimb of hemi-parkinson rats: Compensatory adaptation for contralateral postural instability?

    Woodlee, Martin T.; Kane, Jacqueline R.; Chang, Jitsen; Cormack, Lawrence K.; Schallert, Timothy

    2008-01-01

    In this paper we present two new assays of rat motor behavior which can be used to assess function linked to postural stability in each forelimb independently. Postural instability is a major deficit in Parkinson's disease that is resistant to levodopa therapy and contributes to the risk of falling. We applied both tests, one forelimb at a time, to normal rats as well as rats extensively depleted of dopamine by unilateral infusion of 6-hydroxydopamine (6-OHDA, given in the medial forebrain bu...

  11. Effect of serotonin transporter blockade on L-DOPA-induced dyskinesia in animal models of Parkinson's disease.

    Fidalgo, C; Ko, W K D; Tronci, E; Li, Q; Stancampiano, R; Chuan, Q; Bezard, E; Carta, M

    2015-07-01

    Serotonin transporter blockade with selective serotonin reuptake inhibitors (SSRIs) was recently shown to counteract L-DOPA-induced dyskinesia in 6-hydroxydopamine (6-OHDA)-lesioned rats. However, this effect has never been described in Parkinson's disease (PD) patients, despite that they often receive SSRIs for the treatment of depression. In the present study, we investigated the efficacy of the SSRI citalopram against dyskinesia in two experimental models of PD, the 6-OHDA-lesioned rat and 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP)-treated macaque. First, we studied the acute and chronic effect of citalopram, given at different time points before L-DOPA, in L-DOPA-primed parkinsonian rats. Moreover, the acute effect of citalopram was also evaluated in dyskinetic MPTP-treated macaques. In L-DOPA-primed rats, a significant and long-lasting reduction of L-DOPA-induced dyskinesia (LID) was observed only when citalopram was given 30 min before L-DOPA, suggesting that the time of injection relative to L-DOPA is a key factor for the efficacy of the treatment. Interestingly, an acute challenge with the 5-HT1A/1B receptor agonist eltoprazine, given at the end of the chronic study, was equally effective in reducing LID in rats previously chronically treated with L-DOPA or L-DOPA plus citalopram, suggesting that no auto-receptor desensitization was induced by chronic citalopram treatment. In MPTP-treated macaques, citalopram produced a striking suppression of LID but at the expense of L-DOPA therapeutic efficacy, which represents a concern for possible clinical application. PMID:25907446

  12. Bee Venom Alleviates Motor Deficits and Modulates the Transfer of Cortical Information through the Basal Ganglia in Rat Models of Parkinson's Disease.

    Nicolas Maurice

    Full Text Available Recent evidence points to a neuroprotective action of bee venom on nigral dopamine neurons in animal models of Parkinson's disease (PD. Here we examined whether bee venom also displays a symptomatic action by acting on the pathological functioning of the basal ganglia in rat PD models. Bee venom effects were assessed by combining motor behavior analyses and in vivo electrophysiological recordings in the substantia nigra pars reticulata (SNr, basal ganglia output structure in pharmacological (neuroleptic treatment and lesional (unilateral intranigral 6-hydroxydopamine injection PD models. In the hemi-parkinsonian 6-hydroxydopamine lesion model, subchronic bee venom treatment significantly alleviates contralateral forelimb akinesia and apomorphine-induced rotations. Moreover, a single injection of bee venom reverses haloperidol-induced catalepsy, a pharmacological model reminiscent of parkinsonian akinetic deficit. This effect is mimicked by apamin, a blocker of small conductance Ca2+-activated K+ (SK channels, and blocked by CyPPA, a positive modulator of these channels, suggesting the involvement of SK channels in the bee venom antiparkinsonian action. In vivo electrophysiological recordings in the substantia nigra pars reticulata (basal ganglia output structure showed no significant effect of BV on the mean neuronal discharge frequency or pathological bursting activity. In contrast, analyses of the neuronal responses evoked by motor cortex stimulation show that bee venom reverses the 6-OHDA- and neuroleptic-induced biases in the influence exerted by the direct inhibitory and indirect excitatory striatonigral circuits. These data provide the first evidence for a beneficial action of bee venom on the pathological functioning of the cortico-basal ganglia circuits underlying motor PD symptoms with potential relevance to the symptomatic treatment of this disease.

  13. Bee Venom Alleviates Motor Deficits and Modulates the Transfer of Cortical Information through the Basal Ganglia in Rat Models of Parkinson's Disease.

    Maurice, Nicolas; Deltheil, Thierry; Melon, Christophe; Degos, Bertrand; Mourre, Christiane; Amalric, Marianne; Kerkerian-Le Goff, Lydia

    2015-01-01

    Recent evidence points to a neuroprotective action of bee venom on nigral dopamine neurons in animal models of Parkinson's disease (PD). Here we examined whether bee venom also displays a symptomatic action by acting on the pathological functioning of the basal ganglia in rat PD models. Bee venom effects were assessed by combining motor behavior analyses and in vivo electrophysiological recordings in the substantia nigra pars reticulata (SNr, basal ganglia output structure) in pharmacological (neuroleptic treatment) and lesional (unilateral intranigral 6-hydroxydopamine injection) PD models. In the hemi-parkinsonian 6-hydroxydopamine lesion model, subchronic bee venom treatment significantly alleviates contralateral forelimb akinesia and apomorphine-induced rotations. Moreover, a single injection of bee venom reverses haloperidol-induced catalepsy, a pharmacological model reminiscent of parkinsonian akinetic deficit. This effect is mimicked by apamin, a blocker of small conductance Ca2+-activated K+ (SK) channels, and blocked by CyPPA, a positive modulator of these channels, suggesting the involvement of SK channels in the bee venom antiparkinsonian action. In vivo electrophysiological recordings in the substantia nigra pars reticulata (basal ganglia output structure) showed no significant effect of BV on the mean neuronal discharge frequency or pathological bursting activity. In contrast, analyses of the neuronal responses evoked by motor cortex stimulation show that bee venom reverses the 6-OHDA- and neuroleptic-induced biases in the influence exerted by the direct inhibitory and indirect excitatory striatonigral circuits. These data provide the first evidence for a beneficial action of bee venom on the pathological functioning of the cortico-basal ganglia circuits underlying motor PD symptoms with potential relevance to the symptomatic treatment of this disease. PMID:26571268

  14. Bee Venom Alleviates Motor Deficits and Modulates the Transfer of Cortical Information through the Basal Ganglia in Rat Models of Parkinson’s Disease

    Maurice, Nicolas; Deltheil, Thierry; Melon, Christophe; Degos, Bertrand; Mourre, Christiane

    2015-01-01

    Recent evidence points to a neuroprotective action of bee venom on nigral dopamine neurons in animal models of Parkinson’s disease (PD). Here we examined whether bee venom also displays a symptomatic action by acting on the pathological functioning of the basal ganglia in rat PD models. Bee venom effects were assessed by combining motor behavior analyses and in vivo electrophysiological recordings in the substantia nigra pars reticulata (SNr, basal ganglia output structure) in pharmacological (neuroleptic treatment) and lesional (unilateral intranigral 6-hydroxydopamine injection) PD models. In the hemi-parkinsonian 6-hydroxydopamine lesion model, subchronic bee venom treatment significantly alleviates contralateral forelimb akinesia and apomorphine-induced rotations. Moreover, a single injection of bee venom reverses haloperidol-induced catalepsy, a pharmacological model reminiscent of parkinsonian akinetic deficit. This effect is mimicked by apamin, a blocker of small conductance Ca2+-activated K+ (SK) channels, and blocked by CyPPA, a positive modulator of these channels, suggesting the involvement of SK channels in the bee venom antiparkinsonian action. In vivo electrophysiological recordings in the substantia nigra pars reticulata (basal ganglia output structure) showed no significant effect of BV on the mean neuronal discharge frequency or pathological bursting activity. In contrast, analyses of the neuronal responses evoked by motor cortex stimulation show that bee venom reverses the 6-OHDA- and neuroleptic-induced biases in the influence exerted by the direct inhibitory and indirect excitatory striatonigral circuits. These data provide the first evidence for a beneficial action of bee venom on the pathological functioning of the cortico-basal ganglia circuits underlying motor PD symptoms with potential relevance to the symptomatic treatment of this disease. PMID:26571268

  15. Treadmill exercise alleviates short-term memory impairment in 6-hydroxydopamine-induced Parkinson’s rats

    Cho, Han-Sam; Shin, Mal-Soon; Song, Wook; Jun, Tae-Won; Lim, Baek-Vin; Kim, Young-Pyo; Kim, Chang-Ju

    2013-01-01

    Progressive loss of dopaminergic neurons in substantia nigra is a key pathogenesis of Parkinson’s disease. In the present study, we investigated the effects of treadmill exercise on short-term memory, apoptotic dopaminergic neuronal cell death and fiber loss in the nigrostriatum, and cell proliferation in the hippocampal dentate gyrus of Parkinson’s rats. Parkinson’s rats were made by injection of 6-hydroxydopamine (6-OHDA) into the striatum using stereotaxic instrument. Four weeks after 6-OH...

  16. Human albumin prevents 6-hydroxydopamine-induced loss of tyrosine hydroxylase in in vitro and in vivo.

    Li-Juan Zhang

    Full Text Available Human albumin has recently been demonstrated to protect brain neurons from injury in rat ischemic brain. However, there is no information available about whether human albumin can prevent loss of tyrosine hydroxylase (TH expression of dopaminergic (DA neurons induced by 6-hydroxydopamine (6-OHDA toxicity that is most commonly used to create a rat model of Parkinson's disease (PD. In the present study, two microliters of 1.25% human albumin were stereotaxically injected into the right striatum of rats one day before or 7 days after the 6-OHDA lesion in the same side. D-Amphetamine-induced rotational asymmetry was measured 7 days, 3 and 10 weeks after 6-OHDA lesion. We observed that intrastriatal administration of human albumin significantly reduced the degree of rotational asymmetry. The number of TH-immunoreactive neurons present in the substantia nigra was greater in 6-OHDA lesioned rats following human albumin-treatment than non-human albumin treatment. TH-immunoreactivity in the 6-OHDA-lesioned striatum was also significantly increased in the human albumin-treated rats. To examine the mechanisms underlying the effects of human albumin, we challenged PC12 cells with 6-OHDA as an in vitro model of PD. Incubation with human albumin prevented 6-OHDA-induced reduction of cell viability in PC12 cell cultures, as measured by MTT assay. Furthermore, human albumin reduced 6-OHDA-induced formation of reactive oxygen species (ROS and apoptosis in cultured PC12 cells, as assessed by flow cytometry. Western blot analysis showed that human albumin inhibited 6-OHDA-induced activation of JNK, c-Jun, ERK, and p38 mitogen-activated protein kinases (MAPK signaling in PC12 cultures challenged with 6-OHDA. Human albumin may protect against 6-OHDA toxicity by influencing MAPK pathway followed by anti-ROS formation and anti-apoptosis.

  17. Protective effects of the intracerebral transfer of the lentiviral-mediated GDNF and TH bi-gene on the basis of improved Tet-on system in a rat model of Parkinson's disease%慢病毒介导的新型Tet-On系统大鼠GDNF和TH双基因脑内转移对帕金森病大鼠模型的保护作用

    张阳; 张志坚; 俞晓岚; 黄志新; 吴秀丽

    2011-01-01

    Aim To study the protective effect of lentiviral-mediated rat glial cell line-derived neurotrophic factor( GDNF ) and tyrosine hydroxylase( TH ) on the basis of improved Tet-on system gene transfer on dopaminergic neurons in a rat model of Parkinson's disease( PD ).Methods Recombinant lentivirus( Lv-THGDNF )carrying rat GDNF and TH genes and tetracy cline response element containing mouse albumin gene promoter( Palb ) together with tetracycline-controlled transactivator rtTA2s-M2 virus was injected into the left striate bodies SD rats.After that.the expression of GDNF and TH genes was regulated by doxycycline.One week later, ipsilateral intrastriatal injection of 6hydroxydopamine( 6-OHDA )was to injury dopaminergic neurons.The neuroprotective effects of Lv-TH-GDNF were evaluated by apomorphine-induced rotational behavior.immunohistochemistry assay of the tyrosine hydroxylase positive neurons in the substantia nigra,and the measurement of dopamine level in the striatum by high performance liquid chromatography-electric chemical discharge( HPLC-ECD ).RT-PCR and western blotting were performed to check the expression of Lv-TH-GDNF in the brain.Tests were compared with the PBS control group and the non-injected control group.Results Tests showed apomorphine-induced contralateral turning effect was significantly reduced in Lv-TH-GDNF+ rtTA2s-M2 + DOX-pre-treated rats as compared with PBS-pre-treated rats when measured at 4 weeks post lesion by 6-OHDA( P<0.01 ), the expression of TH-positive cells in the lesioned substantia nigra and DA levels in the lesioned striatum were significantly higher in Lv-TH-GDNF + rtTA2s-M2 + DOXpre-treated rats than that in PBS-pre-treated rats( P <0.01 ) , but both were significantly lower than that of in non-injected rats( P <0.01 ).RT-PCR and western blotting showed the expression of exogenous GDNF and TH genes was significantly raised in the lesioned striatum in Lv-TH-CDNF+rtTA2s-M2 + DOX -pre-treated rats as compared with PBS

  18. Therapeutic effect of human amniotic epithelial cell transplantation into the lateral ventricle of hemiparkinsonian rats

    YANG Xin-xin; XUE Shou-ru; DONG Wan-li; Kong Yan

    2009-01-01

    Background Human amniotic epithelial cells (HAECs) are able to secrete biologically active neurotrophins such as brain-derived neurotrophic factor and neurotrophin-3, both of which exhibit trophic activities on dopamine neurons.Previous study showed that when human amniotic epithelial cells were transplanted into the striatum of 6-hydroxydopamine (6-OHDA)-induced Parkinson disease rats, the cells could survive and exert functional effects. The purpose of this study was to investigate the survival and the differentiation of human amniotic epithelial cells after being transplanted into the lateral ventricle of Parkinson's disease (PD) rats, and to investigate the effects of grafts on healing PD in models.Methods The Parkinson's model was made with stereotactic microinjection of 6-hydroxydopamine (6-OHDA) into the striatum of a rat. The PD models were divided into two groups: the HAECs group and the normal saline (NS) group.Some untreated rats were taken as the control. The rotational asymmetry induced by apomorphine of the HAECs group and the NS group were measured post cell transplantation. The expression of nestin and vimentin in grafts were determined by immunohistology. Ten weeks after transplantation the density of tyrosine hydroxylase positive cells in the substantia nigra of the HAECs group, NS group and the untreated group was determined. The differentiation of grafts was determined by TH immunohistology. High performance liquid chromatography (HPLC) was used to determine monoamine neurotransmitter levels in the striatum.Results The rotational asymmetry induced by apomorphine of the HAECs group was ameliorated significantly compared to the NS group two weeks after transplantation (P <0.01). The grafts expressed nestin and vimentin five weeks after transplantation. TH immunohistochemistry indicated that the TH positive cells in the substantia nigra of the HAECs group increased significantly compared to the NS group (P<0.01). Tyrosine hydroxylase (TH) positive

  19. Increased burst firing in substantia nigra pars reticulata neurons and enhanced response to selective D2 agonist in hemiparkinsonian rats after repeated administration of apomorphine.

    Lee, J. I.; Nam, D H; J.S. Kim; Hong, S.C.; Shin, H. J.; K. Park; Eoh, W.; Kim, J. H.; Lee, W.Y.

    2001-01-01

    Intermittent administrations of dopaminergic agents in hemiparkinsonian rat enhances the behavioral response to subsequent administration of the drugs. This phenomenon is known as "priming" and thought as comparable to drug-induced dyskinesia in patients with Parkinson's disease. We investigated the behavioral and electrophysiological changes in 6-hydroxydopamine (6-OHDA)-lesioned hemiparkinsonian rats after repeated administrations of apomorphine. Administration of apomorphine (0.32 mg/kg, i...

  20. A mouse model of non-motor symptoms in Parkinson’s disease: focus on pharmacological interventions targeting affective dysfunctions

    Alessandra eBonito Oliva

    2014-08-01

    Full Text Available Non-motor symptoms, including psychiatric disorders, are increasingly recognized as a major challenge in the treatment of Parkinson’s disease (PD. These ailments, which often appear in the early stage of the disease, affect a large number of patients and are only partly resolved by conventional antiparkinsonian medications, such as L-DOPA. Here, we investigated non-motor symptoms of PD in a mouse model based on bilateral injection of the toxin 6-hydroxydopamine (6-OHDA in the dorsal striatum. This model presented only subtle gait modifications, which did not affect horizontal motor activity in the open-field test. Bilateral 6-OHDA lesion also impaired olfactory discrimination, in line with the anosmia typically observed in early stage parkinsonism. The effect of 6-OHDA was then examined for mood-related dysfunctions. Lesioned mice showed increased immobility in the forced swim test and tail suspension test, two behavioral paradigms of depression. Moreover, the lesion exerted anxiogenic effects, as shown by reduced time spent in the open arms, in the elevated plus maze test, and by increased thigmotaxis in the open-field test. L-DOPA did not modify depressive- and anxiety-like behaviors, which were instead counteracted by the dopamine D2/D3 receptor agonist, pramipexole. Reboxetine, a noradrenaline reuptake inhibitor, was also able to prevent the depressive and anxiogenic effects produced by the lesion with 6-OHDA. Interestingly, pre-treatment with desipramine prior to injection of 6-OHDA, which is commonly used to preserve noradrenaline neurons, did not modify the effect of the lesion on depressive- and anxiety-like behaviors. Thus, in the present model, mood-related conditions are independent of the reduction of noradrenaline caused by 6-OHDA. Based on these findings we propose that the anti-depressive and anxiolytic action of reboxetine is mediated by promoting dopamine transmission through blockade of dopamine uptake from residual

  1. Astrocytes in the Rat Nucleus Tractus Solitarii Are Critical for Cardiovascular Reflex Control

    Lin, Li-Hsien; Moore, Steven A.; Jones, Susan Y.; McGlashon, Jacob; Talman, William T.

    2013-01-01

    We have shown that an antibody to dopamine-β-hydroxylase conjugated with saporin (anti-DBH-SAP) damages catecholamine neurons in the nucleus tractus solitarii (NTS) of rat, attenuates arterial baroreflexes, and leads to lability of arterial blood pressure, damage to cardiac myocytes, and, in some animals, sudden death. However, others have shown that injection of 6-hydroxydopamine (6-OHDA), a toxin devoid of saporin, also damaged NTS catecholamine neurons but did not lead to these cardiovascu...

  2. R-apomorphine protects against 6-hydroxydopamine-induced nigrostriatal damage in rat.

    Yuan, Hong; Liang, Li-Wu; Chen, Zheng-Jing; Ji, Hui-Ru; Wang, Mei-Kang; Zhang, Hai-Ying; Li, Cao; Xu, Jian-Yang

    2006-11-01

    Objective The aim of the present study was not only to assess the retrograde degenerative changes in the dopaminergic neurons of the substantia nigra (SN) and ventral tegmental area (VTA) after injection of 6-hydroxydopamine (6-OHDA) into the striatum, but also to use this 6-OHDA model of Parkinson's disease to explore the possible neuroprotective effect of R-apomorphine (R-APO). Methods The partial lesion was obtained by intrastriatal administration of 6-OHDA. R-APO administration (10 mg/kg, s.c.) started 15 min prior to lesioning and continued daily for another 22 days post surgery. Testing was carried out 5 weeks after lesioning. We investigated the histology and associated behavior and neurochemical changes. Structural and functional deficits were quantified by tyrosine hydroxylase (TH) / Nissl-staining cell number counting, striatal dopamine (DA) content determination and amphetamine-induced rotation analysis. Results R-APO-treatment attenuated the amphetamine-induced ipsiversive rotation 5 weeks after the lesion induction. R-APO administration for 22 days significantly reduced the size of the lesion at the level of the SN from 50% (control group) to 69%. Moreover, the cell shape resembled that observed in the intact animals. R-APO treatment significantly increased the number of cells in both the lesion and the intact sides of VTA by 60%, suggesting selective neurotrophic effect of R-APO in this area. Finally, R-APO-treatment significantly attenuated the 6-OHDA-induced striatal DA depletion and normalized dihydroxyphenylacetic acid (DOPAC)/DA ratios. Conclusion We conclude that R-APO has neuroprotective and possible neurotrophic effect on a striatal lesion with 6-OHDA, suggesting that this drug may have rescuing properties in patients with early stage Parkinson's disease. These effects are more pronounced in VTA and enhance with duration of treatment. PMID:17690718

  3. 硫酸镁对6-羟基多巴胺诱导的帕金森病模型大鼠血中褪黑素的影响%Effect of magnesium on serum melatonin in a rat model of Parkinson' s Disease

    马杰; 周全; 袁苏涛; 孟涛; 林玲

    2012-01-01

    Objective To explore the relationship between magnesium (Mg) and melatonin (MLT) by observation serum MLT levels in advanced Parkinson' s disease (PD) rats,and to clarify the effect of magnesium on serum melatonin in PD model.Methods PD rat model was established by a unilateral injection of 6-OHDA into the right substantia nigra pars compacta (SNc) and the right medial forebrain bundle (MFB).Rats of control group received saline injection.Twenty animals were divided into four groups.PD model (PD/H2O) and control/H2O groups were vehicle-treated rats,and received drinking water (magnesium sulphate vehicle) daily.Magnesium sulphate (MgSO40.36 g/kg/day dissolved in drinking water) was administered in rats of PD/Mg and control/Mg groups for four weeks.Then apomorphine-induced rotational behaviour,serum MLT levels and histological changes were tested.Results The level of MLT in PD groups was ( 153.4 ±29.8) pg/L,which distinctly higher than those in the controls (77.2 ±13.7) pg/L,while the levels of MLT in PD model and control rats receiving Mg were decreased to ( 126.8 ± 15.9) pg/L and (53.4 ± 18.1 ) pg/L respectively.MLT levels appeared to correlate well with the frequency of apomorphine-induced rotations.The frequency of rotations in PD/Mg group decreased compared with those in PD/H2O group.Conclusion The rotational behaviour in advanced PD rat might ameliorated by magnesium,and magnesium may partly inhibit compensatory increased MLT.%目的 观察晚期帕金森病(PD)大鼠血中褪黑素的变化,以及硫酸镁对这种变化的影响.方法 6-羟基多巴胺(6-OHDA)损毁黑质纹状体通路制备PD模型,大鼠分为PD模型组(PD/H2O)、PD加镁组(PD/Mg)、对照组(对照组/H2O)、对照加镁组(对照组/Mg).大鼠通过饮水摄入硫酸镁(每天0.36 g/kg),4周后观察其对阿扑吗啡诱发的旋转行为,并采用酶联免疫吸附试验(ELISA)检测褪黑素水平.结果 PD鼠血清褪黑素水平为(153.4±29.8) pg/L,明显高于对照组(77.2

  4. Investigations on behavioral effects of an extract of Cannabis sativa L. in the rat.

    Ferri, S; Costa, G; Murari, G; Panico, A M; Rapisarda, E; Speroni, E; Arrigo-Reina, R

    1981-01-01

    The behavioral responses of the rat to an extract of Cannabis sativa were examined after IP injection of 5, 15 and 30 mg/kg (expressed as delta 9 tetrahydrocannabinol). The lowest dose of the extract induced stereotyped behavior (rhythmic head movements, intermittent gnawing and sniffing) together with hypersensitivity to stimuli and hyperthermia. The administration of higher doses of the extract resulted, initially, in similar behavioral effects but of greater intensity, followed by a cataleptic state alternating with atonic muscular prostration; rectal temperature was decreased. Pre-treatment with 6-hydoxydopamine (6-OHDA, which produces degeneration of catecholamine-containing nerve terminals)or pimozide (blocker of dopamine receptors) significantly reduced both stereotype and hyperreactivity. Thermic effects were also antagonized by 6-OHDA pre-treatment. Cannabis-induced catalepsy was enhanced by pimozide but reduced by atropine (3 mg/kg SC). These results support the hypothesis that catecholamines play an important role in the complex behavioral effects of cannabis. PMID:6798604

  5. Modeling nicotine addiction in rats.

    Caille, Stephanie; Clemens, Kelly; Stinus, Luis; Cador, Martine

    2012-01-01

    Among the human population, 15% of drug users develop a pathological drug addiction. This figure increases substantially with nicotine, whereby more than 30% of those who try smoking develop a nicotine addiction. Drug addiction is characterized by compulsive drug-seeking and drug-taking behaviors (craving), and loss of control over intake despite impairment in health, social, and occupational functions. This behavior can be accurately modeled in the rat using an intravenous self-administration (IVSA) paradigm. Initial attempts at establishing nicotine self-administration had been problematic, yet in recent times increasingly reliable models of nicotine self-administration have been developed. The present article reviews different characteristics of the nicotine IVSA model that has been developed to examine nicotine reinforcing and motivational properties in rats. PMID:22231818

  6. Acupuncture inhibits oxidative stress and rotational behavior in 6-hydroxydopamine lesioned rat.

    Yu, Yong-Peng; Ju, Wei-Ping; Li, Zhen-Guang; Wang, Dao-Zhen; Wang, Yuan-Chen; Xie, An-Mu

    2010-06-01

    Increasing evidence suggests the beneficial effects of acupuncture on Parkinson's disease (PD). Although clinical evidence for the acupuncture anti-Parkinson's disease effect has been demonstrated, the precise mechanism still remains elusive. It has been suggested a relationship between PD and reactive oxygen species (ROS) can result in neurodegeneration. The aim of this study was to evaluate the status of oxidative stress, as well as the antioxidant enzyme response, and the role of acupuncture stimulation at GB34 (Yanglingquan), LR3 (Taichong), ST36 (Zusanli) and SP10 (Xuehai) acupoints on regulating oxidative stress in the nigrostriatal system in the 6-hydroxydopamine (6-OHDA) lesioned rat. Two weeks after unilateral injection of 6-OHDA into the left medial forebrain bundle (MFB), an apomorphine induced rotational behavior test was performed. The levels of enzymatic, viz., superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and nonenzymatic, viz., reduced glutathione (GSH), and the levels of malondialdehyde (MDA) in the nigrostriatal system were measured to assess the oxidative stress status. Brain MDA levels significantly increased, while GSH levels were decreased in impaired groups with 6-OHDA injection only, accompanied by a marked reduction in the level of SOD and GSH-Px. The levels of oxidative stress related parameters except CAT, as well as the rotational asymmetry, were reversed by acupuncture stimulation. These results showed that acupuncture treatment displayed antioxidative and/or neuroprotective properties in the 6-OHDA lesioned rat and these protective properties might be mediated, at least in part, by involving regulation of the antioxidant defense system. PMID:20399757

  7. Rat model for human cryptosporidiosis.

    BRASSEUR, P; Lemeteil, D; Ballet, J J

    1988-01-01

    Effective treatment for Cryptosporidium infection in immunocompromised patients has yet to be found. We report a rodent model of persistent Cryptosporidium infection. Sprague-Dawley rats were injected subcutaneously twice a week for 8 weeks with 25 mg of hydrocortisone acetate. Fed a regular low-protein diet for 9 weeks, they were challenged once with 10(5) calf Cryptosporidium oocysts 5 weeks after the start of the hydrocortisone acetate regimen. Oocyst shedding was evaluated in feces daily ...

  8. Effect of Buspirone, Fluoxetine and 8-OH-DPAT on Striatal Expression of Bax, Caspase-3 and Bcl-2 Proteins in 6-Hydroxydopamine-Induced Hemi-Parkinsonian Rats

    Hamdollah Sharifi; Alireza Nayebi; Safar Farajnia; Rasool Haddadi

    2015-01-01

    Purpose: The exact pathogenesis of sporadic parkinson’s disease (PD) is still unclear. Numerous evidences suggest involvement of apoptosis in the death of dopaminergic neurons. In this study we investigated the effect of sub-chronic administration of buspirone, fluoxetine and 8-hydroxy-2-[di-n-propylamino]tetralin (8-OH-DPAT) in 6-hydroxydopamine (6-OHDA)-lesioned rats and assayed striatal concentrations of apoptotic (Bax, Caspase3) and anti-apoptotic (Bcl-2) proteins. M...

  9. Medaka Fish Parkinson's Disease Model

    Matsui, Hideaki; Gavinio, Roberto; Takahashi, Ryosuke

    2012-01-01

    The teleost fish has been widely used in creating neurodegenerative models. Here we describe the teleost medaka fish Parkinson's disease (PD) models we developed using toxin treatment and genetic engineering. 1-Methyl-4-phenyl-1,2,3,4-tetrahydropyridine (MPTP), 6-hydroxydopamine (6-OHDA), proteasome inhibitors, lysosome inhibitors and tunicamycin treatment in our model fish replicated some salient features of PD: selective dopamine cell loss and reduced spontaneous movement with the last thre...

  10. A Novel Approach to Assess Motor Outcome of Deep Brain Stimulation Effects in the Hemiparkinsonian Rat: Staircase and Cylinder Test.

    Rattka, Marta; Fluri, Felix; Krstić, Miloš; Asan, Esther; Volkmann, Jens

    2016-01-01

    Deep brain stimulation of the subthalamic nucleus is an effective treatment option for Parkinson's disease. In our lab we established a protocol to screen different neurostimulation patterns in hemiparkinsonian (unilateral lesioned) rats. It consists of creating a unilateral Parkinson's lesion by injecting 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle, implanting chronic stimulation electrodes into the subthalamic nucleus and evaluating motor outcomes at the end of 24 hr periods of cable-bound external neurostimulation. The stimulation was conducted with constant current stimulation. The amplitude was set 20% below the individual threshold for side effects. The motor outcome evaluation was done by the assessment of spontaneous paw use in the cylinder test according to Shallert and by the assessment of skilled reaching in the staircase test according to Montoya. This protocol describes in detail the training in the staircase box, the cylinder test, as well as the use of both in hemiparkinsonian rats. The use of both tests is necessary, because the staircase test seems to be more sensitive for fine motor skill impairment and exhibits greater sensitivity to change during neurostimulation. The combination of the unilateral Parkinson model and the two behavioral tests allows the assessment of different stimulation parameters in a standardized way. PMID:27284739

  11. 纹状体内单侧注射6-羟多巴制备小鼠帕金森病模型%Preparation of mouse Parkinson's disease model by unilateral injection of 6-hydroxydopamine into striatum

    付爱玲; 王逸麟

    2011-01-01

    Aim Until now. there is no data that show mouse microinjection 6-hydroxydopamine ( 6-OHDA ) for Parkinson ' s disease ( PD ) model in our country. Here a mouse PD model was suggested by injection 6-OHDA into unilateral striatum.Methods The right striatum of mice was injected 6-OHDA, the Apomorphine- and Amphetamine-induced rotation behaviors were measured. and the tyrosine hvdroxvlase ( TH ) activity of cortex,left and right striatum were assayed by radioassay method. Results and Conclusion The results indicate that mouse injected 6-OHDA into striatum can be used to induce acute PD animal model. the successful rate was 95% , and the period is about four weeks.%探讨小鼠纹状体内注射6-OHDA制作PD模型可行性.方法 将6-OHDA注射入小鼠单侧纹状体内,使用阿朴吗啡和安非他命诱发的动物单侧旋转进行行为学检测,同位素法检测皮层、左右纹状体内多巴胺能神经元标志酶酪氨酸羟化酶(tyrosine hydroxylase,TH)的活性.结果 与结论小鼠纹状体内注射6-OHDA后,可成功制作急性PD模型,成功率为95%,模型持续时间大约4周.

  12. Penile autotransplantation in rats: An animal model

    Seyam, Raouf M.; Said A Kattan; Assad, Lina W.; Raafat M El-Sayed; Falah H Almohanna

    2013-01-01

    Context: Penile allotransplantation might be a viable option for patients who need penile reconstruction. Aims: A successful autotransplantation rat model is the first step toward proceeding for allotransplantation. We herein evaluate autotransplantation following transaction of the rat penis just distal to the urethral bulb. Settings and Design: Experimental animal study. Materials and Methods: Five Sprague-Dawely rats weighing 520 g (SD 19) were used. Utilizing a magnification o...

  13. Penile autotransplantation in rats: An animal model

    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.

  14. Protective efficacy of P7C3-S243 in the 6-hydroxydopamine model of Parkinson’s disease

    De Jesús-Cortés, Héctor; Miller, Adam D.; Jeremiah K Britt; DeMarco, Anthony J; De Jesús-Cortés, Mayralis; Stuebing, Emily; Naidoo, Jacinth; Vázquez-Rosa, Edwin; Morlock, Lorraine; Williams, Noelle S.; Ready, Joseph M.; Narayanan, Nandakumar S.; Pieper, Andrew A.

    2015-01-01

    BACKGROUND There are currently no therapeutic options for patients with Parkinson’s disease that prevent or slow the death of dopaminergic neurons. We have recently identified the novel P7C3 class of neuroprotective molecules that blocks neuron cell death. AIMS The aim of this study was to determine whether treatment with highly active members of the P7C3 series blocks dopaminergic neuron cell death and associated behavioral and neurochemical deficits in the rat 6-hydroxydopamine (6-OHDA) mod...

  15. A rat model for embolic encephalitis

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

    2011-01-01

    Objective: To establish a rat model for embolic encephalitis. Methods: 63 Male Sprague-Dawley rats were randomly assigned to three groups: control, sterile and septic. The right external carotid artery (ECA) was catheterized after anesthesia and 300µl blood was aspired. The blood was mixed with 30...

  16. Protective Effect of Oral Hesperetin Against Unilateral Striatal 6-Hydroxydopamine Damage in the Rat.

    Kiasalari, Zahra; Khalili, Mohsen; Baluchnejadmojarad, Tourandokht; Roghani, Mehrdad

    2016-05-01

    Parkinson's disease (PD) is a neurodegenerative disorder due to loss of dopaminergic neurons in the substantia nigra pars compacta (SNC). PD finally leads to incapacitating symptoms including motor and cognitive deficits. This study was undertaken to assess protective effect of the flavanone hesperetin against striatal 6-hydroxydopamine lesion and to explore in more detail some underlying mechanisms including apoptosis, inflammation and oxidative stress. In this research study, intrastriatal 6-hydroxydopamine (6-OHDA)-lesioned rats received hesperetin (50 mg/kg/day) for 1 week. Hesperetin reduced apomorphine-induced rotational asymmetry and decreased the latency to initiate and the total time on the narrow beam task. It also attenuated striatal malondialdehyde and enhanced striatal catalase activity and GSH content, lowered striatal level of glial fibrillary acidic protein as an index of astrogliosis and increased Bcl2 with no significant change of the nuclear factor NF-kB as a marker of inflammation. Hesperetin treatment was also capable to mitigate nigral DNA fragmentation as an index of apoptosis and to prevent loss of SNC dopaminergic neurons. This study indicated the protective effect of hesperetin in an early model of PD via attenuation of apoptosis, astrogliosis marker and oxidative stress and it may be helpful as an adjuvant therapy for management of PD at its early stages. PMID:26700436

  17. Acute L: -DOPA effect on hydroxyl radical- and DOPAC-levels in striatal microdialysates of parkinsonian rats.

    Nowak, Przemysław; Kostrzewa, Rose Anna; Skaba, Dariusz; Kostrzewa, Richard M

    2010-04-01

    The object of the current study was to determine the effect of L: -3,4-dihydroxyphenylalanine (L: -DOPA) on the in vivo striatal microdialysate levels of the respective dopamine and serotonin metabolites 3,4-dihydroxyphenlalanine (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) and hydroxyl radical level (HO(*); 2,3- and 2,5-dihydroxybenzoic acid, 2,3- and 2,5-DHBA) in adult rats made parkinsonian by treatment at 3 days after birth with the neurotoxin 6-hydroxydopamine (6-OHDA; 66.7 microg, base form, on each side; desipramine pretreatment, 1 h). Using HPLC/ED we found that in 6-OHDA-lesioned rats the basal striatal extraneuronal level of DOPAC was dramatically reduced and constituted only approximately 4.5% of referenced value (intact rats). Conversely, the striatal microdialysate level of 5-HIAA was elevated 2-fold in 6-OHDA-lesioned rats. Acute L: -DOPA (60 mg/kg i.p.; S-carbidopa pretreatment, 12.5 mg/kg i.p., 30 min) produced a rapid rise in the extraneuronal DOPAC in both tested groups but to a much greater extent in intact rats (P DOPA did not enhance HO(*) production; acute 6-OHDOPA treatment (60 mg/kg i.p.) also did not alter HO(*) production. In summary, L: -DOPA, an effective drug in ameliorating PD symptoms, did not acutely pose a risk for HO(*) generation in parkinsonian rats. We conclude that L: -DOPA is not likely to generate reactive oxygen species in humans nor is L: -DOPA likely to accelerate PD in humans. PMID:19760476

  18. Duration of drug action of dopamine D2 agonists in mice with 6-hydroxydopamine-induced lesions.

    Tsuchioka, Akihiro; Oana, Fumiki; Suzuki, Takayuki; Yamauchi, Yuji; Ijiro, Tomoyuki; Kaidoh, Kouichi; Hiratochi, Masahiro

    2015-12-16

    Although 6-hydroxydopamine-induced (6-OHDA-induced) rats are a well-known Parkinson's disease model, the effects of dopamine D2 agonists in mice with 6-OHDA-induced lesions are not completely understood. We produced mice with 6-OHDA-induced lesions and measured their total locomotion counts following administration of several dopamine D2 agonists (pramipexole, ropinirole, cabergoline, rotigotine, apomorphine, talipexole, and quinelorane). Cabergoline showed the longest duration of drug action, which was in agreement with its long-lived anti-Parkinson effects in rats and humans. In contrast, pramipexole and ropinirole had notably short durations of drug action. We demonstrated that mice with 6-OHDA-induced lesions accompanied with significant lesions in the striatum may be reasonable models to predict the action duration of anti-Parkinson drug candidates in humans. PMID:26559726

  19. Pre-existing immunity to adeno-associated virus (AAV)2 limits transgene expression following intracerebral AAV2-based gene delivery in a 6-hydroxydopamine model of Parkinson's disease.

    Janelidze, Shorena; Nordström, Ulrika; Kügler, Sebastian; Brundin, Patrik

    2014-01-01

    BACKGROUND: Adeno-associated virus (AAV) vectors are used to deliver potentially therapeutic genes in clinical trials in Parkinson's disease (PD). Pre-existing immunity to AAV and a local neuroinflammatory response might negatively affect the efficacy of such AAV-mediated gene delivery. METHODS: We pre-immunized rats with wild-type AAV-2. Three months later, we created PD-like lesions by intrastriatal injections of 6-hydroxydopamine (6-OHDA) in 50% of the animals. One month later, we inj...

  20. Effects of Nano-MnO2 on Dopaminergic Neurons and the Spatial Learning Capability of Rats

    Tao Li

    2014-08-01

    Full Text Available This study aimed to observe the effect of intracerebrally injected nano-MnO2 on neurobehavior and the functions of dopaminergic neurons and astrocytes. Nano-MnO2, 6-OHDA, and saline (control were injected in the substantia nigra and the ventral tegmental area of Sprague-Dawley rat brains. The neurobehavior of rats was evaluated by Morris water maze test. Tyrosine hydroxylase (TH, inducible nitric oxide synthase (iNOS and glial fibrillary acidic protein (GFAP expressions in rat brain were detected by immunohistochemistry. Results showed that the escape latencies of nano-MnO2 treated rat increased significantly compared with control. The number of TH-positive cells decreased, GFAP- and iNOS-positive cells increased significantly in the lesion side of the rat brains compared with the contralateral area in nano-MnO2 group. The same tendencies were observed in nano-MnO2-injected rat brains compared with control. However, in the the positive control, 6-OHDA group, escape latencies increased, TH-positive cell number decreased significantly compared with nano-MnO2 group. The alteration of spatial learning abilities of rats induced by nano-MnO2 may be associated with dopaminergic neuronal dysfunction and astrocyte activation.

  1. Neuroprotective effect of Tinospora cordifolia ethanol extract on 6-hydroxy dopamine induced Parkinsonism

    Jayasankar Kosaraju; Santhivardhan Chinni; Partha Deb Roy; Elango Kannan; A Shanish Antony; Satish Kumar, M.N.

    2014-01-01

    Objective: The present study investigates the neuroprotective activity of ethanol extract of Tinospora cordifolia aerial parts against 6-hydroxy dopamine (6-OHDA) lesion rat model of Parkinson′s disease (PD). Materials and Methods: T. cordifolia ethanol extract (TCEE) was standardized with high performance thin layer chromatography using berberine. Experimental PD was induced by intracerebral injection of 6-OHDA (8 μg). Animals were divided into five groups: sham operated, negative contro...

  2. Dietary models for inducing hypercholesterolemia in rats

    Sheyla Leite Matos; Heberth de Paula; Maria Lúcia Pedrosa; Rinaldo Cardoso dos Santos; Eduardo Luiz de Oliveira; Deoclécio Alves Chianca Júnior; Marcelo Eustáquio Silva

    2005-01-01

    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...

  3. Progesterone Exerts a Neuromodulatory Effect on Turning Behavior of Hemiparkinsonian Male Rats: Expression of 3α-Hydroxysteroid Oxidoreductase and Allopregnanolone as Suggestive of GABAA Receptors Involvement

    Roberto Yunes

    2015-01-01

    Full Text Available There is a growing amount of evidence for a neuroprotective role of progesterone and its neuroactive metabolite, allopregnanolone, in animal models of neurodegenerative diseases. By using a model of hemiparkinsonism in male rats, injection of the neurotoxic 6-OHDA in left striatum, we studied progesterone’s effects on rotational behavior induced by amphetamine or apomorphine. Also, in order to find potential explanatory mechanisms, we studied expression and activity of nigrostriatal 3α-hydroxysteroid oxidoreductase, the enzyme that catalyzes progesterone to its active metabolite allopregnanolone. Coherently, we tested allopregnanolone for a possible neuromodulatory effect on rotational behavior. Also, since allopregnanolone is known as a GABAA modulator, we finally examined the action of GABAA antagonist bicuculline. We found that progesterone, in addition to an apparent neuroprotective effect, also increased ipsilateral expression and activity of 3α-hydroxysteroid oxidoreductase. It was interesting to note that ipsilateral administration of allopregnanolone reversed a clear sign of motor neurodegeneration, that is, contralateral rotational behavior. A possible GABAA involvement modulated by allopregnanolone was shown by the blocking effect of bicuculline. Our results suggest that early administration of progesterone possibly activates genomic mechanisms that promote neuroprotection subchronically. This, in turn, could be partially mediated by fast, nongenomic, actions of allopregnanolone acting as an acute modulator of GABAergic transmission.

  4. Levodopa replacement therapy alters enzyme activities in striatum and neuropeptide content in striatal output regions of 6-hydroxydopamine lesioned rats.

    Engber, T M; Susel, Z; Kuo, S; Gerfen, C R; Chase, T N

    1991-06-21

    The effects of striatal dopamine denervation and levodopa replacement therapy on neuronal populations in the rat striatum were assessed by measurement of glutamic acid decarboxylase (GAD) and choline acetyltransferase (CAT) activities in the striatum, dynorphin and substance P concentrations in the substantia nigra, and enkephalin concentration in the globus pallidus. Rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal pathway were treated for 21 days with levodopa (100 mg/kg/day, i.p., with 25 mg/kg benserazide) on either an intermittent (b.i.d.) or continuous (osmotic pump infusion) regimen and sacrificed following a three day drug washout. In saline-treated control rats, striatal GAD activity and globus pallidus enkephalin content were elevated and nigral substance P content was reduced ipsilateral to the 6-OHDA lesion. Intermittent levodopa treatment further increased GAD activity, decreased CAT activity, restored substance P to control levels, markedly increased dynorphin content, and had no effect on enkephalin. In contrast, continuous levodopa elevated globus pallidus enkephalin beyond the levels occurring with denervation, but had no effect on any of the other neurochemical measures. These results indicate that striatal neuronal populations are differentially affected by chronic levodopa therapy and by the continuous or intermittent nature of the treatment regimen. With the exception of substance P, levodopa did not reverse the effects of the 6-OHDA lesion but, rather, either exacerbated the lesion-induced changes (e.g. GAD and enkephalin) or altered neurochemical markers which had been unaffected by the lesion (e.g. CAT and dynorphin).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1717109

  5. Experimental rat bladder urothelial cell carcinoma models

    Arentsen, Harm C.; Hendricksen, Kees; Oosterwijk, Egbert; Witjes, J Alfred

    2009-01-01

    Bladder cancer is a major public health problem. Currently available therapeutic options seem to be unable to prevent bladder cancer recurrence and progression. To enable preclinical testing of new intravesical therapeutic agents, a suitable bladder tumor model that resembles human disease is highly desirable. The aim of this topic paper was to discuss the problems associated with current in vivo animal bladder tumor models, focusing on the orthotopic syngeneic rat bladder tumor model. In the...

  6. Neuroprotective effects of protocatechuic aldehyde against neurotoxin-induced cellular and animal models of Parkinson's disease.

    Xin Zhao

    Full Text Available Protocatechuic aldehyde (PAL has been reported to bind to DJ-1, a key protein involved in Parkinson's disease (PD, and exerts potential neuroprotective effects via DJ-1 in SH-SY5Y cells. In this study, we investigated the neuroprotective pharmacological effects of PAL against neurotoxin-induced cell and animal models of PD. In cellular models of PD, PAL markedly increased cell viability rates, mitochondrial oxidation-reduction activity and mitochondrial membrane potential, and reduced intracellular ROS levels to prevent neurotoxicity in PC12 cells. In animal models of PD, PAL reduced the apomorphine injection, caused turning in 6-OHDA treated rats, and increased the motor coordination and stride decreases in MPTP treated mice. Meanwhile, in an MPTP mouse model, PAL prevented a decrease of the contents of dopamine (DA and its metabolites in the striatum and TH-positive dopaminergic neuron loss in the substantia nigra (SN. In addition, PAL increased the protein expression of DJ-1 and reduced the level of α-synuclein in the SN of MPTP lesioned mice. PAL also increased the spine density in hippocampal CA1 neurons. The current study demonstrates that PAL can efficiently protect dopaminergic neurons against neurotoxin injury in vitro and in vivo, and that the potential mechanisms may be related to its effects in increasing DJ-1, decreasing α-synuclein and its growth-promoting effect on spine density.

  7. Properties of Flicker ERGs in Rat Models with Retinal Degeneration

    Jing An; Qun Guo; Li Li(State Key Laboratory of Theoretical Physics, Institute of Theoretical Physics, Chinese Academy of Sciences, Beijing 100190, China); Zuoming Zhang

    2012-01-01

    Purpose. To describe the characteristics of rod and cone functions in rat models for congenital stationary night blindness (CSNB) and retinal cone dysfunction (RCD). Methods. Rod and cone function were isolated by recording the rod-/cone-driven flicker and blue light flicker electroretinograms (ERGs). Results. During dark adaptation, the amplitudes of flicker ERGs in CSNB rats were lower than those in control rats; the responses of RCD rats were similar to control rats. During light adaptatio...

  8. The rat as an animal model of Alzheimer's disease

    Benedikz, Eirikur; Kloskowska, Ewa; Winblad, Bengt

    2009-01-01

    As a disease model, the laboratory rat has contributed enormously to neuroscience research over the years. It has also been a popular animal model for Alzheimer's disease but its popularity has diminished during the last decade, as techniques for genetic manipulation in rats have lagged behind that...... of mice. In recent years, the rat has been making a comeback as an Alzheimer's disease model and the appearance of increasing numbers of transgenic rats will be a welcome and valuable complement to the existing mouse models. This review summarizes the contributions and current status of the rat as an...... animal model of Alzheimer's disease....

  9. Intrastriatal injection of botulinum neurotoxin-A is not cytotoxic in rat brain - A histological and stereological analysis.

    Mehlan, Juliane; Brosig, Hans; Schmitt, Oliver; Mix, Eilhard; Wree, Andreas; Hawlitschka, Alexander

    2016-01-01

    Parkinson's disease (PD) is caused by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta, resulting in a deficiency of dopamine in the striatum and an increased release of acetylcholine by tonically active interneurons. Botulinum neurotoxin-A (BoNT-A) is well known for blocking transmitter release by cholinergic presynaptic terminals. Treating striatal hypercholinism by local application of BoNT-A could be a possible new local therapy option of PD. In previous studies of our group, we analyzed the effect of BoNT-A injection into the CPu of 6-OHDA lesioned hemiparkinsonian rats. Our studies showed that BoNT-A application in hemiparkinson rat model is capable of abolishing apomorphine induced rotations for approximately 3 months. Regularly occurring axonal swellings in the BoNT-A infiltrated striata were also discovered, which we named BoNT-A induced varicosities (BiVs). Résumé: Here we investigated the long-term effect of the injection of 1ng BoNT-A into the right CPu of naive Wistar rats on the number of ChAT-ir interneurons as well as on the numeric density and the volumetric size of the BiVs in the CPu. Significant differences in the number of ChAT-ir neurons between the right BoNT-A treated CPu and the left untreated CPu were not detected up to 12 month post BoNT-A injection. The numeric density of BiVs in the treated CPu reached a maximum 3 months after BoNT-A treatment and decreased afterwards, whereas the volume of single BiVs increased steadily throughout the whole time course of the experiment. PMID:26562665

  10. A model of subarachnoid hemorrhage in rats

    Liao-liaoLI; Xiao-liangWANG

    2004-01-01

    AIM: To build a simple and repeatable animal model of subarachnoid hemorrhage (SAH). METHODS: SAH was introduced by passing a nylon thread up through the right internal carotid artery and piercing a hone in the right anterior cerebral artery. At 12 and 24 h, the rats were evaluated with rotarod test and the behavior scale (5-point scale). RESULTS: The ratswere trained through rotarod test and then randomly divided into

  11. Tau reduction does not prevent motor deficits in two mouse models of Parkinson's disease.

    Meaghan Morris

    Full Text Available Many neurodegenerative diseases are increasing in prevalence and cannot be prevented or cured. If they shared common pathogenic mechanisms, treatments targeting such mechanisms might be of benefit in multiple conditions. The tau protein has been implicated in the pathogenesis of diverse neurodegenerative disorders, including Alzheimer's disease (AD and Parkinson's disease (PD. Tau reduction prevents cognitive deficits, behavioral abnormalities and other pathological changes in multiple AD mouse models. Here we examined whether tau reduction also prevents motor deficits and pathological alterations in two mouse models of PD, generated by unilateral striatal injection of 6-hydroxydopamine (6-OHDA or transgene-mediated neuronal expression of human wildtype α-synuclein. Both models were evaluated on Tau(+/+, Tau(+/- and Tau(-/- backgrounds in a variety of motor tests. Tau reduction did not prevent motor deficits caused by 6-OHDA and slightly worsened one of them. Tau reduction also did not prevent 6-OHDA-induced loss of dopaminergic terminals in the striatum. Similarly, tau reduction did not prevent motor deficits in α-synuclein transgenic mice. Our results suggest that tau has distinct roles in the pathogeneses of AD and PD and that tau reduction may not be of benefit in the latter condition.

  12. Inhibition by anandamide of 6-hydroxydopamine-induced cell death in PC12 cells.

    Mnich, Katarzyna

    2010-01-01

    6-hydroxydopamine (6-OHDA) is a selective neurotoxin that is widely used to investigate cell death and protective strategies in models of Parkinson\\'s disease. Here, we investigated the effects of the endogenous cannabinoid, anandamide, on 6-OHDA-induced toxicity in rat adrenal phaeochromocytoma PC12 cells. Morphological analysis and caspase-3 activity assay revealed that anandamide inhibited 6-OHDA-induced apoptosis. The protection was not affected by antagonists of either cannabinoid receptors (CB(1) or CB(2)) or the vanilloid receptor TRPV1. Anandamide-dependent protection was reduced by pretreatment with LY294002 (inhibitor of phosphatidylinositol 3-kinase, PI3K) and unaffected by U0126 (inhibitor of extracellularly-regulated kinase). Interestingly, phosphorylation of c-Jun-NH2-terminal kinase (JNK) in cells exposed to 6-OHDA was strongly reduced by anandamide pre-treatment. Furthermore, 6-OHDA induced c-Jun activation and increased Bim expression, both of which were inhibited by anandamide. Together, these data demonstrate antiapoptotic effects of anandamide and also suggest a role for activation of PI3K and inhibition of JNK signalling in anandamide-mediated protection against 6-OHDA.

  13. Reduced vocal variability in a zebra finch model of dopamine depletion: implications for Parkinson disease.

    Miller, Julie E; Hafzalla, George W; Burkett, Zachary D; Fox, Cynthia M; White, Stephanie A

    2015-11-01

    Midbrain dopamine (DA) modulates the activity of basal ganglia circuitry important for motor control in a variety of species. In songbirds, DA underlies motivational behavior including reproductive drive and is implicated as a gatekeeper for neural activity governing vocal variability. In the zebra finch, Taeniopygia guttata, DA levels increase in Area X, a song-dedicated subregion of the basal ganglia, when a male bird sings his courtship song to a female (female-directed; FD). Levels remain stable when he sings a less stereotyped version that is not directed toward a conspecific (undirected; UD). Here, we used a mild dose of the neurotoxin 6-hydroxydopamine (6-OHDA) to reduce presynaptic DA input to Area X and characterized the effects on FD and UD behaviors. Immunoblots were used to quantify levels of tyrosine hydroxylase (TH) as a biomarker for DA afferent loss in vehicle- and 6-OHDA-injected birds. Following 6-OHDA administration, TH signals were lower in Area X but not in an adjacent subregion, ventral striatal-pallidum (VSP). A postsynaptic marker of DA signaling was unchanged in both regions. These observations suggest that effects were specific to presynaptic afferents of vocal basal ganglia. Concurrently, vocal variability was reduced during UD but not FD song. Similar decreases in vocal variability are observed in patients with Parkinson disease (PD), but the link to DA loss is not well-understood. The 6-OHDA songbird model offers a unique opportunity to further examine how DA loss in cortico-basal ganglia pathways affects vocal control. PMID:26564062

  14. Ideal Experimental Rat Models for Liver Diseases.

    Lee, Sang Woo; Kim, Sung Hoon; Min, Seon Ok; Kim, Kyung Sik

    2011-05-01

    There are many limitations for conducting liver disease research in human beings due to the high cost and potential ethical issues. For this reason, conducting a study that is difficult to perform in humans using appropriate animal models, can be beneficial in ascertaining the pathological physiology, and in developing new treatment modalities. However, it is difficult to determine the appropriate animal model which is suitable for research purposes, since every patient has different and diverse clinical symptoms, adverse reactions, and complications due to the pathological physiology. Also, it is not easy to reproduce identically various clinical situations in animal models. Recently, the Guide for the Care and Use of Laboratory Animals has tightened up the regulations, and therefore it is advisable to select the appropriate animals and decide upon the appropriate quantities through scientific and systemic considerations before conducting animal testing. Therefore, in this review article the authors examined various white rat animal testing models and determined the appropriate usable rat model, and the pros and cons of its application in liver disease research. The authors believe that this review will be beneficial in selecting proper laboratory animals for research purposes. PMID:26421020

  15. The passive coping Roman Low Avoidance rat, a non-obese rat model for insulin resistance

    Boersma, G. J.; Scheurink, A. J. W.; Wielinga, P. Y.; Steimer, T. J.; Benthem, L.

    2009-01-01

    The aim of the study was develop to an animal model that links coping style to insulin resistance. We hypothesized that the psychogenetically selected Roman Low Avoidance (RLA) rats may serve as such a model. To test this hypothesis, we submitted both RLA and Roman High avoidance (RHA) rats to a ser

  16. A Novel Rat Model of Type 2 Diabetes: The Zucker Fatty Diabetes Mellitus ZFDM Rat

    Norihide Yokoi

    2013-01-01

    Full Text Available The Zucker fatty (ZF rat harboring a missense mutation (fatty, fa in the leptin receptor gene (Lepr develops obesity without diabetes; Zucker diabetic fatty (ZDF rats derived from the ZF strain exhibit obesity with diabetes and are widely used for research on type 2 diabetes (T2D. Here we establish a novel diabetic strain derived from normoglycemic ZF rats. In our ZF rat colony, we incidentally found fa/fa homozygous male rats having reproductive ability, which is generally absent in these animals. During maintenance of this strain by mating fa/fa males and fa/+ heterozygous females, we further identified fa/fa male rats exhibiting diabetes. We then performed selective breeding using the fa/fa male rats that exhibited relatively high blood glucose levels at 10 weeks of age, resulting in establishment of a diabetic strain that we designated Hos:ZFDM-Leprfa (ZFDM. These fa/fa male rats developed diabetes as early as 10 weeks of age, reaching 100% incidence by 21 weeks of age, while none of the fa/+ male rats developed diabetes. The phenotypic characteristics of this diabetic strain are distinct from those of normoglycemic ZF rats. ZFDM rat strain having high reproductive efficiency should serve as a more useful animal model of T2D.

  17. Expression of Tgfβ1 and inflammatory markers in the 6-hydroxydopamine mouse model of Parkinson´s disease

    Stefan Jean-Pierre Haas

    2016-02-01

    Full Text Available Parkinson´s disease (PD is a neurodegenerative disorder that is characterised by loss of midbrain dopaminergic (mDA neurons in the substantia nigra (SN. Microglia-mediated neuroinflammation has been described as a common hallmark of PD and is believed to further trigger the progression of neurodegenerative events. Injections of 6-hydroxydopamine (6-OHDA are widely used to induce degeneration of mDA neurons in rodents as an attempt to mimic PD and to study neurodegeneration, neuroinflammation as well as potential therapeutic approaches. In the present study, we addressed microglia and astroglia reactivity in the SN and the caudatoputamen (CPu after 6-OHDA injections into the medial forebrain bundle (MFB, and further analysed the temporal and spatial expression patterns of pro-inflammatory and anti-inflammatory markers in this mouse model of PD. We provide evidence that activated microglia as well as neurons in the lesioned SN and CPu express Tgfβ1, which overlaps with the downregulation of pro-inflammatory markers Tnfα, and iNos, and upregulation of anti-inflammatory markers Ym1 and Arg1. Taken together, the data presented in this study suggest an important role for Tgfβ1 as a lesion-associated factor that might be involved in regulating microglia activation states in the 6-OHDA mouse model of PD in order to prevent degeneration of uninjured neurons by microglia-mediated release of neurotoxic factors such as Tnfα and nitric oxide (NO.

  18. APLICACIÓN DEL TEST DE LA BARRA TRANSVERSAL MODIFICADO PARA EVALUAR RATAS HEMIPARKINSONIZADAS. Modify Beam Transversal Test to Evauate Hemiparkinsonian Rats.

    LISETTE BLANCO LEZCANO

    Full Text Available La degeneración nigroestriatal que caracteriza a la enfermedad de Parkinson (EP es estudiada en modelos experimentales en roedores por inyección de 6-hidroxidopamina (6-OHDA. El presente estudio presenta una versión modificada del test de la barra transversal (TBT que permite la cuantificación del déficit motor a través de: tiempo que demora la rata en alcanzar una de las plataformas (latencia de escape, LE; tiempo que demora en caer de la barra (latencia de caída, LC; número total de errores cometidos durante la ejecución en cada barra (número de errores, NE. La forma y el diámetro de la sección transversal de la barra se modificaron desde barras rectangulares y circulares de 2,5 cm de diámetro hasta barras con esta misma forma y 1 cm de diámetro respectivamente lo cual impuso la mayor dificultad a la ejecución del test. Tres grupos de ratas Wistar fueron evaluados: no tratadas (n=15, lesionadas con 6-OHDA (n=14 y falsas operadas (n=14. Todas las variables estudiadas mostraron diferencias signifi-cativas entre ratas controles y hemiparkinsonizadas. Para todos los tipos de barras, las variables LE y NE se incrementaron mientras que la LC disminuyó significativamente en las ratas hemiparkinsonizadas en comparación con las ratas controles. La LC mostró diferencias altamente significativas (pThe nigrostriatal degeneration underlying Parkinson’s disease (PD is commonly studied in experimental animals by injection of the neurotoxin 6-hydroxydopamine. The present study describes a modified version of a beam traversal test which allows the quantification of the motor deficit through the time spent to arrive to the platform once all four paws of the animals are in contact with the beam (escape latency, EL, the time spent before falling (tumbled down latency, TDL and the number of errors (NE committed for the animals in each beam. The shape and the diameter of the cross section of the beams were modified from rectangular and circular

  19. Glial activation is associated with l-DOPA induced dyskinesia and blocked by a nitric oxide synthase inhibitor in a rat model of Parkinson's disease.

    Bortolanza, Mariza; Cavalcanti-Kiwiatkoski, Roberta; Padovan-Neto, Fernando E; da-Silva, Célia Aparecida; Mitkovski, Miso; Raisman-Vozari, Rita; Del-Bel, Elaine

    2015-01-01

    l-3, 4-dihydroxyphenylalanine (L-DOPA) is the most effective treatment for Parkinson's disease but can induce debilitating abnormal involuntary movements (dyskinesia). Here we show that the development of L-DOPA-induced dyskinesia in the rat is accompanied by upregulation of an inflammatory cascade involving nitric oxide. Male Wistar rats sustained unilateral injections of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle. After three weeks animals started to receive daily treatment with L-DOPA (30 mg/kg plus benserazide 7.5 mg/kg, for 21 days), combined with an inhibitor of neuronal NOS (7-nitroindazole, 7-NI, 30 mg/kg/day) or vehicle (saline-PEG 50%). All animals treated with L-DOPA and vehicle developed abnormal involuntary movements, and this effect was prevented by 7-NI. L-DOPA-treated dyskinetic animals exhibited an increased striatal and pallidal expression of glial fibrillary acidic protein (GFAP) in reactive astrocytes, an increased number of CD11b-positive microglial cells with activated morphology, and the rise of cells positive for inducible nitric oxide-synthase immunoreactivity (iNOS). All these indexes of glial activation were prevented by 7-NI co-administration. These findings provide evidence that the development of L-DOPA-induced dyskinesia in the rat is associated with activation of glial cells that promote inflammatory responses. The dramatic effect of 7-NI in preventing this glial response points to an involvement of nitric oxide. Moreover, the results suggest that the NOS inhibitor prevents dyskinesia at least in part via inhibition of glial cell activation and iNOS expression. Our observations indicate nitric oxide synthase inhibitors as a therapeutic strategy for preventing neuroinflammatory and glial components of dyskinesia pathogenesis in Parkinson's disease. PMID:25447229

  20. Preventative treatment in an animal model of ADHD: Behavioral and biochemical effects of methylphenidate and its interactions with ovarian hormones in female rats.

    Lukkes, Jodi L; Freund, Nadja; Thompson, Britta S; Meda, Shirisha; Andersen, Susan L

    2016-09-01

    Clinical and preclinical studies on attention deficit hyperactivity disorder (ADHD) show that juvenile males that are exposed to methylphenidate (MPH) show reduced risk for substance use later in life. In contrast, little is known about whether females have the same enduring treatment response to stimulants and how gonadal hormones influence their behavior later in life. Females received either a sham or 6-hydroxydopamine (6-OHDA) microinjection in the prefrontal cortex (PFC) at postnatal day (P)10. Subjects were then treated with Vehicle or MPH (2mg/kg, p.o.) between P20-35 and tested during late adolescence/young adulthood (P60); half of these subjects underwent ovariectomy at P55 to determine hormonal influences. Females with 6-OHDA were depleted of PFC dopamine by 61% and demonstrated increased impulsive choice (delayed discounting) and preferences for cocaine-associated environments relative to control females. Both MPH and ovariectomy reduced impulsive choice and cocaine preferences in 6-OHDA females, but had no enduring effect in Sham females. Ovariectomy itself did not significantly affect impulsivity. Juvenile MPH interacted strongly with 6-OHDA to increase D4, D5, Alpha-1A, Alpha-2A, and 5-HT-1A mRNA receptor expression in the PFC. MPH alone effected D1 mRNA, while 6-OHDA increased BDNF; all markers were decreased by ovariectomy. Together, these data suggest that 6-OHDA changes in dopamine are not only relevant for ADHD-like behaviors, but their long-term modulation by treatment and the influence of cyclical differences in menstrual cycle. PMID:27397110

  1. Neuroprotective Effects of Liraglutide for Stroke Model of Rats

    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.

  2. A Rat Excised Larynx Model of Vocal Fold Scar

    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…

  3. Modeling neuro-vascular coupling in rat cerebellum

    Rasmussen, Tina; Holstein-Rathlou, Niels-Henrik; Lauritzen, Martin

    2009-01-01

    linearizability. We exercised the model on data from rat cerebellar cortex. In anesthetized rats, stimulation of the inferior olive caused climbing fiber activity and blood flow changes. Field potential amplitudes were used as an indicator of neuronal activity and blood flow was measured by laser...

  4. The passive coping Roman Low Avoidance rat, a non-obese rat model for insulin resistance

    Boersma, G.J.; Scheurink, A. J. W.; Wielinga, P Y; Steimer, T. J.; Benthem, L.

    2009-01-01

    The aim of the study was develop to an animal model that links coping style to insulin resistance. We hypothesized that the psychogenetically selected Roman Low Avoidance (RLA) rats may serve as such a model. To test this hypothesis, we submitted both RLA and Roman High avoidance (RHA) rats to a series of intravenous glucose tolerance tests (IVGTT). These IVGTT were followed by post mortem metabolic characterization of the selection lines. It was found that plasma insulin levels are markedly ...

  5. HYPERACTIVITY AND HYPOACTIVITY PRODUCED BY LESIONS TO THE MESOLIMBIC DOPAMINE SYSTEM

    Spontaneous locomotor activity and the locomotor response to amphetamine and apomorphine were studied in rats subjected to either radiofrequency(RF), 6-hydroxydopamine (6-OHDA) of both RF and 6-OHDA lesions of the mesolimbic dopamine (DA) system. Large 6-OHDA lesions of the ventr...

  6. Distinct temporal spike and local field potential activities in the thalamic parafascicular nucleus of parkinsonian rats during rest and limb movement.

    Wang, Min; Qu, Qingyang; He, Tingting; Li, Min; Song, Zhimin; Chen, Feiyu; Zhang, Xiao; Xie, Jinlu; Geng, Xiwen; Yang, Maoquan; Wang, Xiusong; Lei, Chengdong; Hou, Yabing

    2016-08-25

    Several studies have suggested that the thalamic centromedian-parafascicular (CM/PF or the PF in rodents) is implicated in the pathophysiology of Parkinson's disease (PD). However, inconsistent changes in the neuronal firing rate and pattern have been reported in parkinsonian animals. To investigate the impact of a dopaminergic cell lesion on PF extracellular discharge in behaving rats, the PF neural activities in the spike and local field potential (LFP) were recorded in unilaterally 6-hydroxydopamine- (6-OHDA) lesioned and neurologically intact control rats during rest and limb movement. During rest, the two PF neuronal subtypes was less spontaneously active, with no difference in the spike firing rates between the control and lesioned rats; only the lesioned rats reshaped their spike firing pattern. Furthermore, the simultaneously recorded LFP in the lesioned rats exhibited a significant increase in power at 12-35 and 35-70Hz and a decrease in power at 0.7-12Hz. During the execution of a voluntary movement, two subtypes of PF neurons were identified by a rapid increase in the discharge activity in both the control and lesioned rats. However, dopamine lesioning was associated with a decrease in neuronal spiking fire rate and reshaping in the firing pattern in the PF. The simultaneously recorded LFP activity exhibited a significant increase in power at 12-35Hz and a decrease in power at 0.7-12Hz compared with the control rats. These findings indicate that 6-OHDA induces modifications in PF spike and LFP activities in rats during rest and movement and suggest that PF dysfunction may be an important contributor to the pathophysiology of parkinsonian motor impairment. PMID:27238892

  7. Antioxidant Activity of Oral Administration of Rosmarinus Officinalis Leaves Extract on Rat's Hippocampus which Exposed to 6-Hydroxydopamine

    Arashpour Rasoul

    2016-01-01

    Full Text Available Carnosic acid, a diterpene of Rosemarinus officinalis leaves extract (RE, has potent antioxidant activity in vitro. The dopaminergic connection of substantia nigra pars compacta to the hippocampus might be affected by oxidative stress which caused cognitive impairment observed in the early phase of Parkinson's disease (PD. Adult male Wistar rats were lesioned bilaterally by intra-nigral injection of 6-OHDA, and divided into six groups: four groups that orally given RE containing 40% of carnosic acid, at doses of 25, 50 and 100 mg/kg (treated rats and distilled water (H2O, once daily for a period of 14 days before and after the injury. There were also two another groups as control rats which injected by normal saline and untreated lesion group. The injured animals were evaluated for their spatial memory performance by Morris Water Maze test. Lesioned rats showed significant increase in escape latency, as compared with control group. Two weeks after injury, tissue samples were collected from the hippocampus. Levels of catalase (CAT, glutathione peroxidase (GPX and superoxide dismutase (SOD, malondialdehyde (MDA and reactive oxygen species (ROS were determined. There were significant increase of SOD, GPX and CAT enzymes activities in RE50 treated group as compared to lesioned rats. We found a significant decrease of ROS in RE50 treated group as compared to Lesioned rats. These findings provide evidence that 50 mg/kg of RE decreased oxidative damage of the hippocampus induced by 6-OHDA and serve as potential candidate for the treatment of PD.

  8. The LEC rat as a radiosensitive model animal

    The author described the review on the LEC rat which had been firstly established as a model animal of spontaneous hepatitis and hepatoma and had been then found to be highly sensitive to ionizing radiation by the author and his coworkers and to be similar to human AT (ataxia-telangiectasia) as for induced DNA damages. The hepatic failure was primarily caused by Cu accumulation and mutation was detected in the same gene as the causative gene of human Wilson disease. LEC rats exerted 2-times higher radiosensitivity in mortality than the control WKAH rats and this was also true in lung fibroblast and other tissue cells isolated from LEC rat fetus. Breeding experiments of LEC x WKAH and of their offspring F1 x LEC (back cross) revealed that the high radiosensitivity of LEC rats was due to the recessive autosomal gene xhs. Similar to AT cells, LEC rat cells exerted a high incidence of X ray-induced chromosome aberration. In LEC rat cells, the sensitivity spectrum to DNA damaging agents was more broad than that in WKAH cells and the rate to repair DNA damage, particularly double strand break, was slower. The extent of the decrease in DNA synthesis post irradiation was small in AT cells (radioresistant DNA synthesis), which was also seen in LEC rat cells. After the whole body X-ray irradiation, cell apoptosis was seen in spleen and thymus more frequently in LEC rats than in WKAH rats. Abnormal signal transduction system involving p53 protein induced by DNA damage post irradiation caused apoptosis and thereby induced abnormal cell cycle regulation, which was considered to be related with the radiosensitivity of AT cells. Thus the LEC rat can be a good model animal of radiosensitivity. (K.H.)

  9. Animal models of neurological deficits: how relevant is the rat?

    Cenci, M Angela; Whishaw, Ian Q; Schallert, Timothy

    2002-07-01

    Animal models of neurological deficits are essential for the assessment of new therapeutic options. It has been suggested that rats are not as appropriate as primates for the symptomatic modelling of disease, but a large body of data argues against this view. Comparative analyses of movements in rats and primates show homology of many motor patterns across species. Advances have been made in identifying rat equivalents of akinesia, tremor, postural deficits and dyskinesia, which are relevant to Parkinson's disease. Rat models of hemiplegia, neglect and tactile extinction are useful in assessing the outcome of ischaemic or traumatic brain injury, and in monitoring the effects of therapeutic interventions. Studies in rodents that emphasize careful behavioural analysis should continue to be developed as effective and inexpensive models that complement studies in primates. PMID:12094213

  10. A model of gastric precancerous lesions for rats

    Mao Xiang Yan; Zhi Yun Chen; Bai Kang Xiang

    2000-01-01

    AIM To establish an ideal model of gastric precancerous lesions for rats.METHODS Fifty rats were fed with carcinogen MNNG for 35 wk and heat-plaste at 60C for 20 wk, thepathological changes were observed. Data in the groups were analyzed by Ridit test.RESULTS The occurrence rate of dysplasia in rats due to MNNG and heat-damage was 65%, which wasobviously higher than that due to MNNG only. The differences between the two groups were significant.CONCLUSION The animal model made by MNNG and heat-damage was an ideal one which could be usedto investigate the pathologic mechanism of gastric precancerous lesions.

  11. Morphofunctional changes in a rat model of Parkinson's disease - Effects of neurotrophic factors administration

    Requejo Rodríguez, Catalina

    2015-01-01

    255 p. La investigación actual se basa en la búsqueda de estrategias terapéuticas que consigan detener el proceso neurodegenerativo de la enfermedad de Parkinson. Por tanto, la administración de factores neurotróficos puede ser un tratamiento beneficioso. El objetivo de la presente Tesis Doctoral es la caracterización de diferentes modelos inducidos por la administración en rata de 6-hidroxidopamina (6-OHDA), que reproducen diferentes etapas de la enfermedad, y el análisis morfológico y fu...

  12. Effects of garlicin on apoptosis in rat model of colitis

    Xi-Ming Xu; Jie-Ping Yu; Xiao-Fei He; Jun-Hua Li; Liang-Liang Yu; Hong-Gang Yu

    2005-01-01

    AIM: To investigate the effects of garlicin on apoptosis and expression of bcl-2 and bax in lymphocytes in rat model of ulcerative colitis (UC).METHODS: Healthy adult Sprague-Dawley rats of both sexes, weighing 180±30 g, were employed in the present study. The rat model of UC was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) enema. The experimental animals were randomly divided into garlicin treatment group (including high and low concentration), model control group, and normal control group. Rats in garlicin treatment group and model control group received intracolic garlicin daily at doses of 10.0 and 30.0 mg/kg and equal amount of saline respectively 24 h after colitis model was induced by alcohol and TNBS co-enema. Rats in normal control group received neither alcohol nor only TNBS but only saline enema in this study. On the 28th d of the experiment, rats were executed, the expression of bcl-2 and bax protein was determined immunohistochemically and the apoptotic cells were detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate fluorescence nick end labeling (TUNEL) method. At the same time, the rat colon mucosal damage index (CMDI) was calculated.RESULTS: In garlicin treatment group, the positive expression of bcl-2 in lymphocytes decreased and the number of apoptotic cells was more than that in model control group, CMDI was lower than that in model control group. The positive expression of bax in lymphocytes had no significant difference.CONCLUSION: Garlicin can protect colonic mucosa against damage in rat model of UC induced by TNBS enema.

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

    Atsak, Piray; Orre, Marie; Bakker, Petra; Cerliani, Leonardo; Roozendaal, Benno; Gazzola, Valeria; Moita, Marta; Keysers, Christian

    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 wi...

  14. A Rat Model of Hemidystonia Induced by 3-Nitropropionic Acid

    Liu, Huan-Guang; Ma, Yu; Meng, Da-Wei; Yang, An-Chao; Zhang, Jian-Guo

    2013-01-01

    Objective Secondary dystonia commonly presents as hemidystonia and is often refractory to current treatments. We aimed to establish an inducible rat model of hemidystonia utilizing 3-nitropropionic acid (3-NP) and to determine the pathophysiology of this model. Methods Two different doses of 3-NP were stereotactically administered into the ipsilateral caudate putamen (CPu) of Wistar rats. Behavioral changes and alterations in the neurotransmitter levels in the basal ganglia were analyzed. We ...

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

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

    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 into...

  16. Dietary models for inducing hypercholesterolemia in rats

    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

  17. Immunodeficient Parameters in the HIV-1 Transgenic Rat Model

    Sulie L. Chang

    2007-01-01

    Full Text Available Recently an HIV-1 transgenic (HIV-1Tg rat model was created that carries a gag-pol-deleted HIV-1 genome under the control of the HIV-1 viral promoter. However, other viral proteins are expressed in most organs and tissues, and are found in the circulating blood. Since HIV-1 targets the immune system in humans, we examined two immunological parameters, leukocyte-endothelial adhesion (LEA and inflammatory cytokine production, in 5 mo old HIV-1Tg rats to identify immune functions that may be impaired even before the onset of symptoms of HIV-1 infection. We administered a single injection (i.p. of the bacterial endotoxin, lipopolysaccharide (LPS, 250 ug/kg, to 5 mo old HIV-1Tg rats, age-matched transgenic control (Tg rats, and F344/NHsd (F344 control background strain rats. LPS induced an LEA response in both the Tg control and F344 control animals. However, in the HIV-1Tg rats, there was no LEA response to LPS. Following LPS administration, there was significantly greater serum levels of TNF-α and IL-1β, two pro-inflammatory cytokines, in the HIV-1Tg rats compared to the control animals. In contrast, the serum level of IL-10, an anti-inflammatory cytokine, was comparable in the HIV-1Tg, Tg control, and F344 control rats. Our data show that, in the HIV-1Tg rat, there is a negative correlation between the LEA response and the induction of pro-inflammatory cytokines in response to bacterial endotoxin. These findings suggest that the persistent presence of viral proteins may be, at least, partially responsible for the immunodeficiency that occurs with HIV-1 infection, and that the HIV-1Tg rat could be a valid rodent model in which to study various aspects of HIV-1 infection.

  18. The LEC rat: a model for human hepatitis, liver cancer, and much more.

    M. Mori; Hattori, A.; Sawaki, M; Tsuzuki, N; Sawada, N; Oyamada, M.; Sugawara, N; Enomoto, K.

    1994-01-01

    The LEC rat is an inbred mutant strain with spontaneous hepatitis isolated from Long-Evans rats. Since approximately 40% of LEC rats die of fulminant hepatitis, the rat serves an animal model for studying the pathogenesis and treatment of human fulminant hepatitis. The remaining 60% of LEC rats survive and develop chronic (prolonged) hepatitis and subsequently develop liver cancer. Therefore, the LEC rat serves an important animal model for studying the significance of chronic hepatitis in th...

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

    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.

  20. Early increase in dopamine release in the ipsilateral striatum after unilateral intranigral administration of lactacystin produces spontaneous contralateral rotations in rats.

    Konieczny, J; Lenda, T; Czarnecka, A

    2016-06-01

    Since the discovery of the role of the ubiquitin-proteasome system (UPS) in the pathogenesis of Parkinson's disease, UPS inhibitors, such as lactacystin have been used to investigate the relationship between UPS impairment and degeneration of dopamine (DA) neurons. However, mostly long-term neurotoxic effects of lactacystin have been studied in animal models. Therefore, the aim of our study was to investigate behavioral and biochemical changes related to the DA system during the first week following unilateral intranigral injection of lactacystin to rats. We found that lactacystin produced early spontaneous contralateral rotations which were inhibited by combined administration of DA D1 and D2 receptor antagonists. Simultaneously, an increase in the extracellular level of DA and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA) was found in the ipsilateral striatum. In contrast, one week after lesion, when turning behavior was no longer visible, a decrease in the extracellular level of DA, DOPAC and HVA was demonstrated. It was accompanied by a substantial reduction in the tissue levels of DA and its metabolites in the lesioned substantia nigra and striatum. We concluded that unilateral intranigral administration of lactacystin produces an early increase in DA neurotransmission which precedes a decrease in the striatal and nigral tissue DA content. It is manifested by the appearance of spontaneous contralateral rotations and an elevation of the extracellular DA level in the ipsilateral striatum. Since similar behavior was previously observed after intranigral administration of rotenone and MPP(+) but not 6-hydroxydopamine (6-OHDA), it may indicate a common mechanism of action shared by these neurotoxins. PMID:26964686

  1. Targeting the D1-N-methyl-D-aspartate receptor complex reduces L-dopa-induced dyskinesia in 6-hydroxydopamine-lesioned Parkinson’s rats

    Song L

    2016-02-01

    Full Text Available Lu Song,1,* Zhanzhao Zhang,2,* Rongguo Hu,1 Jie Cheng,1 Lin Li,1 Qinyi Fan,1 Na Wu,1 Jing Gan,1 Mingzhu Zhou,1 Zhenguo Liu11Department of Neurology, Xinhua Hospital, 2Department of Plastic and Reconstructive Surgery, Shanghai 9th People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workAbstract: L-3,4-dihydroxyphenylalanine (L-dopa remains the most effective therapy for Parkinson’s disease (PD, but its long-term administration is associated with the development of debilitating motor complications known as L-dopa-induced dyskinesia (LID. Enhanced function of dopamine D1 receptor (D1R and N-methyl-d-aspartate receptor (NMDAR is believed to participate in the pathogenesis of LID. Given the existence of physical and functional interactions between D1R and NMDAR, we explored the effects of uncoupling D1R and NMDA GluN1 (GluN1 interaction on LID by using the Tat-conjugated interfering peptide (Tat-D1-t2. In this study, we demonstrated in 6-hydroxydopamine (6-OHDA-lesioned PD rat model that intrastriatal injection of Tat-D1-t2 alleviated dyskinetic behaviors and downregulated the phosphorylation of DARPP-32 at Thr34 induced by levodopa. Moreover, we also showed intrastriatal administration of Tat-D1-t2 elicited alterations in membranous GluN1 and D1R expression. These findings indicate that D1R/GluN1 complexes may be a molecular target with therapeutic potential for the treatment of dyskinesia in Parkinson’s patients.Keywords: 6-hydroxydopamine, Parkinson’s disease, dyskinesia, L-dopa, D1 receptor, NMDA, protein–protein interaction

  2. Effect of curcumin on diabetic rat model of cerebral ischemia.

    Miao, Mingsan; Cheng, Bolin; Li, Min

    2015-01-01

    To investigate the effect of curcumin on cerebral ischemia in diabetic rats the effects and features. intravenous injection alloxan diabetes model, to give alloxan first seven days the tail measured blood glucose value, the election successful model rats were fed with large, medium and small doses of curcumin suspension, Shenqijiangtang suspension and the same volume of saline, administered once daily. The first 10 days after administration 2h (fasting 12h) rat tail vein blood glucose values measured in the first 20 days after administration of 2h (fasting 12h), do cerebral ischemia surgery; rapid carotid artery blood after 30min rats were decapitated, blood serum, blood glucose and glycated serum protein levels; take part of the brain homogenates plus nine times the amount of normal saline, made 10 percent of brain homogenates. Another part of the brain tissue, in the light microscope observation of pathological tissue. Compared with model group, large, medium and small doses of curcumin can significantly lower blood sugar and glycated serum protein levels, significantly reduced brain homogenates lactic acid content and lactate dehydrogenase activity; large, medium-dose curcumin can significantly increase brain homogenates Na(+)-K(+)-ATP activity, dose curcumin can significantly improve brain homogenates Ca(+)-Mg(+)- ATP activity. Curcumin can reduce blood sugar in diabetic rat model of cerebral ischemia and improve brain energy metabolism, improve their brain tissue resistance to ischemia and hypoxia, cerebral ischemia in diabetic rats have a good drop the role of sugar and protect brain tissue. PMID:25631517

  3. Experimental model of distraction osteogenesis in edentulous rats

    Maria Montserrat Pujadas Bigi; Marianela Lewicki; Angela Matilde Ubios; Patricia Monica Mandalunis

    2011-01-01

    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...

  4. Neuroprotective Effects of Liraglutide for Stroke Model of Rats

    Kenichiro Sato; Masahiro Kameda; Takao Yasuhara; Takashi Agari; Tanefumi Baba; Feifei Wang; Aiko Shinko; Takaaki Wakamori; Atsuhiko Toyoshima; Hayato Takeuchi; Tatsuya Sasaki; Susumu Sasada; Akihiko Kondo; Cesario V. Borlongan; Mitsunori Matsumae

    2013-01-01

    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 perfor...

  5. Expression of exogenous rat collagenase in vitro and in a rat model of liver fibrosis

    Ji-Yao Wang; Jin-Sheng Guo; Chang-Qing Yang

    2002-01-01

    AIM: The present study was conducted to test thehypothesis that the introduction of the collagenase geneinto tissue culture cells and into a rat model of liver fibrosiswould result in the expression of enzymatically active product.METHODS: FLAG-tagged full-length rat collagenase cDNAwas PCR amplified and cloned into a mammalian expressionvector. NIH3T3 cells were then transiently transfected withthis construct. Expression of exogenous collagenase mRNAwas assessed by RT-PCR, and the exogenous collagenasedetected by Western blotting using anti-FLAG monoclonalantibodyEnzymatic activity was detected by gelatinzymography. To determine the effects of exogenouscollagenase production in vivo, the construct was boundto glycosyl-poly-L-lysine and then transduced into rats thathad developed liver fibrosis as a result of CCI4 plus ethanoltreatment. The hepatic expression of the construct and itseffect on the formation of liver fibrosis were demonstratedusing RT-PCR and immunohistochemistry.RESULTS: It was found that exogenously expressed ratcollagenase mRNA could be detected in NTH3T3 cellsfollowing transfection. Enzymatic ally active collagenase couldalso be detected in the culture medium. The recombinantplasmid was also expressed in rat liver after in vivo genetransfer. Expression of exogenous rat collagenase correlatedwith decreased deposition of collagen types I and Ⅲ in thelivers of rats with experimentally induced liver fibrosis.CONCLUSION: The expression of active exogenous ratcollagenase could be achieved in vitro and in vivo. It wassuggested that in vivo expression of active exogenouscollagenase may have therapeutic effects on the formationof liver fibrosis.

  6. Long-term BPA infusions. Evaluation in the rat brain tumor and rat spinal cord models

    In the BPA-based dose escalation clinical trial, the observations of tumor recurrence in areas of extremely high calculated tumor doses suggest that the BPA distribution is non-uniform. Longer (6-hour) i.v. infusions of BPA are evaluated in the rat brain tumor and spinal cord models to address the questions of whether long-term infusions are more effective against the tumor and whether long-term infusions are detrimental in the central nervous system. In the rat spinal cord, the 50% effective doses (ED50) for myeloparesis were not significantly different after a single i.p. injection of BPA-fructose or a 6 hour i.v. infusion. In the rat 9L gliosarcoma brain tumor model, BNCT following 2-hr or 6-hr infusions of BPA-F produced similar levels of long term survival. (author)

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

    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

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

    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...... induced by intradermal serotonin (10 µl) was evaluated against isotonic saline and Methysergide (10µl); 2) dose-temperature relation of intradermal serotonin with different concentrations (1%, 2%, 4%) at the site of injection was tested; 3) the local vasomotor responses in anaesthetized rats 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...

  9. Comparison of Electroacupuncture in Restrained and Unrestrained Rat Models

    Haolin Zhang

    2013-01-01

    Full Text Available Acupuncture and electroacupuncture (EA are widely used to treat a variety of diseases including pain. In preclinical research, EA is usually applied by inserting acupuncture needles into the hindlimbs of rats restrained in small tubes or bags. This restrained model of EA not only causes stress-like behaviors but also is limited in stimulating locations and intensities. In 2004, a novel, unrestrained model of EA was introduced. However, these two EA methods have never been directly compared regarding their analgesic effects and other features such as stress. In the present study, we reported similar analgesic effects between restrained and unrestrained EA in rats of acute inflammatory pain induced by intraplantar injection of CFA. In addition, rats receiving unrestrained EA showed less significant stress-like behaviors and tolerated higher current intensity. These advantages suggest that this unrestrained EA method can replace the traditional restrained procedure with similar analgesic effects and allow for more choices of stimulating intensities and locations.

  10. Development of Wistar rat model of insulin resistance

    Jing Ai; Ning Wang; Mei Yang; Zhi-Min Du; Yong-Chun Zhang; Bao-Feng Yang

    2005-01-01

    AIM: To establish a simplified and reliable animal model of insulin resistance with low cost in Wistar rats. METHODS: Wistar rats were treated with a high fat emulsion by ig for 10 d. Changes of the diets, drinking and body weight were monitored every day and insulin resistance was evaluated by hyperinsulinemic-euglycemicclamp techniques and short insulin tolerance test using capillary blood glucose. Morphologic changes of liver, fat, skeletal muscles, and pancreatic islets were assessed under light microscope. mRNA expressions of GLUT2 and α-glucosidase in small intestine epithelium, GLUT4 in skeletal muscles and Kir6.2 in beta cell of islets were determined by in situ hybridization.RESULTS: KITT was smaller in treated animals (4.5±0.9)than in untreated control Wistar rats (6.8±1.5), and so was glucose injection rate. Both adipocyte hypertrophy and large pancreatic islets were seen in high fat fed rats,but no changes of skeletal muscles and livers wereobserved. mRNA levels of GLUT2, α-glucosidase in small intestinal epithelium and Kir6.2 mRNA in beta cells of islets increased, whereas that of GLUT4 in skeletal muscles decreased in high fat fed group compared with normal control group.CONCLUSION: An insulin resistance animal model in Wistar rats is established by ig special fat emulsion.

  11. Rat gingival model for testing drugs influencing inflammation

    Shaju P Jacob; Sonia Nath

    2013-01-01

    Preclinical drug testing is an important areain new drug development where animals are used.An ideal animal model for this is one which is simple,reliable and can be extrapolated to humans. Topicaldrugs for inflammation are conventionally tested onthe skin of animals after induction of inflammation.A gingival model would be simple as inflammation canbe induced naturally by the action of plaque. Rats area popular animal model for testing drugs as well as tostudy various diseases of the periodo...

  12. Nitric oxide synthase inhibitor improves de novo and long-term L-DOPA-induced dyskinesia in hemiparkinsonian rats

    Fernando Eduardo Padovan-Neto

    2011-06-01

    Full Text Available Inhibitors of neuronal and endothelial nitric oxide synthase decrease l-3,4-dihidroxifenilalanine (L-DOPA-induced dyskinesias in rodents. The mechanism of nitric oxide inhibitor action is unknown. The aims of the present study were to investigate the decrease of L-DOPA-induced abnormal involuntary movements in 6-hydroxydopamine (6-OHDA-lesioned rats by nitric oxide inhibitors following either acute or chronic treatment. The primary findings of this study were that NG-nitro-L-Arginine, an inhibitor of endothelial and neuronal nitric oxide synthase, attenuated abnormal involuntary movements induced by chronic and acute L-DOPA. In contrast, rotational behavior was attenuated only after chronic L-DOPA. L-DOPA improved stepping test performance, and its chronic administration did not alter open field behavior. Our results indicated a correlation between apomorphine-induced rotation and the decrease in the number of adjusting steps performed with the contralateral forepaw in the 6-OHDA-lesioned rats.The 6-OHDA lesion and the L-DOPA treatment induced a bilateral increase (1.5 times in the nNOS protein and nNOS mRNA in the striatum and in the frontal cortex. There was a parallel increase, bilaterally, of the FosB/ΔFosB, primarily in the ipsilateral striatum. The exception was in the contralateral striatum and the ipsilateral frontal cortex, where chronic L-DOPA treatment induced an increase of approximately 10 times the nNOS mRNA. Our results provided further evidence of an anti-dyskinetic effect of NOS inhibitor. The effect appeared under L-DOPA acute and chronic treatment. The L-DOPA treatment also revealed an over-expression of the neuronal NOS in the frontal cortex and striatum. Our results corroborated findings that L-DOPA-induced rotation differs between acute and chronic treatment. The effect of the NOS inhibitor conceivably relied on the L-DOPA structural modifications in the parkinsonian brain. Taken together, these data provided a rationale

  13. The Chemical Molecule B355252 is Neuroprotective in an In Vitro Model of Parkinson's Disease.

    Gliyazova, Nailya S; Ibeanu, Gordon C

    2016-10-01

    6-Hydroxydopamine (6-OHDA) is a neurotoxin frequently used to create in vitro and in vivo experimental models of Parkinson's disease (PD), a chronic neurodegenerative disorder largely resulting from damage to the nigrostriatal dopaminergic pathway. No effective drugs or therapies have been developed for this devastating disorder, and current regimens of symptomatic therapeutics only alleviate symptoms temporarily. Therefore, effective treatments that reverse or cure this disorder are urgently needed. The aim of the study described in this report was to investigate the therapeutic impact of B355252, an aryl thiophene sulfonamide chemical entity, in the widely recognized in vitro model of PD, and to characterize the molecular signaling pathways. We show here that 6-OHDA-induced cell death in HT22, a murine neuronal cell model, through a pathway that involves the mitochondria by increasing the levels of reactive oxygen species (ROS), raising intracellular calcium ([Ca(2+)]i), enhancing the release of cytochrome c to the cytosol, and promoting activation of stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK) signaling pathway. More importantly, we found that B355252 protected HT22 neurons against 6-OHDA toxin-induced neuronal cell death by significant attenuation of ROS production, blocking of mitochondrial depolarization, inhibition of cytochrome c release, sequestration of [Ca(2+)]i, modulation of JNK cascade, and strong inhibition of caspase 3/7 cleavage. Overall, this study demonstrates that death of neurons under toxic conditions characteristic of PD can be efficiently halted by B355252 and suggests that further development of the molecule could be potentially beneficial as a therapeutic prevention or treatment option for PD. PMID:26649727

  14. Changes of serum leptin levels in rat models of septicemia

    Objective: To investigate the role played by leptin in acute traumatic inflammation with determination of the changes of serum leptin levels in rat models of septicemia. Methods: Forty rat models of septicemia were prepared with ligation and artificial perforation of caecum. These models were divided into four equal-numbered groups: (1) no further treatment (2) intraperitoneal injection with 2ml intralipid (3) intraperitoneal injection with 0.025mg estradiol in 2ml solution (4) subcutaneous injection with 0.5u insulin in 2ml solution. Ten other animals underwent sham operation with laparotomy only. Serum leptin levels were determined in all the fifty rats 12h later with a method of RIA developed in this laboratory. Results: Compared with the serum leptin in the sham operation groups, the leptin levels in the intralipid group increased and in the other three groups decreased, but all not significantly. However, the levels in the intralipid group were significantly higher than those in the group without further treatment and the estradiol group (P<0.05). Conclusion: In rat models of septicemia, endogenous expression of leptin was decreased with lower serum levels. Early energy supplement might increase the leptin expression. Intervening the hypothalamus-pituitary-adrenal cortex axis function with exogenous estradiol or reduction of energy reserve with insulin would decrease the leptin expression with less protection against inflammation. (authors)

  15. A New Rat Model for Orthotopic Abdominal Wall Allotransplantation

    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.

  16. The mathematical whisker: A review of numerical models of the rat׳s vibrissa biomechanics.

    Lucianna, Facundo Adrián; Albarracín, Ana Lía; Vrech, Sonia Mariel; Farfán, Fernando Daniel; Felice, Carmelo José

    2016-07-01

    The vibrissal system of the rat refers to specialized hairs the animal uses for tactile sensory perception. Rats actively move their whiskers in a characteristic way called "whisking". Interaction with the environment produces elastic deformation of the whiskers, generating mechanical signals in the whisker-follicle complex. Advances in our understanding of the vibrissal complex biomechanics is of interest not only for the biological research field, but also for biomimetic approaches. The recent development of whisker numerical models has contributed to comprehending its sophisticated movements and its interactions with the follicle. The great diversity of behavioral patterns and complexities of the whisker-follicle ensemble encouraged the creation of many different biomechanical models. This review analyzes most of the whisker biomechanical models that have been developed so far. This review was written so as to render it accessible to readers coming from different research areas. PMID:27260019

  17. Immunodeficient Parameters in the HIV-1 Transgenic Rat Model

    Chang, Sulie L.; Frank Ocasio; Joseq A. Beltran

    2007-01-01

    Recently an HIV-1 transgenic (HIV-1Tg) rat model was created that carries a gag-pol-deleted HIV-1 genome under the control of the HIV-1 viral promoter. However, other viral proteins are expressed in most organs and tissues, and are found in the circulating blood. Since HIV-1 targets the immune system in humans, we examined two immunological parameters, leukocyte-endothelial adhesion (LEA) and inflammatory cytokine production, in 5 mo old HIV-1Tg rats to identify immune functions that may be i...

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

    Irving, Amy A.; Kazuto Yoshimi; Hart, Marcia L.; Taybor Parker; Linda Clipson; Ford, Madeline R; Takashi Kuramoto; 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-canc...

  19. The effects of carnosine in an experimental rat model of septic shock

    Sahin, Sabiha; Oter, Serdar; Burukoglu, Dilek; Sutken, Emine

    2013-01-01

    Background To examine the effect of carnosine on liver function and histological findings in experimental septic shock model, 24 Sprague-Dawley rats were used. Material/Methods Rats were divided into control, septic shock, and carnosine-treated septic shock groups. Femoral vein and artery catheterization were performed on all rats. Rats in the control group underwent laparotomy and catheterization; in the test groups, cecal ligation-perforation and bladder cannulation were added. Rats in the ...

  20. Comparative proteomic approach in rat model of absence epilepsy.

    Gürol, Gönül; Demiralp, Duygu Özel; Yılmaz, Ayça Kasapoğlu; Akman, Özlem; Ateş, Nurbay; Karson, Ayşe

    2015-03-01

    The aim of this study was to investigate cellular proteins in the pathogenesis of the genetic rat model of absence epilepsy. Protein spots were identified with peptide mass fingerprinting analysis using matrix-assisted laser desorption ionization time of flight mass spectrometry. Data were gathered from the frontoparietal cortex and thalamus of Wistar Albino Glaxo/Rij (WAG/Rij) and Wistar by using two-dimensional gel electrophoresis (2D-PAGE). Six proteins (Clathrin light chain-A protein, Transmembrane EMP24 Domain-Containing Protein, Stathmin-4, Myosin Light Chain4, Rheb, phosphoserine phosphatase) were found to be differentially expressed in the frontoparietal cortex of WAG/Rij and Wistar rats in both age groups. Another set of six proteins (Protein FAM89A and Oasl1, Gemin2, NuDEL1, Pur-beta, 3-alpha HSD) were found to be differentially expressed in the thalamus of WAG/Rij and Wistar rats. Findings from the frontoparietal cortex suggest the presence of altered serine metabolism and increased vesicular trafficking in the frontoparietal cortex of WAG/Rij rats compared with Wistar rats. These differences in the protein levels might reflect the crucial role of these proteins and related pathways in the generation of absence seizures. In the thalamic specimens, age-dependent changes in protein expression were remarkable, suggesting that this phenomenon may be a precursor or a consequence of absence seizures. Our findings further highlight the potential role of the mTOR signaling pathway in absence epilepsy. PMID:25323782

  1. Sonic hedgehog expression in a rat model of chronic pancreatitis

    Wang, Luo-Wei; Lin, Han; Lu, Yi; Xia, Wei; Gao, Jun; Li, Zhao-Shen

    2014-01-01

    AIM: To analyze the activation of sonic hedgehog (SHh) signaling pathways in a rat model of chronic pancreatitis. METHODS: Forty Wistar rats were randomly divided into 2 groups: experimental group and control group (20 rats in each group). Dibutyltin dichloride was infused into the tail vein of the rats to induce chronic pancreatitis in the experimental group. The same volume of ethanol and glycerol mixture was infused in the control group. The expression of Ptch, Smo and Gli were analyzed using immunohistochemistry, and real-time reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Compared with the control group, significant histological changes in terms of the areas of abnormal architecture, glandular atrophy, fibrosis, pseudo tubular complexes, and edema were observed at week 4 in the experimental group. The expression of Ptch1, Smo and Gli1 in the pancreatic tissue increased significantly in the experimental group. Using RT-PCR, mRNA levels of Ptch, Smo and Gli in the experimental group increased significantly compared with the control group. CONCLUSION: The SHh signaling pathway is aberrantly activated in rats with chronic pancreatitis. The SHh signaling pathway plays an important role in the development of chronic pancreatitis. These results may be helpful in studies focusing on the relationship between chronic pancreatitis and pancreatic cancer. PMID:24782623

  2. Establishment of novel rat models for premalignant breast disease

    Wang Feng; Ma Zhongbing; Wang Fei; Fu Qinye; Fang Yunzhi; Zhang Qiang; Gao Dezong

    2014-01-01

    Background Breast cancer has become one of the most common malignant tumors among females over the past several years.Breast carcinogenesis is a continuous process,which is featured by the normal epithelium progressing to premalignant lesions and then to invasive breast cancer (IBC).Targeting premalignant lesions is an effective strategy to prevent breast cancer.The establishment of animal models is critical to study the mechanisms of breast carcinogenesis,which will facilitate research on breast cancer prevention and drug behaviors.In this study,we established a feasible chemically-induced rat model of premalignant breast cancer.Methods Following the administration of the drugs (carcinogen,estrogen,and progestogen) to Sprague-Dawley (SD) rats,tumors or suspicious tumors were identified by palpation or ultrasound imaging,and were surgically excised for pathological evaluation.A series of four consecutive steps were carried out in order to determine the carcinogen:7,12-dimethylbenzaanthracene (DMBA) or 1-methyl-1-nitrosourea,the route of carcinogen administration,the administration period of estrogen and progestogen,and the DMBA dosage.Results Stable premalignant lesions can be induced in SD rats on administration of DMBA (15 mg/kg,administered three times) followed by administration of female hormones 5-day cycle.Results were confirmed by ultrasound and palpation.Conclusion Under the premise of drug dose and cycle,DMBA combined with estrogen and progestogen can be used as a SD rat model for breast premalignant lesions.

  3. Experimental model of heterotopic ossification in Wistar rats

    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

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

    Bernhard Kraemer; Christian Wallwiener; Rajab, Taufiek K; Christoph Brochhausen; Markus Wallwiener; Ralf Rothmund

    2014-01-01

    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), isc...

  5. A rat model of radiation injury in the mandibular area

    Sønstevold, Tonje; Johannessen, Anne Christine; Stuhr, Linda

    2015-01-01

    Background Radiation technology focuses on delivering the radiation as precisely as possible to the tumor, nonetheless both acute and long-term damage to surrounding normal tissue may develop. Injuries to the surrounding normal tissue after radiotherapy of head and neck cancer are difficult to manage. An animal model is needed to elucidate good treatment modalities. The aim of this study was to establish a rat model where a certain radiation dose gives reproducible tissue reactions in the ...

  6. Experimental model of distraction osteogenesis in edentulous rats

    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.

  7. A chronic ulcerative colitis model in rats

    Li Zheng; Zhen Qiang Gao; Shu Xian Wang

    2000-01-01

    @@ INTRODUCTION In recent years, there have been many reports about animal model to investigate drugs for inflammatory bowel diseases (IBD). The experimental animal model often used is acetic acid-induced damage of colonic muscosa. In the present study, this animal model was investigated by administering various concentrations of TNBS.

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

    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. Rat gingival model for testing drugs influencing inflammation

    Shaju P Jacob

    2013-07-01

    Full Text Available Preclinical drug testing is an important areain new drug development where animals are used.An ideal animal model for this is one which is simple,reliable and can be extrapolated to humans. Topicaldrugs for inflammation are conventionally tested onthe skin of animals after induction of inflammation.A gingival model would be simple as inflammation canbe induced naturally by the action of plaque. Rats area popular animal model for testing drugs as well as tostudy various diseases of the periodontium. Periodontaldisease including gingival inflammation develops inrats in relation to indigenous plaque or experimentallyinduced bacterial products. A number of features ofrats ranging from anatomy, histology and response tobacterial insult can be seen mirrored to a great extentin humans. There is a lot similarity in the developmentand resolution of inflammation as well as the gingivalwound healing of rats and humans. This paper tries toexplore the feasibility of using the rat gingival modelfor preclinical testing of drugs acting on or influencinginflammation and concludes by identifying potentialareas of research using this model. The addition of sucha simple and inexpensive model for preclinical testing ofdrugs will be welcomed by the drug developers.

  10. Methodological characteristics in establishing rat models of poststroke depression

    Fuyou Liu; Shi Yang; Weiyin Chen; Jinyu Wang; Yi Tang; Guanxiang Zhu

    2006-01-01

    BACKGROUND: Ideal model of poststroke depression (PSD) may be induced in rats guided by the theoretical evidence that "primary endogenous mechanism" and "reactivity mechanism" theories for PSD in human being.OBJECTIVE: To investigate the feasibility of comprehensive methods to induce PSD models in rats.DESrGN: A randomized controlled animal trial.SETTING: Department of Neurology, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine.MATERrALS: Male SD rats of SPF degree, weighing 350-500 g, were provided by the experimental animal center of Chengdu University of Traditional Chinese Medicine. The rats were raised for 1 week adaptively, then screened behaviorally by open-field test and passive avoidance test. Forty-five rats with close scores were randomly divided into normal control group (n =10), simple stroke group (n =10), stress group (n =10) and PSD group (n =15).METHODS: The experiments were carried out in the laboratory of Chengdu University of Traditional Chinese Medicine from July 2002 to February 2003. ① Rat models of focal cerebral ischemia were induced by thread embolization, then treated with separate raising and unpredictable stress to induce PSD models. ②The neurologic deficit was evaluated by Longa 5-grade standard (the higher the score, the severer the neurologic deficit) and horizontal round rod test (normal rat could stay on it for at least 3 minutes). ③ The behavioral changes of PSD rats were evaluated by the saccharin water test, open-field text and passive avoidance test,including the changes of interest, spontaneous and exploratory activities, etc. ④ The levels of monoamine neurotransmitters, including norepinephrine (NE), serotonin (5-HT) and dopamine, in brain were determined using fluorospectrophotometry.MAIN OUTCOME MEASURES: ① Score of Longa 5-grade standard; Stayed time in the horizontal round rod test;② Amount of saccharin water consumption; Open-field text: time stayed in the central square, times

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

    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...

  12. Chronic gastritis rat model and role of inducing factors

    Zun Xiang; Jian-Min Si; Huai-De Huang

    2004-01-01

    AIM: To establish an experimental animal model of chronic gastritis in a short term and to investigate the effects of several potential inflammation-inducing factors on rat gastric mucosa.METHODS: Twenty-four healthy, male SD rats were treated with intragastric administration of 600 mL/L alcohol, 20mmol/L sodium deoxycholate and 0.5 g/L ammonia (factor A), forage containing low levels of vitamins (factor B), and/or indomethacin (factor C), according to an L8(27)orthogonal design. After 12 wk, gastric antral and body mucosae were pathologically examined.RESULTS: Chronic gastritis model was successfully induced in rats treated with factor A for 12 wk. After the treatment of animals, the gastric mucosal inflammation was significantly different from that in controls, and the number of pyloric glands at antrum and parietal cells at body were obviously reduced (P<0.01). Indomethacin induced gastritis but without atrophy, and short-term vitamin deficiency failed to induce chronic gastritis and gastric atrophy, In addition,indomethacin and vitamin deficiency had no synergistic effect in inducing gastritis with the factor A. No atypical hyperplasia and intestinal metaplasia in the gastric antrum and body were observed in all rats studied.CONCLUSION: Combined intragastric administration of 600 mL/L alcohol, 20 mmol/L sodium deoxycholate and 0.5 g/L ammonia induces chronic gastritis and gastric atrophy in rats. Indomethacin induces chronic gastritis only.The long-term roles of these factors in gastric inflammation and carcinogenesis need to be further elucidated.

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

    García-Moreno L.M.

    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.

  14. The Laboratory Rat as an Animal Model for Osteoporosis Research

    Lelovas, Pavlos P; Xanthos, Theodoros T; Thoma, Sofia E; Lyritis, George P; Dontas, Ismene A

    2008-01-01

    Osteoporosis is an important systemic disorder, affecting mainly Caucasian women, with a diverse and multifactorial etiology. A large variety of animal species, including rodents, rabbits, dogs, and primates, have been used as animal models in osteoporosis research. Among these, the laboratory rat is the preferred animal for most researchers. Its skeleton has been studied extensively, and although there are several limitations to its similarity to the human condition, these can be overcome th...

  15. A rat model of spontaneous myopathy and malignant hyperthermia.

    Gonzalez, L. E.; Meléndez-Vásquez, C. V.; Gregson, N. A.; File, S. E.

    1998-01-01

    Malignant hyperthermia is a main cause of death during general anesthesia, particularly in children. However, research has been hampered by the lack of a convenient animal model, the only one available being a special strain of pig. In this study, we describe spontaneous myopathy and a fatal syndrome of generalized muscle rigidity triggered by halothane in an outbred strain of rat. Histological examination of skeletal muscle reveals severe abnormalities indicating chronic underlying myopathy....

  16. Urinary Protein Profiles in a Rat Model for Diabetic Complications*

    Schlatzer, Daniela M.; Dazard, Jean-Eudes; Dharsee, Moyez; Ewing, Rob M.; Ilchenko, Serguei; Stewart, Ian; Christ, George; Chance, Mark R.

    2009-01-01

    Diabetes mellitus is estimated to affect ∼24 million people in the United States and more than 150 million people worldwide. There are numerous end organ complications of diabetes, the onset of which can be delayed by early diagnosis and treatment. Although assays for diabetes are well founded, tests for its complications lack sufficient specificity and sensitivity to adequately guide these treatment options. In our study, we employed a streptozotocin-induced rat model of diabetes to determin...

  17. Efficacy of Female Rat Models in Translational Cardiovascular Aging Research

    Rice, K.M.; J. C. Fannin; Gillette, C.; E. R. Blough

    2014-01-01

    Cardiovascular disease is the leading cause of death in women in the United States. Aging is a primary risk factor for the development of cardiovascular disease as well as cardiovascular-related morbidity and mortality. Aging is a universal process that all humans undergo; however, research in aging is limited by cost and time constraints. Therefore, most research in aging has been done in primates and rodents; however it is unknown how well the effects of aging in rat models translate into h...

  18. Spatial memory impairments in a prediabetic rat model

    Soares, E.; Prediger, R. D.; Nunes, S.; A.A.de Castro; Viana, S .D.; Lemos, C.; C.M. Souza; Agostinho, P; Cunha, R A; Carvalho, E; Ribeiro, C. A. Fontes; Reis, F.; Pereira, F. C

    2013-01-01

    Diabetes is associated with an increased risk for brain disorders, namely cognitive impairments associated with hippocampal dysfunction underlying diabetic encephalopathy. However, the impact of a prediabetic state on cognitive function is unknown. Therefore, we now investigated whether spatial learning and memory deficits and the underlying hippocampal dysfunction were already present in a prediabetic animal model. Adult Wistar rats drinking high-sucrose (HSu) diet (35% sucrose solution duri...

  19. A Model of Chronic Nutrient Infusion in the Rat

    Fergusson, Grace; Ethier, Mélanie; Zarrouki, Bader; Fontés, Ghislaine; Poitout, Vincent

    2013-01-01

    Chronic exposure to excessive levels of nutrients is postulated to affect the function of several organs and tissues and to contribute to the development of the many complications associated with obesity and the metabolic syndrome, including type 2 diabetes. To study the mechanisms by which excessive levels of glucose and fatty acids affect the pancreatic beta-cell and the secretion of insulin, we have established a chronic nutrient infusion model in the rat. The procedure consists of cathete...

  20. Comparative proteomic approach in rat model of absence epilepsy.

    Gürol, Gönül; Demiralp, Duygu Özel; Yılmaz, Ayça Kasapoğlu; Akman, Özlem; Ateş, Nurbay; Karson, Ayşe

    2015-01-01

    The aim of this study was to investigate cellular proteins in the pathogenesis of the genetic rat model of absence epilepsy. Protein spots were identified with peptide mass fingerprinting analysis using matrix-assisted laser desorption ionization time of flight mass spectrometry. Data were gathered from the frontoparietal cortex and thalamus of Wistar Albino Glaxo/Rij (WAG/Rij) and Wistar by using two-dimensional gel electrophoresis (2D-PAGE). Six proteins (Clathrin light chain-A protein, Tra...

  1. Culture Model of Rat Portal Myofibroblasts.

    El Mourabit, Haquima; Loeuillard, Emilien; Lemoinne, Sara; Cadoret, Axelle; Housset, Chantal

    2016-01-01

    Myofibroblasts are matrix-producing cells with contractile properties, usually characterized by de novo expression of alpha-smooth muscle actin, that arise in fibrotic diseases. Hepatic stellate cells (HSCs), known as perisinusoidal cells containing auto-fluorescent vitamin A, are the major although not exclusive source of myofibroblasts in the injured liver. Portal myofibroblasts (PMFs) have been defined as liver myofibroblasts derived from cells that are distinct from HSCs and located in the portal tract. Here, we describe the protocol we have established to obtain rat PMFs in culture. In this method, the biliary tree is (i) separated from the liver parenchyma by in situ enzymatic perfusion of the liver, (ii) minced and further digested in vitro, until bile duct segments are isolated by sequential filtration. Bile duct isolates free of HSC contaminants, form small cell clusters, which initially comprise a large majority of epithelial cells. In culture conditions (fetal bovine serum) that provide a growth advantage to mesenchymal cells over epithelial cells, the epithelial cells die and detach from the substrate, while spindle-shaped cells outgrow from the periphery of the cell clusters, as shown by video-microscopy. These cells are highly proliferative and after 4-5 days, the culture is composed exclusively of fully differentiated myofibroblasts, which express alpha-smooth muscle actin and collagen 1, and secrete abundant collagen. We found no evidence for epithelial-mesenchymal transition, i.e., no co-expression of alpha-smooth muscle actin and cytokeratin at any stage, while cytokeratin becomes undetectable in the confluent cells. PMFs obtained by this method express the genes that were previously reported to be overexpressed in non-HSC or portal fibroblast-derived liver myofibroblasts as compared to HSC-derived myofibroblasts, including the most discriminant, collagen 15, fibulin 2, and Thy-1. After one passage, PMFs retain the same phenotypic features as in

  2. Culture Model of Rat Portal Myofibroblasts

    El Mourabit, Haquima; Loeuillard, Emilien; Lemoinne, Sara; Cadoret, Axelle; Housset, Chantal

    2016-01-01

    Myofibroblasts are matrix-producing cells with contractile properties, usually characterized by de novo expression of alpha-smooth muscle actin, that arise in fibrotic diseases. Hepatic stellate cells (HSCs), known as perisinusoidal cells containing auto-fluorescent vitamin A, are the major although not exclusive source of myofibroblasts in the injured liver. Portal myofibroblasts (PMFs) have been defined as liver myofibroblasts derived from cells that are distinct from HSCs and located in the portal tract. Here, we describe the protocol we have established to obtain rat PMFs in culture. In this method, the biliary tree is (i) separated from the liver parenchyma by in situ enzymatic perfusion of the liver, (ii) minced and further digested in vitro, until bile duct segments are isolated by sequential filtration. Bile duct isolates free of HSC contaminants, form small cell clusters, which initially comprise a large majority of epithelial cells. In culture conditions (fetal bovine serum) that provide a growth advantage to mesenchymal cells over epithelial cells, the epithelial cells die and detach from the substrate, while spindle-shaped cells outgrow from the periphery of the cell clusters, as shown by video-microscopy. These cells are highly proliferative and after 4–5 days, the culture is composed exclusively of fully differentiated myofibroblasts, which express alpha-smooth muscle actin and collagen 1, and secrete abundant collagen. We found no evidence for epithelial-mesenchymal transition, i.e., no co-expression of alpha-smooth muscle actin and cytokeratin at any stage, while cytokeratin becomes undetectable in the confluent cells. PMFs obtained by this method express the genes that were previously reported to be overexpressed in non-HSC or portal fibroblast-derived liver myofibroblasts as compared to HSC-derived myofibroblasts, including the most discriminant, collagen 15, fibulin 2, and Thy-1. After one passage, PMFs retain the same phenotypic features as in

  3. Ideal Experimental Rat Models for Liver Diseases

    Lee, Sang Woo; Kim, Sung Hoon; Min, Seon Ok; Kim, Kyung Sik

    2011-01-01

    There are many limitations for conducting liver disease research in human beings due to the high cost and potential ethical issues. For this reason, conducting a study that is difficult to perform in humans using appropriate animal models, can be beneficial in ascertaining the pathological physiology, and in developing new treatment modalities. However, it is difficult to determine the appropriate animal model which is suitable for research purposes, since every patient has different and dive...

  4. An improved experimental model for peripheral neuropathy in rats

    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.

  5. An improved experimental model for peripheral neuropathy in rats

    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.

  6. An improved experimental model for peripheral neuropathy in rats

    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

  7. Chronic L-DOPA administration increases the firing rate but does not reverse enhanced slow frequency oscillatory activity and synchronization in substantia nigra pars reticulata neurons from 6-hydroxydopamine-lesioned rats.

    Aristieta, A; Ruiz-Ortega, J A; Miguelez, C; Morera-Herreras, T; Ugedo, L

    2016-05-01

    The pathophysiology of Parkinson's disease (PD) and of L-DOPA-induced dyskinesia (LID) is associated with dysfunctional neuronal activity in several nuclei of the basal ganglia. Moreover, high levels of oscillatory activity and synchronization have also been described in both intra- and inter-basal ganglia nuclei and the cerebral cortex. However, the relevance of these alterations in the motor symptomatology related to Parkinsonism and LID is not fully understood. Recently, we have shown that subthalamic neuronal activity correlates with axial abnormal movements and that a subthalamic nucleus (STN) lesion partially reduces LID severity as well as the expression of some striatal molecular modifications. The aim of the present study was to assess, through single-unit extracellular recording techniques under urethane anaesthesia, neuronal activity of the substantia nigra pars reticulata (SNr) and its relationship with LID and STN hyperactivity together with oscillatory and synchronization between these nuclei and the cerebral cortex in 6-OHDA-lesioned and dyskinetic rats. Twenty-four hours after the last injection of L-DOPA the firing rate and the inhibitory response to an acute challenge of L-DOPA of SNr neurons from dyskinetic animals were increased with respect to those found in intact and 6-OHDA-lesioned rats. Moreover, there was a significant correlation between the mean firing rate of SNr neurons and the severity of the abnormal movements (limb and orolingual subtypes). There was also a significant correlation between the firing activity of SNr and STN neurons recorded from dyskinetic rats. In addition, low frequency band oscillatory activity and synchronization both within the SNr or STN and with the cerebral cortex were enhanced in 6-OHDA-lesioned animals and not or slightly affected by chronic treatment with L-DOPA. Altogether, these results indicate that neuronal SNr firing activity is relevant in dyskinesia and may be driven by STN hyperactivity. Conversely

  8. Standardization of model to induce obesity in rats

    Gipsis Suárez Román

    2013-10-01

    Full Text Available Background: Obesity is a risk factor for multiple diseases. There are various rat models to induce this condition. Genetic models and diet-induced obesity are expensive. Within the models of hypothalamic obesity, there is one achieved by the administration of monosodium glutamate during the neonatal period. This substance is not expensive and causes the major metabolic alterations observed in human obesity. Objective: to select an appropriate treatment scheme to induce obesity with monosodium glutamate during neonatal period. Methods: monosodium glutamate was administered to Wistar rats during the neonatal period, using three different treatment schemes (with five, seven and ten doses of 4mg/g/day through two routes of administration: subcutaneous and intraperitoneal routes. Controls were administered 0.9% sodium chloride. To establish the diagnosis of obesity, the following variables were measured at 90 days: weight, snout-anus length and Lee index. Results: with all treatment schemes tested, snout-anus length was statistically different between the group treated with monosodium glutamate and the controls group. 100% of the rats that reached adulthood injected with monosodium glutamate was obese. Conclusion: the scheme of five doses of monosodium glutamate, applied subcutaneously on alternate days, was selected as obesity is obtained with less handling and lower percentage of neonatal deaths.

  9. Gastrodin inhibits neuroinflammation in rotenone-induced Parkinson's disease model rats

    Chun Li; Xin Chen; Nan Zhang; Yangwen Song; Yang Mu

    2012-01-01

    The present study showed that the latency of rats moving on a vertical grid was significantly prolonged, and the number of rats sliding down from the declined plane was increased remarkably, in rotenone-induced Parkinson's disease model rats compared with control rats. The moving latency recovered to normal levels, but the number of slides was significantly increased at 28 days after model establishment. The slope test is a meaningful approach to evaluate the symptoms of Parkinson's disease model rats treated with rotenone. In addition, loss of substantia nigral dopaminergic neurons in model rats was observed at 1 day after the model was established, and continued gradually at 14 and 28 days. The expression of tyrosine hydroxylase-positive cells was significantly increased in gastrodin-treated rats at 14 days. Significant numbers of activated microglia cells were observed in model rats at 14 and 28 days; treatment of rats with Madopar at 28 days suppressed microglial activation. Treatment of rats with gastrodin or Madopar at 28 days significantly reduced interleukin-1β expression. The loss of substantia nigral dopaminergic neurons paralleled the microglial activation in Parkinson's disease model rats treated with rotenone. The inflammatory factors tumor necrosis factor-α and interleukin-1β are involved in the substantia nigral damage. Gastrodin could protect dopaminergic neurons via inhibition of interleukin-1β expression and neuroinflammation in the substantia nigra.

  10. A rat model for embolic encephalitis

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

    2011-01-01

    Sepsis is the combined condition of infection and a systemic inflammatory response. Sepsis causes 10% of all deaths in the western world. The Gram positive bacterium Staphylococcus aureus is one of the leading causes of sepsis and the incidence of Gram positive sepsis is rising. Autopsy studies...... 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...... is difficult to obtain tissue for further examination. This puts a hard demand on animal models of brain lesions in sepsis. We hereby present a novel animal model of embolic encephalitis. Our model introduces bacteria by an embolus to an area of brain necrosis and damage to the blood...

  11. Graft-mediated functional recovery on a skilled forelimb use paradigm in a rodent model of Parkinson's disease is dependent on reward contingency.

    Cordeiro, Karina Kohn; Jiang, Wei; Papazoglou, Anna; Tenório, Sérgio Bernardo; Döbrössy, Máté; Nikkhah, Guido

    2010-10-15

    The Staircase test measures lateralised deficits in skilled paw reaching in rodents, and there is a long-standing discrepancy in the literature on whether the paradigm is sensitive to graft-mediated functional recovery in the rodent model of Parkinson's disease. The aim of the current study was to evaluate the critical influence of test conditions like pellet density on dopamine-dependent graft-mediated functional recovery. Rats were pre-trained on the Staircase test with a configuration of 8 pellets in each of the 6 wells bilaterally prior to receiving unilateral 6-OHDA lesions of the medial forebrain bundle. Later, the lesioned animals received E14 VM grafts into the striatum, and were tested on the Staircase test under one of two test configurations: bilaterally, either with 10 (HIGH) or with 2 (LOW) pellets per well. Subsequent sessions included unilateral forced-choice testing under the same pellet configuration, and second bilateral and forced-choice sessions with the pellet density configurations switched around between the groups (Cross-over). Animals were also tested on the Corridor and the Cylinder test, and subjected to drug-induced rotation. Graft-mediated functional recovery was observed in the pellets taken criteria only under the HIGH pellet configuration during the bilateral and the forced choice condition. When tested under the LOW configuration, the graft provided no measurable benefit. The presence of VM grafts reduced lateralised motor deficits in the Cylinder test, the adjacent version of the Corridor test, and drug-induced rotation. Our results confirm that VM transplants can partially restore skilled forelimb sensorimotor deficits under specific testing configuration. PMID:20394782

  12. Unilateral Ibotenic Acid Lesions of the Prefrontal Cortex Reduce

    Kuriyama,Shigeki

    2006-12-01

    Full Text Available Rats with 6-hydroxydopamine (6-OHDA-induced lesions of the substantia nigra are used as a model of Parkinson’s disease (PD, and these “lesioned” rats exhibit a rotational behavior when further injected with apomorphine (APO. We examined whether lesions in the prefrontal cortex (PFC could modify the rotational behavior in PD model rats. Rats initially received unilateral lesions of the substantia nigra by 6-OHDA injection, and then their rotational behavior was measured. Two PFC lesions were achieved by intracerebral infusions of ibotenic acid, followed by measurement of APOinduced rotation. Rotation was reduced by approximately 30オ after PFC injury. The PFC may have functional infl uences on the basal ganglia and may be involved in the pathophysiology of the rotational behavior of PD model rats.

  13. Stem cell therapy in intracerebral hemorrhage rat model

    Marcos F Cordeiro; Ana P Horn

    2015-01-01

    Intracerebral hemorrhage (ICH) is a very complexpathology, with many different not fully elucidatedetiologies and prognostics. It is the most severe subtypeof stroke, with high mortality and morbidity rates.Unfortunately, despite the numerous promising preclinicalassays including neuroprotective, anti-hypertensive,and anti-inflammatory drugs, to this moment onlysymptomatic treatments are available, motivating thesearch for new alternatives. In this context, stem celltherapy emerged as a promising tool. However, morethan a decade has passed, and there is still much to belearned not only about stem cells, but also about ICHitself, and how these two pieces come together. To date,rats have been the most widely used animal model inthis research field, and there is much more to be learnedfrom and about them. In this review, we first summarizeICH epidemiology, risk factors, and pathophysiology. Wethen present different methods utilized to induce ICHin rats, and examine how accurately they represent thehuman disease. Next, we discuss the different typesof stem cells used in previous ICH studies, also takinginto account the tested transplantation sites. Finally, wesummarize what has been achieved in assays with stemcells in rat models of ICH, and point out some relevantissues where attention must be given in future efforts.

  14. Use of surgical techniques in the rat pancreas transplantation model

    Yi Ma; Zhi-Yong Guo

    2008-01-01

    BACKGROUND:Pancreas transplantation is currently considered to be the most reliable and effective treatment for insulin-dependent diabetes mellitus (also called type 1 diabetes). With the improvement of microsurgical techniques, pancreas transplantation in rats has been the major model for physiological and immunological experimental studies in the past 20 years. We investigated the surgical techniques of pancreas transplantation in rats by analysing the difference between cervical segmental pancreas transplantation and abdominal pancreaticoduodenal transplantation. METHODS:Two hundred and forty male adult Wistar rats weighing 200-300 g were used, 120 as donors and 120 as recipients. Sixty cervical segmental pancreas transplants and 60 abdominal pancreaticoduodenal transplants were carried out and vessel anastomoses were made with microsurgical techniques. RESULTS:The time of donor pancreas harvesting in the cervical and abdominal groups was 31±6 and 37.6±3.8 min, respectively, and the lengths of recipient operations were 49.2±5.6 and 60.6±7.8 min. The time for donor operation was not signiifcantly different (P>0.05), but the recipient operation time in the abdominal group was longer than that in the cervical group (P0.05). CONCLUSIONS:Both pancreas transplantation methods are stable models for immunological and physiological studies in pancreas transplantation. Since each has its own advantages and disadvantages, the designer can choose the appropriate method according to the requirements of the study.

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

    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......-induced striatal degeneration caused a progressive ventricle enlargement, which was significantly different from controls at 21 days posttransplantation. Seven days posttransplantation, T1-weighted images revealed a defined liquid-isointense signal surrounded by a hyperintense rim at the site of graft placement......, which was found unaltered for the first 21 days posttransplantation, whereas a hypointense graft signal was detected at 99 days posttransplantation. At 2 days posttransplantation, T2-weighted images showed the graft region as a hyperintense area surrounded by a rim of low signal intensity but at later...

  16. Dynamic modeling of renal blood flow in Dahl hypertensive and normotensive rats

    Knudsen, Torben; Elmer, Henrik; Knudsen, Morten H; Stoustrup, Jakob; Holstein-Rathlou, N.-H.

    2004-01-01

    A method is proposed in this paper which allows characterization of renal autoregulatory dynamics and efficiency using quantitative mathematical methods. Based on data from rat experiments, where arterial blood pressure and renal blood flow are measured, a quantitative model for renal blood flow ...... describe myogenic responses and tubuloglomerular feedback responses separately. The method is applied to data from normo- and hypertensive Dahl rats, and a discriminator that separates data from normotensive Dahl R rats and hypertensive Dahl S rats is constructed....

  17. A rat model with an isolated bladder in situ

    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...... to the proximal part of the descending colon. The animals were treated with antibiotics, and saline was infused daily into the bladder in order to prevent atrophy. This in situ model is considered to be useful in studies investigating the influence of specific compounds, such as carcinogens, on the...

  18. A Novel Rat Model of Type 2 Diabetes: The Zucker Fatty Diabetes Mellitus ZFDM Rat

    Norihide Yokoi; Masayuki Hoshino; Shihomi Hidaka; Eri Yoshida; Masayuki Beppu; Ritsuko Hoshikawa; Katsuko Sudo; Akihiko Kawada; Sadaaki Takagi; Susumu Seino

    2013-01-01

    The Zucker fatty (ZF) rat harboring a missense mutation (fatty, fa) in the leptin receptor gene (Lepr) develops obesity without diabetes; Zucker diabetic fatty (ZDF) rats derived from the ZF strain exhibit obesity with diabetes and are widely used for research on type 2 diabetes (T2D). Here we establish a novel diabetic strain derived from normoglycemic ZF rats. In our ZF rat colony, we incidentally found fa/fa homozygous male rats having reproductive ability, which is generally absent in the...

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

    Atsak, Piray; Orre, Marie; Bakker, Petra; Cerliani, Leonardo; Roozendaal, Benno; Gazzola, Valeria; Moita, Marta; Keysers, Christian

    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

  20. Evaluating antithrombotic activity of HY023016 on rat hypercoagulable model.

    Chen, Qiu-Fang; Li, Yun-Zhan; Wang, Xin-Hui; Su, You-Rui; Cui, Shuang; Miao, Ming-Xing; Jiang, Zhen-Zhou; Jiang, Mei-Ling; Jiang, Ai-Dou; Chen, Xiang; Xu, Yun-Gen; Gong, Guo-Qing

    2016-06-15

    The generation of thrombus is not considered as an isolated progression without other pathologic processes, which may also enhance procoagulant state. The purpose of this study was to assess whether HY023016, a novel dabigatran prodrug and an oral direct thrombin inhibitor, or dabigatran etexilate, another thrombin inhibitor can improve the state of whole blood hypercoagulability in vitro/vivo. By using whole blood flow cytometry we explored the effects of HY023016 and dabigatran etexilate on thrombin and ADP-induced human platelet-leukocyte aggregation generated in vitro. With the method of continuous infusion of thrombin intravenous, we successfully established a rat hypercoagulable model and evaluated the effect of HY023016 or dabigatran etexilate in vivo. HY023016 was able to inhibit thrombin- or ADP-induced platelet P-selectin or CD40L expression, leukocyte CD11b expression and formation of platelet-leukocyte aggregates in dose-dependent manner. Dabigatran etexilate was unable to affect ADP-induced platelet P-selectin or CD40L expression, leukocyte CD11b expression and formation of platelet-leukocyte aggregates. Based on rat hypercoagulable model, dabigatran etexilate could reverse thrombin-induced circulatory system hypercoagulable state in a concentration-dependent manner. Dabigatran etexilate also inhibited electrical stimulation induced formation of arterial thrombus in rat under hypercoagulable state, and extracorporal circulation-induced formation of thrombus in dose-dependent manner. Compared with dabigatran etexilate, HY023016 showed nearly equal or even better antithrombotic activity, regardless of reversing the cycle of rat hypercoagulable state or inhibiting platelet-leukocyte aggregation. In surrmary, HY023016 could effectively improve hypercoagulable state of circulatory system. PMID:27085896

  1. Inhibitory Effect of Kangjia Pill(抗甲丸) on Thyrocyte Proliferation in Rat Goiter Model

    韩勇; 周静; 于淑静; 崔彬; 张海清; 高聆; 赵家军

    2009-01-01

    Objective:To investigate the inhibitory effects of Kangjia Pill(抗甲丸,KJP)on the cell proliferation in rat goiter model induced by methimazole(MMI).Methods:Fifty-six Wistar rats were randomly divided into four groups:the normal group,MMI model group(MMI),low dose of KJP group(LKJP),and high dose of KJP(HKJP). Except the normal group(20 rats),the other groups(12 rats in each)were given 0.04%(w/v)MMI through the drinking water until the end of the experiment.One week later,the rats in the LKJP and HKJP group...

  2. Studies on the pathogenicity of anaerobes, especially Prevotella bivia, in a rat pyometra model.

    Mikamo, H; Kawazoe, K.; Izumi, K.; Watanabe, K.; Ueno, K.; Tamaya, T

    1998-01-01

    OBJECTIVE: Prevotella bivia is one of the anaerobic bacteria that resides in the flora of the female genital tract. We studied the pathogenicity of P. bivia in a rat pyometra model. METHODS: The experimental animal (rat) model of pyometra was developed to investigate the pathogenicity of P. bivia in a rat pyometra model. RESULTS: In the groups inoculated with aerobes alone, the infection rate was 10% (1/10) in the Staphylococcus aureus- or Staphylococcus agalactiae-inoculated group and 20% (2...

  3. Studies on the Pathogenicity of Anaerobes, Especially Prevotella bivia, in a Rat Pyometra Model

    Mikamo, H; Kawazoe, K.; Izumi, K.; Watanabe, K.; Ueno, K.; Tamaya, T

    1998-01-01

    Objective: Prevotella bivia is one of the anaerobic bacteria that resides in the flora of the female genital tract. We studied the pathogenicity of P. bivia in a rat pyometra model.Methods: The experimental animial (rat) model of pyometra was developed to investigate the pathogenicity of P. bivia in a rat pyometra model.Results: In the groups inoculated with aerobes alone, the infection rate was 10% (1/10) in the Staphylococcus aureus- or Staphylococcus agalactiae -inoculated group and 20% (2...

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

    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

  5. Antifibrotic effect of heparin on liver fibrosis model in rats

    Binita; Shah; Gaurang; Shah

    2012-01-01

    AIM: To evaluate the effect of chronic thrombin inhibition by heparin on experimentally induced chronic liver injury (liver fibrosis) in rats. METHODS: Chronic liver injury (liver fibrosis) was induced in Wistar rats by oral administration of carbon tetrachloride (CCl 4 ) for 7 wk, an animal model with persistent severe hepatic fibrosis. Intravenous administration of the thrombin antagonist (heparin) started 1 wk after the start of CCl 4 intoxication for 6 wk. After completion of treatment (7 wk), markers of hepatic dysfunction were measured and changes evaluated histopathologically. RESULTS: Higher serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), total, direct and indirect bilirubin levels, as well as lower fibrinogen levels, were found in CCl 4 intoxicated rats. Heparin, silymarin and combination of drug (heparin and silymarin) treatment for 6 wk prevented a rise in SGOT, SGPT, ALP, total, direct and indirect bilirubin levels and improved fibrinogen levels. Deterioration in hepatic function determined by the fibrosis area was retarded, as evident from hepatic histopathology. Total protein levels were not changed in all groups.CONCLUSION: Heparin, a thrombin antagonist, preserved hepatic function and reduced severity of hepatic dysfunction/fibrogenesis. Combination of heparin and silymarin produced additional benefits on liver fibrosis.

  6. Occlusive myocardial infarction: cardiac CT perfusion in a rat model

    Oh, Hyung Woo; Kim, Dong Hun; Byun, Joo Nam; Kim, Young Sook [Chosun University Hospital, Gwangju (Korea, Republic of)

    2007-03-15

    To test whether cardiac multidetector CT (MDCT) perfusion imaging can accurately delineate an irreversibly damaged myocardium in animals with an occlusive myocardial infarction. In 16 rats, the left anterior descending coronary arteries were ligated distal to its first diagonal artery after a thoracotomy. Thirty minutes after the procedure, 16-slice MDCT (Sensation 16, Siemens, Erlangen, Germany) was performed and delayed images were obtained up to 5 minutes after injecting the contrast agent (0.2 mL/100g, 0.5 mL/sec). The rats were re-examined one week later. After CT scanning, the rats were sacrificed and their hearts were extirpated for 2, 3, 5-triphenyltetrazolium chloride (TTC) histochemical staining. The stained slices were compared with the CT images. The CT number (HU) of the infarct and non-infarct areas were estimated from the contrast ratio (CR). The CT attenuation in the infarct area was significantly lower than that in the normal myocardium. Quantitative analysis of the CT attenuation revealed a significant difference in the CR and CT attenuation of the infarct and reference areas (0.48 {+-} 0.12 vs 0.64 {+-} 0.13, {rho} < 0.05, 163 {+-} 46 HU vs 216 {+-} 56 HU, {rho} < 0.05). However, there were no significant differences in the CT numbers between the infarct and non-infarct areas on the one-week follow-up. A perfusion defect on MDCT indicates the myocardial damage in an animal model with occlusive myocardial infarction.

  7. ''Drageny I'' has radioprotective effects in radiation-injured rat model induced by heavy ions

    In order to elucidate biological effects and mechanisms of heavy ion radiation in rats and protective effects of anti-radioactive agents ''drageny I'', animal model exposed to heavy ion radiation was established. Rats of model group and ''drageny I'' group were irradiated by heavy ions with 7 Gy in head (other parts of rats were not radiated). Then, all rats will be dealt with at different time points (24 h, 3 d and 7 d after radiation). General conditions, body weights, organs index were observed. The results showed that compared with model group, drug group's general conditions and body weights were better to a certain extent. Two rats of model group were dead and no rats of drug group after radiation. Tested drug could also regulate the immune organs index with statistical significance as compared with model group (P<0.05-0.01). The results obtained here showed that ''drageny I'' had radioprotective effects obviously. (author)

  8. A rat model of radiation injury in the mandibular area

    Radiation technology focuses on delivering the radiation as precisely as possible to the tumor, nonetheless both acute and long-term damage to surrounding normal tissue may develop. Injuries to the surrounding normal tissue after radiotherapy of head and neck cancer are difficult to manage. An animal model is needed to elucidate good treatment modalities. The aim of this study was to establish a rat model where a certain radiation dose gives reproducible tissue reactions in the mandibular area corresponding to injuries obtained in humans. The left mandible of male Sprague Dawley rats was irradiated by external radiotherapy (single fraction 15 Gy, total dose 75 Gy) every second week five times. Endpoint was six weeks after last radiation treatment, and the test group was compared to non-irradiated controls. Morphological alterations of the soft tissues, bone and tooth formation, as well as alterations of salivation, vascularity and collagen content were assessed. An unpaired, non-parametric Mann–Whitney test was used to compare the statistical differences between the groups. Analysis of the soft tissues and mandible within the radiation field revealed severe unilateral alopecia and dermatitis of the skin, extensive inflammation of the submandibular gland with loss of serous secretory cells, hyperkeratinization and dense connective fiber bundles of the gingival tissue, and disturbed tooth development with necrosis of the pulp. Production of saliva and the vascularity of the soft tissues were significantly reduced. Furthermore, the collagen fibril diameter was larger and the collagen network denser compared to non-irradiated control rats. We have established an animal model of radiation injury demonstrating physiological and histological changes corresponding to human radiation injuries, which can be used for future therapeutic evaluations

  9. Characterization of the Prediabetic State in a Novel Rat Model of Type 2 Diabetes, the ZFDM Rat

    Ghupurjan Gheni; Norihide Yokoi; Masayuki Beppu; Takuro Yamaguchi; Shihomi Hidaka; Ayako Kawabata; Yoshikazu Hoshino; Masayuki Hoshino; Susumu Seino

    2015-01-01

    We recently established a novel animal model of obese type 2 diabetes (T2D), the Zucker fatty diabetes mellitus (ZFDM) rat strain harboring the fatty mutation (fa) in the leptin receptor gene. Here we performed a phenotypic characterization of the strain, focusing mainly on the prediabetic state. At 6–8 weeks of age, fa/fa male rats exhibited mild glucose intolerance and severe insulin resistance. Although basal insulin secretion was remarkably high in the isolated pancreatic islets, the resp...

  10. TGF-beta and apoptosis - rat model of radiation pneumonitis

    To measure the involvement of bcl-2, apoptosis, TGF-β, number of neutrophils and other markers in the rat model of induced radiation pneumonitis. To describe sub-sequential changes in irradiated lung tissue. We proved TGF β 1 to be important marker of post-irradiation reaction. Besides, we suggest that TGF-β 3 expression might be closely related to the activity of neutrophils and activity of the process in irradiated lung tissue. We proved our recent findings of suppression of the anti-apoptotic activity after lung irradiation. (authors)

  11. Modeling postpartum depression in rats: theoretic and methodological issues.

    Li, Ming; Chou, Shinn-Yi

    2016-07-18

    The postpartum period is when a host of changes occur at molecular, cellular, physiological and behavioral levels to prepare female humans for the challenge of maternity. Alteration or prevention of these normal adaptions is thought to contribute to disruptions of emotion regulation, motivation and cognitive abilities that underlie postpartum mental disorders, such as postpartum depression. Despite the high incidence of this disorder, and the detrimental consequences for both mother and child, its etiology and related neurobiological mechanisms remain poorly understood, partially due to the lack of appropriate animal models. In recent decades, there have been a number of attempts to model postpartum depression disorder in rats. In the present review, we first describe clinical symptoms of postpartum depression and discuss known risk factors, including both genetic and environmental factors. Thereafter, we discuss various rat models that have been developed to capture various aspects of this disorder and knowledge gained from such attempts. In doing so, we focus on the theories behind each attempt and the methods used to achieve their goals. Finally, we point out several understudied areas in this field and make suggestions for future directions. PMID:27469254

  12. Modeling the distribution of Norway rats (Rattus norvegicus on offshore islands in the Falkland Islands

    Michael A. Tabak

    2015-01-01

    Full Text Available Non-native rats (Rattus spp. threaten native island species worldwide. Efforts to eradicate them from islands have increased in frequency and become more ambitious in recent years. However, the long-term success of some eradication efforts has been compromised by the ability of rats, particularly Norway rats (Rattus norvegicus which are good swimmers, to recolonize islands following eradications. In the Falkland Islands, an archipelago in the South Atlantic Ocean, the distance of 250 m between islands (once suggested as the minimum separation distance for an effective barrier to recolonization has shown to be insufficient. Norway rats are present on about half of the 503 islands in the Falklands. Bird diversity is lower on islands with rats and two vulnerable passerine species, Troglodytes cobbi (the only endemic Falkland Islands passerine and Cinclodes antarcticus, have greatly reduced abundances and/or are absent on islands with rats. We used logistic regression models to investigate the potential factors that may determine the presence of Norway rats on 158 islands in the Falkland Islands. Our models included island area, distance to the nearest rat-infested island, island location, and the history of island use by humans as driving variables. Models best supported by data included only distance to the nearest potential source of rats and island area, but the relative magnitude of the effect of distance and area on the presence of rats varied depending on whether islands were in the eastern or western sector of the archipelago. The human use of an island was not a significant parameter in any models. A very large fraction (72% of islands within 500 m of the nearest potential rat source had rats, but 97% of islands farther than 1,000 m away from potential rat sources were free of rats.

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

    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 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. PMID:23354407

  14. Hypertension and vulnerability to hemorrhagic shock in a rat model.

    Reynolds, Penny S; Song, Kyle Seokhan; Tamariz, Francisco J; Wayne Barbee, R

    2015-02-01

    Trauma mortality may be increased in the presence of preexisting diseases such as chronic hypertension. We hypothesized that systemic and microvascular alterations accompanying chronic hypertension would increase the vulnerability to hemorrhage relative to normotensive controls in a rat model of hemorrhagic shock. We present a novel comparative hemorrhage model of shock vulnerability, quantified by "vulnerability curves" expressing physiological response to hemorrhage as a function of three matched shock metrics: cumulative blood volume, mean arterial pressure (MAP), and oxygen delivery (Do2). Responses were central hemodynamics and respiratory and muscle oxygenation obtained for one hypertensive (spontaneously hypertensive [SHR]) and two normotensive (Sprague-Dawley, Wistar-Kyoto) rat strains. Hemorrhagic shock was induced by incremental (0.5 mL) hemorrhage to cardiovascular collapse in anesthetized and mechanically ventilated animals. Shock vulnerability of SHR rats was primarily pressure-driven; in general, SHR exhibited the expected patterns of more rapid deterioration in MAP and Vo2 over smaller ranges of blood loss and Do2. Sternotomy-related depression of CO and thus Do2 in SHR meant that we could not test hypotheses related to the role of Do2 and contribution to perfusion differences between normotensive and hypertensive subjects. Insensitivity of lactate to strain effects suggests that lactate may be a reliable biomarker of shock status. Unexpected similarities between Wistar-Kyoto and SHR suggest strain-related effects other than those related to hypertension per se contribute to hemorrhage response; body size effects and genetic relationships could not be ruled out. Future studies should incorporate phylogenetically based methods to examine the role of hypertension and physiological response to hemorrhage across multiple strains. PMID:25300030

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

    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.

  16. The rat as an animal model of Alzheimer’s disease

    Benedikz, Eirikur; Kloskowska, Ewa; Winblad, Bengt

    2009-01-01

    As a disease model, the laboratory rat has contributed enormously to neuroscience research over the years. It has also been a popular animal model for Alzheimer’s disease but its popularity has diminished during the last decade, as techniques for genetic manipulation in rats have lagged behind that of mice. In recent years, the rat has been making a comeback as an Alzheimer’s disease model and the appearance of increasing numbers of transgenic rats will be a welcome and valuable complement to...

  17. Establishment of an Invasive Prostate Cancer Model in Transgenic Rats by Intermittent Testosterone Administration

    SATO, SHINYA; Suzuki, Shugo; Naiki-Ito, Aya; Komiya, Masami; Ne, Long; Kato, Hiroyuki; Sagawa, Hiroyuki; Yamashita, Yoriko; Shirai, Tomoyuki; Takahashi, Satoru

    2014-01-01

    We have established a transgenic rat for adenocarcinoma of the prostate (TRAP) model that features uniform adenocarcinoma development in prostatic lobes at high incidence within a short experimental period. However, no invasive carcinomas with reactive stroma characteristics similar to those in man were observed. We therefore have focused on a new model for invasive carcinoma of the prostate using TRAP rats. In experiment 1, male TRAP rats in groups 1 and 2 were treated with orchiectomy at da...

  18. Grape powder prevents cognitive, behavioral and biochemical impairments in a rat model of posttraumatic stress disorder

    Solanki, Naimesh; Alkadhi, Isam; Atrooz, Fatin; Patki, Gaurav; Salim, Samina

    2015-01-01

    Previously, using the single-prolonged stress (SPS) rat model of post-traumatic stress disorder, we reported that moderate treadmill exercise, via modulation of oxidative stress related mechanisms, rescued anxiety and depression-like behaviors and reversed SPS-induced memory impairment. In this study using the SPS model (2 h restrain, 20 min forced swimming, 15 min rest, and 1–2 min diethyl ether exposure), we hypothesized that antioxidant rich grape powder (GP) prevents SPS-induced behavioral and memory impairment in rats. Male Sprague Dawley rats were randomly assigned into: Control (CON; provided tap water), SPS (provided tap water), GP-SPS (provided 15 g/L GP in tap water for 3 wk followed by SPS), or GP-CON (3 wk of GP followed by control exposure). Anxiety and depression-like behaviors were significantly greater in SPS rats when compared to CON or GP treated rats and GP reversed these behavioral deficits. SPS rats made significantly more errors in both short- and long-term memory tests compared to CON or GP treated rats, which were prevented in GP-SPS rats. GP prevented SPS-induced increase in plasma corticosterone level. Furthermore, brain derived neurotrophic factor (BDNF) levels were significantly decreased in amygdala of SPS rats but not in GP-SPS rats compared to CON or GP-CON rats. Additionally, GP significantly increased acetylated Histone3, Histone deacetylase 5 (HDAC 5) in hippocampus and amygdala of SPS rats as compared to CON or GP-CON rats. In conclusion, we suggest protective role of GP in SPS-induced behavioral, cognitive and biochemical impairments in rats. Perhaps, epigenetic regulation of BDNF enables GP-mediated prevention of SPS-induced deficits in rats. PMID:25533441

  19. Comparison of classical heat stroke between conscious and unconscious rat models

    Yan GENG

    2013-09-01

    Full Text Available Objective To reproduce conscious and unconscious classical heat stroke(CHS models in conscious and unconscious rats, and the difference in heat stress response between the two models was investigated. Methods Thirty-two male SD rats were randomly and equally divided into conscious classic heatstroke(C-CHS, unconscious classi cheatstroke(N-CHS, conscious normal control(C-NC and unconscious normal control(N-NCgroups.Rats of C-CHS and N-CHS groups were put into artificial climate chamber, and exposed to 39℃ heat stress.Core temperature and systolic blood pressure(SBP of rats were monitored via rectal thermal couple and by both invasive and non-invasive arterial blood pressure monitor instrument respectively. Heat stress responses of C-CHS and N-CHS rats were quantitatively analyzed and compared, and the survival time was also compared by K-M survival analysis. Results There was a significant difference in regulatory features of the core temperature and SBP betweenC-CHS and N-CHS rats. Although no difference in maximum core temperature has been observed between N-CHS and C-CHS rats, but in comparison with C-CHS rats,N-CHS rats had significantly faster rise in core temperature(P<0.05, shorter heat stress time period,lighter total thermal load and severe thermal load(P<0.05.N-CHS rats had a poorer prognosis than C-CHS rats(P<0.05. Conclusion In comparison with traditional heatstroke in unconscious rats, heatstroke in conscious rats model is more suitable for the investigation of experimental heatstroke, and further investigation of this model may help understand the mechanism ofpathogenesis of classic heatstroke.

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

    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. Effects of Ginkgo biloba leaf extract on Alzheimer' s Disease Model of Rats

    GONGQi-Hai; WUQin; HUANGXie-Nan; SUNAn-Sheng; SHIJing-Shan

    2004-01-01

    AIM: To examine the protective effects of Ginkgo biloba extract (GbE) on the learning and memory in the Alzheimer disease (AD) model induced by aluminum salt in rats, and to examine the potential mechanisms. METHODS. The AD model of rats was induced by administration and drinking of aluminum chloride solution. The abilities of spatial leafing and

  2. A BBDR-HPT Axis Model for the Pregnant Rat and Fetus: Evaluation of Iodide Deficiency

    A biologically based dose response (BBDR) model for the hypothalamic-pituitarythyroid (HPT) axis for the pregnant rat and fetus is being developed to advance understanding of thyroid hormone disruptions and developmental neurotoxicity (DNT). The model for the pregnant rat and fet...

  3. The Effect of Opsteoporotic Model Rats Induced by Retinoic Acid

    Xu Peng; Yao Jianfeng; Jin Weizhang; Cai Qiankun; Guo Xiong

    2005-01-01

    Objective: To study the effect of retinoic acid on inducing osteoporosis in female rat. Methods: 48SD female rats were divided randomly into experiment group and control group. Retinoic acid was administered orally to experiment group with 80mg.kg-1d-1 for 15 days. Then the rats were sacrificed on the 0th, 30th, 60th days after last administration. The serum concentration of Ca, P, BGP, E2, AKP and TRAP were detected. Components of collagen and proteoglycan in the bones and BMD were also assayed .The femoral morphometric change and epiphyseal plate cartilage histological changes were observed. Results: After a 15-day period treatment with retinoic acid, charateristics of experiment group were compared with control, it is shown that the concentration of serum E2 and BGP declined, the activity of AKP and TRAP increased while BMP decreased, the bone mass of both spongy bone and cortical bone reduced, the number of spongy bone osteoclasts and their activity increased, number of epiphyseal plate chondrocyte reduced, cartilage hypertrophic zone displayed dyscalcification, and no difference of other markers was found in the two groups. On the 30th day after the last administration, the experiment group appeared a declined number of cancellous bone osteoclast and level of serum AKP yet they were still higher than control. Number of epiphyseal chondrocyte, serum BGP and tibial BMD, though higher than before, were still lower than control. Other markers were no difference. On the 60th day after treatment, although the femoral cancellous bone mass was still less and cancellous osteoblast was more than control, the cortical bone mass, cancellous osteoclast number and level of serum Ca and P were all remained no different between two groups.Conclusion: Retinoic acid possessed a better short-term effect than long-term effect. Cancellous bone loss lasted much longer than cortical bone and more obviously; the bone matrix in this osteoporosis model was able to repair itself

  4. The rat as an animal model for infant botulism.

    Moberg, L J; Sugiyama, H

    1980-01-01

    Susceptibility to intraintestinal Clostridium botulinum colonization of conventional infant and germfree adult rats is comparable to that of mice. C. botulinum-monoassociated rats pass C. botulinum toxin in their milk.

  5. Relationship between peritoneal macrophages and inflammatory reaction in a rat model of severe acute pancreatitis

    2009-01-01

    Objective To investigate the relationship between peritoneal macrophages(PMAs)and inflammatory reaction in a rat model of severe acute pancreatitis(SAP).Methods Sprague-Dawley rats were randomly divided into control group and SAP group.To induce SAP in rats,40 g/L sodium taurocholate(0.1 mL/100 g)was injected into the pancreatic duct through retrograde exposure of pancreatic bile duct in hepatic porta.One-third of rats were sacrificed at 3,6 or 12 h after modeling.PMAs were extracted,and incubated for 24 h ...

  6. Anti-Parkinson Activity of Petroleum Ether Extract of Ficus religiosa (L. Leaves

    Jitendra O. Bhangale

    2016-01-01

    Full Text Available In the present study, we evaluated anti-Parkinson’s activity of petroleum ether extract of Ficus religiosa (PEFRE leaves in haloperidol and 6 hydroxydopamine (6-OHDA induced experimental animal models. In this study, effects of Ficus religiosa (100, 200, and 400 mg/kg, p.o. were studied using in vivo behavioral parameters like catalepsy, muscle rigidity, and locomotor activity and its effects on neurochemical parameters (MDA, CAT, SOD, and GSH in rats. The experiment was designed by giving haloperidol to induce catalepsy and 6-OHDA to induce Parkinson’s disease-like symptoms. The increased cataleptic scores (induced by haloperidol were significantly (p<0.001 found to be reduced, with the PEFRE at a dose of 200 and 400 mg/kg (p.o.. 6-OHDA significantly induced motor dysfunction (muscle rigidity and hypolocomotion. 6-OHDA administration showed significant increase in lipid peroxidation level and depleted superoxide dismutase, catalase, and reduced glutathione level. Daily administration of PEFRE (400 mg/kg significantly improved motor performance and also significantly attenuated oxidative damage. Thus, the study proved that Ficus religiosa treatment significantly attenuated the motor defects and also protected the brain from oxidative stress.

  7. Anti-Parkinson Activity of Petroleum Ether Extract of Ficus religiosa (L.) Leaves.

    Bhangale, Jitendra O; Acharya, Sanjeev R

    2016-01-01

    In the present study, we evaluated anti-Parkinson's activity of petroleum ether extract of Ficus religiosa (PEFRE) leaves in haloperidol and 6 hydroxydopamine (6-OHDA) induced experimental animal models. In this study, effects of Ficus religiosa (100, 200, and 400 mg/kg, p.o.) were studied using in vivo behavioral parameters like catalepsy, muscle rigidity, and locomotor activity and its effects on neurochemical parameters (MDA, CAT, SOD, and GSH) in rats. The experiment was designed by giving haloperidol to induce catalepsy and 6-OHDA to induce Parkinson's disease-like symptoms. The increased cataleptic scores (induced by haloperidol) were significantly (p < 0.001) found to be reduced, with the PEFRE at a dose of 200 and 400 mg/kg (p.o.). 6-OHDA significantly induced motor dysfunction (muscle rigidity and hypolocomotion). 6-OHDA administration showed significant increase in lipid peroxidation level and depleted superoxide dismutase, catalase, and reduced glutathione level. Daily administration of PEFRE (400 mg/kg) significantly improved motor performance and also significantly attenuated oxidative damage. Thus, the study proved that Ficus religiosa treatment significantly attenuated the motor defects and also protected the brain from oxidative stress. PMID:26884755

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

    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.

  9. [Scintigraphic imaging of macrophages involved in lung vasoreflex: rat model].

    Ndoye, O; Mbodj, M; Gassama Seck, S; Sizaret, P Y; Abeille, B; Le Pape, A

    2003-01-01

    At time of pathological situations, a pulmonary fixation of labelled substances injected by intravenous way is observed. This fixation would result from a phagocytosis of these substances by abnormal cells whose presence was induced in the endothelium: Pulmonary Intravascular Macrophages (PIM's). After activation by phagocytosis, these cells are able to secrete powerful vasoactive mediators capable of inducing cardiopulmonary accidents. Hepatic cholestase was induced in Wistar rats by ligation and section of common bile duct. The recruitment of PIM's was followed in vivo by phagocytosis scintigraphic imaging after labelled colloid injection. During the 35 days of evolution of the pathology, we observe a pulmonary fixation of the colloid agents which progresses up to 70% as well as a concomitant decease in the hepatic activity. Histologic examination showed numerous cells related to pulmonary capillaries' endothelium belonging to mononuclear phagocytes line and expressing an activated phenotype of monocytes. The scintigraphic and histological tests carried out enabled us to validate the model of induction of PIM's in rat by ligation of the choledoque one. The study of the vasoactive response via certain mediators can from now be approached, a Doppler technique on the pig aorta is being in the course of evaluation. PMID:15770812

  10. A new model of progressive pulmonary fibrosis in rats

    Last, J.A.; Gelzleichter, T.R.; Pinkerton, K.E.; Walker, R.M.; Witschi, H. (Univ. of California, Davis (United States))

    1993-08-01

    Sprague-Dawley rats were exposed for 6 h daily to 0.8 ppm of ozone and 14.4 ppm of nitrogen dioxide. Approximately 7 to 10 wk after the initiation of exposure, animals began to demonstrate respiratory insufficiency and severe weight loss. About half of the rats died between Days 55 and 78 of exposure; no overt ill effects were observed in animals exposed to filtered air, to ozone alone, or to nitrogen dioxide. Biochemical findings in animals exposed to ozone and nitrogen dioxide included increased lung content of DNA, protein, collagen, and elastin, which was about 300% higher than the control values. The collagen-specific crosslink hydroxy-pyridinium, a biomarker for mature collagen in the lung, was decreased by about 40%. These results are consistent with extensive breakdown and remodeling of the lung parenchyma and its associated vasculature. Histopathologic evaluation showed severe fibrosis, alveolar collapse, honeycombing, macrophage and mast cell accumulation, vascular smooth muscle hypertrophy, and other indications of severe progressive interstitial pulmonary fibrosis and end-stage lung disease. This unique animal model of progressive pulmonary fibrosis resembles the final stages of human idiopathic pulmonary fibrosis and should facilitate studying underlying mechanisms and potential therapy of progressive pulmonary fibrosis.

  11. Modeling the Nonlinear Motion of the Rat Central Airways.

    Ibrahim, G; Rona, A; Hainsworth, S V

    2016-01-01

    Advances in volumetric medical imaging techniques allowed the subject-specific modeling of the bronchial flow through the first few generations of the central airways using computational fluid dynamics (CFD). However, a reliable CFD prediction of the bronchial flow requires modeling of the inhomogeneous deformation of the central airways during breathing. This paper addresses this issue by introducing two models of the central airways motion. The first model utilizes a node-to-node mapping between the discretized geometries of the central airways generated from a number of successive computed tomography (CT) images acquired dynamically (without breath hold) over the breathing cycle of two Sprague-Dawley rats. The second model uses a node-to-node mapping between only two discretized airway geometries generated from the CT images acquired at end-exhale and at end-inhale along with the ventilator measurement of the lung volume change. The advantage of this second model is that it uses just one pair of CT images, which more readily complies with the radiation dosage restrictions for humans. Three-dimensional computer aided design geometries of the central airways generated from the dynamic-CT images were used as benchmarks to validate the output from the two models at sampled time-points over the breathing cycle. The central airway geometries deformed by the first model showed good agreement to the benchmark geometries within a tolerance of 4%. The central airway geometry deformed by the second model better approximated the benchmark geometries than previous approaches that used a linear or harmonic motion model. PMID:26592166

  12. A novel, minimally invasive rat model of normothermic cardiopulmonary bypass model without blood priming

    Zhu Yaobin; Liu Donghai; Li Xiaofeng; Liu Aijun; Wang Qiang; Qiao Chenhui; Zhang Jing

    2014-01-01

    Background Cardiopulmonary bypass (CPB) has been shown to be associated with systemic inflammatory response leading to postoperative organ dysfunction.Elucidating the underlying mechanisms and developing protective strategies for the pathophysiological consequences of CPB have been hampered due to the absence of a satisfactory recovery animal model.The purpose of this study was to establish a novel,minimally invasive rat model of normothermic CPB model without blood priming.Methods Twenty adult male Sprague-Dawley rats weighing 450-560 g were randomly divided into CPB group (n=10) and control group (n=10).All rats were anaesthetized and mechanically ventilated.The carotid artery and jugular vein were cannulated.The blood was drained from the right atrium via the right jugular and further transferred by a miniaturized roller pump to a hollow fiber oxygenator and back to the rat via the left carotid artery.The volume of the priming solution,composed of 6% HES130/0.4 and 125 IU heparin,was less than 12 ml.The surface of the hollow fiber oxygenator was 0.075 m2.CPB was conducted for 60 minutes at a flow rat of 100-120 ml· kg-1· min-1 in CPB group.Oxygen flow/perfusion flow was 0.8 to 1.0,and the mean arterial pressure remained 60-80 mmHg.Results 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.Conclusions The establishment of CPB without blood priming in rats can be achieved successfully.The nontransthoracic model should facilitate the investigation of pathophysiological processes concerning CPB-related multiple organ dysfunction and possible protective interventions.This novel,recovery,and reproducible minimally invasive CPB model may open the field for various studies on the pathophysiological process of CPB and systemic ischemia-reperfusion injury in vivo.

  13. Rat embryonic stem cells create new era in development of genetically manipulated rat models

    Kazushi; Kawaharada; Masaki; Kawamata; Takahiro; Ochiya

    2015-01-01

    Embryonic stem(ES) cells are isolated from theinner cell mass of a blastocyst, and are used for the generation of gene-modified animals. In mice, the transplantation of gene-modified ES cells into recipient blastocysts leads to the creation of gene-targeted mice such as knock-in and knock-out mice; these gene-targeted mice contribute greatly to scientific development. Although the rat is considered a useful laboratory animal alongside the mouse, fewer genemodified rats have been produced due to the lack of robust establishment methods for rat ES cells. A new method for establishing rat ES cells using signaling inhibitors was reported in 2008. By considering the characteristics of rat ES cells, recent research has made progress in improving conditions for the stable culture of rat ES cells in order to generate gene-modified rats efficiently. In this review, we summarize several advanced methods to maintain rat ES cells and generate gene-targeted rats.

  14. RAT PLACENTATION: AN EXPERIMENTAL MODEL FOR INVESTIGATING THE HEMOCHORIAL MATERNAL-FETAL INTERFACE

    Soares, Michael J.; Chakraborty, Damayanti; Rumi, M. A. Karim; Konno, Toshihiro; Renaud, Stephen J.

    2012-01-01

    The rat possesses hemochorial placentation with deep intrauterine trophoblast cell invasion and trophoblast-directed uterine spiral artery remodeling; features shared with human placentation. Recognition of these similarities spurred the establishment of in vitro and in vivo research methods using the rat as an animal model to address mechanistic questions regarding development of the hemochorial placenta. The purpose of this review is to provide the requisite background to help move the rat ...

  15. EVALUATION OF ANTI-INFLAMMATORY PROPERTY OF VANILLIN IN CARRAGEENAN INDUCED PAW EDEMA MODEL IN RATS

    SRIKANTH D, Vishma Hydie Menezes, Nischal Saliyan, Rathnakar UP*, Shiv Prakash G, Sahana D Acaharya, Ashok Shenoy K, Udupa AL

    2013-01-01

    Introduction: Vanillinis known to have antimutagenic, anti-invasive and metastatic suppression potential. Antinociceptive property in acetic acid induced visceral pain models, antioxidant and hepato-protective properties of in carbon tetrachloride-treated rats have also been demonstrated. Objective of this study is to evaluate the effect of vanillin on acute inflammation induced by carrageenan in rats.Methods: Rats were assigned to five groups [Control, Asprin and three Vanillin groups,] of s...

  16. Development of a standardized laparoscopic caecum resection model to simulate laparoscopic appendectomy in rats

    Lingohr, Philipp; Dohmen, Jonas; Matthaei, Hanno; Schwandt, Timo; Hong, Gun-Soo; Konieczny, Nils; Bölke, Edwin; Wehner, Sven; Kalff, Jörg C

    2014-01-01

    Background Laparoscopic appendectomy (LA) has become one of the most common surgical procedures to date. To improve and standardize this technique further, cost-effective and reliable animal models are needed. Methods In a pilot study, 30 Wistar rats underwent laparoscopic caecum resection (as rats do not have an appendix vermiformis), to optimize the instrumental and surgical parameters. A subsequent test study was performed in another 30 rats to compare three different techniques for caecum...

  17. Inducible Transgenic Rat Model for Diabetes Mellitus Based on shRNA-Mediated Gene Knockdown

    Katarina Kotnik; Elena Popova; Mihail Todiras; Mori, Marcelo A.; Natalia Alenina; Jost Seibler; Michael Bader

    2009-01-01

    The rat is an important animal model in biomedical research, but gene targeting technology is not established for this species. Therefore, we aimed to produce transgenic knockdown rats using shRNA technology and pronuclear microinjection. To this purpose, we employed a tetracycline-inducible shRNA expression system targeting the insulin receptor (IR). Doxycycline (DOX) treatment of the resulting transgenic rats led to a dose-dependent and reversible increase in blood glucose caused by ubiquit...

  18. The Establishment of Metabolic Syndrome Model by Induction of Fructose Drinking Water in Male Wistar Rats

    Norshalizah Mamikutty; Zar Chi Thent; Shaiful Ridzwan Sapri; Natasya Nadia Sahruddin; Mohd Rafizul Mohd Yusof; Farihah Haji Suhaimi

    2014-01-01

    Background. Metabolic syndrome can be caused by modification of diet by means of consumption of high carbohydrate and high fat diet such as fructose. Aims. To develop a metabolic syndrome rat model by induction of fructose drinking water (FDW) in male Wistar rats. Methods. Eighteen male Wistar rats were fed with FDW 20% and FDW 25% for a duration of eight weeks. The physiological changes with regard to food and fluid intake, as well as calorie intake, were measured. The metabolic changes such...

  19. Efficacy of integrative medicine in deficiency of both qi and yin in the rat model of type 2 diabetes

    Jing Zhao

    2015-10-01

    Conclusions: A rat model of T2DM with both qi and yin deficiency was successfully replicated. CHF appeared to be more efficacious than IM and PIO in the rat model of qi and yin deficiency pattern of T2DM, though IM and PIO were each found to have their merits and drawbacks in attenuating T2DM indicators in the rat model.

  20. Clinical and pathological manifestations of cardiovascular disease in rat models: the influence of acute ozone exposure

    This paper shows that rat models of cardiovascular diseases have differential degrees of underlying pathologies at a young age. Rodent models of cardiovascular diseases (CVD) and metabolic disorders are used for examining susceptibility variations to environmental exposures. How...

  1. Determinants of renal tissue hypoxia in a rat model of polycystic kidney disease.

    Ow, Connie P C; Abdelkader, Amany; Hilliard, Lucinda M; Phillips, Jacqueline K; Evans, Roger G

    2014-11-15

    Renal tissue oxygen tension (PO2) and its determinants have not been quantified in polycystic kidney disease (PKD). Therefore, we measured kidney tissue PO2 in the Lewis rat model of PKD (LPK) and in Lewis control rats. We also determined the relative contributions of altered renal oxygen delivery and consumption to renal tissue hypoxia in LPK rats. PO2 of the superficial cortex of 11- to 13-wk-old LPK rats, measured by Clark electrode with the rat under anesthesia, was higher within the cysts (32.8 ± 4.0 mmHg) than the superficial cortical parenchyma (18.3 ± 3.5 mmHg). PO2 in the superficial cortical parenchyma of Lewis rats was 2.5-fold greater (46.0 ± 3.1 mmHg) than in LPK rats. At each depth below the cortical surface, tissue PO2 in LPK rats was approximately half that in Lewis rats. Renal blood flow was 60% less in LPK than in Lewis rats, and arterial hemoglobin concentration was 57% less, so renal oxygen delivery was 78% less. Renal venous PO2 was 38% less in LPK than Lewis rats. Sodium reabsorption was 98% less in LPK than Lewis rats, but renal oxygen consumption did not significantly differ between the two groups. Thus, in this model of PKD, kidney tissue is severely hypoxic, at least partly because of deficient renal oxygen delivery. Nevertheless, the observation of similar renal oxygen consumption, despite markedly less sodium reabsorption, in the kidneys of LPK compared with Lewis rats, indicates the presence of inappropriately high oxygen consumption in the polycystic kidney. PMID:25209412

  2. The touchscreen operant platform for assessing cognitive functions in a rat model of depression.

    Tran, Thao Phuong; Christensen, Helle Lyng; Bertelsen, Freja Cecilia Brandt; Bouzinova, Elena; Møller, Arne; Wiborg, Ove

    2016-07-01

    In the present study we assessed alterations in cognitive functions in a chronic mild stress (CMS) rat model of depression. Cognitive functions were assessed in two different tasks applying the translational operant platform touchscreen technology; the visual discrimination/acquisition task was used to assess the ability to perceive and distinguish visual stimuli and to assess associative stimulus-reward learning. The visual discrimination/reversal learning task was used to assess functional brain plasticity or reprogramming of previously acquired stimulus-reward associations. These tasks permit the dissociation of multiple cognitive domains. The CMS model is a validated depression model with the useful feature that rats upon stress exposure show a graduated, individual stress response allowing the segregation of rats into different phenotypes including stress-resilient and anhedonic-like subgroups. Anhedonic-like rats are less likely to acquire the pairwise discrimination task, and they have a slower acquisition rate than controls. In the reversal learning task, resilient rats performed significantly better than anhedonic-like rats over time and 50% passed criterion as opposed to 25% for controls and only 14% for anhedonic-like rats. This indicates that resilient rats have higher cognitive flexibility than anhedonic-like rats. Thus they perform better in learning a novel task, which at the same time potentially implies an increased ability to inhibit previously rewarded behavior. PMID:27083126

  3. Pharrnacokinetic-pharmacodynarnic modeling of telrnisartan using an indirect response model in spontaneously hypertensive rats

    Kun HAO; Yuan-cheng CHEN; Yan-guang CAO; Dan YU; Xiao-quan LIU; Guang-ji WANG

    2007-01-01

    Aim: To investigate the pharmacokinetic (PK) and the pharmacodynamic (PD) properties of telmisartan in spontaneously hypertensive (SH) rats using an indi-rect response and effect-compartment link models, and compare two PK-PD mod-els fitting quality. Methods: The SH rats received a single oral dose of 2, 4, and 8 mg/kg of telmisartan. The plasma concentrations of telmisartan were determined by the liquid chromatography-mass spectrum method. The mean arterial blood pressure was measured to characterize the pharmacodynamics of telmisartan by tail-cuff manometry. The relationship for the telmisartan concentration-hypoten-sive effect in the SH rats was characterized using an indirect response model.Results: The PK parameters showed dose proportionality, with a long terminal half-life of 16 h, a clearance of 0.15 L.kg-1h-1, and a volume of distribution of 5.36 L-kg-1 in the study. For the indirect response PD model, the estimated Kin were 36.1490.5, and 2086.2 mmHg.h at three doses, respectively. For the effect-compart-ment model, the Keo were 29.4, 33.8, and 28.7 h-1; the IC50 values were 78.2, 85.7, and respectively. Conclusion: According to Akaike's information criterion values, the proposed indirect response model provided a more appropriate and good-fitting PK/PD characterization of telmisartan than the effect-compartment link model in SH rats.

  4. Prostate carcinoma in transgenic Lewis rats - a tumor model for evaluation of immunological treatments

    Johnson, Laura E.; Becker, Jordan T; Dubovsky, Jason A.; Olson, Brian M.; McNeel, Douglas G.

    2013-01-01

    Transgenic rodent models of prostate cancer have served as valuable preclinical models to evaluate novel treatments and understand malignant disease progression. In particular, a transgenic rat autochthonous model of prostate cancer using the SV40 large T antigen expressed under a prostate-specific probasin promoter was previously developed as a model of androgen-dependent prostate cancer (TRAP). In the current report, we backcrossed this strain to the Lewis strain, an inbred rat strain bette...

  5. Comparative Analysis of the Effects of Neurotrophic Factors CDNF and GDNF in a Nonhuman Primate Model of Parkinson's Disease.

    Enrique Garea-Rodríguez

    Full Text Available Cerebral dopamine neurotrophic factor (CDNF belongs to a newly discovered family of evolutionarily conserved neurotrophic factors. We demonstrate for the first time a therapeutic effect of CDNF in a unilateral 6-hydroxydopamine (6-OHDA lesion model of Parkinson's disease in marmoset monkeys. Furthermore, we tested the impact of high chronic doses of human recombinant CDNF on unlesioned monkeys and analyzed the amino acid sequence of marmoset CDNF. The severity of 6-OHDA lesions and treatment effects were monitored in vivo using 123I-FP-CIT (DaTSCAN SPECT. Quantitative analysis of 123I-FP-CIT SPECT showed a significant increase of dopamine transporter binding activity in lesioned animals treated with CDNF. Glial cell line-derived neurotrophic factor (GDNF, a well-characterized and potent neurotrophic factor for dopamine neurons, served as a control in a parallel comparison with CDNF. By contrast with CDNF, only single animals responded to the treatment with GDNF, but no statistical difference was observed in the GDNF group. However, increased numbers of tyrosine hydroxylase immunoreactive neurons, observed within the lesioned caudate nucleus of GDNF-treated animals, indicate a strong bioactive potential of GDNF.

  6. Fractional ventilation mapping using inert fluorinated gas MRI in rat models of inflammation and fibrosis.

    Couch, Marcus J; Fox, Matthew S; Viel, Chris; Gajawada, Gowtham; Li, Tao; Ouriadov, Alexei V; Albert, Mitchell S

    2016-05-01

    The purpose of this study was to extend established methods for fractional ventilation mapping using (19) F MRI of inert fluorinated gases to rat models of pulmonary inflammation and fibrosis. In this study, five rats were instilled with lipopolysaccharide (LPS) in the lungs two days prior to imaging, six rats were instilled with bleomycin in the lungs two weeks prior to imaging and an additional four rats were used as controls. (19) F MR lung imaging was performed at 3 T with rats continuously breathing a mixture of sulfur hexafluoride and O2 . Fractional ventilation maps were obtained using a wash-out approach, by switching the breathing mixture to pure O2 , and acquiring images following each successive wash-out breath. The mean fractional ventilation (r) was 0.29 ± 0.05 for control rats, 0.23 ± 0.10 for LPS-instilled rats and 0.19 ± 0.03 for bleomycin-instilled rats. Bleomycin-instilled rats had a significantly decreased mean r value compared with controls (P = 0.010). Although LPS-instilled rats had a slightly reduced mean r value, this trend was not statistically significant (P = 0.556). Fractional ventilation gradients were calculated in the anterior/posterior (A/P) direction, and the mean A/P gradient was -0.005 ± 0.008 cm(-1) for control rats, 0.013 ± 0.005 cm(-1) for LPS-instilled rats and 0.009 ± 0.018 cm(-1) for bleomycin-instilled rats. Fractional ventilation gradients were significantly different for control rats compared with LPS-instilled rats only (P = 0.016). The ventilation gradients calculated from control rats showed the expected gravitational relationship, while ventilation gradients calculated from LPS- and bleomycin-instilled rats showed the opposite trend. Histology confirmed that LPS-instilled rats had a significantly elevated alveolar wall thickness, while bleomycin-instilled rats showed signs of substantial fibrosis. Overall, (19) F MRI may be able to detect the effects of pulmonary

  7. The Effect of Combined Therapy of Exercise and Nootropic Agent on Cognitive Function in Focal Cerebral Infarction Rat Model

    Song, Min-Keun; Seon, Hyo-Jeong; Kim, In-Gyu; Han, Jae-Young; Choi, In-Sung; Lee, Sam-Gyu

    2012-01-01

    Objective To investigate the effect of combined therapy of exercise and nootropic agent on cognitive function in a focal cerebral infarction rat model. Method Forty 10-week old male Sprague-Dawley rats were subjected to photothrombotic cerebral infarction of the left parietal lobe. All rats were randomly divided into 4 groups: group A was photothrombotic cerebral infarction rats without any treatment (n=10); group B was photothrombotic cerebral infarction rats with swimming exercise (n=10); g...

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

    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.

  9. Characterization of Diabetic Neuropathy in the Zucker Diabetic Sprague-Dawley Rat: A New Animal Model for Type 2 Diabetes

    Davidson, Eric P; Coppey, Lawrence J.; Amey Holmes; Sergey Lupachyk; Brian L. Dake; Oltman, Christine L.; Richard G. Peterson; Yorek, Mark A.

    2014-01-01

    Recently a new rat model for type 2 diabetes the Zucker diabetic Sprague-Dawley (ZDSD/Pco) was created. In this study we sought to characterize the development of diabetic neuropathy in ZDSD rats using age-matched Sprague-Dawley rats as a control. Rats were examined at 34 weeks of age 12 weeks after the onset of hyperglycemia in ZDSD rats. At this time ZDSD rats were severely insulin resistant with slowing of both motor and sensory nerve conduction velocities. ZDSD rats also had fatty livers,...

  10. Minocycline protects against hepatic ischemia/reperfusion injury in a rat model

    Li, Yining; Li, Tao; Qi, Haizhi; Yuan, Fang

    2014-01-01

    Hepatic ischemia/reperfusion (I/R) injury is a common clinical problem. The present study was conducted to investigate the protective effect and mechanism of minocycline (Mino), a tetracycline with anti-inflammatory and antioxidant properties, on I/R injury of liver in rats. In total, 54 male Sprague-Dawley rats were randomly divided into 3 groups with 18 rats in each: Sham-operated (control group), I/R model (I/R group) and Mino preconditioning groups (Mino group). The rats of the Mino group...

  11. Relationship between core temperature change during recovery and prognosis in classic heat stroke rat models

    Liu, Ya-Nan; Geng, Yan; Fu, Wei; Na PENG; Zheng-tao GU; Su, Lei

    2013-01-01

    Objective To construct classic heat stroke rat models, and observe the changes of body temperature in the recovery period after heat stress to explore its relationship with prognosis. Methods Sixty male SD rats were randomly divided into heat stroke group (HS group, n=50) and control group (C group, n=10). Rats in HS group were exposed to 39℃ heat stress. Core temperature and systolic blood pressure (SBP) of rats were monitored until it reached diagnostic criteria of heat stroke. The core bod...

  12. Evaluation of Lercanidipine in Paclitaxel-Induced Neuropathic Pain Model in Rat: A Preliminary Study

    Lekha Saha; Debasish Hota; Amitava Chakrabarti

    2012-01-01

    Objective. To demonstrate the antinociceptive effect of lercanidipine in paclitaxel-induced neuropathy model in rat. Materials and Methods. A total of 30 rats were divided into five groups of six rats in each group as follows: Gr I: 0.9% NaCl, Gr II: paclitaxel + 0.9% NaCl, Gr III: paclitaxel + lercanidipine 0.5 μg/kg, Gr IV: paclitaxel + lercanidipine 1 μg/kg, and Gr V: paclitaxel + lercanidipine 2.5 μg/kg. Paclitaxel-induced neuropathic pain in rat was produced by single intraperitoneal (i....

  13. MODELLING WORKING AND REFERENCE MEMORY IN RATS: EFFECTS OF SCOPOLAMINE ON DELAYED MATCHING-TO-POSITION

    A model of working and reference memory in rats is described, based on a discrete-trial operant procedure with concurrent spatial matching and nonspatial discrimination components. orking memory was assessed by delivery food to rats for pressing one of two retractable levers afte...

  14. Cognitive impairment in the Tg6590 transgenic rat model of Alzheimer's disease

    Kloskowska, Ewa; Pham, Therese M; Nilsson, Tatjana;

    2010-01-01

    Recently, interest in the rat as an animal model of Alzheimer's disease (AD) has been growing. We have previously described the Tg6590 transgenic rat line expressing the amyloid precursor protein containing the Swedish AD mutation (K670M/N671L) that shows early stages of Abeta deposition...

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

    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.

  16. Candidate hippocampal biomarkers of susceptibility and resilience to stress in a rat model of depression

    Henningsen, Kim; Palmfeldt, Johan; Christiansen, Sofie;

    2012-01-01

    Susceptibility to stress plays a crucial role in the development of psychiatric disorders such as unipolar depression and post-traumatic stress disorder. In the present study the chronic mild stress rat model of depression was used to reveal stress-susceptible and stress-resilient rats. Large-scale...

  17. MRI and morphological observation in C6 glioma model rats and significance

    Objective: To establish stable and reliable rat C6 glioma model, and to perform MRI dynamic observation and pathomorphological observation in model animal brain, and to provide experimental basis for pharmaceutical research on anti-glioma drugs. Methods: The C6 glioma cells were cultured and 20 μL cultural fluid containing 1×106 C6 cells was sterotactically implanted into the left caudate nuclei in 10 male Wistar rats, respectively. The changes in the behavior of the rats after implantation were observed and recorded. MRI dynamic scanning was performed in 10 rats 2, 3 and 4 weeks after implantation and the brain tissues were taken for general and pathological examination when the 10 rats were naturally dead. The survival period of tumor-bearing rats was calculated. Results: 2 weeks after implantation the rats showed decreased activities and food intake, fur lackluster, and conjunctival congestion and so on; 3 weeks later, some rats appeared nerve symptoms such as body twitch, body hemiplegy, body distortion, rotation and so on. All the 10 rats died in 8-30 d. The median survival period of the tumor-bearing rats was 18 d, the average survival period was (18.3±7.3) d. The pathological examination showed that the tumor cells were arranged irregularly closely and karyokinesis was easy to see; tumor vascular tissue proliferation and tumor invasive growth into surrounding normal tissues were found. The expression of glial fibrillary acidic protein (GFAP) was positive in the tumors. Conclusion: A stable animal model of intracranial glioma is successfully established by stereotactic implantation of C6 cells into the rat caudate nucleus. The results of MRI dynamic observation and pathohistological observation on the model animal brain tissue. Can provide experimental basis for selecting the appropriate time window to perform the pharmaceutical research on anti-glioma drugs. (authors)

  18. Histopathologic changes of hypothalamus and pituitary in a rat model of polycystic ovary syndrome

    Jiang Yan; Meng Fan-yu; Hu Zhen-hua; Liu Fang

    2010-01-01

    Objective: To investigate the histopathologic changes of hypothalamus and pituitary in a rat model of polycystic ovary syndrome (PCOS).Methods: Rat model of PCOS was established in 6 immature female SD rats and another 6 immature rats treated with placebo were as control. The tissues of hypothalamus and pituitary were obtained and observed by light microscope and transmission electron microscope.Results: Light microscopy revealed little difference in morphology of neurons in arcuate nucleus or basophilic cells in pituitary between PCOS rats and normal rats. Electron microscopic examination showed that, compared with those in normal rats, GnRH neurons in PCOS rats were larger and fuller, with Golgi complex and mitochondria increased. The mitochondria were small, round and swelling. More high-density secretory granules and bright vesicles were observed in the cytoplasm. The Golgi complex near nucleus in pituitary gonadotropin cell in PCOS rats was fractured and expanded, and there were increased number mitochondria and different sizes of the higher electron density secretory granules in the cytoplasm. Conclusion: The morphological alterations in hypothalamus and pituitary could play a very important role in the development of PCOS.

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

    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.

  20. Neuromodulation attenuates bladder hyperactivity in a rat cystitis model

    Su, Xin; Nickles, Angela; Nelson, Dwight E.

    2013-01-01

    Background We investigated the regulation of urinary bladder function by electrical stimulation of the L6 spinal nerve (SN) using cystometry in normal rats and in rats with cystitis induced by intravesical infusion of dilute acetic acid. Methods In anesthetized rats, a cannula was placed into the bladder dome for saline/acetic acid infusion and intravesical pressure monitoring. Threshold pressure (TP), basal pressure (BP) and inter-contraction interval (ICI) were measured from the bladder pre...

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

    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.

  2. The Dimethylnitrosamine Induced Liver Fibrosis Model in the Rat.

    Chooi, Kum Fai; Kuppan Rajendran, Dinesh Babu; Phang, Siew Siang Gary; Toh, Han Hui Alden

    2016-01-01

    Four to six week old, male Wistar rats were used to produce animal models of liver fibrosis. The process requires four weeks of administration of 10 mg/kg dimethylnitrosamine (DMN), given intraperitoneally for three consecutive days per week. Intraperitoneal injections were performed in the fume hood as DMN is a known hepatoxin and carcinogen. The model has several advantages. Firstly, liver changes can be studied sequentially or at particular stages of interest. Secondly, the stage of liver disease can be monitored by measurement of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzymes. Thirdly, the severity of liver damage at different stages can be confirmed by sacrifice of animals at designated time points, followed by histological examination of Masson's Trichome stained liver tissues. After four weeks of DMN dosing, the typical fibrosis score is 5 to 6 on the Ishak scale. The model can be reproduced consistently and has been widely used to assess the efficacy of potential anti-fibrotic agents. PMID:27340889

  3. Cell culture models using rat primary alveolar type I cells.

    Downs, Charles A; Montgomery, David W; Merkle, Carrie J

    2011-10-01

    There is a lack of cell culture models using primary alveolar type I (AT I) cells. The purpose of this study was to develop cell culture models using rat AT I cells and microvascular endothelial cells from the lung (MVECL). Two types of model systems were developed: single and co-culture systems; additionally a 3-dimensional model system was developed. Pure AT I cell (96.3 ± 2.7%) and MVECL (97.9 ± 1.1%) preparations were used. AT I cell morphology, mitochondrial number and distribution, actin filament arrangement and number of apoptotic cells at confluence, and telomere attrition were characterized. AT I cells maintained their morphometric characteristics through at least population doubling (PD) 35, while demonstrating telomere attrition through at least PD 100. Furthermore, AT I cells maintained the expression of their specific markers, T1α and AQ-5, through PD 42. For the co-cultures, AT I cells were grown on the top and MVECL were grown on the bottom of fibronectin-coated 24-well Transwell Fluroblok™ filter inserts. Neither cell type transmigrated the 1 μm pores. Additionally, AT I cells were grown in a thick layer of Matrigel(®) to create a 3-dimensional model in which primary AT I cells form ring-like structures that resemble an alveolus. The development of these model systems offers the opportunities to investigate AT I cells and their interactions with MVECL in response to pharmacological interventions and in the processes of disease, repair and regeneration. PMID:21624488

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

    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.

  5. A Comparison of Neuroinflammation to Implanted Microelectrodes in Rat and Mouse Models

    Potter-Baker, Kelsey A.; Ravikumar, Madhumitha; Burke, Alan A.; Meador, William D.; Householder, Kyle T.; Buck, Amy C.; Sunil, Smrithi; Stewart, Wade G.; Anna, Jake P.; Tomaszewski, William H.; Capadona, Jeffrey R.

    2014-01-01

    Rat models have emerged as a common tool to study neuroinflammation to intracortical microelectrodes. While a number of studies have attempted to understand the factors resulting in neuroinflammation using rat models, a complete understanding of key mechanistic pathways remains elusive. Transgenic mouse models, however, could facilitate a deeper understanding of mechanistic pathways due to an ease of genetic alteration. Therefore, the goal of the present study is to compare neuroinflammation ...

  6. The 9LLUC/Wistar rat glioma model is not suitable for immunotherapy

    Liping Yang; Jingxiang Zhao; Guihong Zhou; Yunfang Wang; Lusi Li; Hongfeng Yuan; Xue Nan; Lidong Guan; Xuetao Pei

    2012-01-01

    The availability of a well-characterized animal brain tumor model will play an important role in identifying treatments for human brain tumors. Wistar rats bearing 9L glioma cells can develop solid, well-circumcised tumors, and may be a useful animal model for the evaluation of various therapeutic approaches for gliosarcomas. In this study, the 9L/Wistar rat glioma model was produced by intracerebral implantation of 9LLUC glioma cells syngenic to Fischer 344 (F344) rats. Bioluminescence imaging showed that tumors progressively grew from day 7 to day 21 in 9LLUC/F344 rats, and tumor regression was found in some 9LLUC/Wistar rats. Hematoxylin-eosin staining verified that intracranial tumors were gliomas. Immunohistochemistry results demonstrated that no CD4- and CD8-positive cells were found in the syngeneic 9LLUC/F344 model. However, many infiltrating CD4- and CD8-positive cells were observed within the tumors of the 9LLUC/Wistar model. Our data suggests that compared with 9L/F344 rats, 9L glioma Wistar rats may not be suitable for evaluating brain glioma immunotherapies, even though the model induced an immune response and exhibited tumor regression.

  7. 多虑平对心理应激大鼠血浆胃动素与血管活性肠肽水平的影响%Effect of doxepin on levels of plasnm motilin and vasoactive intestinal peptide of psychological stress rats

    吴先哲

    2008-01-01

    Objective To study the effect of doxepin on some gut hormones of psychological stress ratsMethods To stimulate the 6-OHDA.treated rats to attack the experimental rats as social psychological stressor,and to detect the change of levels of plasma motilin(MTL) and vasoactive intestinal peptide(VIP) of experimental rats.Results The level of plasma MTL and VIP of the rats in model group were (318.5±89.37)pg/ml and(65.78±12.10)pg/ml.There were significant difference(P<0.01)between model group and normal group [(223.43+73.05)mg,/mol,(88.27±16.90)me/mol].The level of plasma MTL and VIP of the rats in control group were(267.37±80.33)pg/ml and(77.54±13.36)pg/ml.There were significant difference(P<0.05)between control group and model group. Conclusion Strong psychological stress could influence levels of plasma MTL and VIP of the rats.But Doxepin could adjust the emotional state of psychological stress rats and relieve the effect of psychological stress on levels of plasma MTL and VIP of rats,thus affect gastrointestinal motility.%目的 研究多虑平对心理应激大鼠相关胃肠激素的影响.方法 刺激经6-羟多巴胺预处理的大鼠攻击受试大鼠作为心理应激源,检测受试大鼠血浆胃动素(MTL)、血管活性肠肽(VIP)的改变.结果 模型组大鼠血浆MTL、VIP水平分别为(318.5±89.37)pg/ml和(65.78±12.10)pg/ml,与正常组(223.43±73.05)mg/mol,(88.27±16.90)mg/mol比较均差异有显著性(P<0.01);多虑平组大鼠血浆MTL、VIP水平分别为(267.37±80.33)pg/ml和(77.54±13.36)pg/ml,与模型组比较均差异有显著性(P<0.05).结论 强烈的心理应激可影响大鼠血浆MTL、VIP水平,多虑平可以调节心理应激大鼠的情绪状态,可减轻心理应激对大鼠血浆MTL、VIP水平的影响,从而影响结肠运动.

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

    Mizuno, Makoto; Tomizawa, Atsuyuki; Ohno, Kousaku; Jakubowski, Joseph A.; Sugidachi, Atsuhiro

    2016-01-01

    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. PMID:27128503

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

    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.

  10. Dopaminergic neuron destruction reduces hippocampal serotonin 1A receptor uptake of trans-[18F]Mefway

    The purpose of the present study is to investigate the relationship between dopaminergic neuron destruction and 5-HT system changes in a hemiparkinsonian rat model. We performed PET imaging studies with trans-[18F]Mefway in a hemiparkinsonian model of unilateral 6-hydroxydopamine (6-OHDA) rats. Region-of-interests (ROIs) were drawn in the hippocampus (HP) and cerebellum (CB). HP uptake, the ratios of specific binding to non-specific binding in the HP, and non-displaceable binding potential (BPND) in the HP were compared between 6-OHDA and control rats. As a result, unilateral 6-OHDA-lesioned rats exhibited significant bilateral reduction of HP uptake and trans-[18F]Mefway BPND compared to the intact control group. Therefore, the results demonstrate that destruction of the dopaminergic system causes the reduction of the serotonergic system. - Graphical abstract: Serotonin PET after destruction of dopaminergic system. - Highlights: • The 5-HT system is implicated in mood related-non-motor symptoms of parkinson's disease. • We examine changes of 5-HT1A receptor in a hemiparkinsonian rat model. • The non-displaceable binding potential of HP and were calculated. • The destruction of dopaminergic system causes the reduction of the serotonergic system

  11. Neuroprotection by Exendin-4 Is GLP-1 Receptor Specific but DA D3 Receptor Dependent, Causing Altered BrdU Incorporation in Subventricular Zone and Substantia Nigra

    A. Harkavyi

    2013-01-01

    Full Text Available Glucagon-like peptide-1 receptor (GLP-1R activation by exendin-4 (EX-4 is effective in preclinical models of Parkinson’s disease (PD and appears to promote neurogenesis even in severely lesioned rats. In the present study, we determined the effects of EX-4 on cellular BrdU incorporation in the rat subventricular zone (SVZ and substantia nigra (SN. We also determined the specificity of this effect with the GLP-1R antagonist EX-(9-39 as well as the potential role of dopamine (DA D3 receptors. Rats were administered 6-OHDA and 1 week later given EX-4 alone, with EX-(9-39 or nafadotride (D3 antagonist and BrdU. Seven days later, rats were challenged with apomorphine to evaluate circling. Extracellular DA was measured using striatal microdialysis and subsequently tissue DA measured. Tyrosine hydroxylase and BrdU were verified using immunohistochemistry. Apomorphine circling was reversed by EX-4 in lesioned rats, an effect reduced by EX-4, while both EX-(9-39 and NAF attenuated this. 6-OHDA decreased extracellular and tissue DA, both reversed by EX-4 but again attenuated by EX-(9-39 or NAF. Analysis of BrdU+ cells in the SVZ revealed increases in 6-OHDA-treated rats which were reversed by EX-4 and antagonised by either EX-(9-39 or NAF, while in the SN the opposite profile was seen.

  12. Inducible transgenic rat model for diabetes mellitus based on shRNA-mediated gene knockdown.

    Katarina Kotnik

    Full Text Available The rat is an important animal model in biomedical research, but gene targeting technology is not established for this species. Therefore, we aimed to produce transgenic knockdown rats using shRNA technology and pronuclear microinjection. To this purpose, we employed a tetracycline-inducible shRNA expression system targeting the insulin receptor (IR. Doxycycline (DOX treatment of the resulting transgenic rats led to a dose-dependent and reversible increase in blood glucose caused by ubiquitous inhibition of IR expression and signalling. We could neither detect an interferon response nor disturbances in microRNA processing after DOX treatment excluding toxic effects of shRNA expression. Low dose DOX treatment induced a chronic state of diabetes mellitus. In conclusion, we have developed a technology which allows the specific, inducible, and reversible suppression of any gene of interest in the rat. Our first transgenic rat line generated with this method represents an inducible model for diabetes mellitus.

  13. Transcriptomic alterations induced by Ochratoxin A in rat and human renal proximal tubular in vitro models and comparison to a rat in vivo model.

    Jennings, Paul; Weiland, Christina; Limonciel, Alice; Bloch, Katarzyna M; Radford, Robert; Aschauer, Lydia; McMorrow, Tara; Wilmes, Anja; Pfaller, Walter; Ahr, Hans J; Slattery, Craig; Lock, Edward A; Ryan, Michael P; Ellinger-Ziegelbauer, Heidrun

    2012-04-01

    Ochratoxin A (OTA) is a widely studied compound due to its role in renal toxicity and carcinogenicity. However, there is still no consensus on the exact mechanisms of toxicity or carcinogenicity. In the current study, we analysed the effect of OTA on three human renal proximal tubular models (human primary, RPTEC/TERT1 and HK-2 cells) and two rat renal proximal tubular models (rat primary and NRK-52E cells). Global transcriptomics analysis at two exposure times was performed to generate a set of 756 OTA sensitive genes. This gene set was then compared in more detail across all models and additionally to a rat in vivo renal cortex model. The results demonstrate a well-conserved response across all models. OTA resulted in deregulation of a number of pathways including cytoskeleton, nucleosome regulation, translation, transcription, ubiquitination and cell cycle pathways. Interestingly, the oxidative stress activated Nrf2 pathway was not enriched. These results point to an epigenetic action of OTA, perhaps initiated by actin binding as the actin remodelling gene, advillin was the highest up-regulated in all models. The largest model differences were observed between the human and the rat in vitro models. However, since the human in vitro models were more similar to the rat in vivo model, it is more likely that these differences are model-specific rather than species-specific per se. This study demonstrates the usefulness of in vitro cell culture models combined with transcriptomic analysis for the investigation of mechanisms of toxicity and carcinogenicity. In addition, these results provide further evidence supporting a non-genotoxic mechanism of OTA-induced carcinogenicity. PMID:22124623

  14. Modeling fibrosis using fibroblasts isolated from scarred rat vocal folds.

    Kishimoto, Yo; Kishimoto, Ayami Ohno; Ye, Shuyun; Kendziorski, Christina; Welham, Nathan V

    2016-07-01

    Following injury, pathologically activated vocal fold fibroblasts (VFFs) can engage in disordered extracellular matrix (ECM) remodeling, leading to VF fibrosis and impaired voice function. Given the importance of scar VFFs to phenotypically appropriate in vitro modeling of VF fibrosis, we pursued detailed characterization of scar VFFs obtained from surgically injured rat VF mucosae, compared with those obtained from experimentally naïve, age-matched tissue. Scar VFFs initially exhibited a myofibroblast phenotype characterized by increased proliferation, increased Col1a1 transcription and collagen, type I synthesis, increased Acta2 transcription and α-smooth muscle actin synthesis, and enhanced contractile function. These features were most distinct at passage 1 (P1); we observed a coalescence of the scar and naïve VFF phenotypes at later passages. An empirical Bayes statistical analysis of the P1 cell transcriptome identified 421 genes that were differentially expressed by scar, compared with naïve, VFFs. These genes were primarily associated with the wound response, ECM regulation, and cell proliferation. Follow-up comparison of P1 scar VFFs and their in vivo tissue source showed substantial transcriptomic differences. Finally, P1 scar VFFs responded to treatment with hepatocyte growth factor and transforming growth factor-β3, two biologics with reported therapeutic value. Despite the practical limitations inherent to working with early passage cells, this experimental model is easily implemented in any suitably equipped laboratory and has the potential to improve the applicability of preclinical VF fibrosis research. PMID:27111284

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

    Lorette Noiret

    Full Text Available 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 [Formula: see text], 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.

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

    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. PMID:25371325

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

    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.

  18. Improvement of insulin secretion in rat models of diabetes after ACEI/ARB therapy

    Objective To study the effect of ACEI/ARB therapy on the secretion of insulin and glucagon as well as serum lipid peroxidation marker 8-iso PGF-2α levels in streptozoticin (STZ) induced diabetic rat models.Methods Twenty-four rat models of STZ induced diabetes were prepared (random blood sugar>16.7 mmol/L). Of which, 8 models were fed enalaprial 5mg/kg/d, 8 models were fed losartan 10μg/kg/d and 8 models left unterated. Fasting serum insulin,glucagon (with RIA) and 8-iso PGF-2α (with ELISA) levels were measured in these models and 8 control rats three weeks later. Intravenous glucose tolerance test (IVGTT) were performed in 12 rats (3 animals in each group) six weeks later. Results: Serum levels of insulin in the treated models were higher than those in the non-treated models but without significance (P>0.05). Serum levels of glucagon and 8-iso PGF-2α levels in the treated models were significantly lower than those in the non-treated models (P6 x ) in the treated models. Conclusion: ACEI/ARB treatment could improve the secretion of insulin in rat models of diabetes, which might be beneficial for controlling the progression of the disease. This phenomenon is consistent with the result of clinical study. (authors)

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

    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. PMID:24328701

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

    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.

  1. Comparison of classical heat stroke between conscious and unconscious rat models

    Geng, Yan; Fu, Wei; Liu, Ya-Nan; Na PENG; Yu-mei LEI; Su, Lei

    2013-01-01

    Objective To reproduce conscious and unconscious classical heat stroke(CHS) models in conscious and unconscious rats, and the difference in heat stress response between the two models was investigated. Methods Thirty-two male SD rats were randomly and equally divided into conscious classic heatstroke(C-CHS), unconscious classi cheatstroke(N-CHS), conscious normal control(C-NC) and unconscious normal control(N-NC)groups.Rats of C-CHS and N-CHS groups were put into artificial climate chamber, a...

  2. Paroxetine engenders analgesic effects through inhibition of p38 phosphorylation in a rat migraine model

    Chuanming Wang; Wei Bi; Yanran Liang; Xiuna Jing; Songhua Xiao; Yannan Fang; Qiaoyun Shi; Enxiang Tao

    2012-01-01

    In this study, a model of migraine was established by electrical stimulation of the superior sagittal sinus in rats. These rats were then treated orally with paroxetine at doses of 2.5, 5, or 10 mg/kg per day for 14 days. Following treatment, mechanical withdrawal thresholds were significantly higher, extracellular concentrations of 5-hydroxytryptamine in the periaqueductal grey matter and nucleus reticularis gigantocellularis were higher, and the expression of phosphorylated p38 in the trigeminal nucleus caudalis was lower. Our experimental findings suggest that paroxetine has analgesic effects in a rat migraine model, which are mediated by inhibition of p38 phosphorylation.

  3. Improvements of Surgical Technique in Establishment of Rat Orthotopic Pulmonary Transplantation Model Using Cuffs

    2006-01-01

    In order to establish more simple and effective rat orthotopic lung transplantation models, 20 rats were divided into donor and recipient groups. Rat lung transplantation models were established by using improved cuff technique. All the 10 operations were accomplished successfully.The mean operative time of recipients was 45±4 min. The survival time was over 30 days after lung transplantation. The checks of X-ray were almost ncrmal. There was no significant difference in the blood gas analysis before and after clipping the right hilum (P>. 05). This method is more simple,applicable and requires less time.

  4. Transgenic rat model of childhood-onset dermatitis by overexpressing telomerase reverse transcriptase (TERT).

    Kaneko, Ryosuke; Sato, Atsuko; Hamada, Shun; Yagi, Takeshi; Ohsawa, Ichiro; Ohtsuki, Mamitaro; Kobayashi, Eiji; Hirabayashi, Masumi; Murakami, Takashi

    2016-08-01

    Childhood-onset dermatitis is one of the most common skin disorders in children. Although various mouse models that mirror aspects of dermatitis have become available, there is still a need for an animal model that develops dermatitis in childhood and is more suitable for performing tissue transplantation experiments. There is emerging evidence that peripheral blood T lymphocytes from patients with dermatitis have significantly increased telomerase activity. Here, we developed telomerase reverse transcriptase (TERT)-expressing transgenic (Tg) rats that spontaneously developed eczematous skin inflammation in childhood. Newborn TERT-Tg rats developed visible dermatitis in 56 % of cases, and the skin lesions microscopically showed spongiosis and acanthosis with infiltration of lymphocytes, eosinophils and mast cells. TERT-Tg rats with dermatitis exhibited increased CD4 (2.5-fold) and CD8 (fivefold) T cell numbers compared with dermatitis-free TERT-Tg rats. Stronger TERT activity was observed in the peripheral lymphocytes of dermatitis-positive TERT-Tg rats than those of dermatitis-free TERT-Tg rats. RT-PCR analysis revealed that IL-4 was markedly elevated in the spleen of dermatitis-positive TERT-Tg rats, and that interferon-gamma was increased in the dermatitis lesions. Moreover, skin grafting of TERT-Tg rats with dermatitis onto T cell-deficient nude rats demonstrated that the inflamed skin lesions could not be maintained. Taken together, the results suggest that TERT activation in T lymphocytes is one of the potential predisposing factors for dermatitis. Moreover, our results demonstrated that the TERT-Tg rats mirror aspects of human childhood-onset dermatitis and that these animals represent a potential animal model system for studying childhood-onset dermatitis. PMID:26885830

  5. Lung and Intestine: A Specific Link in an Ulcerative Colitis Rat Model

    Yuan Liu; Xin-Yue Wang; Xue Yang; Shan Jing; Li Zhu; Si-Hua Gao

    2013-01-01

    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 ...

  6. Visual functional effects of constant blue light in a retinal degenerate rat model

    Thomas, BB; Seiler, MJ; Aramant, RB; Samant, D; Qiu, G; Vyas, N; Arai, S.; Chen, Z.; Sadda, SR

    2007-01-01

    Retinal degenerative conditions increase susceptibility to light damage, but rapid retinal degeneration (RD) models show less susceptibility to cyclic dim light. We investigated whether constant blue light (BL) exposure can eliminate the residual visual responses in a comparatively rapid RD rat model. Pigmented rhodopsin mutant S334ter line-3 rat pups (21 days old) were exposed for 5-6 consecutive days to constant BL. Visual behavior was evaluated with an optokinetic head tracking apparatus. ...

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

    Salvatore eMagara; Sarah eHolst; Stina eLundberg; Erika eRoman; Maria eLindskog

    2015-01-01

    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 ...

  8. Pretreatment with Darbepoetin Attenuates Renal Injury in a Rat Model of Cisplatin-Induced Nephrotoxicity

    Choi, Dae Eun; Jeong, Jin Young; Lim, Beom Jin; Lee, Kang Wook; Shin, Young-Tai; Na, Ki-Ryang

    2009-01-01

    Background/Aims Darbepoetin alfa (DPO) exhibits comparable renoprotective effects to erythropoietin (EPO) in several animal models of acute renal injury. We examined whether DPO also attenuated renal injury in a rat model of cisplatin nephrotoxicity. Methods Male Spague-Dawley rats were divided into four groups: untreated, DPO-treated, cisplatin-injected, and DPO-treated cisplatin-injected. DPO pretreatment was conducted 24 hours after and just before cisplatin administration. Ninety-six hour...

  9. Extended duration local anesthetic agent in a rat paw model.

    Ickowicz, D E; Golovanevski, L; Domb, A J; Weiniger, C F

    2014-07-01

    Encapsulated local anesthetics extend postoperative analgesic effect following site-directed nerve injection; potentially reducing postoperative complications. Our study aim was to investigate efficacy of our improved extended duration formulation - 15% bupivacaine in poly(DL-lactic acid co castor oil) 3:7 synthesized by ring opening polymerization. In vitro, around 70% of bupivacaine was released from the p(DLLA-CO) 3:7 after 10 days. A single injection of the optimal formulation of 15% bupivacaine-polymer or plain (0.5%) bupivacaine (control), was injected via a 22G needle beside the sciatic nerve of Sprague-Dawley rats under anesthesia; followed (in some animals) by a 1cm longitudinal incision through the skin and fascia of the paw area. Behavioral tests for sensory and motor block assessment were done using Hargreave's hot plate score, von Frey filaments and rearing count. The 15% bupivacaine formulation significantly prolonged sensory block duration up to at least 48 h. Following surgery, motor block was observed for 48 h following administration of bupivacaine-polymer formulation and rearing was reduced (returning to baseline after 48 h). No significant differences in mechanical nociceptive response were observed. The optimized bupivacaine-polymer formulation prolonged duration of local anesthesia effect in our animal model up to at least 48 h. PMID:24726301

  10. The Gene Expression Profile of D-galactose Induced Aging Model Rat Using cDNA Microarray

    Li Min(李珉); Wang Gang; Zhang Wei; Wang Miqu; Zhang Yizheng

    2004-01-01

    In order to study the molecular mechanism of D-galactose induced aging model, cDNA microarray is used to analyze gene expression profiles of both normal and D-galactose induced aging model rats. D-galactose induced aging model rats are injected with D-galactose, while normal rats are injected with physiological saline as control. After 7 weeks, the two groups of rats are killed simultaneously. Their livers are harvested for genome-wide expression analysis. D-galactose treated rats showed changes in gene expression associated with increase or decrease in xenobiotic metabolism, protein metabolism and energy metabolism.

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

    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

  12. An immunohistochemical study of the sciatic nerve in a rat knee immobilization model

    Yoshida, Shinya; Matsuzaki, Taro; Hoso, Masahiro

    2016-01-01

    [Purpose] This study was performed to immunohistochemically evaluate changes in the periphery of the sciatic nerve in a rat model of knee immobilization, and to assess the effects of range of motion exercise. [Subjects and Methods] Twenty-one male rats were divided randomly into three groups: control (C), immobilized (I), and exercise (E group). Rats in the I and E groups had the right knee joint immobilized for 2 weeks. In the E group, range of motion exercise was also performed. After the experimental period, the periphery of the sciatic nerve was immunohistochemically observed. [Results] Immunohistochemical staining revealed that the myelin sheath and the perineurium in all groups were laminin positive. In the C and E groups, all rats showed normal staining. In contrast, 4 rats in the I group exhibited weak labeling. [Conclusion] Our results suggest that immobilization alters the perineurium at a molecular level and the range of motion exercise is essential for maintaining the environment of the perineurium.

  13. Transplantation of microencapsulated human retinal pigment epithelial cells in Parkinsonian rats%微囊化人视网膜色素上皮细胞移植治疗帕金森病的实验研究

    李锐; 宗伟; 郭民侠; 蒋宏伟

    2009-01-01

    目的 观察微囊化人视网膜色素上皮(RPE)细胞移植治疗帕金森病(PD)大鼠的疗效. 方法 采用机械分离法和酶消化法原代培养人RPE细胞,传代后用高压静电微胶囊成型装置制作海藻酸钠-多聚赖氨酸-海藻酸钠微囊化细胞,将其立体定向移植人6-羟基多巴胺(6-OHDA)所致的PD模型大鼠的右侧纹状体.实验分为模型组、裸细胞(RPE)组、空囊对照(APA)组以及微囊化细胞(APA-RPE)组.检测各组大鼠移植前后阿朴吗啡诱导的旋转行为变化和移植后8周纹状体中多巴胺(DA)的含量. 结果 APA-RPE组大鼠在移植后4周阿朴吗啡诱发的旋转次数[(6.25±1.04)r/min]开始减少,与移植前[(12.88±7.34)r/min]相比减少幅度为51.48%,至第8周[(5.87±2.03)r/min]减少更加明显,减少幅度为54.43%,差异均有统计学意义(P<0.05);与模型组[(108.14±1.89)mol/L]比较,APA-RPE组移植后8周[(342.63±28.32)mol/L]大鼠纹状体DA含量明显增加,差异有统计学意义(P<0.05),而RPE组和APA组未见明显变化. 结论 微囊化人RPE细胞对PD大鼠模型有治疗作用,可作为一种前景良好的治疗PD的方法 进一步研究.%Objective To observe the therapeutic effect of microencapsulated human retinal pigment epithelial (RPE) cell transplantation into the striatum in a rat model of Parkinson' disease (PD). Methods Cultured RPE cells were microencapsulated by alginate-polylysine-alginate (APA) using a high voltage electrostatic system. The Parkinsonian rats were divided into 4 groups, namely the model group, RPE group, APA group and RPE-APA group, and in the latter 3 groups, RPE cells, empty APA microcapsules and APA-capsulated RPE cells, respectively, were transplanted into the right striatum of the rats via stereotactic surgery. After the transplantation, the changes in apomorphine-induced rotation of the rats were investigated and the striatum DA contents were measured with high-performance liquid chromatography with

  14. Assessment of multislice CT to quantify pulmonary emphysema function and physiology in a rat model

    Cao, Minsong; Stantz, Keith M.; Liang, Yun; Krishnamurthi, Ganapathy; Presson, Robert G., Jr.

    2005-04-01

    Purpose: The purpose of this study is to evaluate multi-slice computed tomography technology to quantify functional and physiologic changes in rats with pulmonary emphysema. Method: Seven rats were scanned using a 16-slice CT (Philips MX8000 IDT) before and after artificial inducement of emphysema. Functional parameters i.e. lung volumes were measured by non-contrast spiral scan during forced breath-hold at inspiration and expiration followed by image segmentation based on attenuation threshold. Dynamic CT imaging was performed immediately following the contrast injection to estimate physiology changes. Pulmonary perfusion, fractional blood volume, and mean transit times (MTTs) were estimated by fitting the time-density curves of contrast material using a compartmental model. Results: The preliminary results indicated that the lung volumes of emphysema rats increased by 3.52+/-1.70mL (pemphysema rats decreased by 91.76+/-68.11HU (pemphysema rats were 0.25+/-0.04ml/s/ml and 0.32+/-0.09ml/s/ml respectively. The fractional blood volumes for normal and emphysema rats were 0.21+/-0.04 and 0.15+/-0.02. There was a trend toward faster MTTs for emphysema rats (0.42+/-0.08s) than normal rats (0.89+/-0.19s) with ppulmonary emphysema appears promising for small animals.

  15. Rat as a model for direct pulp capping research

    Orhan, Ekim Onur

    2013-01-01

    The aim of this review is to evaluate the suitability of rat teeth in preclinical evaluation of medical materials for direct pulp capping. The international standard states clearly that only non-rodent mammals are suitable species for animal research in dentistry. However, in the past halve of the century many research have been published using rat teeth in order to evaluate direct pulp capping, pulpotomies and tissue reactions after pulp exposure. Numerous studies showed that the healing of ...

  16. Experimental model of multidirectional disc hernia in rats

    LaTorre, A.; Albareda, J.; Castiella, T.; Lasierra, J. M.; Seral, F.

    1998-01-01

    We have carried out an experimental investigation of lesions of the intervertebral disc produced by flexion, lateral bending and rotational forces in an attempt to produce disc herniations. Adult Wistar rats were divided into 4 groups: control and posterior, lateral and rotational herniation. There were 10 rats in each group. The tail between the 5th and 8th vertebral segments was used. A Kirschner wire was inserted into each of 2 adjacent vertebrae and the movement pr...

  17. Evaluation of In Vivo Wound Healing Activity of Bacopa monniera on Different Wound Model in Rats

    Murthy, S; Gautam, M. K.; Shalini Goel; V Purohit; SHARMA, H; Goel, R.K.

    2013-01-01

    Wound healing effects of 50% ethanol extract of dried whole plant of Bacopa monniera (BME) was studied on wound models in rats. BME (25 mg/kg) was administered orally, once daily for 10 days (incision and dead space wound models) or for 21 days or more (excision wound model) in rats. BME was studied for its in vitro antimicrobial and in vivo wound breaking strength, WBS (incision model), rate of contraction, period of epithelization, histology of skin (excision model), granulation tissue free...

  18. Quantitative MR application in depression model of rats: a preliminary study

    Wei Wang; Wenxun Li; Fang Fang; Hao Lei; Xiaoping Yin; Jianpin Qi; Baiseng Wang; Chengyuan Wang

    2005-01-01

    Objective: To investigate findings and value of quantitative MR in depression model of rats. Methods: Twenty male SD rats were divided into model group and control group randomly (10 rats in each group). The depression model of rats was erected by separation and chronic unpredictable stress. The behavior of rat was detected by open-field test and sucrose consumption. The MR images of brain tissues were produced in vivo rats with T2-and diffusion-weighted imaging. The changes of body weight and behavior score and thevalues of T2 and ADC of ROIs were compared between the two groups. Histological verification of hippocampal neuron damage was alsoperformed under ultramicrosopy. Results: Compared with the control group, T2 values in hippocampus prolonged 5.5 % ( P < 0.05),ADC values in hippocampus and in temporal lobe cortex decreased 11.7 % and 10.9% (P < 0.01)respectively in the model group. Histo-logic data confirmed severe neuronal damage in the hippocampus of the model group. Conclusion: This study capitalized on diffusion-weighted imaging as a sensitive technique for the identification of neuronal damage in depression and it provides an experimental evidence ofMRI in depression investigation and clinical application.

  19. Effect of lactulose on establishment of a rat non-alcoholic steatohepatitis model

    Jian-Gao Fan; Zheng-Jie Xu; Guo-Liang Wang

    2005-01-01

    AIM: To explore the relationship between changes of intestinal environment and pathogenesis of non-alcoholic steatohepatitis (NASH).METHODS: Forty-two Sprague-Dawley rats were randomly divided into model group (n = 24), treatment group (n = 12),and control group (n = 6). The rats of model and treatment groups were given high-fat diet, and those of the control group were given normal diet. Furthermore, the rats of treatment group were given lactulose after 8 wk of highfat diet. Twelve rats of the model group were killed at 8 wk of high-fat diet. At the 16 wk the rats of treatment group,control group, and the rest of the model group were killed.The serum levels of aminotransferase were measured and the histology of livers was observed by H&E staining.RESULTS: The livers of rats presented the pathological features of steatohepatitis with higher serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the model group after 16 wk. Compared to the model group, the serum levels of ALT and AST in treatment group decreased significantly and were close to the normal group, and the hepatic inflammation scores also decreased markedly than those in the model group after 16 wk (5.83±2.02 vs 3.63±0.64, P<0.05), but were still higher than those in the model group after 8 wk (3.63±0.64 vs 1.98±0.90, P<0.05). However, the degree of hepatic steatosis had no changes in treatment group compared to the model group after 16 wk.CONCLUSION: Lactulose could ameliorate the hepatic inflammation of rats with steatohepatitis induced by fatrich diet, but could not completely prevent the development of steatohepatitis. Tt is suggested that intestinal environmental changes such as intestinal bacteria overgrowth, are one of the important factors in the pathogenesis of NASH.

  20. Experimental models of small intestinal transplantation in rats: orthotopic versus heterotopic model.

    Nakao A

    2002-04-01

    Full Text Available Two kinds of surgical models of small intestinal transplantation (SITx in rats, namely heterotopic (HIT and orthotopic transplantion (OIT, have been reviewed. In OIT, the small intestine of the recipient is removed and the transplanted intestine replaces it in continuity. On the other hand, in the HIT model, the small intestinal grafts are rendered dysfunctional without alimentary tract continuity. Histological evidence showed that acute rejection appeared earlier in HIT as compared to OIT. Hyperplasia and hypertrophy of the muscularis externa produced in the chronic rejection process were more pronounced in HIT allografts. The HIT grafts showed severe mucosal atrophy due to the lack of intraluminal trophic factors, because oral feedings can stimulate tropic hormones for mucosal growth, and provide nutrients for enterocytes. Intestinal permeability was consistently higher after HIT than after OIT. The HIT grafts demonstrated less contractility and less response to chemical stimulation than did OIT grafts. The OIT models are advantageous in studies of intraluminal nutrients, and intestinal secretions in these models might modulate the intestinal immune status and possibly delay rejection. The superior intestinal barrier function and the delayed onset of rejection in OIT rats suggest that nutrients and other factors in the succus entericus are important for the maintenance of intestinal graft function.

  1. Effects of Electroacupuncture at Auricular Concha Region on the Depressive Status of Unpredictable Chronic Mild Stress Rat Models

    Ru-Peng Liu; Ji-Liang Fang; Pei-Jing Rong; Yufeng Zhao; Hong Meng; Hui Ben; Liang Li; Zhan-Xia Huang; Xia Li; Ying-Ge Ma; Bing Zhu

    2013-01-01

    To explore new noninvasive treatment options for depression, this study investigated the effects of electroacupuncture (EA) at the auricular concha region (ACR) of depression rat models. Depression in rats was induced by unpredictable chronic mild stress (UCMS) combined with isolation for 21 days. Eighty male Wistar rats were randomly assigned into four groups: normal, UCMS alone, UCMS with EA-ACR treatment, and UCMS with EA-ear-tip treatment. Rats under inhaled anesthesia were treated once d...

  2. The effect of radiotherapy on rat pulmonary tumor model with PET/CT

    Objective: The aim of this study was to understand the role of PET/CT in monitoring the therapeutic effect of radiotherapy (RT) on lung cancer with Wistar rats. Methods: Thirty Wistar in-bred strain rats (6-8 weeks, weighed 180-280 g, female, ordinary) were made into Lewis pulmonary tumor model rats. 18F-fluorodeoxyglucose (FDG) PET/CT was performed when tumor reached 1.5-2.0 cm in greatest diameter (4-6 weeks) as a baseline. In order to get the optimal time point of PET/CT for monitoring RT effect in rat cancer model, PET/CT was performed at the 3rd day, 1st, 2n'd, 3rd, and 4th week after giving single dose of 5 Gy to each rat. Standardized uptake values (SUV) from FDG PET were measured and rats were sacrificed at different time point for validation. Besides, the expressions of glucose transport1 (Glut1) in tumor tissue were studied using immunohistochemistry. The level of tumor cell apoptosis, degradation, and necrosis were observed. SPSS 11.0 software was used for data analyses. Results: A negative correlation of SUV uptake and time after RT and negative correlation of Glut1 expression and time after RT were observed in rat tumors, respectively. Positive correlation of SUV uptake and Glut1 expression in rat tumors was observed (Spearman rank correlation test, rs = 0.97, P rd day and 0.18 ± 0.10 at the 4th week after RT (F=15.126, Prd day and 0. 1320 ± 0.04 at the 4th week after RT. The amounts of tumor cell apoptosis, degradation, and necrosis increased with time after RT. Conclusion: Though FDG PET could monitor the therapeutic effect at the 3rd day after giving single dose of RT to rat lung tumor model, the optimal time was the the 4th week after treatment. (authors)

  3. [Metabolic therapy of nephrolithiasis in two different rat models of kidney disease].

    Trashkov, A P; Vasiliev, A G; Kovalenko, A L; Tagirov, N S

    2015-01-01

    108 albino male rats were used in two experimental rat models reproducing urolithiasis for the assessment of metabolic drug medicine Remaxol nephroprotective effect upon the development of this disease. "Ethyleneglycol" model consisted of adding 1% ethylene glycol solution in drinking water for 37 days and "fructose-induced" one--of adding 10% fructose solution in drinking water for the same period. Therapy included a 10-day course of daily i.v. injections of Remaxol (14 ml/kg). Both experimental models were successful in producing urolithiasis with considerable disturbances in the structure and functioning of kidneys up to revealing microconcrement formation. The "ethyleneglycol" model proved to cause maximum changes while the "Fructose-induced" model--only moderate ones. Metabolic correction of these changes was successful in nephroprotection effectively normalizing kidney functions and the total protein concentration, eliminating hyperglycemia and reducing creatinine and urea blood plasma concentration in both rat experimental models. PMID:26036006

  4. Effects of Panax notoginseng saponins in a rat model of Alzheimer's disease

    Zhenguo Zhong; Zeqiang Qu; Yunping Bao; Naiping Wang; Fengfen Zhang; Wenyan Zhang

    2008-01-01

    BACKGROUND: Modern pharmacological studies have demonstrated that Panax notoginseng saponins (PNS) can ameliorate and protect from neuropathological impairment. Whether PNS can improve the abnormality in memory and behavior of rats with Alzheimer’s disease (AD) remains unclear.OBJECTIVE: Based on a Morris water maze test, this study aimed to measure improvements of spatial learning and memory by PNS in a rat model of AD, and to compare effects with huperzine A.DESIGN: A completely randomized grouping design, controlled animal experiment. SETTING: Center of Research & Development of New Drugs, Guangxi Traditional Chinese Medical University.MATERIALS: Ninety healthy Wistar rats of both genders, 15-month-old (n =75) and 3-month-old rats as young controls (n =15), were used for this study. The study was performed in accordance with animal ethics guidelines for the use and care of animals. PNS was provided by Weihe Pharmaceutical Co., Ltd (permission No. Z53021485, Yuxi, Yunan Province, China). Morris water maze equipment was provided by the Institute of Physiology, Chinese Academy of Science.METHODS: This study was performed at the Center of Research & Development of New Drugs, Guangxi Traditional Chinese Medical University from June 2003 to April 2005. Of the included rats, 15 healthy aged rats were randomly chosen as aged controls, and the remaining 60 aged rats were randomly divided into 4 groups with 15 rats in each: model group, PNS high- and low-dose groups, and an huperzine A group. Rats in the model group and the 3 treated groups were treated with intraperitoneal infusion of 9.6 g/L D-galactose (5 mL/kg) every day for 6 weeks successively to induce a subacute aging model. During week 7, animals received 1 μL ibotenic acid (5 g/L) bilaterally into the nucleus basalis of Meynert to create a rat model of AD. The young and old rat controls received, in parallel, a corresponding volume of saline. Two weeks later, rats in the PNS high- and low-dose groups were

  5. Streptozotocin induced diabetes as a model of phrenic nerve neuropathy in rats.

    Rodrigues Filho, Omar Andrade; Fazan, Valéria Paula Sassoli

    2006-03-15

    Phrenic neuropathies are increasingly recognized in peripheral neuropathies but reports on experimental models of the phrenic nerves diabetic neuropathy are scanty. In the present study, we investigated the phrenic nerve neuropathy, due to experimental diabetes induced by streptozotocin (STZ) and the evolution of this neuropathy in diabetic rats treated with insulin. Proximal and distal segments of the left and right phrenic nerves were morphologically and morphometrically evaluated, from rats rendered diabetic for 12 weeks, by injection of STZ. Control rats received vehicle. Treated rats received a single subcutaneous injection of insulin on a daily basis. The nerves were prepared for light microcopy study by means of conventional techniques. Morphometry was carried out with the aid of computer software. The phrenic nerves of diabetic rats showed smaller myelinated axon diameters compared to controls. The g ratio was significantly smaller for myelinated fibers from diabetic rats compared to controls. Insulin treatment prevented these alterations. Histograms of size distribution for myelinated fibers and axons from control rats were bimodal. For diabetic animals, the myelinated fiber histogram was bimodal while the axon distribution turned to be unimodal. Insulin treatment also prevented these alterations. Our results confirm the phrenic nerve neuropathy in this experimental model of diabetes and suggest that conventional insulin treatment was able to prevent and/or correct the myelinated axon commitment by diabetes. PMID:16125783

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

    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.

  7. A Rat Model of Autologous Oral Mucosal Epithelial Transplantation for Corneal Limbal Stem Cell Failure

    Weihua Li; Qiaoli Li; Wencong Wang; Kaijing Li; Shiqi Ling; Yuanzhe Yang; Lingyi Liang

    2014-01-01

    Purpose:.To establish an animal model of autologous oral mucosa grafting for limbal stem cell deficiency. Methods:.The study was carried from August to October 2012. Fourteen SD rats were randomly and evenly allocated to study group A and control group B. Limbal stem cell defi-ciency was established by alkali burn in the right eye of each rat in both groups. Rats in group A received autologous oral mucosa strip transplantation following the chemical burn. Rats in group B did not receive surgery after the chemical burn. Topical antibiotics and dexamethasone were used in all rats. Corneal clarity,.corneal fluorescein staining,.oral mucosal graft survival, and complications at postoperative days 1,3,7, 14 were observed. Results:.The oral mucosa strip graft was detached in one rat in group A. Reepithelialization was observed starting from the graft position and was completed within 14 days in the re-maining 6 eyes in group A. However, persistent corneal ep-ithelium defect was observed in all eyes in group B, among which corneal melting and perforation was observed in 2 eyes and corneal opacification with neovascularization was ob-served in the remaining 5 eyes. Conclusion:.Autologous oral mucosa strip grafting for limbal stem cell deficiency can be achieved by a rat model following chemical burn. The fate of the transplanted oral mucosal ep-ithelial cells warrants further study. (Eye Science 2014; 29:1-5).

  8. Rats

    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.

  9. Pharmacokinetic-pharmacodynamic modeling of diclofenac in normal and Freund's complete adjuvant-induced arthritic rats

    Jing ZHANG; Pei LI; Hai-fang GUO; Li LIU; Xiao-dong LIU

    2012-01-01

    Aim:To characterize pharmacokinetic-pharmacodynamic modeling of diclofenac in Freund's complete adjuvant (FCA)-induced arthritic rats using prostaglandin E2 (PGE2) as a biomarker.Methods:The pharmacokinetics of diclofenac was investigated using 20-day-old arthritic rats.PGE2 level in the rats was measured using an enzyme immunoassay.A pharmacokinetic-pharmacodynamic (PK-PD) model was developed to illustrate the relationship between the plasma concentration of diclofenac and the inhibition of PGE2 production.The inhibition of diclofenac on lipopolysaccharide (LPS)-induced PGE2 production in blood cells was investigated in vitro.Results:Similar pharmacokinetic behavior of diclofenac was found both in normal and FCA-induced arthritic rats.Diclofenac significantly decreased the plasma levels of PGE2 in both normal and arthritic rats.The inhibitory effect on PGE2 levels in the plasma was in proportion to the plasma concentration of diclofenac.No delay in the onset of inhibition was observed,suggesting that the effect compartment was located in the central compartment.An inhibitory effect sigmoid/max model was selected to characterize the relationship between the plasma concentration of diclofenac and the inhibition of PGE2 production in vivo.The /max model was also used to illustrate the inhibition of diclofenac on LPS-induced PGE2 production in blood cells in vitro.Conclusion:Arthritis induced by FCA does not alter the pharmacokinetic behaviors of diclofenac in rats,but the pharmacodynamics of diclofenac is slightly affected.A PK-PD model characterizing an inhibitory effect sigmoid /max can be used to fit the relationship between the plasma PGE2 and diclofenac levels in both normal rats and FCA-induced arthritic rats.

  10. Characterization of SV-40 Tag rats as a model to study prostate cancer

    Eltoum Isam A

    2009-01-01

    Full Text Available Abstract Background Prostate cancer is the second most frequently diagnosed cancer in men. Animal models that closely mimic clinical disease in humans are invaluable tools in the fight against prostate cancer. Recently, a Simian Virus-40 T-antigen (SV-40 Tag targeted probasin promoter rat model was developed. This model, however, has not been extensively characterized; hence we have investigated the ontogeny of prostate cancer and determined the role of sex steroid receptor and insulin-like growth factor-1 (IGF-1 signaling proteins in the novel SV-40 Tag rat. Methods The SV-40 Tag rat was histopathologically characterized for time to tumor development, incidence and multiplicity and in the ventral, dorsal, lateral and anterior lobes of the prostate. Immunoassay techniques were employed to measure cell proliferation, apoptosis, and sex steroid receptor and growth factor signaling-related proteins. Steroid hormone concentrations were measured via coated well enzyme linked immunosorbent assay (ELISA kits. Results Prostatic intraepithelial neoplasia (PIN and well-differentiated prostate cancer developed as early as 2 and 10 weeks of age, respectively in the ventral prostate (VP followed by in the dorsolateral (DLP. At 8 weeks of age, testosterone and dihydrotestosterone (DHT concentrations in SV-40 Tag rats were increased when compared to non-transgenic rats. High cell proliferation and apoptotic indices were found in VP and DLP of transgenic rats. Furthermore, we observed increased protein expression of androgen receptor, IGF-1, IGF-1 receptor, and extracellular signal-regulated kinases in the prostates of SV-40 Tag rats. Conclusion The rapid development of PIN and prostate cancer in conjunction with the large prostate size makes the SV-40 Tag rat a useful model for studying prostate cancer. This study provides evidence of the role of sex steroid and growth factor proteins in prostate cancer development and defines appropriate windows of

  11. Characterization of SV-40 Tag rats as a model to study prostate cancer

    Prostate cancer is the second most frequently diagnosed cancer in men. Animal models that closely mimic clinical disease in humans are invaluable tools in the fight against prostate cancer. Recently, a Simian Virus-40 T-antigen (SV-40 Tag) targeted probasin promoter rat model was developed. This model, however, has not been extensively characterized; hence we have investigated the ontogeny of prostate cancer and determined the role of sex steroid receptor and insulin-like growth factor-1 (IGF-1) signaling proteins in the novel SV-40 Tag rat. The SV-40 Tag rat was histopathologically characterized for time to tumor development, incidence and multiplicity and in the ventral, dorsal, lateral and anterior lobes of the prostate. Immunoassay techniques were employed to measure cell proliferation, apoptosis, and sex steroid receptor and growth factor signaling-related proteins. Steroid hormone concentrations were measured via coated well enzyme linked immunosorbent assay (ELISA) kits. Prostatic intraepithelial neoplasia (PIN) and well-differentiated prostate cancer developed as early as 2 and 10 weeks of age, respectively in the ventral prostate (VP) followed by in the dorsolateral (DLP). At 8 weeks of age, testosterone and dihydrotestosterone (DHT) concentrations in SV-40 Tag rats were increased when compared to non-transgenic rats. High cell proliferation and apoptotic indices were found in VP and DLP of transgenic rats. Furthermore, we observed increased protein expression of androgen receptor, IGF-1, IGF-1 receptor, and extracellular signal-regulated kinases in the prostates of SV-40 Tag rats. The rapid development of PIN and prostate cancer in conjunction with the large prostate size makes the SV-40 Tag rat a useful model for studying prostate cancer. This study provides evidence of the role of sex steroid and growth factor proteins in prostate cancer development and defines appropriate windows of opportunity for preclinical trials and aids in the rational design of

  12. Effect of tramadol on immune responses and nociceptive thresholds in a rat model of incisional pain*

    Liu, Yong-Min; Zhu, Sheng-mei; Wang, Kui-Rong; Feng, Zhi-ying; Chen, Qing-lian

    2008-01-01

    Objective: To evaluate the effects of tramadol on the proinflammatory responses in a rat model of incisional pain by investigating its effects on nociceptive thresholds and serum interleukin-6 (IL-6) and IL-2 levels. Methods: Forty-two male Sprague-Dawley (SD) rats scheduled for plantar incision were randomly divided into 7 groups (n=6 in each group). Rats in Group 1 receiving general anesthesia with no incision were served as control; At 30 min before skin incision, Groups 2~5 were given 5 m...

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

    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. A total of 30 Sprague-Dawley rats were studied to form five groups with 6 rats each. Korea beechwood creosote was supplemented into three test groups with 0.03 g/kg, 0.07 g/kg and 0.1 g/kg body weight/day without antibiotic support, along with a positive control of Apramycin sulph...

  14. Green and Black Cardamom in a Diet-Induced Rat Model of Metabolic Syndrome

    Maharshi Bhaswant; Hemant Poudyal; Mathai, Michael L.; Ward, Leigh C.; Peter Mouatt; Lindsay Brown

    2015-01-01

    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 ...

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

    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.

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

    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. Cardioprotective Effect of the Compound Yangshen Granule in Rat Models with Acute Myocardial Infarction

    Xie Ming

    2012-01-01

    Full Text Available The protective effect of Compound Yangshen Granules was observed in myocardial infarction rat model. Rats were randomly divided into 6 groups: the model group, the control group (sham operated, the positive drug group, and small, medium, and large dosage of the Yangshen granule groups, respectively. The rats in the 3 Yangshen granule groups were orally administrated with 0.7 g/kg, 1.4 g/kg, and 2.8 g/kg for 7 consecutive days, whereas the rats of the positive drug group treated with 0.14 g/kg of Danshen Dropping Pills, and rats in the control and model groups orally administrated with saline. The rat model of acute myocardial infarction was established with ligation of coronary artery. Electrocardiograms at different time points, the blood rheology, myocardial enzymes, infarct size, and myocardial morphologic changes were measured. The results demonstrated that the granules could improve blood rheology, decrease st-segment of electrocardiograms and the activities of LDH and CK in serum, reduce myocardial infarction size, and alleviate myocardial histopathologic changes. In addition, the effect of the granules depended on the dose administrated orally. The results suggest that the Yangshen granules could produce cardioprotection effect and have potential benefits in the prevention of ischemic heart disease.

  18. Fractal analysis of alveolarization in hyperoxia-induced rat models of bronchopulmonary dysplasia.

    Porzionato, Andrea; Guidolin, Diego; Macchi, Veronica; Sarasin, Gloria; Grisafi, Davide; Tortorella, Cinzia; Dedja, Arben; Zaramella, Patrizia; De Caro, Raffaele

    2016-04-01

    No papers are available about potentiality of fractal analysis in quantitative assessment of alveolarization in bronchopulmonary dysplasia (BPD). Thus, we here performed a comparative analysis between fractal [fractal dimension (D) and lacunarity] and stereological [mean linear intercept (Lm), total volume of alveolar air spaces, total number of alveoli, mean alveolar volume, total volume and surface area of alveolar septa, and mean alveolar septal thickness] parameters in experimental hyperoxia-induced models of BPD. At birth, rats were distributed between the following groups: 1) rats raised in ambient air for 2 wk; 2) rats exposed to 60% oxygen for 2 wk; 3) rats raised in normoxia for 6 wk; and 4) rats exposed to 60% hyperoxia for 2 wk and to room air for further 4 wk. Normoxic 6-wk rats showed increased D and decreased lacunarity with respect to normoxic 2-wk rats, together with changes in all stereological parameters except for mean alveolar volume. Hyperoxia-exposed 2-wk rats showed significant changes only in total number of alveoli, mean alveolar volume, and lacunarity with respect to equal-in-age normoxic rats. In the comparison between 6-wk rats, the hyperoxia-exposed group showed decreased D and increased lacunarity, together with changes in all stereological parameters except for septal thickness. Analysis of receiver operating characteristic curves showed a comparable discriminatory power of D, lacunarity, and total number of alveoli; Lm and mean alveolar volume were less discriminative. D and lacunarity did not show significant changes when different segmentation thresholds were applied, suggesting that the fractal approach may be fit to automatic image analysis. PMID:26851258

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

    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.

  20. Decreased accumulation of ultrasound contrast in the liver of nonalcoholic steatohepatitis rat model

    Yuki Miyata; Takeo Miyahara; Fuminori Moriyasu

    2011-01-01

    AIM:To investigate the diagnosis of nonalcoholic steatohepatitis (NASH) using contrast ultrasonography in the NASH rat model. METHODS: The liver in methionine choline-deficient diet (MCDD) rats, a NASH model constructed by feeding an MCDD, was examined by contrast ultrasonography at weeks 2, 4, 8, 12 and 16, with late phase images of contrast ultrasonography (Kupffer imaging) in which contrast enhancement was achieved by incorporation of a contrast agent by Kupffer cells (KCs), and images were compared to those in rats taking a regular chow. RESULTS: Decrease in contrast enhancement was observed first in MCDD rats at week 2. KCs were counted based on immunohistochemistry, but their numbers were not reduced and it was assumed that attenuation of contrast enhancement was attributable to reduced phagocytic activity of the KCs. CONCLUSION: It is suggested that clinical application of contrast ultrasonography may be valuable for noninvasive diagnosis of NASH.

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

    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...

  2. Objective validation of central sensitization in the rat UVB and heat rekindling model

    Weerasinghe, NS; Lumb, BM; Apps, R; Koutsikou, S; Murrell, JC

    2014-01-01

    Background The UVB and heat rekindling (UVB/HR) model shows potential as a translatable inflammatory pain model. However, the occurrence of central sensitization in this model, a fundamental mechanism underlying chronic pain, has been debated. Face, construct and predictive validity are key requisites of animal models; electromyogram (EMG) recordings were utilized to objectively demonstrate validity of the rat UVB/HR model. Methods The UVB/HR model was induced on the heel of the hind paw unde...

  3. Bone marrow mesenchymal stem cells combined with minocycline improve spinal cord injury in a rat model

    Chen, Dayong; Zeng, Wei; Fu, Yunfeng; Gao, Meng; Lv, Guohua

    2015-01-01

    The aims of this study were to assess that the effects of bone marrow mesenchymal stem cells (BMSCs) combination with minocycline improve spinal cord injury (SCI) in rat model. In the present study, the Wistar rats were randomly divided into five groups: control group, SCI group, BMSCs group, Minocycline group and BMSCs + minocycline group. Basso, Beattie and Bresnahan (BBB) test and MPO activity were used to assess the effect of combination therapy on locomotion and neutrophil infiltration. ...

  4. Berberine Ameliorates Cold and Mechanical Allodynia in a Rat Model of Diabetic Neuropathy

    Kim, Si Oh; Kim, Hyun Jee

    2013-01-01

    This study evaluated the antiallodynic properties of berberine on cold and mechanical allodynia after streptozotocin (STZ)-induced diabetes using a rat model. Diabetic neuropathy was induced in rats by intraperitoneal injection of STZ. To measure cold and mechanical allodynia, a 4°C plate and von Frey filament were used, respectively. Cold and mechanical allodynia induced by diabetes were significantly decreased by single and repeated intraperitoneal treatment of amitriptyline at 10 mg/kg, an...

  5. Four-Point Bending as a Method for Quantitatively Evaluating Spinal Arthrodesis in a Rat Model

    Robinson, Samuel T.; Mark T Svet; Kanim, Linda A; Metzger, Melodie F.

    2015-01-01

    The most common method of evaluating the success (or failure) of rat spinal fusion procedures is manual palpation testing. Whereas manual palpation provides only a subjective binary answer (fused or not fused) regarding the success of a fusion surgery, mechanical testing can provide more quantitative data by assessing variations in strength among treatment groups. We here describe a mechanical testing method to quantitatively assess single-level spinal fusion in a rat model, to improve on the...

  6. GASTROPROTECTIVE EFFECTS OF FRUITS OF TRIBULUS TERRESTRIS L. IN PYLORUS-LIGATED WISTAR RAT MODEL

    Sanjay Jain*, Rakesh Barik, Nidhi Yadav and Shivpal Singh

    2013-01-01

    Tribulus terrestris L. (TT; Zygophyllaceae) is employed in the folk medicine against sexual impotence, oedemas, abdominal distention and cardiovascular diseases. Gastroprotective (i.e. antiulcer and anti-secretory) potential of methanolic extract of TT fruits was evaluated in pylorus-ligated rat model of Wistar rat. The methanolic extract of TT was tested orally at the doses of 150, 300 & 600 mg/kg, on gastric ulcerations experimentally induced by pylorus ligation. Preliminary phytochemical s...

  7. Analgesic effect of Minocycline in rat model of inflammation-induced visceral pain

    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 nerv...

  8. Abnormal Motor Activity and Thermoregulation in a Schizophrenia Rat Model for Translational Science

    Gyongyi Horvath; Gabriella Kekesi; Zita Petrovszki; Gyorgy Benedek

    2015-01-01

    Background Schizophrenia is accompanied by altered motor activity and abnormal thermoregulation; therefore, the presence of these symptoms can enhance the face validity of a schizophrenia animal model. The goal was to characterize these parameters in freely moving condition of a new substrain of rats showing several schizophrenia-related alterations. Methods Male Wistar rats were used: the new substrain housed individually (for four weeks) and treated subchronically with ketamine, and naive a...

  9. Rethinking Food Anticipatory Activity in the Activity-Based Anorexia Rat Model

    Hemmings Wu; Kris van Kuyck; Tim Tambuyzer; Laura Luyten; Jean-Marie Aerts; Bart Nuttin

    2014-01-01

    When a rat is on a limited fixed-time food schedule with full access to a running wheel (activity-based anorexia model, ABA), its activity level will increase hours prior to the feeding period. This activity, called food-anticipatory activity (FAA), is a hypothesized parallel to the hyperactivity symptom in human anorexia nervosa. To investigate in depth the characteristics of FAA, we retrospectively analyzed the level of FAA and activities during other periods in ABA rats. To our surprise, r...

  10. Establishing an experimental rat model of photodynamically-induced retinal vein occlusion using erythrosin B

    Wei Chen; Ying Wu; Mi Zheng; Qing Gu; Zhi Zheng; Xin Xia

    2014-01-01

    AIM:To develop a reliable, reproducible rat model of retinal vein occlusion (RVO) with a novel photosensitizer (erythrosin B) and study the cellular responses in the retina.METHODS:Central and branch RVOs were created in adult male rats via photochemically-induced ischemia. Retinal changes were monitored via color fundus photography and fluorescein angiography at 1 and 3h, and 1, 4, 7, 14, and 21d after irradiation. Tissue slices were evaluated histopathologically. Retinal ganglion cell survi...

  11. Lipopolysaccharide-Induced Biliary Factors Enhance Invasion of Salmonella enteritidis in a Rat Model

    Islam, Abul F. M. W.; Nathan D. Moss; Dai, Yung; Smith, Murray S. R.; Collins, Andrew M.; Jackson, Graham D. F.

    2000-01-01

    In this study, the role of the hepatobiliary system in the early pathogenesis of Salmonella enteritidis infection was investigated in a rat model. Intravenous (i.v.) challenge with lipopolysaccharide (LPS) has previously been shown to enhance the translocation of normal gut flora. We first confirmed that LPS can similarly promote the invasion of S. enteritidis. Oral infection of outbred Australian Albino Wistar rats with 106 to 107 CFU of S. enteritidis led to widespread tissue invasion after...

  12. The Effect of Ethanol Extracts of Vitex on Histomorphological Placenta in the Rat Model

    A Louei Monfared; S Hamoun Navard

    2014-01-01

    Backgrounds & aim: Vitexagnus-castus as an herbal medicine has been used for the treatment of female reproductive disorders. The aim of this study was to evaluate the effect of ethanol extracts of Vitexagnus-castus on placental histomorphology in rat models. Methods: In the present experimental study, fourty pregnant rats were randomly divided into four groups (n=10). A control group received only distilled water and three experimental groups were treated with extract of Vitexagnus-cast...

  13. Modified impact of emotion on temporal discrimination in a transgenic rat model of Huntington disease

    Alexis Faure; Brown, Bruce L.; Nguyen, Hoa P.; Stephan Von Horsten

    2013-01-01

    Huntington's disease (HD) is characterized by triad of motor, cognitive, and emotional symptoms along with neuropathology in fronto-striatal circuit and limbic system including amygdala. Emotional alterations, which have a negative impact on patient well-being, represent some of the earliest symptoms of HD and might be related to the onset of the neurodegenerative process. In the transgenic rat model (tgHD rats), evidence suggest emotional alterations at the symptomatic stage along with neuro...

  14. Effect of minimal enteral feeding on recovery in a methotrexate-induced gastrointestinal mucositis rat model

    Kuiken, Nicoline S. S.; Rings, Edmond H. H. M.; Havinga, Rick; Albert K Groen; Tissing, Wim J. E.

    2015-01-01

    Purpose Patients suffering from gastrointestinal mucositis often receive parenteral nutrition as nutritional support. However, the absence of enteral nutrition might not be beneficial for the intestine. We aimed to determine the feasibility of minimal enteral feeding (MEF) administration in a methotrexate (MTX)-induced mucositis rat model and thereby determine the effect of MEF on recovery. Methods Male Wistar rats were attached to swivel systems from day 1 to 5 after 45 mg/kg MTX IV injectio...

  15. Development and Characterization of a Novel Rat Model of Estrogen-Induced Mammary Cancer

    Dennison, Kirsten L.; Samanas, Nyssa Becker; Harenda, Quincy Eckert; Hickman, Maureen Peters; Seiler, Nicole L.; Ding, Lina; Shull, James D.

    2015-01-01

    The ACI rat model of 17β-estradiol (E2)-induced mammary cancer is highly relevant for use in establishing the endocrine, genetic and environmental bases of breast cancer etiology and identifying novel agents and strategies for preventing breast cancer. E2 treatment rapidly induces mammary cancer in female ACI rats and simultaneously induces pituitary lactotroph hyperplasia and adenoma. The pituitary tumors can result in undesired morbidity which compromises long term studies focused on mammar...

  16. Manifestation of Hyperandrogenism in the Continuous Light Exposure-Induced PCOS Rat Model

    Xuezhi Kang; Lina Jia; Xueyong Shen

    2015-01-01

    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 rat...

  17. Health biomarkers in a rat model after intake of organically grown carrots

    Jensen, Maja M.; Jørgensen, Henry; Halekoh, Ulrich; Watzl, Bernhard; Thorup-Kristensen, Kristian; Lauridsen, Charlotte

    2012-01-01

    BACKGROUND: Organic food is perceived as being of better quality and healthier than conventional foods although the scientific research on organic foodstuffs is highly contradictory. The aim of the present study was to investigate if an 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), “minimalisti...

  18. Development of an oral tolerance model in rats for investigation of bioactive food components

    Jacobsen, Maja; Juul-Madsen, Helle Risdahl; Lauridsen, Charlotte

    2010-01-01

    In a recent study on rats, complete diets produced from three cultivation systems were compared on a range of health biomarkers, and notable differences appeared with regard to IgG levels(1). In order to chase this result, the objective of the present study was to develop an oral tolerance model in rats for comparison of diets composed of ingredients from different organic and conventional cultivation systems with regard to immunological responses.

  19. Brinzolamide-induced retinopathy in neonatal rats: an alternative animal model of retinal neovascularization

    DYOMIN, Y. A.; BILETSKA, P.V.; GAPUNIN, I. D.

    2014-01-01

    Background and Purpose: Neovascular retinal pathology is steel uncertain. Thus, there is great need to investigate new modeling, diagnostic and treatment technologies. Brinzolamide induces a metabolic acidosis via an alternative biochemical mechanism (bicarbonate loss). In the present study the influence of brinzolamide-induced acidosis on preretinal neovascularization in neonatal rat was investigated. Materials and Methods. In our study we used newborn Wistar rats raised in two litter...

  20. Renal Podocyte Injury in a Rat Model of Type 2 Diabetes Is Prevented by Metformin

    Junghyun Kim; Eunjin Shon; Chan-Sik Kim; Jin Sook Kim

    2012-01-01

    Hyperglycemia promotes oxidative stress and hence generation of reactive oxygen species (ROS), which is known to play a crucial role in the pathogenesis of diabetic nephropathy. Metformin, an oral hypoglycemic drug, possesses antioxidant effects. The aim of this paper is to investigate the protective effects of metformin on the injury of renal podocytes in spontaneously diabetic Torii (SDT) rats, a new model for nonobese type 2 diabetes. Metformin (350 mg/kg/day) was given to SDT rats for 17 ...

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

    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.

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

    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.

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

    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

  4. Changes of cerebral contents of neuropeptides in rat models of multiple ischemic dementia (MID)

    Objective: To investigate the significance of changes of cerebral contents of the neuropeptides somatostatin (SS), arginine vasopressin (AVP) and substance P in rat models of MID. Methods: The rat models consisted of 15 rats undergoing intracarotid injection of autogenous thrombus powder. Another group of 15 rats undergoing sham operation served as controls. Learning and memory ability in these rats was assessed with daily passive avoidance task testing for 10 consecutive days. The animals were sacrificed on 30d and contents of the neuropeptides in tissue homogenate from different areas of brain (frontal cortex, temporal cortex, hippocampus, thalamus and corpus striatum) were measured with (RIA). Results: On the first day of passive avoidance task testing, the frequency of errors in the MID group and the control group was about the same. From the third day on, the frequency of errors in the MID group was significantly higher than that in the control group (P<0.05). The neuropeptides contents of all these cerebral areas in the MID group were significantly higher than those in the control group (P<0.05 or P<0.01) with the only exception of the contents of substance P in thalamus (no significant difference between the contents in the two groups). Conclusion: The impairment of learning and memory in rat models with MID was possibly related to the lowered contents of SS, AVP and substance P in the brain tissue. (authors)

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

    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.

  6. Effects of Exercise on Behavior and Peripheral Blood Lymphocyte Apoptosis in a Rat Model of Chronic Fatigue Syndrome

    邹军; 苑建齐; 吕爽; 屠嘉衡

    2010-01-01

    This study examined the effects of exercise on behavior and peripheral blood leukocyte apoptosis in a rat model of chronic fatigue syndrome(CFS).Thirty-six healthy male Sprague-Dawley rats were equally randomized into 3 groups:the control group,CFS model group and the exercise group in terms of body weight.A total of 25 rats entered the final statistical analysis due to 11 deaths during the study.CFS model was established by subjecting the rats in CFS model group and exercise group to electric shock,chronic...

  7. Sensitization of the Hypothalamic-Pituitary-Adrenal Axis in a Male Rat Chronic Stress Model.

    Franco, Alier J; Chen, Chun; Scullen, Tyler; Zsombok, Andrea; Salahudeen, Ahmed A; Di, Shi; Herman, James P; Tasker, Jeffrey G

    2016-06-01

    Stress activation of the hypothalamic-pituitary-adrenal (HPA) axis is regulated by rapid glucocorticoid negative feedback. Chronic unpredictable stress animal models recapitulate certain aspects of major depression in humans, which have been attributed to impaired glucocorticoid negative feedback. We tested for an attenuated HPA sensitivity to fast glucocorticoid feedback inhibition in male rats exposed to a chronic variable stress (CVS) paradigm. In vitro, parvocellular neuroendocrine cells of the hypothalamic paraventricular nucleus recorded in slices from CVS rats showed an increase in basal excitatory synaptic inputs and a decrease in basal inhibitory synaptic inputs compared with neurons from control rats. There was no difference between control and CVS-treated rats in the rapid glucocorticoid suppression of excitatory synaptic inputs, a fast feedback mechanism. In vivo, CVS-treated rats showed an increase in ACTH secretion at baseline and after both iv CRH and acute stress and no impairment of the corticosterone suppression of the ACTH response, compared with controls. In an in vitro pituitary preparation, an increase in basal ACTH release, a small increase in CRH-induced ACTH release, and no decrement in the glucocorticoid suppression of ACTH release were seen in pituitaries from CVS rats. Thus, CVS does not suppress rapid glucocorticoid negative feedback at the hypothalamus or pituitary, but increases the synaptic excitability of paraventricular nucleus CRH neurons and the CRH sensitivity of the pituitary. Therefore, increased HPA activity in chronically stressed male rats is due to sensitization of the HPA axis, rather than to desensitization to rapid glucocorticoid feedback. PMID:27054552

  8. Effect of Bile Acid on Fetal Lung in Rat Model of Intrahepatic Cholestasis of Pregnancy

    Ling Yu

    2014-01-01

    Full Text Available Objective. To determine the correlation between maternal bile acid (BA level and fetal pulmonary surfactant in rats and study the effects of BA on fetal lung in rat model of intrahepatic cholestasis of pregnancy. Methods. Forty pregnant rats were treated with (A 5.5 mg/kg BA, (B 1.4 mg/kg BA, and (C 1 ml physiological saline. Levels of total bile acid (TBA, ALT, AST, TBIL, DBIL, and SP-A were determined and the lungs of fetal rats were analyzed for pathological changes. Results. Groups A and B intervened with BA showed significant higher level of TBA in both maternal and fetal serum, more mortality rate of fetal rats, more concentration of SP-A in fetal serum, and wider alveolus mesenchyme of fetal rats than the control Group C. Higher level of BA associated with increased fetal risk and lower numerical density of mitochondria in type II alveolar epithelial cells. The levels of TBA in maternal serum were found to have significant positive correlation with those in fetal serum and SP-A level but negatively with the area of alveolus and the numerical density of lamellar body. Conclusions. The TBA level in maternal serum showed significant association with lung pathological changes in fetal rats.

  9. Expression of survivin in human gastric carcinoma and gastric carcinoma model of rats

    Xiao-Dong Zhu; Geng-Jin Lin; Li-Ping Qian; Zhong-Qing Chen

    2003-01-01

    AIM: To study the expression of survivin, an inhibitor of apoptosis protein, in human gastric carcinomas and gastric carcinoma models of rats.METHODS: With the method of immunohistochemical staining, we studied the expression of survivin in 20 cases of chronic gastritis and 56 cases of gastric carcinomas. We used N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) and high dose sodium-chloride diet to induce rat gastric carcinomas. Survivin expression was studied in glandular stomachs of normal rats, adenocarcinomas and tissues adjacent to the tumor, as well as in rats during the induction period.RESULTS: Survivin was expressed in 27 of 56 (48.2 %)cases of human gastric carcinoma tissues and 1 of 20 (5 %)cases of chronic gastritis. It was found that the expression of survivin had no relation with the elements of age, tumor depth, tumor size, and disease stage, but was significantly related to histological type. The positive rate of survivin expression in cases of intestinal type was significantly higher than that in cases of diffuse type (P<0.05). In animal experiments, survivin expression in glandular stomachs of normal rats, of rats in middle induction period, in adenocarcinomas and tissues adjacent to tumor were 0,40.0 %, 78.3 % and 38.9 %, respectively. Compared with the survivin expression in normal rats, the differences were significant.CONCLUSION: These data imply that survivin plays an important role in the onset of gastric carcinoma and that high survivin expression is an early event of gastric carcinoma.

  10. Characterization of Diabetic Neuropathy in the Zucker Diabetic Sprague-Dawley Rat: A New Animal Model for Type 2 Diabetes

    Eric P. Davidson

    2014-01-01

    Full Text Available Recently a new rat model for type 2 diabetes the Zucker diabetic Sprague-Dawley (ZDSD/Pco was created. In this study we sought to characterize the development of diabetic neuropathy in ZDSD rats using age-matched Sprague-Dawley rats as a control. Rats were examined at 34 weeks of age 12 weeks after the onset of hyperglycemia in ZDSD rats. At this time ZDSD rats were severely insulin resistant with slowing of both motor and sensory nerve conduction velocities. ZDSD rats also had fatty livers, elevated serum free fatty acids, triglycerides, and cholesterol, and elevated sciatic nerve nitrotyrosine levels. The corneas of ZDSD rats exhibited a decrease in subbasal epithelial corneal nerves and sensitivity. ZDSD rats were hypoalgesic but intraepidermal nerve fibers in the skin of the hindpaw were normal compared to Sprague-Dawley rats. However, the number of Langerhans cells was decreased. Vascular reactivity of epineurial arterioles, blood vessels that provide circulation to the sciatic nerve, to acetylcholine and calcitonin gene-related peptide was impaired in ZDSD rats. These data indicate that ZDSD rats develop many of the neural complications associated with type 2 diabetes and are a good animal model for preclinical investigations of drug development for diabetic neuropathy.

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

    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.

  12. Behavioral outcome measures used for human neural stem cell transplantation in rat stroke models

    Matthew B. Jensen

    2011-09-01

    Full Text Available Stroke is a leading cause of death and disability, leading to the development of various stroke models to test new treatments, most commonly in the rat. Human stroke trials focus on disability, related primarily to neurological deficits. To better model the clinical application of these treatments, many behavioral tests have been developed using the rat stroke model. We performed a systematic review of all the behavioral outcome measures used in published studies of human neural stem cell transplantation in rat stroke models. The reviewed tests include motor, sensory, cognitive, activity, and combination tests. For each test, we give a brief description, trace the origin of the test, and discuss test performance in the reviewed studies. We conclude that while many behavioral tests are available for this purpose, there does not appear to be consensus on an optimal testing strategy.

  13. Fibrinogen and P-selectin expression in atherosclerosis model of Sprague Dawley rat

    ZHOU Bi-rong; PAN Ying; ZHAI Zhi-min

    2011-01-01

    Background Platelet P-selectin plays an important role in inflammation and contributes to thrombosis and hemostasis.Fibrinogen may take part in inflammation,thrombosis,and hemostasis via enhancement of platelet P-selectin expression.This study aimed to discover the correlation between them in atherosclerosis model of Sprague Dawley (SD) rat.Methods Diet-induced atherosclerosis SD rats were adopted as experimental models.The blood from the common abdominal aorta of the rats was obtained to measure the biochemical characteristics and for the check of flow cytometry.Then the aortas were separated carefully,taken out,put into 10% (w/v) neutral formalin for later use.Then fibrinogen and P-selectin expression were detected by flow cytometry and immunohistochemistry.Results SD rats were induced to atherosclerosis model by high fat diet and vitamin D2 injected.It was discovered that the binding of fibrinogen and the expression of P-selectin on the platelet increase in atherosclerosis model (Group H)than in that in the control group (Group Z),there were closely interrelated.High levels of fibrinogen and P-selectin express on the artery of atherosclerosis rat model.Conclusions Fibrinogen and P-selectin are concerned with atherosclerosis.Fibrinogen can interact with P-selectin in order to contribute to the development of atherosclerosis,high levels of fibrinogen and P-selectin can be regarded as risk factors for markers of atherosclerosis.

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

    Dinesh T Makhija

    2014-01-01

    Full Text Available 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 < 0.05 in 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.

  15. The Fischer 344 rat as a model of presbycusis

    Syka, Josef

    2010-01-01

    Roč. 264, 1-2 (2010), s. 70-78. ISSN 0378-5955 R&D Projects: GA ČR GA309/07/1336; GA MŠk(CZ) LC554 Institutional research plan: CEZ:AV0Z50390703 Keywords : Rat * Fischer 344 * Presbycusis Subject RIV: FH - Neurology Impact factor: 2.428, year: 2010

  16. Metabolic Disorders and Diabetic Complications in Spontaneously Diabetic Torii Leprfa Rat: A New Obese Type 2 Diabetic Model

    Yusuke Kemmochi

    2013-01-01

    Full Text Available Spontaneously Diabetic Torii Leprfa (SDT fatty rat, established by introducing the fa allele of the Zucker fatty rat into SDT rat genome, is a new model of obese type 2 diabetes. Both male and female SDT fatty rats show overt obesity, and hyperglycemia and hyperlipidemia are observed at a young age as compared with SDT rats. With early incidence of diabetes mellitus, diabetic complications, such as nephropathy, retinopathy, and neuropathy, in SDT fatty rats were seen at younger ages compared to those in the SDT rats. In this paper, we overview pathophysiological features in SDT fatty rats and also describe new insights regarding the hematology, blood pressure, renal complications, and sexual dysfunction. The SDT fatty rats showed an increase of leukocytes, especially the monocyte count, prominent hypertension associated with salt drinking, end-stage renal disease with aging, and hypogonadism. Unlike other diabetic models, the characteristic of SDT fatty rat is to present an incidence of diabetes in females, hypertension, and retinopathy. SDT fatty rat is a useful model for analysis of various metabolic disorders and the evaluation of drugs related to metabolic disease.

  17. Effect of Angiotensin(1-7) on Heart Function in an Experimental Rat Model of Obesity

    Blanke, Katja; Schlegel, Franziska; Raasch, Walter; Bader, Michael; Dähnert, Ingo; Dhein, Stefan; Salameh, Aida

    2015-01-01

    Aim: Obesity is a risk factor for the development of cardiovascular diseases. Recently it was shown that overexpression of the Mas-receptor antagonist angiotensin(1-7) could prevent from diet-induced obesity. However, it remained unclear whether diet-induced obesity and angiotensin(1-7) overexpression might also have effects on the cardiovascular system in these rats. Methods:Twenty three male Sprague Dawley rats were fed with standard chow (SD+chow, n = 5) or a cafeteria diet (SD+CD, n = 6) for 5 months. To investigate the effect of angiotensin(1-7) transgenic rats, expressing an angiotensin(1-7)-producing fusion protein in testis were used. These transgenic rats also received a 5 month's feeding period with either chow (TGR+chow, n = 6) or cafeteria diet (TGR+CD, n = 6), respectively. Hemodynamic measurements (pressure-volume loops) were carried out to assess cardiac function and blood pressure. Subsequently, hearts were explanted and investigated according to the Langendorff technique. Furthermore, cardiac remodeling in these animals was investigated histologically. Results:After 5 months cafeteria diet feeding rats showed a significantly increased body weight, which could be prevented in transgenic rats. However, there was no effect on cardiac performance after cafeteria diet in non-transgenic and transgenic rats. Moreover, overexpression of angiotensin(1-7) deteriorated cardiac contractility as indicated by impaired dp/dt. Furthermore, histological analysis revealed that cafeteria diet led to myocardial fibrosis in both, control and transgenic rats and this was not inhibited by an overproduction of angiotensin(1-7). Conclusion:These results indicate that an overexpression of circulating angiotensin(1-7) prevents a cafeteria diet-induced increase in body weight, but does not affect cardiac performance in this experimental rat model of obesity. Furthermore, overexpression of angiotensin(1-7) alone resulted in an impairment of cardiac function. PMID:26733884

  18. Speech sound discrimination training improves auditory cortex responses in a rat model of autism

    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.

  19. Radiation-induced cognitive dysfunction: An experimental model in the old rat

    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 ≤ 0.001) and two-way avoidance (18% vs. 40%, p ≤ 0.01). Seven months postradiation therapy the reaction time was increased (press-lever avoidance, 11.20 s vs. 8.43 s, p ≤ 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

  20. Radiation-induced cognitive dysfunction: an experimental model in the old rat

    Purpose: To develop a model of radiation-induced behavioral dysfunction. Methods and Materials: 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. Results: 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 ≤ 0.001) and two-way avoidance (18% vs. 40%, p ≤ 0.01). Seven months postradiation therapy the reaction time was increased (press-lever avoidance, 11.20 s vs. 8.43 s, p ≤ 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. Conclusion: 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

  1. A New Experimental Polytrauma Model in Rats: Molecular Characterization of the Early Inflammatory Response

    Sebastian Weckbach

    2012-01-01

    Full Text Available Background. The molecular mechanisms of the immune response after polytrauma are highly complex and far from fully understood. In this paper, we characterize a new standardized polytrauma model in rats based on the early molecular inflammatory and apoptotic response. Methods. Male Wistar rats (250 g, 6–10/group were anesthetized and exposed to chest trauma (ChT, closed head injury (CHI, or Tib/Fib fracture including a soft tissue trauma (Fx + STT or to the following combination of injuries: (1 ChT; (2 ChT + Fx + STT; (3 ChT + CHI; (4 CHI; (5 polytrauma (PT = ChT + CHI + Fx + STT. Sham-operated rats served as negative controls. The inflammatory response was quantified at 2 hours and 4 hours after trauma by analysis of “key” inflammatory mediators, including selected cytokines and complement components, in serum and bronchoalveolar (BAL fluid samples. Results. Polytraumatized (PT rats showed a significant systemic and intrapulmonary release of cytokines, chemokines, and complement anaphylatoxins, compared to rats with isolated injuries or selected combinations of injuries. Conclusion. This new rat model appears to closely mimic the early immunological response of polytrauma observed in humans and may provide a valid basis for evaluation of the complex pathophysiology and future therapeutic immune modulatory approaches in experimental polytrauma.

  2. Role of oxidative stress in surgical cavernous nerve injury in a rat model.

    Wang, Hui; Ding, Xie-Gang; Li, Shi-Wen; Zheng, Hang; Zheng, Xin-Min; Navin, Shrestha; Li, Lu; Wang, Xing-Huan

    2015-06-01

    This study investigates the role of oxidative stress in surgical cavernous nerve (CN) injury in a rat model. Eighty-four male Sprague-Dawley rats were randomly divided into three groups: group 1, sham-operated rats; group 2, bilateral CN-crushed rats; and group 3, bilateral CN-transection-and-sutured-immediately rats. Oxidative stress was evaluated by malondialdehyde levels, super oxide dismutase (SOD) activities, and glutathione peroxidase (GPX) activities in serum. Erectile function was assessed by CN electrostimulation at 3 months with mean maximal intracavernous pressure (ICP) and maximal ICP per mean arterial pressure. Nerve injury was assessed by toluidine blue staining of CNs and nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase staining of penile tissue. GPX protein expression and nitrotyrosine-3 (NT-3) levels in penile tissue were measured. Erectile function and the number of myelinated axons of CNs and NADPH-diaphorase-positive nerve fibers were statistically decreased between groups, from sham to crush to transection. For markers, both nerve-injury groups showed increased oxidative stress markers at early time points, with the transection group showing greater oxidative stress than the crushed group and values normalizing to sham levels by week 12. GPX expression and NT-3 levels in penile tissue were in concordance with the results of SOD and GPX. These results show that oxidative stress plays an important role in injured CNs, and different methods of CN injury can lead to different degrees of oxidative stress in a rat model. PMID:25597854

  3. Characterization of a new animal model of metabolic syndrome: the DahlS.Z-Lepr fa /Lepr fa rat

    Hattori, T.; Murase, T.; Ohtake, M.; Inoue, T.; Tsukamoto, H.; Takatsu, M.; Kato, Y.; Hashimoto, K; Murohara, T; Nagata, K.(Faculty of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Japan)

    2011-01-01

    Objective: The DahlS.Z-Lepr fa /Lepr fa (DS/obese) rat strain was established from a cross between Dahl salt-sensitive rats and Zucker fatty (fa/fa) rats, the latter of which harbor a missense mutation in the leptin receptor gene (Lepr). We examined whether DS/obese rats might be a suitable animal model of metabolic syndrome in humans. Methods: The systemic pathophysiological and metabolic characteristics of DS/obese rats were determined and compared with those of homozygous lean littermates,...

  4. Differential effects of B7-1 blockade in the rat experimental autoimmune encephalomyelitis model

    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...

  5. Genetic animal models for Absence epilepsy: a review of the WAG/Rij strain of rats

    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 clini

  6. Pharmacokinetic/Pharmacodynamic Relationship of Gabapentin in a CFA-induced Inflammatory Hyperalgesia Rat Model

    Larsen, Malte Selch; Keizer, Ron; Munro, Gordon;

    2016-01-01

    provides further knowledge into the understanding of gabapentin's non-linear pharmacokinetics and the link between plasma/brain disposition and anti-hyperalgesic effects. The model suggests that intestinal absorption is the primary source of non-linearity and that the investigated rat model provides...

  7. Experimental tuberculosis in the Wistar rat: a model for protective immunity and control of infection.

    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.

  8. Fused pulmonary lobes is a rat model of human Fraser syndrome

    Highlights: → Fused pulmonary lobes (fpl) mutant rats exhibit similar phenotypes to Fraser syndrome. → The fpl gene harbors a nonsense mutation in Fraser syndrome-associated gene Frem2. → Fpl mutant is defined as a first model of human Fraser syndrome in rats. -- Abstract: Fused pulmonary lobes (fpl) is a mutant gene that is inherited in an autosomal recessive manner and causes various developmental defects, including fusion of pulmonary lobes, and eyelid and digit anomalies in rats. Since these developmental defects closely resemble those observed in patients with Fraser syndrome, a recessive multiorgan disorder, and its model animals, we investigated whether the abnormal phenotypes observed in fpl/fpl mutant rats are attributable to a genetic disorder similar to Fraser syndrome. At the epidermal basement membrane in fpl/fpl mutant neonates, the expression of QBRICK, a basement membrane protein whose expression is attenuated in Fraser syndrome model mice, was greatly diminished compared with control littermates. Quantitative RT-PCR analyses of Fraser syndrome-related genes revealed that Frem2 transcripts were markedly diminished in QBRICK-negative embryos. Genomic DNA sequencing of the fpl/fpl mutant identified a nonsense mutation that introduced a stop codon at serine 2005 in Frem2. These findings indicate that the fpl mutant is a rat model of human Fraser syndrome.

  9. Assessment of Alloxan-Induced Diabetic Rats as a Periodontal Disease Model Using a Selective Cyclooxygenase (COX)-2 Inhibitor

    Nakahara, Yutaka; Ozaki, Kiyokazu; SANO, Tomoya; Kodama, Yasushi; Matsuura, Tetsuro

    2014-01-01

    Several recent studies have reported that alloxan-treated rats with long-term hyperglycemia can develop naturally occurring periodontal disease (PD). Our previous studies detected dental caries in the same model. Therefore, these two lesions of different etiologies are expected to occur concurrently. In this study, we evaluated the use of diabetic rats as a PD model by employing a selective COX-2 inhibitor reported to be effective against PD. Six-week-old female F344 rats were divided into 3 ...

  10. Anti-oxidative and anti-inflammatory effects of spirulina on rat model of non-alcoholic steatohepatitis

    Pak, Wing; Takayama,Fusako; Mine, Manaka; Nakamoto, Kazuo; Kodo, Yasumasa; Mankura, Mitsumasa; Egashira, Toru; Kawasaki, Hiromu; Mori, Akitane

    2012-01-01

    The pathogenesis of nonalcoholic steatohepatitis (NASH) remains unclear, but accumulating data suggest oxidative stress and the relationship between inflammation and immunity plays a crucial role. The aim of this study is to investigate the spirulina, which is a blue-green algae rich in proteins and other nutritional elements, and its component-phycocyanin effect on a rat model of NASH. NASH model rats were established by feeding male Wistar rats with choline-deficient high-fat diet (CDHF) an...

  11. Animal models for medications development targeting alcohol abuse using selectively bred rat lines: Neurobiological and pharmacological validity

    Bell, Richard L.; Sable, Helen J. K.; Colombo, Giancarlo; Hyytia, Petri; Rodd, Zachary A.; Lumeng, Lawrence

    2012-01-01

    The purpose of this review paper is to present evidence that rat animal models of alcoholism provide an ideal platform for developing and screening medications that target alcohol abuse and dependence. The focus is on the 5 oldest international rat lines that have been selectively bred for a high alcohol-consumption phenotype. The behavioral and neurochemical phenotypes of these rat lines are reviewed and placed in the context of the clinical literature. The paper presents behavioral models f...

  12. Glutamatergic signaling and low prodynorphin expression are associated with intact memory and reduced anxiety in rat models of healthy aging

    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. Improvement of Radiation-Mediated Immunosuppression of Human NSCLC Tumour Xenografts in a Nude Rat Model

    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.

  14. A Comparative Study on Several Models of Experimental Renal Calcium Oxalate Stones Formation in Rats

    LIU Jihong; CAO Zhenggno; ZHANG Zhaohui; ZHOU Siwei; YE Zhangqun

    2007-01-01

    In order to compare the effects of several experimental renal calcium oxalate stones formation models in rats and to find a simple and convenient model with significant effect of calcium oxalate crystals deposition in the kidney, several rat models of renal calcium oxalate stones formation were induced by some crystal-inducing drugs (CID) including ethylene glycol (EG), ammonium chloride (AC), vitamin D3 [1α(OH)VitD3, alfacalcidol], calcium gluconate, ammonium oxalate, gentamicin sulfate, L-hydroxyproline. The rats were fed with drugs given singly or unitedly. At the end of experiment, 24-h urines were collected and the serum creatinine (Cr), blood urea nitrogen (BUN), the extents of calcium oxalate crystal deposition in the renal tissue, urinary calcium and oxalate excretion were measured. The serum Cr levels in the stone-forming groups were significantly higher than those in the control group except for the group EG+L-hydroxyproline, group calcium gluconate and group oxalate. Blood BUN concentration was significantly higher in rats fed with CID than that in control group except for group EG+L-hydroxyproline and group ammonium oxalate plus calcium gluconate. In the group of rats administered with EG plus Vitamin D3, the deposition of calcium oxalate crystal in the renal tissue and urinary calcium excretion were significantly greater than other model groups. The effect of the model induced by EG plus AC was similar to that in the group induced by EG plus Vitamin D3. EG plus Vitamin D3 or EG plus AC could stably and significantly induced the rat model of renal calcium oxalate stones formation.

  15. Ovariectomized rats as a model of postmenopausal osteoarthritis

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

    2004-01-01

    , aged 5 and 7 months. In a third cohort, the effect of exogenous estrogen and a selective estrogen receptor modulator was analyzed. Knee joints were assessed by histological analysis of the articular cartilage after 9 weeks. Cartilage turnover was measured in urine by an immunoassay specific for.......008). Ovariectomy also significant increased CTX-I and CTX-II. Both the absolute levels of CTX-II and the relative changes from baseline seen at week 4 correlated strongly with the severity of cartilage surface erosion at termination (r = 0.74, P < 0.01). Both estrogen and the selective estrogen receptor modulator...... inhibited the ovariectomy-induced acceleration of cartilage and bone turnover and significantly suppressed cartilage degradation and erosion seen in vehicle-treated OVX rats. The study indicates that estrogen deficiency accelerates cartilage turnover and increases cartilage surface erosion. OVX rats provide...

  16. Korean red ginseng extract suppresses the progression of alcoholic fatty liver in a rat model

    Alcoholic fatty liver (AFL) is the most common liver disease among Korean men, and Korean red ginseng has been used as a folk medicine to diverse diseases in Korea. Therefore, we examined if Korean red ginseng extract (KRG) could be a suppressive agent on AFL in a rat model or not. Experimental rats were fed the Lieber DeCarli diet with 36% of energy intake from ethanol, and divided into three groups which daily co-administered KRG 0, 700 and 1400 mg/kg for six weeks, respectively. Naive rats were fed iso-caloric control diet without ethanol and KRG. We investigated histopathological hepatic characteristics, hepatic and plasma lipid concentrations, hepatic hydroxyproline contents, heart/liver radioactivity ratio of 201Thallium and liver/body weight of the rats at the end point. Ethanol intake brought about steatotic, inflammatory, necrotic and fibrotic changes of livers significantly, and it also lead the rats to increase hepatic triglyceride and hydroxyproline contents, plasma total cholesterol and low density lipoprotein cholesterol levels, and liver/body weight. However, co-administration of KRG 1400 mg/kg suppressed fat accumulation and fibrotic initiation in AFL rat model significantly. It was also inclined to attenuate inflammatory cell infiltration, hydroxyproline accumulation, and increasing liver/body weight, even though plasma lipid levels and heart/liver ratios were not successfully improved by six-week-long intakes of KRG. In conclusions, co-administration of KRG 1400 mg/kg could significantly suppress steatosis in AFL rat model, and it might need longer ingestion of KRG than six weeks to improve plasma lipid imbalance. (author)

  17. Antipsychotic-like effect of minocycline in a rat model

    Dokuyucu, Recep; Kokacya, Hanifi; Inanir, Sema; Copoglu, Umit Sertan; Erbas, Oytun

    2014-01-01

    Objectives: Tetracycline antibiotic drug minocycline has strongly neuroprotective and anti-inflammatory effects. Minocycline has also remarkable brain tissue penetration, is clinically entirely tolerated and properly absorbed when taken orally. In our study, we class with the effects of minocycline and chlorpromazine, a conventional antipsychotic drug, by evaluating the novelty-induced rearing, apomorphine-induced stereotypic behavior, and brain MDA levels in rats. Materials and Methods: Four...

  18. Preference of organic grown carrorts in a rat model

    Jørgensen, Henry; Halekoh, Ulrich; Lauridsen, Charlotte

    2011-01-01

    Food preference tests represent an approach in food quality research, taking advantage of the instinctive feeding behavior of animals by allowing them to choose between food samples. A great number of investigations using laboratory rats concerning essential and/or dangerous contents are based on this method and have shown its effectiveness. The selection of food is influenced to some degree by smell and taste, but mostly by wholesomeness and need. In the present study a preference test was u...

  19. A simple taurocholate-induced model of severe acute pancreatitis in rats

    Zhong-Hui Liu; Jun-Sheng Peng; Chu-Jun Li; Zu-Li Yang; Jun Xiang; Hu Song; Xiao-Bing Wu; Jun-Rong Chen; De-Chang Diao

    2009-01-01

    AIM: To investigate gut barrier damage and intestinal bacteria translocation in severe acute pancreatitis (SAP),a simple rat model of SAP was induced and studied.METHODS: Pancreatitis was induced by uniformly distributed injection of 3.8% Na taurocholate (1 mL/kg) beneath the pancreatic capsule. Rats in the control group were injected with normal saline in the identical location.RESULTS: Serum amylase, plasma endotoxin, intestinal permeability, and pancreatitis pathology scores were all markedly higher in the pancreatitis group than in the control group ( P < 0.01). The bacterial infection rate was significantly higher in the SAP group than in the control group ( P < 0.01), observed in parallel by both bacterial culture and real-time polymerase chain reaction. Acute damage of the pancreas was observed histologically in SAP rats, showing interstitial edema, leukocyte infiltration, acinar cell necrosis and hemorrhage. The microstructure of the intestinal mucosa of SAP rats appeared to be destroyed with loose, shortened microvilli and rupture of the intercellular junction, as shown by electron microscopy.CONCLUSION: Significant gut barrier damage and intestinal bacterial translocation were definitely observed with few potential study confounders in this SAP rat model, suggesting that it may be an appropriate animal model for study of gut barrier damage and bacterial translocation in SAP.

  20. Establishing a rat model of spastic cerebral palsy by targeted ethanol injection

    Yadong Yu; Liang Li; Xinzhong Shao; Fangtao Tian; Qinglu Sun

    2013-01-01

    Spastic cerebral palsy is general y 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 ste-reotaxic 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 15μL 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 specifical y and thoroughly damages the pyra-midal tract, and therefore, the animals display flexion spasms, which are a typical symptom of the disease.

  1. Resistance to Recombinant Human Erythropoietin Therapy in a Rat Model of Chronic Kidney Disease Associated Anemia

    Patrícia Garrido; Sandra Ribeiro; João Fernandes; Helena Vala; Petronila Rocha-Pereira; Elsa Bronze-da-Rocha; Luís Belo; Elísio Costa; Alice Santos-Silva; Flávio Reis

    2016-01-01

    This study aimed to elucidate the mechanisms explaining the persistence of anemia and resistance to recombinant human erythropoietin (rHuEPO) therapy in a rat model of chronic kidney disease (CKD)-associated anemia with formation of anti-rHuEPO antibodies. The remnant kidney rat model of CKD induced by 5/6 nephrectomy was used to test a long-term (nine weeks) high dose of rHuEPO (200 UI/kg bw/week) treatment. Hematological and biochemical parameters were evaluated as well as serum and tissue ...

  2. Effect of erythropoietin loading chitosan-tripolyphosphate nanoparticles on an IgA nephropathy rat model

    Zhang, Xiaoli; Wu, Yin; Sun, Kun; Tan, Jing

    2014-01-01

    The aim of the present study was to investigate the effect of erythropoietin (EPO) loading chitosan-tripolyphosphate (CS-TPP) nanoparticles on an immunoglobulin A nephropathy (IgAN) rat model. CS-TPP nanoparticles were produced from CS and TPP and EPO was loaded by mixing with the nanoparticles. The IgAN rat models were randomly divided into three groups: the CS-TPP-EPO group, CS-TPP group and EPO group. Hemoglobin (Hb), blood urea nitrogen (BUN) and creatinine (Cr) levels were measured in ea...

  3. Potential neuroprotective effects of acupuncture stimulation on diabetes mellitus in a global ischemic rat model

    Acupuncture (ACU) is known to be effective in ischemia treatment, and glutamate (GLU) excitotoxicity is an important factor in neuronal cell death. We observed the effect of ACU on cerebral blood flow (%CBF) and ΔGLU (the changes in GLU release) in the ischemic stroke rat model of diabetic mellitus (DM). A global ischemia was induced using the eleven-vessel occlusion (11-VO) method in 14 Sprague-Dawley rats (DM), which were randomly divided into two groups: the control group and the ACU-treatment group. Extracellular ΔGLU was assessed using an intra-cerebral biosensor system measuring 256 samples per second, simultaneously with %CBF and electroencephalogram. ACU stimulation was applied to ACU points GB34 and GB39 during the ischemic period. Twenty-three diagnostic parameters were proposed first for a detailed analysis of changes in %CBF and GLU release during ischemia/reperfusion. ACU rats showed a significant decrease in ischemic (p < 0.05) and reperfusion %CBF (p < 0.0001) than control rats, and a significantly larger decrease in ischemic ΔGLU (p < 0.05) and peak level of reperfusion ΔGLU (p < 0.005) than control rats. From these results, we suggest that ACU stimulation is responsible for the potential protection of neurons through suppression of %CBF response in the increased plasma osmolality and extracellular ΔGLU in diabetic rats under ischemic conditions

  4. Levels of oxidative stress parameters and the protective effects of melatonin in psychosis model rat testis

    Bekir S.Parlaktas; Birsen Ozyurt; Huseyin Ozyurt; Ayten T.Tunc; Ali Akbas

    2008-01-01

    Aim: To evaluate the effects of melatonin on antioxidant enzyme levels and histopathologic changes in dizocilpine (MK-801)-induced psychosis model rat testis. Methods: A total of 24 adult male Wistar-Albino rats were divided into three groups with 8 in each. Group Ⅰ was used as control. Rats in Group Ⅱ were injected with MK-801 (0.5 mg/kg body weight i.p. for 5 days). In addition to MK-801, melatonin (50 mg/kg body weight i.p. once a day for 5 days) was injected into the rats in Group Ⅲ. The testes were harvested bilaterally for biochemical and histopathological examinations. Antioxidant enzyme activities, malondialdehyde, protein carbonyl and nitric oxide (NO) levels in tes-ticular tissues were analyzed using spectrophotometric analysis methods. Histopathological examinations of the testes were also performed. Results: MK-801 induced testicular damage, which resulted in significant oxidative stress (OS) by increasing the levels of antioxidant enzymes. The malondialdehyde, protein carbonyl and NO levels were increased in testicular tissues of rats. Treatment with melatonin led to significant decrease in oxidative injury.Administration of melatonin also reduced the detrimental histopathologic effects caused by MK-801. Conclusion:The results of the present study showed that MK-801 cause OS in testicular tissues of rats and treatment with melatonin can reduce the harmful effects of MK-801.

  5. Progesterone Treatment Shows Benefit in Female Rats in a Pediatric Model of Controlled Cortical Impact Injury.

    Rastafa I Geddes

    Full Text Available We recently showed that progesterone treatment can reduce lesion size and behavioral deficits after moderate-to-severe bilateral injury to the medial prefrontal cortex in immature male rats. Whether there are important sex differences in response to injury and progesterone treatment in very young subjects has not been given sufficient attention. Here we investigated progesterone's effects in the same model of brain injury but with pre-pubescent females.Twenty-eight-day-old female Sprague-Dawley rats received sham (n = 14 or controlled cortical impact (CCI (n = 21 injury, were given progesterone (8 mg/kg body weight or vehicle injections on post-injury days (PID 1-7, and underwent behavioral testing from PID 9-27. Brains were evaluated for lesion size at PID 28.Lesion size in vehicle-treated female rats with CCI injury was smaller than that previously reported for similarly treated age-matched male rats. Treatment with progesterone reduced the effect of CCI on extent of damage and behavioral deficits.Pre-pubescent female rats with midline CCI injury to the frontal cortex have reduced morphological and functional deficits following progesterone treatment. While gender differences in susceptibility to this injury were observed, progesterone treatment produced beneficial effects in young rats of both sexes following CCI.

  6. Copper balance and ceruloplasmin in chronic hepatitis in a Wilson disease animal model, LEC rats

    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.)

  7. Analgesic effect of minocycline in rat model of inflammation-induced visceral pain.

    Kannampalli, Pradeep; Pochiraju, Soumya; Bruckert, Mitchell; Shaker, Reza; Banerjee, Banani; Sengupta, Jyoti N

    2014-03-15

    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 5min of administration, systemic injection of the drug produced a delayed effect (60min) 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

  8. Phenotypic modulation of corpus cavernosum smooth muscle cells in a rat model of cavernous neurectomy.

    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.

  9. Genotypic and phenotypic characterization of P23H line 1 rat model.

    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.

  10. Hepatic drug metabolizing profile of Flinders Sensitive Line rat model of depression.

    Kotsovolou, Olga; Ingelman-Sundberg, Magnus; Lang, Matti A; Marselos, Marios; Overstreet, David H; Papadopoulou-Daifoti, Zoi; Johanson, Inger; Fotopoulos, Andrew; Konstandi, Maria

    2010-08-16

    The Flinders Sensitive Line (FSL) rat model of depression exhibits some behavioral, neurochemical, and pharmacological features that have been reported in depressed patients and has been very effective in screening antidepressants. Major factor that determines the effectiveness and toxicity of a drug is the drug metabolizing capacity of the liver. Therefore, in order to discriminate possible differentiation in the hepatic drug metabolism between FSL rats and Sprague-Dawley (SD) controls, their hepatic metabolic profile was investigated in this study. The data showed decreased glutathione (GSH) content and glutathione S-transferase (GST) activity and lower expression of certain major CYP enzymes, including the CYP2B1, CYP2C11 and CYP2D1 in FSL rats compared to SD controls. In contrast, p-nitrophenol hydroxylase (PNP), 7-ethoxyresorufin-O-dealkylase (EROD) and 16alpha-testosterone hydroxylase activities were higher in FSL rats. Interestingly, the wide spread environmental pollutant benzo(alpha)pyrene (B(alpha)P) induced CYP1A1, CYP1A2, CYP2B1/2 and ALDH3c at a lesser extend in FSL than in SD rats, whereas the antidepressant mirtazapine (MIRT) up-regulated CYP1A1/2, CYP2C11, CYP2D1, CYP2E1 and CYP3A1/2, mainly, in FSL rats. The drug also further increased ALDH3c whereas suppressed GSH content in B(alpha)P-exposed FSL rats. In conclusion, several key enzymes of the hepatic biotransformation machinery are differentially expressed in FSL than in SD rats, a condition that may influence the outcome of drug therapy. The MIRT-induced up-regulation of several drug-metabolizing enzymes indicates the critical role of antidepressant treatment that should be always taken into account in the designing of treatment and interpretation of insufficient pharmacotherapy or drug toxicity. PMID:20595028

  11. Diabetic cardiomyopathy: effects of fenofibrate and metformin in an experimental model – the Zucker diabetic rat

    Gadot Nicolas

    2009-03-01

    Full Text Available Abstract Background Diabetic cardiomyopathy (DCM contributes to cardiac failure in diabetic patients. It is characterized by excessive lipids accumulation, with increased triacylglycerol (TAG stores, and fibrosis in left ventricle (LV. The mechanisms responsible are incompletely known and no specific treatment is presently defined. We evaluated the possible usefulness of two molecules promoting lipid oxidation, fenofibrate and metformin, in an experimental model of DCM, the Zucker diabetic rat (ZDF. Methods ZDF and controls (C rats were studied at 7, 14 and 21 weeks. After an initial study at 7 weeks, ZDF rats received no treatment, metformin or fenofibrate until final studies (at 14 or 21 weeks. C rats received no treatment. Each study comprised measurements of metabolic parameters (plasma glucose, TAG, insulin levels and sampling of heart for histology and measurements of TAG content and relevant mRNA concentration. Results ZDF rats were insulin-resistant at 7 weeks, type 2 diabetic at 14 weeks and diabetic with insulin deficiency at 21 weeks. Their plasma TAG levels were increased. ZDF rats had at 7 weeks an increased LV TAG content with some fibrosis. LV TAG content increased in untreated ZDF rats at 14 and 21 weeks and was always higher than in C. Fibrosis increased also moderately in untreated ZDF rats. Metformin and fenofibrate decreased plasma TAG concentrations. LV TAG content was decreased by metformin (14 and 21 weeks and by fenofibrate (14 weeks. Fibrosis was reduced by fenofibrate only and was increased by metformin. Among the mRNA measured, fenofibrate increased Acyl-CoA Oxidase mRNA level, metformin decreased Acyl-CoA Synthase and increased AdipoR1 and pro-inflammatory mRNA levels. Conclusion Fenofibrate had favourable actions on DCM. Metformin had beneficial effect on TAG content but not on fibrosis. PPARα agonists could be useful for the prevention and treatment of DCM.

  12. Evaluate rat myocardial ischemia model by micro-PET with two tracers

    The myocardial ischemia model by LAD ligature was established and evaluate it with 3 methods. The traditional method is T wave changes in ECG. The classic method is TTC staining. The new method is 13NH3 * H2O and 18F-FDG Micro-PET imaging. Using ECG, 9 of 12 rats were judged as successful models. Using Micro-PET, only 6 of 9 rats were judged as successful models, which was consistent with TTC staining results. Micro- PET imaging indicated that before the model was established, the 13NH3 * H2O and 18F- FDG were well-distributed in the myocardial of rats, the standardized uptake value (SUV) of 13NH3 . H2O and 18F-FDG of myocardial ischemia were 3.78±0.59 (n=12) and 2.30±0. 21 (n=12). After the model was established, only 6 rats shows abnormal myocardial perfusion and metabolism, the SUV of 13NH3 * H2O and 18F-FDG of myocardial ischemia model were 2.78±0.46 (n=6) and 1.65±0.21 (n=6). The result showed that the accuracy rate of Micro-PET method was 100%, while the traditional method is 66.67%. In conclusion, 13NH3 . H2O and 18F-FDG Micro-PET image maybe more precise and objective than ECG. (authors)

  13. Shen Wu capsule affects the cognitive function and apoptosis protein in the ischemic-diabetic compound model rats

    Chenlian-zhen; Lilin; Anwen-lin; Zhangli; Chujin

    2004-01-01

    Aim: To explore the mechanism of diabetes mellitus eneephalopathy and the effect of cognitive function of Chinese patent medicine Shen Wu capsule and intervention to apoptosis in the ischemic diabetic compound model rats. Methods:The compound model of Wistar rats was duplicated with streptozotocin (STZ) (60mg/kg) once intraperitoneally and transient

  14. A BBDR-HPT Axis Model for the Lactating Rat and Nursing Pup: Evaluation of Iodide Deficiency

    A biologically based dose response (BBDR) model for the lactating rat and pup hypothalamic-pituitary-thyroid (HPT) axis is being developed to advance understanding of thyroid hormone disruptions and developmental neurotoxicity (DNT). The model for the lactating rat and pup quanti...

  15. Diagnostic value of macrophage activity MRI in rat model of multiple sclerosis

    Objective: To investigate the value of macrophage activity imaging (MAI) in the diagnosis of brain and spinal cord lesions in rat model of multiple sclerosis (MS). Methods: Twenty LEW rats were divided into 15 model rats and 5 control rats. MS animal model, experimental autoimmune encephalomyelitis (EAE) was induced by the injection of peptide 35-55 of myelin oligodendrocyte glycoprotein (MOG35-55), MRI was performed on the third day of the acute stage of disease. The brain and spinal cord of' rats were scanned by 3.0 T MR scanner (Siemens Trio Tim) with quadrature wrist joint coil. The T2W and T1W images, Gadolinium enhanced T1W images in 3D volume were obtained respectively. The MAI were obtained at 24 hours after intravenous injection of ultra small superparamagnetic iron oxide (USPIO) as contrast medium on T2WI. The workstation with special software was used for the reconstruction images of brain and spinal cord of rat in multiple orientations. Results: Fifteen MOG3555-EAE rats model of' MS were successfully induced. The great majority lesions of central nervous system in acute stage were located in the brain (58/63) and less in the spinal cord (5/63). The main manifestation of EAE lesions presented was hyperintensity on T2WI and hypointensity on T1WI, and some lesions had enhancement after Gd-DTPA injection. The EAE lesions presented as hypointensity on MAI images, but some of them were found to be isointensity on T2WI. The enhancement pattern was discrepant between USPIO and Gd-DTPA. The sensitivity of depicting lesions of MOG35-55-EAE rat at acute stage were higher on T2WI (14/15) and MAI (13/15), and the detection rate was 100% (15/15) if they were combined. Gd-DTPA enhanced T1WI had a lower sensitivity (7/15). All the MAI findings were negative in the control rats. Conclusions: MAI can complement the drawback of conventional MRI techniques by continuously monitoring the inflammatory activity of EAE lesions, and it could raise the detection rate of EAE

  16. Experimental model for transcutaneous electrical nerve stimulation on ischemic random skin flap in rats

    Liebano Richard Eloin

    2003-01-01

    Full Text Available The objective of this paper was to develop an experimental model to be used in the study of Transcutaneous Electrical Nerve Stimulation (TENS on viability of random skin flap in rats. The sample was 15 Wistar-EPM rats. The random skin flap measured 10x4 cm and a plastic barrier was placed between the flap and the donnor site. The animals were submited to TENS for 1 hour immediately after the surgery and on the two subsequent days. On the seventh postoperative day, the percentage of necrotic area was measured and calculated. The experimental model proved to be reliable to be used in the study of effects of Transcutaneous Electrical Nerve Stimulation in random skin flap in rats.

  17. A comparative behavioural study of mechanical hypersensitivity in 2 pain models in rats and humans.

    Reitz, Marie-Céline; Hrncic, Dragan; Treede, Rolf-Detlef; Caspani, Ombretta

    2016-06-01

    The assessment of pain sensitivity in humans has been standardized using quantitative sensory testing, whereas in animals mostly paw withdrawal thresholds to diverse stimuli are measured. This study directly compares tests used in quantitative sensory testing (pinpricks, pressure algometer) with tests used in animal studies (electronic von Frey test: evF), which we applied to the dorsal hind limbs of humans after high frequency stimulation and rats after tibial nerve transection. Both experimental models induce profound mechanical hypersensitivity. At baseline, humans and rats showed a similar sensitivity to evF with 0.2 mm diameter tips, but significant differences for other test stimuli (all P positive sensory sign after peripheral nerve injury in humans-is a novel finding in the tibial nerve transection model. By testing outside the primary zone of nerve damage (rat) or activation (humans), our methods likely involve effects of central sensitization in both species. PMID:26859819

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

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

    -response effect of intradermal serotonin (1%, 2% and 4%) on local temperature. The third experiment evaluated the anesthetized rats to test the local vasomotor responses in absent of scratching. Serotonin elicited significant scratching and lowered the local temperature at the site of injection. A dose......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...... experiments. The first experiment evaluated vasomotor response (IR-Th) and scratching behavior (number of bouts) induced by intradermal serotonin (10 μl, 2%). Isotonic saline (control: 10 μl, 0.9%) and Methysergide (antagonist: 10 μl, 0.047 mg/ml) were used. The second experiment evaluated the dose...

  19. Freshly isolated hepatocyte transplantation in acetaminophen-induced hepatotoxicity model in rats

    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.

  20. Simultaneous measurement of hemorheological and hemodynamic properties using a rat extracorporeal model

    Yeom, Eunseop; Lee, Sang Joon; CenterBiofluid; Biomimetics Research Team

    2015-11-01

    It is well known that cardiovascular diseases (CVDs) are closely related with the variations of hemorheological and hemodynamic properties. Accurate measurement of these properties is essential for early diagnosis of CVDs. However, in vitro measurements have technical limitation for the accurate measurement because in vitro exposure can change hemorheological properties. To resolve this problem, a rat extracorporeal model which connects the artery and vein in a rat was employed in this study. Blood flows in the rat extracorporeal model were visualized by an ultrasound imaging system and microfluidic devices for monitoring hemorheological and hemodynamic properties. As a result, the system can be effectively used to measure blood viscosity, red blood cell aggregation and flow rate under ex vivo conditions. The present results would be helpful to develop a diagnostic modality for monitoring the variations in hemorheological and hemodynamic parameters. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea Government (MSIP) (No. 2008-0061991).

  1. Role of group 3 innate lymphoid cells during experimental otitis media in a rat model.

    Cho, Chang Gun; Gong, Sung Ho; Kim, Hee-Bok; Song, Jae-Jun; Park, Joo Hyun; Lim, Yun-Sung; Park, Seok-Won

    2016-09-01

    The objective of this study was to evaluate the role of group 3 innate lymphoid cells (ILC3) in the middle ear (ME) mucosal response to bacterial infection in a rat model. To confirm the role of ILC3 in bacterially induced otitis media (OM), the serum concentrations of IL-17 and IL-22 were determined by ELISA, and the tissue expression of IL-17 and IL-22 in infected ME mucosa was assessed by immunohistochemical staining. Immunohistochemical staining of specific cell surface markers was also assessed to confirm the origin of the cells expressing IL-17 and IL-22. Twenty Sprague-Dawley rats were used in the surgically-induced animal model of OM. OM was induced by inoculation of non-typeable Haemophilus influenzae into the ME cavity of the rats. The rats were divided into four experimental groups: three infected groups and one control group. Infected groups were subdivided into sets of 5 rats, one for each of the three time points (1, 4 and 7 days post-inoculation). For determination of rat IL-17 and IL-22 levels in infected rats and control rats, infected or control ME mucosa sections were analyzed by immunohistochemistry with specific antibodies directed against IL-17 and IL-22. Immunohistochemical staining for CD3, RORγt, and NKp46 were also conducted on the samples to confirm the origin of cells expressing IL-17 and IL-22. IL-17 and IL-22 serum concentrations were significantly increased in the infected rats compared to control rats. Immunohistochemical staining revealed increased IL-17 and IL-22 expressions in all infected ME mucosae from the first day after inoculation. In addition, the results of tissue staining for the specific surface markers were negative for CD3 and NKp46, but were highly positive for RORγt. IL-17 and IL-22 revealed their association with the bacterially induced proliferative and hyperplastic responses of ME mucosa, which are characteristic features in pathogenesis of OM. Surface marker examination showed that the source cells for IL-17

  2. Ranitidine reduced levodopa-induced dyskinesia in a rat model of Parkinson’s disease

    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

  3. A rat model of hypohidrotic ectodermal dysplasia carries a missense mutation in the Edaradd gene

    Hiai Hiroshi

    2011-10-01

    Full Text Available Abstract Background Hypohidrotic ectodermal dysplasia (HED is a congenital disorder characterized by sparse hair, oligodontia, and inability to sweat. It is caused by mutations in any of three Eda pathway genes: ectodysplasin (Eda, Eda receptor (Edar, and Edar-associated death domain (Edaradd, which encode ligand, receptor, and intracellular adaptor molecule, respectively. The Eda signaling pathway activates NF-κB, which is central to ectodermal differentiation. Although the causative genes and the molecular pathway affecting HED have been identified, no curative treatment for HED has been established. Previously, we found a rat spontaneous mutation that caused defects in hair follicles and named it sparse-and-wavy (swh. Here, we have established the swh rat as the first rat model of HED and successfully identified the swh mutation. Results The swh/swh rat showed sparse hair, abnormal morphology of teeth, and absence of sweat glands. The ectoderm-derived glands, meibomian, preputial, and tongue glands, were absent. We mapped the swh mutation to the most telomeric part of rat Chr 7 and found a Pro153Ser missense mutation in the Edaradd gene. This mutation was located in the death domain of EDARADD, which is crucial for signal transduction and resulted in failure to activate NF-κB. Conclusions These findings suggest that swh is a loss-of-function mutation in the rat Edaradd and indicate that the swh/swh rat would be an excellent animal model of HED that could be used to investigate the pathological basis of the disease and the development of new therapies.

  4. Cyclosporin A significantly improves preeclampsia signs and suppresses inflammation in a rat model.

    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 (1.0μg/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 (1.0μg/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. PMID:26954342

  5. Heat Shock Protein 72 Protects Retinal Ganglion Cells in Rat Model of Acute Glaucoma

    Guoping Qing; Xuanchu Duan; Youqin Jiang

    2005-01-01

    Purpose: To investigate whether the induction of heat shock protein (HSP)72 by heat stress (HS) or zinc (Zn2+ ) administration can increase survival of retinal ganglion cells (RGC) in rat model of acute experimental glaucoma.Methods: Acute glaucoma model was made by intracameral irrigation with BSS at 102 mmHg for two hours in right eyes of male Wistar rats. Glaucoma model rats were treated with HS once a week (six rats) or intraperitoneal injection of zinc sulfate (24.6 mg/kg) every two weeks (six rats), and were referred to as HS group and zinc group, respectively. Untreated model rats served as damage group (six rats). In control groups, quercetin (400 mg/kg) was intraperitoneally injected to inhibit the induction of heat shock proteins 6 hours before HS or zinc administration, and were referred to as HS+que group (six rats) and zinc+que group (six rats), respectively. Subsequent to 16 days of IOP elevation, the rats were sacrificed. Eyes were quickly enucleated, and the retinas were dissected. RGC were labeled with Nissl staining and counted under microscope.Results: The average RGC density in normal Wistar rats was (2504±181) cells/mm2. In damage group, it decreased to (2015±111 ) cells/mm2. The RGC densities at 1,2, and 3 mm from the center of the optic nerve head were (2716±215), (2496±168), and (2317±171) cells/mm2, respectively, for normal rats and (2211±133), (1969±154),and (1872±68) cells/mm2, respectively, for damage group. The latter was significantly lower at all locations compared with the former (P=0.027 for each, Mann-Whitney test).The average RGC densities were (2207±200) cells/mm2 for HS group, (2272±155) cells/mm2 for zinc group, (1964±188) cells/mm2 for HS+que group, (2051 ±214) cells/mm2 for zinc+que group and (2015±111 ) cells/mm2 for damage group. There were significant differences in density of labeled RGCs among the five groups (P=0.040,Kruskal-Wallis test). Both HS and zinc group had higher RGC densities than damage group (P

  6. A good resuscitation model of non-transthoracic cardiopulmonary bypass in rats

    AN Yong; XIAO Ying-bin; ZHONG Qian-jin

    2007-01-01

    Objective:To establish a good recoverable rat model of cardiopulmonary bypass (CPB) to lay the foundation for studying the pathophysiology of CPB.Methods:Twenty adult male Sprague-Dawley rats weighing 480 g um via the right jugular vein and further transferred by a miniaturized roller pump to a hollow fiber oxgenator and back to the rat via the left carotid artery. Priming consisted of 8 ml of homologous blood and 6 ml of colloid. The surface of the hollow fiber oxgenator was 0.075 m2. Rats were catheterized and brought in bypass for 120 min at a flow rate of 100-120 ml/kg/min. Oxygen flow/ perfusion flow was 0. 8 to 1. 0, the mean arterial pressure (MAP) kept in 60-80 mmHg. Blood gas analysis, lactate dehydrogenase (LDH), and survival rate were examined subsequently.Results: All CPB rats recovered from the operative process without incident and remained uneventful within one week. Normal cardiac function after successful weaning was confirmed by electrocardiography and blood pressure measurements. MAP remained stable. The results of blood gas analysis at different time points were within a normal range. No significant haemolysis could be detected in the given time frame under bypass condition by using LDH.Conclusions: The rat model of CPB can principally simulate the clinical setting of human CPB. The nontransthoracic model is easy to establish and is associated with excellent recovery. This well reproducible model may open the field for various studies on pathophysiological process of CPB and also of systemic ischemia-reperfusion injury in vivo.

  7. Superoxide dismutase prevents development of adenocarcinoma in a rat model of Barrett's esophagus

    Elena Piazuelo; Carmelo Cebrián; Alfredo Escartín; Pilar Jiménez; Fernando Soteras; Javier Ortego; Angel Lanas

    2005-01-01

    AIM: To test whether antioxidant treatment could prevent the progression of Barrett's esophagus to adenocarcinoma.METHODS: In a rat model of gastroduodenoesophageal reflux by esophagojejunal anastomosis with gastric preservation, groups of 6-10 rats were randomized to receive treatment with superoxide dismutase (SOD) or vehicle and followed up for 4 mo. Rat's esophagus was assessed by histological analysis, superoxide anion and peroxinitrite generation, SOD levels and DNA oxidative damage.RESULTS: All rats undergoing esophagojejunostomy developed extensive esophageal mucosal ulceration and inflammation by mo 4. The process was associated with a progressive presence of intestinal metaplasia beyondthe anastomotic area (9% 1st mo and 50% 4th mo) (94% at the anastomotic level) and adenocarcinoma(11% 1st mo and 60% 4th mo). These changes were associated with superoxide anion and peroxinitrite mucosal generation, an early and significant increase of DNA oxidative damage and a significant decrease in SOD levels (P<0.05). Exogenous administration of SOD decreased mucosal superoxide levels, increased mucosal SOD levels and reduced the risk of developing intestinal metaplasia beyond the anastomotic area (odds ratio = 0.326; 95%CI: 0.108-0.981; P = 0.046),and esophageal adenocarcinoma (odds ratio = 0.243;95%CI: 0.073-0.804; P = 0.021).CONCLUSION: Superoxide dismutase prevents the progression of esophagitis to Barrett's esophagus and adenocarcinoma in this rat model of gastrointestinal reflux, supporting a role of antioxidants in the chemoprevention of esophageal adenocarcinoma.

  8. Manifestation of Hyperandrogenism in the Continuous Light Exposure-Induced PCOS Rat Model

    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.

  9. Establishment of rat model of opening blood-brain barrier with conventional whole-brain irradiation

    Objective: To establish a rat model of opening blood-brain barrier with conventional whole-brain irradiation. Methods: According to different dosage of irradiation, a hundred Sprague-Dowley rats were randomly assigned into five groups, the control group (no irradiation), and four irradiated groups at 10 grays, 20 grays, 30 grays and 40 grays. The rats were administered to conventional fraction irradiation (2 Gy/day and 5 days a week) with routine 60Co gamma-rays. The intake of feed and autonomic activities were observed every day. Changes in skin and hair in the irradiated field, body weight, and center nervous system symptoms and signs were examined and recorded every week during irradiation. The neurological status was ranked on a scale based on the Mickley's Scale. Ultrastructure changes of blood-brain barrier at 16 hours after the last irradiation were examined with electron microscope using lanthanum trace labeling. Results: Neither abnormal nervous sign, nor change of feed intake, skin and hair was observed in all the rats. No statistically significant difference of body weight was observed among the five groups (P>0.05). The effect that radiation can directly damage the function and structure of blood-brain barrier was proportional to irradiation doses. Conclusion: This rat model is a suitable for study on blood-brain barrier pathophysiology and molecular biology after conventional whole-brain irradiation. (authors)

  10. New Wistar Kyoto and spontaneously hypertensive rat transgenic models with ubiquitous expression of green fluorescent protein.

    Garcia Diaz, Ana Isabel; Moyon, Ben; Coan, Philip M; Alfazema, Neza; Venda, Lara; Woollard, Kevin; Aitman, Tim

    2016-04-01

    The Wistar Kyoto (WKY) rat and the spontaneously hypertensive (SHR) rat inbred strains are well-established models for human crescentic glomerulonephritis (CRGN) and metabolic syndrome, respectively. Novel transgenic (Tg) strains add research opportunities and increase scientific value to well-established rat models. We have created two novel Tg strains using Sleeping Beauty transposon germline transgenesis, ubiquitously expressing green fluorescent protein (GFP) under the rat elongation factor 1 alpha (EF1a) promoter on the WKY and SHR genetic backgrounds. The Sleeping Beauty system functioned with high transgenesis efficiency; 75% of new rats born after embryo microinjections were transgene positive. By ligation-mediated PCR, we located the genome integration sites, confirming no exonic disruption and defining a single or low copy number of the transgenes in the new WKY-GFP and SHR-GFP Tg lines. We report GFP-bright expression in embryos, tissues and organs in both lines and show preliminaryin vitroandin vivoimaging data that demonstrate the utility of the new GFP-expressing lines for adoptive transfer, transplantation and fate mapping studies of CRGN, metabolic syndrome and other traits for which these strains have been extensively studied over the past four decades. PMID:26769799

  11. New Wistar Kyoto and spontaneously hypertensive rat transgenic models with ubiquitous expression of green fluorescent protein

    Ana Isabel Garcia Diaz

    2016-04-01

    Full Text Available The Wistar Kyoto (WKY rat and the spontaneously hypertensive (SHR rat inbred strains are well-established models for human crescentic glomerulonephritis (CRGN and metabolic syndrome, respectively. Novel transgenic (Tg strains add research opportunities and increase scientific value to well-established rat models. We have created two novel Tg strains using Sleeping Beauty transposon germline transgenesis, ubiquitously expressing green fluorescent protein (GFP under the rat elongation factor 1 alpha (EF1a promoter on the WKY and SHR genetic backgrounds. The Sleeping Beauty system functioned with high transgenesis efficiency; 75% of new rats born after embryo microinjections were transgene positive. By ligation-mediated PCR, we located the genome integration sites, confirming no exonic disruption and defining a single or low copy number of the transgenes in the new WKY-GFP and SHR-GFP Tg lines. We report GFP-bright expression in embryos, tissues and organs in both lines and show preliminary in vitro and in vivo imaging data that demonstrate the utility of the new GFP-expressing lines for adoptive transfer, transplantation and fate mapping studies of CRGN, metabolic syndrome and other traits for which these strains have been extensively studied over the past four decades.

  12. Generation of a novel transgenic rat model for tracing extracellular vesicles in body fluids.

    Yoshimura, Aya; Kawamata, Masaki; Yoshioka, Yusuke; Katsuda, Takeshi; Kikuchi, Hisae; Nagai, Yoshitaka; Adachi, Naoki; Numakawa, Tadahiro; Kunugi, Hiroshi; Ochiya, Takahiro; Tamai, Yoshitaka

    2016-01-01

    Extracellular vesicles (EVs) play an important role in the transfer of biomolecules between cells. To elucidate the intercellular transfer fate of EVs in vivo, we generated a new transgenic (Tg) rat model using green fluorescent protein (GFP)-tagged human CD63. CD63 protein is highly enriched on EV membranes via trafficking into late endosomes and is often used as an EV marker. The new Tg rat line in which human CD63-GFP is under control of the CAG promoter exhibited high expression of GFP in various body tissues. Exogenous human CD63-GFP was detected on EVs isolated from three body fluids of the Tg rats: blood serum, breast milk and amniotic fluid. In vitro culture allowed transfer of serum-derived CD63-GFP EVs into recipient rat embryonic fibroblasts, where the EVs localized in endocytic organelles. These results suggested that this Tg rat model should provide significant information for understanding the intercellular transfer and/or mother-child transfer of EVs in vivo. PMID:27539050

  13. The Establishment of Metabolic Syndrome Model by Induction of Fructose Drinking Water in Male Wistar Rats

    Norshalizah Mamikutty

    2014-01-01

    Full Text Available Background. Metabolic syndrome can be caused by modification of diet by means of consumption of high carbohydrate and high fat diet such as fructose. Aims. To develop a metabolic syndrome rat model by induction of fructose drinking water (FDW in male Wistar rats. Methods. Eighteen male Wistar rats were fed with FDW 20% and FDW 25% for a duration of eight weeks. The physiological changes with regard to food and fluid intake, as well as calorie intake, were measured. The metabolic changes such as obesity, dyslipidaemia, hypertension, and hyperglycaemia were determined. Data was presented in mean ± SEM subjected to one-way ANOVA. Results. Male Wistar rats fed with FDW 20% for eight weeks developed significant higher obesity parameters compared to those fed with FDW 25%. There was hypertrophy of adipocytes in F20 and F25. There were also systolic hypertension, hypertriglyceridemia, and hyperglycemia in both groups. Conclusion. We conclude that the metabolic syndrome rat model is best established with the induction of FDW 20% for eight weeks. This was evident in the form of higher obesity parameter which caused the development of the metabolic syndrome.

  14. Sodium ferulate inhibits neointimal hyperplasia in rat balloon injury model.

    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.

  15. The Effect of Postoperative Passive Motion on Rotator Cuff Healing in a Rat Model

    Peltz, Cathryn D.; Dourte, LeAnn M.; Kuntz, Andrew F.; Sarver, Joseph J.; Kim, Soung-Yon; Williams, Gerald R.; Soslowsky, Louis J.

    2009-01-01

    Background: Surgical repairs of torn rotator cuff tendons frequently fail. Immobilization has been shown to improve tissue mechanical properties in an animal model of rotator cuff repair, and passive motion has been shown to improve joint mechanics in animal models of flexor tendon repair. Our objective was to determine if daily passive motion would improve joint mechanics in comparison with continuous immobilization in a rat rotator cuff repair model. We hypothesized that daily passive motio...

  16. Accelerated clearance of human red blood cells in a rat transfusion model

    Straat, M.; Klei, TRL; de Korte, D; van Bruggen, R.; Juffermans, NP

    2015-01-01

    Background Animal models are valuable in transfusion research. Use of human red blood cells (RBCs) in animal models facilitates extrapolation of the impact of storage conditions to the human condition but may be hampered by the use of cross species. Methods Investigation of clearance and posttransfusion recovery in a rat model using fresh and stored human RBCs. Results Directly following transfusion, human RBCs could be detected in the circulation of all recipients, with higher recovery rates...

  17. Behavioral assays to model cognitive and affective dimensions of depression and anxiety in rats

    Lapiz-Bluhm, M. Danet S.; Bondi, Corina O.; Doyen, Julianne; Rodriguez, Gustavo; Bédard-Arana, Tania; Morilak, David A

    2008-01-01

    Animal models have been used extensively to investigate neuropsychiatric disorders, such as depression, and their treatment. However, the etiology and pathophysiology of many such disorders are largely unknown, which makes validation of animal models particularly challenging. Further, many diagnostic symptoms are difficult to define, operationalize and quantify, especially in experimental animals such as rats. Thus, rather than attempting to model such complex human syndromes as depression in...

  18. Aerosol and parenteral pneumocandins are effective in a rat model of pulmonary aspergillosis.

    Kurtz, M B; Bernard, E M; Edwards, F F; Marrinan, J A; Dropinski, J; Douglas, C M; Armstrong, D

    1995-01-01

    The pneumocandins are semisynthetic analogs of echinocandin-like compounds that have shown efficacy in animal models of systemic candidiasis, disseminated aspergillosis, and pneumocystis pneumonia. However, the most common form of Aspergillus infection in susceptible patients is pulmonary aspergillosis, which was not directly tested in the mouse models used in the past. We have evaluated three pneumocandins, L-693,989, L-731,373, and L-733,560, in a rat model of pulmonary aspergillosis. Male ...

  19. Cerebral markers of the serotonergic system in rat models of obesity and after Roux-en-Y gastric bypass

    Ratner, Cecilia; Ettrup, Anders; Bueter, Marco;

    2012-01-01

    Food intake and body weight are regulated by a complex system of neural and hormonal signals, of which the anorexigenic neurotransmitter serotonin (5-hydroxytryptamine or 5-HT) is central. In this study, rat models of obesity and weight loss intervention were compared with regard to several 5-HT......DIO rats had higher 5-HT(4) and 5-HT(2A) receptor binding and lower SERT binding when compared to polygenic diet-resistant (pgDR) rats. The most pronounced difference between pgDIO and pgDR rats was observed in the nucleus accumbens shell (NAcS), a brain region regulating reward aspects of feeding. No...... compared to pgDR rats corresponds to what is reported in overweight humans and suggests that the dysfunctions of the 5-HT system associated with overeating or propensity to become overweight are polygenically determined. Our results support that the obesity-prone rat model has high translational value and...

  20. Aortic Cell Apoptosis in Rat Primary Aldosteronism Model

    闫永吉; 欧阳金芝; 王超; 吴准; 马鑫; 李宏召; 徐华; 胡争; 李俊; 王保军; 史涛坪; 龚道静; 倪栋; 张旭

    2010-01-01

    This study aimed to determine whether aldosterone could induce vascular cell apoptosis in vivo.Thirty-two male rats were randomly divided into 4 groups:vehicle(control),aldosterone,aldosterone plus eplerenone or hydralazine.They were then implanted with an osmotic mini-pump that infused either aldosterone or the vehicle.Systolic blood pressure(SBP) was measured weekly by the tail-cuff method.After 8 weeks,plasma aldosterone concentration(PAC) and renin activity(PRA) were determined by radioimmunoassay.Aorti...

  1. Pathogenicity of enterococci in a rat model of fecal peritonitis.

    Matlow, A G; Bohnen, J M; Nohr, C; Christou, N; Meakins, J

    1989-07-01

    The pathogenicity of enterococci in intraabdominal sepsis has not been clarified. Therefore, fecal-type peritonitis was induced in rats by intraperitoneal injection of barium sulfate along with a bacterial inoculum consisting of Escherichia coli, Bacteroides fragilis, and Clostridium perfringens with or without Streptococcus faecalis. Mortality at 19 d and characteristics of intraabdominal abscesses in survivors at 19 d were analyzed. The presence of S. faecalis in the original inoculum was significantly associated with death or large (greater than 20 mm) abscess formation when these two end points were examined together. S. faecalis may synergize with other bacteria in intraabdominal sepsis to augment morbidity and possibly mortality. PMID:2543707

  2. Effect of deep brain stimulation on substantia nigra neurons in a rat model of Parkinson's disease

    WU Sheng-tian; MA Yu; ZHANG Kai; ZHANG Jian-guo

    2012-01-01

    Background Parkinson's disease(PD)is a common neurodegenerative disease,which occurs mainly in the elderly.Recent studies have demonstrated that apoptosis plays an important role in the occurrence and development of PD.Subthalamic nucleus deep brain stimulation(STN-DBS)has been recognized as an effective treatment for PD.Recent clinical observations have shown that STN-DBS was able to delay early PD progression,and experiments in animal models have also demonstrated a protective effect of STN-DBS on neurons.However,the correlation between the neuron-protective effect of STN-DBS and the progression of substantia nigra pars compacta(SNc)neuronal apoptosis is still unknown.The aim of this study was to investigate the protective effect and potential mechanism of STN-DBS on SNc neurons in PD rats.Methods After the establishment of a PD rat model by unilateral/2-point injection of 6-hydroxydopamine in the medial forebrain bundle of the brain,DBS by implanting electrodes in the STN was administered.Behavioral changes were observed,and morphological changes of SNc neurons were analyzed by Nissl staining and DNA in situ end-labeling.Through extracellular recording of single neuron discharges and microelectrophoresis,the causes of and changes in SNc excitability during STN-DBS were analyzed,and the protective effect and potential mechanism of action of STN-DBS on SNc neurons in PD rats was investigated.Results SNc neuron apoptosis was significantly decreased(P<0.05)in the stimulation group,compared with the sham stimulation PD group.Spontaneous discharges of SNc neurons were observed in normal rats and PD model rats,and the mean frequency of spontaneous discharges of SNc neurons in normal rats((40.65±11.08)Hz)was higher than that of residual SNc neurons in PD rats((36.71±9.23)Hz).Electrical stimulation of the STN in rats was associated with elevated excitation in unilateral SNc neurons.However,administering the gamma-aminobutyric acid receptor blocker

  3. Beneficial effect of farnesoid X receptor activation on metabolism in a diabetic rat model.

    Zhang, Hong-Mei; Wang, Xuan; Wu, Zhao-Hong; Liu, Hui-Ling; Chen, Wei; Zhang, Zhong-Zhi; Chen, Dan; Zeng, Tian-Shu

    2016-03-01

    Farnesoid X receptor (FXR) is an important regulator of glucose and lipid homeostasis. However, the exact role of FXR in diabetes remains to be fully elucidated. The present study examined the effects of chenodeoxycholic acid (CDCA), an agonist of FXR, on metabolism profile in a rat model of type 2 diabetes mellitus (T2DM). Male Wistar rats (8‑week‑old; n=40) were randomized into the following four groups (n=10): Untreated control, CDCA‑treated, T2DM, and CDCA‑treated T2DM. To establish the T2DM model, the rats were fed a high‑fat diet (HFD) for 4 weeks and received a single low‑dose intraperitoneal injection of streptozotocin (30 mg/kg), followed by an additional 4 weeks of HFD feeding. CDCA was administrated (10 mg/kg/d) intraperitoneally for 10 days. Reverse transcription‑quantitative polymerase chain reaction and western blotting assays were performed to determine the RNA and protein expression of FXR, phosphoenolpyruvate carboxykinase, G6Pase, proliferator‑activated receptor‑γ coactivator‑1 and short heterodimer partner in rat liver tissue. The results revealed that FXR activation by CDCA did not reduce body weight, but it lowered the plasma levels of fasting glucose, insulin and triglycerides in the T2DM rats. CDCA administration reversed the downregulation of the mRNA and protein expression of FXR in the T2DM rat liver tissue samples. Furthermore, treatment with CDCA reduced the mRNA and protein expression levels of phosphoenolpyruvate carboxykinase, glucose 6‑phosphatase and peroxisome proliferator‑activated receptor‑γ coactivator‑1 in the liver tissue samples of the T2DM rats. By contrast, CDCA treatment increased the mRNA and protein expression levels of short heterodimer partner in the liver tissue samples of the T2DM rats. In conclusion, FXR agonist treatment induces beneficial effects on metabolism in the rat T2DM model. In conclusion, the present study indicated that the FXR agonist may be useful for the treatment

  4. Establishment of 9L/F344 rat intracerebral glioma model of brain tumor stem cells

    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. Estrogen-mimicking isoflavone genistein prevents bone loss in a rat model of obstructive sleep apnea-hypopnea syndrome

    Song, Lige; Liang, Xiao; Zhou, Yun

    2014-01-01

    Objective: Intermittent hypoxia was introduced to mimic obstructive sleep apnea-hypopnea syndrome (OSAHS) in rats. Then, bone mass, bone strength and bone turnover were evaluated, and the influence of genistein on bone mass reduction was investigated in these rats. Methods: OSAHS animal model was established via chronic intermittent hypoxia, and genistein (2.5 mg/kg/day) was used to treat OSAHS rats. The bone mineral density (BMD), bone Histomorphometric indicators, bone biomechanics and expr...

  6. Comparison of the acute effects of hemostatic agents on neural tissues in spine surgery: Histologic analysis in rat models

    Gokhan Meric; Omer Akcali; Serap Cilaker Micili; Alper Bagriyanik

    2016-01-01

    Objective: The most frightening and likely complication of chemical hemostatic agents is neurologic deficit. The histological basis of this potential complication is still unknown. The aim of this study is to observe the acute histologic effects of routinely used hemostatic agents on neural tissues in a rat model. Methods: Eighteen Winstar Albino rats were operated and same-level laminectomies were performed. The rats were divided into three groups. In group 1 (control group), surgical lay...

  7. Protective role of antimannan and anti-aspartyl proteinase antibodies in an experimental model of Candida albicans vaginitis in rats.

    De Bernardis, F.; Boccanera, M; Adriani, D; Spreghini, E; G. Santoni; Cassone, A.

    1997-01-01

    The role of antibodies (Abs) in the resistance to vaginal infection by Candida albicans was investigated by using a rat vaginitis model. Animals receiving antimannoprotein (anti-MP) and anti-aspartyl proteinase (Sap) Ab-containing vaginal fluids from rats clearing a primary C. albicans infection showed a highly significant level of protection against vaginitis compared to animals given Ab-free vaginal fluid from noninfected rats. Preabsorption of the Ab-containing fluids with either one or bo...

  8. Effect of two novel CGRP-binding compounds in a closed cranial window rat model

    Juhl, Louise Kathrine; Edvinsson, Lars; Olesen, Jes;

    2007-01-01

    We investigated the in vivo effects of two novel calcitonin gene-related peptide (CGRP) binding molecules in the genuine closed cranial window model in the rat. The RNA-Spiegelmer (NOX-C89) and the monoclonal CGRP antibody are CGRP scavengers and might be used as an alternative to CGRP-receptor a...

  9. Visceral hypersensitivity and altered colonic motility after subsidence of inflammation in a rat model of colitis

    Jun-Ho La; Tae-Wan Kim; Tae-Sik Sung; Jeoung-Woo Kang; Kyun-Ju Kim; Il-Suk Yang

    2003-01-01

    AIM: Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by visceral hypersensitivity and altered bowel motility. There is increasing evidence suggesting the role of inflammation in the pathogenesis of IBS, which addresses the possibility that formerly established rat model of colitis could be used as an TBS model after the inflammation subsided.METHODS: Colitis was induced by intracolonic instillation of 4 % acetic acid in male Sprague-Dawley rats. The extent of inflammation was assessed by histological examination and myeloperoxidase (MPO) activity assay. After subsidence of colitis, the rats were subjected to rectal distension and restraint stress, then the abdominal withdrawal reflex and the number of stress-induced fecal output were measured,respectively.RESULTS: At 2 days post-induction of colitis, the colon showed characteristic inflammatory changes in histology and 8-fold increase in MPO activity. At 7 days post-induction of colitis, the histological features and MPO activity returned to normal. The rats at 7 days post-induction of colitis showed hypersensitive response to rectal distension without an accompaning change in rectal compliance, and defecated more stools than control animals when under stress.CONCLUSION: These results concur largely with the characteristic features of IBS, visceral hypersensitivity and altered defecation pattern in the absence of detectable disease, suggesting that this animal model is a methodologically convenient and useful model for studying a subset of IBS.

  10. Establishment of an animal model of non-transthoracic cardiopulmonary bypass in rats

    SHANG Hong-wei; XIAO Ying-bin; LIU Mei; CHEN Lin

    2005-01-01

    Objective: To establish an animal model of non-transthoracic cardiopulmonary bypass (CPB) in rats. Methods: Ten adult male Sprague-Dawlay rats, weighing 350-500 g, were used in this study. CPB was established in these animals through cannulating the left carotid and right jugular vein for arterial perfusion and venous return. The components of perfusion circuit, especially the miniature oxygenator and cannula, were specially designed and improved. The mean arterial pressure was measured with a blood pressure meter through cannulating the left femoral artery. The hemodynamic and blood gas parameters were also monitored. Results: The rat model of non-transthoracic CPB was established successfully. The hemodynamical parameters were changed within an acceptable region during CPB. The miniature oxygenator was sufficient to meet the standard of satisfactory CPB.Conclusions: The rat model of non-transthoracic CPB established through the carotid and jugular cannulation is feasible, easily operated, safe, reliable, and economic. It is an ideal model for the pathophysiological research of CPB.

  11. Agmatine reversed mechanical allodynia in a rat model of neuropathic pain

    YANGHong-Ju; ZhAONan; GONGZheng-Hua; YUANWei-Xiou; LIYunFeng; LI-Jin; LUOZhi-Pu

    2004-01-01

    AIM: Agmatine is an endogenous neuromodulator present in the brain and spinal cord, agmatine has both NMDA receptor antagonist and NOS inhibitor activities, which may participate the pathological process in the neuropathic pain. The effect of agmatine on the mechanical allodynia in a rat model of the neuropathic pain was investigated in this experiment.

  12. The brain changes of anisotropy in MAM model of schizophrenia in rat

    Kořínek, Radim; Dražanová, Eva; Bartušek, Karel; Micale, V.; Starčuk jr., Zenon

    Vol. S1. Berlin : Springer-Verlag, 2013, s. 294. ISSN 1352-8661. [ESMRMB 2013. Congress. Tolouse (FR), 03.10.2013-05.10.2013] Institutional support: RVO:68081731 Keywords : The brain changes of anisotropy * MAM model * schizophrenia in rat Subject RIV: BH - Optics, Masers, Lasers

  13. Lactose maldigestion during methotrexate-induced gastrointestinal mucositis in a rat model

    Fijlstra, M.; Rings, E. H. H. M.; Verkade, H. J.; van Dijk, T. H.; Kamps, W. A.; Tissing, W. J. E.

    2011-01-01

    Fijlstra M, Rings EH, Verkade HJ, van Dijk TH, Kamps WA, Tissing WJ. Lactose maldigestion during methotrexate-induced gastrointestinal mucositis in a rat model. Am J Physiol Gastrointest Liver Physiol 300: G283-G291, 2011. First published November 18, 2010; doi:10.1152/ajpgi.00462.2010.-Patients wit

  14. Modeling cerebral arteriovenous lactate kinetics after intravenous lactate infusion in the rat

    Leegsma-Vogt, G; van der Werf, T; Venema, K; Korf, J

    2004-01-01

    Venous-arterial lactate differences across the brain during lactate infusion in rats were studied, and the fate of lactate was described with a mathematical model that includes both cerebral and extracerebral kinetics. Ultrafiltration was used to sample continuously and simultaneously arterial and v

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

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

    2010-01-01

    effectively reduced food intake and body weight in DIO rats. Liraglutide furthermore improved glucose tolerance when compared with sibutramine. Our data highlights the usefulness of a polygenetic animal model for screening of compounds affecting food intake, body weight, and glucose homeostasis. Furthermore...

  16. Application of Mathematical Modelling as a Tool to Analyze the EEG Signals in Rat Model of Focal Cerebral Ischemia

    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.

  17. IN VIVO EVALUATION OF MIMOSA PUDICA LINN. IN THE MANAGEMENT OF POLYCYSTIC OVARY USING RAT MODEL

    Mamata Jadhav

    2013-02-01

    Full Text Available This study aimed to evaluate the effect of Mimosa pudica Linn. (MP in the treatment of polycystic ovary syndrome (PCOS using a Letrozole induced PCOS rat model. PCOS was induced in albino wistar female rats by daily oral administration of Letrozole for 21 days. The low (250 mg/kg, mid (500 mg/kg and high dose (1000 mg/kg of MP was given orally to the PCOS induced rats for 15 days post Letrozole induction to determine the effective dose of MP in the treatment of PCOS. The biomarkers of ovarian function, plasma testosterone, estrogen and progesterone were analyzed to determine the fluctuations in sex steroid levels in PCOS induced rats. The plasma testosterone levels were found to be increased significantly in rats with PCOS whereas plasma estrogen and progesterone levels were significantly decreased. When compared with control, the PCOS induced rats showed characteristic ovary with high incidence of ovarian cysts with a diminished granulosa layer, significant number of atretic follicles and absence of corpora lutea. All the end points assessed were significantly improved after the treatment with mid and high dose of MP and achieved levels close to normal levels. The mid dose (500 mg/kg and high dose (1000 mg/kg of MP were found to be effective in the treatment of PCOS induced by Letrozole in rats. This effect of MP significantly reduced histopathological changes in ovary and endocrinological and biochemical changes induced by hyperandrogenism. Thus MP was found to have a good potential to be a very good alternative therapy in the treatment of PCOS.

  18. Histological response to injected gluteraldehyde cross-linked bovine collagen based implant in a rat model

    Cağlar Melda

    2006-02-01

    Full Text Available Abstract Background The aim of present study is to investigate the short and long term histopathological alterations caused by submucosal injection of gluteraldehyde cross-linked bovine collagen based on an experimental rat model. Methods Sixty Sprague-Dawley rats were assigned into two groups as group I and II each containing 30 rats. 0.1 ml of saline solution and 0.1 ml of gluteraldehyde cross-linked bovine collagen were injected into the submucosa of bladder of first (control and second groups, respectively. Both group I and II were further subdivided into 3 other groups as Group IA, IB, IC and Group IIA, IIB, IIC according to the sacrification period. Group IA and IIA, IB and IIB, IC and IIC rats (10 rats for each group were sacrificed 3, 6, and 12 months after surgical procedure, respectively. Two slides prepared from injection site of the bladder were evaluated completely for each rat by being unaware of the groups and at random by two independent senior pathologists to determine the fibroblast invasion, collagen formation, capillary ingrowth and inflammatory reaction. Additionally, randomized brain sections from each rat were also examined to detect migration of the injection material. The measurements were made using an ocular micrometer at ×10 magnification. The results were assessed using t-tests for paired and independent samples, with p Results Migration to the brain was not detected in any group. Significant histopathological changes in the gluteraldehyde cross-linked bovine collagen injected groups were fibroblast invasion in 93.3%, collagen formation in 73.3%, capillary ingrowth in 46.6%, inflamatory reaction in 20%. Conclusion We emphasize that the usage of gluteraldehyde cross-linked bovine collagen in children appears to be safe for endoscopic treatment of vesicoureteral reflux.

  19. Relationship between core temperature change during recovery and prognosis in classic heat stroke rat models

    Ya-nan LIU

    2013-11-01

    Full Text Available Objective To construct classic heat stroke rat models, and observe the changes of body temperature in the recovery period after heat stress to explore its relationship with prognosis. Methods Sixty male SD rats were randomly divided into heat stroke group (HS group, n=50 and control group (C group, n=10. Rats in HS group were exposed to 39℃ heat stress. Core temperature and systolic blood pressure (SBP of rats were monitored until it reached diagnostic criteria of heat stroke. The core body temperature and survival were continuously monitored until 72h. The risk factors of survival were analyzed by univariate and multivariate Cox regression analyses. Results During the recovery, compared with the control group, the body temperature of the HS rats represented a biphasic change that consisted of an initial hypothermia and a delayed hyperthermia. Univariable analysis showed that both the highest and lowest core body temperatures were correlated with prognosis in the heat stroke rats (P<0.05. Multivariate analysis revealed that both the highest core body temperature (P=0.000, HR=102.386 and lowest core body temperature in the recovery period (P=0.001, HR=0.134 were the independent risk factors for heat stroke. Conclusion In heat stroke rats, the higher the core body temperature and the deeper the depth of hypothermia, the poorer the prognosis. Core body temperature in heat stress and recovery period could serve as prognostic indexes in heat stroke. DOI: 10.11855/j.issn.0577-7402.2013.10.007

  20. Formoterol decreases muscle wasting as well as inflammation in the rat model of rheumatoid arthritis.

    Gómez-SanMiguel, Ana Belén; Gomez-Moreira, Carolina; Nieto-Bona, María Paz; Fernández-Galaz, Carmen; Villanúa, Maria Ángeles; Martín, Ana Isabel; López-Calderón, Asunción

    2016-06-01

    Adjuvant-induced arthritis is an experimental model of rheumatoid arthritis that is associated with body weight loss and muscle wasting. β2-adrenergic receptor agonists are powerful anabolic agents that trigger skeletal muscle hypertrophy and have been proposed as a promising treatment for muscle wasting in human patients. The aim of this work was to determine whether formoterol, a selective β2-adrenoreceptor agonist, is able to ameliorate muscle wasting in arthritic rats. Arthritis was induced in male Wistar rats by intradermal injection of Freund's adjuvant. Control and arthritic rats were injected daily with 50 μg/kg sc formoterol or saline for 12 days. Body weight change, food intake, and arthritis index were analyzed. After euthanasia, in the gastrocnemius mRNA was analyzed by PCR, and proteins were analyzed by Western blotting. Arthritis decreased gastrocnemius weight, cross-sectional area, and myofiber size, whereas formoterol increased those variables in both arthritic and control rats. Formoterol decreased the external signs of arthritis as well as NF-κB(p65) activation, TNFα, and COX-2 levels in the gastrocnemius of arthritic and control rats. Those effects of formoterol were associated with a decreased expression of myostatin, atrogin-1, and MuRF1 and in LC3b lipidation. Arthritis increased the expression of MyoD, myogenin, IGF-I, and IGFBP-3 and -5 in the gastrocnemius. In control and in arthritic rats, treatment with formoterol increased Akt phosphorylation and myogenin levels, whereas it decreased IGFBP-3 expression in the gastrocnemius. These data suggest that formoterol has an anti-inflammatory effect and decreases muscle wasting in arthritic rats through increasing Akt activity and myogenin and decreasing myostatin, the p-NF-κB(p65)/TNF pathway, and IGFBP-3. PMID:27245339